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https://www.readbyqxmd.com/read/28625682/are-circadian-rhythms-new-pathways-to-understand-autism-spectrum-disorder
#1
M-M Geoffray, A Nicolas, M Speranza, N Georgieff
Autism Spectrum Disorder (ASD) is a frequent neurodevelopmental disorder. ASD is probably the result of intricate interactions between genes and environment altering progressively the development of brain structures and functions. Circadian rhythms are a complex intrinsic timing system composed of almost as many clocks as there are body cells. They regulate a variety of physiological and behavioral processes such as the sleep- wake rhythm. ASD is often associated with sleep disorders and low levels of melatonin...
June 15, 2017: Journal of Physiology, Paris
https://www.readbyqxmd.com/read/28625476/feedback-loops-interlocked-at-competitive-binding-sites-amplify-and-facilitate-genetic-oscillations
#2
Koichiro Uriu, Hajime Tei
Positive and negative feedback loops are often present in regulatory networks for genetic oscillations. Relative time scales and integration of these feedback loops are key to robust oscillations in expression levels. Using examples from the circadian clock and synthetic genetic oscillators, we study positive and negative feedback loops interlocked at competitive binding sites. In the mammalian circadian clock, a key clock gene Bmal1 is regulated by the activator ROR and the repressor REV-ERB. Conversely, Bmal1 activates both of them, forming interlocked feedback loops...
June 15, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28602615/pten-mediates-activation-of-core-clock-protein-bmal1-and-accumulation-of-epidermal-stem-cells
#3
Chiara Zagni, Luciana O Almeida, Tarek Balan, Marco T Martins, Luciana K Rosselli-Murai, Petros Papagerakis, Rogerio M Castilho, Cristiane H Squarize
Tissue integrity requires constant maintenance of a quiescent, yet responsive, population of stem cells. In the skin, hair follicle stem cells (HFSCs) that reside within the bulge maintain tissue homeostasis in response to activating cues that occur with each new hair cycle or upon injury. We found that PTEN, a major regulator of the PI3K-AKT pathway, controlled HFSC number and size in the bulge and maintained genomically stable pluripotent cells. This regulatory function is central for HFSC quiescence, where PTEN-deficiency phenotype is in part regulated by BMAL1...
June 5, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28593182/the-circadian-clock-gene-bmal1-coordinates-intestinal%C3%A2-regeneration
#4
Kyle Stokes, Abrial Cooke, Hanna Chang, David R Weaver, David T Breault, Phillip Karpowicz
BACKGROUND & AIMS: The gastrointestinal syndrome is an illness of the intestine caused by high levels of radiation. It is characterized by extensive loss of epithelial tissue integrity, which initiates a regenerative response by intestinal stem and precursor cells. The intestine has 24-hour rhythms in many physiological functions that are believed to be outputs of the circadian clock: a molecular system that produces 24-hour rhythms in transcription/translation. Certain gastrointestinal illnesses are worsened when the circadian rhythms are disrupted, but the role of the circadian clock in gastrointestinal regeneration has not been studied...
