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OPHN1
Oligophrenin-1 is a protein that in humans is encoded by the ''OPHN1'' gene. Function Oligophrenin 1 has 25 exons and encodes a Rho- GTPase-activating protein. The Rho proteins are important mediators of intracellular signal transduction, which affects cell migration and cell morphogenesis. The role of OPHN1 in the medial prefrontal cortex in the behavioural responses to stress, and learned helplessness-inducing effect of OPHN1 deletion in parvalbumin interneurons, is of recent research interest. It is also involved in regulation in inhibitory interneurons in the olfactory bulb. Clinical significance Mutations in this gene are responsible for non-specific X-linked intellectual disability (previously called mental retardation). OPHN1 syndrome is a rare disorder characterized by intellectual disability and changes in the part of the brain which controls movement and balance (cerebellum). The syndrome mainly affects males. It is characterized by low muscle tone (hypotoni ...
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Protein
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 resid ...
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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 g ...
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GTPase-activating Protein
GTPase-activating proteins or GTPase-accelerating proteins (GAPs) are a family of regulatory proteins whose members can bind to activated G proteins and stimulate their GTPase activity, with the result of terminating the signaling event. GAPs are also known as RGS protein, or RGS proteins,Kimple, A.J. "Structural Determinants of G-protein α Subunit Selectivity by Regulator of G-protein Signaling 2 (RGS2)". ''The Journal of Biological Chemistry''. 284 (2009): 19402-19411. and these proteins are crucial in controlling the activity of G proteins. Regulation of G proteins is important because these proteins are involved in a variety of important cellular processes. The large G proteins, for example, are involved in transduction of signaling from the G protein-coupled receptor for a variety of signaling processes like hormonal signaling, and small G proteins are involved in processes like cellular trafficking and cell cycling. GAP's role in this function is to turn the G protein's ...
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Rho Family Of GTPases
The Rho family of GTPases is a family of small (~21 kDa) signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found in all eukaryotic kingdoms, including yeasts and some plants. Three members of the family have been studied in detail: Cdc42, Rac1, and RhoA. All G proteins are "molecular switches", and Rho proteins play a role in organelle development, cytoskeletal dynamics, cell movement, and other common cellular functions. History Identification of the Rho family of GTPases began in the mid-1980s. The first identified Rho member was RhoA, isolated serendipitously in 1985 from a low stringency cDNA screening. Rac1 and Rac2 were identified next, in 1989 followed by Cdc42 in 1990. Eight additional mammalian Rho members were identified from biological screenings until the late 1990s, a turning point in biology where availability of complete genome sequ ...
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Signal Transduction
Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellular response. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding (or signal sensing) in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway. When signaling pathways interact with one another they form networks, which allow cellular responses to be coordinated, often by combinatorial signaling events. At the molecular level, such responses include changes in the transcription or translation of genes, and post-translational and conformational changes in proteins, as well as changes in their location. These molecular events are the basic mechanisms controlling cell gro ...
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Cell Migration
Cell migration is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing and immune responses all require the orchestrated movement of cells in particular directions to specific locations. Cells often migrate in response to specific external signals, including chemical signals and mechanical signals. Errors during this process have serious consequences, including intellectual disability, vascular disease, tumor formation and metastasis. An understanding of the mechanism by which cells migrate may lead to the development of novel therapeutic strategies for controlling, for example, invasive tumour cells. Due to the highly viscous environment (low Reynolds number), cells need to continuously produce forces in order to move. Cells achieve active movement by very different mechanisms. Many less complex prokaryotic organisms (and sperm cells) use flagella or cilia to propel themselves. Eukaryo ...
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Morphogenesis
Morphogenesis (from the Greek ''morphê'' shape and ''genesis'' creation, literally "the generation of form") is the biological process that causes a cell, tissue or organism to develop its shape. It is one of three fundamental aspects of developmental biology along with the control of tissue growth and patterning of cellular differentiation. The process controls the organized spatial distribution of cells during the embryonic development of an organism. Morphogenesis can take place also in a mature organism, such as in the normal maintenance of tissue by stem cells or in regeneration of tissues after damage. Cancer is an example of highly abnormal and pathological tissue morphogenesis. Morphogenesis also describes the development of unicellular life forms that do not have an embryonic stage in their life cycle. Morphogenesis is essential for the evolution of new forms. Morphogenesis is a mechanical process involving forces that generate mechanical stress, strain, and m ...
