Advanced Therapy Medicinal Product (ATMP) Glossary

Biologicals and Advanced Therapy Medicinal Products (ATMPs) Glossary


(Array) comparative genomic hybridisation (CGH, aCGH) – A molecular cytogenetic method for analyzing copy number vari- ants (CNVs) relative to ploidy level in the DNA of a test sample compared with a reference sample, without the need for culturing cells. This technique was originally developed for the evaluation of the differences between the chromosomal complements of solid tumor and normal tissue. This technique is now the first choice to detect unbalanced chromosomal abnormalities in unexplained developmental delay; however this method is not applicable to detect balanced chromosomal abnormalities such as reciprocal translocations, inversions or ring chromosomes because these do not affect copy numbers.

ACAID (anterior chamber-associated immune deviation) – Systemic inhibition of delayed-type hypersensitivity reactions to antigens which have previously been placed into the anterior chamber of the eye.

Adventitious Agents – Adventitious agents are microorganisms that have been unintentionally introduced into the manufacturing process of a biological product. Adventitious agents include bacteria, fungi, mycoplasmas, rickettsia, protozoa, parasites,Transmissible Spongiform Encephalopathy (TSE) agents, and viruses.

Airborne Total Particulate – A measurement of airborne particles in a specified size range (typically determined by mass mean diameter) as recorded by a Discrete Particle Counter (DPC). Since the vast majority of particle counters are incapable of distinguishing between viable and non-viable particulate, this measurement is erroneously called “non-viable”.

Air Change Rate (ACR) or Ventilation Rate – The volume of air supplied to a room (per hour) divided by the volume of the room. This is a purely numerical evaluation used as a rule of thumb in cleanroom design.

Ambient Environment – The environmental conditions where no HVAC systems are present.

Aseptic Operations – Processes that are devoid of measurable (detectable) bioburden. Aseptic operations generally require sterilisation of the environment, equipment and process solutions to achieve the sterile state prior to use.

Aseptic Transfer – Material transfer where the risk of contamination from the environment has been mitigated.

Axenic State – A culture that includes the intended living organism (i.e. monoseptic) but is entirely free of all other contaminating organisms.

A factor – Yeast mating factor that acts as a pheromone, attracting yeast cells of the opposite mating type.

A2E – Phosphatidyl-pyridinium bisretinoid. This derivative of vitamin A can induce apoptosis in retinal pigment epithelial cells.

AAA – Abdominal aortic aneurysm (AAA).

AAA metalloproteases – Mitochondrial ATPase-associated proteases with diverse cellular activities.

AAMC – Association of American Medical Colleges (AAMC).

AAV – Adeno-associated virus; a defective human ssDNA parvovirus with potential as a vector with long-term gene expression, predominantly episomally, for human gene therapy.

AAV8 – Adeno-associated virus type 8 (an example of an AAV serotype).

Ab initio – latin term meaning from the beginning. In disease biology, it refers to a process that begins much the same way that it ends, without going through a series of consecutive steps, over time, leading to the final condition.

Abbreviated New Drug Application (ANDA) – Application for a generic drug filed with the U.S. Food and Drug Administration (FDA).

ABCA1gene ATP – Binding cassette, subfamily B, member 1 gene encoding an ABC transporter- P-glycoprotein- implicated in the transport of various drugs, including clopidogrel, and thereby regulating their intracellular concentrations.

Abcg2 – ATP-binding cassette subfamily G member 2, an ATP-dependent transporter, a glycoprotein that can serve as a molecular marker of CPCs in the adult heart.

ABDS (Athabascan brainstem dysgenesis syndrome) – A syndrome found in American Indians that is also caused by homozygous HOXA1 mutations, but usually with more severe symptoms than BSAS, including primary hypoventilation in childhood, cerebral cortical ischemic injury, and mental retardation.

ABGC – American Board of Genetic Counseling (ABGC).

Ablepharon – Absent eyelids.

ABMGG – American Board of Medical Genetics and Genomics (ABMGG).

ABO antigens – Family of glycoprotein antigens expressed on the surfaces of red blood cells (RBCs) that define the ABO blood group system. Differences in ABO blood types can cause hyperacute graft rejection and severe blood transfusion reactions.

ABO blood group – Set of blood antigens on surface of red blood cells (RBCs) consisting of three different but related glycolipids

Abrin – Plant toxin from seeds of the rosary pea (Abrusprecatorius)

Absorptivity – See Beer’s law.

AC – Adenylyl cyclase; a membrane-bound enzyme that catalyses the synthesis of the second messenger cyclic adenosine 3′, 5′-monophosphate (cAMP) from ATP in response to G-protein-coupled receptor signaling in conjunction with specific signaling ligands (e.g., adrenergic), receptors, and G-proteins.

ACC – Acetyl CoA carboxylase; an enzyme that synthesises malonyl CoA from cytoplasmic and peroxisomal acetyl-CoA.

Acceptor stem – Base-paired stem of tRNA to which the amino acid is attached. The portion of tRNA that binds to an amino acid.

ACCME – Accreditation Council for Continuing Medical Education (ACCME).

Accommodation – This is a term that can be used with two different meanings. In reference to visual acuity, it specifies the ability to focus on near objects. The dioptric increase in optical power of the eye to focus at near. In the young phakic eye, this occurs through an increase in the lens surface curvatures. In reference to neurophysiological phenomena, it specifies the ability of a neuron to adjust to increased or continuous stimuli by turning down or stopping its depolarisation. In the retina, accommodation occurs whenever one is suddenly exposed to bright light or enters a dark theatre.

Accuracy – “Trueness” or proximity to truth based on a gold standard or reference standard.

ACE – Angiotensin-converting enzyme; a central element of the renin-angiotensin system, which converts the decapeptide angiotensin I to the potent pressor octapeptide angiotensin II (Ang II), mediating peripheral vascular tone as well as glomerular filtration in the kidney.

Acetyl CoA – A small water-soluble molecule that carries acetyl groups linked to coenzyme A (CoA) by a thioester bond.

Acetylation – The addition of an acetyl group (CH3–COO–) to another molecule.

Acetylserinesulfhydrylase – Enzyme that converts O-acetylserine plus hydrogen sulfide to cysteine.

aCGH – Array comparative genome hybridisation.

ACGME – Accreditation Council for Graduate Medical Education

ACh – Acetylcholine (ACh).

Achondroplasia – Inherited defect due to mutation of the FGFR3 gene that encodes the fibroblast growth factor (FGF) receptor #3. In achondroplasia, this protein begins to function abnormally, slowing down the growth of bone in the cartilage of the growth plate. Also known as short-limbed dwarfism. 

Acinus – A small grape-shaped group of secretory cells that empty their product into a small duct.

ACIP – Advisory Committee on Immunization Practices, a committee that advises the U.S. Centers for Disease Control and Prevention by recommending immunization strategies for the public health of Americans.

ACM – Alcoholic cardiomyopathy; characterised by cardiomegaly, disruptions of myofibrillary architecture, reduced myocardial contractility, decreased ejection fraction, and enhanced risk of stroke and hypertension.

ACMG – American College of Medical Genetics and Genomics (ACMG).

Acquired immunity – Type of immunity that responds to specific antigens over a course of days, has the ability to distinguish self from non-self, remembers past invading pathogens, and generates new antibodies.

Acquired immunodeficiency – Loss of an immune system component due to an external factor such as a nutritional imbalance or a pathogen.

Acquired immunodeficiency syndrome (AIDS) – A disease caused by the HIV retrovirus, which slowly undermines the immune system by destroying helper T cells.

Acquisition – When one company takes over another and clearly establishes itself as the new owner, the purchase – usually with stock, cash, or a combination of the two is called an acquisition. Legally, the target company ceases to exist, the buyer swallows’ the business, and the buyer’s stock continues to be traded.

Acrocentric – A chromosome having the centromere close to one end.

ACS – Acute coronary syndrome (ACS).

ACS cells – Adult cardiac stem cells.

AD – Alzheimer’s disease (AD).

Action potential – A moving wave of depolarisation (from negative to positive across the cell membrane) through a nerve caused by the rapid, lateral transport of Na+ and K+ ions through its membranes.

Activated sludge process – Processing biological stage in sewerage works where microorganisms metabolise organic pollution, helping to purify waste water.

Activation energy – The energy, in the form of heat or chemically stored energy, that is necessary to bring a reactant (substrate) to conversion to a new compound (product). The minimum energy required for the onset of a non-spontaneous chemical reaction. Activation energy can be visualised as the height of a barrier between two energy levels. Biocatalysts such as enzymes lower this barrier drastically.

Activation-induced cell death (AICD) – Apoptotic death of lymphocytes subjected to prolonged antigenic stimulation. A means of eliminating effector cells after they are no longer needed.

Activator proteins – Protein that switches a gene on.

Active immunisation – Administration of an immunogen to an individual whose own body is then responsible for activating the lymphocytes required to provide defense against future attacks.

Active site – Location on an enzyme where the reaction takes place. The active site of an enzyme contains the binding sites for the substrate and the active biocatalytic site. It is also often the site where an enzyme is inhibited. In such a case, inhibitor and substrate bind to the same site in a competitive way, e.g., acetylcholine (substrate) and nerve gas (inhibitor) and acetylcholine esterase. 

ActRII – Activin receptor; activin-ActR signaling is involved in control of cardiac-specific effector genes.

Acute cellular rejection (ACR) – A form of acute graft rejection in which allogeneic graft cells are destroyed by effector functions of recipient leukocytes.

Acute disease – A disease in which symptoms appear rapidly but remain for only a short time.

Acute graft rejection – Graft rejection occurring within days or weeks of a transplant. Can be cell-mediated (acute cellular rejection) or antibody-mediated (acute humoral rejection).

Acute hemorrhagic conjunctivitis – A corneal infection caused by coxsackievirus A-24 and enterovirus type 70 (single stranded RNA viruses) that includes subconjunctival bleeding. IgG levels are greatly elevated.

Acute humoral rejection (AHR) – A form of acute graft rejection due to production of antibodies directed against allo-MHC in the graft.

Acute inflammation – The first few days of an inflammatory process, characterised by the presence of large numbers of neutrophils.

Acute phase proteins – Early inflammatory proteins made by hepatocytes. Acute phase proteins bind to cell wall components of microbes and activate complement. See also inflammation.

ADA – Anti-Drug Antibodies (ADA) – an unwanted immune response against the pharmaceutical drug or biological that can negatively impact the product’s clinical safety and efficacy.

ADA gene – gene that encodes the enzyme adenosine deaminase (ADA).

Adaptive immune system – Immunity that develops upon exposure to antigens that results in the production of antibodies. Can be passive (movement of antibodies from mother to foetus) or active (production of antibodies by B cells to attack a foreign bacteria or virus).

Adaptive immunity- Host defense’s: either T cell-mediated or humoral, which is mediated by antibodies. Immunity in which the response adapts to the specific chemical properties of foreign antigens. Adaptive immunity is a system wherein somatic T cells and B cells are produced, each with a unique and characteristic immunoglobulin (in the case of B cells) or T-cell receptor (in the case of T cells). Through a complex presentation and selection system, a foreign antigen elicits the replication of a B cell that produces an antibody whose unique immunoglobulin attachment site matches the antigen. Antigen–antibody com- plexes may deactivate and clear circulating antigens or may lead to the destruction of the organism that carries the antigen (e.g., virus or bacteria). The process of producing unique proteins requires that recombination and hypermutation take place within a specific gene region. Recombinations yield on the order of about a billion unique somatic genes, starting with one germinal genome. This process requires the participation of recombination activating genes (RAGs). The acquisition of an immunologically active recombination activating gene is presumed to be the key evolutionary event that led to the development of the adaptive immune system, present in all jawed vertebrates (gnathostomes). In addition, a specialised method of processing immunoglobulin heavy chain mRNA transcript accounts for the high levels of secretion of immunoglobulin proteins by plasma cells. As one might expect, inherited mutations in RAG genes cause immune deficiency syndromes. See Intrinsic immunity and Innate immunity.

Adaptive response – An immune response mediated by uniquely specific recognition of a non-self entity by lymphocytes whose activation leads to elimination of the entity and the production of specific memory lymphocytes. Because these memory lymphocytes forestall dis- ease in subsequent attacks by the same pathogen, the host immune system has “adapted” to cope with the entity.

Adaptors (also called linkers) – A short double-stranded piece of DNA with know sequence that is added to the ends of DNA fragments.

ADCC – see Antibody Dependent Cellular Cytotoxicity (ADCC).

Addiction module – Set of genes that control cell death in bacteria such as Escherichia coli.

Adeno-associated virus (AAV) – A defective or satellite virus that depends on a helper virus e.g. adenovirus (or certain herpesviruses) to supply necessary functions.

Addressing – Cellular adhesion molecules expressed on high endothelial venules (HEVs) that mediate lymphocyte extravasation at particular sites in the body.

Adeno-associated virus (AAV) vectors – Vectors derived from adeno-associated viruses (AAV) and frequently used delivery systems in ocular gene therapy.

Adenohypophysis – The anterior pituitary gland, derived from the adenohypophysis placode, which contains cells that secrete a number of peptide hormones.

Adenosine deaminase – Enzyme involved in purine metabolism whose absence prevents development of B cells and T cells.

Adenosine triphosphate (ATP) – One of several high energy compounds found in cells. This one is the most practical for obtaining useful energy. The energy is contained in ATPs terminal phosphate groups.

Adenoviridae – non-enveloped viruses with an icosahedral (20 surface) capsid and linear dsDNA.

Adenovirus – A common dsDNA vector for gene transfer with a substantial cloning capacity (>30 kb) and high efficiency of transfection in vivo but limited by transient transgene expression and host immunogenic response. Medium-sized (90–100 nm), non-enveloped (without an outer lipid bilayer) icosahedral viruses composed of a nucleocapsid and a double-stranded linear DNA genome.

Adenovirus-36 (Adv36) – Strain of adenovirus that may potentially cause obesity.

Adenylate cyclase – Enzyme that synthesises cyclic AMP.

ADEPT – Antibody-directed enzyme/prodrug therapy (ADEPT). Therapy employing an immunoconjugate in which the monoclonal antibody is linked to an enzyme capable of converting an inert pro-drug into an active cytotoxic drug. Used for anticancer therapy.

Adherens junction – Cell–cell junction having transmembrane proteins called cadherins that connect to cadherins of epithelial cells through extracellular domains and to anchor proteins, known as catenins, through intracellular tails. Anchor proteins also bind to a continuous belt of actin filaments along cytoplasmic side of the cell plasma membrane, ultimately holding neighboring cells together.

Adherent cell lines – Cultured cells that grow attached e.g. to the culture dish.

Adhesin – Bacterial protein that binds to glycoproteins or glycolipids on animal cell surfaces.

Adipose tissue-derived stem cells – adipose tissue-derived SCs can differentiate into adipocytes and many cell types, including osteocytes and chondrocytes.

Adjusted present value (APV) – A variant of the net present value (NPV) approach that is particularly applied in cases when a company’s level of indebtedness changes or it has past operating losses that can be used to offset tax obligations.

Adjuvant (or carrier) – An agent used to increase the antigenicity of a vaccine. A substance added into an immunogen formulation (vaccine) to influence the host immune response. A substance that, when mixed with an isolated antigen, increases its immunogenicity. Adjuvants provoke local inflammation, drawing immune system cells to the site and triggering maturation of DCs. An adjuvant (from Latin, adiuvare- to aid) is a pharmacological and/or immunological agent that modifies the effect of other agents.

ADMA – Asymmetric dimethylarginine (ADMA).

ADOA – Autosomal-dominant optic atrophy (ADOA).

Adoptive transfer – The transfer of mature lymphocytes from one individual to another, most often by intravenous or peritoneal infusion.

ADP – Adenosine diphosphate (ADP).

ADP-ribose – Molecular fragment consisting of adenosine diphosphate plus ribose that is normally obtained by cleavage of NAD

ADP-ribosylation – Addition of ADP-ribose group to a protein, thereby altering its activity or completely inactivating it

Adrenergic – Referring to nerve fibers that use epinephrine or norepinephrine as a transmitter.

Adrenergic (sympathomimetic) drugs – Chemicals that mimic the effects of sympathetic nerve stimulation by stimulating adrenergic receptors and/or increasing the release of catecholamine’s (e.g, the alpha-I adrenergic agonists, phenylephrine and epinephrine)

Adrenergic receptors or Adrenoceptors – Receptors for adrenergic agents, found on cells that are affected by adrenergic drugs. Members of the G-protein-coupled receptor superfamily, linking adrenergic signaling from the sympathetic nervous system and the cardiovascular system with integral roles in the rapid regulation of myocardial function.

Adult Stem Cells (ASCs) – A collection of cells isolated from adult somatic tissues that are able to divide indefinitely, remain undifferentiated, but have the ability to differentiate into specialised cells of the organ or tissue in which they are originally derived. Stem cells present in a tissue or organ after birth; for example, blood stem cells from the bone marrow or intestinal stem cells in the crypts of the gut. This type of stem cell is usually multipotent, not pluripotent.

Advanced glycation end products (AGEs) – The terminal products formed from reactions between proteins and glucose. See also Glycation.

Advanced maternal age (AMA) A designation given to a woman who gives birth at or over the age of 35.

Advanced therapies – Drug and therapeutic strategy produced from a biological source. Cell therapy and tissue engineering are part of innovative therapies and produce advanced therapy medicinal products (ATMPs).

Advanced therapy medicinal products (ATMPs) – Set of medications formerly known as biological drugs, which include products derived from genetic therapy, somatic cell therapy and tissue and cell engineering.

Advanced therapy medicinal products prepared on a non-routine basis (ATMP-pnrb) – The manufacture of which is authorised by the Member State of the European Union and specially designed for a given patient.

Adverse drug reaction (ADR) – Term used to describe serious side effects or lack of drug efficacy in certain patients

Adverse event (AE) – aka Adverse Experience, any untoward medical occurrence that may present itself during the study or following treatment or administration of a pharmaceutical product, and which may or may not have a causal relationship with the treatment. Detrimental side effect associated with administration of a medicine. Something that follows the receipt of a product which is unintended and unwanted. An AE may or may not be caused by the product (relationship) and may be mild, moderate, severe, life-threatening, or result in death (severity or grade). The AE may or may not be serious. The AE may or may not resolve, e.g., it may be self-limiting or it may cause a condition that does not resolve.

Adverse reaction – An unwanted or harmful side effect experienced following the administration of a drug or combination of drugs and is possibly or suspected to be related to the drug.

Aedes aegyptiA mosquito species that transmits yellow fever.

Aequorin – A protein from the luminescent jellyfish Aequorea victoria that emits blue light when triggered by calcium ions.

Aerobes- Organisms that need oxygen from the air (O2) for survival.

Aerobic metabolism – Any metabolic process that requires molecular oxygen.

AF – 1) Transcriptional activation function domain. 2) Atrial fibrillation, the most common dysrhythmia seen in clinical cardiology, can be familial, with both monogenic and more heterogeneous genetic cases reported.

Afferent – Leading to, e.g., an artery supplying an organ is afferent.

Afferent lymphatic vessel – A vessel that conveys lymph into a lymph node.

Affinity – A biochemical value (represented as an equilibrium constant, Kd) that describes how tightly a ligand and target bind to each other. A measure of the strength of the association established at a single point of binding between a receptor and its ligand. For an antibody, the strength of the non-covalent association between a single antigen-binding site on the antibody and a single epitope on an antigen.

Affinity chromatography – Highly specific chromatography separation method, where the substances to be purified in the columns are specifically recognised (bound) by antibodies or in the case of enzymes to be purified-based on specific affinities to ligands such as substrates, inhibitors or cofactors- on the stationary phase.

Affinity HPLC – Chromatography technique in which the stationary phase has a binding site for a specific molecule (e.g., an antibody to a particular protein).

Affinity maturation – Positive selection of developing B cells with BCRs that have undergone somatic hypermutation resulting in increased affinity for specific antigen. Memory cells with this increased affinity for antigen are generated.

Affinity tag – Biochemical indicator that appended to recombinant expressed proteins can serve several functions, e.g., purification of proteins, solubilization of a fusion partner, and indicator of fusion protein folding, and providing a common epitope to allow a single antibody to recognise each fusion protein.

Aflatoxin – A naturally occurring toxic metabolites produced by Aspergillus species that are associated with various diseases and have been shown to cause cancer in animals.

AFM – Atomic force microscopy (AFM); can determine cellular mechanical property changes at nanoscale resolution.

After-market performance – The price level of a newly issued stock after its initial public offering (IPO). After-market performance begins on the first day of trading on the exchange. Typically, the after-market performance is measured through the lockup period, which usually ranges between three and nine months after the IPO date. This allows for the market to digest the insider shares that might be sold quickly after the lock-up period expires. To the company management and its employees, the after-market performance is vital. If the company can reach and sustain a higher market valuation than originally estimated by the underwriting syndicate in open market trading, equity fundings will be better affordable than other methods of raising capital.

A-form – An alternative form of the double helix, with 11 base pairs per turn, often found for double-stranded RNA, but rarely for DNA.

Against-the-rule – Ocular astigmatism in which the meridian with greater optical power in the eye is horizontal.

Agarose – A polysaccharide from seaweed that is used to form gels for separating nucleic acids by electrophoresis.

AGE – Advanced glycation end product.

Age-adjusted incidence – An age-adjusted incidence is the crude inci- dence of disease occurrence within an age category (e.g., age 0–10years, age 70–80 years), weighted against the proportion of persons in the age groups of a standard population. When we age-adjust incidence, we cancel out the changes in the incidence of disease occurrence, in different populations, that result from differences in the proportion of people in different age groups. For example, suppose you were comparing the incidence of childhood leukemia occurrences in two populations. If the first population has a large proportion of children, then it will likely have a higher number of childhood leukemia in its popula- tion, compared with another population with a low proportion of children. To determine whether the first population has a true, increased rate of leukemia, we need to adjust for the differences in the proportion of young people in the two populations. See Incidence.

Age-related macular degeneration (AMD) – An eye disease with its onset usually after age 60 that progressively destroys the macula, the central portion of the retina.

Agenesis – Agenesis is the complete absence of an organ or lack of specific cells within an organ (e.g., lack of germ cells in “Sertoli cell only syndrome”).

Agglutination – Aggregation of cells to form a visible particle.

Aggregate – A collection of proteins whose shape and bonding are not well defined.

Aggressive gene therapy – Therapy of cancers or infections by introducing genes or gene products that act to kill cancer cells or infectious agents.

Aging (or ageing) – A chronic degenerative process that occurs in cells that have lost the ability to divide, while retaining their functional obligations. Such cells include neurons, chondrocytes (i.e., cartilage cells), muscle cells, and cells of the eye lenses. Cells that maintain the ability to divide, indefinitely, such as epithelial lining cells of ducts, mucosal surfaces, glands, and epidermis do not suffer from the degenerative changes associated with aging cells (i.e., nobody dies from an old colon or an old liver). For the purposes of this book, aging is considered a disease differing from other diseases only in its inevitability.

Agonist – Any chemical substance that can act in place of a neurotransmitter; that is, it binds to the same postsynaptic receptor. It refers to a chemical that binds to some receptor of a cell and triggers a response by that cell.

Agouti – Brown coat color in mice due to a dominant allele.

Agrin – A protein known to attach to heparin sulfate in the chick vitreous. Its role in human vitreous has not been studied.

A-Helix – A secondary protein structure in which the amino acid structure forms a helical form having 3.6 amino acids per turn. The helical structure is reinforced by hydrogen bonding.

AHU – Air handling unit (AHU).

AID family – The activation-induced cytidine deaminase family, an enzyme family implicated in DNA methylation. AID plays a central role in mediating somatic hyper mutation and class-switch recombination, processes responsible for antibody diversity in B lymphocytes.

AIDS – Acquired immunodeficiency syndrome (AIDS). Failure of adaptive immunity due to T cell destruction caused by HIV retrovirus infection. A disease caused by the HIV slowly undermines the immune system by destroying helper T cells. 

AIF – Apoptosis-inducing factor (AIF). Released from mitochondrial intermembrane space in early apoptosis and subsequently involved in nuclear DNA fragmentation.

Airway stenosis – Fibrotic airway narrowing.

AKAP – Specific PKA anchoring proteins; regulators of PKA function and signaling by directing and concentrating PKA at specific subcellular sites.

AKIP – A-kinase-interacting protein (AKIP).

Akt – A serine/threonine kinase that inhibits members of the apoptotic pathway by phosphorylating them. Protein kinase B (PKB). Myocardial Akt phosphorylates a number of downstream targets, including cardio protective factors involved in glucose and mitochondrial metabolism, apoptosis, and regulators of protein synthesis.

Ala (of nose) – The soft, fleshy side of the nose.

Ala (plural Alae) – Commonly referred to as the nostril in lay terminology, it is the crescent-shaped convexity just lateral to the nasal tip.

Alacrima – Deficiency or absence of tear production.

Alagille syndrome – An autosomal-dominant disorder caused by dominant mutations in the JAG1 (JAGGED1) gene, which encodes the NOTCH receptor 1 ligand JAG1 leading to defective NOTCH signaling. It is characterised by a highly variable liver disease in conjunction with cardiovascular, skeletal or ocular anomalies   or typical facial features. More than 90% of affected patients have cardiovascular abnormalities, including peripheral pulmonary hypoplasia, TOF, and pulmonary valve stenosis, whereas left-sided lesions and septal defects are less common. These cardiovascular anomalies are responsible for a high morbidity and mortality in individuals with Allagille syndrome.

ALCAR – Acetyl-l-carnitine; supplementation with lipoic acid (LA) appears to improve myocardial bioenergetics and decrease oxidative stress associated with aging.

ALDH2 – Aldehyde dehydrogenase 2.

Algorithm – A step-by-step method for solving a computational problem.

Aligned (In reference to DNA sequence comparison) – Matching the most similar DNA sequences between two or more different genes

Alkaline phosphatase – An enzyme that cleaves phosphate groups from a wide range of molecules.

Allele – One particular version of a gene, or more broadly, a particular version of any locus on a molecule of DNA.

Alkylating agents – Chemicals that form covalent alkyl bridges with nucleic acid bases.

Allee-type model – Population growth model that incorporates existence of a viability threshold. If the population size falls below this threshold, it tends to zero; if it is above the threshold, the population behaves like a logistic model.

Allele – An alternate form of gene present at a particular locus on chromosome. One of a pair of matched genes on paired chromosomes, wherein each of the matched genes is a variant of the other (i.e., each is a different allele of the gene). In most cases one allele comes from the father, the other from the mother. One of several alternate forms of a single gene occupying a given locus on a chromosome or mtDNA. A variant of a gene located at a certain locus. Two slightly different sequences of the same gene. Proteins produced from alleles have the same function.

Allelic exclusion – Cessation of somatic recombination in a second allele of an Ig locus due to productive reco bination in the first allele.

Allelic heterogeneity- Different alleles for one gene. Occurs when different mutations within the different alleles of a gene can yield the same clinical phenotype. For example, hundreds of different alleles of the cystic fibrosis gene can yield the same phenotype. Additionally, a study of 424 families with members affected by hemophilia B found 167 different allelic mutations of the disease gene [5]. Allelic heterogene- ity should not be confused with two diseases being allelic to one another. When two biologically distinct diseases are caused by different mutations in the same gene, the two diseases are said to be allelic to one another. See Locus heteroge- neity and Phenotypic heterogeneity.

Allelic to – One genetic disease is allelic to another genetic disease if both are caused by mutations of different alleles of the same gene (i.e., in different inherited forms of the gene). For example, distal myopathy with rimmed vacuoles is allelic to hereditary inclusion body myopathy. Each results from a different loss-of-function mutation in different alleles of the gene encoding UDP-N- acetylglucosamine 2-epimerase/N-acetylmannosaminekinase . Whenever a gene associated with two or more distinct diseases is mapped to the same physical location in the genome, then the cause of the diseases may be due to allelic variation, or to contiguous gene defects (i.e., defects in several genes located in close proximity to one another). See Phenotypic heterogeneity.

Allergen – An antigen that is innocuous in most individuals but provokes type I hypersensitivity in some. An antigen which causes allergy.

Allergy – A form of immediate hypersensitivity disease. Clinical manifestation of type I hypersensitivity. Mediated by mast cells armed with allergen-specificIgE

Alloantibodies – Antibodies distinguishing between the different forms of a protein encoded by different alleles of a given gene. Often refers to antibodies specific for MHC molecules.

Allogeneic – A situation in which the donor and the recipient are from the same species but a genetically distinct person. Tissues or cells derived from an organism from the same species, but may not be identically matched. Foreign to the own body; in the case of an allogenic transplantation, the transplanted tissues or cells are genetically different from the recipient.

Allogeneic bone – Another person’s bone tissue.

Allogenic TransplantationThe donor is an HLA matched family member, unrelated matched donor or mismatched family donors (haploidentical).

Allogeneic or Allogenic – Having different alleles at one or more loci in the genome compared with another individual of the same species.

Allograft – Tissue transplanted between allogeneic members of the same species.

Alloimmunity – A condition in which the body gains immunity, from another individual of the same species, against its own cells.

Allorecognition – Recognition of allelic differences expressed by cells of one individual by the lymphocytes of another individual. Most often refers to recognition of MHC-encoded differences.

Allosteric enzyme – An enzyme whose activity is influenced by substances that bind at alternate sites.

Allostery- (Greek allos for ‘other’ and stereos for ‘structure’, describing a distinct place/site: A type of enzyme regulation whereby the regulating substance binds to the enzyme outside the active site.

Allotopic expression – Alternative method of mitochondrial gene therapy in which a mitochondrial gene is reengineered for expression from the nucleus and target- ing its translation product to the mitochondria.

Alpha (α) factor – Yeast mating factor that acts as a pheromone, attracting yeast cells of the opposite mating type.

Alpha complementation – Assembly of functional β-galactosidase from N-terminal alpha fragment plus rest of protein

ALS – Amyotrophic lateral sclerosis (ALS).

Alternative complement activation – Activation of the complement cascade initiated by direct binding of complement component C3b to a stabilizing ligand on a microbe. Involves cleavage and activation of Factors B and D and properdin.

Alternative Investment Market (AIM) – A Stock market regulated by the London Stock Exchange for young, high-growth companies.

Alternative RNA splicing – A normal mechanism whereby one gene may code for many different proteins. In humans, about 95% of genes that have multiple exons are alternately spliced. It has been estimated that 15% of disease-causing mutations involve splicing. Cancer cells are known to contain numerous splicing variants that are not found in normal cells. Normal cells eliminate most abnormal splicing variants through a post-transcriptional editing process. Alternative RNA splicing may result from mutations in splice sites or from spliceosome disorders. In hereditary thrombocythemia, characterised by an overproduction of platelets, there is a mutation in the gene coding for thrombopoietin protein. Wiestner and cowork- ers have shown that the gene mutation leads to mRNAs with shortened untranslated regions that are more efficiently translated than the transcripts that lack the muta- tion. This causes the overproduction of the thrombopoietin, which in turn induces an increase in platelet production. See also Spliceosome. A regulatory mechanism by which variations in the incorporation of coding regions (see Exon) of the gene into messenger RNA (mRNA) lead to the production of more than one related protein or isoform. The differential processing of pre-messenger (nuclear) RNA transcripts involving exon and intron sequences. The process of forming different mRNAs from a single gene by joining different combinations of exons.

Alternative splicing library – Library of gene or protein sequences generated by randomised inclusion or exclusion of exons from an original protein

Alternatives to study participation – In a protocol, the section that offers alternative standard clinical procedures or treatments potentially advantageous to the subject, including those of no further aggressive intervention and that may include mention of participation in other clinical trials.

Altruism – A person’s unselfish regard for the benefit of others, assumed to be the reward of research participants.

Alu element – An example of a SINE, a particular short DNA sequence found in many copies on the chromosomes of humans and other primates

Alu repeat (or sequence) – One of a family of about 750,000 inter- spersed sequences in the human genome that are thought to have originated from 7SL RNA gene.

Alu-PCR – A polymerase chain reaction (PCR) reaction that uses an oli- gonucleotide primer with a sequence derived from the Alu repeat.

Amadori rearrangement – Early stage binding of glucose to an amino group on a protein. The relatively stable product formed is a ketamine. These are the initial reactions of glycation.

Amantadine – Antiviral agent that blocks ion channels found in the outer envelope of influenza A virus.

Ambisense – Type of single-stranded RNA genome that contains both positive and negative sense portions.

Amblyopia – Lazy eye with poor vision because of misalignment of the eyes during development.

AMD– see Age-related macular degeneration.

Ameloblasts – Epithelial cells producing dental enamel.

AMI – Acute myocardial infarction (AMI).

AMIA – The American Medical Informatics Association (AMIA).

Amino acid (AA) – A chemical subunit of a protein. Amino acids polymerise to form linear chains linked by peptide bonds called polypeptides. All proteins are made from 20 naturally occurring amino acids. A simple organic acid in which an NH2 replaces one of the hydrogen atoms. An acid containing at least one amino group linked to the carbon adjacent to its carboxylic acid (a-carbon). A class of biological molecules characterised by an amine and carboxylic group along with a particular functional group. They are the main building blocks of proteins and have other important biological functions.

Amino acid sequence – Refers to the order of amino acids in a polypeptide chain.

Aminoacyl tRNA synthetases – Enzyme that attaches an amino acid to tRNA aminopeptidase A protease that removes amino acids from a polypeptide chain starting at the amino-terminal end

Amniocentesis – Procedure for drawing samples of amniotic fluid, for analysis, that contains some foetal cells.

AMP – Adenosine monophosphate (AMP).

AMP-activated kinase (AMPK) – Kinase that signals nutrient scarcity by activating cellular uptake of glucose with other energy producing processes and is implicated in aging

Amphipathic – Literally means having two characteristics. For lipids this means being both hydrophobic (i.e., not compatible with water) and hydrophilic (i.e., compatible with water). Molecule with distinct hydrophobic and hydrophilic domains (e.g., phospholipids and detergents).

Amphiphilic – Of or relating to a molecule having a polar, water-soluble group attached to a non-polar, water-insoluble hydrocarbon chain.

AMPK – AMP-activated protein kinase involved in myocardial metabolic energy sensing.

Amplicon – An amplified fragment of DNA.

Amplification – Generation of many copies of a specific region of DNA.

Amplification plot – Used in real-time PCR, a graph that shows the amplification of DNA compared to the cycle number.

Amplification refractory mutation system (ARMS) – An allele- specific PCR amplification reaction; commonly used for carrier detection, for example cystic fibrosis.

Ampulla – The swollen end of a branch that will give rise to new branches.

Amyloid – It refers to the insoluble fibrous “protein aggregates” sharing specific structural traits.

Amyloid β – A peptide fragment of a protein found in neuritic senile plaques amyloid aggregateInsoluble clump of misfolded proteins found in several disease conditions including Alzheimer’s and prion disease.

Amylopectin – Branched component of starch.

Amylose – Linear component of starch.Amylose is unbranched while amylopectin is branched, but to a lesser degree than glycogen.

Amylose/amylopectin – Polysaccharide components of starch.

Anabolic process – One or more chemical reactions in which energy is used to carry out cellular functions. For example, the synthesis of proteins.

Anabolism – Metabolic pathways that lead to the construction of molecules from smaller units while using energy. Opposite of catabolism.

Anaerobic metabolism – Any metabolic process that does not require molecular oxygen.

Anakinra – Synthetic form of the natural antagonist IL-1Ra that binds to IL-1R and blocks its function, reducing inflammation.

Analyte – Mixture of molecules (such as proteins) that is being studied by chromatography

Anaphylactic shock – Also known as anaphylaxis, is a strong immune reaction that results in a marked blood vessel dilation and smooth muscle constriction that may result in death.

Anaphylatoxins – Biochemical substances capable of causing severe immunological reactions.Complement component cleavage products that have pro-inflammatory and chemoattractant effects; includes C3a, C4a and C5a. A substance which can trigger mast cell degranulation and smooth muscle contraction.

Anaphylaxis – A type of acute severe type I hypersensitivity allergic reaction. The term comes from the Greek word ana “against,” and phylaxis “protection.”Systemic type I hypersensitivity response that may be fatal due to a catastrophic drop in blood pressure induced by the release of large quantities of inflammatory mediators. It’s a  severe allergic reaction that causes effects on the body such as hives, difficulty breathing, vomiting, diarrhea, or shock.

Anastomosis – A direct connection between an arteriole and a venule without an intervening capillary bed. Surgical connection of two tubular structures. A network of streams that both branch out and reconnect forming a communication between two blood vessels or other tubular structures.

Anatomical barrier – Body structure supplying non-specific, non-induced innate defence, such as intact skin.

Anchorage independence – The property of a cell that has lost its requirement to adhere to a substrate.

Anderson syndrome – Also known as Anderson-Tawil syndrome or LQT7; an autosomal-dominant disorder characterised by  a  heterogeneous  phenotype  including a variety of cardiac dysrhythmias, with many patients having mutations in the KCNJ2 gene coding Kir2 subunit of the K+ voltage-dependent channel.

Anencephaly – A neural tube defect (NTD) that results from failure of neurulation in the cephalic region, and characterised by the absence of a large part of the brain and overlying skull.

Aneuploidy – Abnormal chromosomal number. The state in which one or more extra or missing chromosomes are present. The presence of an abnormal number of chromosomes (for the species) in a cell. Most cancers contain aneuploid cells; an observation that holds true for virtually every poorly differentiated cancer. Aneuploidy is seen less often in benign tumours and well-differentiated tumours. Aneuploidy is also found in epithelial precancers and other growing lesions that can some- times regress spontaneously (e.g., keratoacanthoma). These observations have prompted speculation that chromosomal instability and the acquisition of aneuploidy is an underlying cause of the cancer phenotype (i.e., tumour growth, invasion into surrounding tissues, and metastases). Such causal associations invite skepticism, particularly in the realm of cancer biology, as virtually every cel- lular process and constituent of cancer cells has been shown to deviate from the norm. Nonetheless, there is good reason to suspect that aneuploidy is at least a factor in tumour development, as mutations that cause aneuploidy are associated with a heightened risk of cancer (e.g., Brca1 gene mutations and mutations of mitotic checkpoint genes. Others have warned that aneuploidy, by itself, may not cause cancer. Aneuploidy may need to be accompanied by other factors associated with genetic instability, such as the accumulation of DNA damage, cytogenetic abnormalities, and reduced cell death. As usual, a rare disease helps to clarify the role of aneuploidy in carcinogenesis. Mosaic variegated aneuploidy syndrome-1 (MVA1) is caused by a homozygous or com- pound heterozygous mutation in the BUB1B gene, which encodes a key protein in the mitotic spindle check point. This disease is characterised by widespread aneuploidy in more than 25% of the cells of the body, and a heightened risk of developing childhood cancers (e.g., rhabdomyosarcoma, Wilms tumour, and leukaemia). Because the underlying cause of mosaic variegated aneuploidy syndrome-1 is a gene that produces aneuploidy, and because such aneu- ploidy is an early event (i.e., congenital) that precedes the development of cancer and that is found in the developed cancer cells, then it is reasonable to infer that aneuploidy is closely associated with events that lead to cancer. See Mutator phenotype, Carcinogenesis, Cytogenetics, and Karyotype.

Aneurysm – A sac-like protrusion from a blood vessel or the heart, resulting from a weakening of the vessel wall or heart muscle.

ANF – Atrial natriuretic factor (ANP).

Ang II – Angiotensin II.

Angel investor (US)/Business angel (UK) – A wealthy individual who invests in young, high-growth entrepreneurial companies. Although angels can sometimes perform functions identical those of venture capitalists (e.g., through advice, contacts, or hands-on work), they usually invest their own capital rather than that of institutional investors. Individuals and entities that primarily invest their own money in new start-up firms.

Angelmans syndrome – Inherited defect resulting in loss of function of genes on the maternally derived copy of chromosome 15 that are subject to imprinting

Angioblast – Mesenchymal tissue that differentiates into blood cells and vascular endothelium. Mesoderm-derived endothelial precursors that have certain characteristics of endothelial cells but that have not yet assembled into functional vessels.

Angiogenesis – Formation of new vessels from preexisting ones, and in particular the sprouting of new capillaries from post capillary venules. Process by which new blood vessels are formed. The formation of new blood vessels from pre-existing vessels by endothelial sprouting and splitting. This process of remodelling the primary capillary network leads to the formation of mature arteries and veins. The formation of new vessels. Angiogenesis in the adult organism always refers to the growth of small vessels, not arteries and veins. The large vessels in the human body develop in utero. Tumour cells must receive oxygen from blood; hence, every invasive and growing solid tumor is capable of inducing angiogenesis. As the tumour grows, so do the vessels feeding the tumor. The vessels arise from non-neoplastic connective tissue and are induced to grow by angiogenesis factors secreted by the tumor cells.

Angiogenesis regulators – Growth factors and cytokines involved in formation of new blood vessels. These include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), thrombospondin 1 (TSP-1), platelet factor 4 (PF-4), among others. Angiogenesis regulators can act as stimulators or inhibitors of blood vessel formation.

Angiogenic factor – A factor that stimulates the growth of new blood vessels.

Angiomatous – Relating to a tumour consisting of a mass of blood vessels.

Animal research – Research involving whole animals, living or dead, and research on biological materials from animals.

Aniridia – Congenital disorder characterised by the abnormal deficient development of the iris and associated with corneal angiogenesis and poor vision.

Anisometropia – A condition in which the two eyes have unequal refractive power so that the two eyes are in different states of myopia.

Anisotropic substrates – Surfaces that have a regular pattern. Although cells typically grow on native basement membranes with isotropic surfaces, investigation of cellular responses to repeating biophysical cues are often useful as initial studies.

Ankyloblepharon- The interrupted, partial, or complete fusion of the upper and lower eyelids by webs of skin.

Annotation – The descriptive text that accompanies a sequence in a data- base method.

Annual Report – 1) A submission to a regulator reporting annual updates on clinical trials or a marketed product or to an ethics committee (IRB) reporting the status of an ongoing clinical trial. Annual Reports have a required format and content, and timing of submission to the regulator or IRB. 2) A company’s yearly report to shareholdersdocumenting its activities and finances in the previous financial year.

Annulus – The ring around a heart valve where the valve leaflet merges with the heart muscle.

Anomaly – An anatomical departure from the phenotype present in the reference population.

Anonymous variation – A genetic variation for which there is no change in gene function. Today, the bulk of the 3billion base-pair sequence comprising the human genome cannot be assigned to any particular function; a randomly occurring mutation is likely to be anonymous; hence, it is assumed that most SNPs are anonymous. Other commonly encountered anonymous markers include the microsatellites, for which there occur variations in the length of repeated sequences within the microsatellites, but these variations cannot be assigned to a gene or to a particular function. Mutations that occur in somatic, post-mitotic cells (i.e., cells that will never divide) are, for all practical pur- poses, anonymous and undetectable. A mutation must be passed to a population of progeny cells before it can do much damage and before it can be detected by current molecular biological techniques. Some types of mutations are difficult to find, even when they occur in large numbers of cells. For example, when a mutation is a duplicated exon, the alteration cannot be detected by methods that find base sequence alterations.

Anopheles gambiae – A mosquito species that transmits malaria.

Anophthalmia – The unilateral or bilateral absence of ocular tissue secondary to the abnormal development of the optic vesicle.

Anosmia – Loss of smell.

ANP – Atrial natriuretic peptide. See also Atrial natriuretic factor (ANF).

ANRIL – Antisense noncoding RNA in the INK4 locus is transcribed from the INK4b/ARF/INK4a tumor suppressor locus; it serves as a scaffold for the chromatin repressor PRC1 and PRC2 complexes. Interaction between ANRIL and components of both PRC1 and PRC2 is essential for transcriptional repression of the INK4 locus.

ANT – Adenine nucleotide translocator. A mitochondrial inner membrane carrier protein of ADP and ATP and constituent of the mitochondrial permeability transition pore (MPTP).

Antagonist – Any chemical substance that can bind to the same postsynaptic receptor of a given neurotransmitter without causing any postsynaptic effect.

Anterior chamber-associated immune deviation (ACAID) – see ACAID.

Anterior visceral endoderm (AVE) – A population of visceral endoderm cells found in the anterior region of the conceptus, opposite the primitive streak at mouse E6–E6.5, and characterised by the expression of a specific gene repertoire including Hhex, Hesx1, Cer1 and Lefty1. The AVE is formed after cells of the distal visceral endoderm (DVE) have moved, thus breaking the radial symmetry of the egg cylinder. This population is heterogeneous as shown by distinct gene expression in medial and lateral domains, but also dynamic in nature, as its cellular composition changes during the general movement of the Visceral Endoderm (VE) which occurs between mouse E5.5 and E6.5.

Anterograde transport – The transport of virions from a nerve cell body back to the termini of the axon within the tissue.

Anthers – In flowering plants, the pollen- producing organs.

Anthrax – Virulent bacterial disease of cattle that readily infects humans and is caused by Bacillus anthracis.

Anti-angiogenic factor – A factor that inhibits the growth of new blood vessels.

Anti a Shine–Dalgarno sequence – Sequence on 16S rRNA that is complementary to the Shine–Dalgarno sequence of mRNA

Antibiotics – Substances or compounds that inhibit the growth of bacteria (bacteriostatic) or kill bacteria (bactericides and bacteriolytics) that are widely applied in medicine. Antibiotics are often produced by microorganisms, giving them a potential selective advantage over their food competitors.

Antibodies – aka immunoglobulins are proteins that are part of the immune system. They bind noncovalently and specifically to their particular antigens. They are highly variable, which increases the probability that a suitable antibody to any antigen can develop. The economic role of antibodies in biotechnology is considerable, as they are used in treatment (e.g., targeted drug administration with monoclonal antibodies in cancer therapy as well as analytics (e.g., in affinity chromatography). Proteins of the immune system that recognise and bind to foreign molecules (antigens). A globulin protein produced by immune cells that combines with antigenic compounds. A protein that bind to an antigen. Also known as an immunoglobulin (abbreviated- Ig), which usually reacts with a foreign molecule (i.e., antigen) within body tissues and fluids. An adaptor molecule which has a region specific for a particular antigen or micro-organism, and a region specific for receptors on host cells Secreted immunoglobulin that is produced by B lineage plasma cells and binds to specific antigens. Able to recognise antigens that are either soluble, or fixed in a tissue or on a cell surface. An immunoglobulin, or specialised immune protein, produced by special white blood cells to bind and neutralise a foreign substance, or antigen, introduced Biotech Funding Trends  Insights from Entrepreneurs and Investors. Bacteria, viruses, and other invaders stimulate the production of antibodies.

Antibody diversity hypothesis – A hypothesis that states that there are genes to produce antibodies for every known antigen. The hypothesis fails to account for the appearance of new antigens or antigenic determinants.

Antibody-dependent cell-mediated cytotoxicity (ADCC) – An immune effector function that occurs when entities too large to be internalised are coated with antibodies which then bind to the FcRs of lytic cells such as NK cells or eosinophils, triggering degranulation and destruction of the entity. The ability of natural killer
cells and cytotoxic lymphocytes to induce apoptosis in a cell that has already been coated by antibodies.

Anticipation – A phenomenon in which the age of onset of a disorder is reduced and/or the severity of the phenotype is increased in successive generations. That is, the phenomenon by which an offspring develops an inherited disease at a younger age than the age at which the parent developed the disease. In most cases, anticipation is associated with an expansion of the trinucleotide repeat in the inherited gene causing the disease. The expansion of trinucleotide repeats is a common occurrence within the genome, and may have any of sev- eral consequences: (1) producing disease via a gain-of-function mutation within a gene coding for a protein (e.g., Huntington disease); (2) producing disease via a loss-of-function mutation (e.g., myotonic dystrophy); (3) producing anticipa- tion in a pre-existing disease-causing gene, possibly by altering the level of expression; and (4) producing no discernible biological effect. Examples of diseases that may display anticipation include: Behçet’s disease, Crohn dis- ease, dyskeratosis congenita, fragile X syndrome, Friedreich ataxia (rare cases), Huntington disease, myotonic dystrophy, and spinal cerebellar ataxias (several forms). Why such expansions occur is not well understood.

Anticodon – A three-base code on t-RNA that corresponds (i.e. binds) to the codon on mRNA for a specific amino acid i.e. group of three complementary bases on tRNA that recognise and bind to a codon on the mRNA.

Anti-dilution provision – The right of current shareholders to maintain their fraction of ownership in a company by buying a proportional number of shares of any future issue of common stock. It therefore protects an investor from dilution resulting from later issues of stock at a lower price than the investor originally paid.

Antigen – A molecule that is perceived by the immune system to be foreign. A molecule recognised by receptors expressed by T cells (TCR) and B cells (immunoglobulin). A substance (protein or carbohydrate) capable of eliciting an immune response, either antibodies or reactive cells. An agent capable of stimulating an immune response. A specific antigen is an agent capable of being recognised by an antibody or T cell.Any substance that will cause an antibody to be produced against it and to which it will bind.Entity (such as an element of an infectious pathogen, cancer or inert injurious material, or of a self-tissue) that can bind to the antigen receptor of a T or B cell. This binding does not necessarily lead to lymphocyte activation. A substance that enters the body and stimulates the production of an antibody to fight what the immune system perceives as an invader. Proteins, carbohydrates, lipids, or other substances to which antibodies or lymphocyte receptors bind specifically (which leads to the formation of antibodies to the antigen in question). 

Antigen capture immunoassay – Method of protein detection where an antibody is linked to a solid support and captures its cognate protein from a mixture

Antigen presentation – Cell surface display of peptides in association with either MHC class I or II molecules allows T cell recognition of antigenic peptides on the surface of target cells or APCs, respectively. The presentation of antigen within an MHC molecule to a T cell.

Antigen-presenting cell (APC) – A cell that displays foreign antigen complex with major histocompatibility complex on its surface.

Antigen processing – Degradation of a protein into peptides suitable for binding in the peptide binding grooves ofeither MHC class I or II molecules.

Antigen receptor – A cell surface receptor that recognises an antigen.

Anti-gene – Gene that gives a full-length antisense RNA when transcribed

Antigenic determinant – The exact chemical site at which an antibody binds to an antigen (also known as an epitope).

Antigenic drift – It refers to a mechanism for variation that involves the accumulation of mutations within the genes that code for antibody-binding sites. Subtle modification of pathogen antigens through random point mutations. Usually involves surface proteins that would normally be the target of neutralising antibodies. Dramatic modification of viral antigens due to reassortment of genomic segments of two different strains of a virus (that simultaneously infect the same individual) to generate progeny visions with new combinations of genome segments and thus new proteins. It refers to the process by which two or more different strains of a virus combine to form a new subtype having a mixture of the surface antigens of the two or more original strains.

Antigenic shift – A major change in the surface proteins of a virus (e.g. influenza) caused by the reassortment of genomic segments from two viral (e.g. influenza) subtypes.

Antigenic variation– Changes within the surface proteins of a pathogen that prevent them from being recognised by previously formed antibodies.

Antigen-presenting cell (APC) – An immune cell that presents antigenic peptides (epitope) in the context of MHC to T lymphocytes. DC cells, macrophages, and B lymphocytes are said to be “professional APCs.” Cell expressing MHC class II and thus capable of presenting peptides to CD4+ Th cells.

Antigenome – The complementary copy of the complete sequence of a DNA or an RNA genome.

Antihistamines – Agents which block histamine receptors in tissues. Primary role is in the treatment of allergic diseases involving IgE-mediated hypersensitivity reactions.

Antimycin – A specific inhibitor of complex III activity.

Anti-oncogene – Gene that acts to prevent unwanted cell division (same as tumour-suppressor gene).

Antiparallel – Parallel, but running in opposite directions.

Antiport – Transport of substances in opposite directions.

Antisense – (or noncoding) The strand of DNA that has complementary sequence to mRNA

Antisense- DNA oligonucleotide – Short antisense DNA.

Antisense DNA – Single-stranded DNA with a sequence complementary to a specific target molecule of DNA or RNA, usually mRNA; binding of mRNA by antisense DNA may block its translation

Antisense RNA – RNA complementary in sequence to messenger RNA and that therefore base- pairs with it. RNA complementary to a specific transcript of a gene that can hybridise to it and block its function.

Antiserum – The clear liquid (serum) fraction of clotted blood containing antibodies produced when an individual or animal is exposed to a foreign substance or infectious agent.

Antiterminator proteins – Protein that allows transcription to continue through a transcription terminator

Antitoxins – Antibodies made against bacterial exotoxins and endotoxins.

Antiviral state – A metabolic state of viral resistance induced in a cell by exposure to interferons released by neighboring virus-infected cells.

AP – Action potential.

AP1 – Activator protein 1; a transcription factor.

AP-1 (activator protein-1) – Eukaryotic transcription factor that activates a variety of different genes

Apaf – Apoptotic protease-activating factor.

APC – Anesthetic preconditioning; 2) Adenomatosis polyposis coli. 3) Antigen-presenting cell (APC)

APC/C – Anaphase-promoting complex (also known as the cyclostome); ubiquitylates cyclins at specific time points in the cell cycle, targeting them for degradation by the 28 S proteasome.

APD – Action potential duration.

APHMG – Association of Professors of Human and Medical Genetics.

API – Active Pharmaceutical Ingredient (API) – the component of a product that is responsible for its activity and efficacy. A drug product may contain one or more APIs.

API – Application program interface (API).

Apical – The side of a cell that faces the lumen of a body cavity or tube.

Apical constriction – A process by which contraction of the apical surface of neural epithelial cells results in the cell taking on a wedge shape. Apical constriction is essential for hinge point formation during neural fold elevation.

APLA – Antiphospholipid antibodies (APLA).

Aplastic anaemia – A profound reduction in circulating blood cells, resulting from the loss of bone marrow stem cells. Severe or prolonged cases of aplastic anaemia have a high mortality rate. A reduction of all blood cell lineages (whether profound or mild) is called pancytopenia. When an isolated lineage is reduced, the anemia is named after the cell type involved: reticulocytopenia, immature red cell decline; neutropenia, neutrophil decline; thrombocytopenia, platelet decline; lymphopenia, decline in lymphocytes. See Stem cell.

AP-MS – Affinity purification coupled to MS-based analysis of proteins, an approach used in the field of functional proteomics and protein interactomics.

APOBEC3G (apolipoprotein B editing enzyme) – An RNA editing enzyme with cytidine deaminase activity.

Apoprotein – The protein portion of a complete protein (holoprotein) which consists of a prosthetic group (non-protein portion) + an apoprotein (protein portion).

Apoptosis – Orderly programmed cell death. A term from the Greek meaning a falling down. Apoptosis is a coordinated cellular activity leading to cell death. Alternate terms are cell suicide and programmed senescence. During apoptosis, chromosomal DNA is broken into small fragments, the nucleus shrinks (i.e., karyopyknosis), and the cytoplasmic membrane blebs out. Biochemical events leading to programmed cell death. Cell death brought about by an internal cellular program.Programmed cell death.It refers to the programmed cell death that may occur in multicellular organisms. A genetic program that eliminates damaged cells or cells that are no longer needed without activating the immune system.Series of genetically programmed steps that lead to programmed cell death.The controlled death of a cell mediated by in tracellular proteases that cause the orderly breakdown of the cell nucleus and it’s DNA. Death occurs without the release of internal contents and without triggering inflammation.Apoptosis (pronounced- apoptosis) is a form of biochemically programmed cell death. Fragmentation of cellular DNA and cell shrinkage are characteristics of the process.

Apoptosome – A complex of signaling proteins that activates mammalian caspase-3 during apoptosis.

Apoptotic bodies – Dense granular fragments of an apoptotic cell. Small membrane-bound structure in which a cell that is dying by apoptosispackages its remaining organelles to prevent leakage of harmful enzymes or other contents.

Appendicular skeleton – The part of the skeleton that includes the pectoral girdle, the pelvic girdle, and the upper and lower limbs.

Applicant – An organisation or individual who makes a regulatory submission to an agency- see “sponsor” e.g. the commercial entity responsible for the marketing authorisation application or post-approval application in the EU.

Application – A dossier or submission to a regulatory agency.

Applied research – is original investigation undertaken in order to acquire new knowledge directed primarily towards a specific practical aim or objective. Original investigation undertaken in order to acquire new knowledge directed primarily towards a specific practical aim or objective.

APR – Annual product review (APR).

Aptamers – (from the Latin aptus: fit, and Greek meros: part) are oligo nucleic acid or peptide molecules that bind to a specific target molecule. Aptamers are usually created by selecting them from a large random sequence pool, but natural aptamers also exist in riboswitches. Aptamers can be used for both basic research and clinical purposes as macromolecular drugs. Aptamers can be combined with ribozymes to self-cleave in the presence of their target molecules. Oligonucleotide that binds to another molecule, often a protein, but is not encoded by a naturally occurring DNA sequence.

Arbovirus – Arbovirus is a descriptive term applied to hundreds of predominantly RNA viruses that are transmitted by arthropods, notably mosquitoes and ticks. The word arbovirus is an acronym (Arthropod-borne virus).

Argonaut (AGO) family – Enzymes found within the RISC complex that degrade any cut any cellular RNAs that are complementary to the guide strand of the siRNA

Array backbone – Oligonucleotide probes that collectively provide coverage across the whole genome. Probes are usually evenly spaced throughout the genome; the higher the density of probes, the smaller the gap between probes. Additional probes can then be layered onto the backbone in specific regions of interest. These pertain to usually known microdeletion syndromes such as in the DiGeorge syndrome critical region and the Prader-Willi/ Angelman syndrome region.

Array CGH (comparative genomic hybridization; also known as chromosomal microarray; CMA) – method used to detect copy number variations (losses or gains of chromosomal material), which may be benign, pathologic, or of unknown clinical significance that is more sensitive method than traditional karyotype.

Array content – A collective term for the oligonucleotide probes contained on a microarray.

Array density – The number of oligonucleotide probes present on a microarray. This can typically range from 60,000 – 4,000,000 unique probes.

Arthus reaction – Localised type III hypersensitivity characterised by redness and swelling in the site of immune complex deposition.

Artificial chromosome – A self-replicating element used to clone large fragments of DNA that has three main components: an origin of replication, a centromere, and telomeres

Artiodactyls – A group of herbivorous mammals with even-toed hooves, including pigs, hippopotamuses, and ruminants.

Ascospores – Type of spore made inside an ascus by fungi of the ascomycete group, including yeasts and molds.

Ascus – Specialised spore-forming structure of ascomycete fungus.

ASEAN – Association of South-East Asian Nations (ASEAN).

Aseptic Operations – operations that are devoid of measurable (detectable) bioburden. Aseptic operations generally require sterilisation ofthe environment, equipment and process solutions to achieve the sterile state prior to use. Use of Biosafety Cabinets(BSCs) and laminar flow hoods are useful when aseptic open operations are required.

ASHRAE – American Society of Heating, Refrigerating and Air-Conditioning Engineers (ASHRAE).

ASME – American Society of Mechanical Engineers (ASME).

Aspartic protease – A class of protease that has two aspartic acid residues in its active site.

Assay – A test procedure that is quantitative (or semi quantitative) and can measure an amount of an analytic or biological activity.

Assembler – A general-purpose device for molecular manufacturing capable of guiding chemical reactions by positioning molecules

Assent – The right of a child to agree to participate in clinical research if they are of an age to understand the research in which they are being asked to participate. Assent is insufficient but necessary. Parental permission must also be gained, although parents cannot force a child who does not assent to participate.

Asset – An item listed on the left side of a balance sheet that has been acquired by the company in an objectively measurable transaction and has specific future economic benefit, such as additional purchasing power, cash, or the ability to generate revenues.

Associate investigator (AI) – A collaborating investigator on a clinical trial.

Association – Unrelated pattern of anomalies in occurrence more often than expected by chance.

Association (statistical) – In the context of diseases, an association is anything that happens to occur more frequently in the presence of a disease than occurs in the absence of the disease. Even when we know that one thing is associated with another thing, it can be very difficult to express the association in a manner that is mechanistically useful. For example, in 2000, Concorde, a supersonic transport jet, crashed on take-off from Charles de Gaulle Airport, Paris. Debris left on the runway, possibly a wrench, flipped up and tore the underside of the hull. All passengers were killed in the subsequent few seconds as the plane exploded and crashed. What is the association here? Is it, “debris associated with jet crash,” or do we need to be more specific, “wrench associated with jet crash”? Do jets need to be afraid of wrenches in general, or only with wrenches that are left out on the runway: “wrench on runway associated with jet crash”? If the association contains an implied mechanism that ties an object with a result, wouldn’t we need to confine the association to wrenches that are actually run over by the jet, because if the jet tires miss the wrench, the wrench would not flip up and tear the underside of the plane. This would make the assertion: “wrenches that are run over by a tire and flip upwards are associated with jet crashes.” It can be very difficult to develop a sensible way to describe associations. The problem is magnified many times when we are dealing with gene polymorphisms (i.e., gene variants found in a population) associated with diseases that have various causes, poorly understood pathogen- eses, and complex phenotypes. Like so many scientific observations, associations serve as clues, not answers.

Association studies – Studies that test for a correlation between a phenotype and a genetic variation(s) in order to identify candidate genes or genomic regions that potentially contribute to the phenotype.

Assurance – A document that institutions must have in place for conducting clinical research with Common Rule agency funding. The document explains how the institution will comply with U.S. federal regulations.

Astigmat – An individual with ocular astigmatism.

Astigmatism – An optical defect causing blurred images due to failure to focus a point object into a sharp image on the retina.

Asymmetric cell division – A cell division that produces two daughter cells that have different fates. In stem cell niches, one daughter cell retains the stem cell fate and the other daughter cell differentiates into a cell making up the surrounding tissue or organ

Asymmetry – Uneven in distribution of various factors during cell division.

Asymptomatic – Not showing symptoms.

Ataxia telangiectasia – Also known as Louis–Bar syndrome and as Border– Sedgwick syndrome, and caused by a mutation of the ATM gene, resulting in a defect in DNA repair. Cells of individuals with ataxia telangiectasia are highly vulnerable to radiation toxicity. The clinical phenotype consists of cerebellar ataxia (i.e., a body movement disorder secondary to cerebellar impairment), telangiectases (i.e., small focal vascular malformations), immune deficits predisposing to ear, sinus, and lung infections, and a predisposition to malignancy (e.g., lung, gastric, lymphoid, and breast cancers).

ATM (ataxia telangiectasia-mutated) – A tumor suppressor gene identified as a mutated gene in ataxia telangiectasia. Ataxia telangiectasia is a rare, neurodegenerative, inherited disease causing severe disability. ATM, a serine/threonine protein kinase, is activated by double- strand break (DSB), acting as a sensor of the DNA damage.

ATIMP(s) – Advanced Therapy Investigational Medicinal Products (ATIMPs, as per Regulation 2007/1394 EC) are investigational medicines for human use that are based on genes, tissues or cells.

ATMP(s) – Advanced Therapy Medicinal Products (ATMPs, as per Regulation 2007/1394 EC) are medicines for human use that are based on genes, tissues or cells.

Atoh1 – A basic helix-loop-helix transcription factor that is necessary and sufficient for hair cell formation. Atonal Homolog 1a (Atoh1a) and Atonal Homolog 1b (Atoh1b) are the zebrafish homologs of Drosophila Atonal, a bHLH, transcription factor that also determines the specification of mechanoreceptors in Drosophila. Atoh1a expression gives cells in protoneuromasts or neuromasts the potential to become sensory hair cell progenitors.

Atomic Force Microscope (AFM) – An instrument able to image surfaces to molecular accuracy by mechanically probing their surface contours.

Atopic keratoconjunctivitis (AKC) – Allergic conjunctivitis where the conjunctiva is red and swollen. Untreated, AKC can progress to ulceration, scarring, cataracts, keratoconus, and corneal vascularisation.

Atopy – Signs and symptoms of type I hypersensitivity reactions. Tendency of an individual to produce IgE antibodies and to develop Type I hypersensitivity responses.

ATP – Adenosine triphosphate, universal form in which energy is available in cells, due to the energy-rich phosphate bonds (energy maintenance of cells).

ATP synthase – The enzyme in the mitochondrion that converts ADP to ATP and releases it when a proton passes through its structure.

ATP synthetase – Enzyme that synthesises ATP using energy from the respiratory chain

ATR (ataxia telangiectasia and RAD3-related) – ATM-related gene. It is a serine/threonine kinase that is involved in sensing DNA damage and activating the DNA damage checkpoint, leading to cell cycle arrest.

Attenuated – Weakened.

Attenuated vaccine – A live pathogen that no longer causes a disease state but still stimulates the immune system to create antibodies.

Attenuation riboswitch – Type of riboswitch that causes premature termination by inducing an alternative stem and loop structure in the leader region of the mRNA when triggered by a signal.

Atypical silent partnership – This model is based on the participation of an equity donor on the yearly company profits or losses as well as on the value increase of this company. The repayment of the equity investment usually takes place after 5–7 years at the end of the legal duration period. On the one hand, the model allows a tax advantage to those individuals who invest part of their own profits in high-risk areas, such as the biotech industry. On the other hand, this financing form provides the entrepreneur with early and rather easy access to capital without any interference from the investor’s side.

Auditing – The process of verifying data collected are accurate and complete, generally by review of documents like essential documents for a clinical trial or batch records and test worksheets for a product lot.

Autism – A spectrum of mental disorders characterised by impaired communication and social interactions.

Autoinflammatory syndromes – Inherited diseases in which patients suffer from recurrent severe local inflammation and prolonged periodic fevers in the absence of any obvious pathogenic cause. Caused by inappropriate activation of innate leukocytes mediating inflammatory responses.

Autoantibody – Antibody that recognises a self-epitope.

Autoantigen – Self antigen inducing an autoreactive response.

Autocatalytic properties – Properties of an enzyme that can initiate its own activation.

Autocrine – Affecting the same cells. Autocrine hormones affect the same cells that produce the hormones. Producing effects on the same cell that produced the factor.

Autocrine signals – A chemical signaling molecule that is produced from the same cell or same cell type in which it activates.

Autogenous regulation – Self-regulation, i.e., when a DNA-binding protein regulates the expression of its own gene.

Autoimmune disease – Pathophysiological state in which the host’s own tissues are damaged as a result of autoimmunity.

Autoimmunity – The response of an individual’s immune system against self tissues. May cause autoimmune disease if unrestrained by mechanisms of peripheral tolerance.

Autologous – Tissues or cells derived from the same individual. A situation in which the donor and recipient are the same person e.g. in the case of autologous transplantation, the transplanted tissues or cells are derived from the recipient.

Autologous bone – The patient’s own bone tissue.

Autologous Bone Marrow TransplantationThe bone marrow products are collected from the patient and are reinfused after purification methods. The advantages include no GVHD. The disadvantage is that the bone marrow products may contain abnormal cells that can cause relapse in the case of malignancy hence; theoretically, this method cannot be used in all cases of abnormal bone marrow diseases.

Autologous graft – Transplantation of tissue from one part of an individual’s body to another part of his or her body.

Automatic DNA sequencer – Machine that separates a dye-labeled dideoxy sequencing reaction into increasing larger fragments, analyzes the final nucleotide of each fragment by recording the color, and prints the results in a graphical format to determine the sequence

Autonomic nervous system – Nerves under involuntary control (coming from either the brain or the spinal chord) that operate a variety of physiological functions. In the eye this includes control of pupil size, accommodation, intraocular pressure, and blood flow. The sympathetic and parasympathetic divisions tend to control opposing functions (such as increasing and decreasing pupil size), but there are exceptions.

Autonomous growth – The growth of normal cells is highly controlled in most adult animals, so that every tissue contains about the same number of cells from day to day. Such controlled growth is referred to a non-autonomous, because each dividing cell is restricted from growing continuously or in a manner that is not somehow matched against a nearly constant tissue-specific number. Cancer cells, which increase in number every day, are said to grow autonomously, and free of the restraining influences of humoral or other external factors. Of course, no cell growth is truly autonomous. Cells in a tumor require a vascular blood sup- ply. Some tumors are hormone responsive, and when the hormone is withdrawn or blocked, the tumor may stop growing, or may shrink. Such tumors exhibit non-autonomous growth. Some gastric maltomas (i.e., a type of lymphoma aris- ing from mucosa-associated lymphoid tissue) will regress completely after the patient is treated for Helicobacter pylori infection, the presumed cause of the maltoma. These regressed maltomas would be considered non-autonomous.

Autophagolysosome – A digestive vacuole found in the cytoplasm that forms when an autophagosome and lysosome fuse

Autophagosome – A vesicle found in the cytoplasm that contains defective organelles or other cellular components

Autophagy – Engulfment process by which entities in the cytoplasm of a cell can be sequestered in endosomal compartments and digested, or delivered into the exogenous antigen processing pathway. The process that degrades cellular components by the lysosomes.

Autoradiography – Visualization of a chemical component on photographic film or using radiation detectors with the help of radioactive isotopes- important for DNA sequencing using the Sanger method. A technique of allowing radioactive materials to take pictures of themselves by laying them flat on photographic film.

Autoreactive – Status of lymphocytes that recognise and are activated by self antigen are autoreactive.

Autoregulation – The intrinsic ability of a system to maintain constant blood flow despite changes in perfusion pressure and local vascular parameters to maintain homeostasis.

Autosomal dominant – A trait or condition that is expressed in individuals who have inherited only one copy of a gene mutation on one of the 22 pairs of autosomes (non-sex chromosomes).

Autosomal dominant (AD) inheritance – An inheritance pattern in which only one copy of the mutated gene within a nonsex chromosome is needed to get the disease.

Autosomal recessive – A trait or condition that is observed only when an individual has two copies of a gene mutation at a locus on one of the 22 pairs of autosomes (non- sex chromosomes).

Autosomal recessive (AR) inheritance – An inheritance pattern in which two mutated genes, one mutated gene from each parent within the nonsex chromosomes, is needed to get the disease. The effects of those particular inherited chromosomes.

Autosome – A chromosome that is numbered (e.g. 1-22 in humans) and not considered a sex chromosome. Any chromosome other than a sex chromosome (X or Y) and the mitochondrial chromosome.

Autozygosity – In an inbred person, homozygosity for alleles identical by descent.

Autozygosity mapping – A form of genetic mapping for autosomal recessive disorders in which affected individuals are expected to have two identical disease alleles by descent.

Auxins – Natural or synthetic growth and development regulators in plants (class of phytohormones, hormones).

Average manufacturing price (AMP) – The price paid by the wholesaler or other purchaser to the manufacturer.

Average wholesale price (AWP) – The price wholesalers sell to retail pharmacies and non-retail pharmacies.

Avidin – A protein from egg white that binds biotin very tightly.

Avidity – A measure of the total strength of all the associations established between a multivalent receptor and its multivalent ligand.

Axenic state –  A culture that includes the intended living organism, but is free of all other contaminating organisms.

Axis meridian – The meridian of a cylindrical surface that is flat and consequently has no optical power.

Axon – A long cellular process that carries signals away from the cell body of a neuron.

Azidothymidine (AZT) – Nucleoside analog that acts as a chain terminator. It is used against AIDS and is also known as zidovudine.



BAC – see Bacterial artificial chromosome (BAC). 

BAX – Proapoptotic BCL2-associated X protein. BCL2 is an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells.

B cell – A white blood cell (lymphocyte) that can produce any of a large number of antibodies. The label “B” originates from the chicken bursa where these cells were originally found.

B cell receptor (BCR) complex – Antigen–receptor complex of B lineage cells. Composed of a membrane-bound Ig (mIg) monomer plus the Igα/Igβ complex required for intracellular signaling.

B cell receptor blockade Anergisation – of a B cell due to very large amounts of antigen that persistently occupy the BCRs without cross-linking them.

B lymphocyte (B cell) – A leukocyte that matures in a primary lymphoid tissue (bone marrow), becomes activated in secondary lymphoid tissues, and mediates adaptive immunity by differentiating into antibody-producing plasma cells.

B-1 cells – A subset of B cells that resides primarily in the peritoneal and pleural cavities and produces natural antibodies.Considered part of the innate response because they do not differentiate into memory cells.

B7 ligands – B7-1 (CD80) and B7-2 (CD86) are ligands for the costimulatory molecule CD28 and the negative regulator of T cell activation CTLA-4.

Bacillus anthracisBacterium that causes anthrax and that readily infects humans.

Back-crossed – Procedure in which pollen from the progeny of two parents is cross-pollinated onto one of the original parents.

Bacillus Calmette–Guerin – Strain of Mycobacterium bovis used as the BCG vaccine against tuberculosis.

Backward integration – occurs when a firm in one section of the value chain takes on the function of a firm in another section of the value chain and this new function is further away from the end user than the first function.

Bacmid – Hybrid cloning vector made from a baculovirus and a plasmid bacteriocin Toxic protein made by bacteria to kill closely related bacteria bacteriophage virus that infects bacteria

Bacterial artificial chromosome (BAC) – DNA vectors into which large DNA fragments can be inserted and cloned in a bacterial host. It is a DNA construct based on a functional fertility plasmid, used for cloning in bacteria. The bacterial artificial chromosome’s usual insert size is 150–350 kbp.

Bacteriophage (phage) – A bacteriophage (informally, phage) is a virus that infects and replicates within bacteria. The term is derived from Greek word phagein “to eat.” Viruses that have bacteria or Archaea cells as hosts. They are important tools in gene technology, as they are used as vectors to introduce foreign DNA into target cells.

Bacteriophage vector – A bacteriophage genome in which nonessential bacteriophage genes are replaced with a multiple cloning site where other DNA fragments can be cloned. The vector can be maintained within a bacterial cell since it contains all the necessary genes for replication, growth, and lysis.

Baculoviruses – Family of DNA viruses that infect insects and related invertebrates and are widely used as vectors.

Bait – The fusion between the DNA-binding domain of a transcriptional activator protein and another protein as used in two-hybrid screening

Balance sheet – A financial statement that specifies the financial condition of a business as of a given point in time. It includes (current/non-current) assets and liabilities as well as stockholders’ equity and represents a statement of the basic accounting equation.

Baltimore Classification System – A system used to classify viruses based upon their type of genome and replication strategy.

Bankruptcy – The state of a person or company unable to repay debts. If the bankrupt entity is a company, the ownership of its assets passes from the stockholders to the bondholders. Shareholders are always the last in line to get paid if th company goes bankrupt. Secure creditors get first grabs at the proceeds from liquidation.

Barcode sequence – A unique DNA sequence added to the linker or adapter for next- generation sequence that is used to discern one genome from another

Bardet-Biedl syndrome – This human congenital disease is mainly characterised by obesity, pigmentary retinopathy, polydactyly, mental retar dation, hypogonadism, and renal failure in fatal cases.

Barretts esophagus – Precancerous metaplasia of the esophageal epithelium.

Basal cell carcinoma – Basal cell carcinoma is the most common skin cancer, with about 600,000 new cases occurring each year in the U.S. They occur as small, smooth patches on sun-exposed skin (e.g., face, arms, neck). A basal cell carcinoma seldom, if ever, metastasises from its primary site of growth. Along with squamous carcinoma of skin, occurrences of these two conditions equal the occurrences of all other cancers, combined. Neither basal cell carcinoma of skin nor squamous cell carcinoma of skin accounts for many human deaths. Neither of these extremely common tumors is recorded in hospital-based cancer registries, and when statistics are compiled on the incidences of cancers, these tumors are usually excluded. The omission of these two tumors from cancer registries produces an under-representation, by about 50%, of the true biological burden of cancer in the human population.

Base – Alkaline chemical substance; in molecular biology especially, refers to the cyclic nitrogen compounds found in DNA and RNA. See Nucleotide.

Base pair – Two nucleotides on different strands interacting with each other through a hydrogen bond between nitrogenous bases. Adenine base pairs with thymine or uracil, whereas cytosine base pairs with guanine.

Base peak – Peak for the most intense ion detected in a sample.

Base substitution – Mutation in which one base is replaced by another.

Basement membrane – A layer composed of collagen and other proteins and sugars that supports an overlying layer of epithelial or endothelial cells. A tissue scaffolding or sheet that supports or separates cells from other noncellular parts of a tissue. Basement membranes are sheets of extracellular matrix that provide support and anchorage for epithelial and endothelial cells. Typical extracellular matrix components that are found in basement membranes include collagen IV, collagen XVIII, agrin, perlecan, laminin, and nidogen.

Basic peptide – A short length of basic amino acids that facilitate translocation across biological membranes. These are derived from known proteins or made synthetically.

Basic research – Experimental or theoretical work undertaken primarily to acquire new knowledge of the underlying foundationsof phenomena and observable facts, without any particular application or use in view. The study and research on pure science that is meant to increase our scientific knowledge base. This type of research is often purely theoretical with the intent of increasing our understanding of certain phenomena or behavior but does not seek to solve or treat these problems.

Basophil – Circulating granulocyte with an irregularly shaped nucleus. Contains granules that stain a dark blue colour with basic dyes. Basophil granules contain heparin and vasoactive amines, as well as many enzymes capable of promoting inflammation. Leukocytes with a single lobed nucleus and cytoplasmic granules which stain positively with a basic dye.

Basophilic – A property of cells that attracts basic histological dyes, such as hematoxylin.

Batch – Some people use this term interchangeably with the term “lot” but in this book, we will use the term “batch” to refer to a homogenous preparation of drug substance.

Bax protein -Stands for Bcl-2-associated protein X. This protein promotes apoptosis by causing (indirectly) the release of cytochrome C from mitochondria.

Bayh-Dole Act – allows U.S. universities that received federal funding for research leading to an invention to retain ownership to the inventions associated with the federal funding.

B-cell receptors – Membrane bound form of an antibody that is found on the surface of B cells. Responsible for signaling the B cell the presence of a pathogen and for processing the antigens from the pathogen to activate other immune cells (i.e., T cells).

Bcl protein – Also known as Bcl-2 protein. This protein binds to Bax protein and cancels its effects. That is, it is anti-apoptotic.

Bcl-2 – Mitochondrial protein that helps control entry into apoptosis.

Beta-galactosidase or β-galactosidase (LacZ) – Enzyme that splits lactose and related molecules to release galactose.

Beer’s law – Relationship of light to the concentration of a substance expressed as A = abc. “A” is the absorbance of light by a sample. “a” is the absorptivity of the sample that is an empirically determined quantity containing the physical-chemicalcharacteristics of the molecule. “b” is the path length of light through the molecular sample and is usually 1 cm. “c” is the concentration of the sample molecule.

B-Elimination – Chemical reaction in which functional groups (on adjacent carbons) are removed from the compound. Such reactions may be carried out in alkali.

Belmont Report – Ethical Principles and Guidelines for the Protection of Human Subjects Research A U.S. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research report issued in 1979 that shaped the way principles of ethics have been codified into legislation and regulations in the United States and that has influenced ethical thinking about clinical research around the world.

Beneficence – One of the basic principles or tenets of ethical clinical research. Beneficence means non-malfeasance or do no harm and to maximise benefits and minimise possible risks. This basic tenet is accomplished through assuring that there is an assessment of risks and benefits (e.g., through an IRB review process), by increasing benefits while decreasing harms as much as is possible being consistent with sound research practices, by having research conducted only by qualified researchers, and by prohibiting research that does not have a favourable risk/ benefit balance.

Beneficence– The ethical principle that requires that research participants be treated ethically by respecting their decisions, protecting them from harm, and making efforts to secure their well-being.

Benefits section – In a protocol, the section that details if, and if so, what, direct medical benefits a research subject might reasonably expect from study participation and that, at a minimum, knowledge to be gained from the study is anticipated to benefit others in the future through medical progress.

Benign tumour – A mass formed by abnormally dividing cells that are well differentiated and well organised. Resembles the normal tissue from which it originated and is securely encapsulated and relatively slow growing. Causes death only by indirect means.A benign tumor is a mass of cells (tumor) that lacks the ability to invade neighboring tissue or metastasise.

Best effort contract – refers to the arrangement between the underwriter and pre-IPO owners in the primary market phase. The underwriter does not acquire the stock but uses its ‘best efforts’ to see that others do.

Bests disease – A congenital degeneration of the macula.

Betacoronavirus – A virus in the Betacoronavirus genus in the Coronaviridae family.

β2-microglobulin (β2m) – Invariant chain of MHC class I proteins; encoded by a gene outside the MHC.

β3-adrenergic receptor – Receptor found on fat cells that binds noradrenaline (norepinephrine)

β-cell – The predominant endocrine cell type in the pancreatic islets; it is the only cell in the body that is capable of producing and secreting the hormone insulin.

β-galactosidase – Enzyme that splits lactose and related disaccharides into simple sugars

β-lactamase – Enzyme that degrades antibiotics of the β-lactam family.

β-lactams – Large family of antibiotics including both penicillins and cephalosporins.

β-selection – Process in which the TCRβ chain expressed by a DN3 thymocyte becomes part of a pre-TCR that allows the thymocyte to receive a survival/proliferation signal and become committed to the αβ T lineage.Required for a cell to pass the pre-TCR checkpoint, the first major checkpoint in T cell development.

B-form – The normal form of the DNA double helix, as originally described by Watson and Crick.

BFD – Block Flow Diagram (BFD).

Bias – ICH E9 defines bias as- “The systematic tendency of any factors associated with the design, conduct, analysis and evaluation of the results of a clinical trial to make the estimate of a treatment effect deviate from its true value. Bias introduced through deviations in conduct is referred to as ‘operational’ bias. The other sources of bias listed above are referred to as ‘statistical’.”

Bifurcation – Division into two (as in one branch bifurcating to become two) e.g. division of two different taxonomic groups from each other during evolution.

BiMo – Bioresearch Monitoring is a type of U.S. FDA inspection in which the inspectors are not inspecting a manufacturing facility, but instead are inspecting a clinical trial site or a facility where GLP preclinical studies were performed.

BIM – Building Information Modelling.

Bio centers– are regional ventures funded by governments and corporations for the purpose of developing a biopharmaceutical industry within a region.

Bio clusters – are regions that have the components of intellectual and financial capital (e.g. universities and venture capital) and entrepreneurial spirit.

Bioaugmentation – Adding degrading microorganisms (normal or engineered) plus nutrients to remove a contaminant from the environment.

Bioburden-Free – A condition where bioburden is not detectable. Bioreactors used in cell culture or fermentation operations should be sterile prior to use for consistent and reproducible performance. Biosafety Cabinets (BSCs), Restricted Access Barriers (RABs) and isolators should provide an environment free of bioburden for consistent and reproducible aseptic operations. Sterile product manufacturing testing and qualification guidelines are by necessity more stringent and prescriptive than those for active pharmaceutical ingredient manufacturing and therefore are not required.

