• Neurodegenerative disorders have been shown to exhibit substantial interconnectedness with circadian rhythmicity. (frontiersin.org)
  • The cellular stress and subsequent DNA damage signaling imposed by hyperactivity of these multiple molecular systems in addition to aberrant circadian rhythmicity lead to extensive protein aggregation such as α-synuclein pre-formed fibrils (α-Syn PFFs), suggesting a specific molecular pathway linking circadian rhythmicity, PARP1/E3 ligase activity, and Parkinson's disease. (frontiersin.org)
  • The CLOCK/BMAL1 heterodimer activates the transcription of Per/Cry genes, and the production and resulting phosphorylation of PER/CRY inhibit the CLOCK/BMAL1 heterodimer, reducing the transcription of Per/Cry forming the negative feedback loop required to maintain circadian rhythmicity at a basic molecular level. (frontiersin.org)
  • In the August online edition of Public Library of Science (PLOS) Computational Biology, Cornell biomolecular engineer Kelvin Lee, in collaboration with graduate student Robert S. Kuczenski, Kevin C. Hong '05 and Jordi Garcia-Ojalvo of Universitat Politecnica de Catalunya, Spain, hypothesize that the accepted model of circadian rhythmicity may be missing a key link, based on a mathematical model of what happens during the sleeping/waking cycle in fruit flies. (news-medical.net)
  • Perturbation of circadian rhythmicity in mammals, either by environmental influences such as shiftwork or by genetic manipulation, has been associated with metabolic disturbance and the development of obesity and diabetes. (eur.nl)
  • In the course of investigating metabolic defects in Sik3 -deficient mice ( Sik3 -/- ), we observed that circadian rhythmicity of the metabolisms was phase-delayed. (elifesciences.org)
  • However, OOAC technologies do not currently incorporate circadian rhythmicity, which limits their physiological relevance and value as platforms for ex-vivo therapeutic evaluation. (ukri.org)
  • These "clock cells" persist in the adult brain where they regulate behavioral rhythmicity. (rockefeller.edu)
  • It allows direct monitoring of molecular rhythms of the protein PER2 as a real-time reporter of circadian gene dynamics. (molvis.org)
  • Paternal UBE3A-positive cells in the SCN show partial colocalization with the neuropeptide arginine vasopressin (AVP) and clock proteins (PER2 and BMAL1), supporting that paternal UBE3A expression in the SCN is often of neuronal origin. (nature.com)
  • Disruption of the Per2 uORF disrupts the amplitude of circadian rhythms ( left ) and reduces sleep in mice ( right ). (eurekalert.org)
  • Mutating the uORF in the core clock gene Period2 ( Per2 ) yielded intriguing results. (eurekalert.org)
  • It boosted Per2 mRNA expression while significantly reducing total sleep duration in mice, particularly during transitions between light and dark. (eurekalert.org)
  • PER2 protein is at the center of the inhibitory feedback loop that underlies the molecular mechanisms that control circadian rhythms, but its importance goes beyond just regulating sleep. (eurekalert.org)
  • Per2 expression is deregulated in breast cancer, downregulated in patients with acute myeloid leukemia, and disruption of Per2 results in tumorgenesis in mice. (eurekalert.org)
  • Therefore, understanding the post-transcriptional processes that shape Per2 expression has wide-ranging implications for the various fields, including circadian rhythms and medicine, and could provide new insights into how cancer hijacks a cell's normal circadian program or help improve drugs with time-dependent therapeutic efficacy. (eurekalert.org)
  • LUC) to investigate whether circadian rhythms in the clock gene protein PER2 in these extra-SCN tissues were compromised by the absence of the VPAC2 receptor. (ljmu.ac.uk)
  • Recently, oscillators in the oval nucleus of the bed nucleus of the stria terminalis (OV-BNST), the central nucleus of the amygdala (CEA), hippocampus (HIPP) and basolateral amygdala (BLA) of male rats have been shown to rhythmically express Period 2 (PER2), clock gene protein, with peak expression in the early evening. (elsevierpure.com)
  • Female Wistar rats were sacrificed at different circadian times and days of the estrus cycle, and their brains processed for immunocytochemistry for PER2. (elsevierpure.com)
  • Significant differences in the pattern of expression of PER2 in the OV-BNST and the CEA as a function of the day of the estrus cycle were found. (elsevierpure.com)
  • PER2 expression peaked at different times on metestrus, and diestrus than the other two days of the cycle. (elsevierpure.com)
  • In the BLA, HIPP, and suprachiasmatic nucleus, however, time of peak expression of PER2 remained constant across the estrus cycle, peaking in the early evening. (elsevierpure.com)
  • In order to investigate the role of fluctuating gonadal hormones on the pattern of PER2 expression, ovariectomised females were assigned to groups based on circadian time of day. (elsevierpure.com)
  • In ovariectomised females peak expression of PER2 was observed in the early evening in all areas examined. (elsevierpure.com)
  • Expression levels of PER2, a clock protein, were elevated in Sik3 -knockdown cells but down-regulated in Sik3 -overexpressing cells, which could be attributed to a phosphorylation-dependent decrease in PER2 protein stability. (elifesciences.org)
  • Collectively, SIK3 plays key roles in circadian rhythms by facilitating phosphorylation-dependent PER2 destabilization, either directly or indirectly. (elifesciences.org)
  • Datasets used for the fit were: mRNA levels of 7 clock genes, protein level of 7 clock genes and circadian rhythms of nucleus/cytoplasm localization of NLRP3, BMAL1, PER2 and CRY1. (smb.org)
  • Luc oscillations that significantly decrease from 1 to 4-5 months, whereas the endogenous period and rhythmic power increase slightly until 2 to 3 months and then do not change until 8 months. (molvis.org)
  • Besides circadian rhythms, oscillations cycling with a 12 hr period exist. (utmb.edu)
  • Utilizing an unbiased mathematical approach identifying all superimposed oscillations, we uncovered prevalent 12 hr gene expression and metabolic rhythms in mouse liver, coupled with a physiological 12 hr unfolded protein response oscillation. (utmb.edu)
