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Circadian Clock

Stephany M Biello, David R Bonsall, Lynsey A Atkinson, Penny C Molyneux, Mary E Harrington, Gurprit S Lall
Robust physiological circadian rhythms form an integral part of well-being. The aging process has been found to negatively impact systems that drive circadian physiology, typically manifesting as symptoms associated with abnormal/disrupted sleeping patterns. Here, we investigated the age-related decline in light-driven circadian entrainment in male C57BL/6J mice. We compared light-driven resetting of circadian behavioral activity in young (1-2 months) and old (14-18 months) mice and explored alterations in the glutamatergic pathway at the level of the circadian pacemaker, the suprachiasmatic nucleus (SCN)...
February 20, 2018: Neurobiology of Aging
Akihiko Taguchi, Yasuharu Ohta, Yukio Tanizawa
Type 2 diabetes mellitus is characterized by the loss of ß-cell function and mass, resulting from interactions between genetic predisposition and various environmental factors1 . One environmental condition identified as a risk factor for type 2 diabetes mellitus is circadian rhythm disruption, which is induced by shift work or sleep disturbance. However, the mechanism whereby circadian disruption leads to impaired glucose metabolism is not well understood. This article is protected by copyright. All rights reserved...
March 15, 2018: Journal of Diabetes Investigation
Yiran Ao, Qin Zhao, Kai Yang, Gang Zheng, Xiaoqing Lv, Xiaoli Su
Clock genes are the core of the circadian rhythms in the human body and are important in regulating normal physiological functions. To date, research has indicated that the clock gene, period circadian clock 2 ( PER2 ), is downregulated in numerous types of cancer, and that it is associated with cancer occurrence and progression via the regulation of various downstream cell cycle genes. However, it remains unclear whether the decreased expression of PER2 influences the expression of other clock genes in cancer cells...
April 2018: Oncology Letters
Yan-Dong Jiang, Xin Yuan, Wen-Wu Zhou, Yue-Liang Bai, Gui-Yao Wang, Zeng-Rong Zhu
Most living organisms have developed internal circadian clocks to anticipate the daily environmental changes. The circadian clocks are composed of several transcriptional-translational feedback loops, in which cryptochromes (CRYs) serve as critical elements. In insects, some CRYs act as photopigments to control circadian photoentrainment, while the others act as transcriptional regulators. We cloned and characterized two cryptochrome genes, the Drosophila -like ( lscry1 ) and vertebrate-like ( lscry2 ) genes, in a rice pest Laodelphax striatellus ...
2018: Frontiers in Physiology
Jihwan Myung, Christoph Schmal, Sungho Hong, Yoshiaki Tsukizawa, Pia Rose, Yong Zhang, Michael J Holtzman, Erik De Schutter, Hanspeter Herzel, Grigory Bordyugov, Toru Takumi
Mammalian circadian clocks have a hierarchical organization, governed by the suprachiasmatic nucleus (SCN) in the hypothalamus. The brain itself contains multiple loci that maintain autonomous circadian rhythmicity, but the contribution of the non-SCN clocks to this hierarchy remains unclear. We examine circadian oscillations of clock gene expression in various brain loci and discovered that in mouse, robust, higher amplitude, relatively faster oscillations occur in the choroid plexus (CP) compared to the SCN...
March 14, 2018: Nature Communications
Michael Cleary-Gaffney, Andrew N Coogan
Circadian rhythms are recurring patterns in a range of behavioural, physiological and molecular parameters that display periods of near 24 h, and are underpinned by an endogenous biological timekeeping system. Circadian clocks are increasingly recognised as being key for health. Environmental light is the key stimulus that synchronises the internal circadian system with the external time cues. There are emergent health concerns regarding increasing worldwide prevalence of electric lighting, especially man-made light-at-night, and light's impact on the circadian system may be central to these effects...
March 11, 2018: Physiology & Behavior
Jan Cosgrave, Katharina Wulff, Philip Gehrman
PURPOSE OF REVIEW: The review is designed to give an overview of the latest developments in research exploring the relationship between sleep and psychosis, with particular attention paid to the evidence for a causal relationship between the two. RECENT FINDINGS: The most interesting avenues currently in pursuit are focused upon sleep spindle deficits which may hallmark an endophenotype; explorations of the continuum of psychotic experiences, and experimental manipulations to explore the evidence for bidirectional causality; inflammatory markers, psychosis and sleep disturbances and finally, treatment approaches for sleep in psychosis and the subsequent impact on positive experiences...
March 13, 2018: Current Opinion in Psychiatry
Ning Wei, Michelle L Gumz, Anita T Layton
Major renal functions such as renal blood flow, glomerular filtration rate, and urinary excretion are known to exhibit circadian oscillations. However, the underlying mechanisms that govern these variations have yet to be fully elucidated. To better understand the impact of the circadian clock on renal solute and water transport, we have developed a computational model of the renal circadian clock, and coupled that model to an epithelial transport model of the proximal convoluted cell of the rat kidney. The activity of the Na$^+$-H$^+$ exchanger 3 (NHE3) is assumed to be regulated by changes in transcription of the NHE3 mRNA due to regulation by circadian clock proteins...
