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Clara Bien Peek, Daniel C Levine, Jonathan Cedernaes, Akihiko Taguchi, Yumiko Kobayashi, Stacy J Tsai, Nicolle A Bonar, Maureen R McNulty, Kathryn Moynihan Ramsey, Joseph Bass
Circadian clocks are encoded by a transcription-translation feedback loop that aligns energetic processes with the solar cycle. We show that genetic disruption of the clock activator BMAL1 in skeletal myotubes and fibroblasts increased levels of the hypoxia-inducible factor 1α (HIF1α) under hypoxic conditions. Bmal1(-/-) myotubes displayed reduced anaerobic glycolysis, mitochondrial respiration with glycolytic fuel, and transcription of HIF1α targets Phd3, Vegfa, Mct4, Pk-m, and Ldha, whereas abrogation of the clock repressors CRY1/2 stabilized HIF1α in response to hypoxia...
October 19, 2016: Cell Metabolism
Song Wu, Andrew Fesler, Jingfang Ju
AIM: To establish a connection between microRNA (miRNAs), circadian rhythm, and colorectal cancer patient survival. METHODS: Genomic and clinical data were extracted from The Cancer Genome Atlas (TCGA) colorectal cancer database, and the expression levels of candidate miRNAs and a set of circadian rhythm-related genes (Per1, Per2, Per3, Bmal1), and genes associated with chemosensitivity (thymidylate synthase, dihydrofolate reductase) were assessed for any correlations among their expression...
January 2016: Cancer Transl Med
Jennifer Gile, Tobias Eckle
Cardiovascular disease is the number one cause of death worldwide. A powerful strategy for cardioprotection would be to identify specific molecules or targets that mimic ischemic preconditioning (IP), where short non-lethal episodes of ischemia and reperfusion prior to myocardial infarction result in dramatic reduction of infarct sizes. Since 1960 researchers believed that adenosine has a strong cardio-protective potential. In fact, with the discovery of cardiac IP in 1986 by Murry et al., adenosine was the first identified molecule that was used in studying the underlying mechanism of IP...
2016: Journal of Nature and Science
Malini Riddle, Erica Mezias, Duncan Foley, Joseph LeSauter, Rae Silver
The hypothalamic suprachiasmatic nucleus (SCN), locus of the master circadian clock, bears many neuronal types. At the cellular-molecular level, the clock is comprised of feedback loops involving "clock" genes including Period1 and Period2, and their protein products, PERIOD1 and PERIOD2 (PER1/2). In the canonical model of circadian oscillation, the PER1/2 proteins oscillate together. While their rhythmic expression in the SCN as a whole has been described, the possibility of regional differences is unknown...
October 14, 2016: European Journal of Neuroscience
Zsolt Nagy, Alexa Marta, Henriett Butz, Istvan Liko, Karoly Racz, Attila Patocs
Peripheral clocks are set by different nervous, hormonal and metabolic stimuli, and regulate the circadian expression of several genes. We investigated whether a peripheral clock could be induced in the human adrenocortical cell line H295R and whether glucocorticoid receptor isoforms (GRα and GRß) are involved in this clock system. After synchronization of cells with serum shock, the rhythmic oscillation of clock genes PER1, PER2, REV-ERBα, and ARNTL was confirmed. In addition, H295R cells even without serum shock showed rhythmic expression of PER1, PER2, CRY1 and ARNTL...
October 7, 2016: Steroids
Leena Kovanen, Kati Donner, Mari Kaunisto, Timo Partonen
BACKGROUND: Dysfunctions in the intrinsic clocks are suggested in patients with depressive disorders. The cryptochrome circadian clocks 1 and 2 (CRY1 and CRY2) proteins modulate circadian rhythms in a cell and influence emotional reactions and mood in an individual. The protein kinase C delta binding protein (PRKCDBP, or CAVIN3), similar to the serum deprivation response protein (SDPR, or CAVIN2), reduces metabolic stability of the PER2-CRY2 transcription factor complex that plays a role in the circadian rhythm synchronization...
September 28, 2016: Journal of Affective Disorders
Takafumi Fukuda, Atsushi Haraguchi, Mari Kuwahara, Kaai Nakamura, Yutaro Hamaguchi, Yuko Ikeda, Yuko Ishida, Guanying Wang, Chise Shirakawa, Yoko Tanihata, Kazuaki Ohara, Shigenobu Shibata
The peripheral circadian clock is entrained by factors in the external environment such as scheduled feeding, exercise, and mental and physical stresses. In addition, recent studies in mice demonstrated that some food components have the potential to control the peripheral circadian clock during scheduled feeding, although information about these components remains limited. l-Ornithine is a type of non-protein amino acid that is present in foods and has been reported to have various physiological functions...
