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Rev-ErbA Alpha
Rev-Erb alpha (Rev-Erbɑ), also known as nuclear receptor subfamily 1 group D member 1 (NR1D1), is one of two Rev-Erb proteins in the nuclear receptor (NR) family of intracellular transcription factors. In humans, REV-ERBɑ is encoded by the ''NR1D1'' gene, which is highly conserved across animal species. Rev-Erbɑ plays an important role in regulation of the core circadian clock through repression of the positive clock element Bmal1. It also regulates several physiological processes under circadian control, including metabolic and immune pathways. Rev-Erbɑ mRNA demonstrates circadian oscillation in its expression, and it is highly expressed in mammals in the brain and metabolic tissues such as skeletal muscle, adipose tissue, and liver. Discovery Rev-Erbɑ was discovered in 1989 by Nobuyuki Miyajima and colleagues, who identified two ''erbA'' homologs on human chromosome 17 that were transcribed from opposite DNA strands in the same locus. One of the genes encoded a p ...
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Rev-ErbA
The Rev-Erb proteins are members of the nuclear receptor (NR) superfamily of intracellular transcription factors and key regulatory components of the circadian clock. There are two forms of the receptor, Rev-Erb alpha and Rev-Erb beta, which are each encoded by a separate gene (''NR1D1'' and ''NR1D2'', respectively).   These proteins act as key regulators of clock gene expression through transcriptional repression of Bmal1. Through their regulation of clock-controlled genes, the Rev-Erb proteins affect several physiological processes throughout the body, including metabolic, endocrine, and immune pathways. In the NRNC classification scheme, Rev-Erb is nuclear receptor subfamily 1 group D (NR1D). The name "Rev-Erb" derived by truncation from "Rev-ERBA" (Rev-Erbα), which in turn was named because it was on the opposite strand of ERBA ( THRA) oncogene. The paralogous Rev-Erbβ does not seem to have anything special on its reverse strand. Older sources may use "Rev-ERBA ...
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Gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as ...
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Autoregulation
Autoregulation is a process within many biological systems, resulting from an internal adaptive mechanism that works to adjust (or mitigate) that system's response to stimuli. While most systems of the body show some degree of autoregulation, it is most clearly observed in the kidney, the heart, and the brain. Perfusion of these organs is essential for life, and through autoregulation the body can divert blood (and thus, oxygen) where it is most needed. Cerebral autoregulation More so than most other organs, the brain is very sensitive to increased or decreased blood flow, and several mechanisms (metabolic, myogenic, and neurogenic) are involved in maintaining an appropriate cerebral blood pressure. Brain blood flow autoregulation is abolished in several disease states such as traumatic brain injury, stroke, brain tumors, or persistent abnormally high levels. Homeometrics and heterometric autoregulation of the heart Homeometric autoregulation, in the context of the circulato ...
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Response Element
Response elements are short sequences of DNA within a gene promoter or enhancer region that are able to bind specific transcription factors and regulate transcription of genes. Under conditions of stress, a transcription activator protein binds to the response element and stimulates transcription. If the same response element sequence is located in the control regions of different genes, then these genes will be activated by the same stimuli, thus producing a coordinated response. Hormone response element A hormone response element (HRE) is a short sequence of DNA within the promoter of a gene, that is able to bind to a specific hormone receptor complex and therefore regulate transcription. The sequence is most commonly a pair of inverted repeats separated by three nucleotides, which also indicates that the receptor binds as a dimer. Specifically, HRE responds to steroid hormones, as the activated steroid receptor is the transcription factor binding HRE. This regulates the tran ...
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Alternative Splicing
Alternative splicing, or alternative RNA splicing, or differential splicing, is an alternative splicing process during gene expression that allows a single gene to code for multiple proteins. In this process, particular exons of a gene may be included within or excluded from the final, processed messenger RNA (mRNA) produced from that gene. This means the exons are joined in different combinations, leading to different (alternative) mRNA strands. Consequently, the proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions (see Figure). Biologically relevant alternative splicing occurs as a normal phenomenon in eukaryotes, where it increases the number of proteins that can be encoded by the genome. In humans, it is widely believed that ~95% of multi-exonic genes are alternatively spliced to produce functional alternative products from the same gene but many scientists believe that most of ...
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Exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence in RNA transcripts. In RNA splicing, introns are removed and exons are covalently joined to one another as part of generating the mature RNA. Just as the entire set of genes for a species constitutes the genome, the entire set of exons constitutes the exome. History The term ''exon'' derives from the expressed region and was coined by American biochemist Walter Gilbert in 1978: "The notion of the cistron… must be replaced by that of a transcription unit containing regions which will be lost from the mature messengerwhich I suggest we call introns (for intragenic regions)alternating with regions which will be expressedexons." This definition was originally made for protein-coding transcripts that are spliced before being translate ...
