CLOCK

Summary

Gene Symbol: CLOCK
Description: clock circadian regulator
Alias: KAT13D, bHLHe8, circadian locomoter output cycles protein kaput, circadian locomoter output cycles kaput protein, class E basic helix-loop-helix protein 8, clock homolog
Species: human
Products:     CLOCK

Top Publications

  1. Shi J, Wittke Thompson J, Badner J, Hattori E, Potash J, Willour V, et al. Clock genes may influence bipolar disorder susceptibility and dysfunctional circadian rhythm. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:1047-55 pubmed publisher
    ..in a family collection of 36 trios and 79 quads (Sample I), and 10 circadian genes (ARNTL, ARNTL2, BHLHB2, BHLHB3, CLOCK, CRY1, CSNK1D, CSNK1E, DBP, and NR1D1) in an extended family collection of 70 trios and 237 quads (Sample II), ..
  2. Kishi T, Kitajima T, Ikeda M, Yamanouchi Y, Kinoshita Y, Kawashima K, et al. Association study of clock gene (CLOCK) and schizophrenia and mood disorders in the Japanese population. Eur Arch Psychiatry Clin Neurosci. 2009;259:293-7 pubmed publisher
    Recently the clock genes have been reported to play some roles in neural transmitter systems, including the dopamine system, as well as to regulate circadian rhythms...
  3. Curtis A, Seo S, Westgate E, Rudic R, Smyth E, Chakravarti D, et al. Histone acetyltransferase-dependent chromatin remodeling and the vascular clock. J Biol Chem. 2004;279:7091-7 pubmed
    ..coactivators and histone acetyltransferases, p300/CBP, PCAF, and ACTR associate with the bHLH-PAS proteins, CLOCK and NPAS2, to regulate positively clock gene expression...
  4. Garaulet M, Sánchez Moreno C, Smith C, Lee Y, Nicolas F, Ordovas J. Ghrelin, sleep reduction and evening preference: relationships to CLOCK 3111 T/C SNP and weight loss. PLoS ONE. 2011;6:e17435 pubmed publisher
    Circadian Locomotor Output Cycles Kaput (CLOCK), an essential element of the positive regulatory arm in the human biological clock, is involved in metabolic regulation...
  5. Jin X, Shearman L, Weaver D, Zylka M, de Vries G, Reppert S. A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. Cell. 1999;96:57-68 pubmed
    We examined the transcriptional regulation of the clock-controlled arginine vasopressin gene in the suprachiasmatic nuclei (SCN)...
  6. Allebrandt K, Teder Laving M, Akyol M, Pichler I, Muller Myhsok B, Pramstaller P, et al. CLOCK gene variants associate with sleep duration in two independent populations. Biol Psychiatry. 2010;67:1040-7 pubmed publisher
    Sleep is an active and complex behavior, yet it has two straightforward properties-timing and duration. Clock genes are associated with dysfunctional timing of sleep, mood, and obesity disorders, which are commonly associated with sleep ..
  7. Benedetti F, Dallaspezia S, Fulgosi M, Lorenzi C, Serretti A, Barbini B, et al. Actimetric evidence that CLOCK 3111 T/C SNP influences sleep and activity patterns in patients affected by bipolar depression. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:631-5 pubmed
    ..Here we studied the effect of CLOCK 3111 T/C SNP (rs1801260) on the actimetric recorded diurnal activity and nocturnal sleep of 39 bipolar depressed ..
  8. Garaulet M, Lee Y, Shen J, Parnell L, Arnett D, Tsai M, et al. Genetic variants in human CLOCK associate with total energy intake and cytokine sleep factors in overweight subjects (GOLDN population). Eur J Hum Genet. 2010;18:364-9 pubmed publisher
    Despite the importance of total energy intake in circadian system regulation, no study has related human CLOCK gene polymorphisms and food-intake measures...