July 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28588500/temporal-expression-patterns-of-clock-genes-and-aquaporin-5-anoctamin-1-in-rat-submandibular-gland-cells
#5
Ryouichi Satou, Masaki Sato, Maki Kimura, Yoichi Ishizuka, Masakazu Tazaki, Naoki Sugihara, Yoshiyuki Shibukawa
Circadian rhythms are essential for health and regulate various physiological functions. These rhythms are regulated by a negative-feedback loop involving clock genes in the suprachiasmatic nucleus (SCN) and peripheral tissues. The rate of secretion of salivary substances, ions, and water follows a circadian rhythm, however, the relationship between the molecular mechanism of salivary secretion and peripheral circadian rhythm is not yet clear. Anoctamin 1 (ANO1, also known as TMEM16A) and Aquaporin 5 (AQP5) play an important role in the transport of ions and water in the submandibular glands (SGs)...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28588221/ketogenic-diet-induces-expression-of-the-muscle-circadian-gene-slc25a25-via-neural-pathway-that-might-be-involved-in-muscle-thermogenesis
#6
Reiko Nakao, Shigeki Shimba, Katsutaka Oishi
We recently found that the mRNA expression of Slc25a25, a Ca(2+)-sensitive ATP carrier in the inner mitochondrial membrane, fluctuates in a circadian manner in mouse skeletal muscle. We showed here that the circadian expression of muscle Slc25a25 was damped in Clock mutant, muscle-specific Bmal1-deficient, and global Bmal1-deficient mice. Furthermore, a ketogenic diet (KD) that induces time-of-day-dependent hypothermia (torpor), induced Slc25a25 mRNA expression in skeletal muscle. Hypothermia induced by KD did not affect thermogenic genes such as Sarcolipin and Pgc1a in muscles and Ucp1 in adipose tissues...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28585194/circadian-rhythms-in-diet-induced-obesity
#7
Atilla Engin
The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronizes these with daily cycles, feeding patterns also regulates circadian clocks. The clock genes and adipocytokines show circadian rhythmicity. Dysfunction of these genes are involved in the alteration of these adipokines during the development of obesity. Food availability promotes the stimuli associated with food intake which is a circadian oscillator outside of the suprachiasmatic nucleus (SCN)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28556462/gsk3-activity-regulates-rhythms-in-hippocampal-clock-gene-expression-and-synaptic-plasticity
#8
Rachel C Besing, Courtney O Rogers, Jodi R Paul, Lauren M Hablitz, Russell L Johnson, Lori L McMahon, Karen L Gamble
Hippocampal rhythms in clock gene expression, enzymatic activity, and long-term potentiation (LTP) are thought to underlie day-night differences in memory acquisition and recall. Glycogen synthase kinase 3-beta (GSK3β) is a known regulator of hippocampal function, and inhibitory phosphorylation of GSK3β exhibits region-specific differences over the light-dark cycle. Here, we sought to determine whether phosphorylation of both GSK3α and GSK3β isoforms has an endogenous circadian rhythm in specific areas of the hippocampus and whether chronic inhibition or activation alters the molecular clock and hippocampal plasticity (LTP)...
May 27, 2017: Hippocampus
https://www.readbyqxmd.com/read/28543681/activation-of-mmps-in-macrophages-by-mycobacterium-tuberculosis-via-the-mir-223-bmal1-signaling-pathway
#9
Jun Lou, Yongli Wang, Zhimin Zhang, Weiqiang Qiu
An interaction between Mycobacterium tuberculosis and macrophages constitutes an essential step in tuberculosis development, as macrophages exert both positive and negative effects on M. tuberculosis-triggered organ lesions. In this study, we focused on the regulation of the expression of matrix metalloproteinases (MMPs), which is responsible for lung matrix degradation and bacteria dissection, in macrophages following M. tuberculosis infection. Female BALB/c mice were intravenously injected with the M. tuberculosis strain H37Rv at 0h zeitgeber time (ZT0) or 12 h zeitgeber time (ZT12)...
May 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28535183/time-caloric-restriction-inhibits-the-neoplastic-transformation-of-cirrhotic-liver-in-rats-treated-with-diethylnitrosamine
#10
Christian Molina-Aguilar, María de Jesús Guerrero-Carrillo, Jesús Javier Espinosa-Aguirre, Sitlali Olguin-Reyes, Thania Castro-Belio, Olivia Vázquez-Martínez, Julieta Berenice Rivera-Zavala, Mauricio Díaz-Muñoz
Hepatocellular cancer is the most common type of primary liver cancer. Cirrhosis is the main risk factor that generates this malady. It has been proven that caloric restriction protocols and restricted feeding schedules are protective in experimental carcinogenic models. We tested the influence of a time-caloric restriction protocol (2 h of food access during the daytime for 18 weeks) in an experimental model of cirrhosis-hepatocarcinoma produced by weekly administration of diethylnitrosamine. Our results indicate that time-caloric restriction reduced hepatomegaly and prevented the increase in blood leukocytes promoted by diethylnitrosamine...