  • These oscillations are self-driven on a molecular level via complex interactions of transcriptional and translational feedback loops, with BMAL1 and CLOCK comprising the positive and Period (PER) 1-3 and Cryptochrome (CRY) 1-2 proteins comprising the negative feedback loops. (tuni.fi)
  • The core molecular mechanism responsible for circadian oscillations relies on the negative regulation exerted by a protein on the expression of its own gene. (aip.org)
  • Deterministic models account for the occurrence of autonomous circadian oscillations, for their entrainment by light-dark cycles, and for their phase shifting by light pulses. (aip.org)
  • Numerical simulations of the stochastic models show that robust circadian oscillations can already occur with a limited number of mRNA and protein molecules, in the range of a few tens and hundreds, respectively. (aip.org)
  • Various factors affect the robustness of circadian oscillations with respect to molecular noise. (aip.org)
  • Intercellular coupling further increases the robustness of circadian oscillations. (aip.org)
  • These data demonstrate that while the main rhythm parameters of extra-SCN circadian oscillations are maintained in Vipr2−/− mice, the ability of these oscillators to resist phase shifts is compromised. (ljmu.ac.uk)
  • In the first study, 'Flattening of circadian glucocorticoid oscillations drives acute hyperinsulinemia and adipocyte hypertrophy', published in Cell Reports, revealed that stress caused by chronically administering glucocorticoid stress hormones and disturbing the normal daily cycle of release triggers a temporary protective mechanism in mice. (bariatricnews.net)
  • These oscillations, which are autonomously maintained, explain how living organisms adapt their biological rhythm so that it is synchronized with the Earth's revolutions. (sciencedaily.com)
  • Physiological processes are co-ordinated by circadian clocks, that endow tissues with oscillations in gene expression with a period of ~24hr. (ukri.org)
  • It consists of a regulatory network with several intertwine feedback loops that generate sustained oscillations with a period between 20 and 30h. (smb.org)
  • Mammalian circadian rhythms can be observed from the genetic level to the tissue level, and even to the macroscopic level, affecting behavior, biochemical and physiological processes. (frontiersin.org)
  • The physiological properties of most organisms, from cyanobacteria to human, display a circadian (Latin circa dies , or 'about a day') pattern of activity, which is regulated by an endogenous circadian clock. (bioone.org)
  • The circadian clock allows organisms to anticipate periodic changes in environmental circumstance and to change their physiological status accordingly. (bioone.org)
  • Circadian clocks are endogenous oscillators that control 24-h physiological and behavioral processes. (tuni.fi)
  • Circadian rhythms refer to changes in biological processes at the molecular, physiological, and behavioral levels that follow an approximately 24-hour cycle. (medicalnewstoday.com)
  • Our sleep data suggests that disrupting uORFs can have physiological impacts on mice behavior, which shows that you don't have to mutate the protein to have an effect," explains Rikuhiro Yamada who analyzed the phenotype of the mice using the lab's snappy sleep stager system. (eurekalert.org)
  • Biological clock affects the daily rhythm of many physiological processes. (bariatricnews.net)
  • BMAL1 is a core clock transcription factor, which promotes the transcription of downstream clock-controlled genes (CCGs) by targeting the E-box structure in their promoter region to regulate the physiological functions of the body. (biomedcentral.com)
  • Sik3 -/- mice also exhibited other circadian abnormalities, including lengthening of the period, impaired entrainment to the light-dark cycle, phase variation in locomotor activities, and aberrant physiological rhythms. (elifesciences.org)
  • This demonstrates the dual role of the PRRs: as regulators of the central clock components and as physiological repressors of growth," explains Elena Monte. (sciencedaily.com)
  • The mammalian circadian rhythm is controlled by a number of metabolic and physiological core components and the expression of clock genes is a characteristic feature of the central rhythm generator and peripheral oscillators. (wisc.edu)
  • During her postdoctoral research at the University of Chicago, in the lab of Robert Haselkorn, Golden continued to work on developing genetic manipulation techniques for Synechoccus elongatus in order to elucidate mechanisms of gene regulation in photosynthesis genes. (wikipedia.org)
  • New research from a multidisciplinary team helps to illuminate the mechanisms behind circadian rhythms, offering new hope for dealing with jet lag, insomnia and other sleep disorders. (news-medical.net)
  • The research, 'Cryptochrome-Timeless Structure Reveals Circadian Clock Timing Mechanisms' published April 26 in Nature . (news-medical.net)
  • In this talk, I will present the work that we have been doing to not only enhance the understanding of molecular mechanisms regulating circadian clock [1] but also to develop therapeutic interventions to modulate the circadian rhythms in mammals [2, 3]. (imsc.res.in)
  • The variety of mechanisms that have evolved among vertebrates to achieve the same goal-a rhythm in melatonin-underlines the important role melatonin plays as the hormonal signal of environmental lighting in vertebrates. (nih.gov)
  • Although numerous studies exist analyzing the mechanisms of neurodegeneration and circadian rhythm function independently, molecular mechanisms establishing specific links between the two must be explored further. (frontiersin.org)
  • Thus, in this review, we explore the possible intersecting molecular mechanisms between circadian rhythm and neurodegeneration, with a particular focus on Parkinson's disease. (frontiersin.org)
  • To garner a more comprehensive understanding of the effects of circadian rhythms on health and neurodegeneration, the underlying fundamental molecular mechanisms and interrelated processes must be explored ( Cox and Takahashi, 2019 ). (frontiersin.org)
  • Thus, the mechanisms of the central clock seem to be conserved across animal kingdom. (bioone.org)
  • Deborah Bell-Pedersen, Professor and Associate Head of Biology at TAMU is recognized as a leader in understanding the mechanisms by which circadian oscillators control rhythmic gene expression. (tamu.edu)
