CLOCK Proteins
Circadian Clocks
Circadian Rhythm Signaling Peptides and Proteins
Period Circadian Proteins
Biological Clocks
Circadian Rhythm
ARNTL Transcription Factors
Cryptochromes
Casein Kinase Iepsilon
Photoperiod
Suprachiasmatic Nucleus
E-Box Elements
Cyanobacteria
Casein Kinase Idelta
Synechococcus
Drosophila Proteins
Neurospora
Basic Helix-Loop-Helix Transcription Factors
Nuclear Proteins
Photoreceptor Cells, Invertebrate
Transcription Factors
Feedback, Physiological
Drosophila
Trans-Activators
Cell Cycle Proteins
Gene Expression Regulation
Neurospora crassa
Mutation
Phosphorylation
Models, Biological
Molecular Sequence Data
Drosophila melanogaster
Animals, Genetically Modified
Nuclear Receptor Subfamily 1, Group D, Member 1
Arabidopsis Proteins
Amino Acid Sequence
Arabidopsis
Transcription, Genetic
RNA, Messenger
Protein Binding
Active Transport, Cell Nucleus
Dimerization
Mice, Knockout
Protein Structure, Tertiary
Protein Processing, Post-Translational
Mutagenesis
Sequence Homology, Amino Acid
Promoter Regions, Genetic
RNA Interference
Cell Nucleus
Neurons
Gene Expression
Brain
Immunohistochemistry
Base Sequence
PER and TIM inhibit the DNA binding activity of a Drosophila CLOCK-CYC/dBMAL1 heterodimer without disrupting formation of the heterodimer: a basis for circadian transcription. (1/580)
The Drosophila CLOCK (dCLOCK) and CYCLE (CYC) (also referred to as dBMAL1) proteins are members of the basic helix-loop-helix PAS (PER-ARNT-SIM) superfamily of transcription factors and are required for high-level expression of the circadian clock genes period (per) and timeless (tim). Several lines of evidence indicate that PER, TIM, or a PER-TIM heterodimer somehow inhibit the transcriptional activity of a putative dCLOCK-CYC complex, generating a negative-feedback loop that is a core element of the Drosophila circadian oscillator. In this report we show that PER and/or TIM inhibits the binding of a dCLOCK-CYC heterodimer to an E-box-containing DNA fragment that is present in the 5' nontranscribed region of per and acts as a circadian enhancer element. Surprisingly, inhibition of this DNA binding activity by PER, TIM, or both is not accompanied by disruption of the association between dCLOCK and CYC. The results suggest that the interaction of PER, TIM, or both with the dCLOCK-CYC heterodimer induces a conformational change or masks protein regions in the heterodimer, leading to a reduction in DNA binding activity. Together with other findings, our results strongly suggest that daily cycles in the association of PER and TIM with the dCLOCK-CYC complex probably contribute to rhythmic expression of per and tim. (+info)mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. (2/580)
We determined that two mouse cryptochrome genes, mCry1 and mCry2, act in the negative limb of the clock feedback loop. In cell lines, mPER proteins (alone or in combination) have modest effects on their cellular location and ability to inhibit CLOCK:BMAL1 -mediated transcription. This suggested cryptochrome involvement in the negative limb of the feedback loop. Indeed, mCry1 and mCry2 RNA levels are reduced in the central and peripheral clocks of Clock/Clock mutant mice. mCRY1 and mCRY2 are nuclear proteins that interact with each of the mPER proteins, translocate each mPER protein from cytoplasm to nucleus, and are rhythmically expressed in the suprachiasmatic circadian clock. Luciferase reporter gene assays show that mCRY1 or mCRY2 alone abrogates CLOCK:BMAL1-E box-mediated transcription. The mPER and mCRY proteins appear to inhibit the transcriptional complex differentially. (+info)Requirement of circadian genes for cocaine sensitization in Drosophila. (3/580)
The circadian clock consists of a feedback loop in which clock genes are rhythmically expressed, giving rise to cycling levels of RNA and proteins. Four of the five circadian genes identified to date influence responsiveness to freebase cocaine in the fruit fly, Drosophila melanogaster. Sensitization to repeated cocaine exposures, a phenomenon also seen in humans and animal models and associated with enhanced drug craving, is eliminated in flies mutant for period, clock, cycle, and doubletime, but not in flies lacking the gene timeless. Flies that do not sensitize owing to lack of these genes do not show the induction of tyrosine decarboxylase normally seen after cocaine exposure. These findings indicate unexpected roles for these genes in regulating cocaine sensitization and indicate that they function as regulators of tyrosine decarboxylase. (+info)Interlocked feedback loops within the Drosophila circadian oscillator. (4/580)
Drosophila Clock (dClk) is rhythmically expressed, with peaks in mRNA and protein (dCLK) abundance early in the morning. dClk mRNA cycling is shown here to be regulated by PERIOD-TIMELESS (PER-TIM)-mediated release of dCLK- and CYCLE (CYC)-dependent repression. Lack of both PER-TIM derepression and dCLK-CYC repression results in high levels of dClk mRNA, which implies that a separate dClk activator is present. These results demonstrate that the Drosophila circadian feedback loop is composed of two interlocked negative feedback loops: a per-tim loop, which is activated by dCLK-CYC and repressed by PER-TIM, and a dClk loop, which is repressed by dCLK-CYC and derepressed by PER-TIM. (+info)Light-independent role of CRY1 and CRY2 in the mammalian circadian clock. (5/580)
