Instruct: Given a question, retrieve documents that can help answer the question.
Query: Are the heptahelical receptors important?
G protein-coupled receptors (GPCRs), also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors (GPLR), comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal transduction pathways and, ultimately, cellular responses. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and animals. The ligands that bind and activate these receptors include light-sensitive compounds, odors, pheromones, hormones, and neurotransmitters, and vary in size from small molecules to peptides to large proteins. G protein-coupled receptors are involved in many diseases, and are also the target of approximately 30% of all modern medicinal drugs.
At the molecular level, an antigen can be characterized by its ability to bind to an antibody's variable Fab region. Different antibodies have the potential to discriminate among specific epitopes present on the antigen surface. A hapten is a small molecule that changes the structure of an antigenic epitope. In order to induce an immune response, it needs to be attached to a large carrier molecule such as a protein (a complex of peptides). Antigens are usually carried by proteins and polysaccharides, and less frequently, lipids. This includes parts (coats, capsules, cell walls, flagella, fimbriae, and toxins) of bacteria, viruses, and other microorganisms. Lipids and nucleic acids are antigenic only when combined with proteins and polysaccharides. Non-microbial non-self antigens can include pollen, egg white and proteins from transplanted tissues and organs or on the surface of transfused blood cells.
Initial studies of mutants revealed that residues on the back side of the central alpha helix were required for super antigenic activity. Changing the histidine at position 135 to alanine caused TSST-1 to be neither lethal or superantigenic. Changes in residues that were in close proximity to H135A, also had the effect of diminishing the lethality and superantigenic quality of these mutants. Although most of these mutants did not result in loss of antigenicity of TSST-1. Tests done using mutagenic TSST-1 toxins indicated that the lethal and superantigenic properties are separable. When Lys-132 in TSST-O was changed to a Glu, the resulting mutant became completely lethal but non superantigenic. The same results, lethal but not superantigenic, were found for TSST-1 Gly16Val. Residues Gly16, Glu132,and Gln 136, located on the back of the back-side groove of the putative TCR binding region of TSST-1, it has been proposed that they are also a part of a second functionally lethal site in the TSST-1.
Herpes has been used in research with HeLa cells to determine its ability to assist in the treatment of malignant tumors. A study conducted using suicide gene transfer by a cytotoxic approach examined a way to eradicate malignant tumors. Gene therapy is based on the cytotoxic genes that directly or indirectly kill tumor cells regardless of its gene expression. In this case the study uses the transfer of the Herpes simplex virus type I thymidine kinase (HSVtk) as the cytotoxic gene. Hela cells were used in these studies because they have very little ability to communicate through gap junctions. The Hela cells involved were grown in a monolayer culture and then infected with the HSV virus. The HSV mRNA was chosen because it is known to share characteristics with normal eukaryotic mRNA.
The HIV genome presented several additional mysteries. The virus genome contained regions that might specify as yet unknown proteins. The Haseltine laboratory discovered a novel transacting protein and a second protein, both required for virus replication. They named the transactivator tat and the second protein art; the latter was renamed rev. He predicted that drugs that target these proteins will also be effective in treating the infection. A drug that inhibits the "rev" protein has been approved by the USA Food and Drug administration for treatment of HIV infection. His laboratory went on to discover additional viral genes and proteins – "vpr", "vpu", "vif", and "nef" - required for efficient virus growth in some but not all circumstances. The discoveries were summarized in an article in 1988 in "Scientific American".
When an extracellular HHV-6 virion comes across human cells, it encounters the human receptor protein cluster of differentiation 46 (CD46), which plays a role in regulating the complement system. The CD46 protein possesses a single variable region, as a result of alternative splicing. As such, at least fourteen isoforms of CD46 exist, all of which bind HHV-6a.
The innate immune system relies on germline encoded pattern recognition receptors (PRRs) to recognize distinct pathogen-associated molecular patterns (PAMPs). Upon recognition of a PAMP, PRRs generate signal cascades leading to transcription of genes associated with the immune response. Because all pathogens utilize nucleic acid to propagate, DNA and RNA can be recognized by PRRs to trigger immune activation. In normal cells, DNA is confined to the nucleus or mitochondria. The presence of DNA in the cytosol is indicative of cellular damage or infection and leads to activation of genes associated with the immune response. One way cytosolic DNA is sensed is via the cGAS/STING pathway, specifically by the cyclic-GMP-AMP synthase (cGAS). Upon DNA recognition, cGAS dimerizes and stimulates the formation of cyclic-GMP-AMP (cGAMP). cGAMP then binds directly to stimulator of interferon genes (STING) which triggers phosphorylation/activation of the transcription factor IRF3 via TBK1. IRF3 is able to enter the nucleus to promote transcription of inflammatory genes, such as IFN-β.