  • Paul E. Hardin, John W. Lyons Jr. '59 Chair and Distinguished Professor of Biology at TAMU, is internationally recognized as an authority on molecular clock mechanisms and their control of rhythmic outputs. (tamu.edu)
  • To study mechanisms underlying the eclosion gate, we examined eclosion-timing signals from the circadian clock, and the role of 20-hydroxyecdysone in the eclosion gate of the flesh fly, Sarcophaga crassipalpis. (bioone.org)
  • This thermoception may have caused the observed effects through epigenetic mechanisms, since all analysed tissues further revealed differentially expressed genes involved in histone modification. (biomedcentral.com)
  • However, the molecular mechanisms underlying the determination or stabilization of the circadian period and phase remain to be investigated in mammals. (elifesciences.org)
  • In this work, we focus on two deregulated mechanisms in cancer: the immune system and the circadian clock. (smb.org)
  • Since the previous "transmeridian travel", or "circadian disrup- evaluation, new data have become available for tion", and standardized terms for each of the these areas and for carcinogen mechanisms, and relevant outcomes (cancer and mechanisms). (who.int)
  • This internal biological clock regulates a host of cellular responses to the environment, ranging from gene expression and cell division in cyanobacteria, to photosynthesis in plants and finally to the sleep/wake cycles in mammals (commonly referred as circadian rhythms). (imsc.res.in)
  • The internal clock in living beings that regulates sleeping and waking patterns -- usually called the circadian clock -- has often befuddled scientists due to its mysterious time delays. (news-medical.net)
  • The tissue samples were used for multiple molecular analyses, which first of all revealed that the sleep loss condition resulted in a tissue-specific change in DNA methylation, one form of mechanism that regulates gene expression. (neurosciencenews.com)
  • Her work currently focuses on understanding how the clock regulates mRNA transcription and translation, and how defects in the clock are linked to cancer in humans. (tamu.edu)
  • The brain region called the suprachiasmatic nucleus (SCN) serves as the principal circadian clock that regulates these internal rhythms. (medicalnewstoday.com)
  • In this second study, Teruel and her colleagues attached a red fluorescent protein to protein that controls the expression of important circadian clock genes and a yellow fluorescent protein to peroxisome proliferator activated receptor gamma (PPARG), a protein that regulates fat cell production. (bariatricnews.net)
  • At the cell level, the circadian clock is a 24-hour biological oscillator that regulates most intracellular processes. (smb.org)
  • Nuclear receptor subfamily 1 group D member 1 regulates circadian activity of NLRP3 inflammasome to reduce the severity of fulminant hepatitis in mice. (smb.org)
  • Luc) provides a powerful tool to study the regulation of biological clocks in explant tissues, including the retinal clock. (molvis.org)
  • Finally, we compared the phase shift and the period change resulting from two methods of light stimulations of retinal explants: the first involved the transfer of the cultured tissues from the Lumicycle into a light stimulation chamber, while the second used a light delivery apparatus embedded in the Lumicycle. (molvis.org)
  • These participate in transcriptional/translational feedback loops and many homologous clock-components in the fruit fly Drosophila are also expressed in mammalian clock tissues with circadian rhythms. (bioone.org)
  • Food is known to influence clocks in peripheral tissues but it has been unclear how the lack of food influences clock function and the body. (worldhealth.net)
  • A possible explanation for why the two tissues respond in the observed manner could be that overnight wakefulness periods exert a tissue-specific effect on tissues' circadian rhythm, resulting in misalignment between these rhythms. (neurosciencenews.com)
  • In addition to the SCN, almost all cells that are present in tissues and organs in the body contain their own biological clock. (medicalnewstoday.com)
  • The functional role of VPAC2 receptors in rhythm generation and maintenance in these tissues is, however, unknown. (ljmu.ac.uk)
  • Intriguingly, while we found WT SCN and Arc/ME/PT tissues to maintain a consistent circadian phase when cultured, the phase of corresponding Vipr2−/− cultures was reset by cull/culture procedure. (ljmu.ac.uk)
  • Further, our data indicate a link between circadian rhythm strength and the ability of tissues to resist circadian phase resetting. (ljmu.ac.uk)
  • In this study, we used IL-1β, a commonly used inflammatory factor, to induce IDD and found that the IVD clock was dampened in degenerated human nucleus pulposus specimens, rat nucleus pulposus (NP) tissues, and cells. (biomedcentral.com)
  • In addition, NRF2 activation attenuated the dysfunction of NP cells induced by the dampened IVD clock and the degenerative process of NP tissues in an organotypic tissue-explant model. (biomedcentral.com)
  • Human pituitary somatotroph adenoma tissues were obtained at the time of transsphenoidal surgery from 3 acromegalic patients and studied for ghrelin mRNA expression. (nel.edu)
  • Transcriptomes from the tissues of the brain-pituitary-gonad (BPG) axis of T10 samples revealed a differential gene expression profile compared to the other experimental groups, with clustering in a principal component analysis and in heat maps of all differentially expressed genes. (biomedcentral.com)
  • All tissues in the body have an internal biological circadian 'clock' which co-ordinates cellular processes in our tissues and organs according to the time of day or night, creating cycles of biological function every 24h. (ukri.org)
  • Alzheimer's patients exhibit high degradation of the suprachiasmatic nucleus (SCN), the central endogenous circadian timekeeper, and Parkinson's patients have highly disrupted peripheral clock gene expression. (frontiersin.org)
  • The central clock in mammals located in the suprachiasmatic nuclei (SCN) in the brain integrates environmental light transmitted by the retina, and coordinates the peripheral clocks throughout the body. (tuni.fi)
  • Here we extend evidence in AS model mice ( Ube3a m -/ p + ) of paternal UBE3A expression within the suprachiasmatic nucleus (SCN), the master circadian pacemaker. (nature.com)