Cryptochrome (CRY), a photoreceptor for the circadian clock in Drosophila, binds to the clock component TIM in a light-dependent fashion and blocks its function. In mammals, genetic evidence suggests a role for CRYs within the clock, distinct from hypothetical photoreceptor functions. Mammalian CRY1 and CRY2 are here shown to act as light-independent inhibitors of CLOCK-BMAL1, the activator driving Per1 transcription. CRY1 or CRY2 (or both) showed light-independent interactions with CLOCK and BMAL1, as well as with PER1, PER2, and TIM. Thus, mammalian CRYs act as light-independent components of the circadian clock and probably regulate Per1 transcriptional cycling by contacting both the activator and its feedback inhibitors. (+info)Cycling vrille expression is required for a functional Drosophila clock. (6/580)
We identified a novel regulatory loop within Drosophila's circadian clock. A screen for clock-controlled genes recovered vrille (vri), a transcription factor essential for embryonic development. vri is expressed in circadian pacemaker cells in larval and adult brains. vri RNA levels oscillate with a circadian rhythm. Cycling is directly regulated by the transcription factors dCLOCK and CYCLE, which are also required for oscillations of period and timeless RNA. Eliminating the normal vri cycle suppresses period and timeless expression and causes long-period behavioral rhythms and arrhythmicity, indicating that cycling vri is required for a functional Drosophila clock. We also show that dCLOCK and VRI independently regulate levels of a neuropeptide, pigment dispersing factor, which appears to regulate overt behavior. (+info)Phosphorylation of the Neurospora clock protein FREQUENCY determines its degradation rate and strongly influences the period length of the circadian clock. (7/580)
Under free running conditions, FREQUENCY (FRQ) protein, a central component of the Neurospora circadian clock, is progressively phosphorylated, becoming highly phosphorylated before its degradation late in the circadian day. To understand the biological function of FRQ phosphorylation, kinase inhibitors were used to block FRQ phosphorylation in vivo and the effects on FRQ and the clock observed. 6-dimethylaminopurine (a general kinase inhibitor) is able to block FRQ phosphorylation in vivo, reducing the rate of phosphorylation and the degradation of FRQ and lengthening the period of the clock in a dose-dependent manner. To confirm the role of FRQ phosphorylation in this clock effect, phosphorylation sites in FRQ were identified by systematic mutagenesis of the FRQ ORF. The mutation of one phosphorylation site at Ser-513 leads to a dramatic reduction of the rate of FRQ degradation and a very long period (>30 hr) of the clock. Taken together, these data strongly suggest that FRQ phosphorylation triggers its degradation, and the degradation rate of FRQ is a major determining factor for the period length of the Neurospora circadian clock. (+info)dCLOCK is present in limiting amounts and likely mediates daily interactions between the dCLOCK-CYC transcription factor and the PER-TIM complex. (8/580)
In Drosophila melanogaster four circadian clock proteins termed PERIOD (PER), TIMELESS (TIM), dCLOCK (dCLK), and CYCLE (CYC/dBMAL1) function in a transcriptional feedback loop that is a core element of the oscillator mechanism. dCLK and CYC are members of the basic helix-loop-helix (bHLH)/PAS (PER-ARNT-SIM) superfamily of transcription factors and are required for high-level expression of per and tim and repression of dClk, whereas PER and TIM inhibit dCLK-CYC-mediated transcription and lead to the activation of dClk. To understand further the dynamic regulation within the circadian oscillator mechanism, we biochemically characterized in vivo-produced CYC, determined the interactions of the four clock proteins, and calculated their absolute levels as a function of time. Our results indicate that throughout a daily cycle the majority of the dCLK present in adult heads stably interacts with CYC, indicating that CYC is the primary in vivo partner of dCLK. dCLK-CYC dimers are bound by PER and TIM during the late evening and early morning, suggesting the formation of a tetrameric complex with impaired transcriptional activity. Although dCLK is present in limiting amounts and CYC is by far the most abundant of the four clock proteins that have been examined, PER and TIM appear to interact preferentially with dCLK. Our results suggest that dCLK is the main component regulating the daily abundance of transcriptionally active dCLK-CYC complexes. (+info)Chronobiology disorders can result when the body's natural circadian rhythm is disrupted or altered, leading to problems with sleep timing, duration, and quality, as well as other physiological and behavioral issues. Examples of chronobiology disorders include:
1. Circadian rhythm sleep disorders: These are conditions that affect the body's natural sleep-wake cycle, such as delayed sleep phase syndrome (DSPS) and advanced sleep phase disorder (ASPD).