Biocatalysis – Lowering activation energy levels for a chemical reaction with the help of enzymes. The process, catalysis, brings about thermodynamic equilibrium more rapidly. This does not affect the position of the equilibrium (in terms of the reactant- product ratio) and the catalyst is unaffected by the reaction, i.e., it is not used up. The enzymes can, however, lose their activity over time or be degraded by proteases.

Biocatalysts – Mediators of biocatalysis; the term may refer to the enzyme itself, but occasionally also to entire cells (and all the enzymes produced by them).

Biocentres – Regional ventures funded by governments and corporations for the purpose of developing a biopharmaceuticalindustry within a region.

Bioclusters – Regions that have the components of intellectual and financial capital (e.g. universities and venture capital) and entrepreneurial spirit.

Biocompatible – Compatible with living cells, tissues, organs, or systems, and posing no risk of injury, toxicity, or rejection by the immune system.

Biocompatible material – Material which is non-toxic and tolerated in the body.

Biodegradable – Able to decompose naturally; made of substances that will decay relatively quickly as a result of the action of breakdown into elements such as carbon that are recycled naturally.

Biodegradable scaffolds – Engineered extracellular matrices used to fabricate tissues in the laboratory.

Bioengineered corneas – Are natural-based substitutes for human donor tissue that are designed to replace part or the full thickness of damaged or diseased corneas.

Biofilm – An aggregate of microorganisms in which cells adhere to each other on a surface.

Biohydrogen – Hydrogen that is produced by organisms such as algae or bacteria.

Bioinformatics – The application of math and computer science to extract information from biological data sets. The computerised analysis of large amounts of biological sequence data. An applied computational system that includes development and utilisation of facilities to store, analyse, and interpret biological data.

Biologic or Biological – A drug manufactured by biological synthesis in a biological system. Biologicals include blood and blood products, vaccines, antitoxins, allergenic extracts, probiotics, toxins, serums, antivenins, cell therapies, gene therapies, recombinant therapeutic proteins, monoclonal antibodies, etc. Biotechnology products for medicinal use are a subcategory of biologicals in which recombinant DNA technology is part of the construction or manufacturing of the biological.

Biological response modifiers (BRMs) – are antibodies, cytokines, and other immune system substances that can be produced in the laboratory.

Biological safety cabinet (BSC) – A piece of equipment that uses HEPA filters to provide a sterile workspace and an environment that protects the user.

Biological Starting Material – The biological substrates or seeds used to initiate manufacturing, either directly or from which the direct substrate is derived, e.g., Master or Working Cell Banks, Master or Working Viral or Bacterial Seeds.

Biologics License Application (BLA) – is for biotechnology products and is part of the clinical trials process that addresses how the drug is to be manufactured, dosage levels, labeling specifications, and other pertinent information.

Bioluminescence – Radiation of visible light by living organisms without temperature change. The underlying principle of the luminescence is the oxidation of the enzyme luciferase, which is the biocatalyst in this reaction.

Biomaterials – Non-living substance or material implanted into the human organism to replace or repair a tissue. Biomaterials are used in regenerative medicine; they are biocompatible, of natural or synthetic origin.

Biomimetic – Imitation of biological structures in engineering. Imitating nature or a natural process.

Biopanning – Method of screening a phage display library for a desired protein by binding to a bait molecule attached to a solid support.

Biophysical cues – The signals that a cell obtains as a result of external characteristics upon which it is located. Biophysical cues involve both topographic features as well as the rigidity of the substratum.

Bioprocessing – Bioprocessing is the attainment of medicinal products from living organisms. Includes all operations used in the manufacture of biologics including upstream processes such as inoculum preparation, cell culture/fermentation processes, harvest and clarification processes such as sedimentation and filtration processes, downstream processing such as chromatography and filtration processes. Bioprocessing also may include other aqueous processes, such as plasma fractionation and chemically synthesised drug manufacturing performed in nonbacteriostatic solvents.Fill finish operations are not included in this group; however, many of the concepts presented would still apply. Biologics manufacturing. Includes all operations used in the manufacture of biologics including upstream processes such as inoculum preparation, cell culture/fermentation processes, harvest and clarification processes such as sedimentation and filtration processes, downstream processing such as chromatography and filtration processes.Bioprocessing may also include other aqueous processes such as plasma fractionation and chemically synthesised drug manufacturing performed in non-bacteriostatic solvents. Fill finish operations are not included in this group however many of the concepts presented would still apply.

Bioreactor (Fermenter) – Reactors used for cell culture operations. Fermenters: used for microbial fermentation. A device used to scale up biological processes. It can be applied to stem cell culture, for example, to obtain sufficient cell numbers for transplantation or use in biotechnology applications. Various types of containers in which (animal, plant, and microbial) cells are cultured on a substrate (for a particular purpose). The modified product (e.g., cheese or beer), the cells themselves (e.g., single-cell protein (SCP) or components of their metabolic products that were obtained through purification from the fermentation broth, such as ethanol, antibiotics or monoclonal antibodies are then ready for further use. Bioreactors can vary in volume from a few milliliters on a laboratory scale to thousands of cubic meters on a large industrial scale. Large chambers or vats used to grow organisms such as yeast or bacteria so that the biotechnological product can be harvested on a large scale

Bioremediation – Using any microorganism, fungus, plant, or enzyme to clean up or restore the environment to its original condition

Biosafety level – A classification system used to define practices and procedures that must be employed when working with a specific pathogen. Rating system (BL1–BL4) from lowest to highest for high-containment laboratories.

Biosensor – Detection or monitoring device that relies on a biological mechanism. Measuring device in which a biologically active component (sensor) is combined with a signal converter and an electronic detector and amplifier to form a unit. Interaction between molecules and the coupled biological sensor produces a biochemical or optical signal that is displayed by the transducer. First exponents of a new research area called bioelectronics.

Biosensory system – A genetic circuit that is controlled by a specific environmental cue

Biosimilars – are generic biotechnology products, similar to generic medicines. They are marketed after an innovative drug has gone ‘off-patent’.

Biostimulation – Using different chemical compounds to stimulate naturally occurring microorganisms to remove a contaminant from its environment

Biotechnology – The industrial application of biological processes, particularly recombinant-DNA technology and genetic engineering e.g. the manipulation of micro-organic plant or animal cells to produce materials or products which can be used in daily life.

Biotechnology medicinal product – A biological medicinal product that has been constructed or manufactured using recombinant DNA technology. In the United States, biotechnology products may be regulated by CBER, CDER, CDRH, or CVM. In Europe, these products are regulated through the centralised process by EMA, rather than by individual countries’ NRAs.

Bi-specific mAb – A mAb (see also definition of mAbs) that expresses in a single antibody molecule the recognition specificities from two separate B-cells.

BLA –  Biologics License Application (BLA) – the submission to U.S. FDA to gain marketing authorisation (a license) for a biological product.

Black Death – Bubonic plague or more specifically, the great plague epidemic of the mid-1300s.

Blast (blast cell) – A term usually reserved for the dividing cells of the bone marrow (i.e., a hematopoietic stem cell). The cytologic lineages of the bone marrow (i.e., neutrophils, monocytes, lymphocytes, red blood cells, plasma cells, and megakaryocytes) undergo a graded series of morphologic changes as they mature from blast cells to fully bone marrow cell. Blast cells are con- fined under normal circumstances to the bone marrow. Blast cells are found in the circulation in acute leukemias and in so-called blast transformation of chronic myelogenous leukemia (i.e., a shift from indolent disease to an aggres- sive leukemia).

Blastema – A population of (mesenchymal) stem cells that form, for example, at the amputation site of a salamander limb. A healthy new limb can regenerate from the cut surface.

Blastocyst – An early-stage embryo, about 5 days old. A blastocyst is a microscopic clump of about 150 cells. It is produced from an egg that has been fertilised in vitro but has not yet been implanted in the uterus. The blastocyst is about the same size as the cross-section of a human hair. It consists of an outer trophectoderm layer and an inner population of cells from which the foetus derives, called the inner cell mass (ICM). The mammalian embryo at the stage at which it is implanted  into the wall of the uterus.

Blastomere – Cells from an early cleavage stage embryo. In some species, they may be pluripotent.

Blastoporal-ablastoporal axis – An idealised pan-vertebrate axis that runs orthogonally to the zone of internalizing mesendodermal cells. The zone of internalizing mesendodermal cells defines the blastoporal end of this axis.

Blastula – In animals, the stage of development where a hollow ball of cells has a fluid filled cavity. Forms three to five days after fertilization in human development

Bleaching of rhodopsin – Conversion of rhodopsin to opsin plus all-trans retinal.

Blepharitis – Inflammation of eyelids.

Blepharophimosis – Horizontally narrow palpebral fissure.

Blepharoptosis – Abnormal relaxation of upper eyelid.

Blockbuster drug – A drug or therapy that obtains a dominant position in a disease category with significant market share and profitability.

Blood antigens – Glycoproteins and glycolipids on the surface of blood cells that are used for antigenic analysis.

Blood pressure – Refers to the pressure exerted by the blood on the walls of arteries that are accessible to external palpation. The blood pressure oscillates due to the repetitive pumping action of the heart. The peak in blood pressure is the systolic value, normally about 120 mmHg, and the trough is the diastolic value, normally about 80mm Hg. It is important to note that the trough value is not zero, or anything close to zero, indicating that there is an intrinsic ten- sion imposed by blood on arterial walls. Sphygmomanometers (blood pressure cuffs) inflate to constrict arteries to a pressure higher than systolic, at which point blood flow through the artery is severely reduced. As the cuff pressure is released, there comes a point when the systolic pressure exceeds the inflated pressure. At that point pressure waves of blood flow through the artery, producing characteristic sounds heard with the assistance of a stethoscope (i.e., Korotkoff sounds). The sounds begin at the systolic blood pressure value and they continue as the cuff continues to deflate, until the diastolic blood pressure value is reached, at which point the cuff’s resistance to the flow of pumped blood is zero, and the Korotkoff sounds cease.

Blood Stem Cells – Multipotent stem cells that are present in the bone marrow, umbilical cord blood, or placenta that give rise to all the different types of blood cells. They are usually not present in the blood stream unless “mobilised” from the bone marrow by specific growth factors, which may be induced by tissue injury (as in a heart attack) or administered as part of therapy.

Blood typing – Use of differences in blood antigens to determine identity

59-base element (59-be) (see also attC) – A repeated genetic sequence that flanks an integron gene cassette and contains a seven-base-pair core that is highly conserved

5-bromo-2-deoxyuridine (BrdU) – A base analog for thymine that is easily incorporated into DNA during replication

Blood-brain barrier – It refers to a highly selective permeability barrier that separates the circulating blood from the brain extracellular fluid (BECF) in the central nervous system (CNS).

Blue biotechnology – Biotechnology of maritime organisms.

Blue sky qualification fees and expenses – relate to the costs associated with registering a security in a given state.

Blue–yellow (tritan) defect – A color-vision deficiency in which colors along the blue–yellow axis are difficult to distinguish from one another and sensitivity to blue light is decreased. This is typically caused by a defect in the short-wavelength-sensitive cone photoreceptor pathway. The word tritanopia derives from the Greek tritos, meaning third, alluding to the defect being associated with the third of the three primary colors (blue) + anopia, meaning blindness.

Blunt ends – Ends of a double-stranded DNA molecule that are fully base-paired and have no unpaired single-stranded overhang

B-Lymphocytes – also referred to as B-cells. Lymphocytes that develop from activated cells in the bone marrow of adults and the liver of a fetus. These will later produce antibodies and mediate humoral immune response (formation of antibodies).

Board of Directors – A group of individuals, elected annually by the stockholders of a corporation to represent the interests of those stockholders.

Bohr radius – The natural preferred distance between positive and negative charges in a material

Bond – A security issued by a borrower and obligating the issuer to make specified payments to the holder over a specific time period. A coupon bond obligates the issuer to make interest, or coupon payment, over the life of the bond and to repay the face value at maturity.

Bone marrow (BM) – The primary lymphoid tissue (in the adult) in which all lymphocytes and other hematopoietic cells arise.

Bone marrow transplant (BMT) – Replacement of a patient’s dysfunctional immune system by transplantation of healthy whole bone marrow from a donor.

Bone Marrow Transplantation – Transplantation with cells obtained from the bone marrow. Under anesthesia, healthy bone marrow is aspirated from the pelvic bone of the donor and administered intravenously to a recipient patient as therapy. The bone marrow cells find their own way (or “home”) to the recipient’s bone marrow.

Bone Morphogenetic Protein (BMP) – A group of growth factors (proteins) originally discovered by their ability to induce the formation of bone and cartilage, but now known to provide morphogenetic signals throughout the body.

Book value – The value of an account, a company, or a share of stock as indicated by the balance sheet.

Book building – The IPO process where the investment bank conducts a formal assessment in which new investors make non-binding commitments to acquire the offer.

Booster – A second or subsequent immunisation (vaccination) to stimulate memory cell production.

Bootstrapping – The term used to describe the initial funding of the invention or firm, with such funding coming from non-institutional investors (e.g. venture capital or biopharmaceutical firms).

Botox – Botulinum toxin, especially as used for cosmetic purposes.

Botulinum toxin – Protein toxin made by Clostridium botulinum that blocks nerve transmission.

Botulinum toxin type-A – Specific type of botulinum toxin used clinically and for cosmetic purposes.

Bouton – A tiny rounded ending of a terminal nerve process.

Bovine spongiform encephalopathy (BSE) – It is a fatal neurodegenerative disease (encephalopathy) in cattle that causes a spongy degeneration in brain and spinal cord. Official name for mad cow disease, a brain degeneration disease of cattle caused by prions.

BPE – Bioprocessing Equipment (BPE).

BPOG – Biophorum Operations Group (BPOG).

BPR – Batch Production Record (BPR)- the detailed documentation of what was done in each manufacturing run to produce a batch or a lot.

Brachydactyly – This is a term which literally means “shortness of the fingers and toes” (digits). The shortness is relative to the length of other long bones and other parts of the body.

Brachytherapy – Implantation of a metal “seed” containing a radioisotope to mediate radiation therapy internally.

Brain attack – At present, the politically correct term for “stroke” and “cerebrovascular accident” is “brain attack”; a term that emphasises an analogy with “heart attack.” Both terms are ill-conceived as neither the brain nor the heart does much attacking. “Attacked brain” or “attacked heart” would be preferable linguistically, but neither sounds right when spoken.

Branchio-otic renal syndrome  – An autosomal dominant syndrome in humans that presents with craniofacial defects, hearing loss, and kidney or urinary tract defects.

Branchio-otic syndrome  – An autosomal dominant syndrome in humans that presents with branchial cleft fistulas and hearing loss. Some cases are caused by mutations in the Eya1 gene and some are caused by mutations in six genes.

Brand-name drugs – are the initial or innovator drugs that may have been granted a patent or patents and gone through the MHRA/EMA/FDA/other RA approval process and are being sold to the general public.

BRCA1 – Breast cancer A1 gene, involved in DNA repair. Defects in this gene predispose women to breast cancer

BRCA2 – Breast cancer A2 gene, involved in DNA repair. Defects in this gene predispose women to breast cancer

Break-even point (BEP) – The point at which cost or expenses and income are equal so that there is no net loss or gain.

BREEAM – Building Research Establishment Environmental Assessment Method (BREEAM).

Bridge amplification – A specialised type of PCR in which the forward and reverse primers are attached to the surface of a flow cell so the template form a U-shape on the surface. Used for Illumina-type of next-generation sequencing methodology.

Bridge financing – A method of financing, used to maintain liquidity while waiting for an anticipated and reasonably expected inflow of cash.

Briefly Exposed – Open processes containing process and/or product components that are rendered closed by means of an appropriate closing process. Examples of briefly exposed processes include open buffer or media preparations where the solutionis “briefly” exposed to the environment prior to closing by sterile filtration and/or thermal sanitization. For solution preparation, it is important that the interval between formulation and sanitization be defined and validated. Briefly exposed operations may be performed in Controlled Not Classified (CNC) or low bioburden environments if measures used to close the process are appropriate to mitigate risk of contamination from the environment. Pre-closure processing and hold periods and conditions must be carefully monitored and validated. The premise is that in-process(in-line) sterile filtration or thermal sterilization is more effective (and more appropriate) than a classified environment in mitigating the risk of contamination from the environment. The solutes, solvents and personnel used in preparing solutions typically represent more significant sources of contamination that cannot be adequately mitigated with room classification. The method of closing the process needs to be carefully evaluated and selected as some adventitious agents may not be removed by filtration or thermal sanitization alone. Open processes containing process and/or product components that are rendered closed by means of an appropriate closing process. Examples of briefly exposed processes include open buffer or media preparations where the solution is “briefly” exposed to the environment prior to closing by sterile filtration and/or thermal sanitization. For solution preparation, it is important that the interval between formulation and sanitization be defined and validated. Briefly exposed operations may be performed in Controlled Not Classified (CNC) or low bioburden environments if measures used to close the process are appropriate to mitigate risk of contamination from the environment. Pre-closure processing and hold periods and conditions must be carefully monitored and validated. The premise is that in-process (in-line) sterile filtration or thermal sterilization is more effective (and more appropriate) than a classified environment in mitigating the risk of contamination from the environment. The solutes, solvents and personnel used in preparing solutions typically represent more significant sources of contamination that cannot be adequately mitigated with room classification. The method of closing the process needs to be carefully evaluated and selected as some adventitious agents may not be removed by filtration or thermal sanitization alone. Local protected environments: local protected environments may be used for open processes. Examples include BSCs, Unidirectional Down Flow Hoods (UDFHs) or Unidirectional Horizontal Flow Hoods, isolators and RABs. When used, it is critical that the local environment be protected from unexpected breach of the protected environment. Appropriate sanitization and filtration is required to achieve and maintain the stated cleanroom classification within the local protected environment. Appropriate surrounding environments, gowning and other controls may be required to ensure integrity of the local protected environment is maintained especially for BSCs, UDAFs, and RABs. Only a bioburden-free environment should be used for open aseptic operations. A formal risk assessment (see ICH Q9) is required to fully evaluate the appropriateness and quality of the environment used for bioprocess operations and for the environment housing the local protected environments.

Bronchi-associated lymphoid tissue (BALT) – Lymphoid patches and cells in the mucosae of the trachea and lungs. See also mucosa-associated lymphoid tissue (MALT).

Bronchogenic carcinoma – Cancers arising from the pulmonary bronchus and its branches, rather than from the alveoli (oxygen-exchanging sacs). Most of the common cancers of the lung are bronchogenic. The non-bronchogenic tumors account for fewer than 10% of lung cancers and can be considered rare cancers. The bronchogenic cancers are adenocarcinoma, squamous carcinoma, small cell carcinoma, and their various undifferentiated and mixed variants. About 90% of cases of bronchogenic carcinoma arise in smokers. It is safe to presume that some additional percentage of individuals with bronchogenic carcinoma who are non-smokers may have been exposed to second-hand smoke in the workplace or at home (i.e., more than 90% of bronchogenic carcinoma is linked to cigarette smoking or to secondary inhalation of cigarette smoke). Broncho-alveolar car- cinoma, alternately known as bronchioloalveolar carcinoma or as alveolar carci- noma, is a non-bronchogenic lung cancer arising from cells in or near the alveolar sacs. Pure broncho-alveolar carcinoma (i.e., broncho-alveolar carcinoma that is not admixed with adenocarcinoma of bronchogenic origin) and atypical adeno- matous hyperplasia, the putative precancer for bronchioloalveolar carcinoma, do not seem to be linked to cigarette smoking. See Undifferentiated tumor.

Brusch’s membrane – The inner layer of the choroid, separating it from the pigmentary layer of the retina.

BSAS (BosleySalihAlorainy syndrome) – An autosomal recessive syndrome including variable bilateral DRS type 3 (sometimes with complete horizontal gaze restriction bilaterally), deafness due to absence of the hearing apparatus in the petrous bones, cerebrovascular and cardiac malformations, and autism, caused by homozygous mutations in HOXA1.

BSC – see Biosafety Cabinet (BSC).

BSL – see Biosafety Level (BSL).

Bt Corn – Transgenic corn that has the ability to synthesise BT toxin.

BT toxin – Toxin found in the soil bacterium Bacillus thuringiensis, which kills certain caterpillars that destroy crops. Toxin that can be produced by Bacillus thuringiensis and is used as an insecticide in agriculture (e.g., to fight the corn borer- a butterfly whose caterpillars attack corn plantations). It is thought to be nontoxic for organisms that are not direct antagonists (e.g., humans).

Bubonic plague – Virulent bacterial disease spread by fleas and primarily found in rodents.

Bud – The new asexual daughter cell of a yeast that forms as a bulge on the surface of the mother cell.

Buffer – A combination of a salt and acid or salt and base that is able to resist changes of pH in solution.

Bulk – A bulk generally refers to the drug substance, which may be stored in bulk before further manufacturing into a drug product.

Burn rate – The rate at which a new company uses up its venture capital to finance overhead before generating positive cash flow from operations. In other words, it is a measure of negative cash flow i.e. the speed at which the new venture is expending cash to cover its expenses. The speed at which the new venture is expending cash to cover its expenses.

Burst size – Number of infectious virions released per infected cell.

Business model – The combination of factors that describe the business, including the market the business will serve, the perceived value delivered to the customer who determines profitability per unit of sale, and the sustaining factors which will allow the company to drive long-term growth.

Business plan – A document that describes the key components of the business which is used internally and as a capital-raising tool. It usually includes an executive summary, a product or service description, a market and competitive overview, production/operations, the management team, the financial data and projections, and the financial structure of the company.

But-for – From the field of law, the “but-for” test attempts to determine whether a sequence of actions leading to an event could have happened without the occurrence of a particular underlying action or condition. In the realm of death certification, the underlying cause of death satisfies the “but-for” test (i.e., but for the condition, the sequence of events leading to the individual’s death would not have occurred). See also Proximate cause and Underlying cause of death.

BZIP proteins – Family of transcription factors that each have a leucine zipper domain.



CA –  Competent Authority (for the regulation of medicines, either National or EMA)

CA/PA – Corrective Action or Preventative Action.

Carryover – Contaminants detected in process streams arising from insufficient removal of contaminating components fromprevious manufacturing steps or batches. Maximum allowable carryover residues should be estimated and meetdefined criteria. Carryover is typically a result of insufficient cleaning, sanitization, rinsing and/or conditioning.For further information, see the ISPE Baseline® Guide on Risk-MaPP [11].

CCP – Critical Control Point (CCP).

CCS – Container Closure System.

CDC – Centers for Disease Control and Prevention (US).

Cell Culture – Typically refers to Mammalian or Insect cell culture operations.

CFD – Computational Fluid Dynamic (CFD).

CFDA – China Food and Drug Administration (CFDA).

CFR – Code of Federal Regulation (CFR).

CHMP – Committee for Human Medicinal Products.

CHO – Chinese Hamster Ovary (CHO).

CIP – Clean-In-Place (CIP).

Carryover – Contaminants detected in process streams arising from insufficient removal of contaminating components from previous manufacturing steps or batches. Maximum allowable carryover residues should be estimated and meet defined criteria. Carryover is typically a result of insufficient cleaning, sanitization, rinsing and/or conditioning.

Cachexia – Wasting of the body due to uncontrolled cellular catabolism. Cachexia in cancer patients is induced by their high levels of TNF.

CAD (caspase-activated DNase) – A nuclear DNase that cleaves DNA between histones; activated by caspases during apoptosis.

Callus – An unorganised, proliferating mass of undifferentiated plant cells.

Callus culture – Dedifferentiating a mass of plant tissue in vitro and then growing the undifferentiated tissue in a petri dish.

Calmodulin – A small calcium-binding protein of animal cells. Calcium binding protein involved with the second messenger effects of calcium.

Caloric restriction – The theory that decreasing the overall number of calories without altering the nutrient intake will extend the lifespan

cAMP cyclic Adenosine-3′, 5′ Monophosphate – Universal effector for the regulation of enzyme and gene activities. It acts as an intracellular messenger substance between the plasma membrane where it is produced by the enzyme adenylate cyclase from ATP while cleaving off pyrophosphate and certain enzyme systems in the cytoplasm or certain factors in the cell nucleus.

Cancer – Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. It is synonym of a malignant tumour.Derived from the Latin word for crab. It is a cellular tumor composed of cells whose cell division is uncontrolled. The term carcinoma (Greek- crab) has a similar meaning. See also malignant tumour. Tissue or cluster of cells resulting from uncontrolled cell growth and division due to somatic mutations affecting cell division

Cancer immunoediting – Involvement of antitumor immune responses in exerting selective pressure to shape the nature of a cancer. Occurs in three phases- elimination, equilibrium and escape.

Cancer progression – The acquisition of additional properties of the malignant phenotype over time. Progression is achieved through a variety of mechanisms (e.g., genetic instability [18], epigenetic instability, and aberrant cell death regu- lation) and results in the eventual emergence of subclones that have growth advantages over other cells in the same tumor. The presence of subclones of distinctive phenotype and genotype within a single tumor accounts for tumor heterogeneity [19]. Tumors that grow without accumulating changes in geno- type or phenotype tend to be benign (i.e., benign tumors do not progress or their rate of progression is much less than that observed in malignant tumors). See Tumor heterogeneity.

Cancer stem cells (CSCs) – Rare cells within a tumour that are capable of establishing a new tumour if transplanted into a suitable recipient.

Cancer-causing syndrome – There are many inherited conditions that are associated with susceptibility to multiple types of cancers. Cancers that arise in these syndromes often occur in children or at an age earlier than the average age of occurrence of their sporadic equivalents. A few examples of eponymic (named for a person) cancer syndromes are: Bloom syndrome, Carney syn- drome, Cowden syndrome, Fanconi anemia, Li–Fraumeni syndrome, Lynch cancer family syndrome, Muir–Torre syndrome, Von Hippel–Lindau syndrome.

Cancer-testis antigens – Proteins that are normally expressed solely in spermatogonia and spermatocytes but become tumour-associated antigens (TAAs) when transformation causes them to be expressed on other cell types.

Candidate cloning – Approach to cloning that involves making an informed guess as to what kind of protein is likely to be involved in a hereditary disorder.

Candidate gene – Any gene that by virtue of a known property (func-tion, expression pattern, chromosomal location, or structural motif) is considered as a possible locus for a given disease.

Candidate gene approach – One of several methods whereby the gene that causes a disease may be discovered. In the candidate gene approach, the researcher begins with some insight into the disease, and the various pathways and metabolic activities that are affected. The researcher chooses a candidate gene to study, based on knowledge of the function of the gene, and a suspicion that alterations in the gene might play an important role in the pathogenesis of the disease. She studies the sequence of the candidate gene in DNA samples from a set of people with the disease, and compares her findings with the sequence of the gene in DNA samples from a set of people who do not have the disease. Consistent differences between the gene in the disease-carrying individuals and the control subjects would suggest that the gene contributes to the development of the disease. Finding a disease association for a candidate gene does not tell us whether other, unexamined, genes may play an important role in disease devel- opment. Conversely, failing to find an association does not rule out the presence of an association that was not detected in the gene sequence (e.g., a defect in any of the processes that regulate the transcription, assembly, or deployment of the final gene product).

Cap – Structure at the 5′ end of eukaryotic mRNA consisting of a methylated guanosine attached in reverse orientation.

CAP (catabolite activator protein) – A transcription enhancer protein that activates the transcription of sugar metabolizing operons when bound by cAMP (also CRP-cyclic AMP receptor protein)

Cap snatching – It refers to a step in transcription process, which involves the cleavage of RNA fragments from the 50 end of cellular mRNAs.

CA/PA – Corrective Action or Preventive Action—this term refers to the outcomes of an investigation into a deviation or violation, in terms of what actions will be taken to correct the deviation, if possible, in the current situation, and to prevent the deviation from occurring again in the future.

CA/PA review – A review under the umbrella of the CAPA system conducted by dedicated members of the site management to determine if quality events are being reliably identified, investigated, and corrected. This review includes the review of CAPA reports to determine if preventive actions are required and if additional investigations and/or corrective actions need to be initiated and performed.

CA/PA review board (CRB) – A review under the umbrella of the CAPA system is conducted by dedicated members of the site management to determine if quality events are being reliably identified, investigated and corrected. The board reviews the trend analysis from the different quality data sources to determine if preventive actions are required and if additional investigations and/or corrective actions need to be initiated and performed.

Capacitance – The ability of a potential difference to be stored between two charged surfaces. If the density of charge per unit area is increased, the capacitance is increased. If the distance between the charged surfaces is increased, the capacitance is decreased.

Capital – The term refers to funds (generally cash) generated by a company to support its operations. In a very general sense, the term describes funds produced through issuing either debt or equity securities, whereas the capital section of the balance sheet normally refers to owners or stockholders equity.

Capital structure – The term refers to the mixture of equity and debt that a firm has raised.

Capsid – A structure containing the viral genome that is composed of repeating viral proteins. Shell or protective layer that surrounds the DNA or RNA of a virus particle. Protein shell of a virus in which its genome is contained. Capsids consist of regular-shaped subunits called capsomeres that contain one or several proteins. Capsids act as antigens within the immune system. This can make them a good choice for vaccines.

Capsomere – A visible morphological unit that composes the capsid (e.g., pentamer or hexamer).

CAR (Coxsackie-Adenovirus Receptor) – CAR is a type 1 membrane receptor with two Ig-like domain. CAR is an entry receptor for coxsackie type B3 as well as adenovirus type 5. Receptor on animal cells shared by adenoviruses and B-group coxsackieviruses.

Carbohydrate – A polyhydroxy compound with the general formula- Cn(H2O)n that may have other functional groups such as a carbonyl group. Sugar and saccharide are alternate names. Organic molecules composed of simple sugars. They can be simple sugars themselves or polymers containing large numbers of them.

Carboxypeptidase – Enzyme that removes C-terminal amino acid residue from a protein.

Carboxypeptidase H – A particular carboxypeptidase that is needed during the processing of insulin.

Carcinogen – Any substance or agent that significantly increases the incidence of malignant tumors by mutating or deregulating oncogenes, tumor suppressor genes or DNA repair genes. Cancer-causing agent. The term “carcinogen” is used differently by different people. Confusion arises because carcinogenesis is a multi-step process that can be modified at many different biological stages. Some people use the term “carcinogen” to mean a chemical, biological, or physical agent that, when exposed to normal cells, will result in the eventual development of cancers (i.e., the carcinogen acting as the underlying cause of the cancer). Sometimes, the term “complete carcinogen” is used to emphasise the self-sufficiency of the agent as the primary underlying cause of a cancer. Others in the field use the term “carcinogen” to mean anything that will increase the likelihood of tumor development. An agent that causes an increase in the number of tumors that are produced by a complete carcinogen, or an agent that must be followed or preceded with another agent for tumors to occur, or a process that increases the number of cancers occurring in a population known to be at high risk of cancer due to an inherited condition, would all be considered carcinogens under this alternate definition.

Carcinogenesis – Multistep process by which malignant transformation of a cell culminates in cell growth deregulation and the formation of a malignant tumour. Steps are initiation, promotion, progression and malignant conversion. The cellular events in a multi-event process that leads to cancer, equivalent to the pathogenesis of cancer. Carcinogenesis in adults is a long process that involves the accumulation of genetic and epigenetic alterations that confer the malignant phenotype to a clone of cells. The envi- sioned sequence of events that comprise carcinogenesis begins with initiation, wherein a carcinogen damages the DNA of a cell, producing a mutant clonal founder cell that yields a group of cells that have one or more subtle (i.e., morphologically invisible) differences from the surrounding cells (e.g., less likely to senesce and die, more likely divide, less genetically stable, better able to survive in an hypoxic environment). After a time, which could easily extend into years, subclones of the original clone emerge that have additional properties that are conducive to the emergence of the malignant phenotype (e.g., new mutations that confer growth or survival advantage, greater ability to grow in hypoxic conditions). The process of continual subclonal selection continues, usually for a period of years, until a morphologically distinguishable group of cells appear: the precancer. Subclonal cells from the precancer eventually emerge, having the full malignant phenotype (i.e., the ability to invade surrounding tissues and metastasise to distant sites). The entire process can take decades.

Carcinoma – Cancer that originates in epithelial cells.

CARD (caspase recruitment domain) –  CARDs are “interaction motifs” found in a wide array of proteins, typically those involved in processes related to inflammation and apoptosis. These domains mediate the formation of larger protein complexes via direct interactions between individual CARDs.

Cardia bifida  – The formation of two beating and looping heart tubes as a result of the improper fusion of the heart primordia.

Cardiac stem cells – SCs and progenitors distributed within the adult cardiac muscle (myocardium). Under normal conditions, cardiac progenitors are quiescent and do not contribute to the renewal of cardiomyocytes, specific muscle cells of the heart. After an injury or a heart attack, these progenitors are activated and differentiated into new myocytes and vascular cells.

Cardiolipin – A trigycerolic lipid complex variant of a phospholipid that is found significantly in mitochondria. Its function is unknown.

Cardiomyocyte- Heart muscle cell that contracts synchronously with other heart muscle cells in the beating heart.

Cardiotoxicity – The toxic effect of a substance on the heart or, more broadly, on the cardiovascular system. It is expressed by functional disorders of the cardiac muscle (myocardium), such as rhythm disorders, conduction disorders and high blood pressure.

Carrier – A person who carries an allele for a recessive disease (see Heterozygote) without the disease phenotype but who can pass it on to the next generation. In the field of genetics, a carrier is an individual who has a disease- causing gene that does not happen to cause disease in the individual. For example, individuals with one sickle cell gene are typically not affected by sickle cell disease, which usually requires homozygosity (i.e., both alleles having the sickle cell gene mutation) for disease expression. When two carriers mate, they pass the homozygous state to offspring with a likelihood of 25%. As another example, carriers may also have a low-penetrance disease gene. In such cases, offspring with the same gene defect as the carrier may develop disease. In the field of infectious diseases, a carrier is an individual who harbors an infectious organism, but who suffers no observable clinical consequences. If the carrier state is prolonged, and if infectious organisms cross to other individuals, a sin- gle carrier can produce an epidemic.

Carrier (or adjuvant) – An agent used to increase the antigenicity of a vaccine.

Carrier testing – A form of genetic testing used on individuals who may not present with any genetic disorder but are at risk of passing down the trait due to being a carrier. This usually relates to being a carrier of an autosomal recessive or X-linked disorder. Carried out to determine whether an individual carries one copy of an altered gene for a particular recessive disease.

Carrying capacity – Maximal quantity that can be indefinitely supported by the environment. Carrying capacity can be fixed or dynamic, i.e., increase or decrease as a result of dynamics of the other variables in the system.

Cas9 (CRISPR Associated Cas Protein 9) – A specialised endonuclease that has the ability to cut DNA strand. Cas9 is widely used in genome editing.

Cascade – A sequence of biochemical reactions that process a neural signal. A term borrowed from electronics that refers to any enzyme amplifying mechanism that increases the original biological signal made to a cell.

Cash flow – The movement of cash associated with a company’s operating, investing, and financing activities. Cash flow involves inflows and outflows of cash. A company’s cash flow is considered strong if it can generate large amounts of cash relatively quickly. Cash flow is an important part of solvency.

Caspase – Enzyme that carries out the protein degradation characteristic of apoptosis; caspases cleave other proteins after aspartic acid residues. A protease requiring Asp as part of its substrate and which itself contains Cys as part of its amino acid sequence.

Caspase-activated DNase (CAD) – A nuclear DNase that cleaves DNA between histones; activated by caspases during apoptosis.

Catalase – Enzyme that converts hydrogen peroxide to oxygen plus water

Catecholamines – Family of neurotransmitters including dopamine, adrenalin (= epinephrine), and noradrenalin (= norepinephrine).

Cassette – Any segment of DNA that is introduced into a host’s DNA may be referred to as a DNA cassette.

Catabolic process – One or more chemical reactions in which energy is extracted from a chemical compound. For example, the formation of adenosine triphosphate from glucose.

Catabolism – Metabolic pathways by which complex molecules are broken down into smaller molecules and energy is released. It is the opposite of anabolism. Apart from setting free energy, it can also break down toxic substances.

Catalase – Enzyme catalyzing the breakdown of hydrogen peroxide into oxygen and water.

Catalyst – Any chemical substance that can speed up a chemical reaction without itself being altered by the reaction. It achieves its goal by lowering the activation energy for the reaction.

Cataract – Any opacity in the lens that causes an alteration to perceived vision.

Catenated – Structure in which two or more circles of DNA are interlocked.

Cause of death – In the case of a natural death (i.e., not homicidal and not accidental) a cause of death is one item from a standard list of medical conditions known to produce death in humans. The term “causes of death” implies that multiple different conditions may contribute to a person’s death, and the term does not provide a clue as to which condition meets “but-for” criteria. See But- for and Underlying cause of death.

Cause of death error – Cause of death data comes from death certificates. Death certificate data have many deficiencies. The most common error occurs when a mode of death (i.e., the way that an individual dies) is listed as the cause of death. For example, cardiac arrest is not a cause of death, though it appears incorrectly as the cause of death on many death certificates. An international survey has shown very little consistency in the way that death data are collected. Most death certificates are completed without benefit of an autopsy (i.e., without using the most thorough and reliable medical procedure designed to establish the causes of death). In the absence of an autopsy, a death certificate expresses a clinician’s reasonable judgment at the time of a patient’s death. See Cause of death.

Caveolins – A family of integral membrane proteins which are the principal components of caveolae membranes.

CBE – Changes Being Effected- a submission to U.S. FDA notifying them of changes being implemented immediately upon U.S. FDA notification.

CBE30 – Changes Being Effected in 30 days- a submission to the U.S. FDA reporting changes to an approved application for changes that may be implemented after 30 days of U.S. FDA being notified. These changes have moderate potential to impact the product.

CBER – Center for Biologics Evaluation and Research (CBER)- the component of U.S. FDA that regulates most biological products, particularly blood and blood products, vaccines and related products, cell therapies, and gene therapies. Therapeutic proteins are regulated by CDER.

CCR5 – A protein that acts as a coreceptor for entry of HIV into host cells. Its natural role is as a chemokine receptor

CD marker – Cluster of differentiation marker. A cell surface protein identified by the binding to that protein of a cluster of different antibodies. Each CD marker is given a unique numeric designation. Also known as a CD molecule.

CD1 molecules – Unconventional antigen presentation molecules that present non-peptide antigens (lipid or glycolipid antigens) to subsets of αβ and γδ T cells and NKT cells.

CD3 complex – Family of five ITAM-containing accessory chains necessary for TCR signaling and insertion of the TCR complex in the membrane. See also TCR complex.

CD4 – A glycoprotein found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. CD4 is best known as a cellular marker for T helper lymphocyte.

CD4 protein – Protein found on the surface of many T cells that is used as a receptor by the AIDS virus.

CD80 and CD86 – B7 costimulatory ligands expressed by antigen presenting cells. They interact with coreceptors CD28 and CTLA4 on T cells and are necessary, but not sufficient for T-cell activation.

CD81 – A ubiquitously expressed protein and a member of the tetraspanin superfamily.

CDAC – Consortium Data Access Committee.

CDC – Centers for Disease Control and Prevention- the U.S. federal agency responsible for surveillance of disease in the United States.

CDER – Center for Drug Evaluation and Research (CDER)- the component of U.S. FDA that regulates chemical drugs for human use and therapeutic biotechnology protein products, e.g., monoclonal antibodies, interferons, insulin.

cDNA copy/complementary DNA – A piece of DNA copied in vitro from mRNA by a reverse transcription enzyme. cDNA is a single or double-stranded DNA copy of an RNA molecule. The synthesis of cDNA is catalyzed by the enzyme reverse transcriptase.

CDRH – Center for Devices and Radiological Health—the component of U.S. FDA that regulates medical devices and radio-active medicines. Biotechnology products like in vitro diagnostics are regulated by CDRH.

Cell culture – The maintaining of cells generally from vertebrate species in vitro. Cells directly from donor tissue (primary) or from immortalised or transformed lines are supplied with a culture medium that provides nutrients necessary for survival and proliferation.

Cell cycle – The period during which a cell grows, replicates its DNA, and divides into two daughter cells. A series of tightly regulated steps that a cell goes through from its creation to division to form two daughter cells. Cell cycle is the series of events that take place in a cell leading to its division and duplication (replication) that produces two daughter cells. Series of stages that a cell goes through from one cell division to the next.

Cell fate – The neuronal subtype that a progenitor will become. This term does not imply commitment or differentiation, only that the cell will eventually become a certain type.

Cell line – A population of cells maintained in a laboratory that can divide indefinitely without changing. For example, some cancer cells, obtained from tumors, can be cultured as a cell line in the laboratory and give rise to very large cell numbers. Pluripotent stem cells that can be cultured as a cell line are unique in that they are “normal” cells and not cancer cells or “transformed.” Cells that can be maintained and grown in culture and display an immortal or indefinite life-span.

Cell lineage – The developmental history of a cell, tissue, or organ as traced back to the cell from which it arose.

Cell migration – A process during which cells translocate their cell body to a new location according to various signals present in their local environment. Such signals include extracellular matrix, guidance cues and contacts with other cells.

Cell therapy preparation (CTP) –  These preparations are not ATMPs because the changes made to the tissues or cells are not substantial, that is to say their properties are not modified (e.g. hematopoietic SCs for hematological reconstruction).

Cell type – The number of different kinds of cells in an organism varies based on how you choose to categorise and count them, but most would agree that there are at least 200 different cell types in the adult body. The number of cell types that appear for a short period during in utero development, then disappear before birth, is not included in the count. It can be difficult to assign a cell type to a fetal cell whose precise function cannot be specified. Every cell type in the body has the same genome as every other cell; the differences between one cell type and another are determined by the epigenome. Because differentiated cells under normal conditions do not change their cell type (e.g., a hepatocyte does not transform into a neuron), and because cell types of a given lineage produce other cells of the same lineage (e.g., a dividing hepatocyte produces two hepa- tocytes), then we can infer that the epigenome is heritable among somatic cell types.

Cell-mediated immunity (CMI) – An immune response generated by the activities of non-antibody-producing cells. Originally, adaptive immune responses mediated by effector actions of cytotoxic T lymphocytes. Now includes effector actions of NK and NKT cells. Type of immunity that relies on T cells and cell–cell interactions (rather than on antibodies made by B cells).

Cellular senescence – Arrested cell division of cultured mammalian cells; same as replicative senescence.

Cellulose – Structural polymer of β-1,4-linked glucose found in plant cell walls.

Cementoblast – A biological cell that forms from the follicular cells around the root of a tooth, and whose bio- logical function is cementogenesis, which is the creation of cementum (the hard tissue that covers the root of the tooth).

Cementum – A specialised calcified substance covering the root of a tooth.

Centimorgan (cM) – A distance on a chromosome equal to approximately 1 million base pairs. It is computed on the basis of a distance at which a genetic recombination will occur by a given percentage. A unit of genetic distance equivalent to 1% probability of recombination during meiosis. One centimorgan is equivalent, on average, to a physical distance of approximately 1 megabase in the human genome.

Central dogma of molecular biology – Describes the flow of genetic material in that DNA encodes for RNA (transcription), which in turn then encodes for proteins (translation). Exceptions to the classic dogma are now known to exist. A term proposed by Francis Crick in 1957: “DNA is transcribed into RNA which is translated into protein.” Basic plan of genetic information flow in living cells that relates genes (DNA), message (RNA), and proteins.

Central memory T cells (Tcm) – Class of memory T cells that act as a long-term central reservoir of memory T cells in the lymph nodes and other secondary lymphoid tissues.

Central retinal artery – A branch of the ophthalmic artery which pierces the optic nerve close to the globe, sending branches to the internal surface of the retina.

Central tendon (of the diaphragm)  – The central tendon is the unmuscularised region of the diaphragm that has differentiated into a mature tendon. It makes up the center of the diaphragm, and it is attached to the liver by the falciform ligament. Distinct myotendonous junctions form the boundary between the central tendon and the peripherally muscularised regions.

Central tolerance – Mechanism that eliminates most autoreactive T and B cells during lymphocyte development. Es tablished by negative selection processes in the thymus and bone marrow.

Centroblasts – Rapidly proliferating, antigen-activated B cells that fill the dark zone of a germinal center (GC) and undergo somatic hyper mutation.

Centromere – Central location of a chromosome that is an attachment point for proteins involved in chromosome segregation during cell division. Region of eukaryotic chromosome where the microtubules attach during mitosis and meiosis. The constricted region near the center of a chromosome that has a critical role in cell division.

Centromere (Cen) sequence – Sequence at centromere of eukaryotic chromosome that is needed for correct partition of chromosomes during cell division

CEO duality – means that the chief executive officer (CEO) is also the chairperson of the board of directors.

Cephalosporins – Subfamily of antibiotics belonging to the β-lactam family of antibiotics.

CFTR protein – Cystic fibrosis transporter- protein encoded by the cystic fibrosis gene and found in the cell membrane where it acts as a channel for chloride ions.

CEPRES – Abbreviation for the Center of Private Equity Research. It was founded in 2001 as a cooperation between VCM Capital Management GmbH and the chair of banking and finance at the Johann Wolfgang Goethe-University of Frankfurt am Main. Its purpose is to gain insight into the future trends of the private equity industry via quantitative analyses of private equity market data.

Ceramide – The compound formed when a fatty acid is esterfied to sphingosine.

Cerebroside – A ceremide to which a single sugar molecule is bonded via an oxygen bridge.

Certificate of Analysis (CoA) – A document that accompanies a batch or lot showing the release testing, specifications, and results. It should also identify any components used in making it, e.g., which bulk substance batch (es) were used to make the drug product lot. Documents should accompany the COA, when submitting it to the regulators, providing the evidence of the test results.

Certificate of confidentiality – A documented agreement on the part of the DHHS that researchers conducting a particular study will not be required to divulge any personally identifying information about the study’s subjects in any administrative or judicial court proceedings other than those already required by law.

Cervonic acid – Fatty acid, also known as docosahexaenoic acid. This highly unsaturated fatty acid (22-6) is a common constituent of photoreceptor discs and membranes where it imparts a high degree of fluidity to the membrane.

CFEOM (congenital fibrosis of the extraocular muscles) – A group of congenital, nonprogressive strabismus disorders that may be sporadic, familial, or teratogenic.

CFEOM1 – An autosomal dominant congenital bilateral ptosis with globes infraducted bilaterally and unable to elevate even to primary gaze; in general, ocular motility is restricted bilaterally in an asymmetric fashion in all directions; sometimes associated with DRS; caused by heterozygous mutations in KIF21A.

CFEOM2 – An autosomal recessive congenital bilateral ptosis with a large exotropia and complete inability to adduct, elevate, or depress either globe, often with partial restriction of abduction bilaterally as well; associated with unreactive pupils; caused by homozygous mutations in PHOX2A.

CFEOM3 – An autosomal recessive congenital bilateral ptosis and asymmetrically restricted ocular motility similar to CFEOM1, but in general less severe so that globes can be elevated to primary position; associated with heterozygous mutations in KIF21A, a locus at 16q24.2–q24.3, and other heterozygous mutations.

CFR – Code of Federal Regulations- the federal regulations that explain how the U.S. government expects laws to be enforced. Title 21 of the CFR (21 CFR) are the federal regulations that govern U.S. FDA-regulated products.

CG islands – Region of DNA in eukaryotes that contains many clustered CG sequences that are used as targets for cytosine methylation.

cGMP – Current Good Manufacturing Practices- see also GMP definition- regulators expect manufacturers to keep current with best industry practices.

Chain termination sequencing  –  Method of sequencing DNA by using dideoxynucleotides to terminate synthesis of DNA chains. Same as dideoxy sequencing

Chain terminator  – Nucleoside analog that is incorporated into a growing DNA chain but prevents further extension of the DNA chain

Chalazion – Benign, typically painless, inner eyelid nodule due to a blocked oil gland.

Challenge study – In vaccine development, a challenge study is a double-blind, placebo-controlled study of the safety and protective efficacy of a vaccine challenged against a live virus. The challenge study takes place in a specialised clinical trial unit. Its primary purpose is to determine whether antiviral vaccines can prevent development of symptoms in human volunteers. Each volunteer is given either the vaccine or placebo and is then exposed to, or ‘challenged with, a live virus. The volunteers will be monitored for at least one month. After immunogenicity of the vaccine has been demonstrated, a safety board will decide if the volunteers will be challenged with the live virus. The infected volunteers are housed in detached buildings and are physically isolated from both staff and co-volunteers.

Channel – An protein-lined opening in the plasma membrane that allows small molecules or ions to pass through the cell membrane.

Channel forming proteins – Proteins that are capable of initiating a passageway for transport of some substance(s) through a membrane (usually a plasma membrane).

Channel protein – Protein that conducts any substance across a cell membrane. Such substances are often ions. Gate protein has the same meaning.

Channelopathy – Disorders of the electrical systems in humans, all of which depend on the depolarization and repolarization of electrical current (i.e., the flux of charged molecules) across ion channels (e.g., sodium channel, potas- sium channel, chloride channel, calcium channel). Ion channels are found on the membranes of specialised cells. Disorders of these channels are termed channelopathies, and encompass a wide range of neural, cardiac, and muscular disorders and always play at least a contributing role in common seizures and arrhythmias. Specific rare conditions in which channel disorders play a princi- pal role, in at least some forms of the disease, include: Alternating hemiplegia of childhood, Bartter syndrome, Brugada syndrome, congenital hyperinsulin- ism, cystic fibrosis, Dravet syndrome (severe myoclonic epilepsy of infancy), episodic ataxia, erythromelalgia (Mitchell disease), generalised epilepsy with febrile seizures plus, familial hemiplegic migraine, hyperkalemic periodic paralysis, hypokalemic periodic paralysis, long QT syndrome, malignant hyperthermia, mucolipidosis type IV, myasthenia gravis, myotonia congenita, neuromyotonia, non-syndromic deafness, paramyotonia congenita, retinitis pig- mentosa, short QT syndrome, and Timothy syndrome.

Chaperone – A protein that tends to renature denatured proteins; that is, return them to their normal conformation. Protein that mediates the refolding of misfolded or unfolded proteins.

Chaperone-mediated autophagy – A system of protein degradation in which a chaperone protein recognises the protein through a specific amino acid sequence and transfers it to the lysosome for degradation.

Chaperone-mediated folding – Mechanism of repairing misfolded proteins where a chaperone enzymatically unfolds and refolds the defective proteins.

Chaperonin – Protein that oversees the correct folding of other proteins

Characterisation – This term is generally used to mean defining the characteristics of a product (or cell bank or analytical procedure, etc.). These characteristics (when used to describe the product) may be physicochemical, biochemical, immunological, microbiological, or biological ones. Generally, specifications are not set for characterization analyses or studies, but merely that these studies are undertaken to define what the product’s character istics are. Sometimes, characterization studies are used to determine that the product is not optimised and further refinement of the production processes are needed to gain the desirable characteristics for the product. Other times, they are used solely to determine what the characteristics are. Often, characterization analyses are undertaken only once, as opposed to lot release procedures, for which each and every lot of product is tested before releasing the lot to the clinic or market. Characterization results are simply accepted as they are and provide evidence about the product, which requires no further confirmation as new lots are made. Although, if substantial changes are made to the product/process, then new characterization studies might be undertaken to determine the impact of these changes.

Checkerboard hybridization – Technique for mass screening of DNA samples using probes to 16S rRNA genes corresponding to many different bacteria.

Checkpoints – Internal controls that prevent a cell from proceeding into the next stage of the cell cycle until the previous stage has been satisfactorily completed.

Checkpoint inhibitors – Drugs that target mechanisms of immune cell activation and survival (checkpoints). Normally, checkpoints act as protection against autoimmune diseases. Blocking checkpoints allows immune cells to become and stay activated longer, increasing tumor cell kill by the immune system.

Chemoattractant – Any substance that can cause a directional movement of a cell (usually a white blood cell) based on the concentration gradient of that substance.

Chemokine – A chemoattractive cytokine. A cytokine that stimulates white blood cells to move to a tissue target. An allele of the beta-chemokine receptor 5 (CCR5) gene seems to confer a high level of protection against HIV infection. In a study of over 1200 individuals at risk for HIV infection, the homozygous allele was always absent from infected individuals. Among the individuals at high risk of HIV infection who remained infection free, the homozygous allele was found in 3.6% of the population. A class of chemotactic cytokine signaling molecules secreted by cells that direct the chemotactic response of other cells. They are divided into CXC, CC, CX3C and XC subfamilies. Cytokines that induce leukocyte migration. Group of approximately 50 small messenger peptides that activate the white cells of the immune system

Chemokine receptor – Cell surface protein required for uptake of chemokines into animal cells. It refers to cytokine receptors found on the surface of certain cells that interact with a type of cytokine called a chemokine. It belongs to the family of G-protein coupled receptor (GPCR) that has a 7 transmembrane (7TM) domain.

Chemotaxis – A process in which white blood cells are drawn to the site of a complement reaction by complement fragments C3a, C4a, and C5a. Movement of cells along a concentration gradient of chemotactic factors. The directed movement of cells along the concentration gradient of a chemotactic factor. Serves to draw neutrophils, lymphocytes, and other leukocytes from the circulation into an injured or infected tissue.

ChIA-PET – An adaptation of 3C technologies that employs high throughput sequencing. This method utilises ChIP to find regions of DNA looping associated with a specific transcription factor.

Chimera – An organism or DNA derived from two distinct individuals. Organism made up of cells from more than one individual. For example, a chimeric mouse can result from insertion of embryonic stem cells into a blastocyst-stage embryo that is placed into the uterus of a surrogate mother mouse for further development. The mouse that is born contains cells from the blastocyst and from the embryonic stem cells. The definition is sometimes used broadly to include organisms in which cells from another individual have been introduced at later stages of fetal development or in an adult.

Chimeric animal – Animal in which different cells vary genetically.

Chimeric Antigen Receptor (CAR) – A receptor designed and genetically introduced into an immune system cell (e.g. T cells) that can bind to specific antigens such as tumour associated antigens (TAAs).

Chimerism in the Bone Marrow – Usually refers to blood stem cells from a transplant donor being introduced into the bone marrowrecipient prior to an allogenic cell or organ transplantation. This form of chimerism may make recipients “immunotolerant” to othercells and tissues from the same donor and prevent transplant rejection.

ChIP (chromatin immunoprecipitation) – A biochemical technique in which an antibody is bound to chromatin (DNA + protein), genomic DNA is cleaved into small fragments, and DNA bound by the antibody is pulled down and sequenced (ChIP-seq) or hybridised to a microarray (ChIP-chip).

ChIP-chip – Technique to identify the sequence of transcription factor binding sites by whole- genome arrays after the binding sites are cross-linked to the transcription factors and isolated by immunoprecipitation

ChIP-seq – A high throughput sequencing method employing immunoprecipitation of fragmented chromatin to identify sites bound by a protein, genome-wide.

Choriocapillaris – The capillaries forming the inner vascular layer of the choroid.

Choriocapillaris pillars – Lateral walls of the choriocapillaris.

Choroid – The layer of the eye containing blood vessels that furnish nourishment to the other parts of the eye, especially the retina.

Chloroplast transit peptide – A small peptide added to the N-terminus of a protein that directs the protein from the ribosome into the chloroplast

Chinese Hamster Ovary (CHO) cells – Cell lines obtained from the ovaries of the Chinese dwarf hamster species Cricetulus griseus, which are often used in biological and medical research. They can be cultivated in suspension in bioreactors with the amino acid proline as a supplement in the broth.

Cholera toxin – Protein toxin made by Vibrio cholerae that hyperactivates the adenylate cyclase of animal cells

Cholesterol – Sterol derivative found in humans and other animals that has a major effect on atherosclerosis.

Chromatin immunoprecipitation (ChIP) – Immunoprecipitation of transcription factors cross-linked to their binding sites on DNA.

Cholinergic – Referring to nerve fibers that use acetylcholine as a transmitter.

Chondrocyte – A cell that secretes, and resides within, the matrix of cartilage.

Choriocapillaris – A layer of capillaries in the choroid immediately adjacent to Bruch’s membrane.

Choroidal neovascularisation – Formation of new blood vessels that are from the choroidal layer in the eye.

Chromatid – One half of a paired chromosome after DNA replication. The members of the pair are joined at the centrosome before they separate during mitosis.

Chromatin – A compactly packed mass of genetic material containing proteins and DNA that eventually forms a chromosome. Also the genetic material in a cell that is readily stainable in the nucleus. Complex of DNA plus protein that constitutes eukaryotic chromosomes.

Chromatography – Collective term for physical/ chemical methods for the separation of mixtures of substances for analysis or preparation purposes, using a stationary phase and a mobile phase.Assorted techniques that separate a mixture of molecules by size or chemical properties.

Chromatography column – A long tube that contains the stationary phase for chromatography

Chromosomal disorder – Disorders associated with physical abnormalities in the physical structure of the chromosome. An example is found in fragile X syn- drome. In this disease, a not uncommon cause of mental retardation, fragile sites are inherited as poorly condensed regions of the chromosome. Under experi- mental conditions, these regions break easily. Fragile sites have been associated with CCG repeats. Other examples of chromosomal disorders include Pelger– Huet anomaly and Roberts syndrome.

Chromosomal karyotype – A photographic representation of an individual cell’s chromosomes that is used to analyse the number and structure of the chromosomes.

Chromosomal microarray – Evaluates the genome in high resolution by using arrayed small DNA pieces to provide a locus by locus measurement of DNA copy number variation at numerous loci simultaneously.

Chromosome – A long chain of DNA and associated proteins located in the nucleus that contains genetic information. A single double-stranded molecule of DNA and its associated proteins that are found in eukaryotic cells, viruses, bacteria, or even an organelle. However, at metaphase a “chromosome” actually consists of two chromosomes (chromatids) bound together. A thread-like structure of proteins and DNA found in the nucleus of cells. It carries genetic information of an organism in the form of genes and translates them into proteins.An organised and packed structure of DNA, RNA, and proteins located within a cell. Subcellular structures that contain and convey the genetic material of an organism. The physical structure consisting of a large DNA molecule organised into genes and supported by proteins called chromatin.

Chromosome conformation capture (3C or CCC) – An experimental method that employs quantitative polymerase chain reaction (PCR) to identify transcriptional targets of enhancer elements on the basis of physical interactions between enhancers and promoters.

Chromosome painting – Fluorescent labeling of whole chromosomes by a fluorescence in situ hybridization (FISH) procedure, in which labelled probes each consist of a complex mixture of different DNA sequences from a single chromosome.

Chromosome translocation – An abnormality that involves the exchange of genetic material of nonhomologous chromosomes. Translocations can involve the exchange of equal amounts of material (balanced) or involve addi- tional or missing material (unbalanced).

Chromosome walking – Method for cloning neighboring regions of a chromosome by successive cycles of hybridization using overlapping probes

Chronic disease – A disease in which symptoms are experienced on an ongoing or recurring basis. See also persistent infection.

Chronic graft rejection (CGR) – Immune response against an allograft that occurs several months after transplantation and leads to loss of allograft function.

Chronic inflammation – An inflammatory process lasting more than a few days and characterised by the presence of macrophages.

Chronic progressive ophthalmoplegia (CPEO) – This term describes a number of disorders affecting the extraocular muscles that lead to progressive limitation of eye motion.

Chronic wasting disease (CWD) – Prion disease of deer and elk in the northern United States.

Chronological aging – Length of time the yeast cell can live without dividing.

Circum-sporozoite protein – Protein on surface of sporozoite stage of malarial parasite.

Cicatricial lagophthalmos – Inability to close eyelids due to scarring.

Cicatricial pemphigoid – A presumed autoimmune conjunctivitis affecting the mucosal tissue on the ocular surface. An immune attackis made on the conjunctival epithelial cells.

CIE, Commission Internationale de l’Eclairage – The CIE is an independent, nonprofit organization responsible for the international coordination of lighting-related technical standards, including colorimetry standards.

Ciliary margin – The most peripheral region of the retina. In the frog and fish, this region contains dividing retinal progenitor cells that contribute to retinal growth and/or repair.

CIOMS – Council for International Organizations of Medical Sciences, whose mission is to advance public health through guidance on health research including ethics, was established jointly by WHO and UNESCO.

Circadian clock – A cell-autonomous, cyclical autoregulatory molecular mechanism, involving genes – clock genes and their proteins that generate circadian molecular oscillations.

Circadian oscillator – A system that generates self-sustained oscillations or rhythms of about 24 h. Current models include self-sustained transcription and translation feedback loops that operate at the cellular level to provide outputs that are circadian in nature.

Circadian rhythms – Changes in biological processes that occur on a daily basis; they are driven by autonomous circadian clocks; these rhythms provide selective advantage to organisms by allowing them to anticipate temporal changes in their environment.

Cirrhosis – Scarring of the liver. Cirrhosis is a result of advanced liver disease. It is characterised by the replacement of liver tissue by fibrous connective tissue (scar tissue) and regenerative nodules. Cirrhosis (from Greek kirrhos “yellowish” and the common Greek suffix -sis meaning “condition”).

Cis-acting – A gene regulation function that is exerted by some segment of genetic material on another segment of genetic material. In most instances, a short sequence of DNA regulates the transcriptional activity of a nearby gene that codes for a protein. The cis-acting sequence is typically activated or inacti- vated by some diffusible molecule that attaches to the cis-acting sequence. Cis- acting processes apply to RNA as well as to DNA. The regulation of alternative splicing of mRNAs employs proteins that bind to cis-acting sites on pre-mRNA. See Trans-acting.

Cis-acting elements – It refers to the factors that are not diffusible (ie, the sequence element present in the plasmid).

Cis-genetic engineering – is the transfer of genes between organisms of the same species, e.g., different apple varieties. Researchers have created the first fire blight-resistant apple. With the aid of cis-genetic engineering, they transferred a resistance gene from a wild apple into the genome of a Gala apple. Tests in the greenhouse indicate that the gene is effective in protecting the tree from the disease.

Cis-regulatory elements (CREs) – A distinct region of DNA of a gene that influences its transcription. CREs can be located upstream of the transcription start site or may be located downstream. These sequences can be modular in nature.

Cistron – Segment of DNA (or RNA) that encodes a single polypeptide chain.

Citric acid cycle – tricarboxylic acid cycle (TCA cycle), or the Krebs cycle. Respiratory cycle of the cell, comprising a series of chemical reactions in which acetyl-CoA is oxidised to form carbon dioxide and hydrogen atoms which are stored asNADH+ H+ and FADH2.

Clade – A group of organisms that share a common evolutionary ancestor.

Cladistics  – A system of biological classification based on using quantitative analysis of physical traits to construct evolutionary relationships

Clamp-loading complex – Group of proteins that loads the sliding clamp of DNA polymerase onto the DNA

Class I device – Devices in this class are governed by the FDA standards that apply to all medical devices prior to the 1976 Amendments. Class I devices are not designed to support or sustain human life or prevent impairment.

Class I major histocompatibility complex (class I MHC) – MHC proteins consisting of two chains of unequal length and found on the surface of all cells. Their role is to display fragments of proteins originating inside the cell

Class II device – Device that poses some risk and is subject to controls that continue to evolve.

Class II major histocompatibility complexes (class II MHC) – MHC proteins consisting of two chains of equal length and found only on the surface of certain immune cells. Their role is to display fragments of proteins from digested microorganisms

Class III device – Device that requires premarket approval. Class III devices include those that are life supporting or sustaining, have substantial activity in preventing health impairment, or have the potential to cause irtjwyor illness.

Classical complement activation – Initiated by the Fc region of an antigen-bound antibody binding to C1, followed by recruitment and cleavage of C4, C2, C3 and assembly of the terminal complement components. See also complement.

Classified Space – Areas where HVAC systems are specifically designed to reduce airborne contaminants below a specified level as defined in ISO 14644-1 (tested per ISO 14644-2 and ISO 14644-3) and both temperature and Relative Humidity (RH) are controlled more tightly than in the ambient environment. These areas must be performance verified/qualified. These areas may be tested to meet ISO requirements for airborne 0.5 μm particulate and viable organisms in the “in-operation” state to meet US FDA requirements or they may be tested to meet ISO requirements for both airborne 0.5 μm and 5.0 μm particulate as well as viable organisms in both the “in-operation” state as well as the “at-rest” state to meet EMA and PIC/S requirements. Where EMA and PIC/S requirements are to be satisfied the transition between these two states should take place in 15 to 20 minutes. This can be verified via the “recovery test”as specified in ISO 14644-3.

Clathrin – A protein that plays a major role in the formation of coated vesicles.

Clathrin-mediated endocytosis – Process in which binding of a soluble macromolecule to its complementary cell surface receptor induces cellular internalization via polymerization of clathrin, a protein component of the microtubule network.

Cleavage Division- Cell division that is not associated with cell growth. Each cell divides in two and becomes half of its original size.

Cleft palate – A birth defect in which there is an opening in the palate (roof of the mouth) that is caused by incomplete formation during early fetal development.

Clefting – Division of an ampulla by ingrowth of a sharp cleft.

ClfA – (clumping factor A) A protein found on the surface of Staphylococcus aureus that allows the bacteria to adhere to fibrinogen of the host cell

Clinical genetic testing – Genetic testing performed to discover information for the patient and family involved.

Clinical genomics – The application of large-scale, high-throughput genomics technologies in clinical settings, such as clinical trials or primary care of patients.

Clinical Hold – An order by the regulatory agency to not initiate a planned clinical trial or to halt an ongoing clinical trial.

Clinical Laboratory Improvement Amendments (CLIA) – US federal regulatory standards that were first established in 1988 that requires certification for any lab prior to per- forming clinical diagnostic testing on human samples. The Center for Disease Control (CDC), Center for Medicaid Services (CMS), and the Food and Drug Administration (FDA) play a role in the function of CLIA.

Clinical ontology – Defined as hierarchies of concepts that apply to controlled syntax, database schema, semantic networks, or thesau- ruses. An ontological approach may be used to extract knowledge about disease progression, disease presentation, and comorbidities (see Gene annotation).

Clinical proteomics – Translational application of new protein-based technologies in clinical medicine. For example, serum proteomic pattern diagnostics is a new concept in multiplexed biomarker anal- ysis that may offer a new and exciting method for earlier and more accurate disease prediction.

Clinical research – The systematic collection of information from humans and/or from organic material taken from humans to produce generalizable findings; a subset of all scientific research.

Clinical research ethics – The practice of addressing the ethical aspects of research involving human subjects.

Clinical sensitivity – The proportion of persons with a disease pheno- type who test positive (see Positive predictive probability)

Clinical specificity – The proportion of persons without a disease phe- notype who test negative; referred to in terms of positive predictive probability calculated with sensitivity data.

Clinical trial – A supervised and well controlled experiment in lower to higher animals for newly developed clinical applications. It ensures the optimization efficacy at minimal risk. It is obligatory to run clinical trials before a treatment is approved for routine use. Before a drug can be approved for use, it must undergo and pass three phases of a clinical trial. Phase 1 is the safety phase; the drug must be safe for humans. Phase 2 is the effectiveness phase; the drug must have some desired biological effect. Phase 3 is the large, expensive trial wherein individuals are tested against a control group treated with a placebo or with the standard-of-care medication. Phase 3 trials are very expensive to conduct, and many trials are negative (i.e., fail to indicate that the drug is effective in a phase 3 trial) or demonstrate only incremental success. Of the successful phase 3 trials, a significant number of drugs will eventually be withdrawn, because their effectiveness in clinical practice could not meet the earlier expectations observed in the phase 3 trial results. Clinical trials are experiments, and like any other experi- ment they must be repeated over and over in various settings before they can be trusted. Large clinical trials, of the kind designed for common diseases, are impractical for the rare diseases, for which it is never possible to accrue a large number of individuals who have a rare disease. Clinical research in which a new treatment is tested in a group of patients. If the clinical trial is “randomised and double-blind,” the patients are divided randomly into two groups, one group receiving treatment, the other not. The trial is “blind” if neither patient nor clinician administering the treatment knows if the patient is in the control or experimental group. The process through which firms demonstrate that a biopharmaceutical product is safe and efficacious. It is part of the market authorization process. A clinical trial or clinical study is an investigation conducted with human subjects. Clinical trials of biomedical products must be performed in accordance with GCP and be reviewed by an IRB or EC. If the clinical trial involves an investigational agent or a marketed product being used in a manner different from the product label, the plans for the clinical trial may also be reviewed by an NRA. A series of controlled tests of a drug, vaccine or treatment in human volunteers that is used to determine if its safety and efficacy warrant licensing and use in the general population. Generally involves four phases from I to IV.

CLIP – Class II invariant chain peptide. A small fragment of invariant chain that sits in the MHC class II groove and prevents the premature binding of peptides.

Cloaca – A transient embryonic cavity in mammals, lined with endoderm, which contributes to the epithelial lining of the urogenital and anorectal systems.

Clock-controlled genes – Genes that are regulated by circadian oscillators via clock gene transcription factors; the proteins encoded by clock-controlled genes are rhythmically expressed and generate rhythms of physiology.

Clock genes – Genes that encode proteins that form the molecular basis of circadian oscillators; most clock gene proteins are transcription factors. The cyclically, with a cycle about a day, expressed genes engaged in molecular mechanism of circadian clock.

Clonal deletion – The induction of apoptosis in B or T lymphocytes that have bound their cognate antigen.

Clonal exhaustion – A process by which an activated lymphocyte divides so quickly in the face of persistent anti- gen that its progeny burn out before memory cells have been generated.

Clonal expansion – Production of lymphocytes or plasma cell clones initiated by antigen binding to specific lymphocyte receptors

Clonal selection – Selection of B or T cells with receptors corresponding to specific antigen. The activation of only those clones of lymphocytes bearing receptors specific for a given antigen.

Clone – 1) A line of cells derived from a single cell and therefore carrying identical genetic material. 2) An individual genetically identical to another in which there is a common ancestor or one is derived from the other. An example is twin’s originating from one egg.

Cloned animals – Genetically identical animals derived from the same original cell line

Cloning – A process that consists of creating identical copies of the DNA, a cell, or an organism. Generation and multiplication of a DNA molecule in bacterial cells (usually Escherichia coli). The DNA fragment in question is inserted into a vector and introduced in the cells where it will multiply through cell division. See also Reproductive Cloning and Therapeutic Cloning.The process of making identical copies of an individual.

Cloning – In biology, the process in which an organism produces one or more genetically identical copies of itself by asexual means. Cloning may occur, for example, by propagation of cuttings, as in the case of plants; continual budding, as in the case of hydra; fission, as in the case of bacteria and protozoa; or parthenogenetic asexual reproduction as in the case of aphids. The term also refers to creating multiple copies of a product such as a fragment of DNA. The term cloning can be applied to a group of cells undergoing replication by repetitive mitoses (cell divisions). In the case of higher order animals, such as mammals, nuclear transfer can be used to generate embryos with identical nuclear genetic material to an existing animal; the nuclear transfer embryo can be used either to derive embryonic stem cells (see Therapeutic cloning) or for reproductive purposes (see Reproductive cloning).

Cloning vector – A DNA construct such as a plasmid, modified viral genome (bacteriophage or phage), or artificial chromosome that can be used to carry a gene or fragment of DNA for purposes of cloning (for example, a bacterial, yeast, or mammalian cell). Any molecule of DNA that can replicate itself inside a cell and is used for carrying cloned genes or segments of DNA. Usually a small multicopy plasmid or a modified virus

Closed futures – The notion that future choices will be limited by being able to predict early in life that one will develop a serious or lethal condition later in life.

Closed stem cell niches – A tissue that has a defined geographical location for the stem cell population that is enclosed by a specific set of cells or extracellular matrix.

Closed-end fund – A mutual fund whose shares trade on a publicly traded stock exchange. The first venture capital funds were structured as closed-end funds.

Clostridium botulinum – Bacterium that makes botulinum toxin.

Closed System – A process system that is designed and operated such that the product is never exposed to the surrounding environment. Additions to and draws from closed systems must be performed in a completely closed fashion. Sterile filters may be used to provide effective barriers from contaminants in the environment. A system is closed (or isolated from the environment) when the risk of contamination to the product or process cannot be mitigated by housingthe operation in a bioburden-free or particulate-free environment. In Quality Risk Management (QRM) Verification,the environment does not represent a Critical Aspect of a closed process. In a closed system, the probability of detecting a contaminant from the environment within the processing period is less than the process acceptance criteria. A closed process is one that has been validated to show that there are sufficient layers of protection to mitigate the risk of contamination from the environment. Transfers into or from these systems (including sampling)must also be validated as closed. The detection of a contaminant from the environment in an otherwise closed system indicates a breach of the closed system and therefore constitutes a system failure. Examples of closed systems include sterile single use bags supplied with integrated aseptic connection devices.

CNC – Controlled Not Classified (CNC).

CNC+ – Controlled Not Classified with Local Monitoring.

Cohort study – A type of observational study that compares two groups of individuals in real time.

Colour-matching functions – Functions of wavelength l that describe the amounts of three fixed primary lights which, when mixed, match a monochromatic light of wavelength l of constant radiant power. The amounts may be negative. The color-matching functions obtained with any two different sets of primaries are related by a linear transformation.  Particular sets of color-matching functions have been standardised by the CIE.

Concatemer – Several genome copies linked together.

Conjunctivitis – Inflammation of the conjunctiva, the membrane covering the white portion of the eye and the underside of the eyelid.

Contact inhibition – The propensity of normal cells to cease dividing when they contact an adjacent cell.

Control Measure – Action or activity used to prevent, eliminate or reduce a hazard.

Control Point – A step at which a process factor (whether biological, chemical or physical) can be controlled.

Corrective Action – Step taken to reduce or eliminate the occurrence of a deviation as part of the CAPA procedure to be followed when adeviation occurs.

Critical Control Point (CCP) – A step where control is required to prevent or eliminate a product safety or quality hazard or reduce it to anacceptable level.

Critical Limit – A maximum or minimum value to which a parameter (whether biological, chemical or physical) must be controlled.

Critical Process Parameter (CPP) – A measurable input (input material attribute or operating parameter) or output (process state variable or output material attribute) of a process step that must be controlled to achieve the desired product quality and process consistency.

Critical Quality Attribute (CQA) – Physical, chemical, biological or microbiological properties or characteristics that need to be controlled (directly or indirectly) to ensure product quality. Physical, chemical, biological or microbiological properties or characteristics that should be within an appropriate limit, range, or distribution to ensure the desired product quality (see ICH Q8(R2)).

Cross-Contamination – Contamination of the product or processing area of by components or contaminants found in a neighboring productor processing area. Cross contamination typically occurs between open processes. Cross contamination also can occur when there is a breach of integrity of a closed system in an environment shared with an open process or when there is a breach of integrity of two closed processes. The latter is highly unlikely to occur in well-designed systems.Recirculating HVAC can be a source of cross contamination if improperly designed.

Crossover – see also Cross-contamination. 

Crossover (a type of Cross Contamination) – Contamination of a system by components or contaminants found in a neighboring system. Crossover typically occurs with open processes sharing environments. Crossover can also occur when there is a breach of integrity of a closed system in an environment shared with an open process or when there is a breach of integrity of two closed processes. Contamination of a system by components or contaminants found in a neighbouring system. Crossover typically occurs with open processes sharing environments. Crossover also can occur when there is a breach of integrity of a closed system in an environment shared with an open process or when there is a breach of integrity of two closed processes. The latter is highly unlikely to occur in well-designed systems. Circulating CIP systems and glass-washers can be a source of crossover if improperly designed.

Cluster of differentiation (CD) antigen – Cell surface proteins found on leukocytes and used to classify the different types of leukocytes.

CMA – Chromosomal microarray (CMA).

CMC – Chemistry, Manufacturing, and Controls (CMC) – those topics related to how a product is made and analysed (quality controls).

CME – Continuing medical education (CME).

CNV – Copy number variant (CNV).

Cocooning (vaccination) Herd immunity – Established by vaccination within a single household.

Co-development agreement – is a form of joint venture where both parties collaboratively undertake research on a given project.

Codify – To introduce into the code of federal regulations.

Coding DNA (sequence) – The portion of a gene that is transcribed into mRNA.

Coding strand – (see also nontemplate or sense) The strand of DNA equivalent in sequence to the messenger RNA (same as plus strand).

Codominance – Expression of a given gene from both the maternal and paternal chromosomes.

Codon – A three-base sequence of DNA or RNA that specifies a single amino acid. Group of three RNA or DNA bases that encodes a single amino acid. Sequence of three DNA or mRNA nucleotides, containing information for the insertion of a particular amino acid into a polypeptide chain that is being synthesised or for the termination of polypeptide synthesis.

Codon bias – Some organisms use only a subset of redundant codons for a particular amino acid, whereas other organisms will use a different subset. This bias can hinder expression of foreign proteins in genetic engineering

Codon usage – The favoring of different alternative codons for the same amino acid in different organisms.

Codon/anticodon – A codon is the portion of mRNA that contains the code for a specific amino acid (or start or stop signal). The anticodon is the portion of tRNA that binds to an mRNA codon.

Co-enzyme – Another name for a second substrate. Non-protein genic co-substrates of enzymes; low-molecular organic compounds that participate directly in the chemical transformation of a substrate, undergoing changes in the process and being restored in subsequent enzymatic processes.

Cofactors – In many enzymes, additional metal ions, low-molecular organic compounds (coenzymes) or other facilitators are required for biological activity.

Cognate antigen – An antigen known to be recognised by a given lymphocyte antigen receptor because it was used for the original activation of that lymphocyte.

Co-immunoprecipitation – Method of identifying protein interactions by using antibodies to one of the proteins

Co-investment – Either the syndication of a private equity financing round or an investment by an individual general or limited partner alongside a private equity fund in a financing round.

Cold chain (vaccination) – Constant refrigeration of a labile vaccine from the point of manufacture and shipping to the point of use in the field.

Cold markets – These occur when the stock prices of new securities rapidly decrease below their offering prices, with this phenomenon lasting for an extended period of time.

Colicin – Toxic protein or bacteriocin made by Escherichia coli to kill closely related bacteria

Collagen – The most common naturally occurring structural protein found in all multicellular animals and accounts for approximately 30% of all body proteins. An extracellular matrix protein in connective tissue to which cells attach easily. It can be used in the laboratory as a surface on which to grow cells, often in its denatured form called gelatin. An extracellular protein that gives structural support to tissues. Nineteen different types exist.

Collagen fibre – A structural edifice of collagen that is made up of several “fibrils” (10 to 300 nm diameter). 

Collagenopathy – A variety of clinical conditions involving genetic alterations of the various collagen genes or other genes involved in the complex processes of collagen synthesis. Lists of clinical collagenopathies usually include Ehlers– Danlos syndrome, osteogenesis imperfecta, familial aneurysmal disorders or aortic dissection disorders, Caffey disease (infantile cortical hyperostosis), and Bruck syndrome. Some of the non-collagen genes involved in collagenopa- thies include the ACTA2 gene (thoracic aortic aneurysms and aortic dissection) and the PLOD2 gene (procollagen-lysine dioxygenase 2 involved in Bruck syndrome), and familial aneurysm disorders (e.g., smad3, tgfbr1, tgfbr2, and tgfb2). There are over 17 genes coding for the different species of collagen molecules. 

Collecting duct –  The segment of the nephron that conveys the urine to the outside.

Collectins – Soluble pattern recognition molecules (PRMs) that mediate pathogen clearance by opsonization, agglutination or the lectin pathway of complement activation. Includes mannose-binding lectin (MBL).

Colloid osmotic pressure – A type of osmotic pressure, generated by proteins, which tends to pull water into a cell or tissue compartment from surrounding compartments.

Coloboma – A condition where an individual is missing part of his or her eye structure, including, but not limited to, the iris, retina, and eyelid.Treacher Collins syndrome patients usually have coloboma of the eyelid and have a notch in the upper or lower eyelid. A unilateral or bilateral incomplete closure of the embryonic optic fissure resulting in a defect in uveal structures and/or optic nerve. Defects are typically located in the inferior or inferonasal portion of the globe.

Colony-stimulating factor (CSF) – Growth factor promoting the proliferation of granulocytes.

Columellar strut – A cartilage graft placed between the medial crura of the nose to shift the nasal tip forward, rotate the tip upward, and/or increase support of the tip.

Co-marketing agreement – is a form of joint venture that allows one or both parties to the agreement to market and sell the product.

Combination Product – A medicinal product made from a combination of a biological and a pharmaceutical drug, a biological and a medical device, a medical device and a pharmaceutical drug, or all three product constituents. A product that is a combination of constituents that are all the same type, e.g., three different vaccines combined is not a combination product, but is a combination vaccine.

Combination vaccine – Single vaccine containing immunogens from several different pathogens.

Combinatorial library – Large series of related molecules that have been systematically generated by combining chemical groups and/or molecular motifs.

Combinatorial screening – Screening of a large series of related molecules for those with useful properties.

Combined immunodeficiency Primary immunodeficiency – In which both T and B cell responses are compromised. NK and NKT cell functions may also be affected.

Commensal – A symbiotic relationship between two organisms in which one of the organisms benefits and the other is unaffected under normal conditions. A commensal may become an opportunistic pathogen when the host provides a physiologic opportunity for disease, such as malnutrition, advanced age, immunodeficiency, overgrowth of the organism (e.g., after antibiotic usage), or some mechanical portal that introduces the organism to a part of the body that is particularly susceptible to the pathologic expression of the organism, such as an indwelling catheter, or an intravenous line. In addition, a commensal relationship between bacteria and an animal parasite may produce a pathogenic relationship in the parasite’s host. For example, the bacterium Wolbachia pipientishappens to be an endosymbiont that infects most members of the filarial Class Onchocercidae .Onchocerca volvulus is a parasitic filarial nematode in humans. The filaria migrate to the eyes, causing river blindness, the second most common infectious cause of blindness worldwide. Wolbachia pipientislives within Onchocerca volvulus, and it is the Wolbachia organism that is responsible for the inflammatory reaction that leads to blindness. Hence, Wolbachia pipientisis a commensal in Onchocerca volvulus and a pathogen in humans simultaneously. Treatment for river blindness may involve a vermicide to kill Onchocercavoluvuluslarvae, plus an antibiotic to kill Wolbachia pipientis.

Commensal organisms – Beneficial microbes that normally inhabit the surfaces of skin and body tracts. Also called microbiota or microflora.

Commitment – An irreversible decision to produce or become a particular cell type. This is defined operationally as the inability of a cell to change its fate when exposed to different signaling cues. Commitment is always discussed in the context of a particular differentiation step.