  • We previously observed persistent expression of UBE3A in the suprachiasmatic nucleus (SCN) of the hypothalamus, the master circadian regulatory region in the mammalian brain, of AS model mice 15 , thus identifying a novel site for relaxation of maternal expression bias of Ube3a in the adult brain. (nature.com)
  • Circadian rhythms in physiology and behavior are coordinated by the brain's dominant circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. (ljmu.ac.uk)
  • Ex vivo suprachiasmatic nucleus slices from Sik3 -/- mice exhibited destabilized and desynchronized molecular rhythms among individual neurons. (elifesciences.org)
  • Circadian rhythms in mammals are governed by the master oscillator located in the hypothalamic suprachiasmatic nucleus (SCN). (elifesciences.org)
  • D. Ono, S. Honma and K. Honma, Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus. (atto.co.jp)
  • Son, K. Kim, Effect of Mefloquine, a Gap Junction Blocker, on Circadian Period2 Gene Oscillation in the Mouse Suprachiasmatic Nucleus Ex Vivo . (atto.co.jp)
  • The SCN assumes the role as the central pacemaker, and through a series of genetic feedback loops and highly coordinated neuronal innervation, endogenous timekeeping activity arises, giving way to the production of circadian rhythm. (frontiersin.org)
  • A set of core genes constitutes this transcriptional pathway that forms the identity of the endogenous circadian pacemaker. (frontiersin.org)
  • The mammalian 12 hr rhythm is cell autonomous, driven by a dedicated 12 hr pacemaker distinct from the circadian clock, and can be entrained in vitro by metabolic and ER stress cues. (utmb.edu)
  • The internal system that maintains circadian rhythms can be formally represented by three different components: namely, an input pathway, the pacemaker itself, and an output pathway ( Dunlap, 1999 ). (bioone.org)
  • The input pathway transmits light and/or thermal, non-photic information from external stimuli to the clock (pacemaker). (bioone.org)
  • We therefore think that the changes we have observed in our new study can constitute another piece of the puzzle of how chronic disruption of sleep and circadian rhythms may impact the risk of developing for example obesity," notes Jonathan Cedernaes. (neurosciencenews.com)
  • Disruption of the circadian clocks that keep the body and its cells entrained to the 24-hour day-night cycle plays a critical role in weight gain, according to a pair of studies by Weill Cornell Medicine investigators. (bariatricnews.net)
  • There are signs that disruption of the peripheral IVD clock is related to the process of intervertebral disc degeneration (IDD). (biomedcentral.com)
  • Targeted disruption of the gene encoding D4Rs reduces the amplitude of the contrast sensitivity rhythm by reducing daytime sensitivity and abolishes the rhythmic expression of Npas2 and Adcy1 mRNA in the ganglion cell layer (GCL) of the retina. (jneurosci.org)
  • The data from this study suggests that sex hormones modulate the pattern of clock gene expression in the OV-BNST and CEA, and provide some insight into gender differences in mood disorders and disruption of circadian functioning. (elsevierpure.com)
  • For Volume 124, the scope of the system- cancer in humans and cancer in experimental atic review encompassed a comprehensive animals formed the basis of the Working Group's search of the literature, focusing on an agent evaluation of "shift work that involves circadian name reflecting variations on "night shift work", disruption" as Group 2A. (who.int)
  • Whereas the metabolic effects of deletion of the positive arm of the clock gene machinery, as in Clock- or Bmal1-deficient mice, have been well characterized, inactivation of Period genes (Per1-3) as components of the negative arm have more complex, sometimes contradictory effects on energy homeostasis. (eur.nl)
  • In this study, we found that the circadian clock of NP cells was totally disrupted by knockdown of the core clock gene brain and muscle arnt-like protein-1 ( Bmal1 ), which thus induced the dysfunction of NP cells. (biomedcentral.com)
  • Next, we explored the mechanism of dampened clock-induced IDD and found that knockdown of Bmal1 decreased the expression of nuclear factor erythroid2-related factor 2 (NRF2), a downstream target gene of Bmal1 , and increased inflammatory response, oxidative stress reaction, and apoptosis of NP cells. (biomedcentral.com)
  • These studies fully demonstrated that the clock molecule BMAL1 plays an important role in maintaining the homeostasis of ECM in articular cartilage. (biomedcentral.com)
  • Luciferase reporter assays demonstrated that the Adcy1 promoter is selectively activated by neuronal PAS-domain protein 2 (NPAS2)/BMAL1. (jneurosci.org)
  • The expression of CAR mRNA throughout the circadian rhythm is reported for the first time in phase with the clock gene Bmal1 and in antiphase with the clock-controlled gene Rev-erbα mRNAs, with a peak at Zeitgeber time (ZT) 20 and a trough at ZT8, and a peak/trough ratio of 2.0. (biomedcentral.com)
  • Thus, expression of the Car gene is expected to occur in antiphase to that of the Per1 gene and in phase with the Bmal1 gene. (biomedcentral.com)
  • In the present study, the expression profile of the Car gene in rat liver was studied in comparison with those of the clock gene Bmal1 , clock-controlled gene Rev-erbα and CAR-dependent PB-inducible CYP2B1/2 gene. (biomedcentral.com)
  • Apart from the clock gene BMAL1 and clock-directed gene REV-ERBα, a time-dependent profile of CAR mRNA expression was observed for the rat liver. (biomedcentral.com)
  • This line of inquiry necessitated the development of a technique for visualizing changes in gene expression in living organisms. (wikipedia.org)
  • The physiology and behavior of almost all living organisms on earth is synchronized to a 24-hour solar cycle by a well-regulated molecular clock mechanism. (imsc.res.in)
  • The circadian clock is an autonomous oscillator responsible for regulating physiology and behavior, thereby conferring adaptive advantage to living organisms by allowing them to anticipate regular changes in their environment. (jneurosci.org)
  • In fact, the first hypotheses about the existence of a circadian clock in living organisms came with the observation of leaf and flower movements in plants. (sciencedaily.com)