March 14, 2018: American Journal of Physiology. Renal Physiology
Fan Lou, Ming Li, Xiaoguang Luo, Yan Ren
Background: The clock genes controlling biological rhythm play an important role in the pathophysiology of aging. The purpose of this study was to determine whether there is an association between a variant of the circadian locomotor output cycles kaput (CLOCK) gene and circadian dysfunction of Parkinson's disease (PD). Methods: Six hundred and forty-six cases of Parkinson's disease from consecutive outpatients and inpatients ward from our hospital were included in this study...
2018: Parkinson's Disease
Jaebong Jang, Sooyoung Chung, Youjeong Choi, Hye Young Lim, Yeongeon Son, Sung Kook Chun, Gi Hoon Son, Kyungjin Kim, Young-Ger Suh, Jong-Wha Jung
AIMS: We have previously identified a chemical scaffold possessing 2-ethoxypropanoic acid (designated as KS15) that directly binds to the C-terminal region of cryptochromes (CRYs: CRY1 and CRY2) and enhances E-box-mediated transcription. However, it is still unclear how KS15 impairs the feedback actions of the CRYs and which chemical moieties are functionally important for its actions. MAIN METHODS: The E-box-mediated transcriptional activities were mainly used to examine the effects of KS15 and its derivatives...
March 10, 2018: Life Sciences
Deqiang Zhang, Xin Tong, Bradley B Nelson, Ethan Jin, Julian Sit, Nicholas Charney, Meichan Yang, M Bishr Omary, Lei Yin
Alcohol liver disease (ALD) is one of the major chronic liver diseases worldwide, ranging from fatty liver, alcoholic hepatitis, cirrhosis, and potentially hepatocellular carcinoma. Epidemiological studies suggest a potential link between ALD and impaired circadian rhythms, but the role of hepatic circadian proteins in the pathogenesis of ALD remains unknown. Here we show that the circadian clock protein BMAL1 in hepatocytes is both necessary and sufficient to protect mice from alcohol liver disease. Ethanol diet-fed mice with liver-specific knockout (Bmal1-LKO) or depletion of Bmal1 develop more severe liver steatosis and injury as well as a simultaneous suppression of both de novo lipogenesis and fatty acid oxidation, which can be rescued by the supplementation of synthetic PPARα ligands...
March 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Ha Kyun Kim, Hyun Jung Kim, Jae Hyung Kim, Tae Hoon Kim, Sang Hag Lee
Numerous peripheral tissues possess self-sustaining daily biologic rhythms that are regulated at the molecular level by clock genes such as PER1, PER2, CLOCK, and BMAL1. Physiological function of nasal mucosa exhibits rhythmic variability to a day-night environmental cycle. Nevertheless, little is known of the expression and distribution pattern of clock genes in nasal mucosa. The present study investigates the expression level and distribution pattern of PER1, PER2, CLOCK, and BMAL1 genes in nasal mucosa of healthy controls, allergic rhinitis patients, and normal rats...
2018: PloS One
Marie Pariollaud, Julie Gibbs, Thomas Hopwood, Sheila Brown, Nicola Begley, Ryan Vonslow, Toryn Poolman, Baoqiang Guo, Ben Saer, D Heulyn Jones, James P Tellam, Stefano Bresciani, Nicholas Co Tomkinson, Justyna Wojno-Picon, Anthony Wj Cooper, Dion A Daniels, Ryan P Trump, Daniel Grant, William Zuercher, Timothy M Willson, Andrew S MacDonald, Brian Bolognese, Patricia L Podolin, Yolanda Sanchez, Andrew Si Loudon, David W Ray
Recent studies reveal that airway epithelial cells are critical pulmonary circadian pacemaker cells, mediating rhythmic inflammatory responses. Using mouse models, we now identify the rhythmic circadian repressor REV-ERB as essential to the mechanism coupling the pulmonary clock to innate immunity, involving both myeloid, and bronchial epithelial cells in temporal gating and determining amplitude of response to inhaled endotoxin. Dual mutation of REV-ERBα and its paralog REV-ERBβ in bronchial epithelia further augmented inflammatory responses and chemokine activation, but also initiated a basal inflammatory state, revealing a critical homeostatic role for REV-ERB proteins in the suppression of the endogenous pro-inflammatory mechanism in un-challenged cells...
March 13, 2018: Journal of Clinical Investigation
Allan B James, Cristiane P G Calixto, Nikoleta A Tzioutziou, Wenbin Guo, Runxuan Zhang, Craig G Simpson, Wenying Jiang, Gillian A Nimmo, John W S Brown, Hugh G Nimmo
One of the ways in which plants can respond to temperature is via alternative splicing (AS). Previous work showed that temperature changes affected the splicing of several circadian clock gene transcripts. Here we investigated the role of RNA-binding splicing factors (SFs) in temperature-sensitive alternative splicing (AS) of the clock gene LATE ELONGATED HYPOCOTYL (LHY). We characterised, in wild type plants, temperature-associated isoform switching and expression patterns for SF transcripts from a high-resolution temperature and time series RNA-seq experiment...