2. Jet lag: This occurs when traveling across time zones, causing a mismatch between the body's internal clock and the local environment.
3. Shift work sleep disorder: This affects people who work outside of traditional daytime hours and experience difficulty adjusting to irregular sleep schedules.
4. Irregular sleep-wake patterns: This can be caused by factors such as working night shifts, rotating shifts, or having an irregular sleep schedule.
5. Sleep apnea: A sleep disorder in which a person's breathing is interrupted during sleep, often causing them to wake up frequently throughout the night.
6. Insomnia: Difficulty falling asleep or staying asleep, often caused by stress, anxiety, or other factors that disrupt the body's natural sleep-wake cycle.
7. Depression: A mood disorder that can affect the body's circadian rhythm, leading to changes in sleep patterns and other physiological functions.
8. Bipolar disorder: A mood disorder that can cause changes in sleep patterns, energy levels, and other physiological functions.
9. Seasonal affective disorder (SAD): A type of depression that occurs during the winter months when there is less sunlight.
10. Hypersomnia: Excessive sleepiness or prolonged periods of sleep, often caused by factors such as medication side effects, sleep disorders, or other medical conditions.
It's important to note that these are just a few examples of the many potential causes of irregular sleep patterns, and there may be other underlying factors that contribute to this symptom. If you are experiencing persistent changes in your sleep patterns, it is important to speak with a healthcare professional to determine the cause and find appropriate treatment.
Cyanobacterial clock proteins
Non-POU domain-containing octamer-binding protein
Chromosome 9 open reading frame 43
AutoDock
Ageing
Jrk
Bacterial archaeal holin family
Putative holin-2 family
Prophage Hp1 holin family
PhiU53 holin family
Lysin
P68 holin family
3-Hol family
LP holin family
BP holin family
A2 holin family
Treponema 4 TMS holin family
Hol-Tox family
T-A hol family
NP-holin family
ArpQ holin family
M1 hol family
Gene transfer agent-release holin family
T4 holin
Gp36 hol family
T1 holin family
L2 holin family
XanPHol family
BhlA holin family
Enterobacterial holin family
Securigera varia
Extraordinary Measures
Senescence
Promoter (genetics)
Medieval cuisine
Timeline of human evolution
WNT3A
Oxycodone
Postpartum psychosis
Snail (disambiguation)
Age and female fertility
Salmonidae
Culture Club
AP-1 transcription factor
DNA damage theory of aging
Gary Barnacle discography
Annonaceae
Nocturnin
Monotreme
Semaglutide
Sanju
Gliding motility
Paleogenetics
Epigenomics
Molecular anthropology
List of Ig Nobel Prize winners
Judy Liu
PF-4800567
Food-entrainable oscillator
The Rockefeller University » New research shows how proteins make biological clock tick
Circadian clock protein BMAL1 regulates melanogenesis through MITF in melanoma cells - PubMed
CLOCK PROTEIN arÅŸivleri - KURIOUS
Histone Acetyltransferases - CLOCK Proteins | CU Experts | CU Boulder
Did a jaw muscle protein mutation lead to increased cranial capacity in man?
Altered diurnal variation and localization of clock proteins in the remnant kidney of 5/6 nephrectomy rats. | Nephrology ...
Methods for Delivery of dsRNAi Against Canonical Clock Genes and Immunocytodetection of Clock Proteins in Crustacea<...
Frontiers | Cdc42 Effector Protein 3 Interacts With Cdc42 in Regulating Xenopus Somite Segmentation
What Makes Us Tick: Smoking's Effect on Our Biological Clock - Irfan Rahman, Ph.D.
protein | Virology Blog
NEI Research News | National Eye Institute
Nuclear receptors rock around the clock - PubMed
Epigenetic Clock Marks Age of Human Tissues and Cells | National Institutes of Health (NIH)
Alzheimer's Disease Linked to Dysfunction Circadian Clock
NIOSHTIC-2 Search Results - Full View
Clocks and Rhythms
Dynamic cell fate decisions: linking mechanical signals and protein expression dynamics in the developing eye to understand...
Alcohol Saliva Rapid Test | CE-GMP | 818-591 3030-USA.