Committed B cell – A B cell in the process of development toward making a specific Ig.

Common lymphoid progenitor (CLP) – Early descendant of multipotent progenitors (MPPs) that gives rise to B lineage cells.

Common mucosal immune system (CMIS) – A system of extended mucosal defense established when lymphocytes activated in one mucosal inductive site migrate to a large number of effector sites in various mucosal tissues.

Common myeloid progenitor (CMP) – Early descendant of MPPs that give rise to myeloid cells.

Common Rule (46 CFB 46) – The regulations governing human subjects research for studies conducted with U.S. federal funding from the Common Rule agencies.

Common stock – The equity typically held by management and founders. Typically, at the time of an initial public offering, all equity is converted into common stock. These equity claims are the last to be paid upon any liquidation of the company.

Community consent – Consent by the leadership of an identifiable community.

Community consultation – A process of consulting with a whole community, or with a substantially representative group from a whole community, when planning and conducting research.

Community-based research – Research that addresses concrete problems and issues of interest to a community that are generated from within the community. Also called participatory research.

Compassionate use – A request for the use of a test agent or device for an individual outside the inclusion criteria of an approved protocol or within the inclusion criteria of an as-of-yet-unapproved protocol.

Companion diagnostics – The increasing trend for genetic diagnostics and therapeutics to become intertwined. These diagnostics identify the subset of patients who would benefit from a drug.

Comparability exercise – Comparability exercise is a head-to-head comparison of a biotherapeutic product with a licensed originator product, the reference biotherapeutic product (RBP), with the goal to establish similarity in quality, safety, and efficacy. Products should be compared in the same study using the same procedures.

Comparability protocol – A protocol to be followed to support manufacturing or control variations or changes be- ing made to an already licensed product, by comparing the originally (or currently) licensed product to the product with the changes.

Comparable – is the basic valuation method that determines price based on similar projects or firms.

Comparative genomics – Comparing genome sequences of different organisms, especially in attempts to determine potential functions for genes or proteins by comparison with characterised examples. The comparison of genome structure and function across different species in order to further our understanding of biological mechanisms and evolutionary processes.

Comparative metabolism – the process in which different forms of metabolism are contrasted and measured to note their advantage to each cell type.

Compendial method – A test procedure documented in a compendium, such as regulations or a pharmacopeia.

Competence – The ability of a cell to respond to a cue or set of cues to produce a defined outcome.

Competent – Cell that is capable of taking up DNA from the surrounding medium.

Complementarity- determining region (CDRs) – Short segment that forms a loop on the surface of the variable region of an antibody, thus forming part of the antigen-binding site. See also hypervariable region.

Competitive advantage – Anything that allows a company to charge prices above marginal costs.

Complaint – Any written, electronic, or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or performance of a device after it is released for distribution [see Federal Regulations 21 CFR- Part 820.3].

Complement – System of over 30 soluble and membrane-bound proteins that act through a tightly regulated cascade of pro-protein cleavage and activation to mediate cell lysis through assembly of the membrane attack complex (MAC) in a target cell membrane. Intermediates in the complement cascade play a variety of roles in antigen clearance. System of soluble proteins. Causes microorganism killing, phagocyte recruitment, opsonization and release of mediators from mast cells. A collection of proteins that initiate lysis of an antigenic organism. A system of serum proteins and cell surface proteins that combine to form the membrane attack complex that perforates cell membranes. Component proteins of the complement cascade have enzymatic activity and generate inflammatory mediators.

Complement activation – the process in which complement proteins are induced to react in sequence to initiate a complement reaction. This is also known as complement fixation.

Complementary DNA (cDNA) – DNA copy of a gene that lacks introns and therefore consists solely of the coding sequence. Made by reverse transcription of mRNA. DNA generated from an expressed mRNA through a process known as reverse transcription.

Complex disease – A somewhat vague term often indicating that the patho- genesis of a disease cannot be understood. The presumption is that our lack of understanding is not based on our failure to discover the underlying cause of the disease. Our lack of understanding is based on our discovery that there are so many different factors to consider that it is impossible to understand the patho- genesis in a way that we can fully grasp. When the development of a disease involves numerous environmental factors, some known and others assumed, as well as multiple genetic and epigenetic influences, we have no way of fully understanding how all of these factors interact with one another, and we have no way of fully describing the biological steps that lead to the clinical expression of disease. Likewise, we have no way of predicting how different individuals with a complex disease will respond to treatment. In this book, we use the term “common disease” interchangeably with “complex disease.” Without exception, all of the clinically significant common diseases of humans are complex. The rare diseases tend to be simple, though there are exceptions, particularly for the “more common” of the rare diseases. As a rule of thumb, complexity rises in direct proportion to the frequency of occurrences of a disease. Diseases characterised by risk to relatives of an affected individual that is greater than the incidence of the disorder in the population.

Complex trait – One which is not strictly mendelian (ie, dominant, reces- sive, or sex-linked) and may involve the interaction of two or more genes to produce a phenotype, or may involve gene–environment interactions.

Complex transposon – A transposon that moves by replicative transposition.

Compliance –1) Adherence to regulations and procedures (e.g. adhering to the written procedure in a protocol that describes procedures used to measure subject observance of experimental regimens). 2) The ability of a tissue to stretch or become deformed under pressure. See also conformance.

C-onc – Cellular version of an oncogene.

Conception view – Idea in philosophical ethics that an embryo has full moral status from conception.

Conceptus – Contains all the derivatives of the zygote, embryonic (epiblast) and extra-embryonic tissues.

Condensation reaction – The formation of a larger compound from two smaller compounds (also known as ligation).

Conditional allele – An allele that is engineered to function normally until it is recombined by the introduction of a recombinase to produce a mutant allele in a tissue- or temporally-specific manner.

Conditional mutation – Mutation whose phenotypic effects depend on environmental conditions such as temperature or pH

Cone transducing proteins – Proteins similar to rhodopsin that are found in cone photoreceptors.

Confidentiality – Protecting the right of privacy by ensuring that information and/or access provided by an individual to a professional, within the context of a trusting (i.e., fiduciary) relationship, will not ordinarily be divulged without permission.

Conflict of commitment – A situation in which professional judgment about the rights and welfare of human subjects may be unduly influenced by a conflicting, nonfinancial interest.

Conflict of interest – A situation in which professional judgment about the rights and welfare of human subjects may be unduly influenced by a conflicting financial interest.

Confocal Laser Scanning Microscope (CLSM)- A microscope able to make “optical sections” of a three-dimensional specimen using a laser to focus on one optical plane.

Conform or Conformance – Following an SOP or protocol properly without deviation, with results that meet prespecified criteria and specifications.

Conformational determinant – A protein epitope in which the contributing amino acids are located far apart in the linear sequence but which become juxtaposed when the protein is folded in its native shape.

Conformational structure – A three-dimensional structural representation of carbohydrates and other carbon chemical structures based on carbon as the center of a tetrahedron (see Figure 4–2). Term may also apply to any macromolecule.

Conformation-dependent immunoassay (CDI) – Assay that uses specific binding of monoclonal antibodies to distinguish between different forms of the prion protein

Congenital – Any trait, condition, or disorder that exists from birth.

Congenital diaphragmatic hernia (CDH) – This term is used inconsistently to describe a variety of diaphragmatic defects. Among physicians, it is usually used to describe the severe hernias that present at birth. These hernias almost always involve the posterolateral, lateral, or posteromedial diaphragm. They may also present as aplasia of one side of the diaphragm. The term “CDH” is sometimes used interchangeably with “Bochdalek hernia,” a hernia that should only arise from a weak spot along the posterolateral wall of the thorax.

Congenital disorder of glycosylation (CDG) – A group of congenital, multi- organ syndromes caused by post-translational defects in protein glycosylation [30]. The steps in post-translational glycosylation are complex, and may involve systems that move nascent proteins from the endoplasmic reticulum to other sites (e.g., Golgi apparatus). In such cases, there may be overlap between the congenital disorders of glycosylation and the vesicular trafficking disorders. Many different disorders of glycosylation have been identified, involving N-glycosylation, O-glycosylation, or both. Because there are so many different inherited glycosylation disorders, and because these disorders tend to produce neurologic symptoms and multi-organ impairments, physicians should always include congenital disorders of glycosylation in the differential diagnosis when evaluating infants with otherwise unexplained multi-organ involvement or neu- rologic abnormalities. See Vesicular trafficking disorder.

Conjugate – A structure resulting from the physical joining of two other structures. Two cells may form a conjugate, such as Th and B cells during the provision of B–T coop eration, or CTLs and target cells during cytolysis. Two molecules may also form a conjugate, such as the covalent joining of a small inorganic molecule to a protein carrier to induce an immune response.

Conjugate vaccine – A vaccine based on the covalent linkage of a pathogen carbohydrate epitope to a protein carrier such that it induces a B cell response to Td antigens rather than Ti antigens.

Conjugation – Process in which genes are transferred by cell-to-cell contact in bacteria conservative substitution. Replacement of an amino acid with another that has similar chemical and physical properties.

Conjunctiva – The conjunctiva is a thin mucous membrane that lines the inside of the eyelids and covers the sclera (the white of the eye).

Conjunctiva-associated lymphoid tissue (CALT) – It is the physiological protective mucosal immune tissue of the conjunctiva. It consists of lymphoid cells and accessory cells inside the mucosal tissue and can be divided into the epithelial and underlying connective tissue (lamina propria) compartments. It is arranged as a diffuse lymphoid effector tissue along the whole extension of the conjunctiva and has interspersed organised lymphoid follicles for afferent antigen uptake and effector cell generation.

Connexin – A molecule comprising a gap junction that sits in a neuron’s membrane and can join with a connexin from another neuron to create a large nonspecific pore that conducts ions and small molecules.

Conotruncus – Regions of the bulbus cordis that forms the conus cordis and the truncus arteriosus.

Consanguinity – Marriage between two individuals having common ancestral parents, commonly between first cousins; an approved practice in some communities who share social, cultural, and religious beliefs. In genetic terms, two such individuals could be heterozygous by descent for an allele expressed as coefficient of relationship, and any offspring could be therefore homozygous by descent for the same allele expressed as coefficient of inbreeding. Used to describe genetic relatedness between individuals due to a common ancestor of origin.

Consent monitor – An individual unaffiliated with the research team who is attached to a study to observe the consent process.

Consequentialist ethical theory – An ethical theory that evaluates an action based on its potential consequences. The most ethically praiseworthy actions, according to this theory, are those that maximise the good for the greatest number.

Conservative transposition – Same as cut-and-paste transposition

Conserved noncoding elements (CNE) – Areas of the human genome that are conserved in the various other animal genomes but do not encode protein-producing genes

Conserved sequence – A base sequence in a DNA molecule (or an amino acid sequence in a protein) that has remained essentially unchanged throughout evolution.

Constant domain – A domain of an Ig or TCR chain that is encoded by the corresponding constant exon. The constant domains have very little amino acid variability. A domain of an Ig that has a fixed sequence of amino acids. Constant regions, however, may vary between Ig classes.

Constant exon – Exon encoding a constant domain of either an Ig or a TCR protein. A C exon is spliced at the mRNA level to a rearranged variable (V) exon to produce a transcript of a complete Ig or TCR gene.

Constant region – Region of an antibody protein chain that remains constant in sequence. The relatively invariant C-terminal portion of an Ig or TCR molecule. Comprises the constant domains of all the polypeptides involved.

Constitutional mutation – A mutation that is inherited and therefore present in all cells containing the relevant nucleic acid.

Constitutive – Term used to describe genes that are expressed during all conditions.

Constitutive heterochromatin – Regions of more or less permanent heterochromatin found on both copies of homologous chromosomes, especially around centromeres

Constitutive promoter – A promoter that functions in all tissues at all times.

Construct – Term used to describe a cloning vector derived from various different genes and DNA segments assembled into one

Consultant – The person in the family who presents for a genetic counseling evaluation regarding a known or potential inherited condition.

Contact inhibition – Inhibition of cell division that occurs due to contact with neighbouring cells contig a stretch of known DNA sequence, built up from smaller cloned fragments that is contiguous and lacks gaps.

Contact lens-induced papillary conjunctivitis (CLPC) – Enlarged papillae accompanied by redness of the upper palpebral conjunctiva. Symptoms include discomfort, itching, mucous discharge, and foreign body sensation.

Container Closure System (CCS) – The sum of parts that together contain and/or protect the drug product. This includes immediate and secondary packaging, where the latter is intended to provide additional protection to the drug product. The container closure system may include medical devices (or device parts), as defined in Section 1 of this guideline.

Contig – A consensus sequence generated from a set of overlapping sequence fragments that represent a large piece of DNA, usually a genomic region from a particular chromosome.

Contig disease – See Contiguous gene deletion syndrome.

Contig map – A genome map based on contigs.

Contiguous gene deletion syndrome – A syndrome caused by abnormalities of two or more genes that are located next to each other on a chromosome. When the abnormality is a deletion, a contiguous gene syndrome is equivalent to a microdeletion syndrome. See Microdeletion.

Contract research organisations (CROs) – Firms that perform various aspects of research and clinical trials for other firms. They act as outsourcing firms.

Control – According to 21 CFR 600.3 (ii), control is defined to be- “… having responsibility for maintaining the continued safety, purity, and potency of the product and for compliance with applicable product and establishment standards, and for compliance with current good manufacturing practices.”

Control Strategy – A planned set of controls derived from current product and process understanding that ensures process performance and product quality. The controls can include parameters and attributes related to drug substance, drug product, medical device (part), facility and equipment operating conditions, in-process controls, finished product specifications, and the associated methods and frequency of monitoring and control.

Controlled pore glass (CPG) – Glass with pores of uniform sizes that is used as a solid support for chemical reactions such as artificial DNA synthesis.

Conventional aqueous outflow pathway – Comprised of the trabecular meshwork, the juxtacanalicular connective tissue, the endothelial lining of Schlemm’s canal, Schlemm’s canal itself, the collecting channels, and aqueous veins.

Convergence – As applied to diseases, convergence occurs when different genes, cellular events, exposures, and pathogenetic mechanisms all lead to the same clinical phenotype. Convergence is a phenomenon that is observed in vir- tually every common disease. In the case of systemic responses to injury, con- vergence seems to have evolutionary origins. The organism evolves to respond in an orchestrated way to a variety of pathologic stimuli (e.g., systemic inflam- matory response syndrome. Convergence is also observed in rare diseases that have genetic heterogeneity (e.g., multiple causes for epidermolysis bullosa, retinitis pigmentosa, long QT syndrome). It would seem that for any given spe- cies, the variety of pathologic responses is limited.

Convergent extension (CE) – The process in which the cells of a tissue rearrange to converge towards the midline and extend the tissue along the anterior-posterior axis of the embryo.

Convertible debt/bond – A type of bond that can be converted into shares of stock in the issuing company, usually at some pre-announced ratio. It is a hybrid security with debt- and equity-like features. Although it typically has a low coupon rate, the holder is compensated with the ability to convert the bond to common stock, usually at a substantial premium to the stock’s market value.

Convertible preferred (CP) stock – Equity that can either be turned in for its redemption value or converted to common stock.

Coomassie Blue – A blue dye used to stain proteins

Cooperation – Alliance type in form of a cooperation in a specific area with shared risk between two parties. 

Coopetition- Is where a firm cooperates with another firm for one product or venture, but also competes with that same firm on other products or ventures.

COPD – An abbreviation for chronic obstructive pulmonary disease. COPD covers a range of lung disorders characterised by airway damage. COPD is a common sequela of chronic cigarette abuse.

Copy number – The number of copies of a gene or plasmid found within a single host cell. The number of different copies of a particular DNA sequence in a genome. It is possible to produce a rare genetic disease without actually producing a mutation in a gene; simply changing the number of genes can be sufficient. Charcot–Marie–Tooth disease is an inherited neuropathy caused by duplication of a 1.5 megabase segment on chromosome 17. No altered protein is produced. The clinical phenotype is caused by an increased gene dosage. See Gene dosage.

Copy number variant (CNV) – Sequences typically 1 Kb–3 Mb in size, deleted or inserted into the genome; CNVs can be both benigng or pathogenic.

Copy number variation (CNV) disorder – A genetic disorder caused by the heterozygosity of one or more genes (such as in a microdeletion). These disorders result from the reduced expression of the deleted genes, rather than complete absence or a mutation.

Cord Blood – Also known as umbilical cord blood, the blood in the umbilical cord and placenta that supplies nutrients from the mother to the developing fetus. It contains a relatively large number of blood stem cells and can be stored after birth for research or use in transplantation.

Cord Blood Stem Cells – Cord blood stem cells are recovered at birth from the umbilical cord. Even though they come from a newborn infant, they are still limited like adult stem cells in that they can make several cell types, but not all the cell types of body. However, unlike adult stem cells, they can grow indefinitely in culture, giving researchers a limitless supply, enough to create tissue or disease models.

Core competencies – are the bundles of resources and capabilities that a firm possesses.

Core enzyme – The part of DNA or RNA polymerase that synthesises new DNA or RNA (i.e., lacking the recognition and/or attachment subunits).

Coreceptor – Protein required for virus entry into host cell in addition to the main virus receptor. Protein that enhances the binding of a primary receptor to a ligand. The T cell coreceptors CD4 and CD8 bind to non-polymorphic sites on MHC class II and I, respectively, that are outside the peptide-binding groove. This binding stabilises the contact between the peptide- MHC complex (pMHC) and the TCR, and also recruits intracellular signaling enzymes.

Corectopia – Displacement of the pupil.

Corepressor – In prokaryotes—a small signal molecule needed for some repressor proteins to bind to DNA; in eukaryotes—an accessory protein, often a histone deacetylase, involved in gene repression.

Corneal dystrophies – A collection of inherited, bilateral, primary alterations of the cornea that are not associated with a prior disease or pathological condition. They may exist in the epithelium, stroma, and/or endothelium.

Corneal infiltrates – Corneal inflammatory response which appears as single or multiple, focal or diffuse lesions in the corneal stroma.

Corporate venture capital (CVC) – Venture capital (VC) investments by corporations. An initiative by a corporation to invest either in young firms outside the corporation or in business concepts originating within the corporation. These are often organised as corporate subsidiaries, not as limited partnerships. Although traditional VC seeks to maximise financial returns, corporate venture capital often mixes financial and strategic goals.

Corporation – A legal entity, separate and distinct from its stockholders, who annually elect the Board of Directors, which represents the stockholders’ interests in the management of the business. The liability of the stockholders in a corporation is limited to the dollar value of their investments.

Corrective action (CA) – An action taken to eliminate the cause of an existing nonconformity, defect, or other undesirable situation in order to prevent recurrence.

Corrective action or preventive action (CA/PA) process – A systematic approach to review in-process quality data, post-market surveillance, and all other nonconformance information to identify, investigate, prevent, and correct quality issues.

Cortex – The outer layer of an organ such as the thymus.

Cortical thymic epithelial cells (cTECs) – See also thymic epithelial cells (TECs).

Corticosteroids – Drugs derived from steroid hormones that have anti-inflammatory and immunosuppressive activities, affecting leukocyte circulation, cellular functions and chemical mediator secretion.

Corticotomy – Extensive and deep cuts of cortical plate requiring gingival flap for access to the bone.

Cos sequences (lambda cohesive ends) – Complementary 12 base-pair-long overhangs found at each end of the linear form of the lambda genome.

Cosmid – Small multicopy plasmid that carries lambda cos sites and can carry around 45 kb of cloned DNA. Plasmids synthesised on the basis of the circular genome of bacteriophage λ. Cosmids can take up far longer DNA sequences (up to 40,000 base pairs) than ordinary plasmids and are therefore suitable.

Cost of capital – A general term for the risk-adjusted discount rate of an investment project. If a company has available cash, cost of capital is the expected return foregone by investing the cash in a project rather than in any comparable financial security. If a company does not have available cash, the term refers to the cost of acquiring the Cash – i.e., the cost of raising debt (effective interest) capital or the cost of raising equity capital (dilution).

Costimulation – The second signal required for completion of lymphocyte activation and prevention of energy. Sup- plied by engagement of CD28 by B7 (T cells), and of CD40 by CD40L (B cells).

Co-stimulator – Molecule on the surface of an APC which mediates the second signal needed for T cell activation.

Cosuppression – An alternate term used to describe RNA interference-like phenomena.

Cotransport – The simultaneous transport of more than one substance by the same transport mechanism.

Council for International Organizations of Medical Sciences (CIOMS) document – A document focused on ethical considerations for performance of research in developing countries and communities.

Coverage (vaccination) – See also efficacy (vaccine).

Coxsackievirus adenovirus receptor (CAR) – Receptor on animal cells shared by adenoviruses and B-group coxsackieviruses.

CPE (Cytopathic effect) – It refers to any pathological changes (or lesion) in the host cells that are caused by virus infection.

C-peptide – Connecting peptide that originally links the A- and B-chains of insulin but is absent from the final hormone.

CpG island – A short stretch of DNA, often less than 1 Kb, contain- ing CpG dinucleotides that are unmethylated and present at the expected frequency. CpG islands often occur at transcriptionally active DNA. DNA methylation is a form of epigenetic modification that does not alter the sequence of nucleotides in DNA. The most common form of meth- ylation in DNA occurs on cytosine nucleotides, most often at locations wherein cytosine is followed by guanine. These methylations are called CpG sites. CpG islands are concentrations of CpG dinucleotides that have a GC content over 50% and that range from 200 base pairs (bp) to several thousand bp in length. There are about 29,000 to 50,000 CpG islands and most of these are associ- ated with a promoter. Various proteins bind specifically to CpG sites. For example, MECP2 is a chromatin-associated protein that modulates transcription. MECP2 binds to CpGs; hence, alterations in CpG methylation patterns can alter the functionality of MECP2. Mutations in MECP2 cause RETT syndrome, a progressive neurologic developmental disorder and a common cause of mental retardation in females. It has been suggested that the MECP2 mutation disables normal protein–epigenome interactions.

CQA – Critical Quality Attribute.

Crabtree effect – Phenomenon whereby the yeast, Saccharomyces cerevisiae, produces ethanol at high external glucose concentrations despite the presence of oxygen.

Craniorachischisis – A neural tube defect (NTD) that results from failure of neural tube closure along the entire neural axis.

Cranioskeleton (cranial skeleton) – The entire set of bones that make up the head.

Craniosynostosis – Refers to the premature fusion of the fibrous sutures of the skull during infancy, resulting in malformation of the skull.

Cre – A recombinase from bacteriophage P1 that directs recombination at specific sites (loxPsites)

CRE (cyclic AMP response element) –  A specific DNA sequence found in front of genes that are activated by cyclic AMP in higher organisms

Cre recombinase – Enzyme encoded by bacterial virus P1 that catalyzes recombination between inverted repeats (loxPsites)

Cre/loxP – A system allowing a specific gene to be added or removed during development by exploiting Cre recombinase to excise DNA sequences flanked by loxPrecombination sites

CREB protein (cyclic AMP response element binding protein) – Protein that regulates genes in response to cyclic AMP in animal cells by binding to CRE sequences in promoters

Creutzfeldt–Jakob disease (CJD) – Inherited or spontaneous brain degeneration disease of humans caused by prions

CRISPR – (Clustered Regularly Interspaced Small Palindromic Repeats) a bacterial immunity system against bacteriophages based on cleavage of specific DNA sequences. It can be engineers to cleave any sequence as a powerful gene editing tool.

CRISPR (Clustered Regularly-Interspaced Short Palindromic Repeats) – A short stretch of repetitive DNA sequences found in prokaryotic genome that provides immunity against bacteriophage infections. The logic behind CRISPR is now employed in genome editing technology.

CRISPRa – CRISPR activation; where a guide RNA (gRNA) binds with dCas9 (inactive version of Cas9) and the complex fuses with the transcription activation domain to increase transcriptional activity of a gene.

CRISPRi – CRISPR interference; uses a dCas9 fused with or without a repressor that binds with gRNA, and the complex thus formed represses or down-regulates the gene transcription by binding to the promoter region or coding region.

CRISPR/Cas – A biotechnology tool, utilizing components of a prokaryotic immune system, for making highly specific genomic modifications.

Critical event – An event that has resulted in or contributed to a problem leading to a failure resulting in a severity level 1.

Critical requirements – Those process or product requirements that, if not met, would be associated with a failure mode of severity level 1.

Cross-matching – Analysis of a recipient’s blood to ensure that he/she does not possess any pre-formed antibodies that could attack a graft from a particular donor. A positive cross-match occurs when an individual’s blood contains pre-formed alloantibodies to one or more HLA molecules expressed on an allogeneic donor organ, indicating that the transplant should not proceed.

Crossover – Structure formed when the strands of two DNA molecules are broken and rejoined with each other.

Cross-pollination – Taking the pollen from one plant and placing it on the stigma of another in order to direct the exchange of genetic information.

Cross-presentation – Transfers peptides from the exogenous antigen processing pathway into the endogenous antigen processing pathway.

Cross-reactivity – Recognition by a lymphocyte or antibody of an antigen other than the cognate antigen. Cross-reactivity results either when the same epitope is found on two different antigens or when two epitopes on sepa rate antigens are similar. Also, for example,  when antibodies against one virus also recognise and protect against infection with a similar virus.

CRP protein (cyclic AMP receptor protein) – Bacterial protein that binds cyclic AMP and then binds to DNA (see also CAP, catabolite activator protein).

Cry protein – Crystalline protein found in Bacillus bacterial spores that breaks into delta endotoxin (Bt toxin).

Cryoprotectant – A chemical compound that is used to protect cells and tissues from freezing damage.

Cryptochrome – A blue-light absorbing protein, which contains a flavin-binding domain and functions as a circadian photoreceptor and an element of the molecular clock in the central and peripheral clocks of Drosophila, respectively. In the mammalian circadian clock, cryptochromes are the core clock elements.

Crystallins – Proteins unique to the crystalline lens. There are three major classes in the human adult eye.

Crystallography – The science of determining the three-dimensional structure of compounds using x-rays to produce a diffraction pattern from a crystal of a pure compound.

CTA – Clinical Trial Authorisation (CTA), Clinical Trial Application (CTA), Clinical Trial Approval (CTA) – the equivalent of an IND application in other countries, such as in the EU, United Kingdom, various other non-EU European countries, South Africa, and others.

CTD – Common Technical Document (CTD) – format agreed upon by participants in ICH for submission for registration, licensure, or approval of new drugs. The format consists of five modules. The first module consists of country-specific information and the final four modules are common to submissions in all regions/countries. Module 2 is summary information for quality, safety, and efficacy topics. Module 3 is the detailed information on quality topics. Module 4 is the detailed information on safety topics. Module 5 is the detailed information on efficacy topics.

CTO – Clinical Trial Outline (CTO) – a document that summarises the major aspects of study design and procedures.

CTXphi – Filamentous bacteriophage that carries genes for cholera toxin and lysogenises Vibrio cholerae.

C-type lectin receptors (CLRs) – Pattern recognition receptors that act as lectins by binding to bacterial carbohydrates.

Culture Medium – Fluid used to culture cells in the laboratory containing the nutrients they require to divide.

Cultured Meat – Also known as in vitro meat. Edible muscle tissue made from in vitro cultured stem cells from cow or pig that have been differentiated to skeletal muscle tissue.

Cut-and-paste transposition – Type of transposition in which a transposon is completely excised from its original location and moves as a whole unit to another site.

Cutaneous immune responses – Immune responses mediated by leukocytes in the SALT that can respond to antigen attacking the skin without necessarily involving a lymph node.

CV – Curriculum vitae (CV) – like a résumé- a document that details the education, qualifications, training, and experiences of an individual, e.g., a clinical investigator.

CVD – Cardiovascular disease (CVD).

CVM – Center for Veterinary Medicine- the component of U.S. FDA that regulates veterinary drugs and medicated feeds. Veterinary vaccines, including those made by biotechnology, are regulated by USDA.

CX3CR1 – CX3CR1 (Fractalkine receptor) is important for homing of Langerhans-like dendritic cells to the corneal epithelium.

Cyanobacteria – The most influential organisms on earth, cyanobacteria were the first and only organisms to master the biochemical intricacies of photosynthesis (more than 3 billion years ago). Photosynthesis involves a photochemical reaction that uses carbon dioxide and water, and releases oxygen. All photosyn- thesizing life-forms are either cyanobacteria, or they are eukaryotic cells (e.g., algae, plants) that have acquired chloroplasts (an organelle created in the distant past by endosymbiosis between a eukaryote and a cyanobacterium). Before the emergence of oxygen-producing cyanobacteria, Earth’s atmosphere had very little oxygen.

Cycles per degree – The number of complete phases of a grating (e.g., the distance between the center of a white bar and the center of the next bright bar in a square-wave grating; or the distance between two adjacent areas of maximum brightness on a sine-wave grating) contained in 1 of visual angle.

Cycle sequencing – Technique that combines PCR and chain termination sequencing to determine the sequence of a template DNA.

Cyclic AMP (cAMP) (cyclic adenosine monophosphate) – A signal molecule used in global regulation (in bacteria) and as a second messenger (in higher organisms). A cyclic mononucleotide of adenosine that is formed from ATP.

Cyclic AMP response element (CRE) – A specific DNA sequence found in front of genes that are activated by cyclic AMP in higher organisms.

Cyclic AMP response element binding protein (CREB protein) – Protein that regulates genes in response to cyclic AMP in animal cells by binding to CRE sequences in promoters.

Cyclic GMP (cyclic guanosine monophosphate) – A signal molecule used as a second messenger by eukaryotic cells.

Cyclic GMP-gated cation channels (CNGCs) – The nonselective cation channels that are activated through direct binding of cyclic nucleotides onto the channel proteins. In general, cyclic-nucleotide gated channels are heterotetrameric complexes consisting of two or three different subunits (a, ß, and g), with important channel properties determined by the subunit composition.

Cyclic nucleotides – Second messenger hormones that are either cyclised adenosine monophosphate or cyclised guanosine monophosphate.

Cyclic phosphodiesterase – Enzyme that degrades cyclic nucleotides, including cyclic AMP and cyclic GMP.

Cyclin-dependent kinase (CDK) – Specialised protein kinase that is activated by a cyclin and participates in control of cell division.

Cyclin-dependent kinases (Cdks) – Cdks are a family of protein kinases first discovered for their role in regulating the cell cycle. Cdk binds a regulatory protein called a cyclin for the activation.

Cyclins – Family of proteins that controls the cell cycle.

Cyclo-vergence – The torsional rotations of the two eyes in opposite directions.

Cydo-oxygenase pathway – Pathway of arachidonic acid metabolism, forming prostaglandins and thromboxanes.

Cysteine protease – A class of protease with cysteine in its active site.

Cystic fibrosis (CF) – Cystic fibrosis is a genetic disorder that affects the lungs. Affected individuals suffer difficulty breathing and coughing up sputum as a result of frequent lung infections. It is caused by the presence of mutations in both copies of the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR). Congenital metabolic disorder with a malfunction of chloride ion channels. This results in a changed consistency of secretions from exocrine glands. Mucus in the bronchiae and lungs becomes viscous, causing chronic cough and severe pneumonia. CF is one of the first disorders for which clinical gene therapy studies are undertaken. An inherited disease in which the major symptom is the accumulation of fibrous tissue in the lungs, ultimately due to defects in transmembrane chloride channel.

Cytochrome c – Mitochondrial protein that functions in electron transport; released from mitochondria during apoptosis.

Cytochrome P 450 – Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a large and diverse superfamily of hemoproteins found in all domains of life. Cytochromes P450 use a wealth of exogenous and endogenous compounds as substrates in enzymatic reactions.

Cytogenetic map – A visual chromosome map based on light and dark bands due to staining and seen under the light microscope.

Cytogenomic microarray – Genomic approach to detection of copy number variants.

Cytokine – Any of a variety of substances secreted by immune cells that influence the behavior of other cells. Soluble molecules that modulate
immune responses. Low molecular weight, soluble proteins that bind specific cell surface receptors whose engagement leads to intracellular signaling, triggering the activation, proliferation, differentiation, effector action, or death of the cell. Synthesised by leukocytes and some non-hematopoietic cells under tight regulatory controls. Proteins which mediate inflammatory or immune responses. Main signaling molecules between cells of the immune system. Short peptides that stimulate cell growth and division, especially of immune cells. Small glycoproteins that are released by T-cells, macrophages and other cells. They bind to their target cells whose behavior they change.

Cytokine response modifier genes (crmgenes) – Genes of poxviruses that interfere with the action of NK cells and cytotoxic T cells.

Cytokine withdrawal – Induction of activated T cell death due to insufficient levels of cytokines, particularly IL-2.

Cytology – The examination of cells, using microscopy.

Cytoneme – Thin, acting based cellular protrusion several cell diameters long, extending from the apical surface of a cell toward a source of signaling protein (ligand); first observed in Drosophila wing disc cells extending toward Dpp and Wg.

Cytopathic effects – The visible changes of cells due to viral infection.

Cytopenia – A reduction in the normal number of cells of a particular type. The term is usually applied to hematopoietic cells (i.e., marrow-derived blood cells). Anemia is a cytopenia of red blood cells. Thrombocytopenia is a cytope- nia of platelets (i.e., thrombocytes). Neutropenia is a cytopenia of lymphocytes. A pancytopenia refers to a reduction of all the different types of cells of hema- topoietic lineage.

Cytoplasm – The fluid in a cell, surrounded by the outer cell membrane (plasma membrane). The nucleus and cell organelles are located in the cytoplasm. The internal matrix of a cell. The cytoplasm is the area between the outer periphery of a cell (the cell membrane) and the nucleus (in a eukaryotic cell). The part of the cell not including the nucleus.

Cytoplasmic determinant – A cytoplasmic protein/mRNA acting to promote a specific cell fate.

Cytoplasmic domain – Portion of a transmembrane protein that is in the cytoplasm of a cell and transduces the signal initiated by engagement of the extracellular domain into the cell’s interior.

Cytoplasmic hybrid embryos – embryos created through cell nuclear replacement using animal eggs.

Cytosine deaminase – Enzyme, usually from bacteria, that converts cytosine into uracil.

Cytoskeleton – The structural framework of the cell formed by proteins.

Cytotoxic cytokines – Cytokines that directly induce the death of cells. For example, TNF and LT.

Cytotoxic drugs – Pharmacological agents with properties that kill cells capable of self-replication. Commonly used as anticancer therapies or as immunosuppressants. Examples are azathioprine, methotrexate.

Cytotoxic T lymphocytes (CTL) or Cytotoxic T cells – Immune cells that are capable of killing cancer cells. A subset of T lymphocyte that expresses CD8 marker and is capable of killing target cells. One of two major subsets of naïve T lymphocytes. CTLs recognise and destroy target cells displaying foreign peptide complexed to MHC class I. Target cell killing occurs via cytotoxic cytokine secretion, Fas ligation, or perforin/granzyme-mediated cytotoxicity.



DAC – Data access committee (DAC).

DACO – Data Access Compliance Office (DACO).

Dacryocystitis – Infection of the lacrimal sac.

Dalton (D) – A unit of mass nearly equal to that of hydrogen (1.000). One thousand Daltons = one kilodalton (kD).

Damage-associated molecular patterns (DAMPs) – Molecules released by stressed or dying cells that bind to pattern recognition molecules (PRMs) and induce inflammation.

Dark current – The flow of cations through photoreceptors that is maximal in the dark.

Dark zone – Region of a germinal center where somatic hy- permutation occurs.

Data and safety monitoring boards (DSMBs) – Oversight committees created to perform unblinded interim reviews of phase III, blinded, randomised, placebo-controlled trials. An increasing number of studies and research in earlier stages of experimental development have incorporated DSMBs into study oversight. DSMBs are also referred to as data monitoring committees (DMCs).

Data mining – The use of computer analysis to find useful information by filtering or sifting through large amounts of data. The use of statistical and graphical tools to compare expression patterns between data sets.

Dauer – Stage of C. elegans life cycle initiated by low food and water; characterised by lack of movement and eating.

dbGaP – Database of Genotypes and Phenotypes.

Dbgene – Gene that encodes the receptor for the hormone leptin

DCAF (DDB1-Cul4A-associated WD40 domain protein) – It serves as a substrate receptor, linking DDB1 to Vpr. It is also called VprBP (Vpr binding protein).

DCas9 (Nuclease-deficient Cas9 or nuclease-dead Cas9) – A mutated version of the Cas9 that is devoid of catalytic activity but retains binding ability to the target region in the presence of PAM sequences. It cannot generate a double-stranded break at the target region but can be used as an activator or repressor for mediating an RNA-directed transcriptional control.

DC-LAMP/CD208 – A member of the lysosome-associated membrane glycoprotein (LAMP) family, specifically expressed by mature dendritic cells.

DC-SIGN/CD209 – A type 2 transmembrane protein that also contains a mannose-binding (C-type lectin) domain, expressed on dendritic cells.

DDB1 (DNA damage binding protein) – A large subunit of DNA damage binding protein, which is a heterodimer composed of large (DDB1) and small subunit (DDB2). This protein functions in nucleotide excision repair.

DDD – Deciphering Developmental Disorders (DDD).

DDG2P – Developmental Disorder Genotype to Phenotype Database.

Debt/Equity ratio – The ratio of total liabilities to stockholders’ equity. It indicates the extent to which a company can sustain losses without jeopardizing the interests of its creditors. Creditors possess priority claims over stockholders, and in case of liquidation, the creditors have first right to a company’s assets. From an individual creditor’s perspective, therefore, the amount of equity in the company’s capital structure can be regarded as a buffer that helps to guarantee that there are sufficient assets available to cover individual claims.

Deal flow – A term referring to the quantity and quality of any investment opportunities available to an investor.

Debt/loan capital – Capital that is invested in a business in exchange for the legal requirement to pay a certain amount as interest each year on the loan capital provided, and likely also to pay back some of the capital according to a defined schedule. In general, debt will be secured against assets.

Deal terms – The legal terms upon which an investment is organised (e.g., common shares with pre-emptive right).

De novo (sporadic) mutation – An altered gene that appears in the germline or fertilised egg that was not manifested in the family lineage.

De novo germline mutation – In the context of this book, de novo mutations are new (i.e., Latin, de novo, anew) disease-causing mutations found in the germline of organisms (i.e., in every somatic cell of the organism) that were not present in the germline of either parent. A de novo mutation may result as a new mutation in a differentiated germ cell of either parent (i.e., it was not present in all of the cells of the parent, but appeared as a mutation in the specific parental germ cell that contributed to the offspring), or it may be a new mutation in the zygote (i.e., ovum fertilised by sperm) or in an early embryonic cell. Examples of some rare diseases that are caused by de novo gene mutations would include: Baraitser–Winter syndrome, characterised by central nervous system and facial malformation; Borhing–Opitz syndrome, characterised by intellectual disability plus congenital malformations; CHARGE syndrome, an acronym for coloboma of the eye, heart defects, atresia of the nasal choanae, retardation of growth and/or development, genital or urinary abnormalities, and ear abnormalities and deafness, and a leading cause of combined deafness and blindness in newborns; Kabuki syndrome, characterised by intellectual disability and congenital anomalies; KBG syndrome, characterised by a disease-typical facial dysmorphism, macrodontia of the upper central incisors, costovertebral anomalies and developmental delay; and Schinzel–Giedion syndrome, characterised by distinctive facial features, neurological problems, and organ and bone abnormalities. See Somatic mosaicism.

De novo methylase – An enzyme that adds methyl groups to wholly nonmethylated sites

De novo mutation – A mutation that arises in the proband but is not present in the mother’s or father’s germline.

De novo protein – Proteins with new sequences not previously found that perform a new function.

Derivative – A financial instrument whose characteristics and value depend upon the characteristics and value of an underlier, typically a commodity, bond, equity, or currency. Examples of such derivatives include futures and options. Advanced investors sometimes purchase or sell derivatives to manage the risk associated with the underlying security, to protect against fluctuations in value, or to profit from periods of inactivity or decline.

Deamidation – The removal of an amide group from a compound. In lens biochemistry, the conversion of asparagine/glutamine to aspartic acid/glutamic acid.

Death receptor – A cell surface receptor that transmits an external signal to die to the intracellular proteins responsible for killing the cell.A protein receptor on a cell which when bound to a death signal initiates apoptosis. On ocular cells the protein is often Fas.

Death receptor pathway – Program of apoptosis that involves activating membrane-bound receptors with extrinsic factors.

Death signal – Any substance that binds to a receptor on a cell and initiates apoptosis.

Death-inducing signaling complex (DISC) – A complex of proteins activated by binding to a trimerised death receptor; the proteins initiate apoptosis.

Decellularisation – Removal of cellular elements from a tissue, while maintaining general structure.

Declaration of Helsinki – An international document to provide ethical guidance for research involving human subjects.

Decorin – A proteoglycan found in the cornea.

Defensin – A family of small antimicrobial peptides found in neutrophil granules. Cysteine-rich, cationic polypeptides that form pores in bacterial membranes prior to their destruction by lysosomal enzymes in phagocytes.

Defensin A – Antibacterial peptide made by mosquito.

Definitive endoderm – Endoderm tissue that contributes to the embryo proper, in contrast to the extra-embryonic endoderm tissues (visceral and primitive endoderm) which may be required for correct development or embryo survival but do not contribute to the overall body plan.

Definitive haematopoiesis– Occurs shortly after the primitive hematopoiesis and contains two waves. The first definitive wave generates only red cell and myeloid lineages. The second wave generates hematopoietic stem cells (HSC) that differentiate into all adult blood lineages.

Degenerate primer – Primer with several alternative bases at certain positions.

Degradation – The breaking of peptide bonds in proteins.

Degradome – The complete set of proteases that are expressed at one time, under a defined set of conditions.

Degranulation – Extracellular release by a granulocyte of the destructive contents of its granules.

Dehydrogenase – Type of enzyme that removes hydrogen atoms from its substrate.

De-identified sample – See Double-coded sample.

Delayed-type hypersensitivity (DTH) – A Type IV chronic inflammatory reaction mediated by T cells. Immunopathological damage occurring 24–72 hours after exposure of a sensitised individual to an antigen. Cell-mediated rather than antibody-mediated. See also type IV hypersensitivity.

Deletion – Change in the DNA sequence involving a portion of the DNA being removed. Mutation in which one or more bases is lost from the DNA sequence.

Delivery vehicle (in vaccines) – Inert, non-toxic structure designed to protect vaccine antigens from nuclease- or protease- mediated degradation. May also act as an adjuvant or increase antigen display. Includes liposomes, ISCOMs, virosomes and virus-like particles.

Delta endotoxin – Actual toxin released from the Cry protein into the gut of caterpillars that digest Bacillus bacterial spores.

Demethylases – An enzyme that removes methyl groups.

Demographic transition – The change in the society from extreme pov- erty to a stronger economy, often associated by a transition in the pattern of diseases from malnutrition and infection to the intractable conditions of middle and old age; for example, cardiovascular dis- ease, diabetes, and cancer.

Denaturation – 1) Dissociation of complementary strands to produce single-stranded DNA and/or RNA. 2) In reference to proteins, the process in which proteins lose their function by an alteration in their structure.

Dendrimer – A repetitively branched molecule, typically with three distinct characteristics. (1) An initiator core;(2) Interior layers (generations) composed of repeating units, radically attached to the interior core; and an (3) exterior (terminal functionality) attached to the outer- most interior generations.

Dendritic cells (DCs) – Cells of the innate immune system that retrieve, process, and present antigen to T lymphocytes. Irregularly shaped phagocytic leukocytes with finger-like processes resembling neuronal dendrites (except plasmacytoid subset). DC subsets arise from both the myeloid and lymphoid lineages and include conventional and plasmacytoid DCs. They are a special class of professional antigen-presenting cells (APC, together with macrophages and B-cells). They take up external antigens, degrade them into small fragments (epitopes), present them on MHC-class-II to T-helper cells, and hence, induce immune reactions. Depending on their maturation status which is influenced by the presence of inflammatory signals, they modulate between the inductions of tolerance versus inflammation. They also link the unspecific innate to the induced specific immune system and are hence key modulators of the immune reaction.

Dental papilla – A condensation of ectomesenchymal cells called odontoblasts, seen in histologic sections of a developing tooth.

Dentin – The calcified tissue of the tooth that constitutes the bulk of the crown and the root. It is covered by enamel on the crown and cementum on the root and surrounds the entire pulp. A calcified tissue of the body which along with enamel, cementum, and pulp is one of the four major components of teeth.

Deontology – An ethical theory that evaluates an action based on the degree to which the person performing the act meets his or her duties and obligations.

Deoxyribonucleic acid (DNA) – A biological molecule, generally double stranded, that encodes the genetic in- formation of an organism. A double helical arrangement of nucleotides that contains all the genetic information of a living organism.A genetic molecule that preserves the genome of a cell. It consists of four kinds of bases, as well as deoxyribose and phosphate. The phosphate imparts acidity to the molecule.The chemical that comprises the genetic material of all cellular organisms.

Deoxyribose – The sugar with five carbon atoms that is found in DNA.

Deoxyribozyme – Artificial DNA molecule that acts as an enzyme.

Depolarisation – A rapid change of the electrical charge in the inside of a cell from negative to positive as the result of a sudden inrush of sodium ions. The decrease in charge difference between the outside and inside of a cell. Usually, this means that the inside of the membrane becomes more positive while the outside of a membrane becomes more negative.

Depth of coverage – In reference to whole genome sequencing. The number of individual sequence reads for a particular region of a genome where the higher number reflects a greater accuracy.

Depth of field – The range of movement of an object in object space over which there is no perceptible change in focus of the image.

Depth of focus – The range of movement of the image in image space over which there is no perceptible change in focus of the image.

Dermis – Lower layer of skin beneath the epidermis and basement membrane. Contains lymphatics and blood vessels.

Design FMECA – Use of FMECA to analyse the potential failure modes of the product design.

Designated market maker – A firm that agrees to accept the financial risk of owning a certain number of new shares of a security in order to facilitate trading in that security.

Designated personnel – Those individuals who have been appointed by management to perform a specified activity (e.g., nonconformance review board, CAPA review board, change control review board, risk-evaluation team).

Desmosomes – Junctions between keratinocytes that hold a skin layer together.

Detached retina – Separation of the retina from the retinal pigment epithelial (RPE) layer.

Detectability – The potential of a defective product reaching the end user without being detected.

Detection – Detection of problems prior to distribution, or by the customer before damage occurs.

Detergents – Surfactants that comprise hydrophobic (tails) as well as hydrophilic (heads) regions and have the ability to dissolve and disperse hydrophobic molecules, including fats, oils, and lubricants in water.

Determination – An irreversible decision made by an undifferentiated cell that restricts its differentiation.

Determined – Cells are considered to be determined if they are able to assume their natural fate when placed in an antagonistic environment. Therefore, determination represents a higher level of commitment.

Determinism (genetic) – The philosophical doctrine that human action is not free but determined by genetic factors.

Deturgescence– A physiological and biochemical process that maintains the cornea in a clear state.

Deuteranopia – A type of red–green defect in which the middle-wavelength-sensitive photopigment is nonfunctional, leading to decreased hue discrimination and a tendency to confuse reds and greens. Derives from the Greek deuteros, meaning second, alluding to the defect being associated with the second of the three primary colors (green) and anopia, meaning blindness.

Deuterostome – Deuterostome literally means “second mouth” (deutero – two; stome – mouth). The blastopore is formed first during gastrulation and the mouth is formed secondarily. This mode of development applies to all deuterostomes except Tunicata. Echinodermata, Hemichordata, Xenoturbellida and Chordata are considered deuterostome phyla.

Development – Systematic application of knowledge or understanding, directed toward the production of useful materials, devices, and systems or methods, including design, development, and improvement of prototypes and new processes to meet specific requirements.

Deviation – A deviation or violation is any change from an approved procedure. Failure to control to within a critical limit or failure to follow an approved SOP.

Device – A medical device has a particular regulatory definition, which is essentially an instrument of some type that diagnoses, cures, treats, mitigates, or prevents a disease or condition. Examples range from bandaging and syringes, test strips and pregnancy tests, implants, surgical instruments, machines that run clinical chemistries and hematologist on blood specimens, and test kits—like in vitro diagnostics (which are often biotechnology products). Medical devices are regulated differently from drugs and biologicals and the type of information that needs to be submitted for U.S. FDA review differs by the classification. Class 1 are lower risk devices and those that are common in the market already. Class 2 are medium risk and there may already be a similar one on the market to which the new one can be shown to be substantially equivalent. Class 3 are the highest risk, complex novel devices.

DHFR gene – Gene that encodes the enzyme dihydrofolate reductase.

DHHS Office for Human Research Protections (OHRP) – The office with which assurance documents are negotiated.

Diabetes mellitus (or Diabetes) – A disease that results in the unequal distribution of glucose inside and outside of cells as a result of the inability of certain cells to transport glucose sufficiently. A heterogeneous group of diseases in which the pancreas fails to produce insulin in sufficient amounts to maintain euglycemia, thus causing a dramatic rise in blood glucose levels. Group of related diseases causing inability to control level of blood sugar due to defect in insulin production.

Diabetic cataract – In the widest sense, a cataract is any obstruction to light in the lens. A diabetic cataract is one whose cause can be associated with a diabetic state. Diabetic cataracts may occur rapidly in the sub capsular region as a so-called “snowflake” cataract (in more severe diabetes) or as a senescent-like cataract (as is more common in type 2 diabetes).

Diabody – Artificial antibody construct made of two single-chain Fv (scFv) fragments assembled together.

Diacylglycerol (DAG) – In the diabetic state, this compound is synthesised from glyceraldehyde’s 3-phospate and dihydroxyacetone phosphate (E-M pathway metabolites). DAG stimulates protein kinase C and, ultimately, the synthesis of endothelin-1. See Protein kinase C.

Dibenzothiophene (DBT) – Thiophene fused to two benzene rings, widely regarded as a model compound for organic sulfur in coal and oil.

Dicer – An enzyme that cuts double-stranded RNA into small segments of 21 to 23 nucleotides in length (siRNA).

Dichromacy – A color-vision deficiency in which only two primaries are required to perfectly match a monochromatic light. In this deficiency, one of the three types of photopigments is functionally absent so color vision is reduced to only two dimensions.

Dicots (see also dicotyledonous plants) – Plants with broad leaves with netlike veins, whose seedlings have two cotyledons, or seed leaves.

Dicotyledonous plants (see also dicots) – Plants with broad leaves with netlike veins, whose seedlings have two cotyledons, or seed leaves.

Dideoxynucleotide – Nucleotide whose sugar is dideoxyribose instead of ribose or deoxyribose.

Diester – Literally means any compound having two ester bonds. In the peroneal tear film, this refers to any combination of three precursor molecules-hydroxyl fatty acid, long chain alcohol, and cholesterol.

Dietary restriction – The theory that decreasing the overall number of calories without altering the nutrient intake will extend the lifespan.

Differential fluorescence induction (DFI) – Method to identify genes active in infectious agents that might be used for potential vaccines. Fluorescently labeled library clones are used to determine which genes are active after the infectious agent enters the cell.

Differential gel electrophoresis (DIGE) – Two dimensional gel electrophoresis of two or three differentially labeled protein samples on the same gel so as to compare samples within the same gel matrix.

Differential hybridization – Term defining the difference in hybridization capacity of the same oligonucleotide probe on DNA or RNA from different conditions. This term was largely used for DNA or RNA chips or the quantification of hybridization assays (covering the whole genome) obtained through fluorescent markers.

Differential interference microscopy (see also Nomarski optics) – Type of polarization microscopy that transforms differences in density into differences in height so that the image looks like a three-dimensional relief.

Differentiate – During growth or development, the acquisition of cellular traits or behaviors that are specific to one type of tissue or organ.

Differentiation- A process by which a cell changes from one type to another, losing its precursor properties and acquiring new characteristics of a specialised (tissue-specific) derivative. A stem cell is said, for example, to differentiate into a cardiomyocyte, nerve cell, or pancreas cell. In developmental biology, differentiation is the process through which a stem cell or progenitor cell becomes more specialised. The process is the elaboration of particular characteristics expressed by an end-stage cell type, or by a cell enroute to becoming an end-stage cell. This term is not synonymous with commitment, but differentiation features are used to determine when a cell is committed. Specialization of a cell line up to the ultimate stage of the specific functional cell of an organ. SCs have the ability to differentiate into one or more cell types that will form tissues and organs in vivo. This is the signature of SCs. The normal process by which a less specialised cell develops or matures to possess a more distinct form and function. The process of structural and functional specialization of a cell over time. The term “differentiation,” as it is used by pathologists, refers to the cellular process that makes one cell different from other cells, and capable of being identified as a particular named cell type (e.g., red blood cell, neutro- phil, hepatocyte, spermatocyte, neuron, etc.). Every cell in the body has the same genetic sequence in their DNA. The reason why one cell develops into a neutrophil and another cell develops into a neuron is due to the epigenome; the set of modifications to the chemical and physical structure, not the sequence, of the genome. Such modifications are cell-type specific, so that every neutrophil looks and acts like every other neutrophil, and does not look or act like neurons or gut lining cells, or muscle cells. An individual organism can be identified by his or her genomic sequence, which is unique, with some few exceptions: identical twins and organisms that reproduce asexually by division of a somatic cell. The cell types within an organism can be distinguished by their epigenome. See also Epigenome and Erasure. The process that occurs during development by which cells take on their specialised functions, such as the ability of a red blood cell to carry oxygen or a nerve cell to send an electrical signal.

Diffusion – The even dispersal of molecular particles from an area of higher to lower concentration. In transport, simple diffusion is the movement of lipid soluble substances across a plasma membrane to an area of lower concentration.

Diffusion of innovation – Refers to the spread of technologies beyond a biocluster.

Digenic disease – Digenic diseases require mutations in two genes to produce the complete clinical phenotype. There are several rare diseases that are known or suspected to be digenic. Several different forms of Usher disease, combined retinitis pigmentosa and hearing loss, are digenic. A digenic cause of several forms of long QT syndrome, a type of heart arrhythmia, has also been reported. Kallman syndrome, a form of hypogonadotropic hypogonadism, is sus- pected to be digenic. Digenic diseases often have a variable clinical pheno- type, even among family members with the disease. Mice with digenic diabetes have a non-Mendelian pattern of inheritance, typical of a polygenic familial disease . As a group of disorders, the inherited digenic disease occupies an intermediate niche, between monogenic diseases and polygenic diseases. See Monogenic disease and Polygenic disease.

Dihydrofolate reductase – Enzyme that takes part in one carbon metabolism and is needed for the synthesis of thymine and adenine

Dilution – is the lessening of the ownership position in the firm by the addition of new investors in the later rounds of investment. A reduction in the equity position of a shareholder associated with a new financing round.

Dilution Ventilation – Reduction in airborne contamination via mixing of clean incoming air with contaminated air within the room andremoval of an equivalent amount to exhaust or recirculation via treatment (e.g., filtration).

Dimethoxytrityl (DMT) group – Group used for blocking the 5′ hydroxyl of nucleotides during artificial DNA synthesis.

Dimorphism – The expression of two different forms within a population or species; in contrast to monomorphism (one form).

Dioxygenase – Enzyme that inserts two oxygen atoms into its substrate, thus yielding a diol.

Diphtheria toxin – Protein toxin made by Corynebacterium diphtheriae that inactivates elongation factor EF-2 of animal cells.

Diploid – A genome (the total DNA content contained in each cell) that consists of two homologous copies of each chromosome. Cells or organisms with a set of chromosomes consisting of pairs of homologous chromosomes referred to as 2n (see also haploid, polyploid). Having two copies of each chromosome and hence of each gene, one from each parent.

Diplopia – Double vision.

Dipodial – Branching in which all branches are equal, with no central trunk.

Direct allorecognition – A transplant recipient’s T cells recognise peptide/allo-MHC epitopes presented on the surfaces of allogeneic donor cells in the graft. See also allorecognition.

Direct immunoassay – See also reverse-phase array. Method of protein detection in which the protein is bound to a solid support and an antibody with a detection system is added.

Directed differentiation – The process by which embryonic stem cells or induced pluripotent stem cells are progressively differentiated down a particular lineage by using signals that attempt to recapitulate embryonic development.

Directed evolution – Technique for enhancing or altering the original activity of an enzyme by randomly mutating the gene and then screening for the new activity.

Directed mutagenesis – Deliberate alteration of the DNA sequence of a gene by any of a variety of artificial techniques.

Direct-to-consumer genetic testing – Genetic testing mar- keted and sold directly to consumers without the involvement of healthcare professionals.

Direct-to-consumer genetic testing through physician – Genetic testing marketed directly to consumers and physicians, and requires the physician to order the test.

Direct-to-consumer genomic testing – Genomic testing provided without intervention of a health professional.

Disaccharide – A molecule consisting of two simple sugars chemically linked together. A carbohydrate composed of two sugar units. Maltose is an example.

DISC (death-inducing signaling complex) – A complex of proteins activated by binding to a trimerised death receptor; the proteins initiate apoptosis.

Discounted cash flow (DCF) analysis – A method that determines the value of an asset as the sum of the discounted value of all cash flows projected by that asset. DCF analysis is a form of absolute valuation.

Discount rate – A term which is applied to describe the rate used in present value computations. To compute the present value of a future cash flow, for example, the cash flows are discounted at the discount rate. In this sense, the discount rate reflects the company’s cost of capital – the cost of its debt and/or equity.

Disease – A fluid concept influenced by societal and cultural attitudes that change with time and in response to new scientific and medical discoveries. The human genome sequence will dramatically alter how we define, prevent, and treat disease. Similar collections of symptoms and signs (phenotypes) may have very different under- lying genetic constitutions (genotypes). As genetic capabilities increase, additional tools will become available to subdivide disease designations that are clinically identical (see Taxonomy of disease). Condition involving abnormal cognitive or physical function.

Disease etiology – Any factor or series of related events directly or indi- rectly causing a disease. For example, the genomics revolution has improved our understanding of disease determinants and provided a deeper understanding of molecular mechanisms and biological pro- cesses (see Systems biology).

Disease expression – When a disease genotype is manifested in the phenotype.

Disease interventions – A term used in genomics that refers to development of a new generation of therapeutics based on genes.

Disease management – A continuous, coordinated healthcare process that seeks to manage and improve the health status of a patient over the entire course of a disease. The term may also apply to a patient population. Disease management services include disease- prevention efforts and as well as patient management.

Disease modeling – A process of using human or other animal cells to display disease processes that have been observed in the actual disease. Studying disease models helps us to understand how the disease develops and is useful for testing potential treatment approaches.

Disease phenotype – Includes disease-related changes in tissues as judged by gross anatomical, histological, and molecular pathologi- cal changes. Gene and protein expression analysis and interpreta- tion studies, particularly at the whole-genome level, are able to distinguish among apparently similar phenotypes.

Dismutation – Also known as disproportionation is a chemical reaction in which one molecule is reduced while the other is oxidised.

Displacement Ventilation – Reduction in airborne contamination via “plug flow” of clean incoming air forcing contaminated air within the room to exhaust or recirculation via treatment (e.g. filtration).

Disruptive technologies or innovations – Are new technologies that replace existing technologies and oftentimes involve a new set of core competencies for the firm.

Dissociation constant – The ratio of dissociated to non-dissociated components of a buffer.

Distal visceral endoderm (DVE) – A group of visceral endoderm cells found at the distal tip of the mouse egg cylinder at E5.5, characterised by its columnar morphology and the expression of a specific gene repertoire including Hhex, Cer1 and Lefty1. The DVE is formed in two waves. The first wave consists of descendants of precursors already expressing Lefty1 and Cer1 in the primitive endoderm and migrate first anteriorly. The second wave is induced at the distal pole of the mouse embryo after E5.5. As the DVE migrates towards one side, the anterior pole becomes defined, and the group of cells is referred to as the anterior visceral endoderm (AVE).

Distichiasis – Abnormal eyelashes growing from duct of meibomian gland at eyelid margin.

Distillation – Separation method used for example in alcohol production. Liquids in which various components are dissolved are separated as they reach their boiling point—their gaseous phase at different temperatures. Ethanol boils at 78.5°C (173.3°F), far earlier than water. When cooled down, they can be recaptured in separate containers.

Distributed products – Everything that could be used by the customer (e.g., finished products, spare parts, software upgrades, labeling material, user and service manuals).

Disulfide bond – A direct chemical linkage of two sulfide groups within a single peptide or protein or between different proteins. Two sulfur atoms that are bonded together and act as a bridge between the same or different polypeptides (i.e., crosslink). The bond occurs between two cysteine amino acids. A bond between two closely situated cysteine residues in a protein that stabilises the tertiary structure.

Diversification – An investment strategy focusing on making many investments at the same time in order to narrow the variability of the individual returns. Investors in the stock market will typically invest in a lot of different companies and industries whose returns, in the ideal case are not correlated so that any one company failure or industry downturn will be mitigated by their other investments. In early-stage investing, the variability of returns is extreme, since the likelihood of failure of the investment is high.

Diversity, genomic – The number of base differences between two genomes divided by the genome size.

Divestments – Represent the realisation or exiting of a private equity investment. This is generally done by selling the company, writing off the investment, or floating the company on a stock market.

Dividend – A cash payment made to the owner of a stock.

DMC – Data Monitoring Committee (DMC) – a group of experts independent from a clinical trial who monitor the data from the trial in periodic interval(s) and make recommendations to the investigators. Recommendations may be to halt the trial early, to alter some procedures, or to continue. See also DSMC.

DMD gene – Gene located on the X chromosome that encodes dystrophin and is defective in Duchenne’s muscular dystrophy (DMD).

DN thymocytes – Double negative thymocytes. Thymocytes that express neither CD4 nor CD8 molecules. Includes DN1–4 subsets.

DNA methylation – A biochemical process whereby a methyl group is added to the cytosine or adenine DNA nucleotides. This often results in altered gene expression.

DNA (deoxyribonucleic acid) – A long self-replicating chain of linked nucleotides that contains genetic information. Nucleic acid polymer of which the genes are made.

DNA adenine methylase (Dam) – A bacterial enzyme that methylates adenine in the sequence GATC.

DNA cassette – Deliberately designed segment of DNA that is flanked by convenient restriction or recombinase sites.

DNA chain terminator – A nucleotide analog that is incorporated into a growing DNA chain and stops further elongation.

DNA chip technology – Method of hybridization in which a chip is used to simultaneously detect and identify many short DNA fragments. Also known as DNA array technology or oligonucleotide array technology.

DNA cytosine methylase (Dcm) – A bacterial enzyme that methylates cytosine in the sequences CCAGG and CCTGG.

DNA damage response (DDR) – It refers to the signaling pathway that is induced by DNA damage.

DNA enhancers – Regions of DNA that can modify the rate of specific RNA synthesis.

DNA fingerprinting – Individual identification by means of differences in DNA sequence generally visualised as the pattern of DNA fragments after separation by gel electrophoresis. Use of a hypervariable minisatellite probe (usually those developed by Alec Jeffreys) on a Southern blot to produce an individual-specific series of bands for identification of individuals or relationships.

DNA gyrase – An enzyme that introduces negative supercoils into DNA, a member of the type II topoisomerase family.

DNA helicase – An enzyme that forms single-stranded DNA by breaking the hydrogen bonds between bases on opposing DNA strands.Enzyme that unwinds double-helical DNA.

DNA invertase – An enzyme that recognises specific sequences at the two ends of an invertible segment and inverts the DNA between them.

DNA library – A collection of cell clones containing different recombi- nant DNA clones.

DNA ligase – Enzyme that joins DNA fragments covalently, end to end.

DNA methylation – Addition of methyl (dCH3) groups onto DNA to regulated protein access to various regions. DNA methylation is a chemical modification of DNA that does not alter the sequence of nucleotide bases. It is currently believed that DNA methylation plays a major role in cellular differentiation, control- ling which genes are turned on and which genes are turned off in a cell, hence determining a cell’s “type” (e.g., hepatocyte, thyroid follicular cell, neuron). Because cells of a particular cell lineage divide to produce more cells of the same lineage, DNA methylation patterns must be preserved with each somatic cell generation. The cellular process by which DNA is modified and controlled without altering the sequence of nucleotide bases is called epigenomics, and the collection of such modifications in DNA constitutes the epigenome. About 1% of DNA is methylated in human somatic DNA, and DNA methylation occurs primarily on cytosine, usually at locations for which cytosine is followed by guanine, and designated as “CpG.” See CpG island.

DNA microarray – Chip used to simultaneously detect and identify many short DNA fragments by DNA–DNA hybridization. Also known as DNA array or oligonucleotide array detector, same as DNA array or DNA chip. DNA molecules with known sequences are attached to a “chip” or glass slide in an array (or matrix) format. Fluorescently labeled DNA fragments or RNA molecules can be added and will bind specifically to the complementary sequence. The fluorescent signal of the bound DNA or RNA is detected and quantified with specialised software.

DNA mutation – Any alteration in DNA (such as the formation of a pyrimidine dimer) that causes an aberrant function of DNA.

DNA mutation rate – In most normal tissues, the DNA mutation rate is quite low. In humans, point mutations (i.e., mutations that occur in a single nucleotide base within the genome) occur with a frequency of about 1 to 3 × 10−8 per base. This estimate is in line with estimates from other labs, all of which are somewhat speculative. Cancer cells have genetic instability. Cancer cells from the same individuals with low rates of mutation in normal cells had rates that were about a hundred-fold higher, with an average of 210 × 10−8 mutations per base pair. See Mutator phenotype.

DNA polymerase – The enzyme that adds new nucleotides onto a growing strand of DNA. An enzyme that elongates strands of DNA, especially when chromosomes are being replicated.

DNA polymerase III (Pol III) – Enzyme that makes most of the DNA when bacterial chromosomes are replicated.

DNA repair – When damage occurs in DNA, the cell has three options: (1) do nothing and risk that the damaged DNA will be replicated by cell division and passed to somatic daughter cells. If the DNA damage occurs in a germ cell, the genetic alteration may be passed to the progeny as a new, stable mutation in the human gene pool; (2) eliminate the defect by killing the cell that harbors the damaged DNA, employing a cellular suicide process known as apoptosis; (3) repair the damaged DNA. Several tumor suppressor genes regulate normal DNA repair mechanisms. The inactivation of tumor suppressor genes may lead to genetic instability and the likelihood that an increase in the cellular mutation rate will ultimately initiate carcinogenesis.

DNA repair genes – Genes encoding elements of intracellular pathways that correct mutations in DNA to maintain genomic stability.

DNA replication – The process of creating an exact copy of DNA.

DNA SELEX – Method in which catalytically active DNA sequences are altered by mutations to use new substrates.

DNA sequencing – Technologies through which the order of base pairs in a DNA molecule can be determined.

DNA shuffling – Method of artificial evolution in which genes are cut into segments that are mutagenised, mixed, shuffled, and rejoined.

DNA synthesiser – Machine that adds one nucleotide after another in a 3′ to 5′ direction to assemble a length of DNA.

DNA vaccine – Vaccine that consists of DNA that encodes a specific antigenic protein of the disease agent. After entering the host, the DNA is expressed, and the immune system reacts to the foreign protein.

DNAse-seq – A high throughput sequencing method to identify sites of open chromatin based on their relative accessibility to cleavage by DNAse I.

DO – Dissolved Oxygen (DO).

Documentation of informed consent – In the informed consent process, the procedure of obtaining a signature of consent. The signature may be that of a capable adult or of a parent, guardian, or other legally and ethically acceptable person on behalf of a minor or decisionally incapacitated adult.

Domain – A discrete portion of a protein with its own function. The combination of domains in a single protein determines its overall function. A sequence of amino acids in a protein that consists of more than one secondary structure. It may include disulfide bonds. Generally, a domain has some specific function in a protein.

Dome region – Region of mucosal lymphoid follicle overlying a germinal center.

Dominant – An allele (or the trait encoded by that allele) that produces its characteristic phenotype when present in the heterozygous form.

Dominant negative mutation – A mutation that results in a mutant gene product that can inhibit the function of the wild-type gene product in heterozygotes. Mutation giving a gene product that not only is functionally defective but also inactivates the wild-type gene product. Usually occurs with multi- subunit proteins.

Dominant-negative – A mutated protein that interferes with the function of normal copies of the same protein.

Dormancy – The period from the time that a metastatic cell has seeded to a site that is non-adjacent to the primary tumor and the time that the seeded focus grows to a clinically detectable mass. Dormancy has a variable length, varying from days to decades. We know very little about the pathways that control dor- mancy. Most people who die from cancer succumb to their metastatic lesions; the primary cancer seldom kills. If we had a method that prolonged the dor- mancy of metastatic foci, it would have enormous medical benefit to individuals with cancer.

Dosage compensation – The control of X chromosome gene expression chromosomes dependent upon genotype (XX vs. XY).

Dosage effect – The number of copies of a gene; variation in the number of copies can result in aberrant gene expression or be associated with disease phenotype; also used in the context of haploinsufficiency.

Dossier – A French word used commonly in Europe, but also in other countries, to mean an application or submission to a regulatory authority. The complete body of data submitted for regulatory assessment. For example, for the quality assessment, the dossier refers to the administrative and quality constituents of the eCTD, i.e. Module 1 (administrative), Module 2 (Overall Summaries) and Module 3 (quality) respectively, and (typically) more specifically to the content of Module 3.

Dot blot – Hybridization technique in which various DNA samples are attached to a filter in small spot. The blot can then be probed with a gene of interest to find matching sequences.

Double helix – Structure formed by twisting two strands of DNA spirally around each other.

Down syndrome – Defective development, including mental retardation, resulting from an extra copy of chromosome 21 (trisomy).

Double membrane vesicle (DMV) – It refers to double membrane structures formed as protrusions from the ER membrane into the cytosol, frequently connected to the ER membrane via a neck-like structure.

Double-blinded – In a clinical trial when neither the subject nor the investigator knows to which study arm the subject has been assigned.

Double-coded sample – A sample that is labeled with a second coded number that is not related to its original number, also called a de-identified sample. To anonymise the sample, the link between the two codes is destroyed. Also called a de-identified sample.

Double-helix destabilising proteins – Proteins that temporarily prevent the joining of newly formed DNA strands during replication.

Double-strand breaks (DSB) – A break in the double helix of the DNA at a distinct locus.

Downstream – This term refers to the purification or concentration (or dilution) steps in manufacturing such as centrifugation, chromatography, filtration, dialysis, viral clearance, sterilisation, etc. These steps occur “downstream” in the process “flow” from the upstream steps.

2D LC microcapillary column – A column containing two different stationary phases that separates complex peptide fragment mixtures during liquid chromatography (LC).

2-D PAGE – Two-dimensional polyacrylamide gel electrophoresis (2-D PAGE).

Down round – A round of financing where investors purchase stock from a company at a lower valuation than the valuation placed upon the company by earlier investors. Down rounds cause dilution of ownership for existing investors. This often means the company’s founders stock or options are worth much less or even nothing at all. Unfortunately, sometimes the only option is going out of business. In this case, down rounds are necessary and welcomed.

Downstream processing – refers to the recovery and purification of biosynthetic substances after they have been synthesised. See also Upstream processing.

DPC – Discrete Particle Counter (DPC).

DP thymocytes – Double positive thymocytes. Thymocytes that express both CD4 and CD8 molecules.

Draining lymph node – Nearest lymph node that receives the lymph, antigens, lymphocytes and APCs emanating from a particular tissue.

Driver – Normal DNA used in suppressive subtraction hybridization that is used to “subtract” or remove the common sequences.

DRRS (Duane radial ray syndrome) – Also known as Okihiro syndrome, this is an autosomal dominant syndrome marked by DRS together with forearm and hand anomalies and variable expression of cardiac, renal, hearing, and vertebral anomalies; caused by heterozygous mutations in SALL4.

DRS (Duane retraction syndrome) – A congenital horizontal ocular motility disturbance, usually unilateral but occasionally bilateral, defined largely by the presence of retraction of the globe and narrowing of the palpebral fissure on adduction; usually described as types 1, 2, and 3; most often sporadic but familial in 5–10%.

Due diligence – The detailed review of a business plan as well as a thorough assessment of a management team prior to a private equity investment. This process includes reviewing factors such as the management team, market, competition, track record, and finances.

Drug – A substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease. (U.S. FDA definition) Biotechnology products and traditional biologicals intended for human use according to the defi- nitionare considered to be drugs by U.S. FDA.

Drug design – Development of new classes of medicines based on a reasoned approach using gene sequence and protein structure function information rather than the traditional trial-and-error method.

Drug information – In a protocol, the section that describes the physical properties of experimental agents used in the study, including their formulations, strengths, and other relevant details.

Drug interaction – Adverse drug interaction, drug–drug interaction, drug–laboratory interaction, or drug–food interaction. It is defined as an action of a drug on the effectiveness or toxicity of another drug.

Drug Product (DP) – The final formulated product that is used in people.

Drug Substance (DS) – A component of a product that actively contributes to the activity and efficacy of the product, aka the active pharmaceutical ingredient. There may be more than one drug substance in a drug product, and the drug substance(s) is formulated into a drug product that is used for people.

Dry eye – A multifactorial disorder of the tear film characterised by either decreased tear production or increased tear evaporation.

dsDNA – double-stranded DNA.

DSMB or DSMC – Data Safety Monitoring Board (DSMB) or Data Safety Monitoring Committee (DSMC) – a group of experts independent from a clinical trial who monitor the data from the trial in periodic interval(s) and make recommendations to the investigators. Recommendations may be to halt the trial early, to alter some procedures, or to continue.

DszABCoperon – Group of genes encoding pathway for removing sulfur from dibenzothiophene.

Duchennes muscular dystrophy (DMD) – One particular form of muscular dystrophy, degenerative muscle disease.

Duplication – Change in the DNA sequence involving an extra copy or copies of a portion of the DNA. Mutation in which a segment of DNA is duplicated.

Durable Power of Attorney (DPA) for Research Decisions – A document that assigns an agent to be the responsible decision maker at any time the individual is unable to make his or her own research decisions.

Dynamic mutation – Mutation consisting of multiple tandem repeats that increase in number over successive generations.

Dynamin – A GTPase primarily involved in scission of newly formed vesicle during endocytosis.

Dyserythropoiesis – A dysfunctional form of blood cell formation in which there is excessive cell death of precursor and differentiated blood cells, often leading to pancytopenia. The death of precursor blood cells forces hematopoietically active tissues (i.e., blood-forming tissues such as bone marrow) to produce more and more precursor cells, compensating for high cell death rates. This leads to the expansion of hematopoietic tissue, sometimes resulting in blood cell formation in sites other than the bone marrow, such as spleen, lymph nodes, and liver. Ineffective hematopoiesis is a near-synonym for dyseryth- ropoiesis. HEMPAS (hereditary erythroblastic multinuclearity with positive acidified-serum test), also known as congenital dyserythropoietic anemia type II (CDAN2), is an inherited dyserythropoiesis caused by a mutation in the SEC23B gene.

Dysmorphism – A difference of body structure that is suggestive of a congenital disorder, genetic syndrome, or birth defect.

Dysplasia – The term means abnormal growth, and it is used in different ways in different biomedical specialties. Developmental biologists and pediatricians use the term “dysplasia” to refer to organs or parts of organs that have not grown properly. Stunted growth of an organ, or morphologically abnormal tissues within an organism, would be types of developmental dysplasia. Oncologists (i.e., cancer specialists) use the term “dysplasia” to mean “cellular atypia” characteristic of neoplastic cells. Cellular dysplasia is found in precancers, cancers, and benign tumors. Dysplasia is defined as an unequivocal neoplastic lesion strictly limited to the epithelium (intraepithelial).

Dyspnoea – Shortness of breath.

Dystopia canthorum – Lateral displacement of inner canthus.

Dystrophin – Protein encoded by the DMD gene whose malfunction causes muscular dystrophy. Dystrophin helps attach muscle fibrils to the membranes of muscle cells. See also DMD.


E1A protein – An adenovirus early protein that promotes transcription of other early virus genes and binds to host cell Rb protein.

E2F – A transcription factor that was discovered as a DNA-binding protein of adenovirus E2 gene promoter. It is a representative S-phase specific transcription factor. Regulatory protein that controls synthesis of cyclins E and A. Cyclin E2 transcription factor. A protein that promotes the transcription of mRNAs to promote the cell cycle.

E6AP (E6-associated protein) – A host factor first identified as HPV E6 binding protein. It is now classified as a member of HECT (homologous to E6AP carboxyl-terminus)-type ubiquitin E3 ligase family.

EAGDA – Expert Advisory Group on Data Access (EAGDA).

EAU – see experimental autoimmune uveitis (EAU).

EBR – Electronic Batch Record (EBR).

Early genes – Genes expressed early during virus infection and that mainly encode enzymes involved in virus DNA (or RNA) replication.

Early phase reaction – In the effector phase of type I hyper- sensitivity, the rapid onset of clinical symptoms induced by pre-formed inflammatory mediators immediately re- leased via mast cell degranulation.

Early-stage financing – In the preseed or seed phase, financing mostly starts with the ‘three Fs,’ i.e., family, friends, and fools. Afterwards, it is usually the government that steps in with grants and loans, followed by business angels, and early-stage venture capitalists.

Earnings – Also called net income or net profits. A term referring to the difference between revenue and expenses.

Earnings before interest and taxes (EBIT) – A measurement of a firm’s profitability before adjusting for interest expenses or tax obligations. This measure is very often applied to compare individual companies with different levels of indebtedness.

Earnings before interest, taxes, depreciation, amortisation (EBITDA) – The acronym for earnings plus interest expense, taxes, depreciation, and amortisation.

Earnings per share (EPS) – The best known of all financial ratios is derived by dividing net income through the average number of common shares outstanding.

EC or IEC – Ethics Committee or Institutional Ethics Committee or Independent Ethics Committee- see IRB- the terms EC or IEC are used in countries around the globe, other than the United States. The United States refers to these committees as IRBs.

ECBS – Expert Committee on Biological Standardization—an advisory committee to WHO constituted of mem- bers from numerous countries representing both developed country and developing country NRAs and/or NCLs.

Ecdysone – Steroid hormone from insects that is involved in molting.

ECL (enhanced chemiluminescence) – ECL is a common technique for a variety of detection assays in biology. An antibody that is conjugated to an enzyme (either HRP or AP) is used. The enzyme catalyzes the conversion of the enhanced chemiluminescent substrate into a sensitised reagent, which emits light. Enhanced chemiluminescence allows detection of minute quantities of a biomolecule.

eCTD – electronic Common Technical Document.

Ectoderm – One of the three cell lineages in the early embryo. The ectoderm gives rise to the outer cell layers of the embryo, forming, for example, the skin and nerve cells. One of the three germ layers of the embryo. It gives rise to the epidermis, the neural plate, cranial placodes and the neural crest. There are three embryonic layers that eventually develop into the fully developed animal: endoderm, mesoderm, and ectoderm. The ectoderm gives rise to the skin epidermis and the skin appendages (hairs, sebaceous glands, breast glandular tissue). The outer of three germ layers of the early embryo that gives rise in later development to the skin, cells of the amnion and chorion, nervous system, enamel of the teeth, the lens of the eye, placode, and neural crest.

Ectodermal dysplasias – Syndromes that affect two or more ectodermal organs; the most common syndromes involving dental defects.

Ectropion – Outward turned eyelids.

Edema factor (EF) – Protein toxin made by anthrax bacteria that acts as an adenylate cyclase.

Edible vaccine – Vaccine that is expressed in the edible part of a plant. Eating an edible vaccine would confer resistance to the disease state.

Effector cell – Any cell that actively carries out an immunological function. The differentiated progeny of an activated leukocyte that act to eliminate a non-self entity. Includes plasma cells, Th effector cells and CTLs.

Effector functions – The actions taken by effector cells and antibodies to eliminate foreign entities. Includes cytokine secretion, cytotoxicity, and antibody-mediated clearance.

Effector memory T cells (Tem) – Class of memory T cells that is short-lived and circulates through non-lymphoid tissues where pathogens are likely to attack a second time. These cells can also enter sites of inflammation and infection.

Effector site – Remote mucosal location where lymphocytes activated in a mucosal inductive site differentiate and exert effector actions.

Effector stage (hypersensitivity) – The excessive, abnormal secondary response to an antigen (sensitizing agent) that results in inflammatory tissue damage. See type I–IV hypersensitivities.

Efferent – Leading away from some structure.

Efferent lymphatic vessel – A vessel that conveys lymph away from a lymph node.

Efficacy – ICH uses the term efficacy to mean topics related to clinical studies, whether they have to do with safety, activity, or efficacy. Efficacy means the ability to produce a desired or intended result, i.e., that the product “works.” It is normally used in the context of describing results from well-controlled clinical trials, i.e., premarketing; whereas “effectiveness” generally is used to describe information gained through real-world use, i.e., post marketing.

Efficacy (of a vaccine) – The ability of a vaccine to effectively protect individuals from disease. Expressed as the percentage of individuals vaccinated that develop immune responses to the pathogen. Also called “coverage.”

EGA – European Genome Phenome Archive.

Egg cylinder – The mouse conceptus after implantation, from E5 to gastrulation. The conceptus at these stages has the shape of a cylinder and comprises a proximal and a distal region.

Efficacy endpoints – Study variables evaluated for effectiveness.

Eicosanoid – Cyclic lipids derived from eicosanoic acids. They act as short-term hormones.

EIR – Establishment Inspection Report- a document detailing U.S. FDA inspectors’ findings prepared following an inspection of a facility or a bioresearch monitoring inspection.

Elastic modulus – Mathematical description of an object or substance’s tendency to be deformed elastically (i.e., non-permanently) when a force is applied to it.

Elastin – Protein encoded by the ELN gene and found in the elastic tissues of skin, lung, and blood vessels.

Elastin-like polypeptide (ELP) – A protein created in the laboratory that has elastin-like properties.

Electrochemical detector – A device that detects changes in oxidation and reduction of proteins (or other molecules) in the mobile phase during chromatography.

Electrode-oxidizing organisms – Microorganisms that use electrons from a cathode of a microbial fuel cell to reduce substances in the chamber, and establish a flow of electrons to form a current.

Electrode-reducing organisms – Microorganisms that donate electrons to an anode of a microbial fuel cell, thus establishing a current flow.

Electronic health record (EHR) – A real-time patient health record with access to evidence-based decision-support tools that can be used to aid clinicians in decision making, automating and stream- lining the clinician’s workflow, thereby ensuring that all clinical information is communicated. It can also support the collection of data for uses other than clinical care, such as billing, quality management, outcome reporting, and public health disease sur-veillance and reporting.

