Trimeric Intracellular Cation-selective Channel
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Trimeric Intracellular Cation-selective Channel
The trimeric intracellular cation-selective channels or TRIC proteins are a group of homo-trimeric cation channel proteins of ~300 residues in the ER membrane. There are two known TRIC proteins, TRIC-A and TRIC-B. Channel function TRICs are permeable to both Na+ and K+ but not divalent cations like Ca2+. They exhibit marked voltage-dependence, becoming more open when the cytosol is more positively charged than the ER lumen. TRIC-A TRIC-A is predominantly expressed in excitable tissues including brain and skeletal muscle. TRIC-A activity is thought to support RyR1-mediated efflux of Ca2+ ions from the sarcoplasmic reticulum into the cytosol. TRIC-B K+ flux into the ER through TRIC-B is thought to support IP3-induced efflux of Ca2+ ions through IP3-gated Ca2+ channels in the ER membrane. Clinical significance TRIC-A has been implicated in the regulation of arterial blood pressure through regulating the excitability of vascular smooth muscle cells. Several single-nucl ...
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Proteins
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residues ...
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Brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a vertebrate's body. In a human, the cerebral cortex contains approximately 14–16 billion neurons, and the estimated number of neurons in the cerebellum is 55–70 billion. Each neuron is connected by synapses to several thousand other neurons. These neurons typically communicate with one another by means of long fibers called axons, which carry trains of signal pulses called action potentials to distant parts of the brain or body targeting specific recipient cells. Physiologically, brains exert centralized control over a body's other organs. They act on the rest of the body both by generating patterns of muscle activity and by driving the secretion of chemicals called hormones. This centralized control allows rapid and coordinated respon ...
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Dominance (genetics)
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and the second recessive. This state of having two different variants of the same gene on each chromosome is originally caused by a mutation in one of the genes, either new (''de novo'') or inherited. The terms autosomal dominant or autosomal recessive are used to describe gene variants on non-sex chromosomes ( autosomes) and their associated traits, while those on sex chromosomes (allosomes) are termed X-linked dominant, X-linked recessive or Y-linked; these have an inheritance and presentation pattern that depends on the sex of both the parent and the child (see Sex linkage). Since there is only one copy of the Y chromosome, Y-linked traits cannot be dominant or recessive. Additionally, there are other forms of dominance such as incomplete d ...
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Null Allele
A null allele is a nonfunctional allele (a variant of a gene) caused by a genetic mutation. Such mutations can cause a complete lack of production of the associated gene product or a product that does not function properly; in either case, the allele may be considered nonfunctional. A null allele cannot be distinguished from deletion of the entire locus solely from phenotypic observation. A mutant allele that produces no RNA transcript is called an RNA null (shown by Northern blotting or by DNA sequencing of a deletion allele), and one that produces no protein is called a protein null (shown by Western blotting). A genetic null or amorphic allele has the same phenotype when homozygous as when heterozygous with a deficiency that disrupts the locus in question. A genetic null allele may be both a protein null and an RNA null, but may also express normal levels of a gene product that is nonfunctional due to mutation. Null alleles can have lethal effects depending on the importance o ...
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Biomarker
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. as cited in Biomarkers are used in many scientific fields. Medicine Biomarkers used in the medical field, are a part of a relatively new clinical toolset categorized by their clinical applications. The three main classes are molecular biomarkers, cellular biomarkers or imaging biomarkers. All three types of biomarkers have a clinical role in narrowing or guiding treatment decisions and follow a sub-categorization of being either predictive, prognostic, or diagnostic. Predictive Predictive molecular, cellular, or imaging biomarkers that pass validation can serve as a method of predicting clinical outcomes. Predictive biomarkers are used to help optimize id ...
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Locus (genetics)
In genetics, a locus (plural loci) is a specific, fixed position on a chromosome where a particular gene or genetic marker is located. Each chromosome carries many genes, with each gene occupying a different position or locus; in humans, the total number of protein-coding genes in a complete haploid set of 23 chromosomes is estimated at 19,000–20,000. Genes may possess multiple variants known as alleles, and an allele may also be said to reside at a particular locus. Diploid and polyploid cells whose chromosomes have the same allele at a given locus are called homozygous with respect to that locus, while those that have different alleles at a given locus are called heterozygous. The ordered list of loci known for a particular genome is called a gene map. Gene mapping is the process of determining the specific locus or loci responsible for producing a particular phenotype or biological trait. Association mapping, also known as "linkage disequilibrium mapping", is a method of ma ...