  9. Doi M, Hirayama J, Sassone Corsi P. Circadian regulator CLOCK is a histone acetyltransferase. Cell. 2006;125:497-508 pubmed
    ..that governs circadian rhythmicity comprises proteins whose interplay generates time-specific transcription of clock genes. The role of chromatin remodeling in a physiological setting such as the circadian clock is yet unclear...

More Information

Publications76

  1. Monteleone P, Tortorella A, Docimo L, Maldonato M, Canestrelli B, De Luca L, et al. Investigation of 3111T/C polymorphism of the CLOCK gene in obese individuals with or without binge eating disorder: association with higher body mass index. Neurosci Lett. 2008;435:30-3 pubmed publisher
    ..that the functional 3111T/C single nucleotide polymorphism (SNP) of the (Circadian locomotor output cycles kaput) CLOCK gene may have a part in the genetic susceptibility to obesity...
  2. Serretti A, Benedetti F, Mandelli L, Lorenzi C, Pirovano A, Colombo C, et al. Genetic dissection of psychopathological symptoms: insomnia in mood disorders and CLOCK gene polymorphism. Am J Med Genet B Neuropsychiatr Genet. 2003;121B:35-8 pubmed
    We investigated the possible effect of the 3111T/C CLOCK gene polymorphism on sleep disorders in a sample of 620 patients affected by major depressive disorder (MDD) and bipolar disorder (BP)...
  3. Crumbley C, Burris T. Direct regulation of CLOCK expression by REV-ERB. PLoS ONE. 2011;6:e17290 pubmed publisher
    ..cellular level by transcriptional feedback loops leading to oscillations in expression of key proteins including CLOCK, BMAL1, PERIOD (PER), and CRYPTOCHROME (CRY)...
  4. Milagro F, Gómez Abellán P, Campion J, Martinez J, Ordovas J, Garaulet M. CLOCK, PER2 and BMAL1 DNA methylation: association with obesity and metabolic syndrome characteristics and monounsaturated fat intake. Chronobiol Int. 2012;29:1180-94 pubmed publisher
    The circadian clock system instructs 24-h rhythmicity on gene expression in essentially all cells, including adipocytes, and epigenetic mechanisms may participate in this regulation...
  5. Scott E, Carter A, Grant P. Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man. Int J Obes (Lond). 2008;32:658-62 pubmed
    Accumulating evidence raises the hypothesis that dysregulation of intrinsic clock mechanisms are involved in the development of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease...
  6. Katzenberg D, Young T, Finn L, Lin L, King D, Takahashi J, et al. A CLOCK polymorphism associated with human diurnal preference. Sleep. 1998;21:569-76 pubmed
    A single nucleotide polymorphism located in the 3' flanking region of the human CLOCK gene was investigated as a predictor of diurnal preference in a population-based random sample of 410 normal adults...
  7. Pedrazzoli M, Louzada F, Pereira D, Benedito Silva A, Lopez A, Martynhak B, et al. Clock polymorphisms and circadian rhythms phenotypes in a sample of the Brazilian population. Chronobiol Int. 2007;24:1-8 pubmed
    A Clock polymorphism T to C situated in the 3' untranslated region (3'-UTR) has been associated with human diurnal preference. At first, Clock 3111C had been reported as a marker for evening preference...
  8. Sookoian S, Gemma C, Gianotti T, Burgueno A, Castano G, Pirola C. Genetic variants of Clock transcription factor are associated with individual susceptibility to obesity. Am J Clin Nutr. 2008;87:1606-15 pubmed
    ..We investigated the role of gene variants and derived haplotypes of the CLOCK transcription factor in obesity and related quantitative metabolic traits...
  9. Sato T, Yamada R, Ukai H, Baggs J, Miraglia L, Kobayashi T, et al. Feedback repression is required for mammalian circadian clock function. Nat Genet. 2006;38:312-9 pubmed
    Direct evidence for the requirement of transcriptional feedback repression in circadian clock function has been elusive...
