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Temporal Feedback
Within molecular and cell biology, Temporal feedback, also referred to as interlinked or interlocked feedback, is a biological regulatory motif in which fast and slow positive feedback loops are interlinked to create "all or none" switches. This interlinking produces separate, adjustable activation and de-activation times. This type of feedback is thought to be important in cellular processes in which an "all or none" decision is a necessary response to a specific input. The mitotic trigger, polarization in budding yeast, mammalian calcium signal transduction, EGF receptor signaling, platelet activation, and Xenopus oocyte maturation are examples for interlinked fast and slow multiple positive feedback systems. In biological systems, temporal feedback is a ubiquitous signal transduction motif that allows systems to convert graded inputs into decisive, all-or-none digital outputs. A system with interlinked fast and slow feedback loops produces a dual-time switch, which is rapidly ...
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Molecular Biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physical structure of biological macromolecules is known as molecular biology. Molecular biology was first described as an approach focused on the underpinnings of biological phenomena - uncovering the structures of biological molecules as well as their interactions, and how these interactions explain observations of classical biology. In 1945 the term molecular biology was used by physicist William Astbury. In 1953 Francis Crick, James Watson, Rosalind Franklin, and colleagues, working at Medical Research Council unit, Cavendish laboratory, Cambridge (now the MRC Laboratory of Molecular Biology), made a double helix model of DNA which changed the entire research scenario. They proposed the DNA structure based on previous research done by Ro ...
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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 moveme ...
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E-box
An E-box (enhancer box) is a DNA response element found in some eukaryotes that acts as a protein-binding site and has been found to regulate gene expression in neurons, muscles, and other tissues. Its specific DNA sequence, CANNTG (where N can be any nucleotide), with a palindromic canonical sequence of CACGTG, is recognized and bound by transcription factors to initiate gene transcription. Once the transcription factors bind to the promoters through the E-box, other enzymes can bind to the promoter and facilitate transcription from DNA to mRNA. Discovery The E-box was discovered in a collaboration between Susumu Tonegawa's and Walter Gilbert's laboratories in 1985 as a control element in immunoglobulin heavy-chain enhancer. They found that a region of 140 base pairs in the tissue-specific transcriptional enhancer element was sufficient for different levels of transcription enhancement in different tissues and sequences. They suggested that proteins made by specific tissues acted ...
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BMAL1
Aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL) or brain and muscle ARNT-Like 1 (BMAL1) is a protein that in humans is encoded by the gene on chromosome 11, region p15.3. It's also known as ''BMAL1'', ''MOP3'', and, less commonly, ''bHLHe5'', ''BMAL'', ''BMAL1C'', ''JAP3'', ''PASD3'', and ''TIC''. ''ARNTL'' encodes a transcription factor with a basic helix-loop-helix (bHLH) and two PAS domains. The human ''ARNTL'' gene has a predicted 24 exons, located on the p15 band of the 11th chromosome. The ARNTL protein is 626 amino acids long and plays a key role as one of the positive elements in the mammalian auto-regulatory transcription-translation negative feedback loop (TTFL), which is responsible for generating molecular circadian rhythms. Research has revealed that ''ARNTL'' is the only clock gene without which the circadian clock fails to function in humans. ''ARNTL'' has also been identified as a candidate gene for susceptibility to hypertension, diabetes, ...
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Clock Genes
A clock or a timepiece is a device used to measure and indicate time. The clock is one of the oldest human inventions, meeting the need to measure intervals of time shorter than the natural units such as the day, the lunar month and the year. Devices operating on several physical processes have been used over the millennia. Some predecessors to the modern clock may be considered as "clocks" that are based on movement in nature: A sundial shows the time by displaying the position of a shadow on a flat surface. There is a range of duration timers, a well-known example being the hourglass. Water clocks, along with the sundials, are possibly the oldest time-measuring instruments. A major advance occurred with the invention of the verge escapement, which made possible the first mechanical clocks around 1300 in Europe, which kept time with oscillating timekeepers like balance wheels., pp. 103–104., p. 31. Traditionally, in horology, the term ''clock'' was used for a st ...
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Cryptochrome
Cryptochromes (from the Greek κρυπτός χρώμα, "hidden colour") are a class of flavoproteins found in plants and animals that are sensitive to blue light. They are involved in the circadian rhythms and the sensing of magnetic fields in a number of species. The name ''cryptochrome'' was proposed as a ''portmanteau'' combining the '' chromatic'' nature of the photoreceptor, and the ''cryptogamic'' organisms on which many blue-light studies were carried out. The two genes ''Cry1'' and ''Cry2'' code the two cryptochrome proteins CRY1 and CRY2. In insects and plants, CRY1 regulates the circadian clock in a light-dependent fashion, whereas in mammals, CRY1 and CRY2 act as light-independent inhibitors of CLOCK-BMAL1 components of the circadian clock. In plants, blue-light photoreception can be used to cue developmental signals. Besides chlorophylls, cryptochromes are the only proteins known to form photoinduced radical-pairs ''in vivo''. These appear to enable some animal ...
