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WDR47
WD repeat domain 47 is a protein that in humans is encoded by the ''WDR47'' gene. Model organisms Model organisms have been used in the study of WDR47 function. A conditional knockout mouse line, called ''Wdr47tm1a(EUCOMM)Wtsi'' was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty-six tests were carried out on mutant mice and three significant abnormalities were observed. Homozygous mutant animals had an absence of corpus callosum and increased circulating alkaline phosphatase levels. Male homozygous mice also had abnormal indirect calorimetry Indirect calorimetry calculates heat that living organisms produce by measuring either their production of carbon dioxide and nitrogen waste (frequently ammonia in aquatic organ ...
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WD Repeat
The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide. Tandem copies of these repeats typically fold together to form a type of circular solenoid protein domain called the WD40 domain. Structure WD40 domain-containing proteins have 4 to 16 repeating units, all of which are thought to form a circularised beta-propeller structure (see figure to the right). The WD40 domain is composed of several repeats, a variable region of around 20 residues at the beginning followed by a more common repeated set of residues. These repeats typically form a four stranded anti-parallel beta sheet or blade. These blades come together to form a propeller with the most common being a 7 bladed beta propeller. The blades interlock so that the last beta strand of one repeat forms with the first three of the next repeat to form the 3D blade structure. Function WD40-repe ...
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Haematology
Hematology ( always spelled haematology in British English) is the branch of medicine concerned with the study of the cause, prognosis, treatment, and prevention of diseases related to blood. It involves treating diseases that affect the production of blood and its components, such as blood cells, hemoglobin, blood proteins, bone marrow, platelets, blood vessels, spleen, and the mechanism of coagulation. Such diseases might include hemophilia, blood clots ( thrombus), other bleeding disorders, and blood cancers such as leukemia, multiple myeloma, and lymphoma. The laboratory analysis of blood is frequently performed by a medical technologist or medical laboratory scientist. Specialization Physicians specialized in hematology are known as hematologists or haematologists. Their routine work mainly includes the care and treatment of patients with hematological diseases, although some may also work at the hematology laboratory viewing blood films and bone marrow slides under ...
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Indirect Calorimetry
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.Ferrannini "The theoretical bases of indirect calorimetry: a review."Metabolism. 1988 Mar;37(3):287-301. Scientific background Indirect calorimetry measures O2 consumption and CO2 production. On the assumption that all the oxyge ...
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Alkaline Phosphatase
The enzyme alkaline phosphatase (EC 3.1.3.1, alkaline phosphomonoesterase; phosphomonoesterase; glycerophosphatase; alkaline phosphohydrolase; alkaline phenyl phosphatase; orthophosphoric-monoester phosphohydrolase (alkaline optimum), systematic name phosphate-monoester phosphohydrolase (alkaline optimum)) catalyses the following reaction: : a phosphate monoester + H2O = an alcohol + phosphate Alkaline phosphatase has the physiological role of dephosphorylating compounds. The enzyme is found across a multitude of organisms, prokaryotes and eukaryotes alike, with the same general function but in different structural forms suitable to the environment they function in. Alkaline phosphatase is found in the periplasmic space of '' E. coli'' bacteria. This enzyme is heat stable and has its maximum activity at high pH. In humans, it is found in many forms depending on its origin within the body – it plays an integral role in metabolism within the liver and development withi ...
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Corpus Callosum
The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental mammals. It spans part of the longitudinal fissure, connecting the left and right cerebral hemispheres, enabling communication between them. It is the largest white matter structure in the human brain, about in length and consisting of 200–300 million axonal projections. A number of separate nerve tracts, classed as subregions of the corpus callosum, connect different parts of the hemispheres. The main ones are known as the genu, the rostrum, the trunk or body, and the splenium. Structure The corpus callosum forms the floor of the longitudinal fissure that separates the two cerebral hemispheres. Part of the corpus callosum forms the roof of the lateral ventricles. The corpus callosum has four main parts – individual nerve ...
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Mutant
In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosome of an organism. It is a characteristic that would not be observed naturally in a specimen. The term mutant is also applied to a virus with an alteration in its nucleotide sequence whose genome is in the nuclear genome. The natural occurrence of genetic mutations is integral to the process of evolution. The study of mutants is an integral part of biology; by understanding the effect that a mutation in a gene has, it is possible to establish the normal function of that gene. Mutants arise by mutation Mutants arise by mutations occurring in pre-existing genomes as a result of errors of DNA replication or errors of DNA repair. Errors of replication often involve translesion synthesis by a DNA polymerase when it encounters and bypasses a damaged base in the t ...