  10. Pirovano A, Lorenzi C, Serretti A, Ploia C, Landoni S, Catalano M, et al. Two new rare variants in the circadian "clock" gene may influence sleep pattern. Genet Med. 2005;7:455-7 pubmed
  11. Mishima K, Tozawa T, Satoh K, Saitoh H, Mishima Y. The 3111T/C polymorphism of hClock is associated with evening preference and delayed sleep timing in a Japanese population sample. Am J Med Genet B Neuropsychiatr Genet. 2005;133B:101-4 pubmed
    ..we investigated association between the 3111T/C polymorphism in the 3'-flanking region of hClock (Homo sapiens Clock homolog) and ME preference in 421 Japanese subjects...
  12. Bailer U, Wiesegger G, Leisch F, Fuchs K, Leitner I, Letmaier M, et al. No association of clock gene T3111C polymorphism and affective disorders. Eur Neuropsychopharmacol. 2005;15:51-5 pubmed
    b>CLOCK was hypothesised to be related to susceptibility of affective disorders. To test subsamples of affectively disordered patients, we examined age of onset (AoO), numbers of episodes and melancholic type of clinical manifestation...
  13. Benedetti F, Serretti A, Colombo C, Barbini B, Lorenzi C, Campori E, et al. Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness recurrence in bipolar depression. Am J Med Genet B Neuropsychiatr Genet. 2003;123B:23-6 pubmed
    Recent studies showed that a polymorphism (T to C nucleotide substitution) in the 3' flanking region of the human CLOCK gene is associated with diurnal preferences of human healthy subjects, with higher "eveningness" in ..
  14. Garaulet M, Corbalán M, Madrid J, Morales E, Baraza J, Lee Y, et al. CLOCK gene is implicated in weight reduction in obese patients participating in a dietary programme based on the Mediterranean diet. Int J Obes (Lond). 2010;34:516-23 pubmed publisher
    ..Circadian Locomotor Output Cycles Kaput (CLOCK), one of the transcription factors from the positive limb of the molecular clock, is involved in metabolic ..
  15. Kishi T, Kitajima T, Ikeda M, Yamanouchi Y, Kinoshita Y, Kawashima K, et al. CLOCK may predict the response to fluvoxamine treatment in Japanese major depressive disorder patients. Neuromolecular Med. 2009;11:53-7 pubmed publisher
    ..Another study reported an association between clock gene (CLOCK) and improvements in insomnia symptoms from SSRIs treatment...
  16. Hogenesch J, Gu Y, Jain S, Bradfield C. The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc Natl Acad Sci U S A. 1998;95:5474-9 pubmed
    ..We demonstrated that MOP3 interacts with MOP4, CLOCK, hypoxia-inducible factor 1alpha (HIF1alpha), and HIF2alpha...
  17. Garcia Rios A, Gomez Delgado F, Garaulet M, Alcalá Díaz J, Delgado Lista F, Marin C, et al. Beneficial effect of CLOCK gene polymorphism rs1801260 in combination with low-fat diet on insulin metabolism in the patients with metabolic syndrome. Chronobiol Int. 2014;31:401-8 pubmed publisher
    Genetic variation at the Circadian Locomotor Output Cycles Kaput (CLOCK) locus has been associated with lifestyle-related conditions such as obesity, metabolic syndrome (MetS) and cardiovascular diseases...
  18. Lavebratt C, Sjöholm L, Partonen T, Schalling M, Forsell Y. PER2 variantion is associated with depression vulnerability. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:570-581 pubmed publisher
    The circadian clock is driven by transcription-translation feedback loops and regulates rhythms that approximate the 24-hr day-night cycle or light-dark transitions...