  • LUC) circadian reporter knockin mice that differ only in the 3'-UTR region:, which retains the endogenous 3'-UTR and, where the endogenous 3'-UTR was replaced by an SV40 late poly(A). (fsu.edu)
  • An early study in mice showed that expression of Ube3a is nearly exclusively maternal in neurons within the CA3 region of the hippocampus and in cerebellar Purkinje cells, with moderate maternal bias in the cerebral cortex 6 . (nature.com)
  • For instance, mice are nocturnal animals, and most of their food intake occurs during the dark or active period. (medicalnewstoday.com)
  • In addition, mice that are fed a high fat diet during the inactive period (light) show an even greater increase in weight than those maintained on the same diet during the active period, despite consuming the same amounts of calories. (medicalnewstoday.com)
  • We built upon our previous work to precisely quantify the level of circadian proteins in mice held in constant darkness over a 24-hour period, which controls for the confounding effects of light," says corresponding author Hiroki Ueda. (eurekalert.org)
  • And by trying to answer this basic timing question, we found that ribosomes bind an upstream open reading frame in Period2 which altered the amplitude of circadian rhythms and disrupted sleep in mice," adds lead author Arthur Millius. (eurekalert.org)
  • About half of genes in mice and humans have at least one uORF," explains Dimitri Perrin, the team's bioinformatician, "but it's particularly interesting that about 75% of genes associated with circadian rhythms have an uORF, which means that circadian rhythms are particularly susceptible to this type of post-transcriptional regulation. (eurekalert.org)
  • Mice lacking VPAC2 receptors (Vipr2−/−) express disrupted behavioral and metabolic rhythms and show altered SCN neuronal activity and clock gene expression. (ljmu.ac.uk)
  • The second study, 'The circadian clock mediates daily bursts of cell differentiation by periodically restricting cell-differentiation commitment', published in the Proceedings of the National Academy of Sciences, shows that fat cell precursors commit to becoming fat cells during the rest period of mice. (bariatricnews.net)
  • Npas2 −/− and Adcy1 −/− mice show strikingly similar reductions in the contrast sensitivity rhythm to that in mice lacking D4Rs. (jneurosci.org)
  • Moreover, Adcy1 transcript rhythms were abolished in the GCL of Npas2 −/− mice. (jneurosci.org)
  • The coordinated activity of the cellular clock gene network drives rhythmic expression of a plethora of clock-controlled genes that, in turn, regulate rhythmic physiology and metabolism. (tuni.fi)
  • Evidence has been found by University of California scientists of fasting affecting circadian clocks in the liver and skeletal muscle causing them to rewire their metabolism, which can lead to improved health and protection against aging associated diseases, as published in Cell Reports. (worldhealth.net)
  • Fasting influences the circadian clock and fasting driven cellular responses which work together to achieve fasting specific temporal gene regulations, such as skeletal muscle appears to be twice as responsive to fasting as is the liver, explains Paolo Sassone-Corsi who first showed the circadian rhythm metabolism link some 10 years ago, identifying metabolic pathways through which circadian proteins sense cell energy levels. (worldhealth.net)
  • Summary: Researchers report just one night of sleep loss can have a tissue specific impact on metabolism and the regulation of gene expression. (neurosciencenews.com)
  • In a new study, researchers at Uppsala University now demonstrate that one night of sleep loss has a tissue-specific impact on the regulation of gene expression and metabolism in humans. (neurosciencenews.com)
  • The peripheral biological clocks influence the expression of a variety of genes in a cyclical manner, including those involved in metabolic processes, such as glucose and fat metabolism. (medicalnewstoday.com)
  • A lot of forces are working against a healthy metabolism when we are out of circadian rhythm,' explained the senior author of both studies, Dr Mary Teruel, associate professor of biochemistry and a member of the Gale and Ira Drukier Institute for Children's Health at Weill Cornell Medicine. (bariatricnews.net)
  • Effects of bioactive compounds on expression of genes involved in lipid metabolism and fatty acid composition were investigated in Atlantic salmon (Salmo salar L.) primary hepatocytes. (nel.edu)
  • Key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. (affbiotech.com)
  • His subsequent research has defined sequences and factors that control feedback loop progression, identified interlocking feedback loops that control rhythmic transcription and overt rhythms in behavior, and revealed circadian regulation of the olfactory and gustatory systems in Drosophila. (tamu.edu)
  • both VPAC2 receptors and rhythmic clock gene/protein expression have been noted in the arcuate (Arc) and dorsomedial (DMH) nuclei of the mediobasal hypothalamus, and in the pituitary gland. (ljmu.ac.uk)
  • Using innovative cryo-electron microscopy techniques, the researchers have identified the structure of the circadian rhythm photosensor and its target in fruit flies (Drosophila melanogaster), one of the major organisms used to study circadian rhythms. (news-medical.net)
  • As a post-doctoral fellow with Dr. Michael Rosbash at Brandeis University he discovered the first circadian feedback loop in gene expression - regulation of period (per) mRNA cycling by PER protein in Drosophila - which laid the mechanistic framework for circadian timekeeping in all eukaryotes. (tamu.edu)
  • What Is There Left to Learn about the Drosophila Clock? (cshlpress.com)
  • In Drosophila, four to five neurons (brown staining) in each larval brain hemisphere produce autonomous circadian rhythms of period, timeless, Clock and vrille gene expression. (rockefeller.edu)
  • Susan Golden identified genes in the S. elongatus genome that contribute to circadian rhythm through mutational screens using transposons to disrupt genes and their function. (wikipedia.org)
  • Findings suggest that eating late at night may disrupt this rhythm in adipocytes resulting in lower energy expenditure and weight gain. (medicalnewstoday.com)
  • On the other hand, loss of NLRP3 expression may disrupt the circadian regulation necessary for normal lung function. (smb.org)