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Phenotypic Screen
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological properties, its behavior, and the products of behavior. An organism's phenotype results from two basic factors: the expression of an organism's genetic code, or its genotype, and the influence of environmental factors. Both factors may interact, further affecting phenotype. When two or more clearly different phenotypes exist in the same population of a species, the species is called polymorphic. A well-documented example of polymorphism is Labrador Retriever coloring; while the coat color depends on many genes, it is clearly seen in the environment as yellow, black, and brown. Richard Dawkins in 1978 and then again in his 1982 book '' The Extended Phenotype'' suggested that one can regard bird nests and other built structures such as ...
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International Knockout Mouse Consortium
The International Knockout Mouse Consortium (IKMC) is a scientific endeavour to produce a collection of mouse embryonic stem cell lines that together lack every gene in the genome, and then to distribute the cells to scientific researchers to create knockout mice to study. Many of the targeted alleles are designed so that they can generate both complete and conditional gene knockout mice. The IKMC was initiated on March 15, 2007 at a meeting in Brussels. By 2011, ''Nature'' reported that approximately 17,000 different genes have already been disabled by the consortium, "leaving only around 3,000 more to go". The consortium encompasses four major, high-throughput gene-targeted mutagenesis programs: the National Institutes of Health (NIH)-sponsored Knockout Mouse Program (KOMP) and state-funded Texas Institute for Genomic Medicine (TIGM) in the U.S., the North American Conditional Mouse Mutagenesis (NorCOMM) Program in Canada, and the European Conditional Mouse Mutagenesis (EUCOM ...
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Knockout Mouse
A knockout mouse, or knock-out mouse, is a genetically modified mouse (''Mus musculus'') in which researchers have inactivated, or " knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA. They are important animal models for studying the role of genes which have been sequenced but whose functions have not been determined. By causing a specific gene to be inactive in the mouse, and observing any differences from normal behaviour or physiology, researchers can infer its probable function. Mice are currently the laboratory animal species most closely related to humans for which the knockout technique can easily be applied. They are widely used in knockout experiments, especially those investigating genetic questions that relate to human physiology. Gene knockout in rats is much harder and has only been possible since 2003. The first recorded knockout mouse was created by Mario R. Capecchi, Martin Evans, and Oliver Smithies in 1989, for ...
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Model Organism
A model organism (often shortened to model) is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the model organism will provide insight into the workings of other organisms. Model organisms are widely used to research human disease when human experimentation would be unfeasible or unethical. This strategy is made possible by the common descent of all living organisms, and the conservation of metabolic and developmental pathways and genetic material over the course of evolution. Studying model organisms can be informative, but care must be taken when generalizing from one organism to another. In researching human disease, model organisms allow for better understanding the disease process without the added risk of harming an actual human. The species chosen will usually meet a determined taxonomic equivalency to humans, so as to react to disease or its treatment in a way that resembl ...
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Citrobacter
''Citrobacter'' is a genus of Gram-negative coliform bacteria in the family Enterobacteriaceae. The species ''C. amalonaticus'', ''C. koseri'', and ''C. freundii'' can use citrate as a sole carbon source. ''Citrobacter'' species are differentiated by their ability to convert tryptophan to indole (''C. koseri'' is the only citrobacter to be commonly indole-positive), ferment lactose (''C. koseri'' is a lactose fermentor), and use malonate. ''Citrobacter'' shows the ability to accumulate uranium by building phosphate complexes. Clinical significance These bacteria can be found almost everywhere in soil, water, wastewater, etc. They can also be found in the human intestine. They are rarely the source of illnesses, except for infections of the GI Tract, urinary tract and infant meningitis and sepsis. ''Citrobacter freundii'' strains have inducible ''ampC'' genes encoding resistance to ampicillin and first-generation cephalosporin The cephalosporins (sg. ) are a class of β-l ...
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Micronucleus Test
A micronucleus test is a test used in toxicological screening for potential genotoxic compounds. The assay is now recognized as one of the most successful and reliable assays for genotoxic carcinogens, i.e., carcinogens that act by causing genetic damage and is recommended by the OECD guideline for the testing of chemicals. There are two major versions of this test, one '' in vivo'' and the other ''in vitro''. The ''in vivo'' test normally uses mouse bone marrow or mouse peripheral blood. When a bone marrow erythroblast develops into a polychromatic erythrocyte, the main nucleus is extruded; any micronucleus that has been formed may remain behind in the otherwise anucleated cytoplasm. Visualisation of micronuclei is facilitated in these cells because they lack a main nucleus. An increase in the frequency of micronucleated polychromatic erythrocytes in treated animals is an indication of induced chromosome damage. Micronuclei were first used to quantify chromosomal damage ...
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