  19. Benedetti F, Radaelli D, Bernasconi A, Dallaspezia S, Falini A, Scotti G, et al. Clock genes beyond the clock: CLOCK genotype biases neural correlates of moral valence decision in depressed patients. Genes Brain Behav. 2008;7:20-5 pubmed
    Gene polymorphisms in the mammalian biological clock system influence individual rhythms...
  20. Kissling C, Retz W, Wiemann S, Coogan A, Clement R, Hünnerkopf R, et al. A polymorphism at the 3'-untranslated region of the CLOCK gene is associated with adult attention-deficit hyperactivity disorder. Am J Med Genet B Neuropsychiatr Genet. 2008;147:333-8 pubmed
    ..A 3'-UTR polymorphism of the circadian locomotor output cycles protein kaput (CLOCK) gene, rs1801260, has been linked to disturbed sleep patterns, although both the C-allele and more controversially ..
  21. Takao T, Tachikawa H, Kawanishi Y, Mizukami K, Asada T. CLOCK gene T3111C polymorphism is associated with Japanese schizophrenics: a preliminary study. Eur Neuropsychopharmacol. 2007;17:273-6 pubmed
    The CLOCK gene has attracted attention due to its influence on the circadian rhythm, as well as its impacts on the dopaminergic system...
  22. Hogenesch J, Gu Y, Moran S, Shimomura K, Radcliffe L, Takahashi J, et al. The basic helix-loop-helix-PAS protein MOP9 is a brain-specific heterodimeric partner of circadian and hypoxia factors. J Neurosci. 2000;20:RC83 pubmed
    ..Like its homologs, MOP9 forms a transcriptionally active heterodimer with the circadian CLOCK protein, the structurally related MOP4, and hypoxia-inducible factors, such as HIF1alpha...
  23. Nievergelt C, Kripke D, Barrett T, Burg E, Remick R, Sadovnick A, et al. Suggestive evidence for association of the circadian genes PERIOD3 and ARNTL with bipolar disorder. Am J Med Genet B Neuropsychiatr Genet. 2006;141B:234-41 pubmed
    ..Genetic variations altering functions of genes involved with the input to the circadian clock, in the molecular feedback loops constituting the circadian oscillatory mechanism itself, or in the regulatory ..
  24. Wager Smith K, Kay S. Circadian rhythm genetics: from flies to mice to humans. Nat Genet. 2000;26:23-7 pubmed
    ..and biochemical analysis of these evolutionarily conserved proteins has led to detailed molecular insight into the clock mechanism...
  25. Robilliard D, Archer S, Arendt J, Lockley S, Hack L, English J, et al. The 3111 Clock gene polymorphism is not associated with sleep and circadian rhythmicity in phenotypically characterized human subjects. J Sleep Res. 2002;11:305-12 pubmed
    Mutations in clock genes are associated with abnormal circadian parameters, including sleep...
  26. Li S, Wang M, Ao X, Chang A, Yang C, Zhao F, et al. CLOCK is a substrate of SUMO and sumoylation of CLOCK upregulates the transcriptional activity of estrogen receptor-?. Oncogene. 2013;32:4883-91 pubmed publisher
    ..However, the molecular mechanisms underlying the function of core clock proteins in cancer are still largely undefined...
  27. Garaulet M, Lee Y, Shen J, Parnell L, Arnett D, Tsai M, et al. CLOCK genetic variation and metabolic syndrome risk: modulation by monounsaturated fatty acids. Am J Clin Nutr. 2009;90:1466-75 pubmed publisher
    ..The objective was to study the associations of 5 CLOCK polymorphisms with MetS features by analyzing fatty acid (FA) composition from dietary and red blood cell (RBC) ..
  28. Lee C, Weaver D, Reppert S. Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock. Mol Cell Biol. 2004;24:584-94 pubmed
    The mPER1 and mPER2 proteins have important roles in the circadian clock mechanism, whereas mPER3 is expendable...