Among the 5("S")-HETE family members, 5("S")-HETE takes precedence over the other members of this family because it was the first to be discovered and has been studied far more thoroughly. However, 5-oxo-ETE is the most potent member of this family and therefore may be its critical member with respect to physiology and pathology. 5-OxoETE has gained attention in recent studies. 
5-Hydroxyeicosatetraenoic acid is more properly termed 5("S")-hydroxyicosatetraenoic acid or 5("S")-HETE) to signify the ("S") configuration of its 5-hydroxy residue as opposed to its 5("R")-hydroxyicosatetraenoic acid (i.e., 5("R")-HETE) stereoisomer. Since 5("R")-HETE was rarely considered in the early literature, 5("S")-HETE was frequently termed 5-HETE. This practice occasionally continues. 5("S")-HETE's IUPAC name, (5"S",6"E",8"Z",11"Z",14"Z")-5-hydroxyicosa-6,8,11,14-tetraenoic acid, defines 5("S")-HETE's structure unambiguously by notating not only its "S"-hydroxyl chirality but also the cis–trans isomerism geometry for each of its 4 double bonds; E signifies trans and Z signifies cis double bond geometry. The literature commonly uses an alternate but still unambiguous name for 5("S")-HETE viz., 5"(S)"-hydroxy-6"E",8"Z",11"Z",14"Z"-eicosatetraenoic acid.
Magnetoreception refers to the ability of animals to navigate using the inclination of the magnetic field of the earth. A possible explanation for magnetoreception is the entangled radical pair mechanism. The radical-pair mechanism is well-established in spin chemistry, and was speculated to apply to magnetoreception in 1978 by Schulten et al.. The ratio between singlet and triplet pairs is changed by the interaction of entangled electron pairs with the magnetic field of the earth. In 2000, cryptochrome was proposed as the "magnetic molecule" that could harbor magnetically sensitive radical-pairs. Cryptochrome, a flavoprotein found in the eyes of European robins and other animal species, is the only protein known to form photoinduced radical-pairs in animals. When it interacts with light particles, cryptochrome goes through a redox reaction, which yields radical pairs both during the photo-reduction and the oxidation. The function of cryptochrome is diverse across species, however, the photoinduction of radical-pairs occurs by exposure to blue light, which excites an electron in a chromophore. Magnetoreception is also possible in the dark, so the mechanism must rely more on the radical pairs generated during light-independent oxidation.
15-Hydroxyeicosatetraenoic acid (also termed 15-HETE, 15("S")-HETE, and 15"S"-HETE) is an eicosanoid, i.e. a metabolite of arachidonic acid. Various cell types metabolize arachidonic acid to 15("S")-hydroperoxyeicosatetraenoic acid (15("S")-HpETE). This initial hydroperoxide product is extremely short-lived in cells: if not otherwise metabolized, it is rapidly reduced to 15"(S)"-HETE. Both of these metabolites, depending on the cell type which forms them, can be further metabolized to 15-oxo-eicosatetraenoic acid (15-oxo-ETE), 5"S",15"S"-dihydroxy-eicosatetraenoic acid (5("S"),15("S")-diHETE), 5-oxo-15("S")-hydroxyeicosatetraenoic acid (5-oxo-15("S")-HETE, a subset of specialized pro-resolving mediators viz., the lipoxins, a class of pro-inflammatory mediators, the eoxins, and other products that have less well-defined activities and functions. Thus, 15("S")-HETE and 15("S")-HpETE, in addition to having intrinsic biological activities, are key precursors to numerous biologically active derivatives.
In eukaryotes, DNA is organized with the help of histones into compact particles called nucleosomes, where sequences of about 147 DNA base pairs make ~1.65 turns around histone protein octamers. DNA within nucleosomes is inaccessible to many transcription factors. Some transcription factors, so-called pioneering factors are still able to bind their DNA binding sites on the nucleosomal DNA. For most other transcription factors, the nucleosome should be actively unwound by molecular motors such as chromatin remodelers. Alternatively, the nucleosome can be partially unwrapped by thermal fluctuations, allowing temporary access to the transcription factor binding site. In many cases, a transcription factor needs to compete for binding to its DNA binding site with other transcription factors and histones or non-histone chromatin proteins. Pairs of transcription factors and other proteins can play antagonistic roles (activator versus repressor) in the regulation of the same gene.
Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate (the conjugate base of glutamic acid) is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation.