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Prefrontal Cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA13, BA14, BA24, BA25, BA32, BA44, BA45, BA46, and BA47. The basic activity of this brain region is considered to be orchestration of thoughts and actions in accordance with internal goals. Many authors have indicated an integral link between a person's will to live, personality, and the functions of the prefrontal cortex. This brain region has been implicated in executive functions, such as planning, decision making, short-term memory, personality expression, moderating social behavior and controlling certain aspects of speech and language. Executive function relates to abilities to differentiate among conflicting thoughts, determine good and bad, better and best, same and different, future consequences of current activities, working toward a defined goal, prediction of outc ...
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Behavioural Responses To Stress
Behavioural responses to stress are evoked from underlying complex physiological changes that arise consequently from stress. Real or perceived threat in the environment elicits stress response in animals, which disrupts internal homeostasis. Physiological changes cause behavioural responses in animals, including: impairment of response inhibition and lack of motivation, as well as changes in social, sexual, aggression and nurture behaviour in animals. The extent of the impact is dependent upon the type and duration of the stress, as well as the animal's past experiences. Behavioural responses to prolonged stress can also be transferred across generations. Overview A stress, as defined to Walter Cannon (1871–1945), is any disturbance that imbalances the internal environment of an organism (i.e. their homeostasis). There are two major types of stressors that cause stress to animals: abiotic stressors and biotic stressors. Abiotic stressors are any ecological, geological, ...
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Learned Helplessness
Learned helplessness is the behavior exhibited by a subject after enduring repeated aversive stimuli beyond their control. It was initially thought to be caused by the subject's acceptance of their powerlessness, by way of their discontinuing attempts to escape or avoid the aversive stimulus, even when such alternatives are unambiguously presented. Upon exhibiting such behavior, the subject was said to have acquired learned helplessness. In humans, learned helplessness is related to the concept of self-efficacy; the individual's belief in their innate ability to achieve goals. Learned helplessness theory is the view that clinical depression and related mental illnesses may result from a real or perceived absence of control over the outcome of a situation. Foundation of research and theory Early experiments American psychologist Martin Seligman initiated research on learned helplessness in 1967 at the University of Pennsylvania as an extension of his interest in depression. T ...
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Parvalbumin
Parvalbumin (PV) is a calcium-binding protein with low molecular weight (typically 9-11 kDa). In humans, it is encoded by the ''PVALB'' gene. It is not a member of the albumin family; it is named for its size (''parv-'', from Latin ''parvus'' small) and its ability to coagulate. It has three EF hand motifs and is structurally related to calmodulin and troponin C. Parvalbumin is found in fast-contracting muscles, where its levels are highest, as well as in the brain and some endocrine tissues. Parvalbumin is a small, stable protein containing EF-hand type calcium binding sites. It is involved in calcium signaling. Typically, this protein is broken into three domains, domains AB, CD and EF, each individually containing a helix-loop-helix motif. The AB domain houses a two amino-acid deletion in the loop region, whereas domains CD and EF contain the N-terminal and C-terminal, respectively. Calcium binding proteins like parvalbumin play a role in many physiological processes, namely c ...
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Interneuron
Interneurons (also called internuncial neurons, relay neurons, association neurons, connector neurons, intermediate neurons or local circuit neurons) are neurons that connect two brain regions, i.e. not direct motor neurons or sensory neurons. Interneurons are the central nodes of neural circuits, enabling communication between sensory or motor neurons and the central nervous system (CNS). They play vital roles in reflexes, neuronal oscillations, and neurogenesis in the adult mammalian brain. Interneurons can be further broken down into two groups: local interneurons and relay interneurons. Local interneurons have short axons and form circuits with nearby neurons to analyze small pieces of information. Relay interneurons have long axons and connect circuits of neurons in one region of the brain with those in other regions. However, interneurons are generally considered to operate mainly within local brain areas. The interaction between interneurons allow the brain to perform ...
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