  29. Englund A, Kovanen L, Saarikoski S, Haukka J, Reunanen A, Aromaa A, et al. NPAS2 and PER2 are linked to risk factors of the metabolic syndrome. J Circadian Rhythms. 2009;7:5 pubmed publisher
    Mammalian circadian clocks control multiple physiological events. The principal circadian clock generates seasonal variations in behavior as well...
  30. Nicholas B, Rudrasingham V, Nash S, Kirov G, Owen M, Wimpory D. Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis. Mol Psychiatry. 2007;12:581-92 pubmed
    b>Clock gene anomalies have been suggested as causative factors in autism...
  31. McClung C. Role for the Clock gene in bipolar disorder. Cold Spring Harb Symp Quant Biol. 2007;72:637-44 pubmed publisher
    ..However, it is still uncertain whether clock abnormalities are the cause of bipolar disorder or if these rhythm disruptions are secondary to alterations in ..
  32. Serretti A, Cusin C, Benedetti F, Mandelli L, Pirovano A, Zanardi R, et al. Insomnia improvement during antidepressant treatment and CLOCK gene polymorphism. Am J Med Genet B Neuropsychiatr Genet. 2005;137B:36-9 pubmed
    ..In the present study, we investigated the possible effect of the 3111 T/C circadian locomotor output cycles kaput (CLOCK) gene polymorphism on insomnia symptomatology during antidepressant treatment...
  33. Sasaki M, Yoshitane H, Du N, Okano T, Fukada Y. Preferential inhibition of BMAL2-CLOCK activity by PER2 reemphasizes its negative role and a positive role of BMAL2 in the circadian transcription. J Biol Chem. 2009;284:25149-59 pubmed publisher
    In the molecular oscillatory mechanism governing circadian rhythms, positive regulators, including CLOCK and BMAL1, transactivate Per and Cry genes through E-box elements, and translated PER and CRY proteins negatively regulate their own ..
  34. Iwase T, Kajimura N, Uchiyama M, Ebisawa T, Yoshimura K, Kamei Y, et al. Mutation screening of the human Clock gene in circadian rhythm sleep disorders. Psychiatry Res. 2002;109:121-8 pubmed
    We tested whether the human Clock (hClock) gene, one of the essential components of the circadian oscillator, is implicated in the vulnerability to delayed sleep phase syndrome (DSPS) and non-24-hour sleep-wake syndrome (N-24)...
  35. Kovanen L, Saarikoski S, Aromaa A, Lonnqvist J, Partonen T. ARNTL (BMAL1) and NPAS2 gene variants contribute to fertility and seasonality. PLoS ONE. 2010;5:e10007 pubmed publisher
    ..Abnormalities in these clocks may be a health hazard. Circadian clock gene polymorphisms have been linked to sleep, mood and metabolic disorders...
  36. Rutter J, Reick M, Wu L, McKnight S. Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science. 2001;293:510-4 pubmed
    b>Clock:BMAL1 and NPAS2:BMAL1 are heterodimeric transcription factors that control gene expression as a function of the light-dark cycle...
  37. Archer S, Robilliard D, Skene D, Smits M, Williams A, Arendt J, et al. A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference. Sleep. 2003;26:413-5 pubmed
    ..The shorter allele was strongly associated with the delayed sleep phase syndrome patients, 75% of whom were homozygous. The length of the Per3 repeat region identifies a potential genetic marker for extreme diurnal preference. ..
  38. Nakashima A, Kawamoto T, Honda K, Ueshima T, Noshiro M, Iwata T, et al. DEC1 modulates the circadian phase of clock gene expression. Mol Cell Biol. 2008;28:4080-92 pubmed publisher
    DEC1 suppresses CLOCK/BMAL1-enhanced promoter activity, but its role in the circadian system of mammals remains unclear...