October 5, 2016: Scientific Reports
Sarah D Linnstaedt, Kyle D Riker, Margaret G Walker, Jennifer E Nyland, Erin Zimny, Christopher Lewandowski, Phyllis L Hendry, Kathia Damiron, Claire Pearson, Marc-Anthony Velilla, Jeffrey Jones, Robert A Swor, Robert Domeier, Samuel A McLean
Study Design Prospective human cohort study combined with molecular studies. Background A microRNA is a small, noncoding RNA molecule that can play a role in disease onset. Recent studies found that circulating levels of microRNA 320a (miR-320a) are associated with musculoskeletal pain conditions and that miR-320a is stress responsive. Objectives To investigate whether circulating expression levels of miR-320a in the peritraumatic period predict persistent axial musculoskeletal pain 6 months after motor vehicle collision (MVC)...
October 2016: Journal of Orthopaedic and Sports Physical Therapy
Satish Sen, Hélène Raingard, Stéphanie Dumont, Andries Kalsbeek, Patrick Vuillez, Etienne Challet
Restricted feeding during the resting period causes pronounced shifts in a number of peripheral clocks, but not the central clock in the suprachiasmatic nucleus (SCN). By contrast, daily caloric restriction impacts also the light-entrained SCN clock, as indicated by shifted oscillations of clock (PER1) and clock-controlled (vasopressin) proteins. To determine if these SCN changes are due to the metabolic or timing cues of the restricted feeding, mice were challenged with an ultradian 6-meals schedule (1 food access every 4 h) to abolish the daily periodicity of feeding...
September 26, 2016: Chronobiology International
Vaishnavi Jadhav, Qianyi Luo, James M Dominguez, Jude Al-Sabah, Brahim Chaqour, Maria B Grant, Ashay D Bhatwadekar
Period 2-mutant mice (Per2m/m), which possess a circadian dysfunction, recapitulate the retinal vascular phenotype similar to diabetic retinopathy (DR). The vascular dysfunction in Per2m/m is associated with an increase in connective tissue growth factor (CTGF/CCN2). At the molecular level, CTGF gene expression is dependent on the canonical Wnt/β-catenin pathway. The nuclear binding of β-catenin to a transcription factor, lymphoid enhancer binding protein (Lef)/ T-cell factor (TCF/LEF), leads to downstream activation of CTGF...
2016: PloS One
Hye-Min Song, Chul-Hyun Cho, Heon-Jeong Lee, Joung Ho Moon, Seung-Gul Kang, Ho-Kyoung Yoon, Young-Min Park, Leen Kim
Polymorphisms in human circadian genes are potential genetic markers that affect diurnal preference in several populations. In this study, we evaluated whether four polymorphisms in circadian genes CLOCK, ARNTL, PER2, and GNB3 were associated with diurnal preference in a Korean population. In all, 499 healthy subjects were genotyped for four functional polymorphisms in CLOCK, ARNTL, PER2, and GNB3. Composite scale of morningness (CSM) was applied to measure phenotype patterns of human diurnal preference. In addition, three subscale scores, i...
September 23, 2016: Chronobiology International
Zsofia Kiss, Paramita M Ghosh
The androgen receptor (AR) plays a key role in the development and progression of prostate cancer (CaP). Since the mid-1990s, reports in the literature pointed out higher incidences of CaP in some select groups, such as airline pilots and night shift workers in comparison to those working regular hours. The common finding in these 'high-risk' groups was that they all experienced a deregulation of the body's internal circadian rhythm. Here we discuss how the circadian rhythm affects androgen levels and modulates CaP development and progression...
September 22, 2016: Endocrine-related Cancer
Daisuke Ono, Sato Honma, Ken-Ichi Honma
The suprachiasmatic nucleus (SCN) is the site of the master circadian clock in mammals. The SCN neural network plays a critical role in expressing the tissue-level circadian rhythm. Previously, we demonstrated postnatal changes in the SCN network in mice, in which the clock gene products CRYPTOCHROMES (CRYs) are involved. Here, we show that vasoactive intestinal polypeptide (VIP) signaling is essential for the tissue-level circadian PER2::LUC rhythm in the neonatal SCN of CRY double-deficient mice (Cry1,2 (-/-) )...