May 23, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28533986/atorvastatin-alters-the-expression-of-genes-related-to-bile-acid-metabolism-and-circadian-clock-in-livers-of-mice
#11
Wen-Kai Li, Huan Li, Yuan-Fu Lu, Ying-Ying Li, Zidong Donna Fu, Jie Liu
AIM: Atorvastatin is a HMG-CoA reductase inhibitor used for hyperlipidemia. Atorvastatin is generally safe but may induce cholestasis. The present study aimed to examine the effects of atorvastatin on hepatic gene expression related to bile acid metabolism and homeostasis, as well as the expression of circadian clock genes in livers of mice. METHODS: Adult male mice were given atorvastatin (10, 30, and 100 mg/kg, po) daily for 30 days, and blood biochemistry, histopathology, and gene expression were examined...
2017: PeerJ
https://www.readbyqxmd.com/read/28525736/a-flick-of-the-tail-keeps-the-circadian-clock-in-line
#12
Rajesh Narasimamurthy, David M Virshup
Circadian clocks signal and adapt to an ever-changing world by juggling a panoply of transcriptional and post-translational modifications. In this issue of Molecular Cell, Gustafson et al. (2017) report an additional requirement for accurate timekeeping, a cis/trans conformational flicker in the transcriptional activation domain of the core clock protein BMAL1.
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28511934/repeated-manganese-administration-produced-abnormal-expression-of-circadian-clock-genes-in-the-hypothalamus-and-liver-of-rats
#13
Huan Li, Ximin Fan, Ying Luo, Sheng Song, Jie Liu, Qiyuan Fan
Manganese (Mn) neurotoxicity displays non-motor dysfunction and motor impairment like Parkinson's disease (PD), and is called as Manganism. Circadian disruption is a non-motor symptom found in PD and Manganism. Clock genes are essential to drive and maintain circadian rhythm, but little is known about Mn exposure on circadian clock genes expression. Both the brain and liver are targets of Mn, we hypothesize that repeated Mn administration could affect clock gene expression in the hypothalamus and livers. Male Sprague-Dawley rats were intraperitoneally injected Mn(2+) 1mg and 5mg/kg as MnCl2·4H2O, every other day for 30 days...
May 13, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28506462/a-slow-conformational-switch-in-the-bmal1-transactivation-domain-modulates-circadian-rhythms
#14
Chelsea L Gustafson, Nicole C Parsley, Hande Asimgil, Hsiau-Wei Lee, Christopher Ahlbach, Alicia K Michael, Haiyan Xu, Owen L Williams, Tara L Davis, Andrew C Liu, Carrie L Partch
The C-terminal transactivation domain (TAD) of BMAL1 (brain and muscle ARNT-like 1) is a regulatory hub for transcriptional coactivators and repressors that compete for binding and, consequently, contributes to period determination of the mammalian circadian clock. Here, we report the discovery of two distinct conformational states that slowly exchange within the dynamic TAD to control timing. This binary switch results from cis/trans isomerization about a highly conserved Trp-Pro imide bond in a region of the TAD that is required for normal circadian timekeeping...
May 18, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28487473/epigenetic-regulation-of-the-circadian-clock-role-of-5-aza-2-deoxycytidine
#15
Tatsunosuke Tomita, Ryoji Kurita, Yoshiaki Onishi
We have been investigating transcriptional regulation of the BMAL1 gene, a critical component of the mammalian clock system including DNA methylation. Here, a more detailed analysis of the regulation of DNA methylation of BMAL1 proceeded in RPMI8402 lymphoma cells. We found that CpG islands in the BMAL1 and the PER2 promoters were hyper- and hypomethylated, respectively and that 5-aza-2'-deoxycytidine (aza-dC) not only enhanced PER2 gene expression but also PER2 oscillation within 24 h in RPMI8402 cells. That is, such hypermethylation of CpG islands in the BMAL1 promoter restricted PER2 expression which was recovered by aza-dC within 1 day in these cells...