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Single-nucleotide Polymorphisms
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently large fraction of the population (e.g. 1% or more), many publications do not apply such a frequency threshold. For example, at a specific base position in the human genome, the G nucleotide may appear in most individuals, but in a minority of individuals, the position is occupied by an A. This means that there is a SNP at this specific position, and the two possible nucleotide variations – G or A – are said to be the alleles for this specific position. SNPs pinpoint differences in our susceptibility to a wide range of diseases, for example age-related macular degeneration (a common SNP in the CFH gene is associated with increased risk of the disease) or nonalcoholic fatty liver disease (a SNP in the PNPLA3 gene is associated with incr ...
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Vascular Smooth Muscle
Vascular smooth muscle is the type of smooth muscle that makes up most of the walls of blood vessels. Structure Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood vessels. Nerve supply Vascular smooth muscle is innervated primarily by the sympathetic nervous system through adrenergic receptors (adrenoceptors). The three types present are: alpha-1, alpha-2 and beta-2 adrenergic receptors, . The main endogenous agonist of these cell receptors is norepinephrine (NE). The adrenergic receptors exert opposite physiologic effects in the vascular smooth muscle under activation: * alpha-1 receptors. Under NE binding alpha-1 receptors cause vasoconstriction ( contraction of the vascular smooth muscle cells decreasing the diameter of the vessels). Thesea receptors are activated in response to shock or low blood pressure as a defensive reaction trying to restore the normal blood pressure. Antagonists ...
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Muscle Contraction
Muscle contraction is the activation of tension-generating sites within muscle cells. In physiology, muscle contraction does not necessarily mean muscle shortening because muscle tension can be produced without changes in muscle length, such as when holding something heavy in the same position. The termination of muscle contraction is followed by muscle relaxation, which is a return of the muscle fibers to their low tension-generating state. For the contractions to happen, the muscle cells must rely on the interaction of two types of filaments which are the thin and thick filaments. Thin filaments are two strands of actin coiled around each, and thick filaments consist of mostly elongated proteins called myosin. Together, these two filaments form myofibrils which are important organelles in the skeletal muscle system. Muscle contraction can also be described based on two variables: length and tension. A muscle contraction is described as isometric if the muscle tension changes ...
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Arterial Blood Pressure
Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" refers to the pressure in the large arteries. Blood pressure is usually expressed in terms of the systolic pressure (maximum pressure during one heartbeat) over diastolic pressure (minimum pressure between two heartbeats) in the cardiac cycle. It is measured in millimeters of mercury ( mmHg) above the surrounding atmospheric pressure. Blood pressure is one of the vital signs—together with respiratory rate, heart rate, oxygen saturation, and body temperature—that healthcare professionals use in evaluating a patient's health. Normal resting blood pressure, in an adult is approximately systolic over diastolic, denoted as "120/80 mmHg". Globally, the average blood pressure, age standardized, has remained about the same since 1 ...
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Inositol Trisphosphate Receptor
Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a Ca2+ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis, fertilization, development, behavior, learning and memory. Inositol triphosphate receptor represents a dominant second messenger leading to the release of Ca2+ from intracellular store sites. There is strong evidence suggesting that the InsP3R plays an important role in the conversion of external stimuli to intracellular Ca2+ signals characterized by complex patterns relative to both space and time, such as Ca2+ waves and oscillations. Discovery The InsP3 receptor was first purified from rat cerebellum by neuroscientists Surachai Supattapone and Solomon Snyder at Johns Hopkins University School of Medicine. The cDNA of the InsP3 receptor was first cloned in the la ...
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Sarcoplasmic Reticulum
The sarcoplasmic reticulum (SR) is a membrane-bound structure found within muscle cells that is similar to the smooth endoplasmic reticulum in other Cell (biology), cells. The main function of the SR is to store calcium ions (Ca2+). Calcium in biology, Calcium ion levels are kept relatively constant, with the concentration of calcium ions within a cell being 10,000 times smaller than the concentration of calcium ions outside the cell. This means that small increases in calcium ions within the cell are easily detected and can bring about important cellular changes (the calcium is said to be a second messenger). Calcium is used to make calcium carbonate (found in chalk) and calcium phosphate, two compounds that the body uses to make teeth and bones. This means that too much calcium within the cells can lead to hardening (calcification) of certain intracellular structures, including the mitochondrion, mitochondria, leading to cell death. Therefore, it is vital that calcium ion levels a ...
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