September 2016: Science Advances
Li Chang, Lan Li, Wenhui Li, Meiping Jiang, Yunhe Jv, Li Wang, Yu Hou, Qing Long, Shuhui Yu
PURPOSE: To investigate the radiation effects and acute damage in inoperable cervical cancer patients irradiated at different times as well as the underlying mechanisms. METHODS: 67 patients were randomized to a morning group (MG, 9:00 - 11:00 AM) and an evening group (EG, 9:00 - 11:00 PM) and both received external beam radiotherapy (RT) (50 Gy in 25 fractions) at different times. Brachytherapy (36 - 42 Gy in 6 - 7 fractions) was also performed to enhance the radiation response twice every week in all patients at the same time...
November 2016: International Journal of Clinical Pharmacology and Therapeutics
Minghui Chen, Yanwen Xu, Benyu Miao, Hui Zhao, Lu Luo, Huijuan Shi, Canquan Zhou
BACKGROUND: Previous studies have shown that circadian genes might be involved in the development of polycystic ovarian syndrome (PCOS). Hyperandrogenism is a hallmark feature of PCOS. However, the effect of hyperandrogenism on circadian gene expression in human granulosa cells is unknown, and the general expression pattern of circadian genes in the human ovary is unclear. METHODS: Expression of the circadian proteins CLOCK and PER2 in human ovaries was observed by immunohistochemistry...
2016: Journal of Ovarian Research
Fang Song, Yunxia Xue, Dong Dong, Jun Liu, Ting Fu, Chengju Xiao, Hanqing Wang, Cuipei Lin, Peng Liu, Jiajun Zhong, Yabing Yang, Zhaorui Wang, Hongwei Pan, Jiansu Chen, Yangqiu Li, Dongqing Cai, Zhijie Li
The mechanisms of corneal epithelial lesions and delayed wound repair, as well as their association with diabetes mellitus, are critical issues for clinical ophthalmologists. To test whether the diabetic condition alters the circadian rhythm in a mouse cornea and whether insulin can synchronise the corneal clock, we studied the effects of streptozotocin-induced diabetes on the mitosis of epithelial cells, the recruitment of leukocytes to the cornea, and the expression of main core clock genes (Clock, Bmal1, Per2, Cry1, and Rev-erbα) in the corneal epithelium...
2016: Scientific Reports
Hiroyuki Tamiya, Sumito Ogawa, Yasuyoshi Ouchi, Masahiro Akishita
Period circadian clock (Per) genes Per1 and Per2 have essential roles in circadian oscillation. In this study, we identified a new role of Per1-Per2 cooperation, and its mechanism, using our new experimental methods. Under constant light conditions, the period length of Per1 and Per2 knockout mice depended on the copy number ratio of Per1:Per2. We then established a light-emitting diode-based lighting system that can generate any pattern of light intensity. Under gradually changing light in the absence of phase shift with different periods, both Per1((-/-)) and Per2((-/-)) mice were entrained to a broader range of period length than wild-type mice...
2016: Scientific Reports
Andrew P Patton, Johanna E Chesham, Michael H Hastings
UNLABELLED: The suprachiasmatic nucleus (SCN) is the master circadian oscillator encoding time-of-day information. SCN timekeeping is sustained by a cell-autonomous transcriptional-translational feedback loop, whereby expression of the Period and Cryptochrome genes is negatively regulated by their protein products. This loop in turn drives circadian oscillations in gene expression that direct SCN electrical activity and thence behavior. The robustness of SCN timekeeping is further enhanced by interneuronal, circuit-level coupling...
September 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Qin Zhao, Gang Zheng, Kai Yang, Yi-Ran Ao, Xiao-Li Su, Yu Li, Xiao-Qiang Lv
The various clock genes in normal cells, through their interaction, establish a number of positive and negative feedback loops that compose a network structure. These genes play an important role in regulating normal physiological activities. The expression of clock gene PER1 is decreased in many types of cancer. PER1 is highly correlated with the initiation and progression of cancer by regulating numerous downstream genes. However, it is still unclear whether the lower expression of PER1 in cancer can influence the expression of other clock genes in the clock gene network...
September 2, 2016: Oncotarget
Jeff R Jones, Douglas G McMahon
The brain's biological clock, the suprachiasmatic nucleus (SCN), exhibits endogenous 24-hour rhythms in gene expression and spontaneous firing rate; however, the functional relationship between these neuronal rhythms is not fully understood. Here, we used a Per1::GFP transgenic mouse line that allows for the simultaneous quantification of molecular clock state and firing rate in SCN neurons to examine the relationship between these key components of the circadian clock. We find that there is a stable, phased relationship between E-box-driven clock gene expression and spontaneous firing rate in SCN neurons and that these relationships are independent of light input onto the system or of GABAA receptor-mediated synaptic activity...
2016: PeerJ
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