Electronic Visual Acuity (EVA) – A computerised method of visual acuity testing for clinic use as a proven alternative to the standard paper or plastic ETDRS charts.

Electrophoresis – Separation technique whereby substances are separated on the basis of their electric charge and their molecular mass.

Electrophysiology- Technique for measuring electrical currents, voltages, and resistance over the cell plasma membrane that results from ion fluxes.

Electroporation – Method in molecular biology for the transformation of cells. An electric field is generated that makes holes appear in the membrane of exposed cells, allowing DNA from outside the cell to enter the cytoplasm. Technique that uses high-voltage discharge to make cells competent to take up DNA.

Electroretinography – The recording of the changes in electric potential in the retina by stimulating it by light.

Electroretinogram (ERG) – A record of electric activity of cells, measured by inserting an electrode into the eye. A diagnostic test that measures the electrical activity of the retina in response to a light stimulus. In this test, the rods, cones and light sensitive cells of the eyes are examined.

Electrospinning – Process which uses an electrical charge to draw very fine (typically on the micro- or nano-scale) fibers from a liquid.

Electrospray ionization (ESI) – Type of mass spectrometry in which gas-phase ions are generated from ions in solution.

ELISA (enzyme-linked immunosorbent assay) – An immunological diagnostic test that uses enzyme-linked antibodies as indicators. Enzyme-linked immunosorbent assay. Binder– ligand assay in which the antibody or antigen used is linked to an enzyme. The presence of binder–ligand pairs can be determined by adding a chromogenic substrate whose enzymatic conversion causes a detectable color change. ELISA is the most frequently used diagnostic tool for virus detection that combines the exquisite specificity of antigen—antibody binding and the sensitivity of enzyme reaction. A type of assay that links an antigen or an antibody to a plate, a specimen is applied, the corresponding antibody or antigen (analytic) is then detected in the specimen with a secondary antibody bound to an enzyme that produces a measurable effect, such as color or fluorescence.

Elongation – (in reference to protein translation) The process of adding amino acids onto a growing polypeptide chain.

Elongation factors – Proteins that are required for the elongation of a growing polypeptide chain.

Elution – Removing bound molecules from a chromatography column by passing through buffer.

EMA or European Medicines Agency (EMA) – A European agency for the evaluation and approval of medicinal products in the member states of the European Union. A European Union agency responsible for the evaluation of medicinal products and pharmacovigilance. It plays an important role in the licensing of medicinal products in the European Economic Area. European equivalent of the FDA in the USA. European agency that evaluates drugs for human and veterinary use. The EMA’s mission is to promote scientific excellence in the evaluation and supervision of medicines in the European Union. European Medicines Agency, formerly EMEA- the centralised European regulator for biotechnology-derived biomedical products. The European Union and European Commission have established the EMA for this purpose. Is an independent agency associated with the European Commission that is similar in purpose and scope to the U.S. FDA. 

Embden-Meyerhoff pathway – The carbohydrate glycolytic pathway ending at pyruvate that was first described by Gustav Embden, Otto Meyerhof, and five other investigators in 1940.

Embryo – Early stage of development, after fusion of egg and sperm.

Embryoid body – A three-dimensional ball of embryonic stem cells that forms before the stem cells differentiate into specialised cell types.Structure formed after aggregation of pluripotent stem cells. Tight contact between the cells results in outer and inner cell layers that differentiate differently. The outer layer becomes epithelial endoderm, while the inner cells differentiate to cells such as ectoderm, rather like the early differentiation steps that take place in an embryo during gastrulation. Early mesoderm differentiation also takes place within an embryoid body.

Embryonic carcinoma (EC) cells – Pluripotent cell line originating from transformed PGCs. EC cells are derived from teratocarcinomas.

Embryonic germ (EG) cells – Pluripotent cell line derived from explanted PGCs. In contrast to pluripotent ICM and ES cells, PGCs are unipotent but become pluripotent upon explantation in culture. Stem cells derived from primordial germ cells. These cells are pluripotent and behave rather similarly in culture to embryonic stem cells, although they do not form germ cells in chimeric mice.

Embryonic induction – The interaction between an inducing tissue and a responding tissue. As a result, the responding tissue undergoes a change in fate.

Embryonic stem (ES) cells – A cell line derived from undifferentiated, pluripotent cells from the embryo compared with those harnessed from induced adult somatic cells, also referred to as induced adult pluripotent cells (IAPCs). Pluripotent cell line derived from the ICM upon explantation in culture, which can differentiate in vitro into many different lineages and cell types, and, upon injection into blastocysts, can give rise to all tissues including the germ line.Pluripotent stem cells derived from the inner cell mass of a blastocyst-stage embryo and grown in culture. Under the right conditions, ES cells can be cultured as a cell line (an embryonic stem cell line), which is immortal.Stem cell derived from the blastocyst stage of the embryo.

Embryonic stem cell line – A cell line that grows in vitro with the appropriate nutrients and factors that was derived from the inner cell mass of a blastula embryo and retains all the characteristics of a stem cell.

Embryonic stem cells – Totipotent or for generating gene libraries of a genome.

Emergency use – When the FDA allows for emergency administration of test agents and/or devices under specified circumstances.

Emergency Use Authorisation – Temporary authorisation granted by the U.S. Food and Drug Administration that allows for the use of a drug or vaccine for a limited amount of time during a public health emergency.

Emmetropization – The active process of reduction in refractive error toward an ideally focused system that occurs in the human eye during the first 2 years of development.

Emulsion PCR – A PCR reaction that occurs in water droplets of an emulsion of water and oil that is used during 454 sequencing technology.

Enamel knots – Signallingcentres in dental epithelium that regulate tooth morphogenesis.

Enamel matrix derivative – An extract of porcine fetal tooth material used to biomimetically stimulate the soft and hard tissues surrounding teeth to regrow (in a process known as regeneration) following tissue destruction.

Enantiomers – Isomers that are mirror images of each other, but cannot be superimposed- similar to the right and left hand.

Encephalitis – Inflammation of the brain.

End effect – An adverse consequence that a failure mode has on the function of a device.

Endemic – The constant presence (or typical prevalence) of a pathogen or condition within a geographical area.

Endocytosis – The process by which molecules are brought from the exterior to the interior of a cell.

Entrainment – The synchronisation of circadian oscillations of the clock to the external daily changes of day and night or to other cyclically changing environmental cues.

Endlysosome – Intracellular membrane-bound structure formed by the fusion of a late endosome and a lysosome. Degrades internalised entities.

Endochondral ossification – A mechanism of bone formation in which a cartilage model is replaced with ossified tissue produced by invading osteoblasts. The process by which the cartilaginous template of the long bones and skull base is gradually replaced by bone.

Endocrine – A substance secreted into the blood, rather than into a duct system.

Endocrine cells – Cells that secrete chemical substances into the bloodstream. These cells participate in the neuroendocrine system since the first order hormones in the system originate from the hypothalamus. Within the pancreas, the cells that produce hormones such as insulin and glucagon that are secreted directly into the blood- stream, where they travel to their target tissues.

Endocytic processing – Use of an intracellular system of membrane-bound endosomes and end lysosomes containing hydrolytic enzymes and other substances to di- gest internalised materials. Responsible for exogenous antigen processing and presentation.

Endocytosis  – A process by which a cell takes in a large molecule by engulfing it and surrounding it with a membranous covering. A process by which cell membranes envelope and internalise transmembrane and/or extracellular signaling proteins into cytoplasmic vesicles. Cytoplasmic proteins including dynamin mediate the inward budding of vesicles from the plasma membrane; dynamin is often targeted to block endocytosis in genetic studies. Once internalised, endocytic vesicles are sorted into different groups which undergo recycling to the plasma membrane or lysosomal degradation.

Endoderm – One of the three cell lineages in the early embryo. Endoderm gives rise to the innermost cells of the foetus- the gastrointestinal tract (e.g., intestine, liver, and pancreas) and the lungs.The innermost germ layer of vertebrate embryos that gives rise to the epithelial cells lining the digestive and respiratory system as well as visceral organs including the liver, thyroid and pancreas. Note that early in the development of birds and mammals, the definitive endoderm is initially part of the outermost layer of cells.There are three embryonic layers that eventually develop into the fully developed animal: endoderm, mesoderm, and ectoderm. The endoderm forms a tube extending from the embryonic mouth to the embryonic anus. The mucosa of the gastrointestinal tract, the glandular cells of the liver and pancreas, and the lining cells of the respiratory system all derive from the endoderm. The inner of three germ layers of the early embryo that gives rise in later development to tissues such as the lungs, the intestine, the liver, and the pancreas.

Endogenous antigen – An antigenic protein that originates within a cell in the host, as in a protein synthesised in a cell infected by a virus or intracellular bacterium.

Endogenous antigen processing and presentation – Mechanism by which endogenous antigens in the cytosol are degraded into peptides via proteasomes and complexed to MHC class I in the endoplasmic reticulum (ER). The peptide–MHC class I complex is then displayed on the cell surface. This pathway operates in almost all nucleated cell types.

Endomesoderm – Mesoderm that derives from the endoderm of a two-layered blastodisc.

Endonuclease – Unlike exonuclease, this nuclease cuts within the RNA or DNA molecule (following a template or a defined distance).

Endopeptidase – Protease that cuts within a polypeptide chain.

Endosome – An intracellular membrane-bound vesicle produced through endocytosis.

Endosteum – A layer of connective tissue that lies between the bone and bone marrow in long bones.

Endostyle – This is an endodermal structure found in invertebrate chordates in the pharyngeal area. The endostyle secretes mucus to capture small particles and so increase the efficiency of filter feeding. In lancelets and tunicates, the endostyle also accumulates iodine and is considered homologous to the vertebrate thyroid gland.

Endothelial cells – A thin flattened cell found on the surface of blood vessels and lymph vessels.

Endothelin-1 – See Protein kinase C.

Endothelial polymegethism – Variation in the size of the endothelial cells of the cornea as a result of disturbed metabolism.

Endotoxic shock – A sometimes fatal collapse of circulatory and metabolic systems induced by overwhelming amounts of cytokines (particularly IL-1 and TNF) re- leased in response to bacterial endotoxins.

Endotoxin – A toxin not released from the cell, usually bound to the cell surface or intracellular protein. Lipopolysaccharide complex associated with the outer membrane of Gram-negative pathogens. Lipopolysaccharide from the outer membrane of gram-negative bacteria. Released from the cell walls of damaged gram-negative bacteria; lipid portion of lipopolysaccharide (LPS).

Enhancer sequences – Regulatory sequence outside, and often far away from, the promoter region that binds transcription factors.

Endowment funds – Organisations chartered to invest money for specific purposes.

Endothelial cells – The type of cells forming the interior surface of blood vessels; they create an interface between circulating blood in the lumen and the rest of the vessel wall.

Endothelial progenitor cells (EPCs) – They are bone marrow stem cell-derived cells that have the ability to differentiate into endothelial cells. EPCs exist in bone marrow, peripheral blood, umbilical blood, and foetal liver.

Endpoint – The endpoint of a study is the clinical condition or parameter being studied that signifies whether the study product has worked or failed for the study participant. An endpoint is the event that triggers whether the participant counts toward the metric being measured in the study. Examples, for a prevention study—whether or not the disease occurs; for a therapy study—whether or not the disease aspect worsens or improves—e.g., does the patient survive or die, how long does it take the patient to get out of the hospital, does the disease remit or relapse, etc. The endpoint is the parameter used to judge whether or not the product worked or did what it was supposed to do. Safety parameters are also endpoints of studies, e.g., did the subject have an adverse event or experience?

End-to-end anastomosis – Surgical union of two tubular structures, usually by sutures or staples.

Energy – State of lymphocyte non-responsiveness to specific antigen. Induced by an encounter of the lymphocyte with cognate antigen under less than optimal conditions, such as in the absence of costimulation.

EngraftmentThe process of which infused transplanted hematopoietic stem cells produce mature progeny in the peripheral circulation

Enhancer or Enhancer element – A region of DNA that impacts gene transcription in cis through the recruitment of transcription factors or other DNA binding/modifying proteins; also called cis-regulatory modules. A region of DNA that binds to steroid and thyroid protein complexes in order to influence a promoter site.A regulatory DNA sequence that increases transcription of a gene. An enhancer can function in either orientation, and it may be located up to several thousand base pairs upstream or downstream from the gene it regulates. A site on DNA that binds to trans-acting protein factors to enhance the transcription of genes. Unlike promoters, enhancers do not need to be close to their target genes. Enhancers play a major role in the control of gene expression. Fundamental cis-regulator elements for the control of gene expression, providing a platform for the recruitment of transcription factors and the establishment of specific chromatin organization. Many, if not all, functional enhancers are transcribed in a permissive manner, in both directions (sense and antisense) and are called eRNA. Transcribed enhancer regions have specific signatures at the histone level that distinguish them from other transcription units. See also Promoter.

ENSLI amacrine cells – A class of retinal amacrine cells that release the peptide, somatostatin. These cells get their name because they are immunoreactive for enkephalin, neurotensin, and somatostatin (ENSI, enkephalin-, neurotensin-, and somatostatin-like immunoreactive).

Enterochelin (or enterobactin) – A siderophore used by E. coli and many enteric bacteria.

Enterocytes – Simple columnar epithelial cells that line the intestinal villi and absorb nutrients from the intestinal lumen and pass them into the blood stream. Smaller, non-dividing cells arising from Centro blasts that migrate to the light zone of the Germinal center (GC) and undergo affinity maturation and isotype switching. Give rise to plasma cells and memory cells.

Enterotoxin – Protein toxin secreted by enteric bacteria.

Enteroviruses – Group of small RNA viruses that infect animal intestines and includes poliovirus.

Entrepreneur – The owner or founder of an unquoted business. It often relates to an enterprising person setting up or growing a new company which requires capital.

Entrepreneurship – The assumption of risk and responsibility in designing and implementing a business strategy or starting a business.

Enthalpy – A measure for energy (in Joules, J) within a system comprising the internal energy of matter and work (dependent on pressure and volume). Enthalpy is denoted by the letter H.

Entropion – Inward turned eyelids.

Entropy – A thermodynamic quantity that could vaguely be described as the degree of disorganization within a system. Entropy is denoted by the letter S and measured in Joules per Kelvin (J/K).

Entrustable professional activities – Activities that a physician would be expected to be able to carry out without supervision.

Envelope – 1) The lipid bilayer that surrounds the capsid or nucleocapsid of a virus or 2) the membranes and cell wall of a bacterial cell.

Enveloped virus – A virus that possesses a lipid bilayer as its outermost shell. Viral proteins become embedded into the envelope.

Environmental factors – May include chemical factors, dietary factors, infectious agents, and physical and social factors.

EnviropigTM – Transgenic pig with much less phosphorus in its waste.

Enzyme – A macromolecular biological catalysts that accelerate the chemical reactions. A molecule, usually a protein, that catalyzes a biochemical reaction, changing one substance into another. A protein that acts as a biological catalyst that controls the rate of a biochemical reaction within a cell. A protein that is capable of catalytic activity. The term meansin yeast where enzymes were first discovered. Proteins that act as biocatalysts, i.e., they facilitate the transition of chemical groups from one molecule to another in a chemical reaction while remaining intact themselves.

Enzyme-linked immunosorbent assay (ELISA) – Sensitive method to assay the amount of a specific protein in a sample using enzyme-linked antibodies.

Enzyme-substrate complex (ES) – An enzyme having a substrate present at its active site.

Eosinophilic (acidophilic) – A histological term for cellular components that bind to acidic dyes (eosin being the most common example).

Eosinophils – Connective tissue granulocytes with granules that stain reddish with acidic dyes. The granules contain highly basic proteins and enzymes effective in the killing of larger parasites. Eosinophils also play a role in allergy. White blood cell with a multi-lobed nucleus and cytoplasmic granules which stain positively with an acidic dye (eosin).

Ephaptic – Electrical conduction across a synapse between neurons without the mediation of a neurotransmitter.

Epiblast – A tissue formed of pluripotent precursors that will generate all the fetal organs as well as the extraembryonic mesoderm.

Epiblepharon – Inward turning of eyelashes.

Epidemics – It refers to the rapid spread of infectious disease to a large number of people in a given population within a short period of time. The period is usually 2 weeks or less.

Epidemiological research – Research designed to study processes, characteristics, or other facets of particular populations or phenomenon.

Epidemiology – It refers to a discipline that studies the patterns, causes, and effects of disease conditions in defined populations. It is derived from Greek epi, meaning “upon,” demos, meaning “people,” and logos, meaning “study.” Epithelium A type of tissues that cover the surface of various organs in human body.

Epidermis – Top layers of skin that contain mainly keratinocytes plus elements of SALT but no blood vessels.

Epigenetic – A term describing nonmutational phenomena, such as methylation and histone modification, that modify the expression of a gene.

Epigenetic change – Refers to inherited changes that are not due to alterations in the DNA sequence. 2. Changes in gene regulation that persist after tissue culture but are not inherited by any progeny of the plant.

Epigenetic effects – A change in gene expression level without altering original DNA sequences. It may be due to the activation or repression of a gene function. It is called genomic imprinting and altering gene expression. Ex vivo experiment done outside of an organism.

Epigenetic inheritance – Inherited genetic features such as methylation and histone modifications that affect gene expression but do not alter the DNA sequence.

Epigenetic instability – The condition in which the normal epigenetic modifi- cations are progressively changing, within one cell or from one cell generation to another. Epigenomic instability, like genomic instability, is a near-constant feature of tumor progression. Because cellular differentiation is under epigen- etic control, the loss of tumor cell differentiation observed with tumor progres- sion is presumably due to epigenetic instability. Likewise, cancer cells that have an unstable epigenome may inactivate or activate a variety of disease genes in surprising ways. For example, epigenetic instability may produce cancer cells with inactivated Werner syndrome gene, the same gene that causes a premature aging syndrome when it occurs in the germline cells of an organism. In similar fashion, cancer cells may have epigenetic inactivation of the lamin A/C gene, the same gene that, when inactivated in germline cells, causes a form of cardiomyopathy.

Epigenetic Regulation – A change in gene function in the absence of a nucleotide change (mutation). During embryonic development and differentiation, genes are increasingly blocked for use in the cell by epigenetic changes, leaving only the genes that are requiredfor the specialised functions of a differentiated cell available for use. This is the reason that cells cannot easily “de-differentiate” and change into another cell type. The epigenetic regulation may be disturbed after artificial reprogramming, for example, during the formation of induced pluripotent stem cells and cloned animals.

Epigenetics – Term that defines the transmissible and reversible modifications, in the absence of the original signal, of gene expression (and function) that are not followed by nucleotide sequence changes. DNA modification and changes in chromatin (structure, position, modifications, and compaction) in particular are classed as epigenetic modifications whose code, not yet clear, has been suggested.

Epigenome – At a minimum, the epigenome consists of the non-sequence modifications to DNA that control the expression of genes. These modifica- tions include DNA methylations, histones, and non-histone nuclear proteins. Beyond this minimalist definition, there are expanded versions of the definition that would include any conformational changes in DNA that influence gene expression, as well as protein interactions that influence gene expression. As used in this book, the terms “epigenome” and “epigenetics” apply exclusively to non-sequence alterations in chromosomes that are heritable among somatic cell lineages. In general, the epigenome controls differentiation and the biological characteristics of the different somatic cell types of the body. The total number of epigenetic changes that are found in a genome and are passed onto the organism’s offspring.

Epiphora – Excessive tearing.

Episome – A DNA that is stably present in the cell, excluding chromosomal DNA. The term “epi” is derived from Greek word for “above.”

Epistasis – The condition under which the effect of a gene is influenced by another gene. For example, a gene may be active only when a particular allele of one or more additional genes is also active. Because dependencies among genes are built into cellular systems, the role of epistasis in the penetrance of disease genes and the pathogenesis of disease phenotypes is presumed to be profound. For example, there are at least 27 epistatic interactions among genes associated with Alzheimer disease. Epistatic interactions can be synergistic or antago- nistic. See Penetrance and Genome wide association studies.

Epistasis and genetic interactions – Epistatic and genetic interactions are functional interactions between mutations in non-allelic genes suggestive of the gene products acting together in a given process or pathway. A genetic interaction is manifested through a compound mutant phenotype that is more pronounced than the sum of the two single mutant phenotypes, e.g., disrupted development in an animal heterozygous for two mutations for which either heterozygous mutation (in isolation) does not result in a developmental phenotype. An epistatic relation- ship/interaction is manifest through the ability of one allele to suppress the phenotypic consequences of a second mutation, typically indicating dominance of the epistatic mutation or the result of its being downstream in a common genetic pathway.

Epithelial cell – Epithelial cells are polyhedral cells that typically line a surface or a lumen (i.e., an empty gland or duct that leads to a surface). Examples of epithelial lineages are the skin, the mucosa lining the alimentary tract, and the cells that line ducts. Many glandular organs are composed predominantly of epithelial cells (e.g., liver, lungs, kidneys, thyroid). Epithelial cells fit tightly together as polyhedral units fastened together by specialised cell junctions (e.g., desmosomes). Tumors arising from epithelia, and composed of neoplastic epithelial cells, account for over 95% of the cancers that occur in humans.

Epithelial polarity – Regional differences within cells forming an epithelial tissue.

Epithelial-mesenchymal transition (EMT) – A series of changes at the molecular level that converts an epithelial cell into a mesenchymal cell. EMT involves changes in cell-cell and cell-matrix adhesion properties as well as changes in cell polarity.

Epithelium, Epithelial Cells- Epithelial cell layers cover the body (skin) and line the body cavities, such as the intestinal lumen and lungs.

Epithelization – Ingrowth of new epithelium from neighboring epithelium.

Epitope – An epitope represents the part of an antigen that is recognised by the adaptive immune system, specifically by antibodies, B cells, or T cells. The portion of an antigen with which an Ig will bind. The small region of a macromolecule that specifically binds to the antigen receptor of a B or T lymphocyte. B cell epitopes can be composed of almost any structure. T cell epitopes are a complex of antigenic pep- tide bound to either MHC class I or II. Localised regions of an antigen to which an antibody binds.

Epitope spreading – An immune response against one epitope causes tissue destruction that exposes previously hidden epitopes, activating additional lymphocyte clones.

EPSPS – An enzyme essential for making amino acids of the aromatic family in plants and bacteria.

Epstein-Barr virus (EBV) – A human gamma-herpesvirus that is associated with Burkitt’s lymphoma. The virus was named after the two scientists who discovered it- Dr Epstein and Dr Barr.

Equipoise – A term meaning balance, i.e., the balance of not knowing whether participants in a clinical trial will do better in the study arm that gets the investigational intervention or in the control arm. To justify conducting a clinical trial, there must be equipoise. If the answer is already known, there is no scientific basis to justify the trial and there are ethical reasons not to do it. The ethical justification for randomization; the notion that one arm has the potential to be as beneficial as any other study arm.

Equity – The term refers to the ownership stake in a company. Equity holders in a company own common stocks that have been issued by that company. Two rights are associated with owning a common stock, i.e., the right to vote for the Board of Directors at the annual shareholders’ meeting and the right to receive dividends if they are declared by the board.

Equity-based alliance – Is a type of strategic alliance where the established firm acquires a financial interest in a new venture or firm.

ER stress – Cellular stress resulting when the endoplasmic reticulum (ER) machinery of a host cell is overheated due to excessive synthesis of large quantities of proteins, such as occurs during viral infection. Can trigger apoptosis.

Erasure – Every cell in an organism has the same genome. The distinctions between the different types of cells in an organism are determined by the epigenome. When cells differentiate into particular cell types (e.g., hepatocyte, muscle cells, ductal cells, etc.), they obtain a cell-type-specific epigenome. Germ cells differ from other somatic cells because they contribute to a toti- potent and undifferentiated zygote (i.e., the fusion cell produced by sperm and ovum). Somehow, the highly specific epigenome, passed into the zygote by the differentiated germ cell, must be erased in germline cells, so that the development of a new organism can occur. In theory, erasure removes all of the epigenetic patterns of the differentiated germ cell. See Imprinting.

Ergot – Fungus that grows on cereals, especially rye, and produces a mixture of toxins that cause a syndrome called ergotism.

Error-prone PCR – Type of PCR in which mutations are introduced at random during the amplification steps.

Erythema – Redness due to increased local blood flow.

Erythrocytes – Red blood cells (RBCs); carry oxygen to the tissues.

Erythromycin – An antibiotic of the macrolide family that inhibits bacterial protein synthesis.

Erythropoietin (EPO) – A glycoprotein that controls angiogenesis as well as erythropoiesis; required for proper development of red blood cells.

Escape mutants – Viruses that are not recognised by previously generated host antibodies due to point mutations.

Escherichia coli (E coli)A species of bacterium commonly used in genetics and molecular biology.

ESCRT (endosomal sorting complex required for transport) – ESCRT machinery is made up of cytosolic protein complexes referred to as ESCRT-0, -I,-II, and -III. Together with a number of accessory proteins, these ESCRT complexes enable a unique mode of membrane remodeling that results in membranes bending/budding away from the cytoplasm.

Esotropia – Inward misalignment of the eyes, one of which turns in (toward the nose)- cross-eyed.

Essential Documents – The ICH defines this term to mean- “Documents which individually and collectively permit evaluation of the conduct of a trial and the quality of the data produced.” Essential documents verify and confirm compliance with regulations and GCP. Both the investigator(s) and the sponsor must maintain a master file of essential documents for each clinical trial.

EST (expressed sequence tag) – Transcribed nucleotide sequences that can be identified by analyzing cDNA libraries (see also gene library).

Establishment – The location where a product is manufactured.

Esters – A lipid class in which a carboxylic acid and an alcohol are joined by an oxygen bridge (i.e, “ester bond”). It is often a constituent of another lipid class such as a phospholipid.

ETDRS Letters – In clinical trials, visual acuity is often measured using a chart called the ETDRS chart (Early Treatment Diabetic Retinopathy Study). A letter score is calculated based on the number of letters that can be correctly identified from specified distances. Higher letter scores correspond to better visual acuity.

Ethidium bromide – A stain that specifically binds to DNA or RNA and appears orange if viewed under ultraviolet light. Fluorescent dye used in molecular biology to visualise nucleic acids (DNA and RNA). Ethidium bromide is toxic and is suspected to be cancer genic. As it may penetrate through the skin, it is essential to wear nitrile gloves when handling ethidium bromide.

Etiology – The cause of a disease. See Pathogenesis.

Euchromatin – Lightly packed form of chromatin that has more genes that are being actively transcribed. The fraction of the nuclear genome that contains tran- scriptionally active DNA and that, unlike heterochromatin, adopts a relatively extended conformation.

Eugenics – Deliberate improvement of the human race (or other species) by selective breeding

Event – A term used to distinguish different insertions of the same transgene. The transgene is identical, but the integration sites will vary.

Euglycemia – The state of maintaining blood glucose levels within the normal range (70 to 120 mg/dL).

Eukaryote – An organism whose cells show internal compartmentaliza- tion in the form of membrane-bound organelles (includes animals, plants, fungi, and algae).

European Medicines Agency (EMA) – See EMA. 

European Venture Capital Association (EVCA) – A member-based, non-profit trade association established in 1983 and based in Brussels. The EVCA represents, promotes, and protects the interests of the European private equity and venture capital industry.

Euryblepharon – Increased vertical separation of palpebral fissure.

Evaluation – Gathering information and reviewing the facts surrounding an event to understand the problem. An evaluation can be used to determine the need for further investigation or risk analysis.

Event – A potential problem that may affect the quality of a product or the suitability of a material, system, operation, process, document, equipment, or program that is part of the quality system. Events may be identified via the CAPA system including complaints, quality system nonconformances, DMR nonconformances, results of CAPA reviews, and results of management reviews.

Evidenced-based research – See Outcomes research.

Ex Vivo – Outside the body, for example, in the laboratory.

Ex vivo gene therapy – Gene therapy by removal, engineering, and return of cells derived from the same original patient.

Excipient – U.S. FDA defines an “excipient” as an inactive ingredient, added to therapeutic or diagnostic product, which U.S. FDA believes is not intended to provide any therapeutic effect at the doses intended, although they may act to improve product delivery- e.g., by improving bioavailability, uptake, or to control release of the active ingredient. Examples of excipients include, but are not limited to, “fillers, extenders, diluents, wetting agents, sol- vents, emulsifiers, preservatives, flavors, absorption enhancers, sustained-release matrices, and coloring agents.” Vaccine adjuvants are also considered by U.S. FDA to be excipients. If an excipient is a substance considered to be “GRAS,” then preclinical safety studies may not be needed to support its inclusion in a formulation, but if it is a novel excipient, safety studies may be required and U.S. FDA has a guidance document on this subject.

Excisionase (Xis) – Enzyme that reverses DNA integration by removing a segment of double- stranded DNA and resealing the gap. In particular, lambda excisionase removes integrated lambda DNA.

Exit – The term has two related but distinct meanings. First, an exit refers to the sale or initial public offering (IPO) of a company. Second, an exit refers to the sale of an investor’s stake in a company. Both definitions are not always the same (e.g., a venture capitalistmust usually hold his company’s stock for at least six months after an IPO).

Exclusion criteria – In a protocol, the section that identifies the characteristics that would disqualify potential subjects and/or necessitate removal of a subject if the characteristics happen to appear during the study.

Executive management – Management with authority to make changes to the quality system.

Exencephaly – A neural tube defect (NTD) that results from failure of neural tube closure in the cephalic region. As fetal development continues, the exposed brain tissue will degenerate and exencephaly will progress to anencephaly.

Exocrine – The process of moving membrane-bound groups of large molecules (vesicles) out of a cell by the fusion of the membrane of the vesicle with the plasma membrane and its opening to the exterior of the cell, thus releasing its contents.

Exocrine cells – Within the pancreas, the cells that produce the digestive enzymes that are released into the pancreatic duct and eventually into the duodenum.

Exocytosis  – The process of moving membrane-bound groups of large molecules (vesicles) out of a cell by the fusion of the membrane of the vesicle with the plasma membrane and its opening to the exterior of the cell, thus releasing its contents. Process by which the membrane of an exocytic vesicle fuses with the plasma membrane, everting the contents into the extracellular fluid. The process in which a cell directs the contents of secretory vesicles out of the cell membrane into the extracellular space.

Exogenous antigen – An antigenic protein that originates outside the cells of the host, as in a bacterial toxin.

Exogenous antigen processing and presentation – Mechanism by which exogenous antigens are internalised into an APC, degraded by endocytic processing, and complexed to MHC class II in an end lysosomal vesicle. The peptide– MHC class II complex is then displayed on the cell sur- face. This pathway operates almost exclusively in APCs.

Exome – The part of the genome that corresponds to the complete set of exons. The portion of the genome (ie, genes) that encode proteins.

Exome sequencing (also known as targeted exome capture) – Also known as targeted exome capture, exome sequenc- ing is a relatively new laboratory technique wherein only the exons (the sections of DNA that code for proteins) are sequenced, sparing analysts from dealing with the non-coding regions of DNA. In the human genome, there are only about 180,000 exons, accounting for about 1% of the genome, and about 85% of known disease-causing mutations. DNA sequencing of the protein-encoding components of the genome. Uses technology to selectively sequence the coding regions (exons) of the genome. Exons are short, functionally important sequences of DNA which represent the regions in genes that are translated into protein. It is estimated that the protein coding regions of the human genome constitute about 85% of the disease- causing mutations.

Exon – A segment of a DNA gene that carries part of the code for polypeptide synthesis.DNA sequences in eukaryotes, which encodes part of a polypeptide (in contrast to a intron).Segment of a gene that codes for protein and that is still present in the messenger RNA after processing is complete.The sections of a gene that code for all of its functional product. Eukaryotic genes may contain many exons interspersed with noncoding introns. An exon is represented in the mature mRNA product— the portions of an mRNA molecule that are left after all introns are spliced out, which serves as a template for protein synthesis. Sequences in the DNA that corresponds to protein coding regions.

Exonuclease – A nuclease enzyme that cuts nucleic acids (DNA or RNA). The exoprefix shows that the cleavage occurs at the extremities, one nucleotide at a time, in the 5′ to 3′ sense direction or the other way.

Exopeptidase – A protease that cuts starting at either the carboxy- or amino-terminal end of the polypeptide chain.

Exophthalmos – An abnormal extension or proptosis of the eyeball from its orbit.

Exotoxin – A toxin released extracellularly.Protein toxin secreted by bacteria.

Exotropia – Outward misalignment of the eyes, one of which turns out (away from the nose) – wall-eyed.

Experimental autoimmune uveitis (EAU) – A disease of the neural retina induced by immunization with retinal antigens.

Experimental tolerance – Lack of an immune response to a foreign antigen induced by treatment of a mature ani mal with either a non-immunogenic form of the antigen and using the usual dose and route of immunization, or an immunogenic form of the antigen and using a non- immunogenic dose or route of administration.

Expiry – The dating period on a product between when it was manufactured and when it expires and should no longer be used.

Explant – Tissue taken from an original site in a plant and transferred to artificial medium for growth and maintenance.

Expressed – (as pertaining to genes) Converting a DNA region into RNA and/or protein to be used by the living cell.

Expressed sequence tag (EST) – A special type of STS derived from a region of DNA that is expressed by transcription into RNA.

Expression library – (see also expression vector) A library where each cloned piece of DNA is expressed into a protein by the vector.

Expression vector – Vector designed to enhance gene expression, usually by providing a strong promoter that drives expression of the cloned gene.

Extension peptides – Nonchemical portions of collagen that are lyzed or broken off in some collagen types with the formation of tropocollagen.

Extracellular bacteria – Bacteria that do not have to enter host cells to reproduce.

Extracellular domain – Portion of a transmembrane protein that is on the exterior of a cell and binds to a specific ligand.

Extracellular matrix – A complex structural entity com- posed of proteins and carbohydrates surrounding and supporting cells.The extracellular part of animal tissue that usually provides structural support to the animal cells in addition to performing various other important functions.

Extracellular matrix (ECM) – The extracellular part of animal tissue that usually provides structural support to the animal cells. The extracellular matrix is the defining feature of connective tissue in animals, which is largely composed of fibrous protein, collagen, and  glycoaminoglycan (GAG).

Extracellular pathogen – A pathogen that does not enter host cells but reproduces in the interstitial fluid, blood or lumens of the respiratory, urogenital and gastrointestinal tracts.

Extra-embryonic ectoderm (ExE) – An extra-embryonic tissue derived from the (polar) trophectoderm, in contact with the inner cell mass in the mammalian blastocyst. Unlike cells of the ectoplacental cone (another trophectoderm derivative), which differentiate into giant cells, cells of the ExE retain stem cell potential. The ExE contributes to the placenta.

Extra-Embryonic Tissue- Part of the conceptus that will not contribute to the embryo proper but, for instance, gives rise to the embryonic part of the placenta, the umbilical cord, and the membranes surrounding the fetus.

Extrahepatic biliary system – A ductal network for the movement of bile that aids in digestion. It includes the common duct, extrahepatic bile ducts, and the gallbladder.

Extramedullary tissues – Tissues and organs that are neither lymphoid tissues nor bone marrow.

Extraocular muscles (EOM) – A group of six muscles that control the movements of the eye, including the superior, inferior, lateral, and medial recti, and the superior and inferior obliques.

Extrathymic T cell development – Development and maturation of T cells in tissues outside the thymus.

Extravasation – Exit of leukocytes from the blood circulation into the tissues in response to inflammatory signals.

Extrinsic asymmetry – During stem cell division, one of the daughter cells leaves the environment or moves too far from an external signal that is keeping the stem cell in an undifferentiated state. Without the signal, the daughter cell differentiates

Extrinsic factors – Extracellular molecules such as secreted signaling proteins and their transmembrane receptors that provide a cell with information about its environment.

Extrinsic pathway – Pathway of initiating apoptosis that originates as an external signal such as a ligand binding to a cell surface receptor.

Eye field or eye primordia – A domain in the anterior neural plate that is specified to give rise to eye tissue. This domain expresses a combination of eye field transcription factors that are essential for eye formation.

Eye-associated lymphoid tissue (EALT) – This tissue summarises all the lymphoid tissues of the extended mucosal ocular surface, that is, of ocular surface proper (conjunctiva and cornea) along with its mucosal adnexa (the lacrimal-drainage-associated lymphoid tissue, LDALT, and the lymphoid cells inside the lacrimal gland). EALT is in line with the mucosal immune system in other parts of the body (e.g., gut-associated lymphoid tissue (GALT) in the gut and bronchus-associated lymphoid tissue (BALT) in the airways).



F4/80 – Antibody that recognises both dendritic cells and macrophages.

Fermentation – Typically refers to aerobic and anaerobic microbial culture operations including yeasts, fungi, or bacteria.

Functionally Closed – Process systems that may be opened but are “rendered closed” by a cleaning, sanitization and/or sterilizationprocess that is appropriate or consistent with the process requirements, whether sterile, aseptic or low bioburden. These systems shall remain closed during production within the system. According to QRM Verification, the environment does not represent a critical aspect of an appropriately functionally closed process (formerly known as a no impact system but only if appropriate measures have been exercised to render the system closed. A functionally closed process must be validated to show that sufficient layers of protection have been implemented to mitigate the risk of contamination from the environment.Transfers into or from these systems must also be validated as closed. Examples include process vessels that may be cleaned in place and steamed in place between uses. Non-sterile systems such as chromatography or some filtration systems may also be rendered closed in low bioburden operations if appropriate measures are taken during the particular system setup.

Fab fragment/region – Fragment, antigen binding. Originally, the N-terminal portion of an Ig molecule left after digestion with papain. The Fab region contains the two antigen-binding sites of the antibody.

Fab fragments – Antigen-binding fragments of an antibody.

Fab region – Antigen- or microorganism-binding region of an antibody.

Facilitated transport – The process of moving substances across a membrane with the aid of one or more proteins. Passive facilitated transport requires no energy and moves substances to a side of lower concentration. Active facilitated transport requires energy and moves substances to a side of higher concentration.

Facility – A location where a product is manufactured. The term may also be used to describe a location where a test is performed, including preclinical studies. In the latter context, they are generally referred to a testing facility, as opposed to manufacturing facility.

Factor inhibiting HIF-1a (FIH-1) – Enzyme that hydroxylates and represses the transcription activity of HIF-1a.

Facultative heterochromatin – Heterochromatin that has the ability to return to normal euchromatin.

FAD (flavin adenine dinucleotide) – derivative of riboflavin (vitamin B2) and coenzyme involved in redox reactions. Prosthetic group of glucose oxidase.

Failure mode (FM) – The way in which a product or process could fail to perform its desired function.

Failure mode, effects, and criticality analysis (FMECA) – A procedure by which each potential failure in a system is analyzed to determine the results or effects thereof on the system and to classify each potential failure according to its severity.

Familial cancer – Cancer that develops with increased frequency in genetically related individuals.

Family (in relationship to gene sequences) – Group of closely related genes that arose by successive duplication and perform similar roles.

Family history – An essential tool in clinical genetics. Interpreting the family history can be complicated by many factors, including small families, incomplete or erroneous family histories, consan- guinity, variable penetrance, and the current lack of real under- standing of the multiple genes involved in polygenic (complex) diseases.

Fas – Transmembrane death receptor (CD95) that induces cellular apoptosis upon engagement by Fas ligand (FasL).

Fascia – Sheets of fibroelastic connective tissue that separate parts of the body from one another, for example between individual muscles.

Fast neutron mutagenesis – Mutagenesis technique in which seeds are exposed to fast neutrons that induce small deletions.

Fast neutrons –  Free neutrons with kinetic energy around 1 MeV that are used to create DNA deletions in plant seeds.

Fat – A lipid ester of fatty acids and glycerol.

Fat soluble vitamin – A lipid that acts as a vitamin.

Fate domain – An embryonic region whose cellular constituents undertake reproducible pathways of differentiation, under normal circumstances. These cells may or may not be committed and changes in their environment can reveal this.

Fate mapping – A method to trace a group of cells or individual cells through development or to trace cell divisions in a tissue or organ of an adult organism. The method can identify stem cell populations in adult tissues.

Fatty acid – A carboxylic acid of varying chain length.

Fc fragment – The stem region of an antibody, i.e., the fragment that does not bind the antigen ferritin an iron storage protein of animals.

Fc fragment/region – Fragment, crystallizable. Originally, the C-terminal portion of Ig molecule left after digestion with papain; crystallises at low temperature. The Fc re- gion contains the constant region of the antibody.

Fc receptor (FcR) – Leukocyte receptor that binds to the Fc region of a specific antibody isotype. Engagement can trigger clathrin-mediated endocytosis, phagocytosis, ADCC, degranulation or cytokine release. Members of the FcR family are structurally diverse.

Fc region – Non-antigen-binding region of an antibody. This region binds to other components of the host defense system.

FDA – Food and Drug Administration (FDA) is a federal agency of the US Department of Health and Human Services. It supervises the safety and effectiveness of drugs, biological and medicinal products, cosmetics, food (including additives), and radiation-emitting devices. Its tasks also include the implementation of the hygiene regulations of the Public Health Service Act in the USA. US food and drug agency, responsible for drug control and regulation. This government agency is divided into five centers that control food, drugs, animal food, dietary supplements, medical devices, and biological and blood products.

FDA Form 1571 – This is the form required to accompany an IND submission (original or amendments).

FDA Form 1572 – This is the form submitted to an IND when new investigators are to be included, or amendments are being made to investigators in existing clinical protocols in the IND.

FDA Form 3674 – This is the form that provides U.S. FDA with a Certificate of Compliance with the requirements to enter clinical trials into the Data Bank.

FDA Form 482 – This is a form U.S. FDA inspectors give to establishment managers to announce they have arrived to inspect the facility (or to clinicians, etc. upon arriving for a bioresearch monitoring inspection).

FDA Form 483 – This is the form that U.S. FDA inspectors may issue at the close of an inspection if they observe violative findings (i.e., violations of compliance with regulations).

FDAAA – Food and Drug Administration Amendments Act—the re-enactment of PDUFA to cover the period 2007–12.

FDAMA – Food and Drug Administration Modernization Act. The Re-enactment of PDUFA by Congress to cover the period from 1997 to 2002. This Act eliminated the two separate licenses for product & establishment and created the BLA. This Act also introduced accelerated approval and expanded access.

FDARA – Food and Drug Administration Re-authorization Act of 2017—the re-enactment of PDUFA covering the period of 2018–23.

FDASIA – Food and Drug Administration Safety and Innovation Act (FDASIA) – the re-enactment of PDUFA covering the period 2013–17.

Federal Food, Drug, and Cosmetic Act of 1938 (FDC) – Sweeping legislation that extended the FDA’s control so that it could also regulate cosmetics, pharmaceutical drugs, and therapeutic devices.

Federal wide project assurance – The name of the assurance document that a research organization negotiates with the federal government covering the conduct of studies funded by a Common Rule agency.

Feedback inhibition – The inhibition of an enzyme by a product formed along a metabolic pathway in which the enzyme participates.

Feedback regulation – A mechanism by which a signaling pathway regulates its own activity, e.g., by activating a regulatory factor that alters signal transduction, by altering sensitivity of the pathway to upstream signals, and/or by modifying the activity or interactions of proteins in the pathway. In some cases, multiple signaling pathways generate a feedback regulatory circuit, in which activation of one pathway results in regulation of another, and vice versa.

Feeder Cell Layer- A cell layer that “feeds” other cells. Often used in the context of stem cells that may be dependent on feeder cellsto remain undifferentiated. They are sometimes treated to stop cell division so that they do not overgrow stem cells but can still deliver the right factors for their growth.

Fenestration – From the Latin word for window (fenestra), a fenestration is an opening in a wall or membrane.

Fermentation – Aerobic and anaerobic metabolic reactions in bacteria, fungi (mainly yeasts), plants or animal cells. Fermentation is used to obtain products or biomass as well as for biotransformation.

Fetus- Unborn offspring of certain mammals, usually in the later stages of development.

FGFs – Fibroblast Growth Factors are a family of growth factors, whose members are involved in angiogenesis, wound healing, embryonic development and various endocrine signaling pathways.

Fiber or Fibre – Used in reference to collagen. It is a collagen structure made up of several “fibrils.” A fibril has a diameter of 10 to 300 nm and is composed of many “microfibrils.” Each microfibril is formed from five staggered lengths of tropocollagen units.

Fibrosis – Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue. Fibrosis can be used to describe the pathological state of excess deposition of fibrous tissue, as well as the process of connective tissue deposition in healing.

Fidelity – Accuracy (pertaining to nucleic acid replication).

Fierce Mouse – Transgenic mouse with abnormal aggression.

Filing – A submission to a regulatory agency.

Fill/Finish – This term refers to the process of filling drug product into final containers and “finishing” them by sealing them with closures and labeling them. Packaging may or may not occur at this step or may occur later.

Filopodia – Thin, short cellular protrusions containing both actin and microtubules that are not polarised toward a source of signaling protein.

Filoviruses – Family of negative-strand ssRNA viruses that includes Ebola virus and Marburg virus.

Fimbria (plural fimbriae) – Thin helical protein filaments found on the surface of bacteria; same as pilus.

Final Containers – These are the storage vessels for the drug product, e.g., vials, syringes, bottles, bags, and foil- packs. Final containers may contain a single dose or multiple doses.

Financial engineering – A cross-disciplinary field which relies on mathematical finance, numerical methods, and computer simulation to make trading, hedging, and investment decisions as well as facilitating the risk management of those decisions. By using derivatives, financial engineering allows to manage risk and create customised financial instruments.

Financial Industry Regulatory Authority (FINRA) – is an independent regulator of all security firms doing business in the U.S.

Financing round – This term refers to a provision of capital by a private equity/venture capital group to a firm. Since venture capital organizations usually provide capital in stages, a typical venture-backed firm will receive multiple financing rounds over many years.

Firm commitment contract- Refers to a type of arrangement where the underwriter acquires the stock of the firm in the primary market.

First heart field (FHF) – Early differentiating myocardial cells that contribute to the linear heart tube and ultimately to the left ventricle.

First round (Series A) – The first round of investments by venture capitalists.

FISH – Fluorescence in situ hybridisation – nonradioactive method of in situ hybridisation for the detection of nucleic acids. FISH is suitable for the physical mapping of genes and genomic markers in metaphase chromosomes.

Fisher structure – Essentially a staggered ball and stick formation used to represent carbohydrate and other chemical structures (see Figure 4–2).

Fit-for-Purpose – A term used to describe whether an analytical method is scientifically valid and appropriate for its intended use.While the analytical method may be very precise and/or accurate (or easy-to-use or cheap), if it does not actually measure the appropriate analytic in the scientific context of its use, then it would not be fit-for- purpose. For instance, a test for an analytic in human blood may not be suitable for use with saliva, plasma, serum, or other human bodily fluids or with specimens from other species or from cell culture.

Fixed fraction contract – Is a contract that seeks to limit the dilution of an investor’s position in a firm.

Fixed price method – Of stock price determination is where the investment bank prices the shares of the offering based on the informal information discerned during roadshows.

FLAG tag – A short peptide tag (AspTyrLysAspAspAspAspLys) that is bound by a specific anti- FLAG antibody and that may be attached to proteins.

Flavivirus – Flavivirus is a genus of the family Flaviviridae, which includes the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus, hepatitis C and several other viruses which may cause encephalitis. Flaviviruses are characterised by a common size, symmetry, nucleic acid, and appearance in the electron microscope. They are transmitted through the bite of an infected mosquito or tick.

Flight tube – Tube or channel in which ions generated during mass spectroscopy are separated according to size or charge.

Flippase (same as Flp recombinase and Flp protein) – Enzyme encoded by the 2-micron plasmid of yeast that catalyzes recombination between inverted repeats (FRT sites).

Float – The equity share placed on the market in the event of an initial public offering (IPO).

Floor brokers- Are employees of a public market member who buys and sells securities on behalf of their clients.

Floral dip (also called in planta transformation) – Method in which a transgene is carried by Agrobacterium and transformed into Arabidopsis by dipping a developing flower bud into a solution of Agrobacterium plus a surfactant.

Flow Cytometer- Also known as fluorescence activated cell sorter (FACS), a device that can count (and sometimes also sort or select) fluorescently labeled cells in a cell suspension. Analyzing (without sorting) different cells as they flow past a fluorescent detector by observing the attached fluorescent antibodies.

Flow resistance – The flow resistance (R=DP/Q) of a tissue is the ratio between the pressure drop across that tissue (DP) and the flow rate generated by that pressure drop (Q).

Flp protein – Enzyme encoded by the 2-micron plasmid of yeast that catalyzes recombination between inverted repeats (FRT sites).

Flp recombinase – (same as flippase and Flp protein) Enzyme encoded by the 2-micron plasmid of yeast that catalyzes recombination between inverted repeats (FRT sites).

Fluorescein fundus angiography – The visualisation of blood vessels in the interior of the eye following intravenous injection of fluorescein.

Fluorescein isothiocyanate (FITC) – a fluorescent dye that is commonly coupled to antibodies for fluorescent assays.

Fluorescence detector – A detector that records fluorescence emitted by the passing mobile phase after it has been excited by light.

Fluorescence in situ hybridization (FISH) – A form of chromosome in situ hybridization in which a nucleic acid probe is labeled by incor- poration of a fluorophore, a chemical group that fluoresces when exposed to ultraviolet irradiation. Uses a targeted approach to analyze a specific sequence of a chromo- some. The technique consists of using a specific probe DNA that is labeled and is hybridised to a sample DNA of interest. Recording of the labeled hybridization, or lack of, can then be analyzed. Using a fluorescent probe to visualise a molecule of DNA or RNA in its natural location.

Fluorescence-activated cell sorting (FACS) – Technique that sorts cells (or chromosomes) based on fluorescent labelling.

FMEA – Failure Mode and Effects Analysis (FMEA).

Focal adhesions – Cell–matrix junctions having transmembrane proteins called integrins that connect cells to extracellular matrix and also to the actin cytoskeleton. Transmembrane proteins can trigger signaling within and between adjacent cells.

Foetus – The stage in development from the end of the embryonic stage, 7-8 weeks after fertilisation, to developed organism that ends at birth.

FOI – Freedom of Information (FOI).

FokI – A particular type II restriction endonuclease with separate recognition and nuclease domains.

Follicle-associated epithelium (FAE) – Epithelium lying directly over single or aggregated lymphoid follicles. FAE is specialised for carrying out transcytosis due to the presence of M cells.

Follicular dendritic cells (FDCs) – Distinct lineage of DCs found in B cell-rich areas of lymphoid organs. FDCs do not internalise antigen and do not function as APCs but rather trap antigen–antibody complexes on their cell sur- faces and display them for extended periods.

Follow-on – Is the selling of additional shares post IPO.

Follow-up – Procedures or contact by the researcher after completion of a study’s primary procedures.

Fomites – Inanimate objects that may transfer a pathogen from one person to another (e.g., towels or utensils).

Fontanelles – Embryonic and early childhood structures in the skull commonly referred to as soft spots. These allow the skull plates to shift during delivery. Once the skull becomes ossified, around the age of two, the fontanelles close and become the skull sutures.

Food and Drug Act of 1906 – Act that prohibited interstate commerce in misbranded and adulterated foods, drinks, and drugs.

Food and Drug Administration (FDA) – A unit of the US government that is responsible for the regulation of prescription drugs. FDA is the U.S. body responsible for regulating biopharmaceutical products. The FDA is the authority, which approves new prescription drugs, vaccines, and biopharmaceuticals for medical use. The FDA is one of the US federal executive departments.

Foot-and-mouth disease – An animal disease that is caused by foot-and-mouth disease virus (FMDV) that belongs to the family Picornaviridae.

Foregut – Anterior-most of three divisions of the digestive tract (foregut, midgut, hindgut).

Forme fruste – From the French, a crude or unfinished form; plural formes frustes. A term used by diagnosticians and applied to difficult cases wherein a patient presents with some of the features of a recognised disease or syndrome, but who does not quite fit the accepted diagnostic criteria. The clinical presenta- tion is said to be the forme fruste (i.e., wrong, incomplete, or unfinished form) of the disease. In the context of a rare disease, the forme fruste may present as a near-syndrome, lacking one or more of the definitive features of a set of inherited abnormalities. In many, if not all, cases, studying the forme fruste will help us to understand the classic form of a disease. For example, geneticists reported a child who presented with renal angiomyolipoma, a rare tumor some- times found in patients with tuberous sclerosis. Several years later, the same patient developed cystic disease in the contralateral kidney, a condition often associated with polycystic kidney disease. Genetic analysis demonstrated a con- tiguous gene deletion involving both the TSC2 gene for tuberous sclerosis and the PKD1 gene for polycystic kidney disease. The patient’s phenotype was the forme fruste of two rare diseases, but genetic analysis proved that the presenta- tion fitted a contiguous gene syndrome.

Formulated Bulk – A formulated bulk generally refers to a drug product after it has been formulated and/or diluted and before it has been filled into final containers. Sometimes, the drug product may be stored at the stage of formulated bulk.

Forward integration – Occurs when a firm in one section of the value chain takes on the function of a firm in another section of the value chain and moves closer to the end user.

Foster mother – (as used in genetics) Female animal that carries engineered embryos.

Founder animal – Animal that is the original host for a transgene and maintains it stably.

Founder CEO – Is the term used to describe the situation where the chief executive officer (CEO) was one of the creators of the firm.

Founder effect – Changes in allelic frequencies that occur when a small group is separated from a large population and is established in a new location. Occurs when a specific mutation enters the population through the successful procreational activities of a founder and his or her offspring, who carry the founder’s mutation. When all of the patients with a specific disease have an identical mutation, the disease may have been propagated through the population by a founder effect. This is particularly true when the disease is confined to a separable subpopulation, as appears to be the case for Navaho neurohepatopathy, in which the studied patients, all members of the Navaho community, have the same missense mutation. Not all diseases characterised by a single gene mutation arise as the result of a founder effect. In the case of cystic fibrosis, a dominant founder effect can be observed within a genetically hetero- geneous disease population. One allele of the cystic fibrosis gene accounts for 67% of cystic fibrosis cases in Europe. Hundreds of other alleles of the same gene account for the remaining 33% of cystic fibrosis cases. See Gain-of- function mutations.

Fractal – Self-similar (looks the same at all scales).

Fragile X syndrome – Inherited defect resulting in a fragile site within the long arm of the X chromosome that can be seen by microscopic observation.

Frameshift mutation – Change in the DNA sequence, either an insertion or deletion, not a multiple of three, which causes a shift in the reading frame. This shift leads to a change in the reading frame of all parts of a gene that are downstream from the mutation, leading to a premature stop codon, and thus to a truncated protein product.

Framework regions – Relatively invariant parts of the V do- main of an Ig or TCR chain that are outside the hyper- variable regions.

Francisellatularensis – Bacterium that causes tularaemia.

Free cash flow (FCF) – A measure of financial performance, calculated as operating cash flow minus capital expenditures. In other words, free cash flow represents the cash that a company is able to generate after laying out the money required to maintain or expand its asset base.

Free enthalpy Gibbs energy

Freeze-drying – see Lyophilization.

Freund’s complete adjuvant (FCA) – Freund’s adjuvant is a solution of antigen emulsified in mineral oil and used as an immunopotentiator (booster). The complete form, Freund’s Complete Adjuvant (FCA) is composed of inactivated and dried mycobacteria (usually M. tuberculosis).

Frontier research – Is the term Europeans use for basic research that is viewed as highly risky, but promising in terms of spin-offcompanies.

FRT site – Flp recombination target, the recognition site for Flp recombinase

FTA – Fault Tree Analysis (FTA)

Full ratchet – Relates to an anti-dilution measure where the conversion price of preferred stock is adjusted to reflect the price of the common stock in the offering.

Fully-integrated pharmaceutical company (FIPCO) – Is a firm that performs the functions of most, if not all, links in the value chain.

Functional cloning – Approach to cloning that starts with a known protein that is suspected of involvement in a hereditary disorder

Functional genomics – The development and implementation of tech- nologies to characterise the mechanisms through which genes and their products function and interact with each other and with the environment (see Transcriptomics). The study of the whole genome and its expression.

Fund – This term refers to a pool of capital which is raised periodically by a private equity/venture capital organization. It is usually set up in the form of limited partnerships, and has a life span of ten years, though extensions of several years are often possible.

Fund of funds – A fund investing in other private equity/venture capital funds rather than in operating companies. These funds are often set up by an investment bank or investment adviser. Is a type of venture capital fund that invests in a portfolio of venture capital funds.

Fundamental frequency – Phonatory frequency that determines pitch.

Fundamental spectral sensitivities – The colour-matching functions corresponding to the spectral sensitivities of the three cone types, measured at the cornea. The spectral sensitivities may be normalised so that the maximum is unity or according to the nominal population densities of the cone types.

Fungus – Eukaryotic organism that can exist outside a host but will invade and colonise if conditions permit. May be single-celled or multicellular.

Furan – Five-membered carbon ring in which the fifth member of the ring is oxygen. Five-membered carbohydrate compounds are based on the structure of this compound.

Fusion (in virology) – A method of viral entry that involves bringing the virion envelope into close proximity to a cellular membrane (most often the plasma membrane or endosome) so that the two may fuse and create a pore through which the viral genome can be delivered.

Fusion peptide – It refers to a hydrophobic peptide domain that triggers membrane fusion.

Fusion protein – The result of the common expression of two neighboring genes that are not separated by a stop codon.



General Contamination – Contamination of the product or processing area by materials from the ambient environment outside  controlledenvironment. General contamination may be understood as “dirt” which has penetrated clean areas from the ambientenvironment. This does not include particles or organisms from other processes.

G protein receptor – Any receptor of a hormone or other effect or substance that interacts with a G protein.

G proteins – Proteins that normally bind GDP when inactive, but bind GTP when stimulated by a receptor protein. They are intermediates between receptor proteins and enzymes that synthesise or degrade second messengers. G proteins either activate or inhibit these enzymes.

G0 phase – Resting phase in which eukaryotic cells no longer grow or divide.

G1 phase – First stage in the eukaryotic cell cycle, in which cell growth occurs.

G2 phase – Third stage in the eukaryotic cell cycle, in which the cell prepares for division.

G-418 – Aminoglycoside antibiotic that kills animal cells by blocking protein synthesis; also known as geneticin.

GA4GH – Global Alliance for Genomics and Health.

GAIN – Genetic Association Information Network.

Gain-of-function – A mutation that alters gene function by obtaining a new function or pattern of gene expression. Occurs when a mutation produces a new type of function- ality for a gene. It should be noted that the new functionality gained by such mutations is seldom beneficial. It represents a “gain” only in the restricted sense that the mutated gene does something that is different from normal. Most mutations in a gene produce no effect or they reduce the functionality or the expression (e.g., the quantity of expressed protein) of the gene. It is unusual for a mutation to produce a gain in function, and it turns out that most gain-of- function mutations are unique to the disease they cause. For example, everyone with sickle cell disease, caused by a gain-of-function mutation, has precisely the same point mutation causing glutamic acid to be replaced by valine in the sixth position of the beta-globin chain in hemoglobin. Other diseases wherein a particular gain-of-function mutation accounts for most or all affected individuals are hemochromatosis and achondroplasia. Nephrogenic syndrome of inappropriate antidiuresis is an exception to the general rule, being caused by one of two gain-of-function mutations in the same gene.

Gain-of-function mutation – A mutation that   confers new or enhanced activity for the protein harboring that mutation. A mutation that produces a protein that takes on a new or enhanced function.

Gal4 protein – Transcriptional activator from yeast that has a DNA-binding domain and a transcription activating domain.

Galactitol – The polyol that is formed from galactose in galactosemia via the polyol pathway and is osmotically more active than sorbitol since polyol dehydrogenase cannot use it as a substrate.

Galactosemia – A disease involving the inability of cells to metabolize galactose as a result of a deficiency of one of three enzymes.

Galactose-phosphateuridyl transferase (GALT) – An enzyme that converts galactose 1-phosphate to uridyldiphospho-galactose and is the primary enzyme that is deficient in galactosemia.

Gamete- Sex cell, either sperm or egg. After full maturation these cells contain half the number of chromosomes for a new individual and are therefore termed haploid.

Gamma–delta (γδ)  T  cells – T  lymphocytes  bearing  γδ TCRs. Considered cells of innate immunity.

Gamma–delta (γδ) TCRs – Heterodimer of TCRγ and δ chains plus the CD3 complex. Rather than pMHC, γδ TCRs recognize antigens such as stress proteins and heat shock proteins. See also TCR complex.

Ganciclovir – A nucleoside analog that is converted by cells to a DNA chain terminator. Used against virus infections and in cancer therapy.

Ganglioside – The compound formed when more than one carbohydrate is bound to ceramide.

Ganglioside GM1 – Glycolipid found in eukaryotic cell membranes that is used as a receptor by cholera toxin.

Gate protein – A type of transport protein that allows only specific substances (usually ions) to cross a plasma membrane by facilitated diffusion. During action potentials two different gate proteins for Na+ and K+ ions are operative. These proteins are also called channel proteins or voltage-dependent gate proteins. In the postsynaptic membrane, a Na+ ion channel, receptor protein (nicotinic receptor) belongs to a group of channel proteins that are ligand or neurotransmitter activated.

Gateway® cloning vector – Series of cloning vectors that move the gene of interest from one vector to another using the lambda attP, attB, attL, and attRrecognition sites and the two enzymes, integrase and exisionase.

GC ratio – The amount of G plus C relative to all four bases in a sample of DNA. The GC ratio is usually expressed as a percentage.

GCLP – Good Clinical Laboratory Practices—federal government expectations on how laboratories that test or evaluate clinical specimens from clinical trials will be handled, stored, shipped, and tested and how the tests will be qualified and/or validated.

GCP – Good Clinical Practice (GCP)- regulatory expectations for the planning, conduct, monitoring, reporting, and auditing of clinical trials of biomedical products and the clinical trial sites and investigators who perform these clinical trials.

GDP – Good Documentation Practice (GDP).

GDP – Good Distribution Practice (GDP).

Gearing – A measure of financial leverage, demonstrating the degree to which a firm’s activities are funded by owner’s funds versus creditor’s funds. As for most ratios, an acceptable level is determined by its comparison to ratios of companies in the same industry. The best known examples of gearing ratios include the debt-to-equity ratio (total debt/total equity), timesinterest earned (EBIT/total interest), equity ratio (equity/ assets), and debt ratio (total debt/total assets). A company with a high gearing, i.e., more long-term liabilities than shareholder equity, is considered speculative.

Gel – A homogeneously dispersed solid within a liquid that is viscous in nature.

Gel electrophoresis – Electrophoresis of charged molecules through a gel meshwork in order to sort them by size. Electrophoretic separation of molecules using a polymeric gel, usually consisting of agarose or acrylamide. See also Electrophoresis.

GENCODE portal – Aims to identify all the characteristics of genes in the human genome by using a combination of computer analyses, manual labeling and experimental validation.

Gene – A DNA sequence in a chromosome that contains the genetic code for a protein and that functions as a template to produce mRNA. A DNA sequence that will determine a distinct polypeptide chain (protein) or code for a member of a set of closely related polypeptides (protein isoforms). A functional unit of DNA found on chromosome. A sequence of DNA that contains the information needed for the construction of an individual protein. Basic unit of heredity, consisting of a segment of DNA arranged in a linear manner along a chromosome that typically codes for a specific protein or segment of protein leading to a particular characteristic or function. The fundamental unit of heredity; in molecular terms, a gene comprises a length of DNA that encodes a functional product, which may be a polypeptide (a whole or constituent part of a protein or an enzyme) or a ribonucleic acid. It includes regions that precede and follow the coding region, as well as introns and exons. The exact boundaries of a gene are often poorly defined, because many promoter and enhancer regions dispersed over many kilobases may influence transcription. Unit that defines a region containing transcription start and end signals. Originally, a gene was thought to contain information from the genetic code for the expression of a protein. The term is now also applied to regions that do not code for proteins.

Gene cassette – Simple genetic element that has one or two open reading frames flanked by repeats called 59-be or attCand inserts into integrons.

Gene chips – DNA microarrays for the analysis of single-stranded DNA fragments of genes anchored at one end on a matrix for exact location. cDNA from cells to be investigated is isolated and amplified with PCR. A fluorescent marker substance is added and the hybridisation of complementary sequences is analyzed by sending a laser through the back of the chip. A detector picks up the fluorescence excited by the laser.

Gene cloning – The placement of a gene of interest (normally without introns) into a plasmid

Gene creature – Genetic entity that consists primarily of genetic information, sometimes with a protective covering, but without its own machinery to generate energy or replicate macromolecules.

Gene dosage compensation – The phenomena in which the amount of proteins and RNA produced from sex chromosomes is equalized between males and females in diploid organisms.

Gene editing – A tool which allows altering the DNA of a living organism or cell by insertion, deletion or modification.

Gene expression – A process of cellular system in which instruction from gene is used to synthesize protein but sometime small nuclear RNA and transfer RNA is a functional RNA. Alteration in gene expression can change the function of cells and tissue even or even the characteristics of an organism. The process through which a gene is activated at a particular time and place so that its functional product is produced;eg, transcription into mRNA followed by translation into protein.

Gene expression profile – The pattern of changes in the expression of a specific set of genes that is relevant to a disease or treatment. The detection of this pattern depends upon the use of specific gene- expression measurement techniques.

Gene family – A group of closely related genes that make similar protein products.

Gene fusion – Structure in which parts of two genes are joined together, in particular when the regulatory region of one gene is joined to the coding region of a reporter gene.

GENE impedance (GENEi) – An alternate term used to describe RNA interference. Proposed to encompass all the different phenomena that induce the degradation of a specific RNA transcript homologous to a short-interfering RNA.

Gene knockouts – A commonly used technique to demonstrate the phenotypical effects and/or variation related to a particular gene in a model organism; for example, in the mouse (see Knockout); the absence of many genes may have no apparent effect upon phe- notypes (though stress situations may reveal specific susceptibili- ties). Other single knockouts may have a catastrophic effect upon the organism, or be lethal so that the organism cannot develop at all.

Gene library – Also referred to as genomic libraries, they contain cloned DNA fragments from chromosomes or the entire genome obtained using restriction enzymes. Each of these genes is inserted in plasmids, cosmids or other vectors and cloned into a separate cell culture. Collection of cloned segments of DNA that is big enough to contain at least one copy of every gene from a particular organism. Same as DNA library.

Gene locus – The exact location of a gene on a chromosome.

Gene pharming – Word made up from farming and pharmaceuticals to denote the production of pharmaceuticals in animals and plants. Plants and animals are genetically engineered so that their milk, eggs or fruit contains the desired genetic product, e.g., a drug.

Gene regulation – Gene expression is influenced by many different regulatory systems, including the epigenome (e.g., chromatin packing, histone modification, base methylation), transcription (e.g., transcription factors, DNA promoter sites, DNA enhancer sites, trans-acting factors), post-transcription (splicing, RNA silencing, RNA polyadenylation, mRNA stabilizers), translation (e.g., translation initiation factors, ribosomal processing), and post-translational protein modifications. Mutations in any of the genes that control or participate in any of these regulatory mechanisms may contribute to a disease phenotype. Moreover, anything that modifies any regulatory process (e.g., environmental toxins, substrate availability, epistatic genes) can influence gene regulation; hence, can produce a disease phenotype. See Regulatory DNA element and Regulatory RNA element.

Gene regulatory network – A functional map of the relationships between a number of different genes and gene products (pro- teins), regulatory molecules, and so forth that define the regula- tory response of a cell with respect to a particular physiological function.

Gene regulatory network (GRN) – The interactions between transcription factors and their targets that govern developmental processes. A network of transcription factors with cross-regulatory (e.g., repression, activation) relationships, e.g., that translate morphogen signals into discrete gene expression boundaries.

Gene segment – A short, germline sequence of DNA from either the variable (V), diversity (D), or joining (J) families that randomly joins via V(D)J recombination with one or two other gene segments to complete a V exon in either the Ig or TCR loci.

Gene superfamily – Group of related genes that arose by several stages of successive duplication. Members of a superfamily have often diverged so far that their ancestry may be difficult to recognize.

Gene targeting – A method used for alteration or modification in the target gene.

Gene testing – Analyzing DNA sequences to identify potential disease states in a patient.

Gene therapy – Medical treatment that involves use of recombinant DNA technology; originally referred to curing hereditary defects by introducing functional genes. The delivery of a normal copy of a gene into a cell to compensate for a nonfunctional defective gene. A therapeutic medical procedure that involves either replacing/manipulating or supplementing nonfunctional genes with healthy genes. Gene therapy can be targeted to somatic (body) or germ (egg and sperm) cells. In somatic gene therapy, the recipient’s genome is changed, but the change is not passed along to the next generation. In germline gene therapy, the parent’s egg or sperm cells are changed with the goal of passing on the changes to their offspring. A technique that utilizes genes for treating or preventing disease. Introducing a genetic change in the genome in cells to treat or cure hereditary disease. GT is the use of DNA or RNA molecules to treat hereditary conditions and defective genes by therapeutic delivery into patients’ cells. To reach the target genome, the molecules are inserted into vectors such as adenoviruses. They encode the expression of the correct protein or block the expression of proteins, thus compensating defects caused by mutations. The process of inserting genes for the purpose of treatment. 

Gene transcription – The process of copying a specific code onto RNA from DNA by synthesis of the RNA.

Gene transfer – A process wherein a gene is transferred to cells for correction of defective gene in order to obtain a proper function.

Gene-based therapy – Refers to all treatment regimens that employ or target genetic material; examples include: (1) transfection (intro- ducing cells whose genetic makeup is modified), (2) antisense therapy, and (3) naked DNA vaccination.

General partner (GP) – The term refers to an investment manager of a limited partnership venture capital fund. Going concern: An entity that is expected to exist into the foreseeable future. No financial problems indicating financial failure over the planning horizon are apparent.

General secretory system (Sec system) – Standard system for exporting proteins across membranes that is found in most organisms.

General transcription factors – Proteins that work to enhance or repress gene expression for all genes.

Generics – Are copies of brand name drugs and are the same as those brand name drugs in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use.

Genes – A sequence of DNA that corresponds to a unit of hereditary information, usually coding for a protein.

Genetic (genomic) epidemiology – A field of research in which cor- relations are sought between phenotypical trends and genetic or genomic variation across population groups.

Genetic architecture – The full range of genetic effects on a trait. Genetic architecture is a moving target that changes according to gene and genotype frequencies, distributions of environmental fac- tors, and such biological properties as age and sex.

Genetic circuits – Combinations of genes, promoters, enhancers, and repressors that control the output or expression of the final gene product

Genetic code – The determined set of rules that dictate which amino acids correspond to specific codons within mRNA.Represents all the rules that enable the translation of information held within the genome for protein synthesis. It provides the link between the genotype and phenotype of an organism. This code relies on nucleotide triplets (codons), messenger RNA and the amino acids incorporated in the synthesized proteins during translation of messenger RNA by ribosomes. The relationship between the order of nucleotide bases in the coding region of a gene and the order of amino acids in the polypeptide product. It is a universal, triplet, non-overlapping code, such that each set of three bases (termed a codon) specifies which of the 20 amino acids is present in the polypeptide chain product of a particular position. Three-base sequences in nucleic acids that code for amino acids as well as the initiation and halting of protein synthesis.

Genetic counseling – An important process for individuals and families who have a genetic disease or who are at risk for such a disease. Genetic counseling provides patients and other family members information about their condition and helps them make informed decisions.

Genetic counselor – A health professional specialized in the area of genetics and counseling about various genetic information to individuals.

Genetic determinism – The unsubstantiated theory that genetic factors determine a person’s health, behavior, intelligence, or other com- plex attributes.

Genetic discrimination – Unfavorable discrimination against an indi- vidual, a family, a community, or an ethnic group on the basis of genetic information. Discrimination may include societal segrega- tion, political persecution, restriction of opportunities for education and training, lack of or restricted employment prospects, and inadequate personal financial planning; for example, life insurance and mortgages.

Genetic engineering – Linking up DNA molecules of different origin into recombinant DNA that can be multiplied and inserted into a recipient organism in order to propagate recombinant DNA and generate novel gene products (recombinant proteins). The use of molecular biology techniques such as restriction enzymes, ligation, and cloning to transfer genes among organisms (also known as recombinant DNA cloning).

Genetic escape mutant – Pathogen that evades neutralizing antibodies and antigen-specific CTLs due to antigenic variation arising from mutations that occur during replication.

Genetic heterogeneity – In the context of genetic diseases, the term refers to diseases that can be expressed by any one of multiple allelic variants in a gene or by any one of multiple different genes that carry disease-producing alleles (locus heterogeneity). Tuberous sclerosis is an example of the latter. This inher- ited disease can be caused by a mutation in the TSC1 gene on chromosome 9q34, which codes for hamartin; or the TSC2 gene on chromosome 16p13, which codes for tuberin. Retinitis pigmentosa is a disease with enormous genetic het- erogeneity, and can result from allele heterogeneity or from locus heterogeneity. When a rare disease demonstrates genetic heterogeneity, we are provided with an opportunity to learn how a common pathogenesis develops from different genes. Genetic heterogeneity should be contrasted with the concept of genetic pleiotropism, in which one gene may be responsible for several different functions or disorders. See Pleiotropism, Locus heterogeneity, Oligogenic inheritance, and Allelic variants.

Genetic Information Nondiscrimination Act of 2008 (GINA) – Legislation passed by the US Congress that prohibits employers and health insurance agencies from using genetic information in decisions.

Genetic instability – The process whereby the genome accumulates genetic alterations (e.g., SNPs, GSVs) over time. Low levels of unrepaired DNA dam- age are an inescapable feature of living cells. The older the cell, the more muta- tions might be found. Many cancers have a high rate of genetic instability. Mutations that arise in germ cells are sometimes passed onto progeny. See Mutator phenotype, SNP, and Genomic structural variation.

Genetic map – A map showing the positions of genetic markers along the length of a chromosome relative to each other (genetic map) or in absolute distances from each other.

Genetic mapping – Determining the linear order of genetic markers determined by the frequency in which two markers stay together during mating

Genetic maps – Maps of genetic markers and/or genes ordered by using linkage information but without exact base-pair distances

Genetic markers – Physical landmarks used to construct genomic maps that are genetic in origin, such as genes, single nucleotide polymorphisms

Genetic reassortment – It refers to a kind of genetic recombination occurring during assembly of segmented genome.

Genetic screening – Testing a population group to identify a subset of individuals at high risk of having or transmitting a specific genetic disorder.

Genetic surgery – Less common name for gene replacement therapy.

Genetic surplus disorder – Mutations that expand the genome or that pro- duce an increased dosage of one or more genes can produce rare diseases. Examples are: Charcot–Marie–Tooth disease, an inherited neuropathy caused by a duplication of a segment of chromosome 17; and Down syndrome, caused by an extra chromosome 21. In addition, there is a group of rare diseases characterized by trinucleotide repeats. About half of the studied trinucleotide repeat disorders demonstrate repeated CAG sequences. CAG codes for gluta- mine; thus, CAG repeats produce a polyglutamine protein tract. Examples of polynucleotide repeat disorders are: dentatorubropallidoluysian atrophy, fragile X syndrome, Friedreich ataxia, Huntington disease, myotonic dystrophy, spino- bulbar muscular atrophy, several forms of spinocerebellar ataxia.

Genetic susceptibility – Predisposition to a particular disease attributed to the presence of a specific allele or combination of alleles in an individual’s genome.

Genetic test – An analysis performed on human DNA, RNA, genes, and/or chromosomes to detect heritable or acquired genotypes. A genetic test also is the analysis of human proteins and certain metabolites, which are predominantly used to detect heritable or acquired genotypes, mutations, or phenotypes.

Genetic testing – Strictly refers to testing for a specific chromosomal abnormality or a DNA (nuclear or mitochondrial) mutation already known to exist in a family member. This includes diagnostic testing (postnatal or prenatal), presymptomatic or predictive genetic testing, or testing for establishing the carrier status. The individual concerned should have been offered full information on all aspects of the genetic test through the process of non-judgmental and nondirective genetic counseling. Most laboratories require a formal, fully informed, signed consent before carrying out the test. Genetic testing commonly involves DNA/RNA-based tests for single-gene variants, complex genotypes, acquired mutations, and measures of gene expression. Epidemiological studies are needed to establish clinical validity of each method to establish its sensitivity, specificity, and predictive value.

Geneticin (G-418) – Aminoglycoside antibiotic that kills animal cells by blocking protein synthesis.

Genetic changes – Changes in plants after tissue culture that are inherited by the progeny, including alterations in chromosomes.

Geneticist – An individual specialized in the study of genetics, which is composed of genes, heredity, and variation.

Genetics – Refers to the study of heredity, genes, and genetic material. In contrast to genomics, genetics is traditionally related to lower- throughput, smaller-scale emphasis on single genes, rather than on studying the structure, organization, and function of many genes.

Genome – The complete set of genes of an organism or biological entity. A complete set of DNA molecule of living cells or organisms. The collected assortment of an organism’s hereditary information, encoded as DNA. For humans, this would mean the set of chromosomes found in a somatic cell, plus the DNA from one of the cell’s mitochondria. In practice, when an organism’s genome is sequenced, a haploid set of chromosomes is examined, and the mitochondrial DNA is omitted. See Haploid. The complete set of chromosomal and extrachromosomal DNA/RNA of an organism, a cell, an organelle, or a virus. The entire genetic information contained within a cell. The total amount of DNA in a living organism. In humans, this is contained in 23 chromosomes and is made up of around 3 billion base pairs encoding ~23,000 genes.

Genome annotation – The process through which landmarks in a genomic sequence are characterized using computational and other means; for example, genes are identified, predic- tions made as to the function of their products, their regula- tory regions defined, and intergenic regions characterized (see Annotation).

Genome browser – A computer program that allows the scientist to look graphically at the entire genome of an organism to identify regions or genes of interest. An online site that contains a collection of genomic data information.

Genome editing – Techniques that allow making specific changes in DNA of a cell.

Genome map – A graphical representation of an organism’s genome.

Genome ontology – A standard set of consistent nomenclature systems that can be used to describe gene and protein functions in all organ- isms based on molecular function, biological process, and cellular location.

Genome wide association study (GWAS) – A method to find common SNPs (single nucleotide polymorphisms) that are statistically associated with a poly- genic disease. The methodology involves hybridizing DNA from individuals with disease, as well as individuals from a control group, against a DNA array of immobilized fragments of DNA known to contain commonly occurring SNPs (i.e., allele-specific oligonucleotides). The SNPs that hybridize against the DNA extracted from individuals with disease (i.e., the SNPs matching the case samples) are compared with the SNPs that hybridize against the controls. SNPs that show a statistical difference between case samples and control sam- ples are said to be associated with the disease. Of course, there are many weak- nesses to this approach; one being that differences in SNPs do not necessarily imply any functional variance in the gene product. In addition, differences in SNPs may lead to statistically valid results that nonetheless have no relevance to the pathogenesis of disease. Aside from false-positive GWAS associa- tions, the methodology is virtually guaranteed to miss valid SNP associations, simply because SNP arrays are not exhaustive (i.e., do not contain all 50 million SNPs), and are limited to a selected set of commonly occurring polymorphisms. For example, a rare variant of the APOE gene has been shown to be strongly correlated with longevity. This variant, because it is not included among the common APOE variants included in SNP arrays, would have been missed by a GWAS study. True associations are those that can be found repeatedly from laboratory to laboratory, and that can be shown to have pathogenetic relevance. To date, very few disease-associated SNPs found in GWAS studies have met these criteria. It has been suggested that the GWAS studies, in toto, have had little scientific merit and have been misleading. A sympathetic evaluation of GWAS studies is that they help us to see recurrent sets of pathway genes involved in diseases. Knowing that a related set of genes seems to implicate a pathway in the development or expression of a common disease has great value. By focusing attention on a pathway, scientists can start to dissect the important events in the pathogenesis of a disease. If the pathway is known to be disrupted in a monogenic disease, particularly when the monogenic disease replicates the phenotype of a common disease, then an effective new treatment, aimed at the pathway, may be feasible. A genetic approach that uses high throughput sequencing to compare control and affected populations and identify genetic variants (e.g., SNPs, mutated alleles) that are associated with a given phenotype (disease). A technique that is used to study genetic markers across complete sets of DNA in different people to find genetic variation in a particular trait. Examining genetic variation among different individuals to see if the variation associates with a particular trait.

Genomic drugs – Drugs based on molecular targets; genomic knowl- edge of the genes involved in diseases, disease pathways, and drug- response (see Pharmacogenomics).

Genomic instability – An increased tendency of the genome to acquire mutations when various processes involved in maintaining and rep- licating the genome are dysfunctional.

Genomic profiling – Complete genomic sequence of an individual, including the expression profile. This would be targeted to specific requirements; for example, most common complex diseases (diabe- tes, hypertension, and coronary heart disease).

Genomic structural variation (GSV) – A variation in the structure of chromo- somes, usually involving stretches of DNA. GSVs include alterations in karyo- type or cytogenetic alterations observable with special techniques, as well as changes too small to see with a microscope, such as small deletions, insertions, single nucleotide polymorphisms (SNPs), larger insertions, inversions, and translocations. GSVs would also include duplications and other copy-number alterations as well as gene conversions . GSVs among different individuals in the human population occur frequently, and may account for more pheno- typic variations in the human population than do SNPs. Several databases assist scientists in search of GSVs: Ensembl genome database, NCBI dbSNP database, The Genomic Association Database and SNPedia, Varietas. For examples of GSV disorders, see Microdeletion and Copy-number.

Genomics – The study of the genome and its action. The term is com- monly used to refer large-scale, high-throughput molecular analysis of multiple genes, gene products, or regions of genetic material (DNA and RNA). The term also includes the comparative aspect of genomes of various species, their evolution, and how they relate to each other (see Comparative genomics).

Genotype – The genetic makeup of a cell or organism. A set of genes which is responsible for a particular trait of organisms. Exact description of the genetic disposition of an individual, either in terms of a certain trait or a series of traits (in contrast to phenotype). The genetic constitution of an organism; commonly used in reference to a specific disease or trait. The genetic makeup of an individual usually referring to a specific set of alleles or traits. The genetic makeup of an individual, with all the individual variations in the genome.

GEP – Good Engineering Practice (GEP).

Germ Cell – Gamete or sex cell.

Germ Layers – the three cell lineages that originate from the blastocyst- ectoderm, endoderm and mesoderm.