  39. Steeves T, King D, Zhao Y, Sangoram A, Du F, Bowcock A, et al. Molecular cloning and characterization of the human CLOCK gene: expression in the suprachiasmatic nuclei. Genomics. 1999;57:189-200 pubmed
    The Clock gene is an essential regulator of circadian rhythms. It encodes a member of the basic helix-loop-helix/PER-ARNT-SIM family of transcription factors known to play a central role in the control of diverse cellular events...
  40. Delezie J, Dumont S, Sandu C, Reibel S, Pevet P, Challet E. Rev-erb? in the brain is essential for circadian food entrainment. Sci Rep. 2016;6:29386 pubmed publisher
    ..Here we report that deletion of the clock component Rev-erb? impairs food entrainment in mice...
  41. Riede S, van der Vinne V, Hut R. The flexible clock: predictive and reactive homeostasis, energy balance and the circadian regulation of sleep-wake timing. J Exp Biol. 2017;220:738-749 pubmed publisher
    ..This Review illustrates how the timing of daily rhythms is reciprocally linked to energy homeostasis, and it highlights the importance of this link in understanding daily rhythms in physiology and behavior. ..
  42. Fahrenkrug J, Georg B, Hannibal J, Jørgensen H. Hypophysectomy abolishes rhythms in rat thyroid hormones but not in the thyroid clock. J Endocrinol. 2017;233:209-216 pubmed publisher
    ..nucleus (SCN) as well as multiple peripheral clocks, but information on the existence and function of a thyroid clock is limited...
  43. Yamamoto M, Matsumura Y, Gomi R, Matsuda T, Tanaka M, Nagao M, et al. Interspecies Dissemination of a Mobilizable Plasmid Harboring blaIMP-19 and the Possibility of Horizontal Gene Transfer in a Single Patient. Antimicrob Agents Chemother. 2016;60:5412-9 pubmed publisher
    ..Phylogenetic and molecular clock analysis of K...
  44. Jiang N, Wang Z, Cao J, Dong Y, Chen Y. Role of monochromatic light on daily variation of clock gene expression in the pineal gland of chick. J Photochem Photobiol B. 2016;164:57-64 pubmed publisher
    The avian pineal gland is a master clock that can receive external photic cues and translate them into output rhythms...
  45. Scoffone C, Cracco C. The en-bloc no-touch holmium laser enucleation of the prostate (HoLEP) technique. World J Urol. 2016;34:1175-81 pubmed publisher
    ..of the left lobe laterally to the veru montanum, extending the incision retrogradely towards the bladder at 5 o'clock; (2) the en-bloc enucleation of a horseshoe-like adenoma, sparing the 7 and 12 o'clock incisions; (3) the use of ..
  46. Cain S, Chang A, Vlasac I, Tare A, Anderson C, Czeisler C, et al. Circadian Rhythms in Plasma Brain-derived Neurotrophic Factor Differ in Men and Women. J Biol Rhythms. 2017;32:75-82 pubmed publisher
    ..The timing of the acrophase of the BDNF rhythm, however, was unrelated to clock time in women, while it was related to clock time in men...
  47. Abe J, Hiyama T, Mukaiyama A, Son S, Mori T, Saito S, et al. Circadian rhythms. Atomic-scale origins of slowness in the cyanobacterial circadian clock. Science. 2015;349:312-6 pubmed publisher
    ..triphosphate (ATP) catalytic region [adenosine triphosphatase (ATPase)] in the amino-terminal half of the clock protein KaiC as the minimal pacemaker that controls the in vivo frequency of the cyanobacterial clock...
  48. Ren S, Hao Y, Chen B, Yin Y. Global Transcriptome Sequencing Reveals Molecular Profiles of Summer Diapause Induction Stage of Onion Maggot, Delia antiqua (Diptera: Anthomyiidae). G3 (Bethesda). 2018;8:207-217 pubmed publisher
    ..A subset of genes, including circadian clock genes, were expressed differentially under diapause induction conditions, and there was much more variation in the ..