Biological Clock | Encyclopedia.com
Publication Detail
Publication Detail
Biomarkers Search
Disrupted Circadian Rhythms Linked to Alzheimer's Disease Signs
Aging research: Blood proteins show your age | National Institute on Aging
Shibai Li | Sloan Kettering Institute
Publications | Hogenesch Lab
Clock
Circadian clock proteins4
- Research on the mechanisms underlying circadian rhythmicity and the response of brain and body clocks to environmental and physiological challenges requires assessing levels of circadian clock proteins. (umassmed.edu)
- The goal of this project was to generate and characterize antibodies against several circadian clock proteins. (umassmed.edu)
- Our results identify antibodies against PER1, PER2, BMAL1 and CLOCK that are useful for assessing circadian clock proteins in the SCN by immunocytochemistry. (umassmed.edu)
- 16. SnapShot: circadian clock proteins. (nih.gov)
Genes14
- Just as a pocket watch requires a complex system of gears and springs to keep it ticking precisely, individual cells have a network of proteins and genes that maintain their own internal clock-a daily rhythm that, in humans, regulates metabolism, cell division and hormone production, as well as the wake-sleep cycle. (rockefeller.edu)
- In the fly, two of those genes-called period and timeless -produce proteins that fluctuate in a negative feedback loop that takes about 24 hours to complete. (rockefeller.edu)
- At night, two other genes, clock and cycle, stimulate production of Period and Timeless proteins, which begin to accumulate in the cell's cytoplasm. (rockefeller.edu)
- Wilcockson, DC , Zhang, L & Kyriacou, CP 2022, Methods for Delivery of dsRNAi Against Canonical Clock Genes and Immunocytodetection of Clock Proteins in Crustacea . (aber.ac.uk)
- Home News Role Identified for Brain Protein Regulated by Circadian Clock Genes in Clearing. (genengnews.com)
- Their work, reported in Science Translational Medicine , found that YKL-40 is both regulated by clock genes and involved in clearing away the potentially toxic build-up of Alzheimer's proteins in the brain. (genengnews.com)
- Musiek, whose work has long focused on the link between circadian rhythm and neurodegenerative diseases such as Alzheimer's, was conducting a screen for genes regulated by the circadian clock when the Chi3l1 gene caught his attention. (genengnews.com)
- The gene for YKL-40 came up as highly regulated by clock genes," Musiek said. (genengnews.com)
- New single cell live imaging approaches are revealing the importance of protein expression dynamics, particularly pulsatile and short-period oscillatory expression of the Hes genes, on the control of cell fate. (findaphd.com)
- 3. Circadian clock genes cause activation of the human PAI-1 gene promoter with 4G/5G allelic preference. (nih.gov)
- 4. A direct repeat of E-box-like elements is required for cell-autonomous circadian rhythm of clock genes. (nih.gov)
- The circadian clock controls the expression of nearly 50% of protein coding genes in mice and most likely in humans as well. (nih.gov)
- It involves various proteins, some of which serve as transcription factors for their own genes, particularly PER (encoded by the per gene) and TIM (encoded by the tim gene). (encyclopedia.com)
- Clock proteins combine with Arntl proteins to form heterodimeric transcription factors that are specific for E-BOX ELEMENTS and stimulate the transcription of several E-box genes that are involved in cyclical regulation. (nih.gov)
Mammalian circadian1
- Partch CL, Shields KF, Thompson CL, Selby CP, Sancar A. Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5. (proteopedia.org)
BMAL15
- Using human melanocytes and melanoma cells under synchronized clock conditions, we observed that the microphthalmia-associated transcription factor (MITF), a rate-limiting protein in melanin synthesis, is expressed rhythmically with 24-hr periodicity in the presence of circadian clock protein, BMAL1. (nih.gov)
- To investigate the localization and diurnal variation of clock proteins (BMAL1, PER2) and clock output protein (DBP) in the remnant kidney of 5/6 nephrectomy rats (STNx). (bvsalud.org)
- Kidneys were collected to detect the localization and expression rhythm of clock proteins (BMAL1, PER2 and DBP) every 4 h throughout the day by immunohistochemistry and Western blotting . (bvsalud.org)
- 19. Synergistic regulation of the mouse orphan nuclear receptor SHP gene promoter by CLOCK-BMAL1 and LRH-1. (nih.gov)
- Because many cellular functions including the cell cycle and cell division are, at least in part, controlled by the molecular clock components (CLOCK, BMAL1, CRYs, PERs), it has also been expected that appropriate timing of chemotherapy may increase the efficacy of chemotherapeutic drugs and ameliorate their side effect. (nih.gov)
Regulates3
- Musiek is senior author of the researchers' paper, which is titled, " Chi3l1 /YKL-40 is controlled by astrocyte circadian clock and regulates neuroinflammation and Alzheimer's disease pathogenesis . (genengnews.com)
- 20. CLOCK regulates circadian platelet activity. (nih.gov)