  • This alters exposure to the regular photoperiod ical studies of night shift work and cancer since and may disrupt circadian rhythms in humans. (who.int)
  • Furthermore, a functional analysis of differentially expressed genes revealed enriched gene ontology terms involved in the regulation of circadian rhythm, histone modification, meiotic nuclear division, and others. (biomedcentral.com)
  • Previous reports have suggested that protein kinases play important roles in the regulation of circadian clocks ( Reischl and Kramer, 2011 ). (elifesciences.org)
  • Genetic and cellular clocks dictate tau (free running period of the organism ∼24 h) and are often entrained by photo-optic cues ( Dunlap and Loros, 2017 ). (frontiersin.org)
  • Teruel and her colleagues also believe learning how to synchronize the body's cellular and master circadian clocks will be essential. (bariatricnews.net)
  • Thanks to the discoveries that these scientists did using the fruit fly, today we know that the organisms have an internal clock built of a set of cellular proteins whose amount oscillates in periods of 24 hours. (sciencedaily.com)
  • Studies in recent years have shown that this elongation of the stem in the young seedlings is controlled by PIF proteins, whose cellular accumulation depends on sunlight. (sciencedaily.com)
  • The overall aim of this project is, therefore, to incorporate the circadian clock into OOAC systems, allowing the cellular 'time of day' to be monitored and for drugs to be tested at different time points that reflect day and night for our organs. (ukri.org)
  • Cellular circadian rhythms can then be induced and monitored non-invasively. (ukri.org)
  • Based on our studies above and available literature, in a recent publication (FASEB J, 23: 2803-2809, 2009), we proposed a hypothesis that SIRT1 inhibition will impart an anti-proliferative response in age-related cancers via resynchronization of deregulated core clock circuitry (circadian rhythm) at the cellular level ( see figure ). (wisc.edu)
  • The target of the cryptochrome photosensor, known as 'Timeless' (TIM), is a large, complex protein that could not previously be imaged and thus its interactions with the cryptochrome are not well understood. (news-medical.net)
  • Much of the hard work of the study went into figuring out how to produce the complex of cryptochrome-TIM so it could be studied, because TIM is such a large, unwieldy protein, Crane said. (news-medical.net)
  • To achieve their results, first author Changfan Lin, M.S. '17, Ph.D. '21, modified the cryptochrome protein to improve the stability of the cryptochrome-TIM complex and used innovative techniques to purify the samples, making them suitable for high-resolution imaging. (news-medical.net)
  • Suh and K. Kim, Identification and Validation of Cryptochrome Inhibitors That Modulate the Molecular Circadian Clock. (atto.co.jp)
  • With suitable delays between the events of gene expression and repression, an oscillation in protein levels is established. (news-medical.net)
  • This oscillation represents the 'the ticking of the clock and seems to be fairly unique to the circadian rhythm,' said senior author Brian Crane, the George W. and Grace L. Todd Professor and chair of chemistry and chemical biology in the College of Arts and Sciences. (news-medical.net)
  • Blue light, Crane said, changes the chemistry and structure of cryptochrome's flavin cofactor, which allows the protein to bind the TIM protein and inhibit TIM's ability to repress gene expression and thereby reset the oscillation. (news-medical.net)
  • The interaction between the proteins is then modulated and the ability of light to reset the oscillation is changed, thus altering the circadian clock and extending the period of the fly's dormancy, which helps it survive the winter. (news-medical.net)
  • The circadian oscillation of xenosensor gene CAR mRNA expression is partially responsible for chronopharmacokinetics and chronopharmacology in disease. (biomedcentral.com)
  • The CYP2B mRNA expression profile was resembled to the circadian oscillation of CAR mRNA but in a much more blunted manner (Fig. 2B ). (biomedcentral.com)
  • Downregulation of the 12 hr gene expression strongly correlates with human hepatic steatosis and steatohepatitis, implying its importance in maintaining metabolic homeostasis. (utmb.edu)
  • Researchers from Uppsala and other groups have in earlier studies shown that metabolic functions that are regulated by e.g. skeletal muscle and adipose tissue are adversely affected by disrupted sleep and circadian rhythms. (neurosciencenews.com)
  • It is interesting that we saw changes in DNA methylation only in adipose tissue, and specifically for genes that have also been shown to be altered at the DNA methylation level in metabolic conditions such as obesity and type 2 diabetes. (neurosciencenews.com)
  • Epigenetic modifications are thought to be able to confer a sort of metabolic "memory" that can regulate how metabolic programmes operate over longer time periods. (neurosciencenews.com)
  • Consistent with this, time-restricted feeding aims to align food intake with circadian rhythms observed in metabolic processes to optimize metabolic health. (medicalnewstoday.com)
  • Teruel and her colleagues are now working to understand why disturbing the daily rhythms of glucocorticoids triggers temporary protective metabolic changes. (bariatricnews.net)
  • Recruits distinct combinations of cofactors to target gene regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. (affbiotech.com)
  • In collaboration with Carl H. Johnson and Takao Kondo, she demonstrated and described the molecular mechanism regulating circadian rhythms in S. elongatus PCC 7942, the only model organism for a prokaryotic circadian clock. (wikipedia.org)
  • In the chicken, cyclic AMP acts primarily at the protein level and a rhythm in AA-NAT mRNA is driven by a noncyclic AMP-dependent mechanism linked to the clock within the pineal gland. (nih.gov)
  • A potential mechanism linking the circadian clock and RPE-function is via the complex interplay of ion channel activities. (tuni.fi)
  • Although many studies have shown that TRF reduces fat mass, understanding the molecular mechanism helps identify which cells and biochemical pathways are activated under TRF to reduce fat and identify potential genes or proteins that can be potentially targeted by drugs to mimic the benefits of TRF. (medicalnewstoday.com)