Magnetoception (or magnetoreception) is the ability to detect the direction one is facing based on the Earth's magnetic field. Directional awareness is most commonly observed in birds, which rely on their magnetic sense to navigate during migration. It has also been observed in insects such as bees. Cattle make use of magnetoception to align themselves in a north-south direction. Magnetotactic bacteria build miniature magnets inside themselves and use them to determine their orientation relative to the Earth's magnetic field.
Human herpesvirus 7 (HHV-7) is one of nine known members of the Herpesviridae family that infects humans. HHV-7 is a member of Betaherpesviridae, a subfamily of the Herpesviridae that also includes HHV-6 and "cytomegalovirus" (HHV-5 or HCMV). HHV-7 often acts together with HHV-6, and the viruses together are sometimes referred to by their genus, "Roseolovirus". HHV-7 was first isolated in 1990 from CD4+ T cells taken from peripheral blood lymphocytes.
AGEP also differs from the other SCARs disorders in respect to the level of evidence supporting the underlying mechanism by which a drug or its metabolite stimulates CD8 T or CD4 T cells. Studies indicate that the mechanism by which a drug or its metabolites accomplishes this stimulation involves subverting the antigen presentation pathways of the innate immune system. A drug or metabolite covalently binds with a host protein to form a non-self, drug-related epitope. An antigen presenting cell (APC) takes up these proteins; digests them into small peptides; places the peptides in a groove on the human leukocyte antigen (i.e. HLA) component of their major histocompatibility complex (i.e. MHC) (APC); and presents the MHC-associated peptides to the T-cell receptor on CD8 T or CD4 T cells. Those peptides expressing a drug-related, non-self epitope on their HLA-A, HLA-B, HLA-C, HLA-DM, HLA-DO, HLA-DP, HLA-DQ, or HLA-DR proteins may bind to a T-cell receptor to stimulate the receptor-bearing parent T cell to attack self tissues. Alternatively, a drug or metabolite may also stimulate T cells by inserting into the groove on a HLA protein to serve as a non-self epitope, bind outside of this groove to alter a HLA protein so that it forms a non-self epitope, or bypass the APC by binding directly to a T cell receptor. However, non-self epitopes must bind to specific HLA serotypes to stimulate T cells and the human population expresses some 13,000 different HLA serotypes while an individual expresses only a fraction of them. Since a SCARs-inducing drug or metabolite interacts with only one or a few HLA serotypes, their ability to induce SCARs is limited to those individuals who express HLA serotypes targeted by the drug or metabolite. Thus, only rare individuals are predisposed to develop SCARs in response to a particular drug on the bases of their expression of HLA serotypes. Studies have identified several HLA serotypes associated with development of DRESS syndrome, SJS, SJS/TEN, and TEN in response to various drugs which elici these disorders, developed tests to identify individuals who express these serotypes, and thereby determined that these individuals should avoid the offending drug. HLA serotypes associated with AGEP and specific drugs have not been identified. A study conducted in 1995 identified of HLA-B51, HLA-DR11, and HLA-DQ3 of unknown serotypes to be associated with development of AGEP but the results have not been confirmed, expanded to identify the serotypes involved, nor therefore useful in identifying individuals predisposed to develop AGEP in response to any drug. Similarly, a specific T cell receptor variant has been associated with the development of DRESS syndrome, SJS, SJS/TEN, and TEN but not AGEP.
The G protein-coupled receptor kinases (GRKs) are protein kinases that phosphorylate only active GPCRs. G-protein-coupled receptor kinases (GRKs) are key modulators of G-protein-coupled receptor (GPCR) signaling. They constitute a family of seven mammalian serine-threonine protein kinases that phosphorylate agonist-bound receptor. GRKs-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling and desensitization. Activity of GRKs and subcellular targeting is tightly regulated by interaction with receptor domains, G protein subunits, lipids, anchoring proteins and calcium-sensitive proteins.
