Pathogenesis in the context of Gain-of-function

Pathology is the study of disease. The word pathology also refers to the study of disease in general, incorporating a wide range of biology research fields and medical practices. However, when used in the context of modern medical treatment, the term is often used in a narrower fashion to refer to processes and tests that fall within the contemporary medical field of "general pathology", an area that includes a number of distinct but inter-related medical specialties that diagnose disease, mostly through analysis of tissue and human cell samples. Pathology is a significant field in modern medical diagnosis and medical research. A physician practicing pathology is called a pathologist.

As a field of general inquiry and research, pathology addresses components of disease: cause, mechanisms of development (pathogenesis), structural alterations of cells (morphologic changes), and the consequences of changes (clinical manifestations). In common medical practice, general pathology is mostly concerned with analyzing known clinical abnormalities that are markers or precursors for both infectious and non-infectious disease, and is conducted by experts in one of two major specialties, anatomical pathology and clinical pathology. Further divisions in specialty exist on the basis of the involved sample types (comparing, for example, cytopathology, hematopathology, and histopathology), organs (as in renal pathology), and physiological systems (oral pathology), as well as on the basis of the focus of the examination (as with forensic pathology).

A carbohydrate (/ˌkɑːrboʊˈhaɪdreɪt/) is a sugar (saccharide) or a sugar derivative. For the simplest carbohydrates, the carbon-to-hydrogen-to-oxygen atomic ratio is 1:2:1, i.e. they are often represented by the empirical formula C(H₂O)_n. Together with amino acids, fats, and nucleic acids, the carbohydrates are one of the major families of biomolecules.

Carbohydrates perform numerous roles in living organisms. Polysaccharides serve as an energy store (e.g., starch and glycogen) and as structural components (e.g., cellulose in plants and chitin in arthropods and fungi). The 5-carbon monosaccharide ribose is an important component of coenzymes (e.g., ATP, FAD and NAD) and the backbone of the genetic molecule known as RNA. The related deoxyribose is a component of DNA. Saccharides and their derivatives play key roles in the immune system, fertilization, preventing pathogenesis, blood clotting, and development.

A syndrome is a set of medical signs and symptoms which are correlated with each other and often associated with a particular disease or disorder. The word derives from the Greek σύνδρομον, meaning "concurrence". When a syndrome is paired with a definite cause this becomes a disease. In some instances, a syndrome is so closely linked with a pathogenesis or cause that the words syndrome, disease, and disorder end up being used interchangeably for them. This substitution of terminology often confuses the reality and meaning of medical diagnoses. This is especially true of inherited syndromes. About one third of all phenotypes that are listed in OMIM are described as dysmorphic, which usually refers to the facial gestalt. For example, Down syndrome, Wolf–Hirschhorn syndrome, and Andersen–Tawil syndrome are disorders with known pathogeneses, so each is more than just a set of signs and symptoms, despite the syndrome nomenclature. In other instances, a syndrome is not specific to only one disease. For example, toxic shock syndrome can be caused by various toxins; another medical syndrome named as premotor syndrome can be caused by various brain lesions; and premenstrual syndrome is not a disease but simply a set of symptoms.

If an underlying genetic cause is suspected but not known, a condition may be referred to as a genetic association (often just "association" in context). By definition, an association indicates that the collection of signs and symptoms occurs in combination more frequently than would be likely by chance alone.

A laboratory specimen is sometimes a biological specimen of a medical patient's tissue, fluids, or other samples used for laboratory analysis to assist in differential diagnosis or staging of a disease process. These specimens are often the most reliable method of diagnosis, depending on the ailment. For example, breast cancer biopsies, performed on laboratory specimens of breast tissue, yield just a 2% rate of incorrect diagnosis. Laboratory specimens may also include feces.

Neurofibrillary tangles (NFTs) are intracellular aggregates of hyperphosphorylated tau protein that are most commonly known as a primary biomarker of Alzheimer's disease. NFTs also are present in numerous other diseases known collectively as tauopathies. Little is known about their exact relationship to the different pathologies, but it is typically recognized that tauopathy is an important factor in the pathogenesis of several neurodegenerative diseases.

NFTs consist primarily of a misfolded, hyperphosphorylated microtubule-associated protein known as tau, which abnormally polymerizes into insoluble filaments within cells. Under the electron microscope, these polymers of tau are seen to take two basic forms: paired helical filaments (PHFs) and straight filaments. These basic types of tau filaments can vary structurally, especially in different tauopathies. The filaments bundle together to form the neurofibrillary tangles that are evident under the light microscope. Classical NFTs are located within the neuronal cell body, although it is now recognized that abnormal, filamentous tau occurs also in neuronal dendrites and axons (referred to as neuropil threads) and the dystrophic (abnormal) neurites that surround neuritic Abeta plaques. Mature NFTs in cell bodies can have a torch-like or globose appearance, depending on the type of neuron involved. When tangle-containing neurons die, the tangles can remain in the neuropil as extracellular "ghost tangles".

Drosophila melanogaster is a species of fly (an insect of the order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly", or "banana fly". In the wild, D. melanogaster are attracted to rotting fruit and fermenting beverages, and they are often found in orchards, kitchens and pubs.