  • The inhibition could be mimicked by the L-type calcium channel blocker nimodipine (1 μ m ) as well as by protein kinase C (PKC) activators phorbol 12,13-dibutyrate (10 μ m ) and phorbol 12-myristate 13-acetate (500 n m ), and blocked by the PKC inactivator (±)-1-(5-isoquinolinesulfonyl)-2-methylpiperazine (200 μ m ), suggesting a mechanism involving PKC modulation of L-type calcium channels. (jneurosci.org)
  • Hence, we have identified a circadian clock mechanism in a subset of RGCs that modulates an important aspect of retinal physiology and visual processing. (jneurosci.org)
  • Her interest in circadian clocks began with postdoctoral studies in the laboratories of Dr. Jay Dunlap and Dr. Jennifer Loros at Dartmouth Medical School in which she focused on molecular studies of the circadian biological clock in the model organism Neurospora crassa . (tamu.edu)
  • She serves as an Associate Editor of the Journal of Biological Rhythms, and has held several leadership positions in her field, including serving on the Board of Directors for the Society for Research on Biological Rhythms and the Fungal Genetics Society and as Chair of the Neurospora Policy Committee. (tamu.edu)
  • fragmented sleep has been shown to affect tau-protein accumulation in Alzheimer's patients, and rapid eye movement (REM) behavioral disorder is observed in a significant amount of Parkinson's patients. (frontiersin.org)
  • The CRYPTOCHROMEs are critical interaction partners of PERs, and simultaneous deletion of Cry1 and -2 results in behavioral and molecular circadian arrhythmicity. (eur.nl)
  • This indicates that an interval from the Zeitgeber (external environmental cues) input to the behavioral output by the circadian clock is 4.5 h. (bioone.org)
  • The circadian clock of the mammal drives ∼ 24-hour diurnal rhythms in physiology and behavior to adapt to the expected changes of the day-night environment, which plays a pivotal role in maintaining the physical homeostasis [ 10 , 11 ]. (biomedcentral.com)
  • Surprisingly, in Vipr2−/− Arc/ME/PT complex (Arc, median eminence and pars tuberalis), DMH and pituitary, the period, amplitude and rate of damping of rhythms were not significantly different to WT. (ljmu.ac.uk)
  • She transformed Synechococcus elongatus, one of the better studied cyanobacteria species, with a luciferase reporter gene and showed circadian rhythm in bioluminescence. (wikipedia.org)
  • In addition, different parameters may affect the retinal circadian bioluminescence signal and its dynamic in in vitro assays. (molvis.org)
  • In cultured cells, Sik3 -knockdown resulted in abnormal bioluminescence rhythms. (elifesciences.org)
  • H. Kwon, T. Enomoto, M. Shimogawara, K. Yasuda, Y. Nakajima and Y. Ohmiya, Bioluminescence imaging of dual gene expression at the single-cell level. (atto.co.jp)
  • We performed extensive functional characterization of diterpenoid phytoalexin biosynthetic genes in rice, and found that the genes for the biosynthesis of the major diterpenoid phytoalexins, phytocassanes and momilactones, are clustered on chromosomes 2 and 4, and that their expression is coordinately induced in rice cells after elicitation. (go.jp)
  • This study presents a draft hybrid genome assembly for F. religiosa and its functional annotated genes. (biomedcentral.com)
  • One of the best examples of a large functional network is the mammalian circadian oscillator, for which the current core network contains about 30 nodes. (biomedcentral.com)
  • Beginning with time-series gene expression data, the Local Edge Machine (LEM) seeks to find functional network models capable of generating the dynamic behavior of the data (Fig. 1 ). (biomedcentral.com)
  • We are currently evaluating the role and functional significance of SIRT proteins in age-related cancers such as prostate cancer (PCa) and melanoma. (wisc.edu)
  • Researchers at The Rockefeller University have discovered that a variant of the gene CRY1 slows the internal biological clock - called the circadian clock - that normally dictates when you feel sleepy each night and when you're ready to wake. (neurosciencenews.com)
  • Osaka, Japan - Circadian rhythms, the internal biological clocks that regulate our daily activities, are essential for maintaining health and well-being. (eurekalert.org)
  • This reporter system was used to discover three key proteins related to the cyanobacterial clock: KaiA, KaiB, and KaiC. (wikipedia.org)
  • These uORFs were associated with reduced ribosome binding in the main coding sequence and reduced reporter expression in a variety of circadian assays tested by the researchers suggesting a role for uORFs in shaping circadian protein expression. (eurekalert.org)
  • iPSCs can be differentiated into all cell types in the body allowing us to develop a library of novel human iPSC-derived differentiated clock reporter cells. (ukri.org)
  • As such, there's been a surge in interest in time-restricted eating (TRE) , an eating pattern that aligns the time of food intake with the body's circadian rhythms. (medicalnewstoday.com)
  • The research, titled "Circadian ribosome profiling reveals a role for the Period2 upstream open reading frame in sleep," to be published in PNAS , redefines our understanding of how translation and post-transcriptional processes influence the body's internal clock and its impact on sleep patterns. (eurekalert.org)
  • The studies suggest that stress and other factors that throw the body's 'clocks' out of rhythm may contribute to weight gain and suggest new treatment approaches for obesity. (bariatricnews.net)
  • The leaf transcriptomic analysis of the diurnal and nocturnal periods revealed the expression of the significant number of genes involved in the carbon-fixation pathway. (biomedcentral.com)
  • The diurnal difference in CAR mRNA expression might underlie the 1.7-fold difference in the magnitude of the PB-dependent induction of CYP2B1/2 mRNA. (biomedcentral.com)
  • Hepatic PPARα mRNA and protein levels follow a diurnal rhythm which parallels that of circulating corticosterone. (biomedcentral.com)
  • In addition, a basic leucine zipper transcription factor, OsTGAP1, was identified as a key regulator of the coordinated expression of the clustered genes and the methylerythritol phosphate pathway genes. (go.jp)
  • In hypothalamic neurons, modulators such as neuropeptide Y (NPY) and adenosine depress glutamatergic transmission by either a pertussis toxin (PTx)-sensitive G-protein-coupled pathway or by inhibition of voltage-activated calcium channels (VACCs). (jneurosci.org)