  49. Skarke C, Lahens N, Rhoades S, Campbell A, Bittinger K, Bailey A, et al. A Pilot Characterization of the Human Chronobiome. Sci Rep. 2017;7:17141 pubmed publisher
    Physiological function, disease expression and drug effects vary by time-of-day. Clock disruption in mice results in cardio-metabolic, immunological and neurological dysfunction; circadian misalignment using forced desynchrony increases ..
  50. Li A, Lin X, Tan X, Yin B, Han W, Zhao J, et al. Circadian gene Clock contributes to cell proliferation and migration of glioma and is directly regulated by tumor-suppressive miR-124. FEBS Lett. 2013;587:2455-60 pubmed publisher
    Although the roles of circadian Clock genes and microRNAs in tumorigenesis have been profoundly studied, mechanisms of cross-talk between them in regulation of gliomagenesis are poorly understood...
  51. Li G, Cleland T. A coupled-oscillator model of olfactory bulb gamma oscillations. PLoS Comput Biol. 2017;13:e1005760 pubmed publisher
    ..in the gamma band, the phase-restriction of informative spikes in principal neurons with respect to this common clock, and the robustness of this synchronous oscillatory regime to multiple challenging conditions observed in the ..
  52. Zhang L, Prosdocimo D, Bai X, Fu C, Zhang R, Campbell F, et al. KLF15 Establishes the Landscape of Diurnal Expression in the Heart. Cell Rep. 2015;13:2368-2375 pubmed publisher
    ..Depletion of KLF15 in cardiomyocytes leads to a disorganized oscillatory behavior without phasic partition despite an intact core clock. Thus, KLF15 is a nodal connection between the clock and meaningful rhythmicity in the heart.
  53. Ng F, Jackson F. The ROP vesicle release factor is required in adult Drosophila glia for normal circadian behavior. Front Cell Neurosci. 2015;9:256 pubmed publisher
    ..ROP reveals reduced protein in glial cell processes and an accumulation of the Par Domain Protein 1ε (PDP1ε) clock output protein in the small lateral clock neurons...
  54. Ziv Gal A, Flaws J, Mahoney M, Miller S, Zacur H, Gallicchio L. Genetic polymorphisms in the aryl hydrocarbon receptor-signaling pathway and sleep disturbances in middle-aged women. Sleep Med. 2013;14:883-7 pubmed publisher
    ..in the aryl hydrocarbon receptor (AHR)-signaling pathway and circadian locomotor output cycles kaput (CLOCK) are associated with insomnia and early awakening in middle-aged women...
  55. Hasler B. Commentary on Bedroom Light Exposure at Night and the Incidence of Depressive Symptoms: A Longitudinal Study of the HEIJOKYO Cohort (Obayashi et al.). Am J Epidemiol. 2017;: pubmed publisher
    In modern society, we are increasingly disconnected from natural light/dark cycles and beset by round-the-clock exposure to artificial light...
  56. O Reilly J, Donoghue P. The Efficacy of Consensus Tree Methods for Summarising Phylogenetic Relationships from a Posterior Sample of Trees Estimated from Morphological Data. Syst Biol. 2017;: pubmed publisher
    ..The rise of morphological clock and sampled-ancestor methods of divergence time estimation, in which times and topology are co-estimated, has ..
  57. Zhu Y, Stevens R, Hoffman A, FitzGerald L, Kwon E, Ostrander E, et al. Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study. Cancer Res. 2009;69:9315-22 pubmed publisher
    ..rs1012477 in PER3; rs1534891 in CSNK1E; rs12315175 in CRY1; rs2292912 in CRY2; rs7950226 in ARNTL; rs11133373 in CLOCK; and rs1369481, rs895521, and rs17024926 in NPAS2) was significantly associated with susceptibility to prostate ..