- This transcriptional activation also sets into motion a time-dependent feedback loop which in turn down-regulates the expression of clock proteins. (nih.gov)
Antibodies3
- Too often, however, it is difficult to acquire antibodies that specifically and reliably label these proteins. (umassmed.edu)
- by Gertrud U. Rey Antibodies are large proteins that are made by B cells of the adaptive immune system. (virology.ws)
- The light-based technique, called luciferase immunoprecipitation system (LIPS), showed high sensitivity and specificity to antibodies against the spike and nucleocapsid proteins of SARS-CoV-2. (nih.gov)
Synthesis4
- Though DNA repair, cell cycle, and apoptosis are clock controlled, the circadian mechanisms associated with melanin synthesis are not well understood. (nih.gov)
- We show that the cost of toxic protein misfolding is small compared to other costs associated with protein synthesis. (nih.gov)
- Today, we continue with the cell - the basic processes of DNA transcription, RNA translation, and protein synthesis. (coturnix.org)
- On episode #30 of the science show This Week in Microbiology, Vincent, Elio, and Michael review how a toxin from Burkholderia pseudomallei inhibits protein synthesis, and the role of the gut microbiome in modulating insulin resistance in mice lacking an innate immune sensor. (virology.ws)
Arntl1
- This gene is upregulated by CLOCK/ARNTL heterodimers but then represses this upregulation in a feedback loop using PER/CRY heterodimers to interact with CLOCK/ARNTL. (nih.gov)
Gene7
- CLOCK is an acronym for "Circadian Locomotor Output Cycles Kaput," because it is a central regulator of gene expression related to the body's circadian rhythm of sleeping and waking. (neurosciencenews.com)
- A recent study identified a possible deactivating mutation in the gene for a human jaw muscle protein (MYH16). (creation.com)
- Here we describe techniques for delivery of dsRNAi molecules to knock down clock gene transcripts in a small intertidal crustacean, Eurydice pulchra, as well as our method for immunodetection of clock proteins in the brain. (aber.ac.uk)
- 1. Identification of the circadian clock-regulated E-box element in the mouse plasminogen activator inhibitor-1 gene. (nih.gov)
- 2. Involvement of circadian clock gene Clock in diabetes-induced circadian augmentation of plasminogen activator inhibitor-1 (PAI-1) expression in the mouse heart. (nih.gov)
- 15. Role for the Clock gene in bipolar disorder. (nih.gov)
- The pattern of PER-, BMAL-, and aryl hydrocarbon receptor-induced P450 gene expression and BaP metabolism was similar to BaP-induced Cyp1A1 and Cyp1B1 and molecular clock gene expression in mouse mammary glands. (nih.gov)
Expression6
- Protein expression level is the dominant determinant of the clock rate in a number of organisms. (nih.gov)
- In particular they measured a notable decrease in the expression of RNA for CLOCK compared to controls. (neurosciencenews.com)
- Expression of other associated proteins in the pathway were also reduced when CLOCK was missing. (neurosciencenews.com)
- We examined mice and hamsters at peak and trough times of clock protein expression in the suprachiasmatic nucleus (SCN). (umassmed.edu)
- 9. Light-inducible and clock-controlled expression of MAP kinase phosphatase 1 in mouse central pacemaker neurons. (nih.gov)
- 11. Ketogenic diet disrupts the circadian clock and increases hypofibrinolytic risk by inducing expression of plasminogen activator inhibitor-1. (nih.gov)
PER11
- SCFbeta-TRCP controls clock-dependent transcription via casein kinase 1-dependent degradation of the mammalian period-1 (Per1) protein. (proteopedia.org)
Reliably2
- But in a recent study in Nature Medicine , an NIH-funded research team was able to gauge a person's age quite reliably by analyzing a blood sample for levels of a few hundred proteins. (nih.gov)
- As further validation, the clock also reliably predicted the correct chronological age of four groups of people not in the study. (nih.gov)
Biological Clocks2
- Based on presentations by world-renowned investigators at the 72nd annual Cold Spring Harbor Symposium on Quantitative Biology, this volume reviews the latest advances in biological clocks and rhythms. (cshlpress.com)
- Biological clocks underlie many of the biorhythms seen in organisms (e.g. hibernation in animals). (encyclopedia.com)
Kinase1
- Her most recent work demonstrating that activation of CRH transcription requires the CREB coactivator, Transducer of Regulated CREB activity (TORC), regulated by the protein kinase, salt inducible kinase (SIK), uncovered a missing link in current knowledge of the regulation of CRH transcription. (nih.gov)
Cells8
- But now, a new report in this week's issue of Science turns the old model on its head: By providing a glimpse into living cells, Rockefeller University researchers have uncovered a previously undetected clock inside the circadian clock. (rockefeller.edu)
- The study provides evidence that excessive excitation of specific brain cells may be due to a lack of CLOCK in the region of the brain that produces the seizures. (neurosciencenews.com)