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Negative Feedback
Negative feedback (or balancing feedback) occurs when some function of the output of a system, process, or mechanism is fed back in a manner that tends to reduce the fluctuations in the output, whether caused by changes in the input or by other disturbances. Whereas positive feedback tends to lead to instability via exponential growth, oscillation or chaotic behavior, negative feedback generally promotes stability. Negative feedback tends to promote a settling to equilibrium, and reduces the effects of perturbations. Negative feedback loops in which just the right amount of correction is applied with optimum timing can be very stable, accurate, and responsive. Negative feedback is widely used in mechanical and electronic engineering, and also within living organisms, and can be seen in many other fields from chemistry and economics to physical systems such as the climate. General negative feedback systems are studied in control systems engineering. Negative feedback ...
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Positive Feedback
Positive feedback (exacerbating feedback, self-reinforcing feedback) is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance. That is, the effects of a perturbation on a system include an increase in the magnitude of the perturbation. That is, ''A produces more of B which in turn produces more of A''.Keesing, R.M. (1981). Cultural anthropology: A contemporary perspective (2nd ed.) p.149. Sydney: Holt, Rinehard & Winston, Inc. In contrast, a system in which the results of a change act to reduce or counteract it has negative feedback. Both concepts play an important role in science and engineering, including biology, chemistry, and cybernetics. Mathematically, positive feedback is defined as a positive loop gain around a closed loop of cause and effect. That is, positive feedback is in phase with the input, in the sense that it adds to make the input larger. Positive feedback tends to cause system instability. When the loop gain is pos ...
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Transcription Translation Feedback Loop
Transcription-translation feedback loop (TTFL), is a cellular model for explaining circadian rhythms in behavior and physiology. Widely conserved across species, the TTFL is auto-regulatory, in which transcription of clock genes is regulated by their own protein products. Discovery Circadian rhythms have been documented for centuries. For example, French astronomer Jean-Jacques d’Ortous de Mairan noted the periodic 24-hour movement of ''Mimosa'' plant leaves as early as 1729. However, science has only recently begun to uncover the cellular mechanisms responsible for driving observed circadian rhythms. The cellular basis of circadian rhythms is supported by the fact that rhythms have been observed in single-celled organisms Beginning in the 1970s, experiments conducted by Ron Konopka and colleagues, in which forward genetic methods were used to induce mutation, revealed that ''Drosophila melanogaster'' specimens with altered ''period'' (''Per'') genes also demonstrated altere ...
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Fibroblast
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells of connective tissue in animals. Structure Fibroblasts have a branched cytoplasm surrounding an elliptical, speckled nucleus having two or more nucleoli. Active fibroblasts can be recognized by their abundant rough endoplasmic reticulum. Inactive fibroblasts (called fibrocytes) are smaller, spindle-shaped, and have a reduced amount of rough endoplasmic reticulum. Although disjointed and scattered when they have to cover a large space, fibroblasts, when crowded, often locally align in parallel clusters. Unlike the epithelial cells lining the body structures, fibroblasts do not form flat monolayers and are not restricted by a polarizing attachment to a basal lamina on one side, although they may contribute to basal lamina components ...
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Thyroid Hormone Receptor Alpha
Thyroid hormone receptor alpha (TR-alpha) also known as nuclear receptor subfamily 1, group A, member 1 (NR1A1), is a nuclear receptor protein that in humans is encoded by the ''THRA'' gene. Function The protein encoded by this gene is a nuclear hormone receptor for triiodothyronine. It is one of the several receptors for thyroid hormone, and has been shown to mediate the biological activities of thyroid hormone. Knockout studies in mice suggest that the different receptors, while having certain extent of redundancy, may mediate different functions of thyroid hormone. Alternatively spliced transcript variants encoding distinct isoforms have been reported. Role in pathology Mutations of the THRA gene may cause nongoitrous congenital hypothyroidism-6, a subtype of congenital hypothyroidism. Interactions THR1 has been shown to interact with: * COPS2, * EP300, * ITGB3BP, * MED1, * MED6, * MED12, * MED16, * MEF2A, * NCOA6, * TRIP11, and * UBC The University ...
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Library (biology)
In molecular biology, a library is a collection of DNA fragments that is stored and propagated in a population of micro-organisms through the process of molecular cloning. There are different types of DNA libraries, including cDNA libraries (formed from reverse-transcribed RNA), genomic libraries (formed from genomic DNA) and randomized mutant libraries (formed by de novo gene synthesis where alternative nucleotides or codons are incorporated). DNA library technology is a mainstay of current molecular biology, genetic engineering, and protein engineering, and the applications of these libraries depend on the source of the original DNA fragments. There are differences in the cloning vectors and techniques used in library preparation, but in general each DNA fragment is uniquely inserted into a cloning vector and the pool of recombinant DNA molecules is then transferred into a population of bacteria (a Bacterial Artificial Chromosome or BAC library) or yeast such that each o ...
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