Starting with Charles W. Woodworth's 1901 proposal of the use of this species as a model organism, D. melanogaster continues to be widely used for biological research in genetics, physiology, microbial pathogenesis, and life history evolution. In 1946 D. melanogaster was the first animal to be launched into space. As of 2017, six Nobel Prizes have been awarded to drosophilists for their work using the insect.

Studies that are in vivo (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and plants, as opposed to a tissue extract or dead organism.

Examples of investigations in vivo include: the pathogenesis of disease by comparing the effects of bacterial infection with the effects of purified bacterial toxins; the development of non-antibiotics, antiviral drugs, and new drugs generally; and new surgical procedures. Consequently, animal testing and clinical trials are major elements of in vivo research. In vivo testing is often employed over in vitro because it is better suited for observing the overall effects of an experiment on a living subject. In drug discovery, for example, verification of efficacy in vivo is crucial, because in vitro assays can sometimes yield misleading results with drug candidate molecules that are irrelevant in vivo (e.g., because such molecules cannot reach their site of in vivo action, for example as a result of rapid catabolism in the liver).

Indirect calorimetry calculates heat that living organisms produce by measuring either their production of carbon dioxide and nitrogen waste (frequently ammonia in aquatic organisms, or urea in terrestrial ones), or from their consumption of oxygen. Indirect calorimetry estimates the type and rate of substrate utilization and energy metabolism in vivo starting from gas exchange measurements (oxygen consumption and carbon dioxide production during rest and steady-state exercise). This technique provides unique information, is noninvasive, and can be advantageously combined with other experimental methods to investigate numerous aspects of nutrient assimilation, thermogenesis, the energetics of physical exercise, and the pathogenesis of metabolic diseases.

A carbohydrate (/ˌkɑːrboʊˈhaɪdreɪt/) is a sugar (saccharide) or a sugar derivative. For the simplest carbohydrates, the carbon-to-hydrogen-to-oxygen atomic ratio is 1:2:1, i.e. they are often represented by the empirical formula (CH₂O)_n. Together with amino acids, fats, and nucleic acids, the carbohydrates are one of the major families of biomolecules.

Carbohydrates perform numerous roles in living organisms. Polysaccharides serve as an energy store (e.g., starch and glycogen) and as structural components (e.g., cellulose in plants and chitin in arthropods and fungi). The 5-carbon monosaccharide ribose is an important component of coenzymes (e.g., ATP, FAD and NAD) and the backbone of the genetic molecule known as RNA. The related deoxyribose is a component of DNA. Saccharides and their derivatives play key roles in the immune system, fertilization, preventing pathogenesis, blood clotting, and development.

Bacterial adhesins are cell-surface components or appendages of bacteria that facilitate adhesion or adherence to other cells or to surfaces, usually in the host they are infecting or living in. Adhesins are a type of virulence factor.

Adherence is an essential step in bacterial pathogenesis or infection, required for colonizing a new host. Adhesion and bacterial adhesins are also a potential target either for prophylaxis or for the treatment of bacterial infections.

Lipid peroxidation, or lipid oxidation, is a complex chemical process that leads to oxidative degradation of lipids, resulting in the formation of peroxide and hydroperoxide derivatives. It occurs when free radicals, specifically reactive oxygen species (ROS), interact with lipids within cell membranes, typically polyunsaturated fatty acids (PUFAs) as they have carbon–carbon double bonds. This reaction leads to the formation of lipid radicals, collectively referred to as lipid peroxides or lipid oxidation products (LOPs), which in turn react with other oxidizing agents, leading to a chain reaction that results in oxidative stress and cell damage.

In pathology and medicine, lipid peroxidation plays a role in cell damage which has broadly been implicated in the pathogenesis of various diseases and disease states, including ageing, whereas in food science lipid peroxidation is one of many pathways to rancidity.

Tetanolysin is a toxin produced by Clostridium tetani bacteria. Its function is unknown, but it is believed to contribute to the pathogenesis of tetanus. The other C. tetani toxin, tetanospasmin, is more definitively linked to tetanus. It is sensitive to oxygen.

Tetanolysin belongs to a family of protein toxins known as thiol-activated cytolysins, which bind to cholesterol. It is related to streptolysin O and the θ-toxin of Clostridium perfringens. Cytolysins form pores in the cytoplasmic membrane that allows for the passage of ions and other molecules into the cell. The molecular weight of tetanolysin is around 55,000 daltons.

Enterovirus (EV) is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine ('enteric' meaning intestinal).

Serologic studies have distinguished 71 human enterovirus serotypes on the basis of antibody neutralization tests. Additional antigenic variants have been defined within several of the serotypes on the basis of reduced or nonreciprocal cross-neutralization between variant strains. On the basis of their pathogenesis in humans and animals, the enteroviruses were originally classified into four groups, polioviruses, Coxsackie A viruses (CA), Coxsackie B viruses (CB), and echoviruses, but it was quickly realized that there were significant overlaps in the biological properties of viruses in the different groups. Enteroviruses isolated more recently are named with a system of consecutive numbers: EV-D68, EV-B69, EV-D70, EV-A71, etc., where genotyping is based on the VP1 capsid region.