Germ theory – The theory that states that infectious diseases are caused by microorganisms.

Germinal center (GC) – Aggregations of rapidly proliferating B cells and differentiating memory B and plasma cells that develops in a secondary lymphoid follicles. Site of isotype switching,somatic hyper mutation and affinity maturation.

Germinal mutation – A change in the DNA sequence in the germline and therefore can be passed on to the next generation.

Germline – Reproductive cells producing eggs or sperm that take part in forming the next generation (in eukaryotic organisms). The cell line in which the gametes are formed from. The germline consists of the cells that derive from the fertilized egg of an organism. All of the somatic cells (i.e., the cells composing the body), as well as the germ cells of the body (oocyte and spermatozoa), arise from the same germline. The extra-embryonic cells (e.g., placental cells) have the same germline as the somatic cells. An inherited condition can be described as being in the germline; in every cell that derives from the fertilized egg. The word “germline” has confused many students, who use the term “germline cell” interchangeably with “germ cell.” The confusion is exacerbated by the usual sequence whereby a mutation enters the organism’s germline via an inherited mutation present in a parental “germ cell.” It is best to think of a germline muta- tion by its functional definition, a mutation passed to every cell in an organism, and not by its somewhat inaccurate mechanistic definition, a mutation passed from a parental germ cell. See De novo germline mutation.

Germline cell – A cell with a haploid chromosome content (also referred to as a gamete); in animals, sperm or egg; and in plants, pollen or ovum.

Germline mosaic (germinal mosaic, gonadal mosaic, gonosomal mosaic) An individual who has a subset of germline cells carrying a mutation that is not found in other germline cells.

Germline mutation – A gene change in the body’s reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring, also called hereditary mutation.

Germline stem (GS) cells – Unipotent cell line derived from mouse testes, which reconstitutes spermatogenesiswhen transplanted into sterile recipients.

GFP – see Green fluorescent protein (GFP).  

Ghrelin – Peptide hormone that signals hunger.

Giant vacuoles – The outpouchings of the inner-wall endothelium of Schlemm’s canal into its lumen. They are caused by the pressure drop across inner-wall endothelial cells

Giant virus – A novel virus found in ameba, which is bigger than any other known viruses (400 nm in diameter, 1200 kb in genome). Glycan It refers to the carbohydrate moiety of glycoproteins.

Gibbs energy – also known as free enthalpy, denoted with letter G. Calculating the difference in Gibbs energy (ΔG) before and after a chemical reaction shows whether the reaction is exergenic (ΔG < 0) or energenic (ΔG > 0). Gibbs energy is defined as the difference between enthalpy and the product of absolute temperature and entropy. In biology, Gibbs energy can be (imprecisely) described as the energy available for work at constant temperature and pressure.

Gingiva – Part of the soft tissue lining of the mouth, sur- rounding the teeth and provide a seal around them.

GIP – General Investigational Plan (GIP) – information provided in an IND explaining in general terms the sponsor’s plans for investigating an investigational new drug in the coming year.

Glabrous – Smooth; a term applied to regions of hairless skin.

Glaucoma – An eye disease caused by an increase in eye pressure, which causes changes in the optic nerve and loss of vision.

Global moral economy – Recognizing bioethics as a political community in which the trading and exchange of values is normalized and legitimatized.

Glomeruli – A specialized “globe” of neuropil that consists of dendrites from olfactory bulb mitral cells, dendrites from olfactory bulb granule cells, axon endings and synaptic boutons from olfactory receptor neurons, and axonal and dendritic processes from periglomerular cells, whose cell bodies define the limits of each glomerulus.

Glottis – Region of the larynx that encompasses the vocal folds.

GLP – Good Laboratory Practice (GLP)- federal regulations governing how laboratories that conduct animal studies and in vitro tests will plan, conduct, monitor, report, and quality control/assure such studies. These regulations cover the facilities, animal husbandry, and qualified & trained personnel for these studies as well as the studies themselves. The GLP regulations can be found in 21 CFR 58.

GLSP – Good Large Scale Practice

Glucocorticoid activity – Ability of steroid hormones to affect glucose metabolism.

Glucocorticoid hormones – Group of steroid hormones in mammals that are involved in water and ion balance.

Gluconeogenesis – The formation of glucose from lactate. This usually takes place in the liver.

Glucose intolerance – An impaired ability to clear glucose efficiently from the bloodstream after a meal; a prediabetic state. 

Glucose oxidase test – Chemical method for detecting glucose, often used to detect Diabetes mellitus (glucose in urine and blood).

Glucose transport proteins – (Abbreviated as GLUT) are proteins that transport glucose into cells. The GLUT associated with insulin is GLUT-4.

Glucose-stimulated insulin secretion – The increase in insulin released by pancreatic islets is proportional to the elevation in blood glucose; glucose must be metabolized by the β-cell for insulin to be released.

Glucuronic acid (glucoronate) – A glucose molecule having a carboxylic acid group attached to carbon #4 (in the up position in the Haworth structure convention). Iduronic acid is an isomer of glucuronic acid in which the carboxylic acid group is down in the Haworth structure convention.

Glutathione-S-transferase (GST) – Enzyme that binds to the tripeptide glutathione; often used in making fusion proteins.

Glycation – A mechanism of complex binding of glucose with proteins that may cause loss of protein function (denaturation). Early forms of this binding are called ketimineswhile late forms are referred to as advanced glycation end products (AGEs).

Glycerol phosphate shuttle (malate-aspartate shuttle) – Reaction mechanisms by which extra electrons are transported into the mitochondria to obtain additional ATP.

Glycocalix – Literally means “sugar coat.” Refers to sugars that are attached or associated with a cell membrane.

Glycogen – The polymer storage form of glucose in animal cells. It is characterized by extensive branching of the main chain. Polymer of glucose linked by α-1, 4 bonds and used as a storage polysaccharide by animals and bacteria

Glycogen phosphorylase – See Glycogen synthase.

Glycogen synthase – Final enzyme in the glycogen formation pathway that adds glucose onto glycogen. Its kinetics are tightly regulated in the opposite direction with glycogen phosphorylase, the enzyme that breaks down glycogen.

Glycolysis – Catabolic reaction pathway for the stepwise degradation of glucose into two pyruvate molecules. It comprises 10 enzymatically catalyzed steps during which energy is obtained as ATP. The reduction equivalents (NADH+H+) arising in the process are used in various ways, depending on the organism in question and other conditions, such as aerobic conditions in the citric acid cycle, leading to further energy production or formation of ethanol in alcoholic fermentation. Literally the splitting of carbohydrates. The term is synonymous with the Embden-Meyerhof pathway that ends with the formation of pyruvate. Glycolysis can be both anaerobic and aerobic depending upon the metabolic fate of pyruvate.

Glycoprotein – Any protein to which one or more oligosaccharides are bound. “Mucins” are glycoproteins found on the surface of the cornea. Molecule with a protein (amino acid) backbone with sugar (oligosaccharide) molecules attached. Proteins with carbohydrate side chains. These side chains are often species- specific and are therefore very significant in biotechnology. Bacteria are unable to bind carbohydrate chains to proteins produced. Recombinant glycoproteins can only be produced by eukaryotic, usually mammalian cells.

Glycosaminoglycans (GAGs) – Carbohydrate polymers composed of disaccharide units of one amino sugar and one nonamino sugar. They have a high density of negative charges.

Glycosylation – The process by which a carbohydrate is added to protein. The addition of one or more sugars to a compound by enzyme catalysis. The addition of sugar residues (usually several forming short chains) to proteins after translation.

Glyphosate – A weed killer that inhibits synthesis of amino acids of the aromatic family in plants.

GM, GMO – Genetically modified (organism). In the context of food, GM food is food containing GMOs.

GMO – Genetically Modified Organism (GMO). A GMO can be a food organism or can be a medicinal organism, such as a viral vector used for gene therapy. Any living organism that has been genetically modified by recombinant DNA technology (as opposed to by targeted breeding or hybridization). Many countries have specific regulations pertaining to GMOs, and often, they have an agency responsible for that regulation.

Goblet cells – Cells found in mucosal epithelia that produce and secrete mucus i.e. specialised epithelial cells that secrete mucins.

Good Manufacturing Practice (GMP) – A production and testing practice that helps to ensure a quality product. Many countries have legislation so that pharmaceutical and medical device companies must follow GMP procedures, and have created their own GMP guidelines that correspond with their legislation. A term that is recognized worldwide for the control and management of manufacturing and quality control testing of foods and pharmaceutical products. Good Manufacturing Practices- federal regulations that govern the manufacture of biomedical products, both marketed and investigational. The GMP regulations can be found in 21 CFR 210’s and 211’s in the US and in the EU GMP guidelines in EudraLex volume 4 in Europe. Additional expectations for biologicals can also be found in 21 CFR 600’s.

GLSP – Good Large Scale Practice (GLSP).

Golden age of pharmaceuticals – Is the era immediately following World War II when major pharmaceutical firms developed numerous drugs based upon the random screening process.

Golgi complex – The organelle of the cell responsible for the final modification and distribution of proteins.

Gonadotropin Releasing Hormone (GnRH) – Also known as luteinizing releasing hormone. This peptide hormone is synthesized by a small number of cells in the hypothalamus that are generated initially in the olfactory epithelium. They migrate subsequently to the hypothalamus. GnRH is released in pulses from the hypothalamic neurons that produce it, in both males and females. It regulates the secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH), which are essential for generation of gametes in both females and males.

Goniodysgenesis – Malformed ocular drainage angle.

GoNL – Genome of the Netherlands Project

Good Clinical Practice (GCP) – An international quality standard that is provided by the International Conference on Harmonization (ICH), an international body that defines standards, which governments can transpose into regulations for clinical trials involving human subjects.

Gorlin syndrome – This is an autosomal dominant cancer syndrome. Patients with this rare syndrome often have anomalies in multiple organs, many of which are subtle. Gorlin syndrome patients have the propensity to develop multiple neoplasms, including basal cell carcinomas and medulloblastomas, and the patients’ are extremely sensitive to ionizing radiation, including sunlight. Extra digits on the hands or feet also occur in this syndrome. Mutations in the PATCHED gene have been found to cause the Gorlin syndrome.

gp120 – Glycoprotein of 120 kDa found in outer envelope of HIV that binds to CD4 protein on host cell, resulting in entry of the virus.

Government bonds – A bond issued by a national government and denominated in the country’s own currency. They are usually referred to as risk-free bonds and are given the highest rating available.

Government funds – A term used to describe venture capital funds organized by government bodies, or else programs to make venture-like financings with public funds.

G-proteins – Class of GTP-binding eukaryotic proteins involved in signal transmission.

Gradualist view – Idea in philosophical ethics that embryo development is gradual and the moral status ascribed to it also increases gradually.

Graft rejection – Attack by recipient immune system on transplanted donor tissue (a graft). See also hyperacute, acute and chronic graft rejection (CGR). Also known as transplant rejection.

Graft-versus-cancer (GvC) effect – In BMT/HSCT for cancer treatment, destruction of residual cancer cells in a recipient’s solid tumor by T cells from an allogeneic donor.

Graft-versus-host disease (GvHD) – Attack by immuno- competent cells in transplanted donated tissue on recipient tissues due to MHC or MiHA mismatches.

Graft-versus-Host Reaction/Graft-versus-Host Disease (GvHD) – Immune mediated rejection reaction of white blood cells in a bone marrow transplant from a not HLA-identical donor, directed against the host cells. This can lead to serious organ damage and evendeath if it develops into GvHD.

Graft-versus-leukemia (GvL) effect – In BMT/HSCT for cancer treatment, destruction of residual recipient leukemia cells by T cells from an allogeneic donor.

Gram-negative bacteria – Bacteria that have thin cell walls containing LPS.

Gram-negative bacteria – Bacteria with thin peptidoglycan layer surrounded by an outer cell wall. The cell wall does not stain with permanently crystal violet. May be counterstained with carbolfuschin or safranin.

Gram-positive bacteria – Bacteria that have thick cell walls containing peptidoglycan and lip teichoic and teichoic acids.

Gram-positive bacteria – Bacteria with a thick peptidoglycan layer outside the cell wall. The cell wall stains permanently with crystal violet.

Grants – Funds given to tax-exempt non-profit organizations or local governments by foundations, corporations, governments, small business, and individuals. Most grants are made to fund a specific project and require some level of reporting.

Granulocyte-Macrophage-Colony Stimulating Factor (GM-CSF) – A naturally occurring growth factor that is secreted as a result of stress or tissue damage or is administered intravenously to mobilize blood stem cells from the bone marrow into the blood.

Granulocytes Myeloid – leukocytes that harbor large intracellular granules containing microbe-destroying hydrolytic enzymes. Include neutrophils, basophils and eosinophils.

Granuloma – Structure formed by a group of hyper activated macrophages that fuse together to wall off a persistent pathogen from the rest of the body. Also contains CD4+ and CD8+ T cells. Formation depends on TNF produced by activated Th1 effectors.

Graptolites – These abundant Cambrian fossils have been shown to be colonial hemichordates, or members of the hemichordate class Pterobranchia.

GRAS – Generally Regarded as Safe (GRAS)- a list of food additives that U.S. FDA considers to be generally regarded as safe. Generally, U.S. FDA accepts excipients from this list without additional preclinical safety data to support its inclusion in a formulation. However, this depends on the route of administration of the product and the dose of the excipient in the formulation; hence, “generally.”

Gratuitous inducer – A molecule (usually artificial) that induces a gene but is not metabolized like the natural substrate; the best known example is the induction of the lac operon by IPTG.

Gray biotechnology – also known as Environmental Biotechnology covers methods of drinking water purification and waste water treatment, soil remediation, waste recycling, and exhaust gas purification, but also leaching of metals from ores.

Green biotechnology – Plant biotechnology.

Green fluorescent protein (GFP) – A jellyfish protein that emits green fluorescence and is widely used in genetic analysis. Originally isolated from the jellyfish Aequorea victoria that fluoresces green when exposed to blue light. The GFP gene is frequently used as a reporter of expression. The protein is often combined as a label with other proteins to be investigated. The resulting fusion protein is easily detectable due to its fluorescence. Animals have been created that express GFP as a proof-of-concept that a gene can be expressed throughout a given organism. 

Gross domestic product (GDP) – This term describes the monetary value of all finished goods and services that are produced within a country’s borders in a specific time period, usually on an annual basis. It includes all private and public consumption, government outlays, investments, and exports less imports that occur within a defined territory.

Growth factor – A naturally occurring molecule that produces an effect, such as proliferation or differentiation, in other cells. Protein or other chemical messenger circulating in the blood that carries signals for promoting growth to the cell surface.

Growth plate – The area of developing tissue between the diaphysis and epiphysis responsible for the longitudinal growth of bones.

GSPR – General Safety and Performance Requirement.

GSV – See Genomic structural variation (GSV).

Guanylate cyclase – Enzyme that synthesizes cyclic GMP.

Guanylate cyclase binding proteins (GCAPs) – Proteins that, when bound to calcium, inhibit guanylate cyclase.

Guide RNA (gRNA) – A short RNA (w20 bases) which is complementary to target sequences. It is used in genome editing of organisms and cells. It is an artificial sequence which is not found in nature.

Guided search – Is a more sensitive examination of compounds than random screening. This approach began in the mid-1970s. It led firms to screening a wider array of compounds and to a greater codification of basic knowledge.

Guided tissue regeneration – Dental surgical procedures that utilize barrier membranes to direct the growth of new bone and gingival tissue at sites having an insufficient volume or dimension of bone or gingiva for proper function, esthetics, or prosthetic restoration.

Gut-associated lymphoid tissue (GALT) – The Peyer’s patches, appendix and diffuse collections of immune system cells in the linings of the small and large intestine. See also mucosa-associated lymphoid tissue (MALT).

GVP – Good pharmacovigilance Practices—legal and regulatory expectations for the science, interventions, and methods for surveillance, detection, evaluation or assessment, characterization or understanding, and prevention or minimization of adverse events or any other drug-related problem.

GWAS – See Genome wide association studies (GWAS).

1-gene-to-many-diseases – Various alterations in a single gene can result in several different diseases. For example, the ALAS2 gene codes for delta- aminolevulinate synthase-2. A gain-of-function mutation in the ALAS2 gene causes X-linked erythropoietic protoporphyria. A deficiency of the enzyme results in insufficient hemoglobin production in red cells and causes X-linked sideroblastic anemia. Several different diseases may result from mutations that cause graded losses in gene activity. For example, Lesch–Nyhan syndrome and Kelley–Seegmiller syndrome both result from mutations in the HGPRT gene. In the Kelley–Seegmiller syndrome, the deficiency of hypoxanthine guanine phos- phoribosyltransferase is less than that observed in Lesch–Nyhan syndrome, and the symptoms are milder. See Allelic to.


H5N1- Influenza Avirus subtype H5N1, also known as A(H5N1) or simply H5N1, is a subtype of the influenza Avirus which can cause illness in humans and many other animal species. According to the International Committee on Taxonomy of Viruses (ICTV) database (2006), its virus code is A bird-adapted strain of H5N1, called HPAI A(H5N1) for ‘highly pathogenic avian influenza virus of type A of subtype H5N1,’ is the causative agent of H5N1 flu, commonly known as ‘avian influenza’ or ‘bird flu.’ It is enzootic in many bird populations, especially in Southeast Asia.

HACCP- Hazard Analysis and Critical Control Point (HACCP)

Hazard – A real or potential condition, situation or agent that can cause harm to people, product, facility or process. A hazardcan cause damage or loss of a system, equipment or to the environment.

HAZOPS- Hazard and Operability Studies (HAZOPS)

H-2 complex – Murine major histocompatibility complex (MHC).

HAART (highly active antiretroviral therapy) – It refers to the antiviral therapy, in which two or three antiviral drugs are combined and given as a mixture.

Hematological – Dealing with the blood and blood-forming tissues.

Haematopoiesis – The production and maturation of blood cells of all types.

Hairpin- A double-stranded base-paired structure formed by folding a single strand of DNA or RNA back on itself.

Hairpin ribozyme – Small catalytic RNA molecule with four helices around two internal loops.

Halo deal – Is a venture capital investment that is significantly profitable and pays for other less profitable investments.

Hamartoma – Hamartomas are benign tumors that occupy a peculiar zone lying between neoplasia (i.e., a clonal expansion of an abnormal cell) and hyperplasia (i.e., the localized overgrowth of a tissue). Some hamartomas are composed of tissues derived from several embryonic lineages (e.g., ectodermal tissues mixed with mesenchymal tissue). This is almost never the case in can- cers, which are clonally derived neoplasms wherein every cell is derived from a single embryonic lineage. Tuberous sclerosis is an inherited hamartoma syn- drome. The pathognomonic lesion in tuberous sclerosis is the brain tuber, from which the syndrome takes its name. Tubers of the brain consist of localized but poorly demarcated malformations of neuronal and glial cells. Like other hamartoma syndromes, the germline mutation in tuberous sclerosis produces benign hamartomas as well as carcinomas; indicating that hamartomas and can- cers are biologically related. Hamartomas and cancers associated with tuberous sclerosis include cortical tubers of brain, retinal astrocytoma, cardiac rhab- domyoma, lymphangiomyomatosis (very rarely), facial angiofibroma, white ash leaf-shaped macules, subcutaneous nodules, cafe-au-lait spots, subungual fibromata, myocardial rhabdomyoma, multiple bilateral renal angiomyolipoma, ependymoma, renal carcinoma, subependymal giant cell astrocytoma. Another genetic condition associated with hamartomas is Cowden syndrome, also known as multiple hamartoma syndrome. Cowden syndrome is associated with a loss of function mutation in PTEN, a tumor suppressor gene. Features that may be encountered are macrocephaly, intestinal hamartomatous polyps, benign hamartomatous skin tumors (multiple trichilemmomas, papillomatous papules, and acral keratoses), dysplastic gangliocytoma of the cerebellum, and a predisposition to cancers of the breast, thyroid and endometrium.

Hammerhead ribozyme – Small catalytic RNA containing three helices around one core loop.

Hapblocks – Groups of common SNPs that are commonly associated with each other during analysis of the human genome.

Haploid – Cells or organisms with a single set of chromosomes, also denoted as 1n (or n) (see also diploid, polyploid). Containing one set of chromosomes. Describing a cell (typically a gamete) that has only a single copy of each chromosome (ie, 23 chromosomes in humans). From Greek haplous, “onefold, single, simple.” The chromo- some set of a gamete. In humans, this would be 23 chromosomes; one set of unpaired autosomes (chromosomes 1 to 22) plus one sex chromosome (X- or Y-chromosome).

Haplotype – A series of closely linked loci on a particular chromosome that tend to be inherited together as a block.

Haploid spores – A fungal sexual offspring that carries a single copy of all the genes (generally used of organisms that have two or more sets of each gene).

Haploinsufficiency – A situation in which an individual has a single functional copy of a gene due to deletion and/or inactivating mutation of the nonfunctioning copy resulting in a specific disease trait or medical condition (due to insufficient protein production). Occurs when one of two alleles of a required gene is inactivated and the other allele does not express sufficient quantities of the gene product to maintain normal cellular functionality. In the field of carcinogenesis, haploinsufficiency may result in a heightened susceptibility to cancer if one copy of a tumor suppressor gene is inactivated and the other copy cannot pro- vide sufficient functionality to suppress tumorigenesis. Situation in which a defect in one of the two copies of a diploid gene causes significant phenotypic defects. The condition in which having only single functional allele in a diploid organism results in pathology. A situation in which a mutation reduces the level of a gene product below threshold levels and a phenotypic effect results.

12-Hydroxyeicosatetraenoic acid (12-HETE) and 12-hydroxyeicosatrienoic acid (12-HETrE) – Eicosanoid metabolites of arachidonic acid via cytochrome P-450 or lipoxygenase. They have been found to have defined roles in the cornea.

Haplotype – A set of DNA polymorphisms that tend to be inherited together, often as a result of their close proximity on a chromosome. It is often used in a restricted sense to refer to a set of SNPs that are statistically associated with one another on a chromosome. A related term, “haplogroup,” refers to a subpopula- tion of individuals that share a common ancestor and a haplotype.

Haplotype (MHC) – The set of MHC alleles contained on a single chromosome of an individual.

Haplotype blocks (hapblocks) – Groups of common SNPs that are commonly associated with each other during analysis of the human genome.

Hapten – A substance that has become antigenic when combined with a larger molecule.

Harm – Any adverse experience that is the unintended consequence of receiving a drug or investigational new drug.

Haworth structure – A representation of carbohydrates in a ring structure (named after Sir W.N. Haworth, who won the Nobel Prize for his contribution in establishing glucose as predominately a ring form in solution).

Hazard – Potential source of harm.

HCM – Hypertrophic cardiomyopathy (HCM).

Headful system – The process of packing a bacteriophage head with DNA until it can no longer be filled.

Healthy subject – A volunteer with no diagnosed and/or apparent physical or mental disease or condition.

Heat shock proteins (HSPs) – Proteins whose expression is upregulated in cells subjected to environmental stresses such as heat or inflammation. Protein that mediates the refolding of misfolded or unfolded proteins.

Heat-stable oral vaccines – Vaccines that are made by expressing a disease antigen in plant leaf tissue. Once the plant tissue is grown, it can be freeze-dried and encapsulated so that refrigeration is unnecessary.

Heavy chains – The longer of the two pairs of chains forming an antibody molecule helper component proteinase (Hc-Pro) A polyviral protein that inhibits accumulation of plant siRNAs, but has no effect on the spread of RNA interference to other parts of the plant

Heavy-chain antibodies (hcAb) – An antibody that is from camels but has only a single heavy chain molecule.

Helix – A spiral with a defined, static diameter.

Helper T cell (Th) or Helper T-lymphocyte (Th) – One of two major subsets of T lymphocytes. A subclass of T cells which can help to generate cytotoxic T cells and help B cells to generate antibodies. A subset of CD4 T lymphocyte that helps B or CD8 T-lymphocyte to proliferate and differentiate to effector cells.

Helper virus – A virus that provides essential functions for defective viruses, satellite viruses, and satellite RNA. A virus that provides the proteins necessary for a
defective/satellite virus to replicate.

HEMA – Hydroxyethylmethacrylate monomer forming the basis of many soft contact lens material polymers.

Hemagglutinin (HA) – Hemagglutinin refers to a substance that causes red blood cells to agglutinate or to clump together. This process is called hemagglutination.

Hemagglutination – The linking together of red blood cells, mediated by viral proteins or antibodies.

Hemangioblast – A hypothesized common precursor for both blood cells and blood vessel endothelium cells.

Hemangioblastoma – A benign tumour due to an abnormal growth of blood vessels.

Hemangiogenesis – It pertains to the specific growth of blood vessels.

Hematogenous spread – Spread through the bloodstream or by blood cells.

Hematopoiesis – The developmental process by which various types of blood cells are formed. The generation of hematopoietic cells from HSCs in the bone marrow or fetal liver.

Hematopoietic cells – Red and white blood cells (erythrocytes and leukocytes).

Hematopoietic stem cell (HSC) – Pluripotent hematopoietic precursor that either self-renews or differentiates into lymphoid, myeloid or mast cell precursors. It refers to the blood cells that give rise to all other blood cells- myeloid (monocytes, macrophage, etc.) and lymphoid lineages (B lymphocyte, T lymphocyte, and NK cell). The precursor cells that give rise to all types of blood cells. As stem cells, they are defined by their ability to maintain themselves (self-renewal) and to differentiate to form multiple cells types. In mammals, HSCs are located in the adult bone marrow.

Hematopoietic stem cell transplant (HSCT) – Replacement of a damaged immune system by transplantation of isolated healthy HSCs from a donor. The transfer of blood cell precursors from one individual into another. The transplantation of hematopoietic stem cells with blood-forming potential. Hematopoietic stem cells provide rapid and sustained reconstitution of blood formation and are found in adult bone marrow, umbilical cord blood, peripheral blood and in fetal liver.

Hemichordates – This phylum includes enteropneust worms and colonial pterobranchs. Hemichordates are tripartite as adults, having three body regions. The most anterior is the proboscis (protostome), then the collar (mesosome) and the posterior trunk (metasoma). These three regions are reduced and modified in colonial Pterobranchia.

Hemicellulose – Mixture of polymers found in plant cell walls that consist of several sugars, especially mannose, galactose, xylose, arabinose, and glucose.

Hemi-desmosome – Button like, intracellular complex that is anchored to an extracellular material via an anchoring collagen rod. It is differentiated from a desmosome that maintains cell-to- cell contact.

Hemimethylated – Methylated on only one strand.

Hemizygosity – State when only one copy of a gene is present in a diploid cell.

Hemodynamics – The study of the forces generated by the heart and the flow of blood through the cardiovascular system.

Hemogenic endothelium – A rare population of vascular endothelial cells that are able to differentiate into hematopoietic stem cells during embryogenesis, usually located in the lumen side of artery wall.

Hemolysin – Protein toxin that lyses red blood cells.

Hemolytic uremic syndrome – A condition caused by E. coli O157:H7 that causes bloody diarrhea and red blood cell or platelet destruction.

Hemophilia – Blood-clotting disorder. Wounds form only superficial scabs. Spontaneous bleeding without obvious cause may occur. There are several genotypes resulting in hemophilia.

Hemophiliac – An individual who lacks a functional gene for a clotting factor and therefore has reduced clotting capacity in his or her blood.

Henderson-Hasselbalch equation – An equation that can be used to determine pH, the dissociation constant, or the amounts of dissociated and nondissociated components of a buffer. 

Henle fiber – The long axon of a foveal cone that extends laterally to terminate outside of the fovea.

HEPA – High-Efficiency Particulate Air.

HEPA filter – An air filter that removes particles of the most penetrating size. There are, however, different grades of HEPA filters, which range from H10 through H14. The higher the grade, the higher the performance. 

Heparan sulfate (HS) – A component of the extracellular matrix, a polysaccharide that among its other functions, is critical for successful signaling of angiogenesis regulators during neovascularization.

Heparin sulfate proteoglycan (HSPG) – A kind of proteoglycans present abundantly on cell surface, in which heparin sulfate represents the glycan moiety. A macromolecule comprised of a core protein and glycosaminoglycan side chains of the heparin sulfate (polysaccharide) family, abundant in the extracellular matrix and sometimes associated with plasma membranes via lipid moieties. HSPGs are important for many signaling events as revealed by the effects of mutations in HSPG core proteins and synthesis enzymes (e.g., involved in appending the HS side groups).

Hepatitis – A medical condition defined by the inflammation of liver and characterized by the presence of inflammatory cells in liver tissue. The term hepais derived from the Greek word for “liver” and the term itis is derived from the Greek word for “inflammation.”

Hepatitis delta virus (HDV) – A single-stranded RNA satellite virus that has ribozyme activity.

Herceptin – Trade name of trastuzumab, a monoclonal antibody to the HER2 receptor on metastatic breast cancer cells that is used as a therapeutic treatment to block growth and spread of the cancer cells.

Heparin sepharose – This is a media used in chromatography that consists of beads coated with heparin. It is used to isolate heparin-binding molecules.

Hepatosplenomegaly – Enlargement of the liver and spleen.

Hepatotoxicity – The toxic effect of a substance on the liver. An organ that removes harmful substances from the body, the liver is exposed to chemicals and drugs that can cause inflammation (hepatitis) or necrosis of the liver cells.

Herd immunity – It is a form of indirect protection from infectious disease that occurs when a large percentage of a population has become immune to an infection, thereby providing a measure of protection for individuals who are not immune. Protection of non-immune individuals in a population from a given pathogen due to effective vaccination of the majority of the population.

Heritable – A trait that is passed from the parent to the offspring.

Herpesvirus (or herpes virus) – In reference to eye infections, the form that usually infects the eye is Herpes simplex type I or type II. This is a virus whose capsid is filled with double stranded DNA. See text for more information. Family of DNA-containing viruses that cause a variety of diseases and sometimes cause tumors. They contain dsDNA and an outer envelope surrounding the nucleocapsid.

Herpes gladiatorum – A skin infection caused by herpes simplex virus 1 (HSV1).

Herpes zoster – A skin rash better known as shingles.

Herpes zoster opthalmicus – The reactivation of varicella-zoster virus around the eye.

Hertwig’s epithelia root sheath – A proliferation of epithelial cells located at the cervical loop of the enamel organ in a developing tooth. Hertwig’s epithelial root sheath initiates the formation of dentin in the root of a tooth by causing the differentiation of odontoblasts from the dental papilla.

Heterochromatic flicker photometry – The adjustment of the radiant power of one of two spatially coextensive lights presented in alternating sequence at a temporal frequency such that there is a unique value of the radiant power where the sensation of flicker is minimum; that is, with a higher or lower radiant power, the sensation of flicker becomes greater.

Heterochromatin – Tightly packed form of chromatin that is found in centromeres and telomeres; histone 3 is di- and tri-methylated on lysine 9 (H3K9) in these regions of the genome.

Heterologous – Derived from a different species.

Heterologous expression – Describes protein or RNA expressed from a promoter other than its original promoter and/or from another chromosomal/plasmid region and/or in another organism.

Heteroplasmy – Presence of different mitochondrial (or chloroplast) genomes in a single individual.

Heterotaxy – Discordance of sidedness of the organ systems.

Heterozygosity – The presence of different alleles of a gene in one individual or in a population; a measure of genetic diversity.

Heterozygote – Refers to a particular allele of a gene at a defined chromosome locus. A heterozygote has a different allelic form of the gene at each of the two homologous chromosomes.

Heterozygous- Containing different copies of the chromosome pair. A person is usually referred to as heterozygous for a mutation or DNA variant if the copy (allele) on the other chromosome is normal.

Hexon – Protein subunit of virus capsid with six-fold symmetry that is therefore surrounded by six neighboring subunits.

HGP – Human Genome Project.

HGPPS (Horizontal gaze palsy and progressive scoliosis) – An autosomal recessive disorder marked by congenital absent or almost absent horizontal gaze (not caused by DRS) and severe, progressive scoliosis typically beginning in early childhood; caused by homozygous mutations in ROBO3.

HGVS – Human Genome Variation Society.

HHMI – Howard Hughes Medical Institute.

High endothelial venules (HEVs) – Specialized post-capillary venules in most secondary lymphoid tissues that allow lymphocyte extravasation from the blood into these sites. They have an endothelium of bright roundish cells compared to the ordinary flat dense ones. They are located in lymphoid tissues and have tissue-specific adhesion molecules (vascular addressins) on the cell surface that specifically interact with homing receptors on circulating lymphocytes in order to maintain a regulated immigration of lymphocytes into the tissue.

High-order wave front aberrations – Wave-front aberrations that are expressed using cubic, or higher, powers of the light ray’s distance from the pupil center to predict the amount of aberration.

High-pressure liquid chromatography (HPLC) – A type of chromatography in which a liquid phase containing a mixture of molecules is passed over a solid phase under high pressure.

High-throughput screening – High-throughput analyses used in pharmaceutical research. Potential drugs (drug candidates) are tested in miniaturized cell cultures with automated systems that enable the screening of hundreds of molecules or different culture conditions.

High-throughput sequencing – A rapid method of determining a DNA sequence.

Hilus – The concave part of an organ that serves as the entry and exit point for blood and lymphatic vessels.

Hindgut – Posterior-most region of the digestive tract.

Hinge region – Site in the Ig monomer where the Fab region joins the Fc region.

Histamine – A chemical derivative of the amino acid histidine that causes white blood cells to be released from blood vessels as part of an inflammatory mechanism. A major vasoactive amine released from mast cells and basophils.

Histocompatibility – Ability of a recipient to accept a tissue graft from another individual.

Histocompatible – A tissue or organ from a donor (the person giving the organ or tissue) that will not be rejected by the recipient (the patient in whom the tissue or organ is transplanted). Rejection is caused because the immune system of the recipient sees the transplanted organ or tissue as foreign and tries to destroy it. Tissues from most people are not histocompatible with other people. In siblings, the probability of histocompatibility is higher, while identical twins are almost always histocompatible.

Histology – The study of tissues with the aid of a microscope.

Histone – A basic protein that binds to DNA in order to compact and store it within the cellular nucleus. Special positively charged protein that binds to DNA and helps to maintain the structure of chromosomes in eukaryotes.

Histone acetyl transferase (HAT) – Enzyme that adds acetyl groups to histones.

Histone deacetylases (HDACs) – Enzyme that removes acetyl groups from histones.

Histone modification – The addition of methyl or acetyl groups onto histones that modulates the access various transcription regulators has to genes.

Histones – A group of alkaline proteins associated with DNA in nucleosomes, the basic DNA packaging unit in a chromosome. Proteins located in the eukaryote cell nucleus and in archaebacteria. They are the main protein constituents of chromosomes and are strongly associated with DNA whose compaction they enable by forming the nucleosome.

Histopathological – Dealing with the minute structure of diseased tissues.

Histopathology – Pathologists render diagnoses by examining biopsied specimens. Sampled tissues are fixed in formalin and embedded in paraffin (wax). Thin slices of the paraffin-embedded tissues are mounted on glass slides and stained so that the cellular detail can be visualized under a microscope. A histopathologic diagnosis is based on finding specific cellular alterations that characterize diseases.

Histoplasmosis – A disease of the reticuloendothelial system that is concerned with blood formation and destruction as well as other functions. In the eye, the disease can affect the retina.

HIV (human immunodeficiency virus) – The member of the retrovirus family that causes AIDS. Human immunodeficiency virus (HIV). HIV infection causes AIDS.

HLA genes – Family of genes for proteins found on the cell surface and acting in cell recognition. 

HLA complex – Human leukocyte antigen complex. Human major histocompatibility complex (MHC).

HLA typing – Identification of HLA alleles expressed on an individual’s cells. Used to determine the degree of HLA mismatching between a donor and recipient in a transplant situation.

HMI – Processing Terminals/Human Machine Interface

Hodgkin’s lymphoma – Lymphoma in which the tumor mass is made up of a reactive infiltrate of non-trans- formed lymphocytes, macrophages and fibroblasts plus scattered, malignant Reed–Sternberg cells.

Hole – The absence of an electron from an atom. Used in combination with electrons to create current in a semiconductor.

Homeobox – Genes that code for transcription factors involved in anatomic development in animals, fungi, and plants. Hox genes are homeobox genes found in animals that determine the axial relationship of organs. Mutations of homeobox genes are associated with remarkably specific, often isolated, anatomic alterations. Examples are: MSX2 homeobox gene mutation, which produces enlarged parietal foramina; PITX1 homeobox gene mutation, which produces Rieger syndrome (hypodontia and malformation of the anterior cham- ber of the eye including microcornea and muscular dystrophy); PITX3 homeo- box gene mutation, which produces anterior segment dysgenesis of the eye, moderate cataracts, and anterior segment mesenchymal dysgenesis; NKX2.5 homeobox gene, which produces atrial septal defect and atrioventricular conduc- tion defects; SHOX homeobox (short stature homeobox) gene mutation causes Leri–Weill dyschondrosteosis (deformity of distal radius, ulna, and proximal carpal bones as well as mesomelic dwarfism). The reason why homeobox muta- tions tend to produce diseases in isolated anatomic locations or involve some specific function probably results from the coordinated regulatory activity of the individual homeobox genes. For example, one gene might regulate the syn- thesis of a group of proteins exclusively involved in growth of particular skull bones; another homeobox gene might regulate proteins involved in insulin pro- duction. Disorders caused by alterations in homeobox genes include: aniridia, Axenfeld–Rieger syndrome, branchiootorenal syndrome, coloboma, combined pituitary hormone deficiency, congenital central hypoventilation syndrome, congenital fibrosis of the extraocular muscles, congenital hypothyroidism, craniofacial-deafness-hand syndrome, enlarged parietal foramina, hand-foot- genital syndrome, Langer mesomelic dysplasia, Leri–Weill dyschondrosteosis, microphthalmia, Mowat–Wilson syndrome, nail–patella syndrome, forms of non-syndromic deafness, non-syndromic holoprosencephaly, Partington syn- drome, Potocki–Shaffer syndrome, renal coloboma syndrome, septo-optic dysplasia, Turner syndrome, Waardenburg syndrome, Wilms tumor aniridia genitourinary anomalies and mental retardation syndrome, Wolf–Hirschhorn syndrome, X-linked infantile spasm syndrome, X-linked lissencephaly.

Homeostasis – The maintenance of a steady internal condition despite changes in the external environment. The natural state of physiological balance of all organs, tissues and cells within a living organism. The process of active regulation of bodily components so that their concentration remains within very tight limits.

Homing receptors – Receptors expressed by lymphocytes that direct lymphocyte trafficking by binding to specific addressing expressed on particular tissues at particular times.

Homologous – Characteristics that are similar because they originated from a common ancestor.

Homologous cosuppression – A type of RNAi in which multiple copies of a transgene decrease the expression of related host genes.

Homologous recombination – A type of genetic recombination involving exchange of homologous or similar DNA sequences. Switching of DNA pieces between two strands of DNA that is initiated by two regions of the DNA with very high homology. A technique used to inactivate, or “knock out,” a gene to determine its function in a living animal. The process of homologous recombination is more efficient in embryonic stem cells than in other cell types. It is achieved by introducing a stretch of DNA that is similar or identical (homologous) to part of a gene and to some of the DNA surrounding the gene, but different (not homologous) to a specific section of the gene. The DNA is then introduced into the stem cells and the stretch of homologous DNA will recognize the similar sequences of the gene within the cell, and replace it. But the cell is then left with a piece of DNA in the gene that has the wrong sequence and this interrupts the function of the gene. The gene is then said to be knocked out, and this provides important information about how the gene works.

Homology – Relation by descent, inferred by similarity. Often used synonymously with ‘similarity’. Similarity between two sequences because of their evolu- tion from a common ancestor often referred to as homologs.

Homozygote The same allelic form of a gene on each of the two homologous chromosomes.

Homology modeling – The use of similar protein sequences with known structures in protein modeling.

Homology-directed repair (HDR) – A natural repair mechanism in cells to repair dsDNA lesion when homologous DNA or template is available to cells. In genome editing, a homologous DNA is supplied that can be incorporated into genome for achieving desired cells function. In vitro Experiment performed in a laboratory dish or test tube or artificial environment. In vivo Experiment performed inside the living organism.

Homoplasmy – Condition in which the population of mitochondria within an individual are all identical.

Homozygosity – Occurs when only one allele of a gene is expressed in cells. This may occur when both of the inherited alleles of a gene (the maternally derived allele and the paternally derived allele) are identical to each other. It may also result when the expression of one of the inherited alleles is unattained or lost, in which case homozygosity is said to result from loss of heterozygosity.

Homozygosity mapping – A genetic mapping technique that can be used to identify a gene mutation for an autosomal recessive condition specifically when the mutation is segregating within a small, closed population. In this situation the inherited disease occurs when affected individuals inherit two copies of the same mutation from a common ancestor. As the affected individuals are likely to be homozygous for the DNA surrounding the gene mutation, techniques are used to survey the genome and identify regions of overlapping homozygosity that may contain the disease gene.

Homozygous- Containing the same copy of the chromosome pair. A person is homozygous for a mutation or DNA variant if it is present on both copies (alleles) of a gene.

Horizontal gene transfer – The transfer of genetic material from one biological entity to a genetically unrelated organism.

Horizontal transmission – Transmission between individuals of the same generation.

Hormonal response – The physiological response to a hormone is brought about either by a biochemical receptor-second messenger cascade or by a biochemical receptor-enhancer interaction. The first mechanism activates several enzymes in sequence while the second either promotes or inhibits protein synthesis at the DNA level.

Hormone – A chemical messenger, belonging to several classes, released from cell-to-cell in the bloodstream (or the interstitial fluid) or released within the confines of a single cell. Originally, a hormone was only considered to be a substance that was released from a cell and delivered via the bloodstream to another cell. That concept is now outdated. Molecule that carries signals inside multicellular organisms. Chemical messenger substances produced and secreted by cells in specific organs which are targeted to other body regions to elicit an effect. The process could be compared to neurotransmission. However, the speed at which the hormone signals are transduced is significantly slower. The time lapse between hormone secretion and effect can vary between hormones.

Horner’s syndrome -A lesion in a sympathetic autonomic nerve that results in reduced pupil size and causes the eyelid to droop on the affected side.

Horopter – The locus of points in space imaged on corresponding regions of the two retinae that results in identical visual directions (singleness).

Horseradish peroxidase (HRP) – An enzyme extracted from horseradish root used to visualize the location of the attached molecule (such as DNA or antibody); the enzyme oxidizes various substrates, such as luminol that releases light when it reacts with HRP.

Host – The organism in which the infectious agent resides.

Host range – The species that can be infected by a particular virus.

Hot markets – Occur when the stock prices of new securities rapidly increase above their offering prices, with this phenomenon lasting for an extended period of time.

Housekeeping genes – Genes that are switched on all the time because they are needed for essential life functions.

HOX genes – Code for a family of conserved transcription factors that regulate the spatial organization of the embryonic body and that contribute to the cell specification of several differentiation processes. In mammals, there are 39 HOX genes that are classified into four groups (HOXA, HOXB, HOXC and HOXD), with a precise spatiotemporal coordination of their respective expressions.

HPO – Human Phenotype Ontology (HPO).

HPW – High Purity Water (HPW).

hRS – Human retinoschisin (hRS).

HUGO – Human Genome Organization.

Human chorionic gonadotropin (hGC) – Hormone produced by the placenta during pregnancy.

Human Embryonic Stem Cells (hESCs) – Early stage cells that can become any type of cell in the body. They come from blastocysts leftover from infertility treatments that would otherwise be destroyed. Smaller than the point of a needle, these blastocysts are grown in a Petri dish. They are small clumps of cells, 5 to 7 days old- long before a foetus would be formed. They have also known as human pluripotent stem cells, as they can give rise to all cell types of the body.

Human factor IX – One of the proteins involved in blood clotting.

Human Genome Project – A program to determine the sequence of the entire three billion bases of the human genome.

Human genome project – An international research study that sequenced the entire human genome and determined the genes that are encoded.

Human herpesvirus 8 (HHV8) – Virus of the herpesvirus family that causes Kaposi’s sarcoma, often seen in AIDS patients.

Human immunodeficiency virus (HIV) – The member of the retrovirus family that causes AIDS.

Human leukocyte antigen (HLA)These are the proteins expressed on the cellular surface and play an important role in alloimmunity. HLA can be divided into (HLA-A, B, and C) which are encoded by class I MHC and are expressed on all cell types and present peptides derived from the cytoplasm and are recognized by CD8+ T cells. The other HLA type is classified as (HLA- DP, DQ, and DR) which are encoded by MHC II and can be found on antigen-presenting cells (APCs) and this class is recognized by CD4+ T cells. A system of the major histocompatibility complex (MHC) in humans. It contains of a number of genes and their respective encoded proteins (that can act as antigens). The term HLA is frequently used to describe immunological self and nonself in the context of transplant rejection. HLA is any human Class I or II MHC protein. These proteins are critical for distinguishing between host and foreign cells. Another name for the proteins of the major histocompatibility complex (MHC) of humans, due to their presence on the surface of white blood cells.

Human Subjects – The participants who volunteer to accept the risks and take part in a clinical trial. Their rights and welfare must be safeguarded by the investigator.

Humanized (of an antibody) – Replacing all of a protein, except the antigen-binding region, with human-encoded sequences.

Humanized antibodies – Engineered antibodies in which the V domains of non-human antibodies that recognise a human antigen are combined genetically with the C domains of human antibodies.

Humoral immunity – Adaptive immune responses mediated by B cells that differentiate into plasma cells producing antibodies. An immune response involving the activities of antibodies. Type of immunity that relies on B cells to produce antibodies.

Huntingtons disease – Inherited defect affecting nerve cells that results in loss of control of the limbs, impaired cognition, and dementia.

Humoral response – The immune response carried out by B lymphocytes and antibodies.

Hurlers syndrome – A mucopolysaccharidosis characterized by a deficiency of a-iduronidase.

HVAC – Heating, Ventilation, and Air conditioning (HVAC).

HVEM (herpes virus entry mediator) – It is a membrane protein that belongs to TNF-α superfamily.

Hyalocytes – The monocytic cells that reside in vitreous through life and have been called the dendritic cell of vitreous. These cells are capable of producing many of the angiogenic and antiangiogenic factors found in vitreous.

Hyaloid vasculature – This occupies the vitreous during fetal life and then regresses to become a vestige called Cloquet’s canal. This vasculature has its origins in the central retinal artery and is composed of the hyaloid artery, the vasa hyaloidea propria, which nourishes retina before it is vascularized, and the tunica vasculosa lentis, which nourishes the lens during development.

Hyaluronic acid – A non-sulfated glycosaminoglycan that is a major component of vitreous and other extracellular matrices throughout the body. Also known as hyaluronate to refer to its ionized form as it exists in the vitreous. A long chain and principal GAG in the vitreous.

Hybrid drugs – Are a third classification by EMA to describe drugs that meet neither the reference medicinal product nor generic medicine definition for drugs.

Hybrid dysgenesis – A genetic mechanism causing abnormally low frequency of viable offspring in a mating between two parents.

Hybridization – Pairing of single strands of DNA or RNA from two different (but related) sources to give a hybrid double helix. 

Hybridization – 1) The complementary binding of a probe to a portion of DNA. Technique used in molecular genetics- experimental joining of nucleic acid strands (DNA or RNA) sequences, based on the principle that single strands connect to other single strands with identical or similar structure by forming hydrogen bonds. 2) Cross-breeding of closely related species.

Hybridoma – A cell made by researchers in which an antibody-producing cell (B cell) is fused with a myeloma cell to form a self-proliferating cell that produces one specific monoclonal antibody. An immortalized cell secreting large amounts of pure monoclonal antibody of a single known specificity; created by fusion of a myeloma cell with an activated B cell producing antibody of known specificity.

Hybridoma cells – see hybridoma technology.

Hybridoma technology Method – used in the production of monoclonal antibodies. B-lymphocytes are fused with cancer (myeloma) cells. The myeloma cells cannot die through apoptosis, which means that the hybridoma cells that produce the antibodies have an unlimited division potential.

Hydraulic conductivity (Lp) – A measure of the ease with which a fluid passes through a tissue: Lp=Q/A/DP where A is the cross-sectional area of the tissue facing flow.

Hydrogen bond -A relatively weak bond between a hydrogen atom and an atom of oxygen or nitrogen. Such bonds are temporary, but their number can be quite large and influential. They occur very often between water and their solutes or within protein structures themselves.

Hydrogen peroxide – H2O2; has a cytotoxic as well as a caustic effect and can act as a reducing agent. Metabolically produced hydrogen peroxide is cleaved by the enzyme catalase to O2 and H2O.

Hydrolase –Type of enzyme that degrades its substrate by hydrolysis.

Hydrolysis – A chemical reaction in which ionic components of H2O are bound to cleavage sites in a molecule. Chemical reaction whereby molecules are cleaved by reacting with water: AB + H2O → AH + BOH.

Hydrolysis reaction – Cleavage of a compound by the addition of a water molecule.

Hydrophilic – A molecule that associates with water.

Hydrophobic – The property of being lipid soluble or soluble in organic solvents such as hexane. The name literally means water hating or fearing.

Hydrostatic pressure – The pressure (force per unit area) in a liquid. The physical pressure of a fluid within a vessel or some container.

Hygiene hypothesis – The theory that excessive zeal in preventing exposure to pathogens in infancy leads to a lack of activation of the immature immune system. The resulting bias toward Th2 responses may predispose an individual to hypersensitivity and/or autoimmunity.

Hyperactivated macrophage – See macrophage.

Hyperacute graft rejection (HAR) – Extremely rapid destruction of a graft almost immediately after transplantation.Mediated by classical complement activation initiated by pre-formed antibodies recognizing allogeneic epitopes on the graft vasculature.A form of type II hypersensitivity.

Hypermetropia – Also known as farsightedness, it is a defect of vision caused by an imperfection in the eye (often when the eyeball is too short or when the lens cannot become round enough), causing difficulty focusing on near objects.

Hyperosmotic – A condition (e.g., renal medulla) in which the dissolved components in one compartment are more highly concentrated than those in another compartment.

Hyperpolarization -Increase in the negative charge (usually) within a cell.

Hypersensitivity – An immune reaction, usually harmful to the host, caused either by antigen-antibody reactions or by cellular immune processes. See immune hypersensitivity.

Hypervariable region – Region of extreme amino acid variability in the V domain of an Ig or TCR chain. The hypervariable regions largely form the antigen-binding site. Also known as complementarity-determining regions (CDRs).

Hypertelorism – Abnormally large spacing between the eyes. Hypohydrosis – Diminished sweating response.

Hyperthyroidism -Any condition in which the thyroid gland releases more than the normal amount of T3 and T4. One form of hyperthyroidism is Graves’ disease.

Hypertonic – A term describing a concentration of solutes that is greater than normal for the body.

Hypertrophy – An increase in bulk without concomitant multiplication of parts.

Hypodermis – Fatty layer of the skin below the dermis.

Hypodontia – Tooth agenesis (the congenital absence of one or more teeth).

Hypomorphic allele – A mutant allele that results in reduced activity or level of the protein.

Hypoosmotic – A condition in which the dissolved components in one compartment are less concentrated than those in another compartment.

6HIS – Six tandem histidine residues that are fused to proteins, thus allowing purification by binding to nickel ions that are attached to a solid support. Also known as polyhistidine tag.

Hypoplasia – A clinical term for the reduced size of an organ or structure, often caused by disruptions in embryonic development. Underdevelopment or incomplete development of a tissue or organ.

Hypotelorism – Abnormally small spacing between the eyes.

Hypotrichosis – Abnormal hair loss.

Hypothalamic function -A brain function attributed to the hypothalamus, the region of the brain that forms the floor and part of the wall of the third ventricle. Nucleated cells of the region control body housekeeping functions such as temperature, sleep, and water balance.

Hypothesis-generating research – Research intended to investigate previously unexplored or under-explored areas to begin the data accumulation process needed to develop hypotheses.

Hypothesis-testing research – Research designed to produce statistical support or refutation of a formally articulated research hypothesis.

Hypotonic – A term describing a concentration of solutes that is less than normal for the body.

Hypoxia – Low levels of oxygen in the blood. A biological condition in which cells suffer from insufficient amount of oxygen. A condition in which the body or a region of the body is exposed to low oxygen supply.

Hypoxia inducible factors (HIFs) – Transcription factors that respond to decreases in oxygen.

Hypoxia-inducible factor-1a (HIF-1a) – A bHLH transcription factor regulated by hypoxia.


ISO Classifications

ISO 9: A space that has been classified to meet ISO 14644 requirements (35,200,000 particles/m3) for airborne 0.5μm particulate in the “in-operation” state. This classification does NOT actually appear in FDA guidance, but is found in some FDA regulated facilities.

ISO 8: A space that has been classified to meet ISO 14644 requirements (3,520,000 particles/m3) for airborne 0.5 μm particulate in the “in-operation” state.

ISO 7: A space that has been classified to meet ISO 14644 requirements (352,000 particles/m3) for airborne 0.5 μm particulate in the “in-operation” state.

ISO 6: A space that has been classified to meet ISO 14644 requirements (35,200 particles/m3) for airborne 0.5 μm particulate in the “in-operation” state.

ISO 5: A space that has been classified to meet ISO 14644 requirements (3,520 particles/m3) for airborne 0.5 μm particulate in the “in-operation” state. These spaces are normally constructed with unidirectional flow with an air velocity of .20 to .45 m/s

IB – Investigators’ Brochure (IB)- a document provided by the sponsor to investigators in a multisite clinical trial, with sufficient information about the investigational new drug, the preclinical data that support the safety and activity of the product, and any prior human experience, which permits the investigators to make informed decisions while conducting the clinical trial to protect the human subjects participating in the trial.

IBC – Institutional Biosafety Committee (IBC) – a standing committee within a research institution that reviews research using recombinant DNA technology. Human research of biotechnology medicinal products may require review by an IBC before and while the research is being performed.

IBC – International Building Code

IBD – Inflammatory bowel disease (IBD).

ICAM1 (intercellular adhesion molecule 1) – Protein found on the surface of animal cells that is used as a receptor by many viruses of the picornavirus family.

ICC – Inherited cardiac condition (ICC).

Ice nucleation factor – Protein that acts as a seed for ice crystals to form.

ICF – Informed Consent Form (ICF)- the process of informed consent is essential and central to clinical research ethics and the basic principle of “respect for persons.” The form is just one part of the informed consent process in which potential trial participants are fully informed about the study in which they may volunteer to participate before gaining their consent to enroll them in the study. The form is the written documentation that is proof of the informed consent process and is an “essential document” in terms of GCP.

ICGC – International Cancer Genome Consortium.

ICH – International Council for Harmonisation of Technical requirements for Pharmaceuticals for Human Use – an organization the original intent of which was to agree to harmonized regulatory policies and guidelines for the United States, EU, and Japanese medicinal products regulators and the pharmaceutical industry, with observers from numerous other countries. The Council has now been broadened to include several other countries for whom their guidelines would require adherence.

Icosahedron – A 20-sided figure where each side is an equilateral triangle.

ID – Intellectual disability (ID).

IDAC – International Data Access Committee (IDAC).

IDE – Investigational Device Exemption (IDE)- comparable to the IND for drugs and biologicals, this is the type of application submitted to U.S. FDA for review of investigational devices.

Identity method/test – The method used to determine that a product is what it is labeled to be and not something else, such as breakdown products or other materials manufactured or used within the same facility.

Identity by descent – Alleles in an individual or in two people that are identical because they have been inherited from the same com- mon ancestor, as opposed to “identity by state”; that is, coinci- dental possession of similar alleles in unrelated individuals (see Consanguinity).

Iduronic acid – An isomer of glucuronic acid. See Glucuronic acid.

IEST – Institute of Environmental Sciences and Technology

IFI16 (interferon gamma-inducible protein 16) – It is a type of pattern recognition receptor (PRR) that recognizes the DNA genome of DNA viruses. It is also known as a “nuclear DNA sensor.”

Ig domain – Protein motif of 70–110 amino acids with intrachain disulfide bond. Folds back on itself to form a characteristic Ig barrel (or Ig fold) structure. Mediates inter- and intramolecular interactions.

Ig superfamily – Group of proteins in which each contains one or more Ig domains.

IGF1 gene – Gene that encodes insulin-like growth factor 1.

Igα/Igβ complex – Accessory heterodimer within the BCR complex. Required to transduce intracellular signaling initiated by mIg engagement by antigen.

Immediate hypersensitivity – See type I hypersensitivity.

Immobilisation – In biotechnology, cells or enzymes can be attached to the surface, cross- linked or included in various types of matrices. Thus, biocatalysts can be recycled more easily in industrial processes. Immobilization can also enhance the stability of the system.

Immune blockade – Artificial interference with T cell negative regulatory molecules like CTLA-4 and PD-1 to liberate protective T cell responses, or with T cell costimulatory molecules like CD28 and CD40 to shut down harmful T cell responses.

Immune complex – Lattice-like structure composed of interlinked antigen–antibody complexes. Large immune complexes are insoluble and can become trapped in vessel walls or narrow body channels, provoking inflammation and type III hypersensitivity. Cluster formed by the binding of antigen by

Immune deviation – Conversion of an adaptive immune response that is harmful to a less harmful response via a switch between Th1 and Th2 responses. A form of peripheral T cell control.

Immune hypersensitivity – Excessive immune reactivity to a generally innocuous antigen that results in inflammation and/or tissue damage. Includes type I–IV hypersensitivities.

Immune memory – Memory of antigens previously encountered by the immune system due to specialized memory B cells.

Immune privilege – Property of certain anatomical sites in which immune responses are actively or passively sup- pressed.

Immune regulation (tolerance) – The absence of an im- mune response to a given antigen due to the regulation of the activities of effector leukocytes.

Immune response – A coordinated action by numerous cellular and soluble components in a network of tissues and circulating systems that combats pathogens, injury by inert materials, and cancers. The immune reaction against an invader (e.g., a pathogen or foreign (transplanted) cells) that results in its removal or destruction.

Immune system – A system of cells, tissues and their soluble products that recognizes, attacks and destroys internal entities that threaten to endanger the health of an individual. In humans, there are three known host defense systems that recognize and destroy foreign organisms: intrinsic, innate, and adaptive. See Intrinsic immunity, Innate immunity, and Adaptive immunity.

Immunity – The ability to rid the body successfully of a foreign entity. The state in which a person is protected against becoming infected by a pathogen.

Immunity protein – Protein that provides immunity. In particular, bacteriocin immunity proteins bind to the corresponding bacteriocins and render them harmless.

Immunocompetent – Possessing a functional immune system.

Immunocompromised – Possessing a defective or reduced immune system.

Immunoconjugate – Chimeric protein in which a whole mAb (or a structural derivative of that mAb) is linked to a cytokine, radioisotope or toxin either chemically or at the DNA level.

Immunocytochemistry – Technique of visualizing specific cellular proteins by using antibodies. When the antibody binds the protein, the label reveals its position.

Immunodeficiency – A failure in some aspect of immune system function. See also primary immunodeficiency and secondary immunodeficiency.

Immunodominant epitope – The epitope against which the majority of antibodies is raised, or to which the majority of T cells responds.

Immunofluorescence- Usually used to demonstrate the presence of a protein in or on a cell; a fluorescently labeled antibody binds to another antibody that in turn recognizes a specific protein, usually in a tissue or cell. In the dark, the fluorescent label can be excited by light of a particular wavelength and the resulting fluorescent signal can be seen in a microscope. This shows where the labeled protein is and how much of it is present.

Immunogen or Immunogenic – An antigen that can induce lymphocyte activation. A substance that elicits an immune response.

Immunoglobulin (Ig) – A protein that binds to an antigen at its epitope or antigenic determining site. Antigen-binding protein expressed by B lineage cells. An Ig monomer is composed of two identical light and two identical heavy chains (H2L2). In its plasma membrane-bound form, an Ig is the antigen-binding component of the BCR complex. In its secreted or secretory form, an Ig is an antibody. Another name for antibody proteins.  Class of proteins with a characteristic structure that enables them to act as receptors and effectors within the immune system. Membrane-bound or soluble antigen-binding proteins produced by plasma cells (B cells).

Immunoglobulin G (IgG) – The class of antibody with a γ (gamma) heavy chain.

Immunohistochemistry – Technique of visualizing specific proteins in a tissue section using labeled antibodies.

Immunological memory – During the primary adaptive response to a pathogen, each antigen-specific lymphocyte clone that is activated generates many memory lymphocytes of identical specificity and greater affinity. When the same pathogen attacks the body a second time, it is eliminated more rapidly and efficiently by the secondary response mediated by the activation of these memory lymphocytes. It refers to the function of memory lymphocytes that are differentiated from the activated lymphocytes, and can swiftly respond to the antigens. The ability of lymphocytes to respond faster against a pathogen because the immune system has been previously exposed to the pathogen or parts of the pathogen.

Immunological synapse – An immunological synapse is the interface between an antigen-presenting cell or target cell and a lymphocyte such as an effector T cell, which is termed as an analogy to neural synapse. The contact zone between a T cell and an APC.

Immunology – The study of the cells and tissues that mediate immunity and the investigation of the genes and proteins underlying their function.

Immunopathic damage – Collateral damage to tissues caused by an immune response.

Immunoprivileged Sites- Locations in the body that are relatively well protected against attack by the immune system, such as brain, central nervous system, eye, and testicle.

Immunosenescence – As people age, the hematopoietic stem cells lose their ability to form new white blood cells, and result in an age-related decline in immune function.

Immunosuppressive molecules – Molecules, such as the cytokines IL-10 and TGFβ or certain drugs that reduce or eliminate immune responses.

Immunosurveillance – Concept that the immune system monitors the body for pathogens and tumor cells and destroys them.

Immunotherapy – The manipulation of the immune system to prevent, mitigate or cure disease.

IMPD – Investigational Medicinal Product Dossier—a submission to the EMA (or other regulators who use the same term) that provides information about the investigational new drug in terms of product information (chemis try, manufacturing, and controls) and preclinical data.

Imprinting- A form of epigenetic regulation where one of the two gene copies (alleles) are permanently inactivated. An example is the genes on the inactivated X chromosome in women. Early in mammalian embryogenesis, the pattern of epigenetic modifications (e.g., methylations) inherited from the paternal and maternal gametes is erased, forcing the embryo to develop its own unique pattern of methylations. This process of epigenome erasure is necessary; otherwise, the embryonic germline would have a differentiated epigenome, and the normal process of gradual epigenetic modifications, applied throughout embryogen- esis, could not occur. Erasure is not a totally thorough process. There are about 100 known genes that retain their parental epigenetic patterns. Retention of parental epigenetic patterns is known as imprinting. When imprinted genes contain disease-causing mutations, the disease that develops will express a phenotype that is influenced by paternal lineage. For example, Prader–Willi syndrome is a genetic disease characterized by growth disorders (e.g., low mus- cle tone, short stature, extreme obesity, and cognitive disabilities). Angelman syndrome is a genetic disease characterized by neurologic disturbances (e.g., seizures, sleep disturbances, hand-flapping), and a typifying happy demeanor. Both diseases can occur in either gender and both diseases are caused by the same microdeletion at 15q11-13. When the microdeletion occurs on the pater- nally derived chromosome, the disease that results is Prader–Willi syndrome. When the microdeletion occurs on the maternally derived chromosome, the disease that results is Angelman syndrome. Another example is the NOEY2 tumor suppressor gene, which is imprinted in females and which contributes to some cases of breast and ovarian cancers . See Loss of imprinting and Epigenomic syndrome. When the expression of a particular allele depends on whether it originally came from the father or the mother (imprinting is a rare exception to the normal rules of genetic dominance).

Imputation – In statistics, imputation is a process of replacing missing data with other estimated probable values. In genetics, imputation is a method used to fill in missing genotypes in a study dataset.

Inactivated virus vaccine – A vaccine that uses whole virus that is unable to infect because it has been treated with high heat or a chemical, such as formaldehyde.

Inadvertent autoinoculation – The accidental transfer of a virus from the site of vaccination to a distal site, such as the eye or face.

Incidence – The frequency of new cases among a population during a specific period.

Inclusion body – Visible structures formed by viral material that are observed in the nucleus or cytoplasm of a cell as a result of viral replication.

Incubation period – The time before which symptoms of an infection are apparent.

Incubator – A company or facility designed to foster entrepreneurship and help startup companies, usually technology-related, to grow through the use of shared resources, management expertise, and intellectual property.

Induction – The process by which prophage DNA is excised from a bacterial chromosome to begin a lytic replication cycle.

Innate immune system – The arm of the immune system that nonspecifically recognizes a pathogen and stimulates the adaptive immune response.

Initial public offering (IPO) – A company’s first offer to sell stock to the public. An investment bank typically underwrites these offerings. Historically, IPOs have been the most lucrative exits for venture capitalists.

InaZgene – Gene encoding ice nucleation protein of Pseudomonas syringae.

Incidence – How many individuals are diagnosed as having a particular condition over a certain period. The number of new cases of a disease occurring in a chosen time interval (e.g., 1year), expressed as a fraction of a predetermined population size (e.g., 100,000 people). For example, if there were 10 new cases of a rare disease occurring in a period of 1year, in a population of 50,000 people, then the incidence would be 20 cases per 100,000 persons per year. See Age-adjusted incidence and Prevalence.

Incidence rate – Is a   measure   of   the   frequency   with which a disease occurs within a population over a given period. A measure of the frequency with which a disease occurs within a population over a given period.

Incidental findings (IFs) – DNA sequence variants that cause a deleteri- ous phenotype in a subject that are not linked to the primary clinical presentation. For example, a coincidental finding may be that the subject has a breast cancer (BRCA1) mutation.

Inclusion bodies – Dense crystals of misfolded, nonfunctional proteins found in host cells that are expressing a foreign protein.

Inclusion criteria – In a protocol, the section in which medical, demographic, and psychosocial conditions or characteristics of subjects should be specified in precise detail.

Incomplete penetrance – Refers to the presence of a gene change that is not phenotypically expressed in some individuals but is expressed in others.

IND – Investigational New Drug Application – the submission made to the Food and Drug Administration gain exemption from marketing authorization in order to ship in interstate commerce an investigational (as opposed to marketed) new drug, for the purpose of conducting clinical trials.

Indel – Insertion and deletion. A variation (benign or pathogenic) caused by the insertion or deletion of 2 or more bases of DNA. 

Independent ethics committees (IECS) – The international counterparts of IRBs in the United States. Also called research ethics committees (RECs) or simply ethics committees (ECs).

Independent IRBs  – Institutional review boards (IRBs) set up largely by for-profit companies to provide IRB reviews for a fee.

Index subject – The primary subject of a study involving persons related, in some way, to the primary subject.

Indexing – Mixing multiple DNA samples together in one next-generation sequencing reaction. Each sample has a different barcode sequence in the adapters.

Indication – A clinical indication is the reason a medication or treatment is prescribed, the disease or condition and benefit provided by the therapy.

Indigo – Bright blue pigment based on the indole ring system.

Indirect allorecognition – Peptides derived from allogeneic proteins of the graft are presented to recipient T cells by recipient APCs. See also allorecognition.

Indole – Ring system containing nitrogen and found in tryptophan and indigo.

Indoleamine – Another name for serotonin. A neurotransmitter derived from the amino acid tryptophan.

Induced fit – Antigen influences the conformation of the antigen binding site of an antibody such that it better ac- commodities the antigen.

Induced Pluripotent Stem (iPS) Cells – A type of stem cell that is derived from somatic or non-pluripotent cell sources by misexpressingtran scription factors present in pluripotent stem cells. A method of “reprogramming” adult cells to a pluripotent state so that they can divide indefinitely and form all cells of the body. They are often referred to as iPS cells. The discovery of the reprogramming method resulted in a shared Nobel Prize for Shinya Yamanaka in 2012. Normal somatic cells from either mouse or human that can be induced to de-differentiate by expressing a cocktail of four different transcription factors that are only expressed in stem cells.

Inducer (signal molecule) –Molecule that exerts a regulatory effect by binding to a regulatory protein.

Inducible nitric oxide synthetize (iNOS) – Enzyme induced mainly in phagocytes by the presence of microbial products or pro-inflammatory cytokines. Generates nitric ox- ide, which is toxic to endocytosed pathogens.

Inducible promoter – A promoter that functions only under special circumstances.

Induction – Embryonic signal-calling, in which one group of embryonic cells emits a signal that influences the development of another group of cells. The process by which one group of cells signals to a second group in a way that influences their development. This is achieved through signaling by diffusible growth factors.

Inductive site – A local area of the mucosae where antigen is encountered and a primary mucosal response initiates.

Infection – The attachment and entry of a pathogen into a host’s body such that the pathogen successfully reproduces.

Infectious disease – A disease caused by an organism on or in the human body. The term “infectious disease” is sometimes used in a way that excludes dis- eases caused by parasitic animals. In this book, the term “infectious disease” is all-inclusive.

Infectivity -The ability of a virus to infect other cells in addition to the cell in which it is present.

Inflammasome – A protein complex expressed by white blood cells that acti- vates an inflammatory process. Some inflammasome proteins are caspase 1 and 5, and NALP. The inflammasome promotes other inflammatory cytokines and is part of the innate immune system. Cytoplasmic multimeric complex that ac tivates caspase enzymes required for the processing of certain pro-inflammatory interleukins into their active forms. See Innate immunity.

Inflammation – A local response at a site of infection or injury initiated by an influx of innate leukocytes that fight infections using broadly specific recognition mechanisms. Clinically, inflammation is characterized by heat and pain as well as swelling and redness. Also called inflammatory response. A process in which a local area of tissue becomes swollen, reddened and, possibly, pus-filled. Reaction to foreign particles and stimuli, resulting in redness, swelling, heat, loss of function and pain. The hallmark of an immune response characterized by edema, redness, and pain. Inflammatory mediators induce vasodilation of local vessels which are leaky and promote edema and facilitate immune cell infiltration. While inflammation controls infection, it can also cause tissue damage, as the effector function of the innate immune response is nonspecific. A localised protective reaction of tissue to irritation, injury, or infection, characterized by pain, redness, swelling, and sometimes loss of function.

Influenza virus – Member of the orthomyxovirus family with eight separate ssRNA molecules.

Informed consent – Explicit agreement to participate in a research study given by a decisionally capable adult. Subjects who are put at risk in an experimental study must first confirm consent. To this end, researchers must provide prospective human subjects with a consent form that informs the subject of the purpose and risks of the study, and discloses any information that might reasonably affect the par- ticipant’s decision to participate, such as financial conflicts of interest among the researchers. The informed consent must be understandable to laymen, must be revocable (i.e., subjects can change their mind and withdraw from the study), must not contain exculpatory language (i.e., no waivers of responsibility for the researchers), must not promise any benefit for participation, and must not be coercive.

Inhalational anthrax – Form of anthrax in which the spores of Bacillus anthracis enter via the lungs and the death rate is high.

Inhibition – The process of decreasing the normal velocity of an enzyme catalyzed reaction with an inhibitor substance.

Inhibitors of apoptosis (IAP) – A family of proteins that inhibit cell death by modulating caspases during apoptosis.

Initial public offering (IPO) – Refers to the process by which a firm sells its stock for the first time on an open, public market. The acronym IPO can also refer to the firm itself.

Initiation – In the field of cancer, the term “initiation” refers to the inferred changes in cells following exposure to a carcinogen that may eventually lead to the emergence of a cancer in the cell’s descendants. Though we know much about the many possible changes that can occur in cells exposed to carcino- gens, the essential and defining changes that begin the process of carcinogenesis are still unknown. The process that begins with initiation and extends to the emergence of a cancer is called carcinogenesis. In molecular biology, the term “initiation” has a distinctly different meaning, referring instead to the necessary molecular events that allow a process (e.g., replication, transcription, or transla- tion) to begin.

Initiation factor – Synonymous with translation factor; not to be confused with cancer initiation. Proteins that are required for the initiation of a new polypeptide chain. See Translation factor.

Initiator box – Sequence at the start of transcription of a eukaryotic gene.

Innate immunity – A person’s natural immunity as a result of their genetic make-up or physiology, not that arising from a previous infection or vaccination. An ancient and somewhat non-specific immune and inflammatory response system found in plants, fungi, insects, and most multicellular organisms. This system recruits immune cells to sites of infection, using cytokines (chemical mediators). Innate immunity includes the complement system, which acts to clear dead cells. It also includes the macrophage system, also called the reticuloendothelial system, which engulfs and removes foreign materials. Examples of rare, monogenic disorders of the innate immune system include: familial Mediterranean fever; TNF receptor-associated periodic syndrome; hyperimmunoglobulin D syndrome; familial cold autoinflammatory syndrome; Muckle–Wells syndrome; neonatal-onset multisystem inflammatory disease, also known as chronic infantile neurologic, cutaneous, and arthritis syndrome; pyogenic arthritis, pyoderma gangrenosum, and acne; Blau syndrome; early-onset sarcoidosis, and Majeed syndrome. See Adaptive immunity and Inflammasome.

Innate immunity – Non-specific mechanisms which either prevent the entry of pathogens or prevent them from causing disease.

Innate response – Non-specific and broadly specific mechanisms that deter entry or promote elimination of foreign entities. These include (1) physical, chemical and molecular barriers that exclude antigens in a totally non- specific way and (2) soluble and membrane-bound that recognize a limited number of molecular patterns that are common to a wide variety of pathogens or produced by host cells under stress.

Inner blood-retinal barrier – It regulates the transport of fluid, ions, and metabolites between the neurosensory retina and the retinal vasculature.

Inner Cell Mass (ICM) – The inner group of pluripotent cells in a blastocyst-stage embryo. Thickened area of cells of a blastula that forms by cell division and cell migration. A small group of cells attached to the wall of the blastocyst. Embryonic stem cells are made by isolating and culturing the cells that make up the inner cell mass. In development, it is the inner cell mass that will eventually give rise to all the organs and tissues of the future embryo and foetus, but do not give rise to the extraembryonic tissues, such as the placenta.

Inner-wall region – Comprised of the inner-wall endothelium of Schlemm’s canal, its basement membrane, and the adjacent juxtacanalicular tissue.

Innovation – Is an idea, practice or object this is perceived as new by an individual or other unit of adoption.

In-process – This term refers to material or intermediates that are taken from some step of the manufacturing process, but not necessarily the end material. For example, specimens taken during upstream or downstream pro cessing for quality control purposes or intermediate materials that will be stored before use in further downstream manufacture.

Insertion – Change in the DNA sequence involving an additional amount of DNA added in a new location. Mutation in which one or more extra bases are inserted into the DNA sequence.

Insertional mutagenesis – An alternation in gene sequence by addition of one or more base pairs. Insertion of a viral genome near endogenous genes, resulting in gene activation or silencing. Retrovirus-mediated insertional mutagenesis in hematopoietic cells can enhance self-renewal in vitro and cause cancer in vivo. Mutagenesis of DNA by the insertion of one or more bases. Insertional mutations can occur naturally, mediated by virus or transposon, or can be artificially created for research purposes in the laboratory.

Insertional activation – The activation of a gene as a result of retrovirus integration.

Insertional inactivation – The inactivation of a gene as a result of retrovirus integration. Inactivation of a gene by inserting a foreign segment of DNA into the middle of the coding sequence.

Insertional mutagenesis –  The modification of a gene as a result of retrovirus integration.

In situ – Latin for “in its place.” When referring to a cancer, in situ implies that the cancer has not invaded surrounding tissues and has not metastasized to lymph nodes or to distant organs. The term “in situ epithelial neoplasm” (i.e., neoplasms arising from mucosal surfaces, epidermis, or glandular tissues) is virtually synonymous with the alternate terms “intraepithelial neoplasm” or “epithelial precancer.” See Precancer.

In situ ethics – An approach to ethical discussion that emphasizes the importance of empirical data collection with the individuals involved in the practices being considered.

In situ hybridization – A technique used to detect RNA or DNA. In this case, it is used to localize messenger RNA (mRNA) in tissue sections using labeled complementary RNA as a probe. Hybridization of a labeled nucleic acid to a target nucleic acid that is typically immobilized on a microscopic slide, such as DNA of denatured metaphase chromosomes (as in FISH) or the RNA in a section of tissue [as in tissue in situ hybridization (TISH)].

In situ tissue engineering – Implantation of a construct, designed to mediate tissue healing and regeneration, into the body in the site from which the tissue was lost. Induced pluripotent stem (iPS) cells generated by the overexpression of specific transcription factors in mouse or human somatic cells, which are molecularly and functionally highly similar to ES cell counterparts.

International Committee on Taxonomy of Viruses – The international body responsible for the official naming and classification of viruses.

Intellectual property (IP) – A term used to describe intangible assets, such as knowledge, brand names, or patents.

Inspectorate – a federal agency in a country responsible for conducting inspections of facilities and/or investigators. This agency may be separate from the country’s NRA or NCL, if those agencies do not perform the inspections themselves.

Institutional review boards (IRBs) – The review bodies required by law and by international guidance documents to approve and monitor the conduct of human subject’s research.

Insulator – DNA sequences sometimes found between two genes or groups of genes, thus protecting them from the effects produced by other regulator sequences. These elements act as genetic barriers preventing interaction between enhancer/amplifier elements and the promoter. They can bind protein factors such as CTCF to form a physical barrier. DNA sequences that shield promoters from the action of enhancers and also prevent the spread of heterochromatin.

Insulator binding protein (IBP) – Protein that binds to insulator sequence and is necessary for the insulator to function.

Insulator sequence – A DNA sequence that shields promoters from the action of enhancers and also prevents the spread of heterochromatin.

Insulin – Small protein hormone made by the pancreas that controls the level of sugar in the blood.

Insulin and IGF-1 signal transduction pathway (IIS pathway) – Signal transduction pathway that is activated by insulin and insulin-like growth factor-1 (IGF-1), which controls cellular growth and is implicated in aging.

Insulin receptor – Protein on cell surface that acts as a receptor for insulin.

Insulin resistance – The physiologic state in which insulin target tissues in the periphery (mainly liver and muscle) become insensitive to insulin, thereby requiring elevated plasma insulin levels to elicit the same biologic effect. The process in which circulating insulin is not able to cause glucose uptake into insulin-dependent cells properly. This is usually associated with type 2 diabetes.

Insulin-like growth factor 1 (IGF1) – Peptide that stimulates the growth and division of certain animal cells.

Integral protein – A protein that exists in a bilipid membrane. Also known as an intrinsic protein. A protein possessing a portion embedded into a membrane, such as the plasma membrane. 

Integration – Performed by viruses, the process of joining the viral genome (or a cDNA copy) into the host chromosome. Internal ribosome entry site: A site within a piece of mRNA at which translation initiation factors and a ribosome can bind.

Integrase (intI) – Enzyme that inserts a segment of dsDNA into another DNA molecule at a specific recognition sequence. In particular, lambda integrase inserts lambda DNA into the chromosome of E. coli.

Integrin – Integrins are transmembrane proteins that mediate the attachment between a cell and its surroundings, such as other cells or the extracellular matrix (ECM).

Integron – Genetic element consisting of an integration site (for gene cassettes) plus a gene encoding an integrase.

Integron analysis – Identifying the genes embedded within integrons in order to identify useful new genes from the environment.

Intellectual property – Intangible products (e.g., methods, preparative pro- cesses, certain types of information) owned by their creator (i.e., a human or corporate entity). The owner has the right to determine how the intellectual property can be used and distributed. Protections for intellectual property come in three forms: (1) copyrights; (2) patents; and (3) secrecy (e.g., hiding the intel- lectual property from the public). Intellectual property can be sold outright, essentially transferring ownership to another entity. Alternately, intellectual property can be retained by the creator who permits its limited use to others via a legal contrivance (e.g., license, contract, transfer agreement, royalty, usage fee, and so on). The legal rules that apply to intellectual property may influence the cost and availability of new diagnostic tests and therapeutic interventions for the rare diseases.

Intercellular adhesion molecule (ICAM) – Molecules facilitating cell–cell and cell–matrix adhesion as well as extravasation. See also homing receptors and addressing.

Intercellular adhesion molecule 1 (ICAM-1) – An adhesion molecule (CD54 according to the immunological cluster of differentiation, CD, nomenclature) mainly on vascular endothelial cells which is upregulated in inflammation and promotes the increased immigration of leukocytes, that carry corresponding integrin receptors, into the tissue.

Interferon γ (INF γ) – Protein induced in animal cells in response to intracellular pathogens.

Interferon (IFN) – Family of proteins induced in animal cells in response to virus infection or intracellular pathogens. Group of cytokines in the immune system of vertebrates with a range of effects. They are glycoproteins produced by specific immune cells or virus-infected cells to strengthen the virus resistance of neighboring cells. Interferons are pharmaceutically relevant (e.g., in the treatment of hepatitis C). Recombinant interferons are therefore important biotech products. Interferons are a group of cytokines, which trigger the induction of a broad array of antiviral proteins. Interferons are named for their ability to “interfere” with viral replication by protecting cells from virus infections. Mediators which increase the resistance of cells to viral infection. A major family of cytokines.

Intermolecular region – Tissue between lymphoid follicles positioned in a group. Contains mature T cells surrounding HEVs.

Interferons α and β (INF α and INF β) – Proteins induced in animal cells in response to virus infection and that induce antiviral responses.

Interleukins (ILs) – A type of cytokine of the immune system contributing the organism’s response to microbial infection (increases lymphocyte proliferation) and to the auxiliary T lymphocyte response. Group of cytokines produced by activated macrophages and lymphocytes during an immune response. They transduce signals between various immune functions and control the development of cells. Subclass of cytokines involved in development of immune system cells. A group of molecules involved in signaling between cells of the immune system. A major family of cytokines.

Interleukin-4 (IL-4) – A cytokine that (among other effects) stimulates the division of B cells, which synthesise antibodies.

Intermediate host – Same as secondary host. An organism that contains a parasite for a period of time during which the parasite matures in its life cycle, but in which maturation does not continue to the adult or sexual phase. Maturation to the adult or sexual phase only occurs in the primary or definitive host. A parasitic eukaryotic organism may have more than one intermediate host. The survival advantages offered to the parasite by the intermediate host stage may include the following: to provide conditions in which the particular stages of the parasite can develop, which are not available within the primary host; to disseminate the parasite (e.g., via water or air) to distant sites; to protect the immature forms from being eaten by the adult forms; to protect the parasite from harsh conditions that prevail in the primary host; to protect the parasite from external environmental conditions that prevail when the parasite leaves the primary host. See Primary host.