Like other SCARs-inducing drugs, SJS-inducing drugs or their metabolites stimulate CD8 T cells or CD4 T cells to initiate autoimmune responses. Studies indicate that the mechanism by which a drug or its metabolites accomplishes this involves subverting the antigen presentation pathways of the innate immune system. The drug or metabolite covalently binds with a host protein to form a non-self, drug-related epitope. An antigen presenting cell (APC) takes up these alter proteins; digests them into small peptides; places the peptides in a groove on the human leukocyte antigen (i.e. HLA) component of their major histocompatibility complex (i.e. MHC); and presents the MHC-associated peptides to T-cell receptors on CD8 T cells or CD4 T cells. Those peptides expressing a drug-related, non-self epitope on one of their various HLA protein forms (HLA-A, HLA-B, HLA-C, HLA-DM, HLA-DO, HLA-DP, HLA-DQ, or HLA-DR) can bind to a T-cell receptor and thereby stimulate the receptor-bearing parent T cell to initiate attacks on self tissues. Alternatively, a drug or its metabolite may stimulate these T cells by inserting into the groove on a HLA protein to serve as a non-self epitope or bind outside of this groove to alter a HLA protein so that it forms a non-self epitope. In all these cases, however, a non-self epitope must bind to a specific HLA serotype (i.e. variation) in order to stimulate T cells. Since the human population expresses some 13,000 different HLA serotypes while an individual expresses only a fraction of them and since a SJS-inducing drug or metabolite interacts with only one or a few HLA serotypes, a drug's ability to induce SCARs is limited to those individuals who express HLA serotypes targeted by the drug or its metabolite. Accordingly, only rare individuals are predisposed to develop a SCARs in response to a particular drug on the bases of their expression of HLA serotypes: Studies have identified several HLA serotypes associated with development of SJS, SJS/TEN, or TEN in response to certain drugs. In general, these associations are restricted to the cited populations.
Hair cells in fish are used to detect water movements around their bodies. These hair cells are embedded in a jelly-like protrusion called cupula. The hair cells therefore can not be seen and do not appear on the surface of skin.
The vast majority of marketed H-antihistamines are receptor antagonists and only a minority of marketed compounds are inverse agonists at the receptor. Clinically, H-antihistamines are used to treat allergic reactions and mast cell-related disorders. Sedation is a common side effect of H-antihistamines that readily cross the blood–brain barrier; some of these drugs, such as diphenhydramine and doxylamine, are therefore used to treat insomnia. H-antihistamines can also reduce inflammation, since the expression of NF-κB, the transcription factor the regulates inflammatory processes, is promoted by both the receptor's constitutive activity and agonist (i.e., histamine) binding at the H receptor.
5("S")-HETE may also be made in combination with 5("R")-HETE along with numerous other "(S,R)"-hydroxy polyunsaturated fatty acids as a consequence of the non-enzymatic oxidation reactions. Formation of these products can occur in any tissue subjected to oxidative stress.
While kidneys can routinely be obtained from human donors, most organs are in short supply leading to consideration of xenotransplants from other species. Pigs are especially likely sources for xenotransplants, chosen for the anatomical and physiological characteristics they share with humans. However, the sugar galactose-alpha-1,3-galactose (αGal) has been implicated as a major factor in hyperacute rejection in xenotransplantation. Unlike virtually all other mammals, humans and other primates do not make αGal, and in fact recognize it as an antigen. During transplantation, xenoreactive natural antibodies recognize αGal on the graft endothelium as an antigen, and the resulting complement-mediated immune response leads to a rejection of the transplant.
"We designed the building from the inside out, not the outside in,” said Loretta H. Cockrum, Foram’s founder, chairman and CEO. “We wanted the most efficient office building ever designed, with no wasted space or wasted energy. This is a building of the future more than a building of the present. A lot of love has gone into that building, and a lot of pride."
Glycolipids are important for cell recognition, and are important for modulating the function of membrane proteins that act as receptors. Glycolipids are lipid molecules bound to oligosaccharides, generally present in the lipid bilayer. Additionally, they can serve as receptors for cellular recognition and cell signaling. The head of the oligosaccharide serves as a binding partner in receptor activity. The binding mechanisms of receptors to the oligosaccharides depends on the composition of the oligosaccharides that are exposed or presented above the surface of the membrane. There is great diversity in the binding mechanisms of glycolipids, which is what makes them such an important target for pathogens as a site for interaction and entrance. For example, the chaperone activity of glycolipids has been studied for its relevance to HIV infection.
Ephrin receptors, the largest subfamily of receptor tyrosine kinases (RTKs), and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape, and mobility in neuronal and epithelial cells. See MIM 179610 for additional background on Eph receptors and ephrins.
The function of the 5-HT receptor is unknown due to the lack of selective pharmacological tools, specific antibodies, and permissive animal models. The 5-HT receptor gene lacks polymorphisms amongst humans (few mutations), indicating a high degree of evolutionary conservation of genetic sequence, which suggests that the 5-HT receptor has an important physiological role in humans. It is hypothesized that the 5-HT receptor is involved in the regulation of memory in humans due to the high abundance of receptors in the frontal cortex, hippocampus, and olfactory bulb, all of which are regions of the brain integral to memory regulation.