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Period (gene)
Period (per) is a gene located on the X chromosome of ''Drosophila melanogaster''. Oscillations in levels of both ''per'' transcript and its corresponding protein PER have a period of approximately 24 hours and together play a central role in the molecular mechanism of the ''Drosophila'' biological clock driving circadian rhythms in eclosion and locomotor activity. Mutations in the per gene can shorten (''perS''), lengthen (''perL''), and even abolish (''per0'') the period of the circadian rhythm. Discovery The period gene and three mutants (''perS'', ''perL'', and ''per0'') were isolated in an EMS mutagenesis screen by Ronald Konopka and Seymour Benzer in 1971. The ''perS'', ''perL'', and ''per0'' mutations were found to not complement each other, so it was concluded that the three phenotypes were due to mutations in the same gene. The discovery of mutants that altered the period of circadian rhythms in eclosion and locomotor activity (''perS'' and ''perL'') indicated the ...
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Hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is the size of an almond. The hypothalamus is responsible for regulating certain metabolic processes and other activities of the autonomic nervous system. It synthesizes and secretes certain neurohormones, called releasing hormones or hypothalamic hormones, and these in turn stimulate or inhibit the secretion of hormones from the pituitary gland. The hypothalamus controls body temperature, hunger, important aspects of parenting and maternal attachment behaviours, thirst, fatigue, sleep, and circadian rhythms. Structure T ...
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Suprachiasmatic Nuclei
The suprachiasmatic nucleus or nuclei (SCN) is a tiny region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regulate many different body functions in a 24-hour cycle. The mouse SCN contains approximately 20,000 neurons. The SCN interacts with many other regions of the brain. It contains several cell types and several different peptides (including vasopressin and vasoactive intestinal peptide) and neurotransmitters. Neuroanatomy The SCN is situated in the anterior part of the hypothalamus immediately dorsal, or ''superior'' (hence supra) to the optic chiasm (CHO) bilateral to (on either side of) the third ventricle. The nucleus can be divided into ventrolateral and dorsolateral portions, also known as the core and shell, respectively. These regions differ in their expression of the clock genes, the core expresses them in response to stimuli whereas t ...
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Circadian Rhythms
A circadian rhythm (), or circadian cycle, is a natural, internal process that regulates the sleep–wake cycle and repeats roughly every 24 hours. It can refer to any process that originates within an organism (i.e., endogenous) and responds to the environment ( entrained by the environment). These 24-hour rhythms are driven by a circadian clock, and they have been widely observed in animals, plants, fungi and cyanobacteria. The term ''circadian'' comes from the Latin ''circa'', meaning "approximately", and ''dies'', meaning "day". Processes with 24-hour cycles are more generally called diurnal rhythms; diurnal rhythms should not be called circadian rhythms unless they can be confirmed as endogenous, and not environmental. Although circadian rhythms are endogenous, they are adjusted to the local environment by external cues called zeitgebers (German for "time givers"), which include light, temperature and redox cycles. In clinical settings, an abnormal circadian rhythm in humans ...
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Limb Bud
The limb bud is a structure formed early in vertebrate limb development. As a result of interactions between the ectoderm and underlying mesoderm, formation occurs roughly around the fourth week of development. In the development of the human embryo the upper limb bud appears in the third week and the lower limb bud appears four days later. The limb bud consists of undifferentiated mesoderm cells that are sheathed in ectoderm. As a result of cell signaling interactions between the ectoderm and underlying mesoderm cells, formation of the developing limb bud occurs as mesenchymal cells from the lateral plate mesoderm and somites begin to proliferate to the point where they create a bulge under the ectodermal cells above. The mesoderm cells in the limb bud that come from the lateral plate mesoderm will eventually differentiate into the developing limb’s connective tissues, such as cartilage, bone, and tendon. Moreover, the mesoderm cells that come from the somites will eventually ...
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BMP4
Bone morphogenetic protein 4 is a protein that in humans is encoded by ''BMP4'' gene. BMP4 is found on chromosome 14q22-q23. BMP4 is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamily. The superfamily includes large families of growth and differentiation factors. BMP4 is highly conserved evolutionarily. BMP4 is found in early embryonic development in the ventral marginal zone and in the eye, heart blood and otic vesicle. Discovery Bone morphogenetic proteins were originally identified by an ability of demineralized bone extract to induce endochondral osteogenesis in vivo in an extraskeletal site. Function BMP4 is a polypeptide belonging to the TGF-β superfamily of proteins. It, like other bone morphogenetic proteins, is involved in bone and cartilage development, specifically tooth and limb development and fracture repair. This particular family member plays an important role in the onset of endochondral bone ...
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