- One genetically "knocked out" CLOCK in excitatory neurons and the other knocked it out of inhibitory cells. (neurosciencenews.com)
- They found that the excitatory neurons lacking CLOCK were not inherently more excitable, but they received significantly less inhibitory current than similar cells in the same region in healthy controls. (neurosciencenews.com)
- Liu acknowledged that study does not explain why disruption of the CLOCK pathway reduces the inhibitory current within the cells after it arrives via their connections, or "synapses," with other neurons in their circuits. (neurosciencenews.com)
- Cells in nearly every human tissue and organ contain proteins that govern circadian rhythms. (nih.gov)
- After all, those proteins found circulating in the bloodstream come not just from blood cells but also from cells throughout the body. (nih.gov)
- Geldanamycin, an Hsp90 inhibitor, reduces the steady-state abundance of all polyalanine-expanded proteins in transfected cells. (nih.gov)
Regulation3
- While segmentation clock and wave front mechanisms have been elucidated to control the size and time of somite formation, regulation of the segmentation process that physically separates somites is not understood in detail. (frontiersin.org)
- 8. Role of angiotensin and the clock system in the circadian regulation of plasminogen activator inhibitor-1. (nih.gov)
- Basic helix-loop-helix (bHLH) domain-containing proteins that contain intrinsic HISTONE ACETYLTRANSFERASE activity and play important roles in CIRCADIAN RHYTHM regulation. (nih.gov)
Degradation1
- Thus, the difference between HOXA13 polyalanine expansion loss-of-function and HOXD13 polyalanine expansion dominant-negative effect is not the ability to aggregate wild-type group 13 paralogs but perhaps to variation in activities associated with refolding, aggregation or degradation of the proteins. (nih.gov)
Immunocytochemistry1
- To address this paradox we examined the cellular consequences of polyalanine expansions on HOXA13 protein using COS cell transfection and immunocytochemistry. (nih.gov)
Molecular clock2
- The nature of the protein molecular clock, the protein-specific rate of amino acid substitutions, is among the central questions of molecular evolution. (nih.gov)
- The purpose of this study was to define the impact of circadian rhythms on benzo-a-pyrene (BaP) metabolism in the mouse mammary gland and develop a circadian in vitro model for investigating changes in BaP metabolism resulting from cross-talk between the molecular clock and aryl hydrocarbon receptor. (nih.gov)
Body clocks1
- But the 50 subjects in the study whose brains had Alzheimer's-related proteins all had disrupted body clocks. (businessinsider.com)
Mice2
- The mice with loss of CLOCK in excitatory neurons displayed symptoms of epilepsy very similar to the human patients, including greater susceptibility to seizures, particularly arising out of sleep. (neurosciencenews.com)
- Similarly, genetically engineered mice with clock disruption do not exhibit spontaneous or radiation-induced cancers at higher incidence than wild-type controls. (nih.gov)
Disruption3
- Circadian rhythm disruption (i.e., misalignment of circadian rhythms), which results from the lack of synchrony between the master circadian clock located in the suprachiasmatic nuclei (SCN) and the environment (i.e., exposure to day light) or the master clock and the peripheral clocks, has been associated with increased risk of and unfavorable cancer outcomes. (cdc.gov)
- Test whether, and how, molecular and cellular processes, acute or chronic disruption of sleep, and/or circadian rhythms modulate accumulation and/or spreading of pathological protein aggregates. (nih.gov)
- Therefore, disruption of the circadian clock is presumed to have serious pathological effects including cancer. (nih.gov)
Affects4
- Although we cannot rule out the possibility that selection against misfolding toxicity significantly affects the protein clock in species other than E. coli, our results suggest that it is unlikely to be the dominant and universal factor determining the clock rate in all organisms. (nih.gov)
- Because the study directly implicates a specific protein pathway in a specific part of a patient's brain, Liu said a strategy for further research could be to deliver a drug that compensates for the lack of CLOCK, or perhaps a protein it affects, directly in that location. (neurosciencenews.com)
- This process, known as methylation, affects interactions between DNA and protein-making machinery. (nih.gov)
- We hope that a better understanding of how the circadian clock affects YKL-40 could lead to a new strategy for reducing amyloid in the brain. (genengnews.com)
Rhythm3
- Summary: A protein associated with circadian rhythm appears to play a significant role in some forms of epilepsy, researchers say. (neurosciencenews.com)
- Clock proteins showed diurnal rhythm in the kidney of the control. (bvsalud.org)
- But diurnal rhythm of clock proteins changed in the STNx rats . (bvsalud.org)
Endogenous1