March 13, 2018: Plant, Cell & Environment
Arisa Hirano, Pei-Ken Hsu, Luoying Zhang, Lijuan Xing, Thomas McMahon, Maya Yamazaki, Louis J Ptáček, Ying-Hui Fu
Adequate sleep is essential for physical and mental health. We previously identified a missense mutation in the human DEC2 gene ( BHLHE41 ) leading to the familial natural short sleep behavioral trait. DEC2 is a transcription factor regulating the circadian clock in mammals, although its role in sleep regulation has been unclear. Here we report that prepro-orexin , also known as hypocretin ( Hcrt ), gene expression is increased in the mouse model expressing the mutant h DEC2 transgene (h DEC2-P384R ). Prepro-orexin encodes a precursor protein of a neuropeptide producing orexin A and B (hcrt1 and hcrt2), which is enriched in the hypothalamus and regulates maintenance of arousal...
March 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
Shirley L Zhang, Zhifeng Yue, Denice M Arnold, Gregory Artiushin, Amita Sehgal
Endogenous circadian rhythms are thought to modulate responses to external factors, but mechanisms that confer time-of-day differences in organismal responses to environmental insults/therapeutic treatments are poorly understood. Using a xenobiotic, we find that permeability of the Drosophila "blood"-brain barrier (BBB) is higher at night. The permeability rhythm is driven by circadian regulation of efflux and depends on a molecular clock in the perineurial glia of the BBB, although efflux transporters are restricted to subperineurial glia (SPG)...
February 27, 2018: Cell
Ariel Amir, Nathalie Q Balaban
For many decades, the wedding of quantitative data with mathematical modeling has been fruitful, leading to important biological insights. Here, we review some of the ongoing efforts to gain insights into problems in microbiology - and, in particular, cell-cycle progression and its regulation - through observation and quantitative analysis of the natural fluctuations in the system. We first illustrate this idea by reviewing a classic example in microbiology - the Luria-Delbrück experiment - and discussing how, in that case, useful information was obtained by looking beyond the mean outcome of the experiment, but instead paying attention to the variability between replicates of the experiment...
March 8, 2018: Trends in Microbiology
Youqiong Ye, Yu Xiang, Fatma Muge Ozguc, Yoonjin Kim, Chun-Jie Liu, Peter K Park, Qingsong Hu, Lixia Diao, Yanyan Lou, Chunru Lin, An-Yuan Guo, Bingying Zhou, Li Wang, Zheng Chen, Joseph S Takahashi, Gordon B Mills, Seung-Hee Yoo, Leng Han
Cancer chronotherapy, treatment at specific times during circadian rhythms, endeavors to optimize anti-tumor effects and to lower toxicity. However, comprehensive characterization of clock genes and their clinical relevance in cancer is lacking. We systematically characterized the alterations of clock genes across 32 cancer types by analyzing data from The Cancer Genome Atlas, Cancer Therapeutics Response Portal, and The Genomics of Drug Sensitivity in Cancer databases. Expression alterations of clock genes are associated with key oncogenic pathways, patient survival, tumor stage, and subtype in multiple cancer types...
March 1, 2018: Cell Systems
Tim S Nawrot, Nelly D Saenen, Julie Schenk, Bram G Janssen, Valeria Motta, Letizia Tarantini, Bianca Cox, Wouter Lefebvre, Charlotte Vanpoucke, Cristina Maggioni, Valentina Bollati
In mammals, a central clock maintains the daily rhythm in accordance with the external environment. At the molecular level, the circadian rhythm is maintained by epigenetic regulation of the Circadian pathway. Here, we tested the role of particulate matter with an aerodynamic diameter ≤ 2.5 μm (PM2.5 ) exposure during gestational life on human placental Circadian pathway methylation, as an important molecular target for healthy development. In 407 newborns, we quantified placental methylation of CpG sites within the promoter regions of the following genes: CLOCK, BMAL1, NPAS2, CRY1-2 and PER1-3 using bisulfite-PCR-pyrosequencing...
March 7, 2018: Environment International
Fangjia Lu, Qingyang Liu
The impact of unrhythmic circadian clock on obesity has started to be increasingly appreciated nowadays. Recently it was discovered that interaction between intestinal microbiota and unrhythmic circadian clock plays a key role in such a process. It involves relaying signals from microbiota through dendritic cells to group 3 innate lymphoid cells in the intestine and in the end impacting some of the key transcription factors of circadian clock. Breaking such a signal relay may prove to be an effective way reducing unrhythmic circadian clock-induced obesity...
April 2018: Medical Hypotheses
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