Intermediate mesoderm (IM) – A strip of mesenchyme adjacent to the somites that is the embryonic source of all kidney tissue.

Intermediate Precision – Also known as interassay variability. The impact of use of different equipment or differ ent reagent lots or analysis by different operators on an analytical method’s performance.

Internal rate of return (IRR) – A term which is equivalent to the compound rate of return of an investment. The discount rate that makes the net present value (NPV) equal to zero is the IRR.

Internal ribosomal entry site (IRES) – Sequence allowing the translation of multiple coding sequences on the same message in a eukaryotic cell. IRES sequences are found on some animal viruses.

Interpenetrating polymeric networks (IPNs) – Polymeric structures comprising two or more networks that are interconnected on a molecular scale through chemical (covalent) and physical bonds.

Interstitial – In between structures, or spaces within a structure.

Interstitial deletion – See Contiguous gene deletion and Microdeletion.

Interventional trials – Part of the clinical trials process that determines whether experimental treatments or new ways of using known therapies are safe and effective under controlled environments.

Interzone – A region of non-chondrogenic cells that forms at the site of a future joint.

Intestinal follicles – Lymphoid follicles located in the intestinal lamina propria, either grouped in Peyer’s patches or in the appendix, or scattered singly. Composed of a germinal center containing B cells and FDCs topped by a dome containing APCs and T cells.

Intestinal stem cells – Epithelial SCs of the intestine that ensure the extremely rapid renewal of the intestinal epithelium at the origin of different cell types of the intestinal epithelium.

Intracellular bacteria – Bacteria that must enter host cells to reproduce.

Intracellular pathogen – Pathogen that spends a significant portion of its life cycle within a host cell; reproduction is usually within the host cell.

Intracellular signaling – The binding of a ligand to its recep tor initiates a series of interactions between various proteins which culminate in the activation of transcription factors that enter the nucleus and alter the transcription patterns of genes controlling cellular proliferation, differentiation and effector functions.

Intracultural mesenchyme – The non-ossified or undifferentiated cells located between opposing osteogenic fronts of membranous bones.

Intraepithelial lymphocytes (IELs)– αβ and γδ T cells dispersed among the epithelial cells lining a body tract.

Intraepithelial neoplasm – A term applied to an early stage of growth of epi- thelial tumors, primarily tumors that arise from the epithelial cells, such as those found on epithelial surfaces lining various tissues (such as the mucosal lining of the gastrointestinal tract or the epidermal surface of the skin). The word intraepithelial conveys the idea that the malignant cells reside within the epithelium, and have not invaded down into the underlying connective tissues. Intraepithelial neoplasms are subtypes of precancers. See In situ and Precancer.

Intraepithelial pocket – Pocket within the FAE created by invagination of the basolateral surface of an M cell. Invariant chain (Ii) Transmembrane protein that binds to the peptide-binding groove of a newly synthesized MHC class II molecules and chaperones it out of the rER into the endocytic system. Upon cleavage, Ii gives rise to CLIP.

Intramembranous ossification – The process of bone formation in the flat bones of the skull and mandible, where bone forms directly within mesenchyme arranged in sheet-like layers that resemble membranes.

Intraocular pressure (IOP) – The pressure generated inside the ocular globe that averages approximately 16 mm Hg.

Intrapartum transmission -Transmission of a virus during the process of labour.

Intra-tissue genetic heterogeneity – Refers to the expression of different gene variants in different cells within the same organism or lesion (i.e., the cells directly involved in the disease process). The term is most often applied to can- cers, wherein subclones of cell emerge, each with a unique genotype and phe- notype. The expression of different forms of the same gene in different cells is a type of somatic mosaicism. The full extent of intra-tissue genetic heterogeneity in normal tissues of the body is not known. Hypothetically, somatic mosaicism may play a significant role in the development of polygenic or multifactorial diseases.

Intravitreal injection – A procedure to place a medication directly into the space in the back of the eye called the vitreous cavity, which is filled with a jelly-like fluid called the vitreous humour gel.

Intrinsic asymmetry – The unequal inheritance of a specific factor such as a protein, RNA, or macromolecule that changes the fate of one daughter cell during stem cell division.

Intrinsic immunity – A cell-based (i.e., not humoral) anti-viral system that is always “on” (i.e., not activated by the presence of its target, as seen in adaptive immunity and innate immunity). Intrinsic immunity is a newly discovered immune response system, and there is much we need to learn about this type of immunity. Intrinsic immunity has been studied for its role in controlling retrovirus infections (e.g., HIV infection). It is known that intrinsic immunity is not restricted to retroviruses, but its role in blocking infection by other classes of virus is something of a mystery. See Innate immunity and Adaptive immunity.

Intrinsic membrane protein – A protein whose structure crosses the lipid membranes of cells.

Intrinsic pathway – Pathway of initiating apoptosis that originates from an internal event that activates the mitochondrial Bcl-2 family of proteins.

Introduction – In a protocol, the section that explains the purpose of the study and its scientific importance.

Intron – A noncoding sequence within eukaryotic genes that separates the exons (coding regions). Introns are spliced out of the messenger RNA molecule created from a gene after transcription and before protein translation (protein synthesis). A segment of a DNA gene that acts as a noncoding spacer and is removed from hnRNA as mRNA is formed. Noncoding section in a DNA sequence within a gene that is transcribed and then removed by RNA splicing to produce a functional mRNA. Segment of a gene that does not code for protein but is transcribed and forms part of the primary transcript. Noncoding sequence found in DNA that is usually excised before translation.

Intussusception – Formation of new blood vessels by splitting of existing vasculature.

Intussusceptive branching – Branching by longitudinal division of a tube (by local ingrowth and meeting of the walls).

Invagination – A permanent infolding of a cell’s external membrane, associated in photoreceptors with their synaptic ribbons, and containing fine dendritic processes of bipolar and horizontal cells.

Invasin- Bacterial protein that provokes an animal cell to swallow the bacteria.

Invasion – In the field of cancer, invasion occurs when tumor cells move into and through normal tissues. All tumors that can metastasize can also invade, and, for this reason, it is inferred that invasion is involved in the process of metastasis. For metastasis to occur tumor cells invade through the walls of lymphatic and blood vessels, thus gaining access to the general circulation; likewise, tumor cells invade through vessels at the site of distant seeding. The opposite assertion is not true; tumors that invade do not necessarily metastasize. Examples of non-metastasizing invasive tumors include basal cell carcinoma of skin and most tumors arising within the brain.

Invasive pathogen – Pathogen that is highly adept at entering and spreading within the body.

Invert – In a postsynaptic cascade, to convert a rising signal into a falling signal.

Investigator bias – Unconscious inclination to observe hoped-for scientific outcomes and/or to interpret scientific data in a way that is consistent with hoped-for scientific outcomes; this bias is created by an investigator’s enthusiasm for supporting anticipated scientific outcomes.

Inverse agonist – Produces an opposite effect to that of the agonist.

Inverse PCR – Method for using PCR to amplify unknown sequences by circularizing the template molecule.

Inversion – Mutation in which a segment of DNA has its orientation reversed but remains at the same location.

Invertase (strictly, DNA invertase) – An enzyme that recognizes specific sequences at the two ends of an invertible segment and inverts the DNA between them.

Investigation – 1) A clinical trial, aka a clinical study, when used to describe a clinical investigation. When used to describe a quality control investigation, the term refers to the procedures followed to determine the root cause of a deviation or protocol/SOP violation. 2) A planned and documented analysis of events and circumstances contributing to a problem to determine the cause of the problem and the most appropriate corrective and/ or preventive action(s). May involve any combination of experiments, testing, and review of data, statistical analysis, interviews, expertise, and product inspection.

Investigational New Drug (IND) – Is the term used for a potential new drug whose pre-clinical trials material has been submitted to the FDA.

Investigator – Individual who conducts a clinical trial, aka a clinical investigation.

Investment round – Signifies phases of investment without necessarily the associated milestone event precipitating it. These can include Series A, Series B, etc., which are also known as alphabet rounds.

Investment staging – Is a venture capital practice where the new firm receives set amounts of funds from its investors only after certain contractual obligations have been met.

In vitro – (Latin) Literally “in glass,” meaning outside of the organism in the laboratory, usually is a tissue culture. In the laboratory, outside the body.

In vitro fertilisation (IVF) – Artificial fertilization of an egg in the laboratory. A procedure where an egg cell (the oocyte) and sperm cells are brought together in a Petri dish (i.e. in vitro), so that a sperm cell can fertilise the egg. The resulting fertilised egg, called a zygote, will start dividing and after a several divisions forms the embryo that can be implanted into the womb of a woman and give rise to pregnancy.

In vivo – (Latin) Literally “in life,” meaning within a living organism.

In vivo induced antigen technology (IVIAT) – Method used to identify genes active after an infectious agent enters the host cell. The technique identifies antibodies from the patient that react with intracellular proteins of the disease agent.

Ion-exchange HPLC – Chromatography technique that separates noncharged from charged molecules. The stationary phase has a net charge that attracts charged molecules, but neutral molecules are not retained.

IPC – In-Process Control (IPC).

IPD – Integrated Project Design (IPD).

ipRGC – The term stands for intrinsically photosensitive retinal ganglion cell, which is a small subset of retinal ganglion cells that are rendered light sensitive because they express melanopsin, implicated in nonvisual photoresponses.

IPTG (isopropyl-thiogalactoside) – A gratuitous inducer of the lac operon.

IQ/OQ/PQ – Installation Qualification/Operational Qualification/Performance Qualification- three different aspects of validating equipment in a GMP facility. DQ may also be expected, i.e., design qualification (DQ).

IRB – Institutional Review Board (IRB) – a standing committee of defined structure and responsibilities, who review research involving human subjects before and during the performance of that research. See also Independent Ethics Committee (IEC).

IRES – Internal ribosomal entry site (IRES).

IS – International Standard (IS)- a reference reagent prepared by a central laboratory that is recognised by the WHO’s ECBS as an appropriate material to assess assays for lot release.

ISCC – Intersociety Coordinating Committee (for coordination of initiatives in genomic medicine).

Ischemia – A biological condition in which cells suffer from an insufficient blood supply. A reduced blood supply to a tissue or organ, leading to pathological changes.

Islet transplantation – The experimental surgical procedure that is used to treat some patients with type 1 diabetes; cadaver donor islets are transplanted into the liver of patients via the portal vein, where they then begin to secrete insulin and reverse diabetes.

Islets – Spherical clusters of pancreatic endocrine cells that are comprised mainly of insulin-producing β-cells.

Isoelectric focusing (IF) – Technique for separating proteins according to their charge by means of electrophoresis through a pH gradient.

Isoelectric point – pH value at which a molecule carries the same amount of positive and negative charges (no net charge) and therefore does not move within an electric field.

Isoforms/Isozymes – One of several alternative forms of a protein that are encoded by the same gene. They differ because of alternative splicing of mRNA or alternative processing of precursor protein. Alternative forms of protein/enzyme resulting from posttranslational modifications of the gene product. Different polypeptide forms of the same enzyme. These forms alter the kinetic properties of the enzyme. Isoform is an alternate term.

Isograft – Graft between two genetically identical individuals.

Isomerisation – Relocation of a portion of a molecule to a different site on the same molecule. The alteration of a compound by the movement of one or more of its functional groups to new positions.

Isomers – Organic molecules with the same sum formula, but different spatial arrangements of their atoms. There are many different classes of isomers, like positional isomers, cis-trans isomers and enantiomers, etc. Isomers may differ in their properties. For instance, one of the enantiomers of thalidomide led to malformations in newborns. The biological synthesis of substances, however, is nearly always free from enantiomers and thus a safer production method for drugs in this respect.

Isoprenoids – A lipid class that contains isoprene units. Cholesterol and its derivatives are important members of this class.

Isotypes – A form of an antibody. Different isotypes are produced by B cells during primary or memory responses and can be used to differentiate between a primary or subsequent infection. Classes of Igs defined on the basis of the amino acid sequences of their constant regions. Include IgM, IgD, IgA, IgG and IgE heavy chain isotypes and Igκ and Igλ light chain isotypes.

Isotype switching – Mechanism by which a B cell producing an Ig heavy chain of one isotype can then switch to producing Ig of the same variable region but a different constant region. See also switch recombination.

ITAM – Immunoreceptor tyrosine-based activation motif (ITAM). Activator sequence in receptor tails that facilitates recruitment of kinases promoting intracellular signaling.

ITIM – Immunoreceptor tyrosine-based inhibition motif (ITIM). Inhibitory sequence in receptor tails that facilitates recruitment of phosphatases downregulating intracellular signaling.

iTreg cell – CD4+Foxp3+ regulatory T cells that block conventional T cell activation via IL-10 and TGF secretion. Generated in the periphery from Th0 cells that have in teracted with a mature DC.

IV-IG – Intravenous immunoglobulin. A pooled plasma preparation from thousands of healthy blood donors that is administered intravenously to an antibody-deficient pa tient as a form of immunoglobulin replacement therapy.



J chain – A polypeptide that will link immunoglobulins (found in IgM and secretory IgA). J stands for “joining.” Joining chain. Small polypeptide that binds to the tail pieces of α and μ Ig heavy chains; stabilizes polymeric IgA or IgM.

Jaundice – Yellowing of the eyes and skin.

Jitter – Deviation from true periodicity.

JNK (Jun amino-terminal kinase) – A eukaryotic protein that transfers a phosphate group from itself to AP-1 in order for AP-1 to bind and activate gene transcription.

Joint venture (JV) – Is a type of strategic alliance where two parties contribute their different but complementary core competencies to achieve a shared goal.

Jumping gene – Popular name for a transposable element.

Junctional diversity – Variation in the amino acid sequences of Igs and TCRs that arises during V(D)J recombination. Due to imprecise joining of gene segments as well as deletion and/or addition of nucleotides to the joint.

Junk DNA – Term used to describe defective selfish DNA that is of no use to the host cell it inhabits and that can no longer move or express its genes.

Justice – The ethical principle that requires a fair distribution of benefits and burdens. This is a basic principle or tenet of ethical clinical research. This principle means to assure fairness in those who benefit from the research and those who bear the burden of the research or assuring equitable enrollment of subjects. This tenet is accomplished by selecting subjects through the use of equitable inclusion/exclusion criteria and by avoiding exploitation of vulnerable populations or populations of convenience.

Justification – In a protocol, the section that includes a description of specific characteristics of study design, such as proposed subjects, blinding and randomization strategies, and why these study components are optimal for the proposed study.

k1 [E][S] = (k2 + k3) [ES].



Kappa particles – Symbiotic bacteria (Caedibacter) that grow inside killer Paramecium and make toxin.

KapparentAlso known as Kappor K0.5and is equal to the concentration of substrate at which Vmax is one-half its normal value. It is used for enzymes that do not follow Michaelis-Menten kinetics and have no absolute Km value and for Michaelis-Menten enzymes in the presence of an inhibitor.

Karyotype – From the Greek root karyon, meaning nucleus, the karyotype is a standard shorthand describing the chromosomal complement of a cell. The normal karyotype of a human male diploid somatic cell is 46 XY, a somewhat confusing way to express that there are two sets of 23 chromosomes, produc- ing a total complement of 46 chromosomes, which includes one X and one Y sex chromosome. The normal female karyotype is 46 XY. Abnormalities in karyotype are described using the International System for Human Cytogenetic Nomenclature (ISCN). Photographic representation of the chromosomes of a single cell, arranged in pairs based on their size and banding pattern according to a standard classification. The chromosomes in a nucleus, visualized by a specific staining.

Kb – Kilobase pairs (1000 base pairs DNA).

Kearns–Sayre syndrome – One cause of CPEO that is inherited from the mother and affects other tissues, such as the heart.

Keratinocytes – Epidermal squamous epithelial cells that produce keratin. Stratified layers are held together as units by desmosomes.

Keratoconjunctivitis sicca – Dryness of cornea and conjunctiva.

Keratomalacia -Literally corneal melting. A condition in which the cornea is in the process of degeneration possibly leading to perforation.

Keratoplasty – Corneal transplantation.

Keratoprosthesis – A type of artificial cornea that is designed to be implanted in a patient who has severe bilateral corneal disease for which a corneal transplant is not an option.

Ketimine – See Amadori rearrangement.

Ketone bodies -Acidic metabolites of fatty acids formed from their excessive catabolism (as occurs in more severe forms of diabetes).

KIInhibitor constant that is equivalent to the Km for a substrate. It is an indirect measure of the affinity of an inhibitor for an enzyme.

Killed vaccine – A vaccine in which the whole pathogen of interest is killed or inactivated by treatment with gamma irradiation or a chemical agent.

Killer Paramecium – Paramecium carrying kappa particles and therefore capable of killing sensitive paramecia.

Kinase – An enzyme that transfers phosphate groups from high-energy donor molecules to specific substrates. Enzyme that catalyzes the addition of phosphate groups onto another protein. Proteins that phosphorylate other proteins.

Kinetics – Discipline referring to enzyme activity and the rates (velocities) at which enzymes operate and the conditions that influence the rates.

Kinetochore – A protein structure on chromatids, allowing the spindle fibers to attach and pull the sister chromatids apart during cell division.

KmMichaelis-Menten constant that is equivalent to k2/k1 (with k3 sufficiently small) or the concentration of a substrate at which Vm is one-half its normal value.

Knockin – A method to introduce a functional gene inside a deficient mutant genome.

Knockout – A method to destroy a functional gene inside a wild-type genome. A technique used primarily in mouse genetics to inactivate a particular gene in order to define its function.

Knockout mouse (KO) – Mutant mouse strain in which a single gene in the DNA of a mouse embryo is deliberately deleted or rendered defective by genetic engineering techniques. Mice containing genes that have been inactivated by genetic engineering, usually by insertion of a DNA cassette to disrupt the coding sequence. A mouse in which a specific gene is inactivated by deletion of part of its DNA usually using homologous recombination in embryonic stem cells. 

510(k) – A premarket notification for a medical device that can be shown to be substantially equivalent to one already on the market in the United States. Most class 2 devices require submission of this type of dossier to U.S. FDA. These are cleared (vs. approved).

Kochs postulates – A set of observations and experimental requirements pro- posed by Heinrich Hermann Robert Koch in the late 1800s, intended to prove that a particular organism causes a particular infectious disease. For the experi- mentalist, the most important of the Koch’s postulates require the extraction of the organism from a lesion (i.e., from diseased, infected tissue), the isolation and culture of the organism in the laboratory, and the consistent reproduction of the lesion in an animal inoculated with the organism. Over the ensuing century, some modifications to Koch’s original postulates were necessary to accommo- date our expanding experience with infectious agents and our increasing aware- ness of the limits of biological causality. As an example, Helicobacter pylori is known to cause gastric lymphoma, but H. pylori fails Koch’s postu- lates. It is currently presumed that H. pylori lymphoma arises as a consequence of chronic H. pylori infection with gastritis. H. pylori-associated lymphoma cells do not contain H. pylori bacteria (i.e., the organism cannot be consistently isolated from lymphoma cells), and the gastric injection of cultured H. pylori is not likely to induce stomach cancers. In his thoughtful paper, Inglis discusses that biological causation is an elusive concept. Inglis proposes the concept of the “priobe,” referring to a biological agent that is a necessary and sufficient cause of a series of events that eventually leads to a disease (i.e., an underlying or antecedent cause). It refers to a set of criteria that Koch developed to establish a causative relationship between a microbe and a disease. Koch applied the postulates to describe the etiology of cholera and tuberculosis.

Krebs cycle – see citric acid cycle, named after Sir Hans Krebs.

Kupffer cells – Macrophages in the liver.

Kuru – Brain degeneration disease of cannibals caused by prion.



Label – A description of a drug product, including what it is used for, who should take it, side effects, instructions for use, and safety information.

LacI repressor – Repressor protein that controls lac operon.

Lacrimal mucocele – Lacrimal duct cyst extending into nose.

Lactate dehydrogenase (LDH) – Enzyme that interconverts pyruvate and lactate lactoferrin an iron transport protein of animals.

Lactose acetylase – Protein product of the LacA gene that has unknown function in lactose metabolism.

Lactose permease (LacY) – The transport protein for lactose.

LacZ gene – Gene encoding β-galactosidase; widely used as a reporter gene.

Lagging strand / leading strand – The new strand of DNA that is synthesized in short pieces during replication and then joined later. Forms of daughter DNA made during replication. Leading strands are made in a simple fashion 5’ —> 3’ while lagging strands require the initial formation of Okazaki fragments prior to joining in a 5’ —> 3’ direction.

Lamella (pl. Lamellae) – In reference to the cornea, flat sheets of collagen fibers that are stacked one upon another, but whose fiber direction varies from lamella to lamella.

Lamina cribrosa – The perforated portion of the back part of the white of the eye (sclera) through which nerve fibers from the retina exit.

Lamina propria – A thin layer of connective tissue that underlies an epithelium. Layer of loose connective tissue between the basolateral surface of the mucosal epithelium and the underlying muscle layer. Vibratory unit of the vocal fold.

Laminin – An extracellular membrane (matrix) protein. This protein is required, for example, in the spreading and attachment of corneal epithelial cells during corneal repair.

Lancelets – The common name for cephalochordates. These animals are frequently referred to by the incorrect term amphioxus.

Langerhans cells (LCs ) – Dendritic cells that typically reside in the epithelium or epidermis. APCs of the epithelium which migrate to the lymph nodes to become dendritic cells.

LAR – Legally Authorized Representative (LAR) – this is an individual who may have the legal right to consent to participation in clinical research on behalf of another who is incapable of consenting on his/her own for some specific reason (e.g., they are unconscious at the time they would be asked to participate or their psychological state does not permit- e.g., senility).

Large scale genomic analysis – Methods or techniques to analyze a significant fraction of the information coded in RNA or DNA present in cells.

Large-offspring syndrome – Imprinting defect that causes abnormal body size.

Laser trabeculoplasty – The surgical treatment of glaucoma, in which a laser beam is focused on the trabecular meshwork making tiny, evenly spaced burns.

Late domain – A peptide motif (four amino acids), that involves in the budding of enveloped viruses. It is composed of four amino acids such as “PTAP” or “PPXY” residues.

Late genes – Genes expressed later in virus infection and that mainly encode enzymes involved in virus particle assembly.

Late phase reaction – In the effector phase of type I hyper- sensitivity, leukocytes (especially eosinophils) that entered the site of allergen penetration in the early phase reaction release additional cytokines, enzymes and inflammatory mediators that do further damage.

Late-stage financing – In the later stages of development, strategic alliances with corporate companies are key to success, as are deals with late-stage venture capitalists or banks. Last but not least important is the exit, usually in form of an initial public offering (IPO), trade sale, or management buy-out (MBO).

Latency – The state in which a virus becomes dormant (inactive) within the body. A stage of viral infection when a virus is apparently inactive biochemically (also called the latency stage). An extended period during which a pathogen is present in the body but is non-infectious and does not cause clinical symptoms. State in which a virus replicates its genome in step with the host cell without making virus particles or destroying the host cell. Same as lysogeny, but generally used to describe animal viruses.

Latency associated transcript – Also known as LAT, a mRNA in herpesvirus that is associated with the latency stage.

Lateral crura – The most lateral portion of the lower lateral (or alar) cartilage.

Lateral geniculate nucleus – A subcortical structure in which ganglion cells from the retina synapse onto neurons sending processes to area 17 of the brain (the primary visual cortex).

Lateral inhibition – A conserved developmental process in which a population of equipotential cells become sorted into one of more unique phenotypes through a process in which some cells acquire a particular fate and then express membrane bound ligands that bind to membrane receptors on neighboring cells to prevent those cells from developing with the same fate.

Lawn – A uniform growth of bacteria that coats the entire surface of the growth medium. Single colonies of bacteria are not visible.

LCME – Liaison Committee on Medical Education (LCME).

Le Fort I–III – Named after the French surgeon, Le Fort fractures are common patterns of facial fractures that occur based on naturally occurring fusion patterns of facial bones. Le Fort I results from an impact to the lower mandible in a downward direction. Fractures extend from the nasal septum, travel horizontally above the teeth, and cross below the zygomatic maxillary junction. Le Fort II fractures occur from a blow to the lower or mid-maxilla and usually involve the inferior orbital rim. A Le Fort II fracture has a pyramidal shape and extends from the nasal bridge at or below the nasofrontal suture through the frontal processes of the maxilla. Le Fort III fractures result from impact to the nasal bridge or upper maxilla. These fractures start at the nasofrontal and front maxillary sutures and extend posteriorly along the medial wall of the orbit through the nasolacrimal groove and ethmoid bones, and are otherwise known as craniofacial dissociation. Surgeons use the Le Fort fractures to assist in resetting bones after surgical procedures like distraction osteogenesis or craniosynostosis repair.

Lead compound – In drug discovery, the term refers to a compound that has pharmacological or biological activity and whose chemical structure is used as a starting point for chemical modifications in order to improve its potency, selectivity, or pharmacokinetic parameters. Lead compounds are often found in high-throughput screenings or are secondary metabolites from natural sources.

Lead investor – An investor who is either the first, largest or most active investor in an early-stage financing round. The lead investor can sometimes, though unintentionally, influence investment decisions of other investors.

Lead underwriter – Is the investment bank in charge of the IPO process from the underwriting perspective.

Lead venture – capital firm relates to the firm that is primarily responsible for investment and other (e.g. management, governance) activity for all venture capital firms.

Lead venture capital firm – Relates to the firm that is primarily responsible for investment and other (e.g. management, governance) activity for all venture capital firms.

Leading strand – The new strand of DNA that is synthesized continuously during replication.

Lectin – A protein that binds to particular carbohydrate moieties on membrane glycoproteins or glycolipids on cell surfaces.

LEED – Leadership in Energy and Environmental Design (LEED).

Lef1 – Lymphoid enhancer-binding factor 1, a transcription factor that binds Lef/TCF sites in the DNA to mediate ß catenin Wnt signaling.

Lens-induced chronic hypoxia – Corneal oxygen deprivation that results from contact lenses that greatly impede oxygen diffusion to the cornea. Chronic hypoxia may cause changes in corneal structure and neovascularisation.

Lenticles – A tiny disk slipped into the pocket of the patient’s own cornea between corneal epithelium and Bowman’s membrane for vision correction.

Lentiviruses – A genus of viruses of the Retroviridae family, characterised by a long incubation period. Lentiviruses can deliver a significant amount of viral RNA into the DNA of the host cell and have the unique ability among retroviruses of being able to infect non-dividing cells.

Leptin – A protein hormone that controls the appetite and the burning of fat by the body leptin receptor Receptor for leptin, encoded by the dbgene.

Lethal factor (LF) – Protein toxin made by anthrax bacteria that is a protease and cleaves several host cell mitogen-activated protein kinase kinases (MAPKKs).

Letter of Authorisation (LoA) – An agreement between the person, known as the principal, authorising another, known as an agent, to perform certain functions or powers in order to perform the duties of the principal.

Leukapheresis – Removal of leukocytes from a donor’s blood, followed by return of the remaining blood products to the donor.

Leukemia – “Liquid” malignancy of hematopoietic cells. Manifested as greatly increased cell numbers in the blood and bone marrow.

Leukemia Inhibitory Factor (LIF) – A blood cell protein originally identified as essential for keeping embryonic stem cells undifferentiated.

Leukocytes – White blood cells, including lymphocytes, granulocytes, monocytes, macrophages, NK and NKT cells.

Leukostasis – Increased blood viscosity and tendency to clotting.

Leukotrienes – Products of the lipoxygenase pathway of arachidonic Lipopolysaccharide.

Leveraged buy-out (LBO) – This term describes an acquisition of a firm or business unit, typically in a mature industry, with a significant amount of debt. The debt is then repaid according to a clearly defined schedule that binds most of the firm’s cash flow.

Leverage effect – A general term describing a financial ratio that compares some form of owner’s equity (or capital) to borrowed funds. The higher a company’s degree of leverage, the more the company is considered risky.

Leverage ratio – This term describes the ratio of debt to total capitalization of a firm.

Liability – The probable future sacrifice of economic benefits that derives from present obligations of a particular entity to transfer assets or provide services to other entities in the future as a result of past events or transactions.

License (e.g. R&D licensing agreement) – A contract between a technology provider (licensor) and a user of that technology (licensee). The license agreement (either an in-licensing or an out-licensing deal) may be exclusive or non-exclusive.

License (marketing) – Is granted by a governing body that allows a firm to sell a biopharmaceutical product. It is sometimes referred to as a marketing authorization (MA).

License agreement – Is a form of strategic alliance where the owner of the rights of a technology grants permission to use the intellectual property to another and receives payment for use.

License is granted – by a governing body that allows a firm to sell a biopharmaceutical product. It is sometimes referred to as a marketing authorization.

Licensing – (DC) Th-induced upregulation of dendritic cell (DC) costimulatory molecules that allow the DC to mediate full activation of an antigen-stimulated Tc cell in the absence of further Th cell involvement.

Licensee – In a licensing agreement, the party who receives the right to use a specific technology or product in exchange for payments.

Licensor – In a licensing agreement, the party who receives payments in exchange for providing the right to use a specific technology or a certain product that it owns.

Life Cycle Assessment (LCA) – The ecological cradle-to-grave analysis of a product, including the sourcing of raw materials, energy consumption in the production process and disposal. This is done as accurately as possible.

Life science – Term often used to categorise health-care- related firms, including but not limited to biopharmaceutical firms.

Ligand – A molecule that binds to a receptor on the surface or the interior of a cell.

Ligase – A cellular enzyme that joins the sugar phosphate backbones of two adjacent fragments of DNA. An enzyme that can use adenosine triphosphate to create phos- phate bonds between the ends of two DNA fragments, effectively joining two DNA molecules into one. An enzyme that joins DNA. Enzymes that catalyze the joining together of two molecules. DNA ligase is a major representative of this class, catalyzing the formation of an ester bond between a phosphate residue and the sugar deoxyribose.

Ligated – In biotechnology, joining up DNA fragments end to end using an enzyme such as DNA ligase.

Light adaptation – A change in the membrane voltage of photoreceptor and other retinal cells that occurs in response to continued exposure of light of the same intensity. Other definitions are possible.

Light chains – The shorter of the two pairs of chains forming an antibody molecule.

Light scattering – A phenomenon in which light is reflected from a surface in all directions in a non uniform manner.

Light zone – Region of the germinal center where isotype switchingand affinity maturation occur.

Lignin – Insoluble polymer of cross-linked aromatic residues found in plant cell walls.

Limbus – The edge of the cornea where it joins the conjunctiva and the sclera.

Limit of detection – The lowest amount of an analytic that can be reliably measured as being detected, whether or not it can be accurately or precisely quantified. Amount at which method is able to discriminate positive or negative.

Limit test – A method that is positive above and negative below a threshold for the presence of impurities in a product. Such a method is not considered to be quantitative, even if the read-out or threshold is a numerical result.

Limited partner (LP) – In a private equity fund, the limited partners provide the capital, which is then invested by the general partner.

Limited partnership – Is a legal structure related to venture capital funds where the venture capital firm’s professionals serve as the general partner, and the investors act as passive limited partners.

Limits of Quantitation – Upper and lower amounts that bound the linear range of a quantitative assay to accurately and precisely measure an analytic.

Lineage analysis – A method to trace a group of cells or individual cells through development or to trace cell divisions in a tissue or organ of an adult organism. The method can identify stem cell populations in adult tissues.

Lineage restricted precursor cells – Cells that are still dividing but have a more restricted developmental potential than stem cells.

Linear range – The portion of a quantitative curve over which the curve is essentially linear, i.e., the read-out is directly proportional to the quantity of the analytic.

Linkage – A model showing the evolution of an entity from its ancestral predecessor. The phenomenon whereby pairs of genes that are located in close proximity on the same chromosome tend to be co-inherited. Two markers are linked when they are inherited together more often than would be expected by chance, usually because the two markers are found close to one another on the same chromosome.

Linkage analysis – A process of locating genes on the chromosome by measuring recombination rates between phenotypical and genetic markers (see Lod score).

Linkage disequilibrium – Nonrandom association of alleles at two or more loci. The nonrandom association in a population of alleles at nearby loci.

Linkage mapping – Determining the linear order of genetic markers determined by the frequency in which two markers stay together during mating.

Linkage studies – Studies based on the tendency of genes that are located proximal to each other on a chromosome to be inherited together during meiosis, and are thus said to be linked.

Linked genes – Genes on the same chromosome tend to be segregated and inherited together.

Linked recognition – The requirement that B and T cell epitopes be physically linked to induce an efficient humoral response.

Linkers (also called adapters) – A short double-stranded piece of DNA with known sequence that is added to the ends of DNA fragments.

Lipid – A carbon-based molecule that is insoluble in water, but is soluble in many nonpolar liquids. A class of non-protein compounds that are predominantly hydrophobic, but which have hydrophilic moieties or parts.

Lipid droplet (LD) – Lipid-rich cellular organelles which regulate the storage and hydrolysis of neutral lipids. They are found largely in adipose tissue. They also serve as reservoirs of cholesterol and acyl-glycerols for membrane formation and maintenance.

Lipid nanoparticle – A microscopic sphere composed of lipids that encloses a payload to be delivered to cells.

Lipofection – Use of liposomes to transfer DNA or proteins into a target cell.

Lipofuscin – Fatty deposit in the retina containing chromogenic (color producing) material.

Lipofuscin autofluorescence – Lipofuscin is composed of many molecules that are by-products of the visual or retinoid cycle. These accumulate in the retinal pigment epithelium with aging and can be visualized in the living eye because they fluoresce when exposed to short wavelength light.

Lipophilic – Lipid soluble, literally “fat loving.”

Lipopolysaccharide (LPS) – Complex lipid structure containing sugars and fatty acids found in the outer cell membrane layer of Gram negative bacteria. Component of Gram-negative bacterial cell walls that generates endotoxin and induces endotoxic shock. A component of the outer cell membrane of the wall of Gram-negative bacteria that acts as an endotoxin. The presence of LPS, that is detected for example, by toll-like receptors, signals the pathogenic nature of antigens to the immune system and elicits a strong inflammatory reaction.

Lipoprotein – A protein joined with lipid moieties.

Liposomes – Vesicles with an aqueous core surrounded by a phospholipid shell that may be used to deliver oligonucleotides, drugs, or other molecules across the cell membrane.

Lipoxygenase -Enzymes that form HETE and leukotriene eicosanoids.

Liquidation – A term describing the process of selling assets for cash. When companies go through liquidation, they normally sell their existing assets for cash which is used to pay off creditors in order of priority. Any remaining cash is distributed to the shareholders.

Liquidation preference – In its simplest meaning, the order in which different security holders receive their payments in the event of a liquidation. In a more complex meaning, some preferred stock holders may dispose over an excess liquidation preference, which guarantees a multiple of the aggregate purchase price in case of a liquidation.

Liquid crystal – A state in which a substance exists in an intermediate flexible phase between a liquid and a solid.

Liquid market – A term describing a market with a high degree of liquidity, often resulting from a large number of buyers and sellers. Changes in supply or demand have a smaller impact on price. A liquid market is the opposite of a thin market.

Lisch nodules – Dome-shaped melanocytic hamartomas on the iris.

Literature review – In a protocol, the section that presents information from the existing scientific literature to explain and justify the proposed study.

Live attenuated virus vaccine – The type of vaccine that uses weakened but “live” (infectious) virus.

Live cell microarrays – A method used to analyze siRNA library clones in which the library DNA is spotted onto a glass slide and eukaryotic cells are grown over the slide. The siRNA library clones are taken up, and the cells are assessed for physical differences.

Liver – The largest gland in the vertebrate body which has a role in digestion, glucose regulation and storage, blood clotting and removal of wastes from the blood.

Local mediator – Molecule that carries signals between nearby cells.

Local Protected Environments – Local protected environments may be used for open processes. Examples include Biosafety Cabinets (BSCs),Unidirectional Down Flow Hoods (UDFHs) or unidirectional horizontal flow hoods, isolators and Restricted AccessBarriers (RABs). When used, it is critical that the local environment be protected from unexpected breach ofthe protected environment. Appropriate sanitization and filtration is required to achieve and maintain the statedcleanroom classification within the local protected environment. Appropriate surrounding environments, gowningand other controls may be required to ensure integrity of the local protected environment is maintained especially forBSCs, RABs and UDFHs. Only a bioburden-free environment should be used for open aseptic operations. A formalrisk assessment is required to fully evaluate the appropriateness and quality of the environment used for bioprocessoperations and for the environment housing the local protected environments.

Local Protection – An area within a room where only airborne particulate control is enhanced from the surrounding environment. Local protection devices provide a flow of HEPA filtered air over an area of concern to displace particulate and maintain lower airborne particle and viable organism counts than the background. Common examples of local protection are:horizontal and vertical unidirectional flow hoods. Common environmental definitions for local protection areas are: “Airborne particulate and viable counts meet the requirements of one class higher than the background”or“Meets ISO 5 requirements for airborne particulate and viable organisms at rest only”

Locus – The location or the physical site of an individual gene or DNA sequence on a chromosome. The specific site on a chromosome at which a particular gene or other DNA landmark is located.

Locus 8q24 – Discovered in 2006, this was one of the first loci associated with a genetic risk to be validated in a reproducible way. Since then, it has also been confirmed for other cancers such as colon, breast and bladder cancer. The exact mapping of the locus revealed alleles covering distances of nearly 490 kilobases. Curiously, risk variants are found in the non-coding region and the mechanism by which they contribute to cancers remains unknown. These alleles are close to the MYC oncogene and results suggest one or more interconnected roles between these non-coding RNA and MYC as the risk factor.

Locus control region (LCR) – Regulatory sequence in eukaryotes found in front of a cluster of genes that it controls.

Locus heterogeneity – Also known as non-allelic heterogeneity, occurs when mutations in different genes can produce the same disease. For example, muta- tions in c-KIT or PDGFR alpha can lead to gastrointestinal stromal tumor. Mutations in the gene encoding the protein hamartin or the gene encoding the protein tuberin can produce the disease tuberous sclerosis. Carney complex can be caused by mutations in the PRKAR1A gene on chromosome 17q23-q24, or it may be caused by a mutation in chromosome 2p16. Both types of mutation produce the same clinical phenotype, which carries an increased risk of devel- oping several types of tumors, including cardiac myxoma. Locus heterogeneity is a special case of the broader concept of genetic heterogeneity. See Genetic Heterogeneity, Allelic heterogeneity, and Oligogenic inheritance.

Lod score – A measure of the likelihood of genetic linkage between loci. A lod score greater than +3 is often taken as evidence of link- age; one that is less than −2 is often taken as evidence against linkage.

Logistic growth – Growth that results in the population increasing until it reaches its carrying capacity.

Long interspersed element (LINE) – Long sequence found in multiple copies that makes up much of the moderately repetitive DNA of mammals.

Long terminal repeats (LTRs) – Direct repeats of several hundred base pairs found at the ends of retroviruses and some other retroelements required for insertion into host DNA.

Loss of heterozygosity (LOH) – Loss of alleles on one chromosome detected by assaying for markers for which an individual is constitutionally heterozygous. Presence of only one copy of an allele, such as the loss of a portion of a chromosome within tumor tissue.

Loss of imprinting (LOI) – During normal embryogenesis, genes are imprinted with epigenetic modifications that suppress the expression of various genes. When there is an acquired loss of this normal imprinting, the affected gene may be overexpressed. The first discovered example of loss of imprinting was the overexpression of insulin-like growth factor-2 (Igf2) in Wilms tumor. In this case, a mutation disrupts the H19 imprinting control region that would normally silence the maternally inherited Igf2 allele.

Loss-of-function – A mutation that alters the gene product such that it no longer remains active and loses its function.

Loss-of-function mutation – A mutation that decreases the production or function (or both) of the gene product.

Lot – This term refers to a homogenous preparation of drug product. Some people use the term interchangeably with “batch.”

Lot Release – The process of reviewing testing data and executed BPR and any other pertinent documentation before deciding to release the lot to the clinic (investigational product) or the market (licensed product). Lots that have not been “released” must be held in quarantine until a decision is reached regarding their disposition. A released lot may be shipped. For marketed products, the NRA or NCL may be involved in the process and may also be responsible for releasing the lot, in addition to the manufacturer’s release.

Low Bioburden (Operation) – Process where a limited and controlled level of measurable bioburden is acceptable under specific conditions. (e.g.,WFI, chromatography operations).

Low copy repeats (LCR) – A term for the highly homologous segments of DNA, which are the result of segmental duplications and other recombination events that mediate microdeletion events. There are four primary LCRs in the 22q11.2 region, which are named LCR A–D.

Low density lipoprotein (LDL) – It refers to a nanoparticle of 22 nm diameter composed of phospholipid, cholesterol, and apolipoproteins.

Low-pass filter – A filter that removes high frequencies and passes low frequencies.

Low zone tolerance Experimental tolerance -induced by administration of very small doses of immunogen over an extended period.

LoxPsite – Specific sequence that is recognized by Crerecombinase.

L-type voltage-gated calcium channels (L-VGCCs) – The membrane channels that mediate a voltage-dependent and depolarization-induced calcium influx. They regulate diverse biological processes such as contraction, secretion, neurotransmission, differentiation, and gene expression in many different cell types. The L-VGCCs are composed of a pore-forming a1-subunit and the auxiliary b-, a2d-, and g-subunits. They can be blocked by divalent cations (e.g., cobalt) and organic L-VGCC antagonists, including dihydropyridines, phenylalkylamines, and benzothiazepines.

Lucgene – Gene encoding luciferase from eukaryotes.

Luciferase – Enzyme from certain insects or bacteria catalyzing the oxidation of polycyclic aromatic luciferin (colorless) with molecular oxygen, thus generating bioluminescence.

Luciferase – Enzyme that emits light when provided with a substrate known as luciferin.

Luciferin – Chemical substrate used by luciferase to emit light.

Lumen – The interior of a tube or vessel.

Lumican – A proteoglycan found in the cornea.

Luminous efficiency function Vl – The inverse of the radiant power of a monochromatic stimulus of wavelength l that produces a luminous sensation equivalent to that of a monochromatic stimulus of fixed wavelength l0. The units and l0 may be chosen so that the maximum of this function is unity. It is also known as the relative luminous efficiency or relative luminosity function.

Lumi-Phos – An artificial substrate that is split by alkaline phosphatase, releasing an unstable molecule that emits light.

Lung – Organ containing sac-like structures where blood and air exchange oxygen and carbon dioxide.

Lux gene – Gene encoding luciferase from bacteria.

Lymph – Nutrient-rich interstitial fluid that bathes all cells in the body. Lymph filters slowly through the tissues, collects antigen, and eventually enters the lymphatic system.

Lymph nodes – Bean-shaped, encapsulated secondary lymphoid tissues located in clusters along the length of the lymphatic system. Contain the concentrations of the T and B lymphocytes and DCs required for primary adaptive immune responses.

Lymphadenopathy – Swollen lymph nodes.

Lymphangiogenesis – Pertains to the specific growth of lymphatic vessels.

Lymphatic system A blind-ended system of vessels that protects and maintains the fluid environment of the body by filtering and draining away lymphatic fluid. Under normal conditions, the lymphatic vascular system is necessary for the return of extravagated interstitial fluid and macromolecules to the blood circulation, for immune defense, and for the uptake of dietary fats.

Lymphatic system – A network of lymphatic capillaries, vessels and trunks through which lymph and lymphocytes travel. The lymphatic trunks connect with certain veins of the blood circulation.

Lymphoblasts – Daughter cells immediately produced by the division of an activated naïve lymphocyte. Lympho- blasts rapidly proliferate and differentiate into effector lymphocytes.

Lymphocyte – Non-granular leukocyte which may be either a T cell or a B cell. Small round leukocytes with a large nucleus and little cytoplasm. Concentrated in the secondary lymphoid tissues while in the resting state. Two major types exist, T cells and B cells, which are responsible for adaptive immune responses. Types of white blood cells that are part of the immune system.

lymphocyte recirculation – Continual migration of lympho- cytes from the tissues back into the blood via the lymphatic system, followed by return to the tissues via extravasation from the blood circulation.

Lymphoid cells – T and B lymphocytes, NK cells and NKT cells.

Lymphoid follicles – Organized spherical aggregates of lymphocytes.

Lymphoid organs – Encapsulated groups of lymphoid follicles.

Lymphoid patches – Groups of lymphoid follicles that are not encapsulated.

Lymphoid tissues – Specialized anatomical regions containing lymphocytes, such as the spleen, tonsils and lymph nodes. Lymphoid tissue (GALT), the bronchi associated lymphoid tissue (BALT) and the nasopharynx- associated lymphoid tissue (NALT).

Lymphokines – Substances secreted by T cells which stimulate the activity of macrophages.

Lymphoma – Cancer of the lymph nodes. Solid malignancy of lymphoid cells arising in a structured or diffuse secondary lymphoid tissue rather than in the blood or bone marrow. Classified as Hodgkin’s or non-Hodgkin.

Lymphopoiesis – The process of HSC differentiation into lymphoid cells.

Lyonization – The process of random X chromosome inactivation in mammals.

Lyophilizatlon or freeze-drying – Dehydration process typically used to preserve a perishable high-grade material such as a pharmaceutical. The material is frozen at normal pressure, which is then reduced to allow the frozen water in the material to sublimate directly from the solid phase to the gas phase.

Lysins – Proteins made by bacterial viruses that destroy the cell membrane to release newly made virus particles.

Lysis – Killing of a cell or molecule through the action of a specific agent.

Lysogenic conversion – A new bacterial phenotype caused by expression of prophage genes.

Lysogeny – Type of virus infection in which the virus becomes largely quiescent, makes no new virus particles, and duplicates its genome in step with the host cell. Same as latency but used of bacterial viruses.

Lysosome – A membrane-bound vesicle that contains enzymes for digesting intracellular molecules. A cellular vacuole containing digestive enzymes active against bacteria.

Lysozyme – An enzyme found in many bodily fluids that degrades the peptidoglycan of bacterial cell walls. Enzyme that cleaves the polysaccharides of bacterial cell walls. It is found, for instance, in egg white, human saliva, tears, and nasal secretions. It is part of the nonspecific immune system. Protease that digests particular bacterial cell wall components. Found in lysosomes, neutrophil granules, tears and body secretions.

Lytic cycle – The sequence following infection that leads to bacteriophage replication and lysis of the host bacterium.

Lytic phase – Type of growth in which a virus generates many virus particles and destroys the cell



M (mitosis) phase – Fourth phase of the eukaryotic cell cycle, in which the cell divides; also known as mitosis.

MAL – Material Air Lock (MAL)

MCB – Master Cell Bank (MCB)

MEP – Mechanical, Electrical, Plumbing, and Fire Protection

MERV – Multiple Efficiency Reporting Value (MERV), the ASHRAE Standard 52.2 method of testing filter efficiency by challenging filters with particles of multiple sizes and integrating the efficiency into a single number rating. The higher the MERV number the more efficient the filter. MERV 14/15 is approximately equivalent to a 95% (ASHRAE) efficient filter.

M cells – Membranous or micro fold cells. Large epithelial cells with an intraepithelial pocket. Transcytoses antigens from a body tract lumen across the epithelial layer. Most M cells reside in the dome overlying intestinal follicles.

MAA – Marketing Authorisation Application (MAA) – the submission made to the EMA to gain marketing authorization in Europe for a new drug, including biotechnology-derived products. In this book, MAA may be used as a generic term for an application for marketing authorization, be it a BLA, NDA, or MAA.

MAb – Monoclonal Antibody (MAb). Monoclonal antibodies are expressed from cell clones derived either as hybridisms or by recombinant DNA technology to express an antibody from a single B-cell. MAb can be murine, human, or humanized (or from other species).

Macroautophagy – Autophagy involving preliminary formation of an isolation membrane in the cytoplasm that circularizes around a large cytosolic entity to form an autophagosome. Fusion of the autophagosome with a lysosome forms an auto phagolysosome in which the entity is degraded. The process that degrades cellular components like organelles inside a double-membrane structure.

Macroalgae – Larger multicellular photosynthetic plant-like organisms commonly called seaweed.

Macrolide – A class of antibiotics that inhibit proteins synthesis by bacteria at the 50S ribosome. Examples include erythromycin and clarithromycin. Class of antibiotics derived from the polyketide pathway.

Macrophage  -A white blood cell that enters into a tissue in response to an infection as part of the inflammatory response. A mature phagocytic cell derived from a circulating monocyte. Powerful phagocyte that also secretes a large array of proteases, cytokines and growth factors and can act as an APC. In the presence of high levels of IFNγ, an activated macrophage becomes “hyperactivated” and acquires enhanced antipathogen activities and the capacity to kill tumor cells.

Macropinocytosis – An endocytic mechanism normally involved in fluid uptake. Internalization of extracellular fluid containing soluble macromolecules. Droplets are engulfed and form macropinosomes that undergo endocytic processing.

Macropinosome – Membrane-bound vesicle formed by plasma cell invagination around a droplet of extracellular fluid. See also macropinocytosis.

Macula flava – Sites of active collagen and elastin synthesis in newborns.

Mad cow disease – Brain degeneration disease of cattle caused by prions, also known as bovine spongiform encephalopathy (BSE).

Madarosis  – Loss of eyelashes.

Magnetosomes – Prokaryotic organelle that contains mineralized magnetic crystals of Fe3O4 or Fe3S4 surrounded by a protein layer.

MAH – Marketing Authorisation Holder (MAH).

Maillard reaction – Chemical reactions involved in the formation of AGEs from glucose and proteins.

Maintenance methylase – Enzyme that adds a second methyl group to the other DNA strand of half-methylated sites.

Major event – An event that has resulted in or contributed to a problem leading to a failure resulting in a severity level 2.

Major histocompatibility complex (MHC)The group of genes on the short arm of chromosome 6 (p6) that encodes human leukocyte antigens (HLA) which are considered being highly polymorphic leading to a large difference in the resultant expressed proteins on human cells. Region of the genome containing genes encoding the chains of the MHC class I, class II and class III proteins. MHC class I and class II proteins combine with antigenic peptides and display them on the surface of host cells for recognition by T cells. The MHC class III genes encode various proteins important in complement activation, inflammation and stress responses. It is differentiated mainly into class-I and class-II. Their encoded proteins on the surface of cells perform the presentation of protein antigen fragments (epitopes) to immune cells. MHC-class-I is found on all nucleated cells and presents antigens produced inside the cell (either own or viral proteins after infection) to cytotoxic CD8 lymphocytes and natural killer cells. MHC-class-II, in contrast, occurs physiologically only on specialized antigen-presenting cells and presents foreign antigens to the CD4 receptor of T-helper cells. In inflammation, it can be upregulated by other cells. 

Major requirements – Those process or product requirements that, if not met, would be associated with a failure mode of severity level 2.

MALDI – Matrix-assisted Laser Desorption/Ionisation, method of ionising molecules used in mass spectrometry. MALDI-TOF (time of flight) is the most relevant, where ions are accelerated in an electric field. A time-of-flight mass spectrometer measures their flight time, which depends on its charge and mass. This permits the composition of an unknown substance (e.g., an unknown protein) to be determined.

MalE protein – Carrier protein for maltose found in the periplasmic space of E. coli.

Malformation – A nonprogressive congenital anomaly.

Malignant – A disease that can kill its host. Cancers are often malignant if left untreated. Severe hypertension is referred to as malignant hypertension if the untreated condition has a high likelihood of producing stroke or renal failure.

Malignant tumor – A malignant tumor, also known as cancer, is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. A mass formed by abnormally dividing cells. Appears disorganized, is rarely encapsulated, and may undergo metastasis. Directly lethal to the host unless removed or killed.

Malthusian growth – Growth law that predicts the population reaching infinite size in finite time. The term is named after Thomas Robert Malthus, who described potential resource depletion problems that an exponentially growing population can encounter in his 1798 essay on population growth.

Maltose-binding protein (MBP) – Protein of E. coli that binds maltose during transport; often used in making fusion proteins.

Mammalian Target of Rapamycin (mTOR) – A kinase that regulates cell growth, cell proliferation, cell survival, protein synthesis, and transcription.

Managed Review Process – The manner in which U.S. FDA oversees and conducts the review of submissions to ensure quality and timeliness of the reviews and communications with sponsors.

Management – The process composed of inter-related technical and social functions and activities, occurring in a formal organizational environment for the purpose of accomplishing pre-determined goals through the use of human and other resources.

Management buy-in (MBI) – This situation occurs when a manager or a management team from outside the company raises the necessary finances, buys the company, and becomes the company’s new management. A management buy-in team often competes with other purchasers in the search for a suitable business.

Management buy-out (MBO) – A term refering to a leveraged buy-out (LBO) which is initiated by an existing management team, which then solicits the involvement of a private equity group.

Mannose-binding lectin (MBL) – A serum collection that specifically binds to distinctive mannose structures on microbial pathogens in the blood. Engagement of MBL triggers lectin-mediated complement activation.

Mantle cells (outer support cells) – These are cells that surround the inner support cells and serve as a proliferative population that can replenish the population of inner support cells, which are progressively lost as they are specified as sensory hair cell progenitors.

Manufacturing material – Any material or substance used in or used to facilitate the manufacturing process, a concomitant constituent, or a by-product constituent produced during the manufacturing process, which is present in or on the finished device as a residue or impurity not by design or intent of the manufacturer.

MAO-A gene – Gene that encodes monoamine oxidase A.

MAPK signaling (mitogen-activated protein kinase) – A signal transduction pathway that plays a role in cell proliferation. Also known as the Ras-Raf-MEK-ERK pathway.

MAR proteins – Proteins that form the connection between the chromosomes and the nuclear matrix.

Marathon Mous- Transgenic mouse that runs farther than a normal mouse.

Marketing authorization – Authorisation (license) granted by a governing body that allows a firm to sell a biopharmaceutical product. It is sometimes referred to as a license.

Market capitalisation (market cap) – This term refers to the equity market value. It is calculated by multiplying the number of shares outstanding by the current market price of one share.

Marketing Authorisation Holder (MAH) – The company that has been granted a marketing authorisation for a medicinal product by a competent authority of a member state in accordance with Directive 2001/83/EC (as amended) or by the European Commission in accordance with Regulation (EC) No 726/2004, and is responsible for marketing the medicinal product.

Masking -The biochemical alteration of the N-terminal end of a protein in order to prevent its degradation. This is often done in cells by adding acetyl groups.

Mass Spectrometry Peptide Mapping – A protein analysis technology where proteins are “cut” into peptides and their amino acid sequence determined. By comparing this information with a protein database, the original protein can be identified. 

Mass spectrometry – Measuring the mass/ charge ratio of a substance by ionizing it and measuring the deviation of accelerated ions in an electric field.

Massively parallel sequencing – Sequencing technologies that use miniaturized platforms for sequencing millions of DNA fragments in parallel. High-throughput DNA sequencing that allows for numerous strands of DNA to be sequenced in a parallel fashion. Also called next- generation sequencing (NGS).

Mast cell – Granular inflammatory cell which predominates in allergic responses.

Mast cell progenitor (MCP) – Early descendant of MPPs that gives rise to mast cells.

Mast cells – Leukocytes with granules containing preformed mediators such as histamine. Mast cell degranulation is important for inflammation and allergy.

MAT locus – Chromosomal locus in yeast that controls the mating type and exists as two alternative forms: MATaor MATα.

Maternal- Originating from the mother. A normal human nucleus contains 2 x 23 chromosomes, of which one set comes from the mother and one from the father (paternal).

Maternal-fetal tolerance – Tolerance of a mammalian mother for her fetuses despite their expression of allogeneic paternal MHC.

Matrix – A structure or scaffold on which cells can grow in two or three dimensions.

Matrix attachment regions (MAR) – Site on eukaryotic DNA that binds to proteins of the nuclear matrix or of the chromosomal scaffold—same as SAR sites.

Matrix-assisted laser desorption-ionization (MALDI) – Type of mass spectrometry in which gas-phase ions are generated from a solid sample by a pulsed laser.

Mature onset diabetes of the young – A dominant monogenic form of type 2 diabetes.

MAVS (mitochondrial antiviral signaling) – It was discovered as a mitochondrial protein essential for antiviral signaling (ie, IFN induction). It is also termed as IPS (interferon promoter stimulator) or VISA or Cardif.

Maximally tolerated dose (MTD) – The dose just below that which produces unacceptable toxicities.

Mb – Megabase pairs (1,000,000 base pairs DNA).

MCAT – Medical College Admission Test (MCAT).

MDA5 (melanoma differentiation associated gene) – It serves as an RNA sensor for the detection of viral RNAs and belongs to the DEAD- box RNA helicase family. It was first discovered as the melanoma differentiation associated gene, as the name implies.

MDD – Major depressive disorder (MDD).

MDR – Medical Device Regulation (EC 2017/745).

MDR – Medical device record (MDR).

MDUFA – Medical Device User Fee Act- comparable to PDUFA, but for medical devices. 

MES – Manufacturing Execution System (MES)

Mechanism-of-Action (MoA) – The manner in which a product acts at a molecular level. The way in which a product works.

Mechanosensory hair cell – Specialised sensory cells found in the inner ear of birds, fish, amphibians, reptiles and mammals. Modified microvilli located at the luminal surface of each cell detect small movements or pressure waves.

MedDRA – Medical Dictionary for Adverse Event Reporting- an ICH agreed-upon terminology dictionary for reporting medical conditions that may be associated with investigational or new drugs by common terms consistently used by all sponsors.

Medial crura – The columellar segment of the lower lateral (or alar) cartilage that extends from the floor of the nose to the tip.

Mediator – A multiprotein complex that acts as a coactivator of transcription in eukaryotes. It was discovered in the laboratory of Roger D. Kornberg, the 2006 Nobel Prize in Chemistry laureate. The mediator interacts with transcription factors and RNA polymerase II. Its main function is to transmit transcription factor signals towards the polymerase.

Mediator complex – A protein complex that transmits the signal from transcription factors to the RNA polymerase in eukaryotic cells.

Medical Device – A device that fulfils the definition of a medical device, as defined in the relevant EU legal framework, and is intended to be placed on the EU market or made available on the EU market. This also applies to part of a device that fulfils the definition of Article 2(1) Medical Device Regulation (EU 2017/745 MDR).

Medical Device Manufacturer – The commercial entity manufacturing and supplying sterile/non-sterile devices and/or device parts to the medicinal product manufacturer.

Medicinal product (MP) – Term used by EMA and EU member states in the same manner as U.S. FDA uses the term “drug”.

Medicinal Product Manufacturer – The physical location and commercial entity legally responsible for the manufacture of the integral and/or co-packaged medicinal product.

Medulla – Inner region of an organ such as the thymus.

Medullary thymic epithelial cells (mTECs) – See thymic epithelial cells.

Megakaryocytes – Multinucleate myeloid leukocytes giving rise to platelets.

Megalocornea – Horizontal cornea length exceeding 13 mm or 12 mm in the newborn.

Meiosis – A form of cell division consisting of two nuclear divisions of a diploid cell resulting in the formation of haploid gametes. Reduction division, a type of cell division that results in a reduction (usually by half) in chromosome number. Reductive cell division occurring exclusively in testes and ova- ries and resulting in the production of haploid cells, including sperm cells and egg cells.

Melanocortin receptor – Receptor for one of several hormones of the melanocortin family.

Melanocortins – Family of peptide hormones all derived from the same precursor protein: pro-opiomelanocortin (POMC).

Melanopsin – The opsin-based photopigment of intrinsically photosensitive RGCs.

Melt – When DNA is used, refers to its separation into two strands as a result of heating.

Melting temperature (Tm) – Temperature at which 50% of a protein is denatured. Temperature at which DNA has separated into two strands (melted).

Membrane attack complex (MAC) – Final product in the complement pathway which causes microorganism death by forming pores in cell membranes. Pore-shaped structure assembled in the membrane of a pathogen or target cell as a consequence of complement activation. Facilitates osmotic imbalance and lysis.

Membrane-bound Ig (mIg) – Cell surface form of Ig molecule. BCR antigen-binding moiety.

Membraneous cells (M-cells) – Also called microfolded cells, they are a special type of cells in the modified epithelium overlying organized lymphoid follicles, the so-called follicle-associated epithelium (FAE). Their name refers to the fact that they have a different, usually smooth, surface ultrastructure compared to the ordinary epithelial cells. They form cellular pockets populated by groups of leukocytes which are separated from the lumen by a thin luminal cytoplasmic sheet. M-cells actively transcytose luminal antigens for uptake by the leukocytes and their subsequent presentation to and activation of T- and B-cells in order to generate antigen-specific effector cells.

Memory cells – Lymphocytes generated during a primary immune response that remain in a quiescent state until fully activated by a subsequent exposure to specific anti- gen (a secondary immune response). Specialized B cells that wait for possible infections instead of manufacturing antibodies.

Mendelian disease – A disorder that is inherited from one generation to the next in a similar pattern as a trait studied by Mendel which is usually attributed to a mutation to a single gene such that one allele is dominant over another allele.

Mendelian genetics – Classical genetics, focuses on monogenic genes with high penetrance. Mendelian genetics is a true paradigm and is used in discussing the mode of inheritance (see Monogenic disease). Genetic inheritance pattern proposed by Gregor Mendel that is composed of three main laws. The Law of Segregation states that allele segregation results in one allele per gamete. The Law of Independent Assortment states genes from different traits segregate independently. The Law of Dominance states that alleles may be dominant or recessive, and dominant alleles overshadow recessive alleles.

Mendelian inheritance – A pattern of inheritance observed for traits that are determined by genes contributed by the mother or the father.

Mendelian segregation – The process whereby individuals inherit and transmit to their offspring one of the two alleles present in homologous chromosomes.

Meristem culture – Cell culture grown from undifferentiated plant cells taken from meristem tissue.

Merger – When two firms, often of about the same size, agree to go forward as a single new company rather than remain separately owned and operated (also referred to as a ‘merger of equals’).

Mergers and Acquisitions (M&A) – The phrase mergers and acquisitions refers to the aspect of corporate strategy, corporate finance, and management dealing with the buying, selling, and combining of different companies that can aid, finance, or help a growing company in a given industry grow rapidly without having to create another business entity.

Meridional amblyopia – A lack of contrast sensitivity to high and medium spatial frequency contours oriented along a particular meridian without any refractive error or ocular pathological process affecting the visual function.

Mesenchymal condensation – Formation of a densely packed mass of mesenchymal cells that occurs during the formation of many epithelial organs (e.g., tooth, lung, pancreas, kidney, heart valve, breast, salivary gland, bone, cartilage and hair follicle).

Mesenchymal Stem (or Stromal) Cells (MSC)- Multipotent stem cells derived by culturing various tissue of the body in the laboratory on plastic. MSCs can easily be derived from bone marrow and fat tissue.

Mesendoderm – A transient vertebrate tissue that forms during gastrulation and is equally capable of differentiating into mesoderm and endoderm.

Mesoderm – One of the three germ layers in the developing embryo, forming tissues such as bone, muscle, and fat. One of the three vertebrate germ layers formed during gastrulation that gives rise to connective tissue, muscle, and the skeletal and circulatory systems. The middle of three germ layers that gives rise later in development to such tissues as muscle, bone, and blood.

Mesopic – The 3-log unit range of background illuminance in which rod and cone signals temporally sum in cones and the cone bipolar pathway.

Messenger RNA (mRNA) – RNA molecules that are synthesized from a DNA template in the nucleus (a gene) and transported to ribosomes in the cytoplasm where they serve as a template for the synthesis of protein (translation). RNA that carries the genetic code for the synthesis of polypeptides (proteins) on a ribosome.

Metabolic fingerprinting – Characterising all the metabolites that are present under a certain set of conditions or at a certain time.

Metabolic syndrome – The combination of obesity plus hypertriglyceride- mia plus low levels of HDL cholesterol plus hypertension plus hyperglycemia (i.e., prediabetes or diabetes). Metabolic syndrome occurs in nearly one in four adults in the U.S. and carries an increased risk of death from a variety of com- mon causes, including heart attacks.

Metabolism -The sum total of chemical reactions that occur in cells. Anabolic reactions are involved with synthesis while catabolic reactions are concerned with degradation and the generation of energy.

Metabolome – The total complement of small molecules and metabolic intermediates of a cell or organism.

Metagenomic library – A library of DNA sequences isolated from an environmental sample. Contains gene sequences from many different organisms and genetic elements.

Metagenomics – The study of all the genomes in a particular environment.

Metal chelation – Binding of metals (e.g., iron, copper, cobalt) by surrounding the metal with a molecular cagelike structure.

Metalloprotease – A protease that uses a metal cofactor to facilitate protein digestion.

Metallothionein – A metal-binding protein whose synthesis is induced only when certain heavy metals are present.

Metallothionein promoter – Promoter of gene encoding metallothionein; used in genetic engineering because it is very strong and is induced by traces of zinc or other metals.

Metaphase – Early part of the mitotic phase of the cell cycle in which chromatids become aligned along the center of a cell.

Metaplasia – A change in the properties of a cell or tissue from one type to another.

Metastable epiallele – Genes that are variably expressed in genetically identical individuals due to epigenetic modifications established during early development.

Metastases – Secondary tumors established by metastasis of a primary tumor to sites in a different organ or tissue.

Metastasis – Process by which malignant cells break away from a primary tumour and spread via the blood to secondary sites. Process in which cancer cells from a primary tumor move around the body and form secondary cancers.

Methionine sulfoximine – Toxic analog of methionine.

Methotrexate – Antibiotic that inhibits the enzyme dihydrofolate reductase in animal cells.

Methyl tert-butyl ether (MTBE) – A fuel additive that oxygenates gasoline so the engine runs with less knocking and the gasoline burns more completely.

Methylation of DNA – Cytosine nucleotides (when followed by a guanine) can be methylated by adding a methyl group. This pattern is transferred to daughter cells after cell division.

Methylcytosine binding proteins – Type of protein in eukaryotes that recognizes methylated CG islands Metronomic chemotherapy- Low-dose high-frequency administration of cytotoxic drugs (administered regularly, like a metronome, hence the term).

Mezzanine Financing – often called bridge financing as it acts as a bridge between the initial investors (e.g. venture capitalists and founders) and IPO owners or acquirers (e.g. other biopharmaceutical firms). This term either refers to a private equity financing round shortly before an initial public offering (IPO) or an investment that uses subordinated debt with fewer privileges than bank debt but more than equity and often has attached warrants.

MFL – Maximum Foreseeable Loss (MFL)

MHC – Major Histocompatibility Complex: Class I surface proteins involved in the cellular immune response to virus infections or mutations. They are produced by almost all body cells. Class II surface proteins are involved in the humoral immune response and produced by antigen-presenting cells. Class III non-membrane-bound plasma proteins are complementary factors, stress proteins, and tumor necrosis factors.

MHC (major histocompatibility complex) – MHC molecule displays an oligopeptide, called epitope, of antigens on cell surface of antigen- presenting cell (APC) such as DCs and macrophages.

MHC class I proteins – Cell-surface proteins composed of a polymorphic MHC class I α chain non-covalently associated with the invariant β2-microglobulin (β2m) chain. Expressed by most nucleated cells. They present peptide antigens to CD8+ T cells.

MHC class Ib and IIb proteins – Non-classical MHC proteins with restricted polymorphism. Most are not involved in antigen presentation.

MHC class II proteins – Cell surface proteins composed of a polymorphic MHC class II α chain and a polymorphic MHC class II β chain. Expressed on APCs. Present peptide antigens to CD4+ T cells.

MHC class III proteins – Proteins encoded by the MHC class III loci. Include certain complement proteins, heat shock proteins, TNF and LT.

MHC molecules – Proteins encoded by genes within the major histocompatibility complex. See also MHC class I, Ib, IIb, II, and III proteins.

MHC class II molecules (major histocompatibility complex class II molecules) – These molecules typically acquire autoantigen epitopes in endosomes and antigen processing compartments of antigen presenting cells and present them to antigen receptors of CD4+ T cells.

MHC restriction – The principle that a T cell recognizing a given antigenic peptide presented by a particular MHC molecule will not recognize the same peptide if presented by a different MHC molecule.

MHC-like proteins – Non-polymorphic proteins encoded outside the MHC (e.g., CD1). Structurally and function- ally similar to MHC proteins.

MICA, MICB – MHC class I chain related A and B. Hu- man stress ligands upregulated in response to heat, infection or transformation.

Michaelis-Menten enzyme – An enzyme whose activity is governed by Michaelis-Menten kinetics (see text and “velocity”).

Microalgae – Prokaryotic or eukaryotic photosynthetic microorganisms that are unicellular or simple multicellular structures that live in terrestrial or aquatic environments.

Microarray diagnostics – A rapidly developing tool increasingly used in pharmaceutical and genomics research that has the potential for applications in high-throughput diagnostic devices. Microarrays can be made of DNA sequences with known gene mutations and polymorphisms, as well as selected protein molecules.

Microarray Technology- Method to analyze expression of many genes simultaneously in the same cell sample. Short single-stranded.

Microautophagy-lysosome system – A system of protein degradation where the proteins are taken into the lysosome by direct transfer.

Microbial fuel cells – Device that uses microorganisms to obtain electrons for creating electrical currents

Microbiota – See commensal organisms.

Microbiota-associated molecular patterns (MAMPs) – Common molecular patterns borne by microbiota. May engage certain PRRs in the same way DAMPs or PAMPs engage other PRRs, enhancing inflammation.

Microblepharon – Vertical shortening of eyelids.

Micrococcus Agar Diffusion Assay -An assay for lysozyme activity (and tear disfunction) in which lysozyme in sample tears clear anagar plate containing the organism Micrococcus lysodeiticus over a set time period. The area of clearing is proportional to the amount (i.e., activity) of enzyme present. The assay is also known as the Schirmer Lysoplate Assay. 

Microcoria – Pupils less than 2 mm in diameter bilaterally.

Microcornea  – A small cornea, measuring less than 10 mm in diameter in adults or less than 9 mm horizontally in newborns.

Microdeletion – A chromosomal deletion of between hundreds to the low millions of base pairs. Unlike larger chromosomal deletions, micro- deletions are not readily detectable in microscopic analysis of chromosomal banding patterns (karyotype). Microdeletions are cytogenetic abnormalities that typically span several megabases of DNA. Microdeletions are too small to be visible with standard cytogenetics, but they can often be detected with FISH (fluorescent in situ hybridization). All of the microdeletion syndromes are rare diseases, and they typically arise as de novo germline aberrations (i.e., not inherited from mother or father, in most instances). Conditions that occur rarely and sporadi- cally to produce a uniform set of phenotypic features in unrelated subjects may be new cases of microdeletion syndromes. DiGeorge syndrome is a typical microdeletion disease, with a germline 22q11.2 deletion encompassing about 3 million base pairs on one copy of chromosome 22, containing about 45 genes. Neurofibromatosis I sometimes occurs as a microdeletion syndrome involving a region of chromosome 17q11.2 that includes the NF1 gene. Microdeletion disorders are a subtype of contig disorders (i.e., contiguous gene disorder). Examples of microdeletion syndromes include: cri du chat, Kallman syndrome, Miller–Dieker syndrome, Prader–Willi/Angelman syndrome, retinoblastoma, Rubinstein–Taybi syndrome, Smith–Magenis syndrome, steroid sulfatase def- iciency (ichthyosis), velocardiofacial syndrome (also known as DiGeorge syn- drome), Williams–Beuren syndrome, and Wolf–Hirschhorn syndrome. See Genomic structural variation and De novo germline mutation.

Microdeletion syndromes  – A group of disorders affecting multiple genes, resulting from deletions of a chromosome segment spanning less than 5 Mb.

Microenvironment – An area within a room where environmental control is enhanced from the surrounding environment. Microenvironments typically control particulate, but also may provide added control of the temperature and humidity beyond that provided in the background. Common examples of microenvironments are: unidirectional flow or “local protection” hoods, isolators, RABS, and biological safety cabinets.

Microflora – See commensal organisms.

Microfluidics – Manipulation of fluids on a micrometer scale.

Microglia – Macrophages in the brain.

Micrognathia and retrognathia – Conditions in which the jaw is underdeveloped. Micrognathia is specific to the lower jaw (mandible), where- as those with retrognathia have a smaller, often receding, upper (maxilla) and lower jaw.

2-micron circle (2μ circle) – A small multicopy plasmid found in the yeast Saccharomyces cerevisiae, whose derivatives are widely used as vectors.

Microperforation – Small and shallow perforations of the cortical plate without need for a gingival flap.

Microperimetry or fundus-controlled perimetry – A type of visual field test which uses one of several technologies to create a “retinal sensitivity map” of the quantity of light perceived in specific parts of the retina in people who have lost the ability to fixate on an object or light source.
The main difference with traditional perimetry instruments is that, microperimetry includes a system to image the retina and an eye tracker to compensate eye movements during visual field testing.

Microphakia  – Abnormally small lens.

Microphthalmia – A small, disorganized globe that is two standard deviations below the age-adjusted mean axial length.

MicroRNA (miRNA) – A kind of short RNA (ie, 20—22 nt in length) found in eukaryotic cells, that regulates mRNA translation and mRNA stability. Small but abundant species of RNA that regulate gene expression by pairing with complementary sequences of mRNA. Such complementation usually causes silencing of the mRNA. It is estimated that humans have more than 1000 different microRNA, also called miRNA species. A form of autosomal dominant hearing loss is caused by mutations in MIRN96 microRNA. See Regulatory RNA element. Small regulatory RNA molecules of eukaryotic cells.

Microsatellite – Also known as simple sequence repeats (SSRs), microsatellites are DNA sequences consisting of repeating units of 1–4 base pairs. Microsatellites are inherited and polymorphic. Within a population there may be wide variation in the number of repeats at a chosen microsatellite locus. Friedreich ataxia, a neurodegenerative disease characterized by ataxia and an assortment of neuro- logic and muscular deficits is an example of a microsatellite disease. A common molecular abnormality of Friedreich ataxia is a GAA trinucleotide repeat expansion within an intron belonging to the gene encoding frataxin. Normal levels of frataxin are apparently necessary for the health of nerve cells and muscle cell. See Microsatellite instability and Anonymous variation.

Microsatellite DNA – Small array (often less than 0.1kb) of short, tandemly repeated DNA sequences.

Microsatellite instability – When there is a deficiency of proper mismatch repair (a type of DNA repair), DNA replication is faulty, and novel microsatellites appear in chromosomes. This phenomenon is called microsatellite instabil- ity and it occurs in some types of cancers, particularly colon cancers arising in hereditary non-polyposis colorectal cancer syndrome.

Microsatellite polymorphisms – Genetic markers that consist of very short repeated sequences of 2 to 5 nucleotides in length.

Microtia – A condition in which the ear is underdeveloped, misshapen, and lacking the external auditory meatus. There are varying degrees of  microtia, from mild, in which the ears are smaller, but have all the main features of the ear, to severe, in which no ear is formed (anotia).

Microtubule – A small tubule composed of the protein tubulin, often found as arrays in neural axons, involved in transport of cellular components.

Midface – The middle part of the face (includes the upper jaw, nose cheekbones and eye sockets).

Mifepristone – A synthetic steroid that is used in high concentrations to induce abortions and, in low concentrations, to induce genes artificially.

Mighty Mouse – Transgenic mouse with colossal muscle development.

Migration of Cells- Can move to different locations individually or as group, actively in response to attracting or propelling signals, or passively during growth. Considerable cell migration takes place during embryonic development and during formation of metastasesin cancer.

MIICs – MHC class II compartments. Late endosomal compartments that are part of the exogenous antigen processing pathway.

Milestone payments – In a licensing agreement, the payments which are either made by the licensee to the licensor at specified times in the future or when certain technological/business objectives have been accomplished. In drug development, typical milestones are the achievement of Phase II, Phase III, and FDA/EMEA approval. Are associated with license agreements and are paid when one party makes progress such as movement through the clinical trial process.

MIM number – An ID from OMIM specifying a disease with a genetic component.

Mineralocorticoid activity – Ability of steroid hormones to affect the concentration of cations in the bloodstream by alteration of transport of such ions in the kidney tubules.

Mini-gene – Miniature gene encoding part of a protein, usually made by artificial DNA synthesis.

Minimal risk – Risk that is inherent in the daily lives of healthy individuals.

Minimum angle of resolution – The size of the angle subtended at the eye of the smallest feature which can be reliably identified on an optotype.

Minisatellite – Another term for variable number tandem repeat, a cluster of tandemly repeated sequences in DNA whose number of repeats differs from one individual to another.

Minisatellite DNA – An intermediate-size array (often 0.1–20kb long) of short, tandemly repeated DNA sequences. Hypervariable minis- atellite DNA is the basis of DNA “fingerprinting” and many vari- able number tandem repeat markers.

Minor allele frequency – The frequency of the least common allele in a given population.

Minor event – An event that has resulted in or contributed to a problem leading to a failure resulting in a severity level 3.

Minor H peptides – Peptides derived from donor minor his tocompatibility antigens.

Minor histocompatibility antigens (MiHA) – Proteins that exist in a small number of different allelic forms in a population. In a transplant situation, peptides derived from allogeneic MiHA of the donor are recognized as non- self by the recipient’s T cells.  Generally invoke slower, weaker graft rejection than MHC incompatibilities.

Minor histocompatibility loci – Genes encoding minor histocompatibility antigens.

Minor requirements – Those process or product requirements that, if not met, would be associ- ated with a failure mode of severity level 3.

Minos – A transposon originally found in insects.

Minus (−) strand – The noncoding strand of RNA or DNA.

Minute of arc – One-sixtieth of a degree.

miRISC– an RNA-induced silencing complex that contains mature miRNA and guides its inhibitory function to the target mRNA.

Misexpression – The addition of RNA, DNA or protein into a developing embryo that naturally receives less or none of that same product.

Mismatch repair system – DNA repair system that recognizes mispaired bases and cuts out part of the DNA strand containing the wrong base.

Mispricing – Occurs when the secondary market consistently pays above or below the offer price.

Missense mutation – Change in the DNA sequence involving a single base pair which causes an amino acid being substituted for another. Mutation in which a single codon is altered so that one amino acid in a protein is replaced with a different amino acid. Substitution of a single DNA base that results in a codon that specifies an alternative amino acid.

Mitochondria – Cellular organelles present in eukaryotic organisms that enable aerobic respiration and generate the energy to drive cellular processes. Each mitochondrion contains a small amount of circular DNA encoding a small number of genes (approximately 50). Self-replicating organelles wherein respiration, the production of cellular energy from oxygen, occurs. As far as anyone knows, the very first eukaryote came fully equipped with a nucleus, one or more undulipodia, and one or more mitochondria. Similarities between mitochondria and eubacteria of Class Rickettsia suggest that the eukaryotic mitochondrium was derived from an ancestor of a modern rickettsia. All existing eukaryotic organisms, even the so-called amitochondriate classes (i.e., organisms without mitochondria), contain vestigial forms of mitochondria (i.e., hydrogenosomes and mitosomes). A single eukaryotic cell may contain thousands of mitochondria, as is the case for human liver cells, or no mitochondria, as is the case for human red blood cells. The control of mitochondrial number is determined within the nucleus, not within the mitochondrion itself. The mitochondria in a human body are descended from mitochondria contained in the maternal oocyte; hence, mitochondria have a purely maternal lineage. See Mitochondriopathy. Organelles in the cell that generate chemical energy to power cellular processes and also serve as sites for numerous metabolic processes and reactions.

Mitochondrial death pathway – Program of apoptosis that involves activating mitochondrial proteins to kill the cell; often activated by internal factors such as DNA damage.

Mitochondrial DNA – Circular DNA present in mitochondria that codes for about 10 genes and plays an important role in cell metabolism. The “power- house” of a cell.

Mitochondrial inheritance – A form of inheritance from the genetic material located within the mitochondria. This form of inheritance is maternal and is always inherited by the progeny due to being part of the ovum.

Mitochondrial replacement – A potential therapy to prevent certain mitochondrial diseases by replacing mutant maternal mitochondria in an oocyte (egg) with those from an unaffected individual prior to in vitro fertilisation

Mitochondrion (pl. Mitochondria) – A subcellular oganelle in which certain metabolic processes are isolated from the remainder of the cell, prominently oxidative phosphorylation. This organelle is composed of an outer membrane, an intermembrane space, an inner membrane containing infoldings (cristae), and an inner space (matrix).

Mitochondriopathy – A disease whose underlying cause is mitochondrial pathology (i.e., dysfunctional mitochondria, or an abnormal number of mito- chondria). Mitochondriopathies can be genetic or acquired. Most of the genetic mitochondriopathies are caused by nuclear gene mutations. Though mitochondria have their own genes, the mitochondrial genome codes for only 13 proteins of the respiratory chain. All the other proteins and structural components of the mitochondria are coded in the nucleus. Mitochondriopathies can involve many different organs and physiologic processes. Mitochondrial defects affect- ing muscles include myopathy (i.e., weakness), fatigue, and lactic acidosis. The peripheral and central nervous systems disorders include: polyneuropathy, leu- cencephalopathy, brain atrophy, epilepsy, upper motor neuron disease, ataxia, and extrapyramidal side effects. Endocrine manifestations may include hyperhi- drosis, diabetes, hyperlipidemia, hypogonadism, amenorrhea, delayed puberty, and short stature. Heart damage may include conduction abnormalities, heart failure, and cardiomyopathy. Ocular changes may include cataract, glaucoma, pigmentary retinopathy, and optic atrophy. Hearing changes may include deaf- ness, tinnitus, and vertigo. Gastrointestinal disorders may include dysphagia, diarrhea, liver disease, motility disorder, pancreatitis, and pancreatic insuffi- ciency. Renal disease may include renal failure and cyst formation. Blood cells may develop sideroblastic anemia. A mitochondriopathy should be in the dif- ferential work-up for any unexplained multi-system disorder, especially those arising in childhood.

Mitogen -Molecule that non-specifically stimulates cells to initiate mitosis.

Mitogen-activated protein (MAP) kinases – Family of signal transmission proteins that form part of a phosphotransfer cascade in animal cells.

Mitogen-activated protein kinase (MAPK) – A phosphorylating enzyme that acts at the cell nucleus. In the diabetic state, this enzyme probably acts in a manner similar toprotein kinase C.

Mitophagy – Degradation of mitochondria by autophagy or engulfment and degradation by a lysosome.

Mitosis – A form of cell division in which somatic cells produce identical daughter cells. Cell division in somatic cells. The phase in the cell cycle of somatic cells (i.e., not germ cells) wherein the replicated chromosomes condense and separate to form two daughter cells.

Mitotic – Relating to mitosis. See Post-mitotic.

MLPA – Multiplexligation-dependentprobeamplification.