- biological clock An endogenous, physiological mechanism, whose exact nature has not been determined, that keeps time independently of external events, enabling organisms to determine and to respond to daily, lunar, seasonal, and other periodicities. (encyclopedia.com)
Bind2
- They discovered that, rather than randomly colliding, the two proteins bind together in the cytoplasm almost immediately and create what Young and Meyer refer to as an "interval timer. (rockefeller.edu)
- This method, which does not require fractionation of the sample by gel electrophoresisis, is based on the property of proteins to readily bind to a plastic surface. (virology.ws)
Blog Around The C1
- Welcome to A Blog Around The Clock. (scienceblogs.com)
Aging3
- The researchers then used data from more than half of the participants to assemble a "proteomic clock" of aging. (nih.gov)
- However, because the effect of aging on the most important proteins of the clock is much stronger than the differences in gender, the proteomic clock still could accurately predict the ages in all people. (nih.gov)
- Overall, the findings show that protein substances in blood can serve as a useful measure of a person's chronological and biological age and - together with Wyss-Coray's earlier studies - that substances in blood may play an active role in the aging process. (nih.gov)
Generate2
- It has been suggested that highly expressed proteins evolve slowly in all species mainly to maintain robustness to translation errors that generate toxic misfolded proteins. (nih.gov)
- Positive feedback loops with substrate depletion can also generate oscillations, inspiring other circadian clock models. (nature.com)
Plaques3
- If your circadian clock is not quite right for years and years-you routinely suffer from disrupted sleep at night and napping during the day-the cumulative effect of chronic dysregulation could influence inflammatory pathways such that you accumulate more amyloid plaques," said Musiek. (genengnews.com)
- This isn't the first study to connect bad sleep with the buildup of proteins known as amyloid plaques, which can be indications of Alzheimer's and dementia. (businessinsider.com)
- They also analyzed their brains to look for Alzheimer's-related proteins and plaques. (businessinsider.com)
Tick1
- Some proteins did gradually tick up or down over time in an almost linear fashion. (nih.gov)
Aggregates4
- Determine processes interrupted by disordered sleep and circadian disruptions that lead to AD/ADRD-related pathologies such as accumulation of protein aggregates, synaptic loss, or dendritic pruning. (nih.gov)
- Assess how various patterns of neuronal activity and sleep architecture modulate accumulation and/or spreading of pathological protein aggregates. (nih.gov)
- HOXA13 polyalanine expansion proteins form cytoplasmic aggregates, and distribution between cytoplasmic aggregates or the nucleus is polyalanine tract size-dependent. (nih.gov)
- We also found that wild-type HOXA13 or HOXD13 proteins are sequestered in HOXA13 polyalanine expansion cytoplasmic aggregates. (nih.gov)
Drosophila2
- What Is There Left to Learn about the Drosophila Clock? (cshlpress.com)
- Studies in the fruit fly Drosophila have revealed the molecular basis of the biological clock, and similar mechanisms are thought to occur in other animals, including mammals. (encyclopedia.com)
Nucleus4
- Prior studies, which examined the placement of Period and Timeless during different stages of the cycle, seemed to indicate that the two proteins idle in a cell's cytoplasm until they bump into each other and then, bound together, enter the nucleus. (rockefeller.edu)
- Then, six hours after coming together, the complexes rapidly break apart and the proteins move into the nucleus singly, all of them within minutes of each other. (rockefeller.edu)
- The proteins pop apart and roll into the nucleus," Young says. (rockefeller.edu)
- The timing of each cycle is determined by the time required for transcription, export of messenger RNA to the cytoplasm, translation, and, crucially, the formation of PER-TIM dimers - the only form in which these two proteins can enter the nucleus. (encyclopedia.com)
Inhibitory2
- Further analysis including in tissues from more patients with other forms of epilepsy also showed that CLOCK RNA and protein were often significantly lacking in both in excitatory and inhibitory neurons in affected brain regions. (neurosciencenews.com)
- The D 2L R/5-HT 1A R inhibitory G-protein-coupled heteromer may function as a negative feedback regulator to suppress psychosocial stress. (jneurosci.org)
Specific protein1
- A more rapid method than Western blot analysis to detect a specific protein in a cell, tissue, organ, or body fluid is enzyme-linked immunosorbent assay, or ELISA. (virology.ws)
Spike1
- One recent study found that even disrupting someone's sleep for a night could lead to a spike in Alzheimer's-related proteins. (businessinsider.com)
Peripheral1
- 17. Peripheral circadian oscillators require CLOCK. (nih.gov)
Mechanisms1
- In addition, research addressing the mechanisms of pulsatility of glucocorticoid secretion recently demonstrated that each ACTH-induced secretory pulse is associated with induction of steroidogenic proteins transcription. (nih.gov)