  58. Fraïsse C, Gunnarsson P, Roze D, Bierne N, Welch J. The genetics of speciation: Insights from Fisher's geometric model. Evolution. 2016;70:1450-64 pubmed publisher
    ..and asymmetry), and the major patterns in overall hybrid fitnesses (including Haldane's Rule, the speciation clock, heterosis, hybrid breakdown, and male-female asymmetry in the F1)...
  59. Das S, Mohamed A, Sangwan V. Clinical course and outcomes in patients with Mooren ulcer who had cataract surgery. J Cataract Refract Surg. 2017;43:1044-1049 pubmed publisher
    ..Of 22 patients (26 eyes), the mean corneal ulceration was 6.8 clock hours ± 2.9 (SD). Corticosteroids were the most commonly used (84...
  60. Xiang J, Reding K, Heffer A, Pick L. Conservation and variation in pair-rule gene expression and function in the intermediate-germ beetle Dermestes maculatus. Development. 2017;144:4625-4636 pubmed publisher
    ..Our results suggest general conservation of clock-like regulation of PR stripe addition in sequentially segmenting species while highlighting regulatory rewiring ..
  61. Barry C, Schmitz M, Jiang P, Schwartz M, Duffin B, Swanson S, et al. Species-specific developmental timing is maintained by pluripotent stem cells ex utero. Dev Biol. 2017;423:101-110 pubmed publisher
    ..These results suggest the existence of a cell autonomous, species-specific developmental clock that pluripotent stem cells maintain even out of context of an intact embryo.
  62. Tokuda I, Okamoto A, Matsumura R, Takumi T, Akashi M. Potential contribution of tandem circadian enhancers to nonlinear oscillations in clock gene expression. Mol Biol Cell. 2017;28:2333-2342 pubmed publisher
    ..studies have long suggested that multiple nonlinear processes are required for autonomous circadian oscillation in clock gene expression, the underlying mechanism remains controversial...
  63. Potdar V, Hinge D, Dakhave M, Manchanda A, Jadhav N, Kulkarni P, et al. Molecular detection and characterization of Influenza 'C' viruses from western India. Infect Genet Evol. 2017;54:466-477 pubmed publisher
    ..Bayesian clock studies conclude that the Indian strains may have emerged through multiple reassortment events.
  64. Hosoda H, Kato K, Asano H, Ito M, Kato H, Iwamoto T, et al. CBP/p300 is a cell type-specific modulator of CLOCK/BMAL1-mediated transcription. Mol Brain. 2009;2:34 pubmed publisher
    ..tissue-specific regulation of the rhythm of circadian transcription, suggesting that transcription factor complex CLOCK/BMAL1, essential for maintaining circadian rhythm, regulates transcription in a tissue-specific manner...
  65. Nitabach M, Sheeba V, Vera D, Blau J, Holmes T. Membrane electrical excitability is necessary for the free-running larval Drosophila circadian clock. J Neurobiol. 2005;62:1-13 pubmed
    ..of period (PER) and timeless (TIM) proteins that constitute the core of the cell-autonomous circadian molecular clock. Despite similarities between the adult and larval molecular oscillators, adults and larvae differ substantially ..
  66. Whitt J, McNally B, Meredith A. Differential contribution of Ca2+ sources to day and night BK current activation in the circadian clock. J Gen Physiol. 2018;150:259-275 pubmed publisher
    ..In neurons within the suprachiasmatic nucleus (SCN)-the brain's circadian clock-BK current, VGCC current, and Ca2+i are diurnally regulated, but paradoxically, BK current ..
  67. Nippe O, Wade A, Elliott C, Chawla S. Circadian Rhythms in Visual Responsiveness in the Behaviorally Arrhythmic Drosophila Clock Mutant ClkJrk. J Biol Rhythms. 2017;32:583-592 pubmed publisher
    ..potentials (SSVEPs) to examine how visual responsiveness in wild-type Drosophila melanogaster and the circadian clock mutant ClkJrk varies over circadian time...