  • Our results indicate that the contrast sensitivity rhythm is modulated by D4Rs via a signaling pathway that involves NPAS2-mediated circadian regulation of Adcy1 . (jneurosci.org)
  • This research not only deepens our understanding of circadian rhythm regulation but also opens up new possibilities for developing therapies targeting related processes. (news-medical.net)
  • Circadian clocks regulate a plethora of processes in the RPE including the permeability of the blood-retinal barrier, renewal of photoreceptor outer segments and ion transport. (tuni.fi)
  • Circadian rhythms refer to biologic processes that oscillate with a period of ~24 hr. (nih.gov)
  • These rhythms are sustained by a molecular clock and provide a temporal matrix that ensures the coordination of homeostatic processes with the periodicity of environmental challenges. (nih.gov)
  • While the role of transcription in these rhythms is well-established, a new study sheds light on the critical importance of post-transcriptional processes. (eurekalert.org)
  • They discovered significant differences in the timing of these processes, suggesting a complex post-translational control of circadian protein production. (eurekalert.org)
  • Circadian rhythms work via what are basically genetic feedback loops. (news-medical.net)
  • Circadian clocks are based on transcriptional/translational feedback loops, comprising positive and negative components. (eur.nl)
  • We also found that chitin elicitor receptor kinase OsCERK1 and a mitogen-activated protein kinase cascade, the OsMKK4-OsMPK6 cascade, play essential roles in the elicitor-induced production of diterpenoid phytoalexins. (go.jp)
  • These flies have more of a certain genetic variant that involves a change in the TIM protein, and it wasn't clear why the variation could help them. (news-medical.net)
  • Extensive evidence has revealed that the core clock machinery involves "clock genes" and "clock proteins" functioning as molecular cogs. (bioone.org)
  • Our study demonstrates a circadian rhythm of contrast sensitivity that peaks during the daytime, and that its regulation involves interactions of D4Rs, the clock gene Npas2 , and the clock-controlled gene adenylyl cyclase 1 ( Adcy1 ) in a subset of retinal ganglion cells (RGCs). (jneurosci.org)
  • This involves using the gene editing technique CRISPR to link a luminescent tag to key genes that control the clock. (ukri.org)
  • Summary: A new study reveals those with the 'night owl' variant of the CRY1 gene have longer circadian cycles than other people, making them stay awake for longer at night. (neurosciencenews.com)
  • The SCN receives light cues from the eyes and synchronizes the internal rhythms with daily light-dark cycles. (medicalnewstoday.com)
  • During the last five years, enormous progress has been made in understanding the molecular basis of circadian systems, mainly by molecular genetic studies using the mouse and fly. (bioone.org)
  • Indeed, the network inference problem persists in systems biology, despite an abundance of regulatory evidence in the form of TF binding experiments, genetic screens for candidate nodes, and mutant expression profiling experiments. (biomedcentral.com)
  • Because circadian rhythms play a critical role in determining sleep onset, duration and quality 16 , the possibility has been raised that disruptions in circadian rhythms might underlie the sleep disturbances observed in AS. (nature.com)
  • a mutation in CRY1, a gene that had already been implicated in the circadian cycle. (neurosciencenews.com)
  • The protein made by CRY1 is normally responsible for suppressing some of these genes during certain parts of the cycle. (neurosciencenews.com)
  • But Young and Patke discovered that the mutation identified in the patient made the CRY1 protein more active than usual, keeping other clock genes switched off for a longer period of time. (neurosciencenews.com)
  • During her time as a professor at the Texas A&M, Golden attempted to solve this problem by attaching a luciferase gene to the promoters of the cyanobacterial genes of interest and viewing the colonies with a night vision scope. (wikipedia.org)
  • To find out whether mutations in any known circadian genes were linked to DSPD, Young- - along with research associate Alina Patke, the first and co-corresponding author of the new paper - collaborated with sleep researchers at Weill Cornell Medical College. (neurosciencenews.com)
  • Mutations or deletions of the maternal allele of the UBE3A gene cause Angelman syndrome (AS), a severe neurodevelopmental disorder. (nature.com)
  • Molecular rhythms are blocked, or the pace of the rhythm is altered, in these cells and in the adult by mutations that affect production of the PER, TIM, DBT, CLK, CYC, SGG or VRI proteins. (rockefeller.edu)
  • Incubation with lipoic acid, sesamin and episesamin/sesamin for 48h had significant effect on all analysed genes involved in lipid uptake, β-oxidation, elongation and desaturation, some effects were detected on the expression of peroxisome prolifertor-activated receptor (PPARs). (nel.edu)
  • These lines of evidence suggest that the transcriptional-translational feedback loop mediated by the clock genes, and the post-translational modification of their products, are indispensable to the circadian clock machinery. (elifesciences.org)
  • Young's lab has studied the circadian clock for more than three decades, identifying a number of the genes involved in keeping flies, humans, and other animals on schedule when it comes to eating and sleeping. (neurosciencenews.com)
  • The research focused on fruit fly cryptochromes, key components of the circadian clocks of plants and animals, including humans. (news-medical.net)
  • The evaluation of ghrelin mRNA expression in human somatotroph adenomas. (nel.edu)
  • This finding led her to investigate more generally how light influences expression of photosynthetic genes in the organism and contributes to the overall understanding of bacterial responses to environmental input. (wikipedia.org)
  • This reflects the influences of internal circadian clocks and of light. (nih.gov)
  • Previous studies have shown that NLRP3 transcription is regulated indirectly by REV-ERB α (a nuclear receptor of the circadian clock) in macrophages [1][2]. (smb.org)