Genetic2
- Researchers from two independent research teams have discovered how the mislocalization of a protein, known as TDP-43, alters the genetic instructions for UNC13A, providing a possible therapeutic target that could also have implications in treating amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and other forms of dementia. (nih.gov)
- Broadly speaking what I do is take proteins and use chemical and genetic approaches to change their sequence or modify their characteristics and then use a range of techniques to see what has happened. (scienceblogs.com)
Investigate1
- Here we investigate this hypothesis experimentally by comparing the growth rate of Escherichia coli expressing wild type and misfolding-prone variants of the LacZ protein. (nih.gov)
Interactions2
- The method makes it possible to gauge interactions between proteins by fluorescently tagging them and measuring how they react to different wavelengths of light. (rockefeller.edu)
- He notes that this precise timer shows how carefully orchestrated interactions between proteins really are. (rockefeller.edu)
Produce1
- The first step was to analyze the "transcriptome" of the tissues, or the various RNA transcribed from DNA to produce proteins. (neurosciencenews.com)
Neurons2
- In other words, excitatory neurons lacking CLOCK aren't as effectively restrained as they should be, potentially leading to a lower threshold for the onset of seizures, the researchers found. (neurosciencenews.com)
- Notably, D 2L R formed a heteromer with 5-HT 1A R in serotonergic neurons, thereby suppressing 5-HT 1A R-activated G-protein-activated inwardly rectifying potassium conductance in D 2L R-KO serotonergic neurons. (jneurosci.org)
Organisms1
- Among different types of biological oscillations, circadian oscillation is widely spread, as the internal clock of most organisms gets synchronized to the environmental day/night cycle changes. (nature.com)
Variation1
- Altered diurnal variation and localization of clock proteins in the remnant kidney of 5/6 nephrectomy rats. (bvsalud.org)
Molecules1
- In essence, these molecules together act as a microscopic clock timed to waxing and waning sunlight. (nih.gov)
Rhythms2
- Our daily rhythms are set by a master clock in the brain that is driven by the day and night cycle. (genengnews.com)
- A study recently published in the journal JAMA Neurology found that adults with healthy memories who had disrupted circadian rhythms - also known as sleep cycles - had protein buildups of a substance called amyloid plaque, which can serve as an early sign of Alzheimer's. (businessinsider.com)
Cell3
- But no one had ever thought to use it to follow proteins in a single cell for an extended period of time. (rockefeller.edu)
- No one had ever labeled the components to follow them over time, to see one clock as it ticks away in a single cell," Young says. (rockefeller.edu)
- Each cell also maintains its own internal clock, pegged to the master clock. (genengnews.com)
Mechanism3
- While the segmentation clock and wave front mechanism has been established to control the timing and space of somite segmentation, the cellular events that mediate the separation of somites are less understood. (frontiersin.org)
- The circadian system is an innate clock mechanism that governs biological processes on a near 24-hour cycle. (cdc.gov)
- biological clock The mechanism, presumed to exist within many animals and plants, that produces regular periodic changes in behaviour or physiology. (encyclopedia.com)
Humans3
- The protein appeared to have a mutation in all humans that they examined. (creation.com)
- However, chimpanzees, gorillas, orangutans and macaques all express the full-length protein, which is incorporated into Type II bundles, so the jaw muscle is comparatively larger in these animals than in humans (figure 1). (creation.com)
- However, in this case, the mRNA for the protein is transcribed and appropriately spliced, although the protein was undetectable in the humans examined. (creation.com)
Search1
- In search of additional clues in the new study, the Wyss-Coray team tracked how the protein composition of blood changes as people age. (nih.gov)
Metabolic2
- Even in the presence of metabolic fluctuations, the circadian clock functions as a precise biological timekeeper 20 . (nature.com)
- 5. Plasminogen activator inhibitor-1 and the circadian clock in metabolic disorders. (nih.gov)
Disorders1
- Specifically, how and which extracellular matrix proteins promote proliferation over differentiation, a key step in developing potential postnatal treatments for developmental ocular disorders. (findaphd.com)
Human1
- KC1E_HUMAN Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. (proteopedia.org)
Dysfunction1
- The aim of this NOSI is to advance basic and clinical research on the causes and consequences of sleep deficiency and circadian clock dysfunction in AD/ADRD, and the roles of sleep and the circadian clock as modifiers of the onset and progression of neurodegeneration. (nih.gov)