MMR vaccine – MMR vaccine is an immunization against measles, mumps, and rubella. It is a mixture of live attenuated viruses of the three diseases, administered via injection.

MoA – The mechanism of action (MoA) of a small molecule refers to the mechanism by which the small molecule produces its effect.

Mobile DNA – Segment of DNA that moves from site to site within or between other molecules of DNA.

Mobile phase – The liquid or solvent containing the mixture of molecules that moves over the stationary phase in column chromatography.

MOC – Maintenance of certification (MOC).

Modeling – A computer strategy that can be used to justify the involvement of humans in research.

Mode-of-Action – The manner in which a product acts at a cellular level. The way in which a product works.

Modification enzyme – Enzyme that binds to the DNA at the same recognition site as the corresponding restriction enzyme but methylates the DNA.

Modifier gene – A gene whose expression can influence a phenotype resulting from mutation at another locus.

Module – The word “module” has many different implications for biopharmaceutical facilities. It is important to differentiate during the design process the extent or type of modularization intended and to define the effect on the disciplines involved. Modules in the biopharmaceutical design context, e.g., may consist of:

– Integrated process lines (individual continuous bioprocessing modules)

– Total integrated facility sections, including building, process, services and utilities elements

– Process or building services/HVAC/utilities skids or repetitive items

– Building sectional modules

– Modular process or building elements

Modular design – Taking various useful domains of different proteins and combining them into a new engineered protein.

Moebius syndrome – A congenital neurologic disorder marked by unilateral or bilateral facial weakness, often with horizontal ocular motility restriction, usually in abduction.

MOI (multiplicity of infection) – It refers to as the number of virus particles imposed to one cell.

Molar absorptivity – The absorbance of a 1 molar solution of pure solute at a given wavelength. The higher it is, the more light is absorbed.

Molarity (molality) – The number of moles of a substance per liter of solution. For practical purposes, there is little difference between molarity and molality.

Molecular chaperone – Protein that oversees the correct folding of other proteins.

Molecular evolution – The study of the evolution of DNA, RNA, orproteins.

Molecular genetic testing – Molecular genetic testing for use in patient diagnosis, management, and genetic counseling; this is increas- ingly used in presymptomatic (predictive) genetic testing of at- risk family members using a previously known disease-causing mutation in the family.

Molecular mimicry – Concept that a pathogen epitope may resemble a self-epitope closely enough to activate an autoreactive lymphocyte, if the appropriate cytokine mi croenvironment is present.

Molecular phylogenetics – Study of evolutionary relationships using DNA or protein sequences.

Molecular weight standards – Mixture of varying sized DNA or proteins of known size used to compare to unknown proteins.

Monitoring – The process of oversight.

Monoamine oxidase (MAO) – Enzyme involved in degradation of neurotransmitters of the catecholamine family.

Monochromacy – A complete lack of ability to distinguish colors caused by defects in the morphology or function of the cones.

Monocistronic mRNA – An mRNA transcript that encodes one protein. The mRNA carrying the information of a single cistron that is a coding sequence for only a single protein.

Monoclonal antibodies – Antibodies derived from a single B-lymphocyte or cell culture of clones. They are specific to a single antigen and even a single epitope of the antigen in question. They are very important biotechnological products.

Monoclonal antibodies (Mab) – It refers to monospecific antibodies that are made by identical immune cells that are all clones of a unique parent cell. Monoclonal antibodies have monovalent affinity, in that they bind to the same epitope.

Monoclonal antibody (mAb) – Antibodies of a single, known specificity produced by a single B cell clone.  A pure antibody with a unique sequence that recognizes only a single antigen and that is made by a cell line derived from a single B cell. See also hybridoma.

Monoclonal gammopathy of undetermined significance (MGUS) – MGUS is the precancer for multiple myeloma. It consists of a clonal proliferation of plasma cells that all produce an identical immunoglobulin molecule. The cumu- lative effect of a clone of plasma cells, all synthesizing the same immunoglobulin species, is a distinctive protein spike on blood examined by a technique known as electrophoresis, which separates out different molecular species of proteins in serum samples. MGUS is a common condition found in the elderly and may occur in about 1% of the population over 70 years of age. Progression of MGUS to multiple myeloma is infrequent, with a conversion of about 1–2% per year. Because MGUS occurs in an elderly population, the chance of MGUS progress- ing to myeloma within the lifespan of the patient is quite low. Still, it seems as though every case of multiple myeloma follows a preceding MGUS.

Monocyte  – Large non-granular leukocyte which is recruited in the later stages of acute inflammation. A mononuclear white blood cell. They have a number of roles in the cellular immune system, one of which is to engulf and consume tagged antigenic cells (phagocytosis). Myeloid cell in the blood that enters the tissues and matures into a macrophage.

Monogenetic Disease- A disease caused by a DNA mutation in a single gene.

Monogenic – Pertaining to a disorder occurring as a direct consequence of single gene defects.

Monogenic disease – Disease caused by an alteration in a single gene. It should be noted that a single gene may have pleiotropic effects on multiple cellular pathways, on different cell types, and at different stages of organismal devel- opment. Hence, monogenic diseases may have complex phenotypes. This is sometimes true for altered regulatory elements (e.g., genes that code for tran- scription factors). It should also be noted that every monogenic disease will have polygenic modifiers. The expression of a normal or mutant gene depends on complex interactions with cellular machinery, and those interactions will depend on epigenetic and genetic conditions that vary among individuals. In general, most inherited rare diseases are monogenic disorders; common diseases seem to be polygenic. Some of the specific types of genetic alterations that account for many monogenic rare diseases are: deletions (e.g., Duchenne muscular dys- trophy), frame-shift mutations (e.g., factor VIII and IX deficiencies), fusions (e.g., chronic myelogenous leukemia, hemoglobin variants), initiation and ter- mination codon mutations (e.g. alpha thalassemia), inversions (a type of beta thalassemia), nonsense mutations (familial hypercholesterolemia), point muta- tions (e.g., sickle cell disease, glucose-6-phosphate dehydrogenase deficiency), promoter mutations (a type of thalassemia), RNA processing mutations, includ- ing splice mutations (e.g. phenylketonuria). Not all rare diseases are mono- genic and not all common diseases are polygenic. There are examples of rare diseases that are digenic (i.e., caused by two genes), and there are examples of common diseases for which a small subset of individuals has a non-syndromic monogenic form of a common disease (e.g., MODY 4, also known as mono- genic diabetes). There are also examples of common diseases for which a syndromic monogenic disease accounts for a small subset of individuals who have the common disease (e.g., Werner syndrome, which produces a complex disease phenotype, including diabetes). See Polygenic disease, Digenic disease, Non-syndromic disease, Syndromic disease, and Mody 4.

Monomorphic gene – A gene that exists in a single allelic form within a species so that all individuals share the same nucleotide sequence at that locus.

Mononucleosis – A condition caused mainly by Epstein–Barr virus that causes the proliferation of white blood cells.

Monopodial – Branching in which side-branches form from a main trunk.

Monosaccharide – A carbohydrate consisting of a single sugar unit.

Monozygotic twins – Two individuals developed from one fertilized oocyte that share identical genomes.

Monte Carlo analysis (or Monte Carlo simulation) – Term describing the estimation of the expected value by computing the average from a simulated sample of a large number of observations. A mathematical technique developed in 1946 by John von Neumann, Stan Ulam, and Nick Metropolis. The technique employs computers to calculate the outcomes of probabilistic events by generating random numbers and using the resultant values, constrained within a model system, to simulate repeated biological trials. Monte Carlo simulations can be used to model polygenic diseases or pathways composed of proteins coded by polymorphic genes.

Mooren’s ulcer – A corneal disease beginning in the stroma presumably of autoimmune origin. The cornea eventually becomes scarred.

Morphogen – A protein that acts on target cells at a distance from its cell of origin, that forms an expression or activity gradient over a field of responsive cells, and that drives different cellular responses at different distances from the signal source. Morphogens can have non- synonymous or synonymous activity gradients, based on whether the signaling downstream of ligand-receptor activation exhibits a gradient that correlates with the extracellular ligand concentration.

Morpholino-antisense oligonucleotides – Synthetic oligonucleotides with morpholino rings instead of ribose and phosphorodiamidate linkages between nucleotides

Morula- A very early mammalian embryo (~2.5 days after fertilization in mice, 3-4 days in humans) just before the blastocyst forms;a small clump of cells, not bigger than the period at the end of this sentence.

Mosaic – A genetic mosaic is an individual who has two or more geneti- cally different cell lines derived from a single zygote.

Mosaicism – The presence of two or more cell populations in one individual that differ in their chromosomal genotype.

Motif – A DNA sequence pattern within a gene that, because of its simi- larity to sequences in other known genes, suggests a possible func- tion of the gene, its protein products, or both. A subset of a domain. Two or more motifs may form a domain, but not a complete polypeptide. Sometimes the distinction between motifs and domains is not apparent.

Mouse xenografts – Implanting human-derived cancerous tissue into mice that are often immune deficient.

Mousepox (Ectromelia virus) – Relative of smallpox virus that infects mice.

MP – Master Production procedure or Manufacturing Procedures- the methods that must be followed for every production of a batch or lot.

MRN (Mre11-Rad50-Nbs1) – A trimeric complex involved in DSB repair that senses the DNA damage (Box 8.1). It also exhibits endonuclease and exonuclease activity.

MRNA or messenger RNA – Messenger RNA, the molecule carrying the code for the series of amino that make up a protein; transfers the information to the ribosomes in the cytoplasm. The class of RNA molecule that carries genetic information from the genes to the rest of the cell

MTD – Maximum tolerated dose (MTD), the standard protocol for chemotherapy administration. It involves administering highest doses of cytotoxic drugs that a patient can tolerate and requires prolonged periods of time between treatments to allow the patient to recover. Since cancer cells are not equally susceptible to chemotherapeutic drugs, this approach can result in killing therapy-sensitive cells, leaving behind therapeutically resistant cancer cells.

Mucins – Large, highly glycosylated proteins. Mucus glycoproteins found principally in a mucoid layer of the precorneal tear film.

Mucopolysaccharide (MPS); Mucopolysaccharidosis – Mucopolysaccharide is the discontinued name for a glycosaminoglycan (GAG). A mucopolysaccharidosis is a lysosomal storage disease involving the incomplete metabolism of GAGs. The term, based on the discontinued name for GAGs, is still used.

Mucosa-associated lymphoid tissue (MALT) – Collections of APCs and lymphocytes in the mucosae.

Mucosae – Mucosal epithelial layers that cover the luminal surfaces of body passages such as the gastrointestinal, respiratory and urogenital tracts. Singular is “mucosa.”

Mucosal epithelium – Epithelial cells that line the internal, mucus-producing areas of the body (e.g., lungs or small intestine).

Mucosal immunity – It refers to an immune response pertaining to the mucous membrane, which is distinct in that IgA, instead of IgG, is the type of immunoglobulin that acts.

Mucosal wave – Wave motion of the vocal folds during phonation caused by airflow passing a closed glottis; essential to the production of sound.

Mucous membrane – The mucous membrane (or mucosa) is the lining covered in epithelium, which is involved in absorption and secretion. It lines cavities that are exposed to the external environment and internal organs. The sticky and thick fluid secreted by the mucous membranes termed “mucus” plays a critical role in eliminating invading microbes.

Mucous membrane (mucosa) – The moist lining (epithelium plus underlying connective tissue) of a passageway or vesicle in the body.

Müller cell – A glial cell in the vertebrate retina that spans from the vitreal surface to the external limiting membrane, with apical processes that extend into the interphotoreceptor matrix. These cells perform multiple functions in the retina including the processing of visual retinoids.

Müllerian ducts – Two embryonic tubes that extend along the mesonephric that become the uterine tubes, the uterus, and part of the vagina in the female and that form the prostatic utricle in the male. Also known as paramesonephric ducts.

Multidimensional protein identification technique (MuDPIT) – A method of analyzing complex mixtures of proteins with mass spectroscopy that separates the proteins using a liquid chromatography microcapillary column (2D LC microcapillary column).

Multifactorial – Related to, or arising through the action of many factors.

Multifactorial disease – Any disease or disorder caused by the interac- tion of multiple genetic (polygenic) and environmental factors.

Multifactorial inheritance – A combination of various genetic and environmental factors that contribute to the devel- opment of a trait.

Multigene family – A set of evolutionarily related loci within a genome, at least one of which can encode a functional product.

Multigene lysis – The bacteriophage process of using more than one gene product to disrupt bacterial envelope components to induce lysis.

Multigenic – Due to interaction of several genes

Multi-layered approach – Use of a multi-layered polymer scaffold characterised by a range of well-defined pore sizes and porosities within each layer, in order to influence the cell response.

Multiple cloning site (MCS) – Usually a synthetically produced oligonucleotide with unique individual binding sites for several restriction enzymes, which is then normally inserted into a vector. See also polylinker. A stretch of artificially synthesized DNA that contains cut sites for seven or eight widely used restriction enzymes

Multiple locus probing (MLP) – Variant of DNA fingerprinting in which multiple probes are used.

Multiple nuclear polyhedrosis virus (MNPV) – A particular baculovirus widely used as a cloning vector.

Multiple sclerosis (MS) – Autoimmune disorder where the myelin sheath of nerve cells is damaged or destroyed. Treatment methods often involve biotechnology such as the use of interferons or monoclonal antibodies.

Multiple-sequence alignment – An alignment of several sequences, often used in phylogenetic and protein modeling.

Multiples – This term is equal to comparables analysis. It refers to the valuation of an asset by using data on similar assets (multiples analysis, method of multiples).

Multiplex PCR – Running several PCR reactions with different primers in the same tube.

Multiplexing – Mixing multiple DNA samples together in one next-generation sequencing reaction. Each sample has a different barcode sequence in the adapters.

Multiplicity of infection (MOI) – The ratio of infectious viral particles to cells used for infection.

Multipotency – ability of a cell to differentiate into several cell types, having the same embryonic origin. Ability of a cell to give rise to different cell types of a given cell lineage. These cells include most adult stem cells, such as gut stem cells, skin stem cells, hematopoietic stem cells and neural stem cells.

Multipotent- Capacity of a cell to differentiate to multiple cell types. The ability of a progenitor to generate more than one class of terminally differentiated cells. A term that describes a cell that can develop into a limited number of specialized cell types.

Multipotent germline stem (mGS) cells – Pluripotent stem cell line derived from GS cells. mGS cells cannot reconstitute spermatogenesis, but have gained the potential to produce teratomas and chimeric animals.

Multipotent progenitor (MPP) – Descendant of HSCs that gives rise to NK/T, CLP and MCP precursors.

Multivalent vaccine – A vaccine prepared from two or more related pathogen species or multiple antigens from a single pathogen.

Multivesicular bodies (MVBs) – It refers to an intracellular structure that is generated by the inward vesiculation in late endosomes.

Murine leukemia virus (MuLV) – A simple retrovirus frequently used to construct vectors for gene therapy.

Muscular dystrophy – Several diseases that result in the wasting away of muscle tissue and cause premature death.

Mutagen – A chemical that produces alterations in the genetic sequence of DNA molecules. With few exceptions, carcinogens (i.e., chemicals that cause cancer) are mutagens. There are some mutagens that have not been shown to be carcinogens, and these chemicals tend to be so highly reactive with cellular molecules (e.g., lipids, proteins, RNA, etc.) that they cannot effectively reach nuclear DNA, the target molecule, or they kill cells rather than inflicting heritable damage. Agent causing mutation, e.g., high- energy radiation or chemical compounds such as base analogs.

Mutation – A change in one or more nucleotides in the DNA is called a variation or polymorphism if it is relatively frequent (and therefore not associated with serious disease) or a mutation if it is very rare; this can be associated with serious disease. A change in the DNA sequence of a gene. A change in the DNA sequences which can be either spontaneous or artificial triggered by stress, radiation and chemicals. A heritable alteration in the DNA sequence. A permanent change in hereditary material, typically a gene or chromosome. An alteration in a DNA sequence from its natural state. The effect of any mutation might be deleterious or benign. An alteration in the DNA (or RNA) that composes the genetic information. Changes in the DNA sequence, relative to a non-mutant (wild-type) sequence. Mutations may affect individual nucleotides (point mutations) or entire regions (deletions, insertions, and other rearrangements).

Mutation breeding – Using mutagens to induce genetic changes in plants in order to make or increase a desirable trait.

Mutation hot spot – Region of DNA where alterations in DNA due to mutation are common.

Mutator gene – Gene that affects the rate at which mutations occur.

Mutator phenotype – One of the hallmarks of cancer is genetic instability. The common cancers typically have thousands of genetic mutations, and these muta- tions perturb virtually every aspect of cellular physiology. It is hypothesized that during carcinogenesis, cells acquire a mutator phenotype that increases the rate at which genetic aberrations occur in cells, thus raising the likelihood that a cell will emerge with an oncogenic mutation that confers a malignant or pre- malignant phenotype.

Mx proteins – Antiviral proteins of animal cells that interfere with RNA polymerase of negative strand RNA viruses.

Myalgia – Muscle pain.

Myasthenia gravis – A disorder causing muscle fatigue that is due to failure of the nerves to stimulate the muscles to contract.

Myc – A small DNA segment that encodes for a peptide epitope that can be recognized by antibodies. The tag is used to mark uncharacterized proteins for analysis

Myc protein – Transcription factor involved in switching on several genes involved in cell division

Myconcogene – Oncogenic version of gene encoding Mycprotein

Myelin (layer) – A spiral wound coating of lipid around a nerve that insulates it and makes saltatory conduction possible.

Myeloablative conditioning – Complete elimination of a patient’s hematopoietic cells in the bone marrow using chemotherapy and irradiation, leading to eventual depletion of immune system cells from the peripheral blood and all secondary lymphoid tissues.

Myelodysplasia – Synonym for myelodysplastic syndrome. See Myelodysplastic syndrome.

Myelodysplastic syndrome – The myelodysplastic syndromes, formerly known as pre-leukemias, are several closely related diseases characterized by anemia, pancytopenia, disordered myeloid growth and maturation, the appearance of circulating blast cells, chromosomal abnormalities, and the frequent progression to leukemia. The myelodysplasias have a bimodal age distribution. Most cases occur in the elderly. Rare instances of myelodysplasia occur in children. A secondary type of myelodysplasia occurs following a bout of aplastic anemia or following chemotherapy for some other neoplasm.

Myeloid cells – Cells that develop from common myeloid progenitors (CMPs). Include erythrocytes, neutrophils, monocyte/macrophages, eosinophils, basophils and megakaryocytes.

Myeloma cells – Cancer cells derived from B cells, which therefore express immunoglobulin genes.

Myeloma Plasma cell – tumor that secretes large quantities of an Ig protein of (usually) unknown specificity. When tumors are present in multiple body sites, the disease is referred to as multiple myeloma.

Myelomas – Naturally occurring cancers derived from B cells that express antibodies, which are used to create hybridomas.

Myelopoiesis – The process of HSC differentiation into myeloid cells.

Myeloproliferative disorder – A blood disorder characterized by a clonal expansion of hematopoietic cells. These would include all of the non-lymphoid leukemias, plus the non-neoplastic diseases characterized by an increased number of normal or abnormal circulating blood cells (e.g., essential thrombocythemia, . When cells of lymphoid lineage proliferate in the blood, the analogous term, lymphoproliferative disorder, is applied.

MYOC – A gene on chromosome 1 whose mutations are associated with the formation of primary open angle glaucoma. The gene, variously known as GLC1A and TIGR, has an unknown normal function.

Myocardial Infarction or Heart Attack – Lack of oxygen to parts of the   heart cause heart cells to die. This may be life-threatening due to acute loss of heart function, and caused by block of a cardiac blood vessel (e.g., a blood clot).

Myocarditis – Inflammation of the heart muscle.

Myoepithelial cell – A cell found in glands between the base of the epithelium and the basal lamina. They contain myosin and can contract, assisting the expulsion of glandular material.

Myopia – The ability to see close objects more clearly than distant objects. Myopia can be caused by a longer-than-normal eyeball or by any condition that prevents light rays from focusing on the retina.



30-nanometer fiber – Chain of nucleosomes that is arranged helically, approximately 30 nm in diameter.

N nucleotides – Non-templated nucleotides. Nucleotides that are added randomly by TdT onto the ends of two antigen receptor gene segments undergoing V(D)J re- combination.

Na+K+ATPase (sodium-potassium pump) – Enzyme providing active transport mechanism in the retinal pigment epithelial and other cells. By catalyzing an ATP-dependent transport of three Na+ ions out and two K+ ions into the cell, a transmembrane sodium gradient is created (necessary for other Na+ coupled transport systems) and an osmotic gradient (drives water toward the choroidal or basal side of the RPE and away from the subretinal space).

NAD – Nicotinamide adenine dinucleotide; a cofactor that carries reducing equivalents during dehydrogenations; NAD usually acts in degradative pathways.

NAD+ – Nicotinamide adenine dinucleotide, acts as hydrogen acceptor in many biochemical reactions in the catabolic pathway and is reduced to NADH, in which form it becomes a hydrogen donor.

NADP – Nicotinamide adenine dinucleotide phosphate; a cofactor that carries reducing equivalents during dehydrogenations; NADP usually acts in biosynthetic pathways

NADPH – Nicotinamide adenine dinucleotide phosphate; a substance similar to NAD+ that plays a similar role in anabolism. Northern Blot Transfer of RNA that has been separated in gel electrophoresis onto a membrane. Once attached to the membrane, the RNA can be analyzed through hybridization, similar to Southern blotting.

NAI – No action indicated (NAI) – an inspectional outcome.

Naïve lymphocytes – Resting mature B and T cells that have not interacted with specific antigen; also known as virgin or unprimed.

Naked DNA vaccine – A vaccine based on an isolated DNA plasmid (no vector) encoding the vaccine antigen.

Nano – A prefix meaning one billionth (1/1,000,000,000)

Nanobody (Nb) – Recombinant antibody fragment that contains only the variable region of the single heavy chain of the Camelidae family

Nanocarpets – Structure formed by stacking a large number of nanotubes together, with their cylindrical axes aligned vertically. The carpet has antibacterial qualities and the ability to change color

Nanodensitry- The science and technology of diagnosing, treating and/or preventing oral and dental disease, relieving pain, and of preserving and improving dental health, using nanoscale-structured materials.

Nanofiber – Fiber less than one micron in size and approximately 50 nanometers (nm) in diameter. Nanofibers generate a large surface area to volume ratio and are used in many biomedical applications.

Nanoparticles – Particles of submicron scale—in practice from 100 nm down to 5 nm in size—that can be constructed in a variety of shapes

Nanophthalmos – A small eye, typically with no other asso- ciated structural ocular defects.

Nanorods – Nanoparticles that have a long cylindrical shape. Only the diameter must be in the nanoscale range

Nanoscale ion channel – Small nanoscale channel created using biological molecules that puncture small holes in the membrane and allow passage of ions under controlled conditions

Nanoshells – Hollow nanosized particles that can hold different materials

Nanotechnology – Control of the structure of matter based on molecule-by-molecule control of products and by-products; the products and processes of molecular manufacturing, including molecular machinery. The technology that works at the scale of the molecule, between 1 and 100 nanometers (nanoscale). The nanometer (nm) represents one thousandth of a micron, that is, 10–9 meters, the distance between two atoms. The goal of this technology is to individually control atoms and molecules in order to create new functional structures. The architecture of the biomaterial designs a topography and a surface, which influence the future of the SCs.

Nanotubes – Cylinders made of pure carbon with diameters of 1 to 50 nanometers that have novel properties that make them potentially useful in a wide variety of applications

Nanowires – Wires of dimensions in the order of a nanometer (10−9 meters) range, which can be metallic, semiconducting, and insulating. They can be designed of repeating organic units such as DNA

Naphthalene oxygenase – Enzyme that carries out the first step in naphthalene breakdown by inserting oxygen into the aromatic ring.

Nascent – Newly formed.

Nasopharynx-associated lymphoid tissue (NALT) – Mucosal lymphoid elements in the tonsils and upper respiratory epithelium. See also mucosa-associated lymphoid tissue (MALT).

National Institutes of Health (NIH) – Is the U.S. agency that funds the majority of basic research.

Natural antibodies Serum IgM – Antibodies that are produced by B-1 cells and generated without the need for exogenous antigen. Often recognize fungal components. Natural cytotoxicity Perforin/granzyme-mediated cytotoxicity of target cells carried out by NK cells.

Natural killer (NK) cells – Lymphoid lineage cells that recognise non-self entities with broad specificity. Activated when a target cell expresses ligands that bind to NK activator receptors but lacks sufficient MHC class I to adequately engage NK inhibitory receptors. Sentinels of innate immunity.

Natural killer T (NKT) cells – Lymphoid lineage cells that express a semi-invariant TCR recognizing glycolipid or lipid antigens presented on CD1d. Activated NKT cells quickly secrete cytokines that affect DCs, and NK, T and B cells. Sentinels of innate immunity.

Natural selection – A tendency for favorable heritable traits to become more common over successive generations. The traits are selected from pre-existing genetic variations among individuals in the population. The genetic variations may take the form of genetic sequence variations (e.g., SNPs) or genetic struc- tural variations. See SNP and Genomic structural variation.

Natural selection – The process whereby some of the inherited genetic variation within a population will affect the ability of individuals to survive to reproduce (“fitness”).

NB – Notified Body.

NBOp – Notified Body Opinion.

NCHPEG – National Coalition for Health Professional Education in Genetics (NCHPEG).

NCI – National Cancer Institute (NCI).

NCL – National Control Laboratory—a federal agency in a country responsible for quality control and lot release of investigational and marketed drugs.

NCR – see noncoding region (NCR).

NDA – New Drug Application – the submission to the U.S. FDA to gain marketing authorization for a new drug, which may include biotechnology-derived products.

Necroptosis – Type III programmed cell death pathway that is triggered by TNF-alpha binding to the TNF receptor in the presence of caspase inhibitors; cells death is disordered but triggers an immune response

Necrosis – Death of a cell characterized by cellular swelling and rupture; elicits an immune response. Non-programmed cell death in which cell membranes become permeable and cell contents are destroyed by lysosomal enzymes. Sudden, uncontrolled cell death due to infection or trauma. The cell spills its contents into the surround- ing milieu, releasing DAMPs that trigger inflammation. The pathological death of cells or tissues.

Negative (−) strand – The noncoding strand of RNA or DNA. The strand of RNA that is not able to be directly translated by ribosomes.

Negative predictive value – The chance a person who tested negative does not have the condition.

Negative regulation – Regulatory mode in which a repressor keeps a gene switched off until the repressor is removed.

Negative selection – A central tolerance process that removes autoreactive cells from the developing B or T lymphocyte pool destined for the peripheral tissues. Based on high affinity/avidity of antigen receptors for self-antigens.

Neglected disease – A near-synonym for rare disease. The assumption is that the rare diseases are often neglected: underfunded, underdiagnosed, under- treated, and generally lacking the kind of support systems available to the more common diseases. Though support for the rare diseases has been increasing, it is reasonable to conclude that with about 7000 rare diseases to consider, most of these conditions will be, to some extent, neglected. Terms that are commonly used interchangeably are: “rare disease,” “orphan disease,” and “neglected disease.”

Negligible event – An event that has resulted in or contributed to a problem leading to a failure resulting in a severity level 4.

NEI – National Eye Institute (NEI) in the US.

NEMA – National Electrical Manufacturers Association (US).

Neo-antigen – An antigen formed when a small, chemically reactive molecule binds to a self-protein. Can precipitate contact hypersensitivity, a form of type IV hypersensitivity.

Neogenesis – The process of generating new β-cells from stem or progenitor cells.

Neomycin phosphotransferase – Enzyme that confers resistance to antibiotics such as kanamycin and neomycin.

Neonatal immunity – Immunity in the newborn due to maternal circulating antibodies passed on to the fetus via the placenta, or maternal secretory antibodies consumed by the newborn in breast milk. A form of passive immunization.

Neonatal tolerance – Phenomenon that tolerance to an antigen is established more easily in neonatal than mature animals. Due to functional immaturity and low numbers of neonatal T and B cells, DCs, macrophages and FDCs, and altered lymphocyte recirculation.

Neoplasm – Neoplasm means “new growth” and is a near-synonym for “tumor.” Neoplasms can be benign or malignant. Leukemias, which grow as a population of circulating blood cells, and which do not generally produce a visible mass (i.e., do not produce a tumour), are included under the general term “neoplasm.” Hamartomas, benign overgrowths of tissue, are generally included among the neoplasms, as are the precancers, which are often small and scarcely visible. See also tumour.

Neovascularisation – Formation of functional microvascular networks with red blood cell perfusion. The formation of abnormal new blood vessels.

Nephric duct – An epithelial tube that is the source of the collecting ducts and that plays an essential role in inducing formation of the tubule in most kidney types.

Nephron – The functional unit of the kidney. Kidneys are comprised of as few as one or as many as one million or more nephrons. Nephrons are divided into segments, including the glomerulus, tubule, and collecting duct.

NES (nuclear export signal) – It refers to a peptide motif encoded by nuclear export proteins that is essential for nuclear export.

Neural crest – A cellular component of early embryos that gives rise to a wide variety of adult tissue derivatives, ranging from pigment cells, to sensory nerve cells, to bone.

Net present value (NPV) – A valuation method that calculates the expected value of one or more future cash flows and discounts them at a rate that presents the cost of capital (which will vary with the riskiness of the cash flow).

Networking – In venture capital investing, networking is the process of meeting people in order to create deal flow or identify coinvestors.

Net worth – For a company, the term refers to total assets minus total liabilities. Net worth is an important determinant of the value of a company, considering it is composed primarily of all the money that has been invested since its inception, as well as the retained earnings for the duration of its operation. It is also called shareholders’ equity or net assets.

Neural crest – A transient, multipotent, migratory cell population unique to vertebrates that is derived from the roof plate neuroectoderm at the time of neural tube closure giving rise to melanocytes, craniofacial cartilage, bone, smooth muscle, peripheral and enteric neurons, and glia. The transient tissue found in vertebrate embryos that is formed at the border of the neural plate and that undergoes a transformation into migrating cells, which differentiate into a huge variety of cells. It gives rise to most of the cartilage and bones of the head, the peripheral nervous system, and the pigments of the skin, among other things.

Neural crest cells – A transient, multipotent, migratory cell population from the embryonal neural plate, which possess great migratory potential and consist of diverse celllineages.

Neural induction – Intercellular communication that converts ectodermal cells into neural tissue.

Neural precursor cells – Partially differentiated cell in the neural lineage.

Neural retina – The sensory neuroepithelium of the eye that contains multiple neuronal cell types organized into three cellular layers. This tissue is part of the central nervous system, and it is specialized for transducing light information and transmitting it to the brain.

Neural stem cells – SCs of the adult neural tissue, responsible for neurogenesis. Neural SCs give rise to new neurons and glial cells involved in learning and memory; this is the locus of adult neurogenesis, as opposed to embryonic neurogenesis. Self-renewing, multipotent cells that can differentiate into neurons, oligodendrocytes and astrocytes.

Neuraminidase – An enzyme that cleaves a sialic acid of glycan.

Neurocranium  – The boney or cartilaginous portion of the skull that encloses and protects the brain.

Neurocutaneous – Pertaining to the skin and the nervous system.

Neurogenesis – Generation of neurons from uncommitted ectodermal cells.

Neurological- Pertaining to nerves and the nervous system.

Neuromasts – Sensory organs deposited by the migrating PLLp to initiate establishment of the Posterior Lateral Line (PLL) system. They have paired sensory hair cells at the center. Support cells (also called inner support cells) surround sensory hair cells and mantle cells (also called outer support cells).

Neuromodulator – Any chemical substance that alters normal nervous transmission without acting as a transmitter.

Neuron – Nerve cell.

Neuropeptide Y (NPY) – Peptide in brain that increases feeding and so makes animals fatter.

Neuropil – A collection of axons, dendrites, synaptic specialization, and supporting glial processes. Cell bodies are not included in the neuropil. Most synapses in invertebrate as well as vertebrate brains are made in the neuropil.

Neurosensory progenitor cells – Multipotent progenitor cells found in the ventral anterior region of the otocyst. These cells have the ability to develop as both the neurons comprising the VIIIth ganglion or the hair cells and supporting cells that constitute the sensory epithelia of the inner ear.

Neurosphere – An in vitro, usually clonally derived, accumulation of proliferative neuronal precursors grown from primary stem or progenitor cells taken from the central or peripheral nervous system. Primary neurosphere cultures rely upon selection by beta fibroblast growth factor (bFGF) and epidermal growth factor (EGF) to stabilize and propagate dividing cells from the primary neural tissue. Once established, primary neurospheres can be dissociated and these dissociated cells will go onto generate additional secondary neurospheres.

Neurotoxin – Toxin that attacks nerve cells.

Neurotransmitter – Any chemical substance capable of transmitting a chemical signal across a nerve synapse. Molecule that carries signals across synapses between cells within the nervous system. A chemical substance that is released at synaptic connections that are used to relay, amplify, and modulate signals between cells
and neurons.

Neurotropic spread – Spread through neurons.

Neurulation – The developmental process in vertebrate embryos through which the flat, disc-shaped neural plate ectoderm folds into the elongated neural tube, which will develop into the central nervous system. Neurulation can be primary or secondary, where the flat neural plate rolls into a tube, or mesenchyme cells coalesce into a medullary cord that cavitates to form a tube, respectively. Failures in neurulation result in neural tube defects (NTDs).

Neutral drift – A population of stem cells will divide and differentiate such that over time,the entire population of descendant cells will be derived from only one of the stem cells. The other stem cells are lost over time, and do not produce descendants that populate the tissue

Neutralization – Ability of an antibody to bind to an anti- gen and physically prevent it from binding to and harming a host cell.

Neutrophil  – White blood cell with neutral cytoplasmic granules and multilobed nucleus

Neutrophil extracellular trap (NET) – Microbe-trapping network formed from chromatin, histones and granule proteases released from a dying neutrophil.

Neutrophils – Most common leukocytes. Function as both granulocytes and phagocytes. Enter tissues from the circulation immediately in great numbers in response to in- jury or pathogen attack. Neutrally staining cytoplasmic granules.

New Drug Application (NDA) – Is for pharmaceutical products and is part of the clinical trials process that addresses how the drug is to be manufactured, dosage levels, labeling specifications, and other pertinent information.

New drug or device application – Application necessary for most pharmaceutical research involving untested drugs or devices. Either an investigational new drug (IND) or an investigational device exemption (IDE) number is required prior to initiation.

New chemical entity (NCE) – A chemical molecule developed by an innovator company in the early drug discovery stage, which after undergoing clinical trials could translate into a drug that could be a cure for some disease. Synthesis of an NCE is the first step in the process of development of a drug. Once the synthesis of then has been completed, companies can either go for clinical trials on their own or license the NCE to another company.

Newborn screening – Testing performed on newborn babies to detect for a wide variety of disorders such as inborn errors of metabolism.

Next-generation sequencing (NGS) – A rapid method of determining a DNA sequence. A high-throughput sequencing technology relative to capillary electrophoresis–based Sanger sequencing, producing thousands or millions of sequences simultaneously. This technology can be applied to DNA analysis, RNA analysis, and gene regulation analysis. See Massively parallel sequencing. Sequencing technologies that use miniaturized platforms for sequencing millions of DNA fragments in parallel

NF-kB signaling – A signal transduction pathway that plays a key role in regulating the immune response and cell survival.

N-formylmethionine (fMet) – Modified methionine used as the first amino acid during protein synthesis in bacteria

NGS – see Next generation (DNA and RNA) sequencing

Niche- A small space. Undifferentiated stem cell populations (progenitor cells) reside in many organs in a stem cell niche, wherespecialised factors are locally active in maintaining the cells in a healthy but quiescent state until needed.

Nick – A break in the backbone of a DNA or RNA molecule (but where no bases are missing) nicotine Alkaloid in tobacco that raises levels of uncoupling protein 1 in brown fatty tissue, hence promoting fat metabolism

Nickase – A restriction endonuclease that can make single cut in just one strand of double helix DNA.

NIH – National Institutes of Health (NIH)- the U.S. federal agency that funds, supports, and conducts biomedical re-search. Biologicals were regulated by NIH until 1972, when the responsibility was turned over to U.S. FDA. The NIH is composed of numerous institutes or centers, e.g., the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, and the new National Center for Advancing Translational Sciences.

Nitric oxide (NO) – Gaseous molecule used in signaling by animal cells

Nitric oxide synthase (NO synthase) – Enzyme that synthesizes nitric oxide

Nitrocellulose – A pulpy or cotton-like substance formed into sheets and used to attach proteins in Western blotting

Nitrofen (2,4-dichlorophenyl 4-nitrophenyl ether) – An herbicide (and banned carcinogen) used to create a rodent model of congenital diaphragmatic hernia. Embryos from pregnant dams exposed to nitrofen develop diaphragm, lung, and other structural malformations. The chemical affects the retinoic acid signaling pathway.

Nitrous oxide – Second messenger hormone in gaseous form. Penetrates its target cell to activate a cGMP mechanism.

NK activator receptors – Receptors whose engagement induces natural cytotoxicity and cytotoxic cytokine secretion by NK cells if not counteracted sufficiently by inhibitory receptor engagement.

NK inhibitory receptors – Receptors whose engagement by self MHC class I molecules on a potential target counter- acts the effects of NK activator receptor engagement, preventing target cell destruction.

NK/T precursor MPP – derived precursor that can develop into T, NKT or NK cells but not B cells.

NO synthase (nitric oxide synthase) – Enzyme that synthesizes nitric oxide

NOD proteins – Nucleotide-binding oligomerization domain proteins. Member of the NLR family of cytoplasmic PRMs that detect products of intracellular pathogens. Engagement induces inflammasome formation and inflammatory cytokine production.

Nodal – A TGF-beta signaling ligand that is a key regulator of the vertebrate endoderm GRN controlling first the induction of mesendoderm and then its segregation into distinct endoderm and mesoderm germ layers.

Node – An area around a myelinated nerve where myelin is not present. Transport of ions across the membrane occurs there.

NOD-like receptors (NLRs) – Cytoplasmic PRMs whose engagement induces inflammasome formation and inflammatory cytokine production.

Nomarski optics – Type of polarization microscopy that transforms differences in density into differences in height so that the image looks like a three-dimensional relief

Nomenclature – A nomenclature is a specialized vocabulary containing all, or nearly all, terms that comprehensively cover a well-defined field of knowledge. For example, there may be a nomenclature of genes or genetic mechanisms, cel- lular pathways, or rare diseases. Some nomenclatures are ordered alphabetically. Others are ordered by synonymy, wherein all synonyms and plesionyms (near- synonyms) are collected under a canonical (best or preferred) term. Indexes pre- pared from medical records or scholarly documents can be harmonized under a nomenclature that collects synonymous terms under a canonical term.

Non-allelic homologous recombination (NAHR) – A mechanism responsible for causing microdeletions and other chromosomal rearrangements. NAHR occurs during meiosis if inappropriate recombination events occur between non-homologous segments of chromosome (either on the same chromosome, or different chromosomes).

Nonclinical – Nonclinical means the same as preclinical, i.e., generally means animal studies. Since not all animal studies are done preclinically, i.e., before clinical studies begin, the term nonclinical was invented.

Noncoding (or antisense) – The strand of DNA that has complementary sequence to mRNA.

Noncoding region (NCR) – It refers to the region of the genome in which no protein is encoded.

Noncoding RNA – A biologically functional RNA actively transcribed from a gene that contains no open reading frame.

Noncoding sequence – A region of DNA that is not translated into protein. Some noncoding sequences are regulatory portions of genes and others may serve structural purposes (telomeres, centromeres), whereas still others may not have any function.

Non-communicating defect or muscularization defect – A non-communicating diaphragmatic defect is one in which there is no direct communication of the abdominal contents with the thoracic cavity. These include muscularization defects of the diaphragm. These defects include massive herniations covered by a membrane contiguous with the diaphragm (a sac hernia) and mild diffuse muscularization defects causing a slight elevation of the diaphragm (sometimes called eventration).

Nonconformance – Any noncompliance with a device master record or the quality system.

Nonconformity – Defect or other undesirable situation. Example- Corrective actions identified as a result of a nonconformance for one product are PAs when implemented to prevent a similar nonconformance in another product.

Nonenveloped virus – A virus whose virions do not possess an external lipid membrane.

Non-Hodgkins lymphoma – Heterogeneous group of lymphomas in which the solid tumor mass consists almost entirely of malignant lymphocytes.

Non-homologous end joining (NHEJ) – A natural DNA repair process where DSB are joined. It can be either through addition or deletion of sequences in gene which may lead to loss or gain gene function. NHEJ is used in genome editing for creating a knock out or knock in inside organisms. DNA repair system found in eukaryotes that mends double-stranded breaks, but can introduce deletions or insertions. Pathway of DNA repair in which double-stranded DNA breaks are joined in the absence of a homologous sequence to guide repair. Certain enzymes involved are also active in somatic recombination.

Non-inherited genetic disease – A significant but unquantified portion of genetic diseases is non-inherited; occurring from de novo (new) mutations in the germ cells of the affected individuals. In humans, point mutations (i.e., mutations that occur in a single nucleotide base within the genome) occur with a frequency of about 1 to 3×10−8 per base. There are many types of mutational alterations other than point mutations (e.g., mutations in microsat- ellites) [86]. Our knowledge of the likelihood of most of these alternate types of mutation is limited. In many cases de novo mutations cause lethal genetic diseases that occur in children, through the action of a dominant gene (i.e., one gene copy that produces the disease). Such diseases are seldom inherited because they cannot be conserved in the population; those with the gene die early in life, without passing the gene to progeny. Sometimes, non-inheritance accounts for some proportion of cases that would otherwise occur as domi- nant gene disorders. Neurofibromatosis is an example of a disease that occurs through autosomal dominant inheritance in about half of the cases. The other half of occurrences are de novo mutations incurring in the affected individual. In general, de novo mutations are often suspected as the cause of diseases that occur in early childhood for which no other cause (e.g., no evidence of familial or parental inheritance, infectious etiology, or environmental influences) can be determined (e.g., autism) . See De novo mutation.

Noninvasive prenatal testing (NIPT) – Test that uses cell-free circulating fetal DNA in maternal blood during pregnancy to screen for fetal chromosome anomalies.

Non-Mendelian inheritance – Inheritance by virtue of a combination of poly- morphisms (i.e., gene variants) that are prevalent within a family. In non-Men- delian inheritance, it is possible that neither the mother nor the father will carry the complete set of gene variants that cause inherited disease, but that the com- bination of disease-causing gene variants will occur in an offspring, through meiotic recombination. Generally, Mendelian inheritance is monogenic; non- Mendelian inheritance is polygenic. Diseases that have Mendelian patterns of inheritance tend to be less common than diseases with polygenic inheritance.

Non-myeloablative conditioning – Partial elimination of a patient’s hematopoietic cells in the bone marrow using chemotherapy and irradiation, leading to eventual reductions of immune system cells in the peripheral blood and secondary lymphoid tissues. Less toxic than myeloablative conditioning.

Non-natural amino acids – Modified amino acids that have functional groups that are useful for biochemical analysis or protein engineering

Non-nucleoside reverse transcriptase inhibitor (NNRTI) – Antiviral agent that inhibits the reverse transcriptase of viruses such as HIV but is not a nucleoside analogue.

Nonparalytic aseptic meningitis – Inflammation of the brain and spinal cord membranes as a result of poliovirus infection.

Nonpermissive host – A host that permits only early phase of the virus life cycle, but not late phase of virus life cycle or viral progeny production.

Nonpigmented ciliary epithelium – This is a monolayer of cells that is an anterior extension of neuroretina and lines the inner surface of the ciliary body. Underlying this layer is another monolayer of cells called the pigmented ciliary epithelium that is an anterior extension of the retinal pigment epithelium.

Non-profit organizations (NPO) – A legally constituted organization whose primary objective is to support or to actively engage in activities of public or private interest without any commercial or monetary profit purposes. NPOs are active in a wide range of areas, including the environment, humanitarian aid, animal protection, education,the arts, social issues, charities, early childhood education, health care, politics,religion, research, sports, or other endeavors.

Non-responder – Individual who fails to mount an immune response to a foreign protein that provokes a strong response in other individuals.

Non-selection in central tolerance – The apoptotic death of CD4+CD8+ thymocytes expressing TCRs with little or no affinity for self MHC. Also called “neglect.”

Nonsense mutation – Change in the DNA sequence involving a single base pair that results in a premature stop codon, which leads to a shortened protein. Mutation due to changing the codon for an amino acid to a stop codon nontarget organism Any organism exposed to a specific insecticide, herbicide, or transgenic plant which that product was not intended to harm

Nonsense mutation – Substitution of a single DNA base that leads in a stop codon, thus leading to the truncation of a protein.

Non-steroidal anti-inflammatory drugs (NSAIDs) – Anti-inflammatory and analgesic chemicals most commonly affecting the cyclo-oxygenase pathway. Examples include ibuprofen and naproxen. A drug (e.g., aspirin) that inhibits prostaglandin synthase. These drugs differ from steroidal anti-inflammatory drugs that inhibit phospholipase A. Both drugs inhibit formation of prostaglandins that may be inflammatory.

Non-syndromic disease – A disease that affects a single organ or function, unaccompanied by abnormalities of other organs or physiologic systems. A syndromic disease is a constellation of pathologic features associated with a single disease or condition, involving multiple organs or physiologic systems. Non-syndromic deafness affects hearing and no other structures or functions. When inherited deafness is syndromic, it is accompanied by other abnormali- ties, possibly involving facial structure or nerve function.

Nontemplate – The strand of DNA equivalent in sequence to the messenger RNA (same as plus strand).

Nonvisual photoresponses – Physiological or behavioral responses to light that do not require the formation of images. Circadian photoentrainment is an example of a nonvisual photoresponse.

Noradrenalin – Neurotransmitter of the catecholamine family (also known as norepinephrine)

Noradrenergic – Neurosecretory elements that produce norepinephrine as a transmitter.

Norepinephrine – Neurotransmitter of the catecholamine family (also known as noradrenalin)

Northern blots – Hybridization technique in which a DNA probe binds to an RNA target molecule

Nosocomial infections – Those infections acquired in a hospital setting.   

Notified Body Opinion (NBOp) – An opinion provided by a Notified Body on the conformity of a device (part) with the relevant GSPRs set out in Annex I of Regulation 2017/745, as required by Article 117 of the MDR.

Notochord – The key morphological character of chordates is the notochord. The notochord forms a stiff rod running from anterior to posterior in chordates beneath the dorsal neural tube, usually surrounded by a sheath of extracellular matrix. The gut is found just under the notochord in vertebrates and lancelets, but there is only an endodermal strand in the nonfeeding ascidian tadpole larvae. In lancelets and appendicularians, the notochord persists in the adult, while in ascidians the notochord undergoes apoptosis before metamorphosis and tail resorption. In vertebrates, the notochord persists as the intervertebral discs (nucleus pulposa) as the vertebrae develop from somites.

npt – The gene that encodes neomycin phosphotransferase.

NRA – National Regulatory Authority – the agency in a country responsible for the regulation of biomedical products, including investigational and marketed drugs.

NS1 – The NS1 influenza protein is produced by the internal protein-encoding, linear negative-sense, single-stranded RNA, NS gene segment detected in Influenzavirus A, Influenzavirus B, and Influenzavirus C. The NS1 protein of the highly pathogenic avian H5N1 viruses circulating in poultry and waterfowl in Southeast Asia is believed to be responsible for the enhanced virulence of the strain

NTCP (sodium taurocholate cotransporting polypeptide) – It is an integral membrane glycoprotein that participates in the enterohepatic circulation of bile acids. It is also an entry receptor necessary for hepatitis B virus infection.

nTreg cells or Natural Regulatory T cells (nTregs) – CD4+Foxp3+ regulatory T cells that block conventional T cell activation via intercellular contacts rather than immunosuppressive cytokines. Generated in the thymus from DP thymocytes.

Nuclear atypia – Refers to variations from normal nuclear morphology. The term is typically applied to cancer cells and precancer cells, whose nuclei look different from normal nuclei. Cancerous and precancerous nuclei are larger than normal nuclei, with irregular shape (i.e., not oval or round or smooth), with indentations in the nuclear membrane, coarse chromatin, areas of light and dark within the nucleus, and enlarged, irregularly shaped nucleoli. Traditionally, pathologists were taught that genetic changes accounted for the atypia present in cancer cells. This opinion was based on several observations and assump- tions: (1) cancer cells were known to contain genetic abnormalities, such as increased numbers of chromosomes, missing pieces of chromosomes, dupli- cated pieces of chromosomes, and translocated pieces of chromosomes; (2) the genetic material of the cell resides in the nucleus, and it was natural to assume that morphologic changes to the nucleus would result in damage to DNA; and (3) little was known about the epigenome when the genetic code was broken in the late 1950s. In recent years, cancer biologists have been rethinking the cause of cellular atypia in cancer, focusing their attention on the role of the epigenome. Observations that support an epigenetic cause of nuclear atypia include the fol- lowing: (1) some cancers have marked atypia with little or no genetic instability (e.g., rhabdoid tumor); (2) profound changes in nuclear morphology can be produced by alteration in a single protein, as is seen in rare Pelger–Huetanom- aly, suggesting that marked changes in gene sequence are not necessary to produce misshapen nuclei; (3) the common histologic stains with which we assess nuclear atypia bind to the histone and non-histone proteins of the epig- enome; hence, the morphologic abnormalities of cancer nuclei reflect changes in the nuclear distribution of epigenetic constituents.

Nuclear domain 10 (ND10) – A small proteineous subnuclear structure, which is composed of multiple factors including PML (promyelocytic leukemia protein) and Sp100. It is also called PML nuclear bodies.

Nuclear envelope – Two concentric membranes that surround the nucleus of eukaryotic cells.

Nuclear microinjection – Technique for insertion of foreign DNA into a host cell nucleus.

Nuclear pore – Pore in nuclear membrane that allows proteins, RNA, and other molecules into and out of the nucleus.

Nuclear transcription factors – Proteins that reside in or translocate into the nucleus, bind to gene promoters, and initiate or regulate mRNA transcription.

Nuclear Transfer- Transfer of a nucleus, or complete cell, from one cell to the other. This technique is used for cloning and the recipient cell is then an egg cell.

Nuclear transplantation – Technique in which nuclei from one cell are transplanted into another cell from which the nucleus has previously been removed.

Nuclear-receptor superfamily – Large family of proteins that act as transcription factors; includes receptors to many hormones that are poorly water soluble.

Nuclease – An enzyme that can cut DNA or RNA strands.

Nucleic acid bases – Nitrogen containing, hydrophobic compounds that form the inner, hydrophobic components of nucleic acids. A sequence of three bases may form a genetic code for an amino acid. 

Nucleic acid sequence – Refers to the arrangement of letters that make up the nucleotide order in RNA and DNA.

Nucleic acid testing – Testing a specimen for the presence of specific nucleic acid sequences, such as those of a virus.

Nucleocapsid – The viral nucleic acid enclosed by capsid proteins. Inner structure of certain viruses that consists of RNA or DNA surrounded by protein. It refers a viral capsid that is associated with the viral genome.

Nucleoporins – Cellular proteins that comprise the nuclear pore complex.

Nucleoside analog – Molecule that mimics a nucleoside well enough to be incorporated into a growing chain of DNA by synthetic enzymes

Nucleoside –  A nucleoside is a nucleotide that lacks the phosphate group. The sugars found in DNA or RNA nucleotides are deoxyribose and ribose, respectively. A nucleoside is a base bound to a pentose. 

Nucleosome – Composed of a dimer formed from the 4 histones H3, H2A, H2B and H4, around which 147 DNA base pairs are wrapped. Subunit of a eukaryotic chromosome consisting of DNA coiled around histone proteins.

Nucleotide – The building blocks of nucleic acids, a nucleotide is composed of a sugar attached on one side to a phosphate group and to a nitrogenous base on the other (either adenine, guanine, cytosine, thymine, or uracil). A nitrogenous base attached to a phosphate group and a pentose sugar molecule. A ribonucleotide, the main unit of RNA, is composed of a phosphate group, a ribose sugar, and a nitrogenous base (adenine [A], cytosine [C], guanine [G], or uracil [U]). A deoxyribonucleotide, the main unit in DNA, is composed of a phosphate group, deoxyribose sugar, and a nitrogenous base (adenine [A], cytosine [C], guanine [G], or thymine [T]). A subunit of the DNA or RNA molecule. A nucleotide is a base molecule [adenine, cytosine, guanine, and thymine (A, C, G, and T) in the case of DNA], linked to a sugar molecule (deoxyribose or ribose) and phosphate groups. Monomer or subunit of a nucleic acid, consisting of a pentose sugar plus a base plus a phosphate group. Organic molecules that are fundamental building blocks of nucleic acids. They contain a nitrogenous base, a five-carbon sugar, and a phosphate group. A nucleotide is a base bound to a pentose plus one or more bound phosphates.

Nucleus – The central region of a eukaryotic cell that contains the genetic material and is separated from the rest of the cell by a double membrane. A part of the cell, situated more or less in the middle of the cell, that is surrounded by a specialized membrane and contains the DNA of the cell. This DNA is packaged into structures called chromosomes, which is the genetic, inherited material of cells.

Nullizygous – When both copies of a gene are fully inactivated

Nuremberg Code – Ethical code resulting from the atrocities committed by Nazi physician/investigators during World War II. The core notion set forth by the code is that the voluntary consent of a research participant is essential.

Nystagmus – An oscillation of the eyes (shimmering or jumping eyes).




Open Process – A process that is exposed to the environment and therefore requires environmental conditions to mitigate the risk of contamination from the environment. Under QRM verification, the environment within the RABs and/or BSCs represents a critical aspect of the open process (formerly known as direct and indirect impact systems). Open sterile and aseptic operations must be performed in an environment where the probability of contamination is acceptably low. Open bioburden-controlled processing may be performed in a Grade 7 or 8 environment as appropriate for the unit operation.

OAI – Official action indicated- an inspectional outcome in which the observations of the U.S. FDA inspectors rise to the level that legal action is deemed warranted by U.S. FDA. Warning letters are generally issued in these situations. Legal actions can include seizure, injunction, fines, jail, disqualification (of clinical investigators), disbarment (of clinical investigators), etc. Generally, a firm has the opportunity to address the violative observations, and if they are addressed adequately, U.S. FDA may not take legal action. The general order of events is the inspection, issuance of the FDA Form 483, firm must respond to Form 483 observations in writing, in the meantime an EIR is prepared, decision taken that the situation is OAI, a warning letter is issued, firm must respond to warning letter, then, if responses are adequate, sometimes a reinsertion is performed to assure that the firm has actually addressed the matters as they claim; if the responses are inadequate or the firm does not reply, legal actions may be taken.

ob (obese) gene – Gene that encodes the protein hormone leptin.

Obligate carrier – Individual that must be a carrier of the genetic mutation of concern based on the known disorder inheritance pattern and family history obtained.

Obligate intracellular organism – An obligate intracellular organism can only reproduce within a host cell. Obligate intracellular organisms can include spe- cies from various classes of organisms, but the term applies to all viruses and all members of Class Chlamydia. Examples of other genera that contain obli- gate intracellular species include: Coxiella, Leishmania, Plasmodia, Rickettsia, Toxoplasma, Trypanosoma. Such organisms have adapted to life within human cells, shucking most of their genetic material, and opting to survive on the cel- lular machinery provided by their hosts.

483 (Observation) – FDA form for listing observations.

Observational studies – Studies that observe participants and collect data but do not have any influence over the exposure of the participant.

Observational trials – Part of the clinical trials process that address health issues in large groups of people among populations in natural settings.

Occurrence – The likelihood (probability) that a specific failure mode, which is the result of a specific cause and which is under current control, will happen.

OCTGT – Office of Cellular, Tissue, and Gene Therapy – a previous name of a component of CBER responsible for Cellular, Tissue, and Gene Therapy products. Now called the Office of Tissues and Advanced Therapies (OTAT).

Ocular fluids – These include the aqueous humor, vitreous and precorneal tears as well as blood, interstitial fluid, and intracellular cytoplasm (when in the eye).

Odontoblast – Highly differentiated, post-mitotic cells that are organized at the periphery of the pulp as a cellular palisade. A biological cell of neural crest origin that is part of the outer surface of the dental pulp, and whose biological function is dentinogenesis, which is the creation of dentin, the substance under the tooth enamel. Mesenchymal cells producing dentin.

Odontogenesis  – Tooth development. Tooth organ formation.

Orthotopic – in the normal or usual position.

OECD – Organization for Economic Cooperation and Development (OECD).

Oedema – Tissue swelling due to leakage of acellular vascular fluid.

Offer price – Is the initial price that the underwriters offer the stock for sale to the public.

Off-label – Refers to the use of a drug to treat a condition other than the con- dition for which the drug was awarded FDA approval. The term “off-label” comes from the section of the pill-bottle label that describes the intended use or uses of the drug. Treatments other than those described on the drug’s label are “off-label.” The FDA does not regulate the practice of medicine. Hence, physi- cians who use good professional judgment to prescribe an off-label treatment for an FDA approved drug may do so. Prudent physicians will not prescribe off-label until such uses are supported by credible, repeated studies published in highly regarded medical journals. It is impossible to know with any precision or confidence the prevalence of off-label treatments in the rare diseases. Still, it is a commonly held view that about 90% of all treatments for rare diseases are conducted without specific FDA approval. Medicare and private insurers, at present, tend to pay for off-label uses of drugs, particularly when these drugs are used to treat rare diseases.

Off-target – Effect unintended and non-specific changes in the gene function by binding other undesired region than the target location.

Okazaki fragments – The shorter pieces of replicated DNA that form the lagging strand during DNA replication. Small segments of newly synthesised DNA in the lagging strand of DNA replication. They consist of both an RNA primer and new DNA. The short pieces of DNA that make up the lagging strand

Oligodontia – Severe tooth agenesis that affects more than six teeth (wisdom teeth not included).

Oligogenic inheritance – In the context of genetic diseases, occurs when the expression of several genes (i.e., not one gene and not many genes) produces a disease phenotype. If two genes are required, the term “digenic disease” applies. Macular degeneration may qualify as a common disease with oligogenic inheri- tance. A few gene variants present in the general population may account for 70% of the risk of developing age-related macular degeneration , the third leading cause of blindness worldwide . Examples of oligogenic rare diseases are Bardet–Biedl syndrome and Williams–Beurensyndrome . See Allelic heterogeneity and Locus heterogeneity.

Oligonucleotide (oligos) – Short fragments of nucleic acids. A molecule of 25 nucleotides or fewer used to prime in vitro DNA replication, sequencing, or PCR reactions

Oligopoly – A market dominated by a small number of participants who are able to collectively exert control over supply and market prices. This refers to a market condition in which sellers are so few that the actions of any one of them will materially affect price and have a measurable impact on competitors.

Oligosaccharide – A carbohydrate generally consisting of between three and nine sugar units. The units may be branched (see Figure

Omnipotent- See totipotent.

Oncogene – A gene that can cause changes within cells that lead to cancer. An acquired mutant form of a gene that acts to transform a normal cell into a cancerous one. An oncogene is a gene that has the potential to cause cancer. In tumor cells, the oncogenes are often mutated (activated) or expressed at high levels. Genes that are key drivers of the malignant phenotype in cancer cells. Oncogenes need to be activated before they can contribute to the phe- notype of cancer cells. Prior to activation, oncogenes are called proto-oncogenes. Activation usually involves mutation or amplification (i.e., an increase in gene copy-number), translocation, or fusion with an actively transcribed gene, or some sequence of events that increases the expression of the gene product. Some retroviruses contain oncogenes and can cause tumors by integrating their oncogene into the host genome. See Tumor suppressor gene. Mutant gene that promotes cancer. A gene whose deregulation is directly associated with carcinogenesis. Oncogenes often encode positive regulators of cell growth. Cancer-promoting, mutant forms of proto-oncogenes, genes that encode essential proteins important in processes that are deregulated in cancer.

Oncogenesis – The development of a tumour/cancer.

Oncogenic virus – Cancer-causing virus.

Oncolytic virus – Cancer-destroying virus.

Oncotic pressure – The hydrostatic pressure needed to stop the movement of water due to a protein concentration gradient.

Oocyte – Female egg cell.

Online Mendelian Inheritance in Man (OMIM) – A catalog of human genes and genetic disorders developed by the National Center for Biotechnology Information. A regularly updated electronic catalog of inherited human disorders and phe- notypical traits accessible on the National Center for Biotechnology Information network. Each entry is designated by a number (MIM number).

Open reading frame (ORF) – A continuous stretch of nucleotides that encodes a protein or polyprotein. Sequence of bases (either in DNA or RNA) that can be translated (at least in theory) to give a protein

Open stem cell niche – A tissue that has stem cells randomly distributed within the differentiated cells so there is no geographic boundary between the stem cell niche and the tissue.

Operator – Site on DNA to which a repressor protein binds.

Operon – A cluster of prokaryotic genes that are transcribed together to give a single mRNA (i.e., polycistronic mRNA).

Ophthalmoscopy – The examination of the interior of the eye with the instrument called ophthalmoscope.

Opines – Amino acids and sugar phosphate derivatives produced by Agrobacterium that are found in crown gall tumors

Opportunism – Refers to where one party in a strategic alliance uses knowledge gained within the strategic alliance to its advantage to the detriment of the other party.

Opportunistic infection – Infections that occur when a person’s immune system is weakened. An opportunistic infection is an infection caused by pathogens, particularly “opportunistic pathogens” that usually do not cause disease in a healthy host. Infections seen in patients with defective immune systems that are caused by normally harmless microorganisms. Opportunistic infections are diseases that do not typically occur in healthy individuals, but which can occur in individuals who have a physiologic status favoring the growth of the organisms (e.g., diabetes, malnutrition). Sometimes, opportunistic infections occur in patients who are very old or very young. Most often, opportunistic infections occur in immune- compromised patients. A disease may increase susceptibility to specific types of organisms. For example, diabetics are more likely to contract systemic fungal diseases than are non-diabetic individuals. Some opportunistic infections arise from the population of organisms that live within most humans, without caus- ing disease under normal circumstances (i.e., commensals). The concept of an opportunistic organism is, at best, a gray area of medicine, as virtually all of the organisms that arise in immune-compromised patients will, on rare occasions, cause disease in immune-competent patients (e.g., Cryptococcus neoformans). Moreover, the so-called primary infectious organisms that produce disease in normal individuals will tend to produce a more virulent version of the disease in immunosuppressed individuals (e.g., Coccidioides immitis). Examples of organisms that cause opportunistic infections are:Acinetobacter baumanni, Aspergillus sp., Candida sp., Clostridium difficile, Cryptococcus neofor- mans, Cryptosporidium parvum, Cytomegalovirus, herpes zoster, Histoplasma capsulatum, human herpesvirus-8, Pneumocystis jirovecii, polyomavirus JC, Proteus sp., Pseudomonas aeruginosa, Streptococcus pyogenes, Toxoplasma gondii. See Commensals.

Opportunistic pathogen – A pathogen that does not cause disease unless offered an unexpected opportunity by a failure in host defense. Pathogens that usually do not cause disease in a healthy host, one with a healthy immune system, but do cause disease in compromised immune system.

Opsin – The apoprotein of rhodopsin to which no vitamin A is attached.

Opsin visual pigment – A member of the G-protein-coupled receptor superfamily that functions as the light receptor in rods and cones. These pigments represent a complex between an opsin protein and a visual chromophore.

Opsonin – A host protein that coats a foreign entity such that it binds more easily to phagocyte receptors, enhancing phagocytosis. Host-derived molecules that bind antigens, i.e., antibodies or C3b components. Mark the antigen for recognition, usually leading to phagocytosis

Opsonisation – A process by which phagocytosis is facilitated by the deposition of opsonins. The process of tagging an antigen with Ig and other protein markers prior to phagocytosis. The coating of cell surfaces with molecules that facilitate phagocytosis.

Opsonize – The process coating a foreign object or molecule with molecules, e.g., antibodies, that facilitate phagocytosis of the foreign object.

Ophthalmic artery – A branch of the internal carotid artery which enters the orbit through the optic canal, along with the optic nerve, to supply structures in the orbit.

Optic vesicle – An evagination of the eye domain from the lateral walls of the embryonic forebrain that will give rise to eye tissues, including the neural retina and retinal pigment epithelium.

Optical coherence tomography (OCT) – A non-invasive imaging test which uses light waves to take cross-section pictures of your retina to show the retina’s distinctive layers and map and measure their thickness. 

Optical density (OD) – Absorbance; see spectral absorbance.

Opticin – A protein that binds to vitreal collagen and prevents the aggregation of collagen fibers.

Options/Stock options – Financial instruments which give the holder the right to buy an underlying instrument (e.g., common stock) at an agreed amount.

Optokinetic reflexes – Eye movements induced by moving a visual pattern in front of the eyes.

Optotype – A letter, symbol, or other figure presented at a controlled size to measure vision.

Oral tolerance – Experimental tolerance induced by oral feeding of an immunogen.

Oral vaccine – A vaccine that is taken by mouth, as either a liquid or a pill

Ordinary differential equations (ODEs) – Equations that describe the rate of change of a variable or variables (i.e., population size) with respect to time. The term ordinary is used in contrast to partial differential equations, which track the changes over time of more than one independent variable (i.e., time and space, or age).

Organ bath – Standard for in vitro pharmacodynamics dose-response experiments involving suspension of an isolated section of organ/ tissue in a controlled solution and sensors to measure the contraction or relaxation of the tissue when drugs are added.

Organ of Cortex  – The specialized sensory epithelium of the mammalian cochlea. It contains a highly regular mosaic of hair cells and supporting cells. Hair cells are arranged in four distinct rows while supporting cells separate each hair cell from each of its neighbors.

Organ or Tissue Stem Cells- In an adult, most organs and tissues contain a small number of stem cells, which are often quiescent but are capable of dividing when needed (for repair or replacement) and developing into the cell types that are normally present in the organ of tissue they are multipotent or unipotent.

Organelle – A subcellular structure within a cell. An organelle is usually enclosed by its own membrane for executing its specific function independently of other organelles in a cell, particularly a eukaryotic cell.

Organism – Any living system that has the ability to grow, reproduce, maintain homeostasis within itself, and function independently. An organism may be either unicellular or multicellular. All organisms on Earth can be further divided into eukaryotes and prokaryotes.

Organizer – The mesodermal region of the vertebrate embryo that is the source of signaling molecules that dorsalize and pattern both the mesoderm and the ectoderm.

Organogenesis – Development of organs during embryonic development.

Organoid- Small, three-dimensional organ-like structure formed (“self-assembled”) by cultured adult stem cells that can give rise to all different cell types of that organ; organoids can mimic some of the organ’s function

Organ-on-a-Chip Models- Technology to micro engineer the smallest functional organ or tissue modules in the laboratory on a “chip,” where the chip enables recreation of the cellular/tissue environment, very much like in vivo. Their envisioned use is to develop organ and disease models for drug development.

Oriented basic– research is research carried out with the expectation that it will produce a broad base of knowledge likely to form the background to the solution of recognized or expected current or future problems or possibilities.

Oriented basic research – Is research carried out with the expectation that it will produce a broad base of knowledge likely to form the background to the solution of recognized or expected current or future problems or possibilities.

Origin – Site on a chromosome or any other DNA molecule where replication begins.

Origin of chromosome (oriC) – Origin of replication of a chromosome.

Origin of replication (ori) – Site on a chromosome or any other DNA molecule where replication begins.

Orphan drug – A drug that is helpful to a small number of people, usually indicating a drug developed for individuals who have a rare disease. In the past, the term “orphan drug” was applied to existing drugs that were not marketed due to their perceived unprofitability. Today, the term is generally applied to any drug that happens to have a limited market. A term referring to a product that treats rare diseases which affect fewer than 200 000 Americans. The Orphan Drug Act was signed into law in the US in 1983. The intent of the Orphan Drug Act is to encourage the research, development, and approval of products that treat rare diseases. Because medical research and development of drugs to treat such diseases is financially disadvantageous, companies that do so are rewarded with tax reductions and marketing exclusivity (a ‘monopoly’) on that drug for an extended time (seven years postapproval). A similar status exists in the European Union. administered by the Committee on Orphan Medicinal Products of the European Medicines Agency (EMA).

Orphan medicines – Medicines used for rare human diseases.

Orthodisease – A genetic disease in humans caused by an alteration of a gene that is orthologous to a known gene in a different species. Though we can expect phenotypes to diverge among species with orthologous genes, the pathways perturbed by orthologous genes will tend to be conserved. By studying the role of orthologous genes in different species, we may learn something about the pathogenesis of the human disease. For example, the 2013 Nobel Prize in Physiology or Chemistry was awarded for work on vesicular transport disorders (see Section 10.4). Much of the progress in this area came from studies of human inherited transport disorders. Because vesicular transport is an ancient cel- lular system, researchers could dissect the transport pathway in mutant ortholo- gous genes from yeast.

Orthokeratology – The practice of reshaping the cornea by wearing specially designed rigid contact lenses. These lenses are usually worn only during sleep and they reshape the front surface of the eye, correcting the refractive error and allowing clear vision.

Ortholog – A corresponding gene in different species that has descended from the same ancestral gene. One of set of homologous genes or proteins that perform similar functions in different species; that is, identical genes from different species, such as SRY in humans and Sryin mice.

Orthology – Homology where the sequences have deviated by speciation.

Orthomyxoviruses – Family of negative-strand ssRNA viruses that includes influenza

OSCE – Objective structured clinical examination

Osmosis – The movement of water down its concentration gradient. The movement of water or a solvent across a semipermeable membrane from a region of lower to higher concentration of solute. For example, water will move across a semipermeable membrane from a compartment with a low sodium concentration (high water concentration) to a compartment with a high sodium concentration (low water concentration).

Osmotic pressure – The hydrostatic pressure needed to stop the movement of water due to a solute concentration gradient.

OSP – U.S. NIH Office of Science Policy, a new original structure that replaced OBA or the Office of Biotechnology Activities. The RAC now reports to OSP.

Osteoarthritis- Breakdown of cartilage particularly in joints such as knees and hips. It can be caused by aging (“wear and tear”) but can also be hereditary or arise from metabolic disorders. The main symptoms are pain and stiffness of the joints.

Osteoblast – A mononucleate bone-forming cell. Mononucleate cells that are responsible for bone formation; in essence, osteoblasts are specialized fibroblasts that in addition to fibroblastic products, express bone sialoprotein and osteocalcin.

Osteoclast – A large multinucleate cell that resorbs bone. Macrophages in bone.

Osteoclastogenesis – The biological process of osteoclast formation.

Osteoconductive – Supporting bone formation. Having the capacity to allow growth of bony tissue into the structure of an implant or graft.

Osteogenic – Derived from or made up of bone-forming tissue.

Osteoinductive – Bone formation inducing. The capacity to activate or process of stimulating osteogenesis.

Osteoprogenitor cell – A mesenchymal cell that differentiates into an osteoblast (i.e., a preosteoblast).

OTAT – Office of Tissues and Advanced Therapies (OTAT) – the new name for what was previously known as the Office of Cellular, Tissue, and Gene Therapy (OCTGT).

Otic placode – An ectodermal thickening that develops in the dorsal anterior region of the embryo adjacent to the developing hindbrain.

Otocyst – A hollow sphere derived from the otic placode. As development proceeds, it will undergo a series of morphological changes to give rise to all of the structures within the inner ear.

Oto-facial-cervical syndrome – Patients present with hearing loss, a long narrow face and various facial and cervical structural abnormalities. Some cases are caused by mutations in the Eya1 gene.

Outbreak In epidemiology  – an outbreak is an occurrence of disease greater than expected at a particular time and place. Outbreaks may also refer to epidemics which affect a particular region in a country or a group of countries.

Outer blood-retinal barrier – It regulates the transport of fluid, ions, and metabolites between the neurosensory retina and the choroidal vasculature.

Outer segment – An elongated light-sensitive structure attached to the connecting cilium of rod and cone photoreceptors. The rod outer segment in humans comprises a stack of approximately 1000 membranous disks. These disks are loaded with rhodopsin or cone opsin visual pigments.

Outsourcing – Is a practice where a firm transfers portions of work to outside firms in an attempt to lower costs or provide someother value added aspect rather than completing them internally. A practice where a firm transfers portions of work to outside firms in an attempt to lower costs or provide some other value added aspect rather than completing them internally. This term refers to contracts for certain projects with a fixed timeline and limited risk for the partner in order to cut costs (e.g., the procuring of a service, such as the manufacturing of a vaccine by an outside supplier).

Overallotment or allotment – An option allowing the lead underwriter to purchase additional shares at a set price. This is also known as a green shoe.

Overlap PCR – PCR technique that uses overlapping primers to match small regions of two different gene segments and is used in joining segments of DNA from different sources

Overpricing – occurs when the price of the security at the end of the first day of trading is lower than the offer price.

Ovum – A mature female haploid gamete.

Oxidant – An agent that oxidizes another.

Oxidation-reduction reaction – A chemical transformation in which electrons are transferred from one substance (oxidation) to another (reduction).

Oxidative phosphorylation -The formation of ATP by a complex metabolic process requiring oxygen, electron transport, and protonflow inside of mitochondria. (See Adenosine triphosphate and Substrate-level phosphorylation.)

Oxidative stress – The damage to a cell as a result of exposure to an oxidative environment. In general, an oxidative environment contains reactive oxygen species (ROS), such as hydrogen peroxide or oxygen radicals. A biochemical process in which the compound glyoxal is formed from glucose and oxygen in the diabetic state during the Maillard reaction. Glyoxal is an intermediate that occurs prior to the formation of advanced glycation end products (AGEs).  

Oxidize – The process of adding oxygen or removing hydrogen to a molecule.

Oxygen partial pressure (pO2) – Pressure of oxygen gas when it alone occupied the volume.

Oxygenase – Enzyme that inserts one or more oxygen atoms into its substrate.



P arm -The shorter arm of a chromosome extending out from its centromere. The other longer arm is referred to as a q arm.

P elements – Transposons found in Drosophila and other insects.

P&ID – Piping and Instrument Diagram (P&ID).

P nucleotides – If two gene segments undergoing V(D)J re- combination are nicked elsewhere than at their precise ends, a recessed strand end and an overhang are generated. The nucleotides added to fill the gaps on both strands are considered P nucleotides.

p14ARF (alternative reading frame) – It refers to a tumor suppressor gene product, whose gene was discovered as an alternate reading frame (ARF) product of the CDKN2A locus, and is an inhibitor of Mdm2.

P16INK4A-RB (retinoblastoma protein) pathway – A signal transduction pathway that regulates the cell cycle where mutations in the p16INK4A are found in many cancers

P21 protein – A protein that blocks cell division by binding to and inhibiting the cyclins.

P53 gene – A notorious anti-oncogene often mutated in cancer cells. p53 is one of the most important as tumour suppressor gene. It was discovered as a T-antigen binding protein with a molecular mass of 53 kDa. Tumour suppressor transcription factor protein involved in the regulation of the cell cycle, DNA repair and apoptosis. The p53 gene is mutated in many cancers.

P53 pathway – A key signal transduction pathway that can activate proteins that promote apoptosis, cellular senescence, or cell cycle arrest.

P53 protein (also known as TP53) – DNA-binding protein, encoded by the p53 gene, that acts to stop cell division; causes some cancer cells to enter senescence.

Packaging construct – Defective provirus that is integrated into the DNA of a producer cell to manufacture virus particles but which is not packaged itself because of lack of the packaging signal

Packaging signal – A sequence element in the viral genome that is essential for the genome packaging.Pandemic An epidemiology term that refers to epidemic that affects multiple continents. Site on retrovirus genome that is essential for packaging the RNA into the virus particle.

PAGE – see Polyacrylamide gel electrophoresis (PAGE).

PAI or  Prior Approval Inspection (PAI) – A facility inspection performed generally immediately prior to approval of an establishment for manufacture of an about-to-be licensed product.

PAMP – see Pathogen-associated molecular pattern (PAMP).

Pancreas – A gland in the abdominal cavity with both exocrine and endocrine function that secretes digestive enzymes into the duodenum and also secretes the hormones insulin and glucagon into the blood.

Panel tests – Used to assess for mutations in multiple genes.

Paneth Cell- A highly specialized cell type that is part of the epithelial layer of the intestine.

Panretinal photocoagulation – The application of an intense beam of laser light to the entire retina.

Papillomaviruses – Family of small DNA-containing viruses that sometimes cause tumors parasite-derived resistance making a plant resistant to a parasite by creating a transgenic plant that expresses a parasite protein

Paracortex – In an organ such as the thymus, the layer of cells lying just under the cortex.

Paracrine – A mode of action of secreted substances that influences neighboring cells through local channels, rather than through the blood. Producing effects on adjacent cells

Paracrine cells -Cells that secrete chemical substances only to the immediately surrounding (i.e., local) tissue via the interstitial fluid.

Paralog – A gene that is derived from the same ancestral gene but reside in different locations in the same genome. Similar genes (members of a gene family) or proteins (homologous) in a single species or different species that perform different functions.

Paralogy – Homology where the sequences have deviated by gene duplication.

Pararetinal intravitreous injection – An intravitreal injection close to the retina.

Parasite – A parasite is an organism that lives and feeds in or on its host. In common usage, the term “parasite” was often reserved for multicellular ani- mals that are parasitic in humans and other animals, and at other times the term was extended to include the once-called one-celled animals (i.e., members of the class formerly known as Protoctista). We now know that members of Class Protoctista are not one-celled animals. Furthermore, some of the once-called one-celled animal parasites are now known to be members of Class Fungi (e.g., Pneumocystis jiroveci). As we know more and more about classes of organisms, the term “parasite” seems to have diminishing biologic specificity and utility. In this book, the term “parasite” refers to any infectious organism. See Protozoa.

Parasite – A pathogen that depends on a host organism for both habitat and nutrition at some point in its life cycle. Includes protozoans, helminth worms and ectoparasites.

Parathyroid – Calcium homeostatic organ that secretes parathyroid hormone.

Paratope – Variable region of the antibody that binds to the antigen

Paraxial mesoderm – The middle of the three primary germ layers (mesoderm) of the embryos of vertebrates and other complex animals that gives rise to the muscles, bones, cartilage, connective tissue, blood, blood and lymph vessels, dermis, kidneys, and gonads.

Paraxial optics – Image forming through an optical system where only rays traveling close to the optical axis of the system and/or at small angles to this axis are considered.

Parenchyma – The epithelial component of a gland or organ.

Parenteral – Administration of a substance by a non-oral route (injection).

Paretos principle – Also known as the 80/20 rule, Pareto’s principle holds that a small number of items account for the vast majority of observations. For example, a small number of rich people account for the majority of wealth. Just two countries, India plus China, account for 37% of the world population. Within most countries, a small number of provinces or geographic areas contain the majority of the population of a country (e.g., east and west coastlines of the U.S.). A small number of books, compared with the total number of published books, account for the majority of book sales. Likewise, a small number of dis- eases account for the bulk of human morbidity and mortality. For example, two common types of cancer, basal cell carcinoma of skin and squamous cell carci- noma of skin, account for about 1 million new cases of cancer each year in the U.S. This is approximately the sum total for all other types of cancer combined. We see a similar phenomenon when we count causes of death. About 2.6 million people die each year in the U.S. The top two causes of death account for 1,171,652 deaths (596,339 deaths from heart disease and 575,313 deaths from cancer), or about 45% of all U.S. deaths. All of the remaining deaths are accounted for by more than 7000 conditions. Sets of data that follow Pareto’s principle are often said to follow a Zipf distribution, or a power law distribution. These types of distributions are not tractable by standard statistical descriptors because they do not produce a symmetric bell-shaped curve. Simple measure- ments such as average and standard deviation have virtually no practical mean- ing when applied to Zipf distributions. Furthermore, the Gaussian distribution does not apply, and none of the statistical inferences built upon an assumption of a Gaussian distribution will hold on data sets that observe Pareto’s principle. See Zipf distribution.

Pars membranacea – Membranous wall, present in the dorsal side of the trachea, connecting C-shaped cartilaginous rings.

Parthenogenesis- An unfertilized egg is artificially stimulated to start dividing (by an electrical or chemical stimulus) just like a normal embryo. It can often develop to the blastocyst stage but not further.

Partial agonist – Stimulates the receptor to a limited extent but also prevents any further stimulation by naturally occurring agonists.

Partial charge – A positive or negative charge less than that exhibited by a single electron or proton. These weak charges are formed(induced) when molecules (e.g., water) possess one or more atoms that attract electrons more strongly than the other atoms in the molecule and slightly move (displace) electrons within the molecule.

Partial pancreatectomy – A surgical procedure used in experimental animal models to stimulate pancreas and β-cell regeneration; a portion of the pancreas is removed, and new pancreas tissue is generated from the remnant organ.

Partial pressure -Usually indicated by a small p in front of a gas, represents the pressure exerted by that gas (in a mixture of gases) as if it were present alone in a container or a given tissue.

PAS – Prior Approval Supplement (PAS) – a submission to the U.S. FDA to gain regulatory authorization for changes to an approved application for changes that require U.S. FDA approval before they are implemented.

Passage – Refers to cell culture. When cells have filled a culture flask they need to be transferred (passaged) to new culture flasks or dishes. This usually happens twice to three times per week for tumor cells and cell lines, less for primary (non-transformed) cells.

Passaging – Repeated forced replication of a microorganism in cell cultures in a laboratory. A method of producing a live attenuated vaccine.

Passive immunisation – Transfer of antibodies to a non- immune recipient to provide immediate protection against a particular pathogen.

Pasteurization – Method of killing microorganisms by brief heating up to 60–90°C, used for food preservation and safety. Milk, for instance, is heated to 72°C for 15–20 seconds.

PAT – Process Analytical Technology (PAT).

Patent – A legal title which protects a technical invention for a limited period.

Patent Cooperation Treaty (PCT) – allows for the filing of patents in several countries at once.

Paternal- From the father. (See also Maternal).

Pathogen – Any organism that causes disease. Organism that causes disease in its host as it attempts to reproduce. Includes extracellular bacteria, intracellular bacteria, viruses, parasites, fungi and prions.

Pathogen-associated molecular patterns (PAMPs) – Structural patterns present in components or products common to a wide variety of microbes (but not host cells). Ligands for pattern recognition molecules (PRMs).

Pathogenesis – The origin, development or mechanism that causes disease. The successive changes in tissues and their cells that eventually lead to the expression of a disease. The term “pathogenesis” is occasionally confused with the term “etiology.” The term “etiology” refers to the cause of the disease. The term “pathogenesis” is the process leading to the disease, set in motion by some etiologic agent or event. It must be noted that knowing the defective gene underlying a disease (i.e., the genetic alteration without which the disease would not have occurred) is a far cry from understanding the pathogenesis of the disease. For example, a form of congenital neutropenia, a disease characterized by low white blood cells in newborns, is caused by mutations in the gene that codes for neutrophil elastase. You would think that after identifying the gene, its gene product, and knowing the role of the gene product in a target cell (i.e., metabolizing elastase in neutrophils) that we would be well on our way to claiming that we understand the pathogenesis of this disease. Not so. Neutrophil elastase may have any number of cellular substrates, and may be involved in many different cellular pathways. The steps through which an altered neutrophil elastase may eventually lead to neutropenia cannot be directly inferred. It is easy to find rare diseases whose causes are known, but whose pathogenesis is obscure. For example, a mutation in the gene encoding fumarate hydratase is the underlying cause of HLRCC, hereditary leiomyomatosis and renal cell cancer. A mutation in the gene encoding magnesium transporter-1 causes XMEN, the acronym for X-linked immunodeficiency with magnesium defect, Epstein–Barr virus infection, and neoplasia. What is the pathogenesis that connects these gene defects with their clinical phenotype? For thousands of rare diseases, their underlying genetic causes have been identified, but we have much to learn about the events that lead from an altered gene to the expression of a characteristic clinical phenotype.

Pathogenic variant – Mutation that predisposes an individual to a specific disease.

Pathogenicity island – Region of bacterial chromosome flanked by inverted repeats that carries many genes involved in virulence and pathogenicity

Pathologist – Pathology is the study of disease. Broadly speaking, patholo- gists are individuals whose careers are devoted to the study of disease. In a sense, pathology is all of medicine minus the hands-on patient care. In the past 150 years, the field of pathology has become specialized. Medical pathologists are physicians who perform diagnostic tests on tissue samples (e.g., biopsies and excised tissues), or cells (e.g., exfoliated cells in urine, scraped cells from cervix, aspirated cells from fine needle samplings of tissues), or on blood and other body fluids. Within the specialty of medical pathology, there are numerous subspecialties (e.g., molecular diagnostics, clinical pathology, surgical pathol- ogy, cytopathology, dermatopathology, forensic pathology). Research patholo- gists are scientists who study diseases in laboratories.

Pathway – According to traditional thinking, a pathway is a sequence of bio- chemical reactions, involving a specific set of enzymes and substrates that produce a chemical product. The classic pathway was the Krebs cycle. It was common for students to be required to calculate the output of the cycle (in moles of ATP) based on stoichiometric equations employing known amounts of substrate. As we have learned more and more about cellular biology, the term “pathway” has acquired a broader and more complex meaning. It can apply to activities (not just chemical products). One pathway may intersect or subsume other pathways. Furthermore, a pathway may not be constrained to an anatomi- cally sequestered area of the cell, and the activity of a pathway may change from cell type to cell type or may change within one cell depending on the cell’s physiologic status. Still, the term “pathway” is a convenient conceptual device to organize classes of molecules that interact with a generally defined set of partner molecules to produce a somewhat consistent range of biological actions. Throughout this book, the term pathway will apply to cellular actions produced by groups of interacting molecules. In most cases, the pathways are not named; the existence of the pathway is inferred whenever a complex cellular activity occurs (e.g., replication of DNA, post-translational modifications of a protein, synthesis of a molecule, DNA repair, apoptosis). See Apoptosis and Pathway- driven disease.

Pathway – An illustration of the pharmacokinetics or pharmacodynamics of a PGx-relevant drug, accompanied by informative text.

Pathway engineering – The assembly of a new or improved biochemical pathways, using genes from one or more organisms

Pathway-driven disease – Diseases with similar clinical phenotypes can often be grouped together according to shared pathways. Examples would include the channelopathies, ciliopathies, and lipid receptor mutations. At this point, our ability to sensibly assign diseases to pathways is limited because the effects of a mutation in a single gene may indirectly affect many different pathways, and those pathways may vary from cell type to cell type. Syndromes involving mul- tiple pathways and multiple tissues occur frequently when the mutation involves a regulatory element, such as a transcription factor . One transcription fac- tor may regulate pathways in a variety of cell types with differing functions and embryologic origins. Nonetheless, whenever one pathway has a dominant role in the pathogenesis of a group of diseases, we can begin to ask how we might develop diagnostic tests and treatments that apply to the rare members and the common members of the group.

Pattern recognition molecules (PRMs) – Proteins recognizing PAMPs. Soluble PRMs include the collections (MBL), acute phase proteins and NOD proteins. Membrane-bound PRMs are pattern recognition receptors (PRRs).

Pattern recognition receptors (PRRs) – Widely distributed membrane-bound PRMs fixed in either the plasma mem- brane of a cell or in the membranes of its endocytic vesicles. Includes Toll-like receptors (TLRs) and scavenger receptors. Engagement of PRRs induces pro-inflammatory cytokines.

Patterning – The act of subdividing embryos or tissues into distinct domains along the embryonic axes.

PAX-6 genes -The name PAX stands for paired box-containing genes. Such genes produce proteins with a very high degree of protein similarity (i.e., they are nearly identical as if a box [area] of their sequences were compared). Pax genes are a family of genes whose protein products are involved in organizational development of an embryo where the genes are expressed in the anteroposterior axis of the neural tube. See Walther et al., 1991. The PAX-6 gene is involved in ocular development.

Pandemic – An epidemic that spreads through a large area, such as several countries, a continent, or the entire world.

PAL – Personnel Airlock (PAL).

Papilloma – A benign epithelial tumour, such as a wart.

Papules – Raised red bumps.

Paralytic poliomyelitis – Infection with poliovirus that leads to temporary or permanent paralysis.

Particle generation rate – The number of particles of a target size released into a room (per hour) by processes, people, or in the supply air.

Particulate organic matter – Matter originating from a living organism that does not dissolve in an aqueous environment.

Partnership – 1) Generally speaking, a term that refers to a relationship of two or more entities conducting business for mutual benefit. 2) A legal, binding contract defining the association of two or more persons in a business or professional relationship.

Passive immunity – The transfer of immune system components, such as antibody, that temporarily provides protection from infection.

Pathogen-associated molecular patterns – Molecules that are associated with a specific group of pathogens.

Pattern recognition receptors – Cellular proteins that recognise pathogen-associated molecular patterns.

Patent – This term describes a government grant of rights to one or more discoveries for a set period, based on a specified set of criteria.

Paucisymptomatic – Infected but with a subclinical infection that does not show symptoms

Penetration – The stage of the viral life cycle in which the virus passes into the cell from the extracellular environment.

Percutaneous – Through the skin.

Period of communicability – The period during a person’s infection in which the individual can transmit the pathogen to others.

Peripheral proteins – Proteins that are not embedded but are associated with a cellular membrane, such as the plasma

Permissivity – Containing all of the intracellular factors that support viral replication.

Persistent infection – Infections that are not completely cleared by the host immune system.

Phage therapy – The use of bacteriophages as an alternative therapy for the treatment of bacterial infections.

Phagocytosis – The cellular process of engulfing large particulate matter by forming a plasma membrane vesicle around it.

Phospholipid – The major type of molecule that creates the plasma membrane.

Phosphorylation – The addition of a phosphate group to a molecule.

Placebo-controlled – A trial or study that includes a group that receives all treatments as the test subjects but does not receive the
active ingredient, drug, vaccine, or material being tested.

Plaque assay – An assay used to determine the number of infectious viral particles within a sample.

Plaque-forming units – A unit of measure that represents the number of infectious viral particles within a sample.

Plasma cell – The term for a B cell that is producing antibody.

Plasmid – A circular piece of double-stranded DNA that is often used for manipulating or cloning genes. Also refers to the circular genome of a temperate virus that does not integrate its genome into a bacterial chromosome.

Pneumonia – Inflammation of the lungs.

Poliomyelitis – The disease caused by poliovirus.

Poly(A) tail – The string of adenine nucleotides added to the end of an mRNA transcript.

Polycistronic – An mRNA transcript in which several open reading frames are used to create proteins.

Polymerase chain reaction (PCR) – A laboratory procedure that rapidly replicates pieces of DNA. See PCR.

Polyprotein – A long chain of amino acids that is cleaved into several separate proteins.

Portal of entry – The anatomical site at which a virus enters a host.

Portal of exit – The anatomical site at which a virus leaves a host.

Positive sense (positive strand) – A strand of RNA that can be translated by ribosomes.

Post-COVID syndrome – A condition with symptoms or complications lasting months or years after initial infection with SARS-CoV-2.

Posttranslational modification – The modification of proteins following their translation by ribosomes.

Postvaccinial encephalitis – A low-frequency complication of smallpox vaccination that leads to inflammation of the brain due to the immune response against the vaccine material.

Precellular hypothesis – The hypothesis that proposes that viruses existed before or alongside cells and may have contributed to the development of life. Also known as the virus-first hypothesis.

Presymptomatic – Infected but not yet showing symptoms.

Prevalence – The total number or proportion of cases among a given population.

Primary infection – The initial infection.

Primary vaccine failure – When an individual fails to mount an immune response against vaccine material.

Prime-boost strategy – A vaccine strategy that uses a DNA vaccine followed by a recombinant vector vaccine.

Primer – A short piece of nucleic acid used to initiate the replication of DNA.

Prion – A subviral infectious agent caused by the misfolding of a normal cellular protein.

Product Contact Surface – Surfaces of piping, components, equipment or systems that are exposed to product. When systems used inmultiple products, batches or process steps are reused, their product contact surfaces require cleaning andsanitization to reduce bioburden and the potential for carryover and crossover (e.g., product vessels, filtration skids,chromatography skids and circulating CIP systems). Product contact surfaces are a subset of process contactsurfaces. Product contact surfaces should be identified as such by the drug substance manufacturer.

PCNA (proliferating cell nuclear antigen)  – PCNA was discovered as a nuclear antigen in dividing cell, as its name implies. It acts as a sliding clamp at the replication fork, leading to increase of the “processivity” of DNA polymerase.

PCR – Polymerase Chain Reaction—a genomic method in which nucleic acids are amplified to detectable or manipulatable amounts can be used for blood screening or QC of other biologicals.

PDB file – A file listing coordinates for the atoms of a protein.

PDUFA – Prescription Drug User Fee Act—An Act of the U.S. Congress passed to cover the period 1992–97. This Act was a negotiation between regulated industry and the U.S. FDA regulators to impose a more structured “Managed Review Process” to speed up the process of regulatory review in exchange for greater resources to be able to do so through the payment by industry of “user fees.” For the first time, Congress imposed upon U.S. FDA timelines for regulatory review of marketing applications, as well as timelines for granting meetings with industry. They also imposed user fees on industry for the submission of marketing applications, and for marketed prescription drugs. (Remember biologicals, including biotechnological products, are defined as drugs by U.S. FDA.)

PDUFA III – The Re-enactment of PDUFA to cover the period of 2003–07. This Act tightened the timelines for standard review from 12 months to 10 months.

Pedicle -The cone terminal, with a foot-like flat base, which contains synaptic ribbons. The end or terminal structure of a cone photoreceptor. Each pedicle contains several cone triad synaptic complexes into which are inserted one bipolar and at least two horizontal cell processes.

Pedigree – A genetic representation of a family lineage that demonstrates various inheritance patterns in the family tree.

Pedigree -Lineage, family history, or family traits.

Peg-IFN – It is an abbreviation for the pegylated interferon. Pegylation, the process of covalent attachment of polyethylene glycol (PEG) polymer chains, prolongs its circulatory time by reducing renal clearance, thereby improving the efficacy of drugs.

Penetrance – An individual may have a gene that is necessary for the expression of a particular disease; yet the individual may not express that disease. In medi- cal genetics, the penetrance is the proportion of individuals with the mutation who exhibit clinical symptoms. There are several reasons why the penetrance of a disease-causing gene may be significantly lower than 100%. Some dis- eases, particularly the common diseases, are polygenic. It may take many genes to produce the disease phenotype. Epistasis may also modify penetrance; one gene may be influenced by a particular allele of another gene. Environmental and epigenetic factors can also influence gene function. An inherited mutation may require environmental triggers (e.g., excessive sunlight exposure in por- phyria cutanea tarda) or conditional physiological conditions (e.g., fatigue or starvation preceding the hyperbilirubinemia associated with Gilbert syndrome) to fully express the clinical trait. Such factors may influence whether a dis- ease-causing mutation is expressed as disease (i.e., its penetrance), and may also influence the age at which the disease emerges, or the severity of the dis- ease, or phenotype of the disease (i.e., which clinical problems will develop). Because we cannot know all the factors that may influence penetrance, it is safe to say that “penetrance” is a word invented to describe observations that we do not understand. The concept of disease penetrance serves as a reminder that an inherited mutation can be the underlying cause of a disease, but additional factors will have important roles in the series of events that lead to a clinical phenotype. See Epistasis.

Penetrance – Probability of a characteristic being present given a certain genotype. The likelihood that a person carrying a particular mutant gene will have an altered phenotype (see Phenotype).

Penetrating keratoplasty – A surgical procedure where a damaged or diseased cornea is replaced by donated corneal tissue which has been removed from a recently deceased individual having no known diseases which might affect the viability of the donated tissue.

Penicillins – Subfamily of antibiotics belonging to the β-lactam family of antibiotics

Penicillium notatum – The original mold that makes penicillin

Penton – Protein subunit of virus capsid with five-fold symmetry that is found at vertexes surrounded by five neighboring subunits

Pentose – A five-carbon sugar, such as ribose or deoxyribose

Peptidase – Same as proteinase; an enzyme that degrades polypeptides by hydrolysis peptide nucleic acid (PNA) Artificial analog of nucleic acid with a polypeptide backbone

Peptide – A compound molecule composed of several amino acids linked by peptide bonds. Generally, two or more amino acids joined by a peptide bond. Polypeptides are high molecular weight peptides and may fall under the definition of a protein.

Peptide vaccine – A vaccine that uses a small antigenic peptide for immunization. Vaccines that contain a single epitope or peptide attached to a carrier protein. The immune system forms antibodies to the peptide and gains immunity to the disease agent

Peptidoglycan -A polymer composed of both peptides and sugar derivatives.

Peptidyl transferase – Enzyme activity on the ribosome that makes peptide bonds; actually 23S rRNA (bacterial) or 28S rRNA (eukaryotic)

Peptidyl transferase activity – Catalytic activity of the 23S rRNA that forms a peptide bond. No enzyme is involved.

Perforin/granzyme-mediated cytotoxicity – Mechanism of apoptotic target cell destruction triggered when CTLs or NK cells degranulate to release granzymes (proteases) and perforin (pore-forming protein).

Perforating keratoplasty – Corneal transplant with replacement of all layers of the cornea, but retaining the peripheral cornea.

Periarteriolar lymphoid sheath (PALS) – A cylindrical lymphoid tissue surrounding each splenic arteriole. Populated by mature T cells, some B cells, plasma cells, macrophages and DCs.

Perichondrium – The border region of primordial cartilage anlagen that eventually differentiate into osteoblasts.

Perimeter – An apparatus used to test the visual field.

Perineum – The region between the anus and the vulva in females and the scrotum in males.

Periodontal ligament – A group of specialized connective tissue fibers that essentially attach a tooth to the alveolar bone within which it sits.

Periodontitis – A disease that attacks the gum and bone and around the teeth.

Periodontium – The specialized tissues that both surround and support the teeth, maintaining them in the maxillary and mandibular bones.

Peripheral nervous system – In the strict sense includes both the somatic and autonomic nervous systems. As used in this text, it only refers to the somatic system that includes innervation of the skin, muscles, and joints.

Peripheral protein – A protein that is attached to a bilipid membrane but does not enter it. Also known as an extrinsic protein.

Peripheral tissues – Tissues and organs other than the bone marrow and thymus; also referred to as the periphery.

Peripheral tolerance – Functional silencing or deletion of autoreactive peripheral lymphocytes that escaped elimination by central tolerance.

Permissive transcription – Represents an RNA transcription event in which the DNA structure is weak or does not lead to RNA that is competent for translation and therefore rapidly degrades.

Permissive translation – Same notion as for translation but where the RNA reading by the ribosome does not lead to a stable or functional protein or a protein of insufficient size.

Peroxisome disorder – Eukaryotic organisms contain small organelles that are involved in the catabolism of very long chain fatty acids. In humans, peroxisomes are also involved in the synthesis of various phospholipids essential to the brain. Hence, inherited peroxisomal disorders are neurologic disorders that are accom- panied by developmental and organ (e.g., liver) dysfunctions. Examples of per- oxisome disorders include Zellweger syndrome, rhizomelic chondrodysplasia punctata, neonatal adrenoleukodystrophy, and infantile Refsum disease.

Persistent infection – An infection in which the pathogen remains in the body for a prolonged period. May be latent or cause chronic disease.

Personalized medicine – A form of medical practice that uses an individual’s genetic makeup to guide treatment. The use of an individual’s genetic information (e.g., by doctors) to customize the prevention, detection, or treatment of a disease.

Personhood view – Idea in philosophical ethics that moral status is afforded to an embryo when it meets a certain threshold.

PEST sequence – Region of 10–60 amino acids that is rich in P (proline), E (glutamate), S (serine), and T (threonine) and is recognized by proteases

Peters anomaly – Cleavage of the anterior chamber with central corneal opacity.

PFD – Process Flow Diagram (PFD)

PHA – Process/Preliminary Hazard Analysis (PHA).

PHA/PHB – Polyhydroxyalkanoate/ polyhydroxybutyrate; Polyesters produced by bacteria during the fermentation of sugar and lipids. PHA and some other copolymers can be thermoformed and have properties similar to petroleum-based plastic. They are usually biodegradable.

Phage – Short for bacteriophage, a virus that infects bacteria

Phage biopanning – Fusion of a protein or peptide to the coat protein of a bacteriophage by creating a genetic fusion of the two genes. The recombinant phage are then screened for a particular function or for a particular binding partner

Phage display – Fusion of a protein or peptide to the coat protein of a bacteriophage whose genome also carries the cloned gene encoding the protein. The protein is displayed on the outside of the virus particle, and the corresponding gene is carried on the inside. Method by which peptides, parts of proteins, or entire proteins are carried on the surface of bacteriophages. Such phage displays can constitute whole libraries and when the molecule in question has bound to its ligand in a next step, individual molecules can be targeted for further studies, such as the interaction of a specific antibody fragment (from among millions of other possible fragments) with an antigen.

Phage therapy – Treatment of infections caused by bacteria with bacteriophage (i.e., bacterial viruses)

Phages – Short for bacteriophages.

Phagocyte – Cell capable of carrying out phagocytosis. Phagocytosis Process by which a phagocyte captures particulate entities by membrane-mediated engulfment.

Phagocytosis – A process in which the cell actively takes up material from the extracellular environment. Phagocytosis results in the expenditure of energy by the cell to engulf extracellular components. The process is usually performed by the cell to reconstruct the external environment or structures, or to remove noxious components. Ingestion and digestion of microorganisms by polymorphonuclear leukocytes and macrophages. The engulfment and lytic digestion of foreign substances by white blood cells associated with immune reactions. This process also occurs under other circumstances (e.g., the phagocytosis of rod outer segments by pigment epithelial cells). The process by which a cell ingests a foreign object by engulfing it. The process of pathogen engulfment through recognition of surface receptors.

Phagolysosome Vesicle – formed by fusion of a phagosome with a lysosome during phagocytosis.

Phagosome – Intracellular vesicle in which a captured entity is first sequestered during phagocytosis. Vacuole inside a phagocyte containing an ingested micro-organism

Pharmacodynamics -The study of the physiological and molecular effects of drugs on their recipient and the relationship between plasma drug concentration and drug effect.

Pharmacodynamics (PD) – The study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body, the mechanisms of drug action, and the relationship between drug concentration and effect. Pharmacodynamics is often summarized as the study of what a drug does to the body.

Pharmacogene – A gene involved in drug response.

Pharmacogenetics – A branch of pharmacology that studies the genetic responses to drug treatments. Specific genes and variants that influence drug metabolism and response of an individual to a drug, often inherited in the mendelian manner. Study of inherited differences in drug metabolism and response.

Pharmacogenetics (PGt) – The study of variations in DNA sequence as related to drug response.

Pharmacogenomic – Pharmacogenomics refers to pharmacologic studies wherein the entire genome is examined and correlations are pursued among sets of genes. Drug response predictions based on gene expression profiles could be described with the term “pharmacogenomics.” Tests on a single gene, or on several individual genes, intended to predict the response to a drug might be described with the term “pharmacogenetics.” The central dictum of pharma- cogenomics seems to be that every individual’s genome is unique; hence, every disease occurring in an individual is unique; hence, every response to treatment is unique for each individual; hence, every occurrence of disease deserves to be treated with a medication designed for the unique individual. Underlying these hypotheses is the assumption that the key elements of an individual’s disease are captured in the unique sequence of the individual’s genome. This assump- tion short-changes the complexity of genetics. Biological systems have multiple dependencies, and the genome is one player among many. Furthermore, the artifactual distinction between “etics” and “omics” creates a dichotomy where none exists. A gene belongs in a genome and a genome contains genes; they are interrelated and co-dependent concepts. As it happens, the terms “pharmacoge- netics” and “pharmacogenomics” are commonly used interchangeably. In this book, the term “pharmacogenetics” is used throughout the chapters.

Pharmacogenomics – Investigates the impact of genetics on effectiveness and side effects of drugs. Study of genes involved in drug metabolism and efficacy. The identification of the genes and genomic vari- ants that influence individual variation in the efficacy or toxicity of therapeutic agents, and the application of this information in new drug development and clinical practice.

Pharmacogenomics (PGx) – The study of variations in DNA and RNA characteristics as related to drug response.

Pharmacokinetics (PK) – A branch of pharmacology dealing with the reactions between drugs or synthetic food ingredients and living structures (e.g., tissues, organs) through studies on the absorption, distribution, metabolism, and elimination of the compound in a living system. In short, pharmacokinetics is the study of what the body does to the drug. Pharmacophore models: The term describes a set of structural features in a molecule which is recognized at a receptor site and is responsible for that molecule’s biological activity (Gund, 1977). The IUPAC definition of a pharmacophore is ‘an ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target and to trigger (or block) its biological response.’ In modern computational chemistry, pharmacophores support the process of identifying the essential features of one or more molecules with the same biological activity. Databases of diverse chemical compounds can be searched for molecules which share the same features.

Pharmacovigilance – The activities associated with monitoring, collecting, evaluating, and acting upon signals of risks (both to safety and efficacy) throughout a medicine’s life-cycle.

Pharmerging countries – are countries that are in the early stages of developing a biopharmaceutical industry within their borders. Examples include Brazil, China, India, and South Korea.

Pharyngeal – The area of the digestive system that serves as a respiratory and feeding organ in hemichordates, tunicates and lancelets. The vertebrate homolog is the pharynx, which develops into gills in early vertebrates, but is the area of the throat, including the thyroid gland and thymus in amniotes (birds and mammals).

Pharyngeal gill bars – Cartilaginous elements made of extracellular matrix and located between the pharyngeal endoderm, giving structure to the pharynx of hemichordates, lancelets and vertebrates. Pharyngeal gill bars are secreted from endoderm in hemichordates and lancelets, but develop from neural crest cells in vertebrates.

Phase I – The first phase of clinical trials for a drug after preclinical testing usually in animals. Phase I trials test for the safety of the drug in healthy volunteers. Phase I clinical testing also seeks to determine how the pharmaceutical is absorbed, distributed, how long it is active in the body, how it is metabolized by the body, and how and when it is excreted (pharmacokinetics).

Phase II: The second phase of clinical trials for a drug. Phase II trials test for efficacy and safety of the drug in patients who suffer from the relevant disorder. In addition, side effects, effective dose strength, and dosing schedule are determined.

Phase III – The third and final phase of human trials for a drug before approval status. Phase III trials study efficacy and safety of the drug using patients who have the relevant disorder. They differ from Phase II trials as these clinical studies are usually much larger, take longer, and are much more expensive.

Phase variation – Reversible inversion of a segment of DNA leading to differences in gene expression

Phenocopy disease – A non-hereditary disease or condition produced by an exogenous factor that replicates a disease produced by a genetic mutation. Examples would include acquired porphyria due to alcohol abuse; acquired Parkinson-type syndrome due to anti-psychotic medications; myopathy produced by AZT (i.e., azidothymidine), a drug that interferes with mitochondrial DNA replication; Antabuse (disulfiram), an acetaldehyde dehydrogenase inhibitor that induces alcohol intolerance, mimicking genetic diseases of alcohol metabolism. Phenocopy diseases provide important clues to the pathogenesis of rare and com- mon diseases. The drug that produces a phenocopy disease may share the same pathway employed in a specific genetic disease or in a common disease whose phenotype overlaps with the genetic disease. Pharmacologic treatments for the phenocopy disease may apply to pathways operative in the genetic form of the disease or in the common diseases. For a full discussion, see Section 9.5.

Phenol – Organic chemical with the formula C6H5OH consisting of a hydroxyl group attached to a phenyl ring. It is used to remove protein from nucleic acids by dissolving the proteins

Phenotype – An organism’s observable characteristic or trait, such as biochemical or physiological properties or behavior. Phenotypes result from the expression of an organism’s genes as well as the influence of environmental factors and the interactions between the two. Physical characteristics of an organism through the interaction of genotype and environment. The clinical and/or any other manifestation or expression of a condition, such as a biochemical immunological alteration of a specific gene or genes, environmental factors, or both. The observable physical representation of an expressed gene. The physical and functional characteristics of genes. The set of observable traits and features in an organism. The normal phenotype would be the complete set of morphologic and physiologic patterns that characterize the organism. As used herein, a “disease phenotype” is the set of observable traits and features that characterize a disease. Geneticists typically think in terms of a process in which a genotype (i.e., the genetic composition of an organism) is expressed as a phenotype. Visible or otherwise recognizable characteristic of an individual, resulting from genetic as well as environmental factors (see also genotype).

Phenotype catalogue – A listing of proteins that cause the same phenotype when their function is disrupted.

Phenotypic heterogeneity – Occurs when a given genotype may produce dif- ferent phenotypes. In the context of disease, it occurs when a gene mutation may produce any of several different clinical disorders. If you look closely enough at any genetic disease, phenotypic heterogeneity is a universal phenomenon. No two individuals will ever express the same exact set of clinical problems; even identical twins.

Phenotypic signature – A set of physical features that are categorized together to classify a particular cell function, such as adherence, motility, or cell division.

Phenylalanine hydroxylase – The enzyme that converts the amino acid phenylalanine into tyrosine.

Phenylboronate – Resin used to bind betalactamases.

Phenylketonuria (PKU) – Inherited defect causing lack of the enzyme phenylalanine hydroxylase and hence a buildup of phenylalanine.

Pheromone – Molecule that carries signals between organisms.

φ and ψ angles – Rotation angles of certain bonds of a protein backbone.

ΦC31 (phiC31) integrase – A DNA integrase from bacteriophage phiC31 used to insert segments of foreign DNA at a specific site in genetic engineering.

PhoAgene – Gene encoding alkaline phosphatase; widely used as a reporter gene.

Phonation – Production of sound by the vocal folds.

Phosphate group – Group of four oxygen atoms surrounding a central phosphorus atom found in the backbone of DNA and RNA

Phosphatidyl serine – A kind of phospholipid, which is a major constituent of membrane lipid.

Phosphodiester bond – The linkage between nucleotides in a nucleic acid that consists of a central phosphate group esterified to sugar hydroxyl groups on either side

Phosphodiesterase 5 (PDE5) – One particular cyclic phosphodiesterase of animal cells that degrades cyclic GMP.

Phospholipase – Enzyme that degrades phospholipids.

Phospholipase C – Enzyme that hydrolyzes membrane bound phosphatidyl 4, 5-bisphosphate to 1,2-diacylglycerol and 1,4,5- trisphosphate (IP3).

Phospholipid – A lipid in which two fatty acids and a polar head group are esterified to glycerol. Phospholipids are important membrane components.

Phosphoramidite – A monoamide of a phosphite diester found on nucleoside phosphoramidites which are used during chemical synthesis of DNA.

Phosphorelay – Term to describe transferring one phosphate from one location to another to successively activate different proteins.

Phosphorodiamidate – An uncharged version of the phosphodiester group linking nucleotides in which one of the oxygen atoms is replaced with an amidate group.

Phosphorothioate – A phosphate group in which one of the four oxygen atoms around the central phosphorus is replaced by sulfur.

Phosphorothioate oligonucleotide – A synthetic oligonucleotide with a sulfur replacing one of the four oxygen atoms in the phosphodiester linkage between nucleotides.

Phosphorylation – The process of adding a phosphate group (PO –3) to a compound or metabolic intermediate. In the generation of high energy ATP (see text) phosphorylation can be either simple (substrate level) or complex (oxidative). In the latter case, electron and proton transports are involved.

Phosphotransferase system – System found in many bacteria that transports sugars and regulates metabolism. It operates by transferring phosphate groups.

Photodetector – Sensitive instrument that detects an optical signal and converts it into an electrical signal.

Photoentrainment – The synchronisation of circadian rhythms to the daily light:dark cycle.

Photolithography –  Method used to synthesize oligonucleotides directly on a DNA chip where light is passed through a mask to selectively activate some regions and keep other regions blocked.

Photolyase – Enzyme that catalyzes the repair of DNA thymine dimers in response to blue light.

Photopic vision – The scientific term for color vision mediated by multiple cone photoreceptor types in bright light. In the human retina, photopic vision is trichromatic.

Photopigment – A light-sensitive protein in the photoreceptors (rods and cones) that undergoes a conformational change when absorbing light and initiates the process of visual transduction.

Photorefractive keratectomy (PRK), laser-assisted sub-epithelial keratectomy (LASEK), or laser-assisted in situ keratomileusis (LASIK) – Laser eye-surgery procedures for correcting a person’s vision can reduce the need for glasses or contact lenses.

Phototransduction – A process by which light is converted into electrical signals in rod and cone photoreceptor cells in the retina of the eye.

Phylogenetic tree – A diagram showing the evolutionary relationship of different organisms physical mapping Determining the actual distance between genetic markers by physically.

Phylogenetics  – The identification of evolutionary relationships between organisms or between genes.

Physical maps – Genetic maps that give physical DNA base-pair lengths between features.

Physiological barriers – Body elements supplying non- specific, non-induced innate defense, such as the low pH of stomach acid and hydrolytic enzymes in body secretions.

Phytoremediation – Using plants to sequester various water or soil contaminants so that it cannot effect other wildlife.

PI – Package Insert – the labeling accompanying a medicinal product that documents the clinical indication, directions for use, precautions & warnings, data which support the safety & efficacy of the product & other details as required by the regulatory authority. The PI generally is packaged in the containers (e.g., carton) in which the medicinal product is distributed, whether it is a single-dose container/carton or a multidose container/carton. Other terms for this include package leaflet and prescribing information.

PI – see Principal investigator (PI).

Picornaviruses – Virus family that includes enteroviruses (such as poliovirus) and rhinoviruses (which cause the common cold).

Pigment-dispersing hormones – A family of peptides that regulates migration of pigment granules in the crustaceans’ eye and in chromatofores of their body surface and also plays the role of neurotransmitters in circadian systems of crustaceans and insects. In insects, these peptides are called pigment-dispersing factors.

Pigment-epithelium-derived factor (PEDF) – A monomeric peptide that is a member of the serpin serine protease inhibitor family that is neurotrophic as well as anti-angiogenic.

Piezoelectric ceramics – Materials that change shape in response to an applied voltage.

piggyBac – A transposon originally found in insects.

Pilin – Protein that makes up the main part of a pilus.

Piloerection – The erection of a hair through the contraction of the smooth muscle at its base.

Pilot – A study of only a few subjects in which the design, materials, and/or procedures anticipated for a larger trial o-re tested for feasibility.

Pilus (plural pili) – Thin helical protein filaments found on the surface of bacteria; same as fimbria.

Pinocytosis – Engulfment of free antigen by a phagocyte.

Pioneer translation – Represents the first “round” of translation by one or several ribosomes of a messenger RNA. This first cycle is considered as a stage necessary for the establishment of robust translation of an mRNA molecule.

PITX genes – pituitary homeobox genes. These genes make transcription factors for RNA associated with eye and other organ development.

Pivotal – Clinical trials that form the primary basis for making licensure decisions, generally Phase 2 (or 2b) and 3 trials that test efficacy and safety.

Piwi-interacting RNAs – A class of small non-coding RNAs that are encoded by genes in the organism’s genome, and are used to inhibit transposon movement; specific to germ cells

PKPD – Pharmacokinetics and pharmacodynamics (PKPD). Pharmacokinetics describes the dynamics of the drug as it goes through absorption, distribution, metabolism, and eventually excretion. Pharmacodynamics describes the effect the drug has on its target when it is present in the body.

PKR (protein kinase RNA-activated) – A serine/threonine kinase that is activated by double-stranded (dsRNA).

pl -Isoelectric point (pI). The pH at which all of the positive and negative charges on a protein or other compound are equal.

Placebo- Pharmaceutical drug or treatment that by itself is ineffective. It is used as control drug or treatment to test efficacy of realdrugs and treatments. Because of the subjective perception of treatment effects, the condition of the patient may improve. This isknown as a placebo effect.

Placebo arm – An arm of a trial in which the administered study agent is an inert substance.

Placodes  –  An area of an ectodermal thickening from which cells delaminate and eventually achieve a cell fate that is not epidermal. There are both neurogenic and non-neurogenic cranial placodes, which are associated with the peripheral nervous system in vertebrates. Placodes were thought to be found only in vertebrates, but have recently been described in tunicates, using both molecular markers and careful morphological analyses.

Planar cell polarity (PCP) – This establishes the polarity of cells within an epithelium, or for migrating cells controls the localization of polar ized protrusions. PCP signaling is essential for the convergent extension movement that drives neural tube closure.

Plaque – It refers to an area of empty hole in the monolayer of cells in plate, resulting from the cell lysis induced by virus infection.

Plaques (when referring to viruses) – A clear zone caused by virus destruction in a layer of cultured cells or a lawn of bacteria

Plasma – Fluid component of blood.

Plasma cell dyscrasias – Hematopoietic cancers of plasma cells.

Plasma cells – B cells that are actively producing antibodies. Terminally differentiated B cells that secrete antibody. May be short-lived (no isotype switching or somatic hypermutation) or long-lived (undergo isotype switching and somatic hypermutation).

Plasmablasts – Proliferating progeny of an activated B cell.

Plasmapheresis – A process by which an individual’s blood is withdrawn and passed through a machine designed to remove antibody proteins. The machine then returns the treated blood to the patient.

Plasmid – A self-replicating circular DNA molecule. It contains origin of replication, selectable marker and multiple cloning sites. It is widely used for cloning and expression of gene for biotechnological applications. Circular extrachromosomal DNA molecules present in bac- teria and yeast. Plasmids replicate autonomously each time a bacterium divides and are transmitted to the daughter cells. DNA segments are commonly cloned using plasmid vectors. Self-replicating genetic elements that are sometimes found in both prokaryotic and eukaryotic cells. They are not chromosomes or part of the host cell’s permanent genome. Most plasmids are circular molecules of double-stranded DNA, although rare linear plasmids and RNA plasmids are known

Plasmid incompatibility – The inability of two plasmids of the same family to coexist in the same host cell

Plasmids – Small circular extra-chromosomal dsDNA molecules found in bacteria and some yeasts. They contain only very few genes and are replicated as independent genetic units. Plasmids often carry antibiotic resistance genes as selectable markers.

Plasmodium falciparumProtozoan parasite that causes the malignant form of malaria

Platform technologies – Technologies (e.g., in preclinical development, genomics, bioimaging, structural biology) that can be used to facilitate a wide range of application-based activities. The use of appropriate platform technologies can reduce costs and avoid unnecessary duplication of facilities, increase international R&D competitiveness, and provide an environment of effective networking and collaboration.

Platelet activating factor -A phospholipid plasmologen having a vinyl ether linkage on one fatty acid (glycerol–CH2–O–CH=CH–R1). This compound causes blood pressure lowering, blood clotting, and other effects.

Platelet-activating factor (PAF) – A lipid inflammatory mediator that activates platelets.

Platelet-rich plasma (PRP) – Blood plasma that has been enriched with platelets.

Platelets – Micro particles produced by megakaryocytes in the bone marrow, which circulate in the body, store angiogenesis regulators, and are involved in clotting and neovascularization.

Pleiotropic – (alternate spelling, pleiotrophic)—See Pleiotypia.

Pleiotropy -Multiple physical effects caused by a single gene. The underlying mechanism of pleiotropy may be a gene involved in different metabolic pathways that contribute to different phenotypes. The phenomenon observed when one gene influences multiple traits and phenotypes.

Pleiotypia – Refers to an effect wherein one gene influences more than one phenotypic trait. A gene that has a pleiotypic effect is said to be pleiotropic (alternate spelling, pleiotrophic). An example of pleiotypia is found in X-linked heterotaxy-1. Heterotaxy is a developmental disorder in which one or more organs are found in abnormal locations. X-linked heterotaxy-1 is characterized by situs inversus, wherein the positions of the major organs are reversed along the body axis. Because normal development requires the customary positioning of organs, X-linked heterotaxy-1 is accompanied by complex cardiac defects, and splenic defects. All these changes are caused by a single alteration in a single gene: ZIC3.

Pleuroperitoneal fold (PPF) and post-hepatic mesenchymal plate (PHMP) – These terms describe primordial diaphragmatic mesenchymal tissue that is most easily visualized at mouse embryonic days 11.5–12.5 in the thoracoabdominal region. There is disagreement in the literature about which tissues grow to make up the majority of the posterior diaphragm. This is partially complicated by inconsistent application of the terms to the embryonic anatomy, as plane of sectioning artifacts and other factors can make it very difficult to delineate these structures.

PLLp– Posterior Lateral Line Primordium, a cluster of approximately 100 cells that migrates collectively from the ear to the tip of the tail periodically depositing neuromasts.

Pluripotency – Ability of a cell to give rise to all cells of the embryo. Cells of the inner cell mass and its derivative, embryonic stem (ES) cells, are pluripotent. The ability of a cell to differentiate into any tissue of the organism, but the inability to give rise to a complete individual. Pluripotent cells give rise to the three embryonic compartments (endoderm, mesoderm and ectoderm). Each embryonic layer generates determined cells for each organ. Ability of pluripotent stem cells to differentiate into cells of any of the three germ layers: ectoderm, entoderm, and mesoderm. This enables them to become any cell type in an organism. In contrast to totipotent cells, however, they have lost the ability of forming an entire organism.

Pluripotent stem cell – The ability to yield, after cell divisions, differentiated cell types from any of the three embryonic layers (i.e., endoderm, ectoderm, and mesoderm). Pluripotent stem cells differ from totipotent stem cells as they do not yield cells of extra-embryonic type (e.g., trophoblasts). It is now possible to induce the formation of human pluripotent stem cells from cultured fibroblasts treated with a cocktail of transcription factors. Pluripotent stem cells, including the embryonic stem cells, epiblast stem cells, and induced pluripotent stem cells, possess the abilities of infinite self-renewal and differentiation into all the cell types of three germ layers.

Pluritest – A microarray-based method for gene expression profiling, used to assess whether a stem cell is pluripotent. It is expected that pluritest will replace teratoma formation in mice as an assay of pluripotency.

Plus (+) strand – The coding strand of RNA or DNA

PMA – Premarket application (PMA).

PMN- Polymorphonuclear leukocytes (PMN) – Cells of the innate immune response characterized by a multilobed nucleus including neutrophils and eosinophils.

Precision – Closeness of results to one another, e.g., from replicates; from testing the same samples on different days, with different reagents, or by different operators; or from testing the same samples between or among laboratories.

pMHC– The peptide-MHC complex formed by the covalent binding of peptide in the peptide-binding groove of an MHC molecule.

POU – Point Of Use (POU)

Podocyte – Specialized cell type of the glomerulus that plays an essential role in filtration and lies at the interface between glomerular capillaries and the entrance to the kidney tubule.

Point mutation – Mutation in which just one base pair in the DNA is changed, which may well revert to the wildtype, as the reading frame remains unchanged. Such mutations are often innocuous because many amino acids are encoded by more than one codon (due to degeneration [redundance] of the genetic code). The substitution of a single DNA base in the normal DNA sequence.

Poison sequence – Base sequence, often found in virus genomes, that is not stably maintained or replicated on plasmids in bacterial hosts

Polar interactions -See Hydrogen bonding.

Polar nature – The property or ability of a molecule to possess displaced electrons causing partial charges to exist in the molecule.

Polarity – It refers to the strandness of a single-strand DNA or RNA. The strand that corresponds to that of mRNA is defined as “plus” or “positive.” The strand that is complementary to mRNA is defined as “minus” or “negative.”

Poliomyelitis – The term “poliomyelitis” is derived from Greek word for “gray”-polio 1 for “marrow”-myelos1 “inflammation”-titis. The term implies paralytic poliomyelitis, resulted from destruction of motor neurons within the spinal cord in the CNS.

Poly (A) tail – A stretch of multiple adenosine residues found at the 3′ end of mRNA.

Polyacrylamide gel electrophoresis (PAGE) – Technique for separating proteins by electrophoresis on a gel made from polyacrylamide.

Poly (glycolic acid) – A biodegradable, thermoplastic polymer and the simplest linear, aliphatic polyester.

Poly (lactic acid) – A thermoplastic aliphatic polyester derived from renewable resources, such as corn starch (in the United States), tapioca roots, chips or starch (mostly in Asia), or sugarcane (in the rest of the world).

Poly N-isopropyl acylamide – A temperature-responsive polymer that can be synthesized from NIPAM which is commercially available.

Poly(lactic-co-glycolic acid) – A copolymer which is synthesized by means of random ring-opening co-polymerization of two different monomers, the cyclic dimers (1,4-dioxane-2,5-diones) of glycolic acid and lactic acid.

Polyadenylation complex – Protein complex that adds the poly (A) tail to eukaryotic mRNA

Polycistronic mRNA – mRNA carrying multiple coding sequences (cistrons) that may be translated to give several different protein molecules; only found in prokaryotic (bacterial) cells.

Polyclonal antibodies – mix of antibodies produced by different B-lymphocytes that bind to different epitopes of the same protein. This distinguishes them from monoclonal antibodies. Natural antibody that actually consists of a mixture of different antibody proteins that all bind to the same antigen.

Polyclonal antiserum – Antiserum that contains antibodies produced by many different B cell clones responding to different epitopes of an antigen.

Polycomb – Polycomb proteins were discovered for the first time in Drosophila melanogaster and can remodel chromatin to switch off gene expression. For example, HOX genes are mainly regulated by polycomb factors during development. It is now clear that these factors are themselves controlled, targeted or activated by non-coding RNA in a genome region- specific manner.

Polycythemia – Polycythemia is an increase in the number of circulating red blood cells. An increase in red blood cells can occur as a response to a physi- ologic stimulus (e.g., chronic anoxia, high-altitude living). When polycythemia occurs as an intrinsic defect of red blood cells, it is called primary polycythemia. The term polycythemia vera, or “true” polycythemia, is reserved for a clonal disorder of the red blood cell lineage in cells that have a genetic aberration that drives proliferation. The cause of polycythemia vera is a mutation of the JAK2 gene occurring in a single hematopoietic stem cell from which a clonal expan- sion eventually raises the number of circulating erythrocytes. Mutations in JAK2 are associated with a variety of myeloproliferative conditions, includ- ing myelofibrosis, and at least one form of hereditary thrombocythemia.

Polydactyly – Also known as hyperdactyly, this is the anatomical variant consisting of more than the usual number of digits on the hands and/or feet. When each hand or foot has six digits, it is sometimes called hexadactyly.

Polygenic – A particular phenotype that is influenced by more than one gene.

Polygenic disease – A disease whose underlying cause involves alterations in multiple genes. See Monogenic disease, Digenic disease, and Oligogenic disease.

Polygenic trait or character – A character or trait determined by the combined action of a number of loci, each with a small effect.

Polygenicity – The existence of multiple genetic loci encoding polypeptides with identical function.

Polyglutamine tract – Run of multiple glutamine residues in a protein

Polyhedrin – Protein that comprises polyhedron structure of baculoviruses

Polyhedron – In reference to viruses, the packages of virus particles embedded in a protein matrix that are formed by baculoviruses

Polyhistidine tag (His6 tag) – Six tandem histidine residues that are fused to proteins, thus allowing purification by binding to nickel ions that are attached to a solid support

Polyhydroxyalkanoate (PHA) – Type of bioplastic polymer made by certain bacteria from hydroxyacidsubunits

Polyhydroxybutyrate (PHB) – Bioplastic polymer made by certain bacteria from hydroxybutyrate subunits

Poly-Ig receptor (pIgR) – Polymeric immunoglobulin receptor. Receptor positioned on the basolateral surface of mucosal epithelial cells. Binds to the J chain in secreted polymeric Ig and facilitates transcytosis of the Ig into external secretions. Cleavage of pIgR leaves secretory component attached to the Ig molecule.

Polyketide – Class of natural linear polymers whose backbone consists of two carbon repeats with keto groups on every other carbon (when first synthesized)

Polylinker – (see also multiple cloning site [MCS]) A stretch of artificially synthesized DNA that contains cut sites for seven or eight widely used restriction enzymes

Polymer – A chemical compound or mixture of compounds consisting of repeating structural units created through a process of polymerization.

Polymerase – An enzyme that synthesizes nucleic acids. There are several types, a DNA directed DNA polymerase makes DNA from a DNA template. DNA-directed RNA polymerases make RNA from a DNA template. Viruses use other types as well.

Polymerase chain reaction (PCR) – A molecular biology technique developed in the mid-1980s through which specific DNA segments may be amplified selectively. Amplification of a DNA sequence by repeated cycles of strand separation and replication. Method that allows a certain region of DNA to be amplified through a repetitive process of denaturation, attachment of specific primers, and DNA Taq polymerase. The amplified concentration of the DNA fragment increases exponentially with each cycle. Technique that allows a short sequence of DNA or RNA to be amplified. 

Polymicrogyria – A disorder of the cerebral cortex, distinguished by the presence of smaller than normal folds (gyri) in the cortical surface. This condition can be very local, affecting only a small segment of the cortex, or it can encompass entire cortical lobes.

Polymorph nuclear leukocyte – Neutrophil. White blood cell with neutral granules and multilobed nucleus. Original name for neutrophils, referring to their irregularly shaped, multi-lobed nuclei. 

Polymorph nuclear lymphocytes – PMNs. White blood cells having polylobulated nuclei.

Polymorphism – The term “polymorphism” can have several somewhat different meanings in various fields of biology. Polymorphism can refer to genetic polymorphism, indicating that variants of a gene occur in the general population. A polymorphism is usually restricted to variants that occur with an occurrence frequency of 1% or higher. If a variant occurs at a frequency of less than 1%, it is considered to be sufficiently uncommon that it is probably not steadily maintained within the general population. All commonly occurring polymorphisms are assumed to be benign or, at worst, of low pathogenicity; the reasoning being that natural selection would eliminate frequently occurring polymorphisms that reduced the fitness of individuals within the population. Nonetheless, different polymorphisms may code for proteins with at least some differences in functionality. A difference in DNA sequence between two related individual organisms polyploid Having more than one set of chromosomes per cell. A variation in DNA sequence that is present at an allele frequency of ≥1% of the population. Existence of different alleles of a gene within a population. The stable existence of two or more variant allelic forms of a gene within a particular population or among different populations.

Polyols – Polyhydroxy intermediates formed in the polyol pathway that are a source of osmotic stress for cells, especially those of the lens.

Polyploid – Cells or organisms with more than two sets of chromosomes (see also haploid, diploid).

Polyprotein – It refers to a large protein that is later processed to multiple functional proteins.

Polysaccharide – A polysaccharide consisting of 10 or more sugar units branched or unbranched. Glycogen is an example. Long carbohydrate molecules of repeated monomer units joined together by glycosidic bonds.

Polysome – Group of ribosomes bound to and translating the same mRNA

Polytene chromosomes – Giant chromosomes found in cells that replicate their DNA without dividing into separate cells. Found in Drosophila salivary gland cells.

Polyvalent inhibitor – Inhibitor consisting of several linked inhibitor molecules that consequently binds multiple copies of its target, giving a very high overall binding affinity

Population equivalent (PE) – or unit per capita loading, the equivalent of the daily per inhabitant quantity of pollutants and water consumption (e.g., nitrogen, phosphorus, oxygen demand, particular matter, etc.) in waste water.

Portfolio company – A company that has received one or more venture capital investments, but has not yet been exited.

Position effect variegation (PEV) – The effect of chromosomal position on the expression of a particular gene. For example, genes embedded within heterochromatin are not expressed, but if positioned in euchromatin, the same gene would be expressed

Positional cloning – Approach that attempts to locate a gene by its position on a chromosome and is used when the nature of the gene product is unknown. The candidate genes are located in the genome through their coinheritance with linked markers. It allows genes to be identified that lack information regarding the biochemical actions of their functional product.

Positive (+) strand – The coding strand of RNA or DNA

Positive predictive value – The chance a person who tested positive has the condition.

Positive regulation – Control by an activator that promotes gene expression when it binds.

Positive selection – A central tolerance process that promotes the survival and maturation of developing B or T lymphocytes with the potential to bind to non-self antigen upon release into the periphery.

Posterior embryotoxon – Displacement of Schwalbe’s line anterior to limbus in cornea.

Post-implantation embryo – Implanted embryo in the early stages of development until the establishment of the body plan of a developed organism with identifiable tissues and organs.

Post-mitotic – Refers to fully differentiated cells that have lost the ability to divide. For example, the epidermis of the skin has a basal layer of cells that are capable of dividing to produce a post-mitotic cell and another basal cell. The post-mitotic cells sit atop the basal cells to flatten out and lose their nucleus as the cells rise through the epidermal layers. The top layer of the epidermis sloughs off the body and is replaced by post-mitotic epidermal cells in the next lower layer. This cycle of cell renewal from the bottom and cell sloughing from the top is typical of most epithelial surfaces of the body (e.g., epidermis of skin, gastrointestinal tract, and glandular organs). Aside from epithelial surfaces, post-mitotic cells arise from populations of mitotic cells that have exhausted their regenerative potential. One theory of aging holds that certain cell types of the body (e.g., fibroblasts) have a limited number of mitotic cell cycles. When a predetermined number of cell cycles have elapsed, cells cannot divide further, becoming post-mitotic. See Mitosis.

Post-money valuation – The value or total price of a start-up including the new investment. Thus, pre-money value plus investment equals post-money value.

Postsynaptic inhibition – The process in which nervous transmission is prevented in the postsynaptic nerve or muscle cell. This may take the form of an increased hyperpolarization of that cell. The term inhibitory postsynaptic potential (IPSP) is also used. An IPSP may be caused by an inhibitory neurotransmitter or by a decrease in the amount of neurotransmitters released across the cleft (as occurs with cone photoreceptors).

Postsynaptic stimulation – The process in which nervous transmission or depolarization is continued in the postsynaptic nerve or muscle cell. The term excitatory postsynaptic potential (EPSP) is also use. However, note that in photoreceptor cells that an EPSP is caused by a presynaptic hyperpolarization that stops the release of neurotransmitters.

Post-transcriptional gene silencing (PTGS) – Plant version of RNA interference.

Posttranscriptional modification – A series of steps through which pro- tein molecules are biochemically modified within a cell after syn- thesis by translation of mRNA. A protein may undergo a complex series of modifications in different cellular compartments before its final functional form is produced. 

Post-translational modification – The biochemical alteration of a protein after the synthesis of its polypeptide chain.

Posttranslational processing – Modification of the structure of a polypeptide after the basic polypeptide chain has been assembled.

Post-translational protein modification – Much happens between the moment when the amino acid sequence of a protein is translated from an RNA template and the moment when the fully modified protein, in its optimal conformation, arrives at its assigned station. Errors in the post-translational process, including timing errors (i.e., the proper sequence of events that lead to the finished prod- uct), can have negative consequences. An example of a rare disease caused by a defect in a post-translational process is congenital disorder of glycosylation type IIe, caused by homozygous mutation in a gene that encodes a component of a Golgi body protein that is involved in post-translational protein glycosylation; the COG7 gene. This rare disease produces a complex disease phenotype in infants, with multiple disturbances in organs and systems plus various ana- tomic abnormalities. In the few reported cases, death results in a few months. See Vesicular trafficking disorder.

Post-transplant lymphoproliferative disease (PTLD) – A complication of transplantation in which recipient B cells that are infected with EBV proliferate uncontrollably due to the immunosuppressive treatment necessary to prevent graft rejection.

Potency – U.S. FDA defines this term in 21 CFR 600.3(s) as- “specific ability or capacity of the product, as indicated by appropriate laboratory tests or by adequately controlled clinical data obtained through the administration of the product in the manner intended, to effect a given result.” ICH defines the term as- “the measure of the bio- logical activity using a suitably quantitative biological assay (also called a potency assay or bioassay), based on the attribute of the product which is linked to the relevant biological properties.”

Potential difference – A charged force, usually given in mV, that exists across a cell membrane. Strictly defined, it is the work that must be accomplished to move a charge over a defined distance.

Poiseuille’s law – A physical law that describes slow, viscous, incompressible flow through a circular cross section. It states that for a laminar, nonpulsatile fluid flow through a uniform straight tube, the vascular resistance is inversely proportional to the fourth power of the radius of a vessel, and is directly proportional to the blood viscosity and length of the vessel.

Poxviruses – Family of large animal viruses with dsDNA and approximately 150 to 200 genes

Prader–Willi syndrome – Inherited defect resulting in loss of function of genes on the paternally derived copy of chromosome 15 that are subject to imprinting

PRB (retinoblastoma protein) – Protein associated with a malignant cancer of the retina; involved with cellular senescence

Preactivation-The state of a provirus that remains untranscribed in the host cell genome due to the absence of host cell stimulation.

Pre-BCR – Complex composed of surrogate light chain (SLC), a candidate μ chain, and the Igα/Igβ complex. The pre-BCR is inserted transiently in the membrane of a developing B cell to test the functionality of a particular heavy chain VDJ combination.

Precancer – Precancers are the lesions from which cancers derive. Most pre- cancers are non-invasive and non-metastatic, so eliminating precancers cures the patient of the cancer that might have eventually developed. Two of the most interesting properties of precancers, lacking in fully developed cancers, are their propensity for spontaneous regression and the ease with which they can be treated and cured. Precancers have fewer of the genetic and epigenetic altera- tions that accumulate in cells during the long process of carcinogenesis and tumor progression. Like rare diseases, they are genetically and epigenetically simple; at least, they are simpler than the cancers into which they develop. They seem to obey the general rule that diseases with the simplest genetic alterations are the easiest to treat successfully..

Precancer regression – One of the properties of precancers is regression. It is not unusual for a precancer to stop growing, or to shrink and disappear. See Spontaneous regression.

Precancerous condition – A condition or event that predisposes a person to the development of a precancer and to the eventual development of a cancer. For example, patients with cirrhosis have a high risk of eventually developing cancer. Over time, the cirrhotic liver becomes nodular, and precancerous lesions develop from the nodules. In some cancers, the precancerous nodules develop into cancer (i.e., hepatocellular carcinoma). Cirrhosis is a precancerous condition, but it is not a precancer. Cirrhosis simply sets the stage for precancers to develop.

Precautionary principle – The principle that the burden of proving that a proposed change is safe falls on those proposing the change

Precipitation – Deposition of a soluble component in solution as a solid due to the addition of another substance such as a poorly soluble compound.

Précis – In clinical trials it is a clinical trial outline. In a protocol, a brief summary of what the study is about.

Preclinical – The stage of drug testing (in animals) that precedes clinical trials (in humans).

Preclinical study/trial – A preclinical study often involves the use of animals for evaluation of an investigational new drug. Preclinical studies may be performed to assess the product’s safety (toxicology studies), activity (e.g., bio- availability, immunogenicity), or efficacy (proof-of-concept studies, challenge-protection studies). Investigations of drug activity prior to human studies. The term often applies to animal experiments that determine how candidate human drugs are metabolized in animals, and to measure various parameters of animal toxicity. One of the measures that come from animal trials is the “no observable adverse effect level,” which is used to calculate a range of dosages that might be used in the earliest clinical trials. A series of controlled tests of a drug, vaccine or treatment that is carried out in cell cultures or experimental animals and used to determine if the treatment should progress to clinical trials in humans.

Preconception screening – Testing couples for carrier status of autoso- mal recessive traits to provide counseling regarding risks to a future child.

Precursor cell – Fully engaged cell that differentiates into a specialized cell. The precursor is not capable of infinite self-renewal; it can be divided a limited number of times. Under differentiation conditions, the precursor, for example osteoblastic or hepatic, no longer divides. It transforms into the final cell, the osteocyte or the hepatocyte, which has stopped dividing.

Predentin – The newly secreted dentin which is unmineralized.

Predictive test – A test that estimates a patient’s response to a particular treat- ment. The terms “predictive test” and “prognostic test” should not be confused with one another. See Prognosis.

Predictive testing – Determines the probability that a healthy individual with or without a family history of a certain disease might develop that disease.

Predictive toxicology – Evaluation and prediction of the toxicity of a drug in pharmaceutical research. High-throughput analyses and modeling are new technologies that complete the toxicological test strategy.

Predisposition, genetic – Increased susceptibility to a particular disease attributed to the presence of one or more gene mutations, and/or a combination of alleles (haplotype), not necessarily abnormal, that is associated with an increased risk for the disease, and/or a family history that indicates an increased risk for the disease.

Preferred stoc – Shares with preferential rights over common stock with respect to  any dividends or payments in association with the liquidation of the company.Moreover, the preference shares may also have additional rights, such as the ability to block mergers and/or to displace the management team.

Pre-genomic era – A period in the history of molecular biology during which no genomes had yet been characterized and/or techniques for measuring the whole genome had not yet been fully developed.

Pre-implantation embryo – Fertilized egg (zygote) and all of the developmental stages up to, but not beyond, the blastocyst stage (day 5).

Preimplantation genetic diagnosis (PIGD) – Used following in vitro fertilization to diagnose a genetic disease or condition in a pre-implantation embryo.

Pre-IND – A formalized process of obtaining presubmission guidance from the U.S. FDA.

Premature senescence – Entering senescence before the normal number of cell divisions.

Pre-microRNAs – Longer precursor molecules that are converted into microRNAs.

Pre-money valuation – The value or total price of a company start-up before the investment is included.

Prenatal diagnosis – Used to diagnose a genetic disease or condition in a developing fetus.

Prenatal Diagnostics- Genetic analysis of an early embryo. In one variant, one cell is removed from an 8-cell stage embryo to perform a diagnostic test to exclude a genetic disease or determine the gender of an embryo. The embryo with seven remaining cells can continue to develop in the laboratory while the diagnostic test is done and, if healthy, be transferred to the womb of the mother to develop into a baby. In a second variant, a small sample of extra- embryonic tissue is collected from the conceptus (from the chorion) or from the amniotic fluid surround the fetus (amniocentesis) and also used for genetic diagnosis.

Pre-placodal ectoderm – The region of the embryonic ectoderm that surrounds the anterior neural plate and that will give rise to all of the cranial sensory placodes. It is characterized by the expression of Six and Eyagenes.

Preproinsulin – Insulin as first synthesized, with both a signal sequence and the connecting peptide

Pre-seeding – Adding cells to a scaffold before implantation.

Presenilins – Transmembrane proteins found in the Golgi apparatus and endoplasmic reticulum; associated with Alzheimer’s disease

Present value – This term refers to a technique which is used to place a value, as of the present day, on a set of future cash flows. It is computed by discounting future cash flows at an interest rate that reflects a company’s cost of capital.

Presymptomatic test – See Predictive testing.

Pre-T alpha chain – Invariant TCRα-like chain expressed only in DN thymocytes. Used to test the functionality of candidate TCRβ chains. Not required for γδ T cell development. See also pre-TCR.

Pre-TCR – Transient complex composed of a candidate TCRβ chain plus the pTα chain plus the CD3 chains. Used to test the functionality of a particular VDJ rearrangement in the TCRβ gene.

Pre-TCR checkpoint – First major checkpoint in T cell development, dependent on β-selection and formation of a pre-TCR that allows a thymocyte to receive a survival/ proliferation signal and become committed to the αβ T lineage.

Prevalence – A measure of the number of individuals in a population who have a disease at a particular time. Prevalence differs from incidence; the latter indi- cating the rate of new cases of a disease that occur in a population. Chronic diseases, especially those that persist through the patient’s normal lifespan, may have a high prevalence and a low incidence. Diseases that have a short clinical span, such as influenza or the common headache, will have a lower prevalence than incidence. See Age-adjusted incidence. Total number within a population who have a condition at a particular time, often expressed as a percentage.

Prevalence rate – Is equal to the total number of cases of a disease within a given period.

Preventive action (PA) – Action taken to eliminate the cause of a potential nonconformity, defect, or other undesirable situation in order to prevent occurrence. Example- Corrective actions identified as a result of a nonconformance for one product are PAs when implemented to prevent a similar nonconformance in another product.

Prey – The fusion between the activator domain of a transcriptional activator protein and another protein as used in two-hybrid screening

PriA – Protein of the primosome that helps primase bind.

Price/Earnings (P/E) ratio – The ratio of the firm’s share price to the firm’s earnings per share (calculated by dividing net income through shares outstanding). It is also referred to as the P/E multiple.

Price based – Relates to an anti-dilution measure that increases the number of shares in which a preferred stock converts.

Primary antibody – First antibody to the protein of interest used to identify a protein in Western blotting

Primary cilium – A single cilium projecting from a cell that may play a number of sensory and/or mechanical roles in the cell. A solitary organelle that extends from the cell surface of most mammalian cell types during growth arrest and serves as a sensory cellular antenna. Microtubule-based cytoplasmic extension comprised of a membrane ensheathed axoneme extending from the basal body, which is a modified centriole. In primary cilia, the axoneme is comprised of nine microtubule (MT) pairs in a 9+0 arrangement (in contrast to motile cilia which have 9 MT pairs surrounding two central fibrils, i.e., 9+2 arrangement). Proteins are moved into and out of the primary cilium via intraflagellar transport (IFT) along the axoneme. Plasma membranes around primary cilia are distinct/segregated from the cellular plasma membrane. Disruption of ciliary or IFT proteins results in a broad range of human ciliopathies.

Principal investigator (PI) – Lead researcher responsible for entirety of a clinical trial (or research study). Sub investigators may have responsibilities for specific parts of the trial, but the PI has the overarching responsibility.

Private companies – These companies have equity shares that are not listed and not traded on the public stock exchange.

Primary dentin – constitutes the major part of the dent in bulk and is produced at a relatively high rate by odontoblasts during the tooth organogenesis.

Private equity – In its broadest meaning, private equity includes all investments that cannot be resold in public markets. In a more narrow term, private equity refers to a class of investments, managed by private equity firms, which make investments in venture capital, leveraged buy-outs, mezzanine, or distress.

Primary follicles – Spherical aggregates of resting mature B cells, macrophages, and FDCs within B cell-rich regions of secondary lymphoid tissues such as spleen, lymph nodes and Peyer’s patches.

Primary host – Also called final host or definitive host, the primary host is infected with the mature or reproductive stage of the parasite. In most cases, the mature stage of animal parasite is the stage in which eggs, larvae, or cysts are produced. See Intermediate host.

Primary immune response – The adaptive immune response mounted upon a first exposure to a non-self entity. The primary response is slower and weaker than secondary (or subsequent) immune responses.

Primary immunodeficiency (PID) – Failure of a component of the immune system due to an inborn genetic mutation.

Primary lymphoid tissue – Lymphoid tissues (bone marrow and thymus) where lymphocytes are generated and mature.

Primary market – Refers to the marketplace where pre-market owners (e.g. entrepreneurs and founders) negotiate with underwriters for the selling of their stock.

Primary sex differentiation – Refers to the specification and determination of the gonads (testes, ovaries) and associated production of sexually distinct gametes (spermatogenesis vs. oogenesis).

Primary transcript – The original RNA molecule obtained by transcription from a DNA template, before any processing or modification has occurred

3D printing – Consists of creating a three-dimensional object by superimposing thousands of layers of matter, on the basis of a numerical model. This process requires software, a 3D printer and materials.

5′-pppRNA – A characteristic nucleotide present at the 5′ end of the viral RNA genome such as influenza virus. Note that cellular mRNA has a cap structure at the 5’end, while tRNA and rRNA have a monophosphate at the 5′ end.

Primary tumor – Original tumor mass established by the first transformed cell.

Primase – Enzyme that starts a new strand of DNA by making an RNA primer

Primer – A short nucleic acid sequence, often a synthetic oligonucle- otide, that binds specifically to a single strand of a target nucleic acid sequence and initiates synthesis, using a suitable polymerase, of a complementary strand.

Priming – First encounter of a naïve lymphocyte with specific antigen. Leads to a primary immune response.

Primitive endoderm – A polarized epithelium covering the epiblast precursors and facing the blastocoel cavity in the implanting mouse blastocyst (E3.75 to E4.5). The primitive endoderm is an extra-embryonic tissue derived from inner cell mass precursors. It will give rise to the visceral endoderm.

Primitive hematopoiesis – A transient wave of hematopoiesis that generates the first blood cells in embryos. Most primitive blood cells are red cells. Macrophages and megakaryocytes are also found in this wave.

Primitive streak – The primitive streak forms opposite to the anterior visceral endoderm. It is a region of the epiblast along which precursor cells of the mesoderm and the definitive endoderm ingress during gastrulation when they undergo an epithelial to mesenchymal transition. Cells are progressively recruited into the primitive streak as it elongates distally, to give rise to regionally distinct precursors in an orderly fashion, both along the mediolateral and anterior–posterior axes. Epiblast cells located at the anterior pole, do not ingress trough the primitive streak, remain epithelial and contribute to the anterior surface ectoderm and neurectoderm.

Primordia – Cells, tissues or organs at the earliest stage of development.

Primordial Germ Cells (PGCs) – PGCs give rise to oocytes and sperm in vivo and to embryonic germ (EG) cells when explanted in vitro. Progenitor cells of the gametes (sex cells). These cells are around the first to be formed in the developing embryo. They later travel to the gonads where they differentiate into either sperm or egg. An embryonic cell that gives rise to a germ cell from which a gamete (i.e., an egg or a sperm) develops.

Principal investigator (PI)  – The primary and ultimately responsible investigator of a human research protocol.

Principle of independent assortment – Alleles of a gene sort independently during formation of a gamete

Principle of segregation – Alleles of a gene segregate or separate into different gametes during gamete formation, but then reunite during fertilization

Prion – Infectious protein of abnormal conformation. Prions spread by altering the conformation of their normal protein counterparts in infected brain, causing spongiform encephalopathies. The word prion, is derived from the words protein and infection, in reference to a prion’s ability to self-propagate and transmit its conformation to other prions. Short for proteinaceous infectious particles, the cause of transmissible spongiform encephalopathy in humans and mammals (bovine spongiform encephalopathy, Creutzfeldt-Jakob disease). Prions primarily or entirely consist of aggregates of an abnormally folded pathogenic isoform of a normal cellular protein.

Prion protein (PrP) – Brain protein that may exist in two forms, one of which is pathogenic and may cause transmissible prion disease

Priority Review – This is the designation U.S. FDA may grant to an NDA or BLA for a product intended to treat, mitigate, or prevent a serious condition and which provides a significant improvement in safety or efficacy in comparison to already available therapies. (It may be granted for a serious condition for which there is no existing therapy, as a successful therapy is a significant improvement over no therapy at all.) U.S. FDA has only 6 months to complete their review and make a decision on marketing for NDAs or BLAs given priority review designation.

Privacy – As a positive right, privacy means that a person has the right to control access to and distribution of personal information, property, and/or knowledge of behaviors. As a negative right, privacy ensures absence of interference or the right to be left alone.

Private equity firms – Are organisations that invest in start-ups (e.g. venture capital) and buyout firms (i.e., firms that acquire established private and public firms).

Private placement – Is the selling of a firm’s stock outside of a public exchange or market.

PRMs – see Pattern Recognition molecules (PRMs).

Prnp – Gene that encodes the prion protein.

Probability – The likelihood of an event (occurrence).

Proband – An individual who is being studied in genetics studies. Usually refers to the first affected family member with a genetic disorder or trait that begins the study of the family. The index subject in a genetic study involving multiple members of the same family.

Probe – A DNA or RNA fragment that has been labeled in some way and used in a molecular hybridization assay to identify closely related DNA or RNA sequences.

Probe molecule – Molecule that is tagged in some way (usually radioactive or fluorescent) and is used to bind to and detect another molecule

Proceed – The amount of value (in cash and in stock) that is received in an exit.

Process – In manufacturing this term is used to refer to the methods and steps used to manufacture a product.

Process Contact Surface – Surfaces of piping, components, equipment or systems that may or may not be exposed to product, but may contain solutions that are potentially exposed to product or product intermediates (e.g., clean utilities, process gases, all CIP solutions). Surfaces that are process contact but not product contact typically are maintained to a defined specification and/or monograph (e.g. WFI, PW, HPW, clean steam). Surfaces of piping, components, equipment or systems that are exposed to product. When systems used in multiple products, batches or process steps are reused, their product contact surfaces require cleaning and sanitization to reduce bioburden and the potential for carryover and crossover (e.g., product vessels, filtration skids,chromatography skids and circulating CIP systems). Systems used in aseptic operations (e.g. bioreactors) require sterilization prior to use. Product contact surfaces are a subset of process Contact surfaces. Product contact surfaces should be identified as such by the drug substance manufacturer.

Process effect – All the effects of each failure mode including current step effects and downstream subassembly effects.

Process FMECA – Process FMECA is to analyse the potential failure modes of the manufacturing processes that build the product.

Process Validation – The manner in which a manufacturer demonstrates the consistency and reliability of process steps. 

Processivity – It refers to the extent of DNA or RNA synthesis per engagement of RNA/DNA polymerase to template.

Prodromal period – The period of illness characterized by nonspecific symptoms.

Prodrug – A drug that must be metabolised by the body in order to become active. A harmless compound that is converted to an active drug by a specific enzyme programmed cell death Genetic program that eliminates damaged cells or cells that are no longer needed without activating the immune system. It refers to a medication that is initially administered to the body in an inactive (or less than fully active) form, and then becomes converted to its active form by the normal metabolic processes of the body. Prodrugs can be used to improve how the intended drug is absorbed, distributed, metabolized, and excreted (ADME).

Product – Components, manufacturing materials, in-process devices, finished devices, and returned devices.

Product class – A grouping of similar or related products that share a characteristic, e.g., monoclonal antibodies are a product class, oncology drugs are a product class.

Product impact – The final part of an investigation when a type of risk assessment is performed to determine whether the root cause of the deviation had any deleterious effects on the product or whether the product is still okay and can be released.

Progenitor cell – A mitotic cell that is not capable of indefinite self-renewal and which will produce a limited repertoire of cell types. Stem cell committed to a cell line which, after several stages, will give rise to one (or more) differentiated cell(s) of this line. For example, in the line of hematopoietic SCs, two types of progenitor exist, myeloid and lymphoid, which will guide towards these two differentiation pathways. The progenitor is pluripotent, ensuring the creation of a progeny. Organ stem cells that still have the capacity to divide but have restricted differentiation capacity. Often confused with stem cell, an early descendant of a stem cell that can only differentiate but can no longer renew itself. A progenitor cell is often more limited in the kinds of cells it can become than a stem cell. In scientific terms, it is said that progenitor cells are more differentiated than stem cells.

Prognosis – The likelihood that a patient will recover. Prognostic markers are used to produce a quantitative estimate of the likelihood of recovery. See Predictive test.

Proinsulin – Precursor to insulin that contains both the A and B chains plus the connecting peptide.

Progressive vaccinia/vaccinia necrosum – A low-frequency complication of smallpox vaccination in which the vaccination site forms a nonhealing wound.

Prokaryote – A single-celled organism, such as a bacterium, that does not contain a nuclear membrane or other specialized organelles. An organism lacking a membrane-enclosed nucleus. Most prokaryotes are unicellular. No membrane-bound organelles are present in the prokaryotic cells. The intracellular components of a prokaryotic cell are gathered together and enclosed only by the cell membrane. An organism or cell lacking a nucleus, and other membrane-bound organelles. Bacteria are prokaryotic organisms.

Proliferative diabetic retinopathy (PDR) – Most severe diabetes-induced retinopathy with pathological neovascularisation.

Promoter – A combination of short-sequence elements to which RNA polymerase binds in order to initiate transcription of a gene. DNA region of a gene that determines the start point and the frequency of transcription and which is the binding site of RNA polymerase. Region of DNA in front of a gene that binds RNA polymerase and so promotes gene expression. Sequence constituting the basic unit for the recruitment of transcription machinery to which transcription factors and the transcription preinitiation complex (PIC) bind. Many promoters are activated through enhancers situated at mid to long distances upstream or downstream of them. The DNA site that binds RNA polymerase plus transcription factors, thus initiating RNA transcription. Examples of promoter mutations causing disease include beta-thalassemia, Bernard–Soulier syndrome, pyruvate kinase deficiency, familial hypercholesterolemia, and hemophilia. Monogenic promoter mutations generally cause disease by reducing the quantity of a normal protein, not by producing altered protein and not by reducing the quantity of multiple proteins. Because the drop in protein production may be small, promoter diseases may be hard to detect. See Transcription element.

Promoter site (region) – Location on a DNA strand where the synthesis of new RNA is controlled. It is also called a promoter element.

Promulgate – To proclaim or announce publically, generally in writing. To make known to the public.

Proneural gene – A basic helix-loop-helix transcription factor that is both necessary and sufficient to initiate the development of neuronal line- ages and to promote the generation of progenitor cells which are committed to neuronal differentiation.

Pronuclei – The parental male and female nuclei in a fertilized egg just before nuclear fusion

Proof of concept – This term refers to studies, generally preclinical or nonclinical, although it can be used to refer to pilot clinical studies, which aim to elucidate the activity of a product or the potential for a product to act in the manner it is intended, i.e., “does it work?”

Prophage – Bacteriophage genome that is integrated into the DNA of the bacterial host cell

Prophylactic vaccination – See vaccination (prophylactic).

Proprietary IBBs – Institutional review boards set up by for-profit research sponsors to review specific sponsor’s research studies. Little is known about the membership, functions, and processes of proprietary IRBs.

Prospect of (potential for) benefit – Term used by U.S. FDA (prospect of benefit) to mean that an investigational new drug is supported by data suggesting that some clinical benefit will occur when studied in humans. It is not a guarantee, but there is evidence upon which to base this hope for benefit.

Prospectus – Is a document containing information prescribed by the SEC and includes the initial selling price of the offer.

Prostaglandin synthase – Also known as cyclooxygenase or COX, is a multifunctional enzyme that converts arachidonic and other long-chain fatty acids into an initial prostaglandin product. The synthase has both cyclooxygenase and peroxidase activities.

Prostaglandins – Pharmacologically active derivatives of arachidonic acid capable of modulating cell mobility and immune responses.

Prosthetic group – A nonprotein portion of a complete or holo-protein. Additional (often covalent) chemical groups (e.g., home group) that are bound to a protein, but which are not inserted into the polypeptide chain.

Protease – Same as proteinase; an enzyme that degrades polypeptides by hydrolysis.

Protease inhibitor – Inhibitor of protease enzymes, in particular antiviral agent that inhibits the protease of viruses such as HIV.

Proteasome – Cytoplasmic organelle containing multiple proteases that digest proteins into peptides. Integral component of the endogenous antigen processing and presentation pathway. “Standard” proteasomes carry out housekeeping degradation of self proteins in all cells, while “immunoproteasomes” are induced in cells exposed to inflammatory cytokines and play a role in digestion of foreign proteins for antigen presentation. Multisubunit complex that degrades proteins labeled with ubiquitin.

Protective antigen (PA) – Protein that acts as the delivery system for both anthrax toxins.

Protective epitopes – In vaccination, epitopes of a pathogen that induce an immune response preventing subsequent infection by that pathogen.

Protein – A macromolecule consisting of many amino acids joined together by peptide bonds. An essential component of cell which is derived from DNA (in turn RNA) through translation process. It is the building blocks of body tissue. It plays a variety of role in cells. Polymer made from amino acids; may consist of several polypeptide chains. Polymer of amino acids linked by peptide bonds usually with a molecular weight of 10,000 Daltons or greater. Polymer of amino acids. The biological effector molecule encoded by sequences of a gene. A protein molecule consists of one or more polypeptide chains of amino acid subunits. The functional action of a protein depends on its three-dimensional structure, which is determined by its amino acid composition.

Protein A – Antibody binding protein from Staphylococcus that is often used in making fusion proteins

Protein engineering – Altering the sequence of a protein by genetic engineering of the DNA that encodes it. Creation of proteins with modified properties. There are two fundamentally different approaches: rational design (based on knowledge of structure and function of the protein in question, targeted modifications are carried out) and directed evolution (accidental mutagenesis combined with selection constraints, which lead to the survival of a modified protein with improved properties). In addition, DNA shuffling is used to reproduce natural recombination and the obtained proteins are then improved by further recombination.

Protein fusion – Hybrid protein made by joining the coding sequences of two proteins together in a frame

Protein fusion vector – Vector designed for fusing cloned proteins to a carrier protein to help expression and/or export

Protein interactome – The total of all the protein–protein interactions in a particular cell or organism

Protein kinase – Enzyme that transfers phosphate groups to other proteins, thus controlling their activity

Protein kinase A (PKA) – One particular protein kinase of animal cells that is activated by cyclic AMP

Protein kinase C (PKC) – An enzyme that is involved in hormonal signal transduction by catalytic phosphorylation. It is calcium dependent. In the diabetic state, PKC induces the synthesis of endothelin-1, a protein responsible for pathological changes to blood vessels. PKC itself is stimulated by a metabolite of glucose (i.e., diacylglyerol) derived indirectly from the E-M pathway.

Protein misfolding cyclic amplification (PMCA) – Protocol that amplifies misfolded prions in a manner analogous to PCR

Protein modeling – The estimation of a protein’s structure using its sequence.

Protein structure – There are several divisions of this term. Primary- the amino acid sequence; Secondary- the unique shapes of part of the sequence (a-helices, b-pleated sheets, b-turns, and random coils); Tertiary- conformation of a single polypeptide; Quaternary- conformation of two or more polypeptides that comprise one protein. A domain is an intermediary form between secondary and tertiary structure.

Protein truncation test – A method of screening for chain-terminating mutations by artificially expressing a mutant allele in a coupled transcription-translation system.

Protein tyrosine kinase (PTK) – Enzymes that, when activated, phosphorylate the tyrosine residues of substrate proteins.

Protein von Hippel-Lindau (pVHL) – E3-ubiquitin ligase that degrades ubiquitin-conjugated HIF-1a and a protein that determines the characteristic of von Hippel–Lindau syndrome.

Proteinase – Same as protease; an enzyme that degrades polypeptides by hydrolysis.

Protein-priming – It refers to RNA synthesis that is initiated by protein primer.

Proteins – A class of biological molecules that are composed of chains of amino acids. Polymers composed of individual amino acids, which may also contain prosthetic groups. Proteins are not only the main components of cell structures, but also enable most metabolic functions within a cell.

Proteoglycan -The complex that results from the binding of a GAG to a protein.

Proteome – All of the proteins present in a cell organism. The total set of proteins encoded by a genome or the total protein complement of an organism.

Proteomics – Study or analysis of an organism’s complete protein complement. The development and application of techniques to investigate the protein products of the genome and how they interact. The study of all proteins found in a cell under certain conditions, using various methods, such as two-dimensional gel electrophoresis.

Proto-oncogene – Original, unmutated wild-type allele of an oncogene.

Protocol – A prospectively written and approved document that governs the conduct of a study (whether preclinical or clinical). The protocol details the study design, responsible parties, materials to be used, and procedures to be followed, statistical analysis, monitoring/auditing procedures, and reporting of the study.

Protomer – It refers to a structural subunit of poliovirus capsid. It is also called 5S structural unit, based on its sedimentation coefficient (ie, Svedberg sedimentation coefficient).

Protoneuromasts – These are nascent neuromasts forming within the migrating PLLp. The migrating PLLp contains 2–3 protoneuromasts at progressive stages of maturation. It consists of a cluster of about 15–30 cells that form epithelial rosettes in which a sensory hair cell progeni tor gets specified at the center.

Protanopia – A type of red–green defect in which the long-wavelength-sensitive photopigment is nonfunctional, leading to a loss of sensitivity to red light and a tendency to confuse reds and greens. Derives from the Greek protos, meaning first, alluding to the defect being associated with the first of the three primary colors (red) and anopia, meaning blindness.

Proto-oncogene – A cellular gene that, when mutated, is inappropriately expressed and becomes an oncogene. It refers to a normal gene that can become an oncogene due to mutations or increased expression.

Protoplast fusion – In vitro technique to fuse protoplasts of two different species, leading to the fusion of the nuclei. This results in somatic hybrids and is a way of cross-breeding species that would normally not cross-breed.

Protoplasts – Bacterial, fungal or plant cells from which the cell walls have been removed. Plant cells that have been dissociated and whose cell walls are removed

Protozoa – Microbiologic nomenclature has many terms that have persisted long after they have outlived their usefulness; “protozoa” is a perfect example. A commonly found definition for protozoa is “one-celled animal,” but this is an oxymoron, as all animals are multi-cellular. Over the years, the term protozoa has come to include any one-celled heterotrophic (i.e., lacking chloroplasts) eukaryotic organism. This definition crosses classes (i.e., includes unrelated organisms) and hence has no phylogenetic meaning. With luck, the term “proto- zoa” will soon disappear from the scientific literature].

Provirus – It refers to the virus genome DNA integrated into the host cell chromosomal DNA. 

Provirus Viral– DNA that has been integrated into the host cell genome.

Proximate cause – The proximate cause of any event is the closest direct action that can be held to be the cause of the event. For example, the rupture of a blood vessel in the lung may be the proximate cause of death, while an invasive lung cancer may have been the underlying cause of death. The erosion of a vessel by tumor cells was one of a sequence of events leading from the und