June 30, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28483667/effect-of-brain-derived-neurotrophic-factor-bdnf-on-hepatocyte-metabolism
#16
Yoni Genzer, Nava Chapnik, Oren Froy
Brain-derived neurotrophic factor (BDNF) plays crucial roles in the development, maintenance, plasticity and homeostasis of the central and peripheral nervous systems. Perturbing BDNF signaling in mouse brain results in hyperphagia, obesity, hyperinsulinemia and hyperglycemia. Currently, little is known whether BDNF affects liver tissue directly. Our aim was to determine the metabolic signaling pathways activated after BDNF treatment in hepatocytes. Unlike its effect in the brain, BDNF did not lead to activation of the liver AKT pathway...
May 5, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28470120/cell-intrinsic-bmal1-dependent-circadian-regulation-of-temozolomide-sensitivity-in-glioblastoma
#17
Emily A Slat, Jasmin Sponagel, Luciano Marpegan, Tatiana Simon, Najla Kfoury, Albert Kim, Andrea Binz, Erik D Herzog, Joshua B Rubin
The safety and efficacy of chemotherapeutics can vary as a function of the time of their delivery during the day. This study aimed to improve the treatment of glioblastoma (GBM), the most common brain cancer, by testing whether the efficacy of the DNA alkylator temozolomide (TMZ) varies with the time of its administration. We found cell-intrinsic, daily rhythms in both human and mouse GBM cells. Circadian time of treatment affected TMZ sensitivity of murine GBM tumor cells in vitro. The maximum TMZ-induced DNA damage response, activation of apoptosis, and growth inhibition occurred near the daily peak in expression of the core clock gene Bmal1...
April 2017: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/28469105/long-term-levodopa-treatment-accelerates-the-circadian-rhythm-dysfunction-in-a-6-hydroxydopamine-rat-model-of-parkinson-s-disease
#18
Si-Yue Li, Ya-Li Wang, Wen-Wen Liu, Dong-Jun Lyu, Fen Wang, Cheng-Jie Mao, Ya-Ping Yang, Li-Fang Hu, Chun-Feng Liu
BACKGROUND: Parkinson's disease (PD) patients with long-term levodopa (L-DOPA) treatment are suffering from severe circadian dysfunction. However, it is hard to distinguish that the circadian disturbance in patients is due to the disease progression itself, or is affected by L-DOPA replacement therapy. This study was to investigate the role of L-DOPA on the circadian dysfunction in a rat model of PD. METHODS: The rat model of PD was constructed by a bilateral striatal injection with 6-hydroxydopamine (6-OHDA), followed by administration of saline or 25 mg/kg L-DOPA for 21 consecutive days...
May 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28461004/disruption-of-normal-circadian-clock-function-in-a-mouse-model-of-tauopathy
#19
Korey Stevanovic, Amara Yunus, Aurelie Joly-Amado, Marcia Gordon, David Morgan, Danielle Gulick, Joshua Gamsby
Disruption of normal circadian rhythm physiology is associated with neurodegenerative disease, which can lead to symptoms such as altered sleep cycles. In Alzheimer's disease (AD), circadian dysfunction has been attributed to β-amyloidosis. However, it is unclear whether tauopathy, another AD-associated neuropathology, can disrupt the circadian clock. We have evaluated the status of the circadian clock in a mouse model of tauopathy (Tg4510). Tg4510 mice display a long free-running period at an age when tauopathy is present, and show evidence of tauopathy in the suprachiasmatic nucleus (SCN) of the hypothalamus - the site of the master circadian clock...
August 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28460049/tumor-necrosis-factor-alpha-tnf-%C3%AE-disrupts-kir4-1-channel-expression-resulting-in-m%C3%A3-ller-cell-dysfunction-in-the-retina
#20
Iraj Hassan, Qianyi Luo, Sreeparna Majumdar, James M Dominguez, Julia V Busik, Ashay D Bhatwadekar
Purpose: Diabetic patients often are affected by vision problems. We previously identified diabetic retinopathy (DR) as a disease of clock gene dysregulation. TNF-α, a proinflammatory cytokine, is known to be elevated in DR. Müller cells maintain retinal water homeostasis and K+ concentration via Kir4.1 channels. Notably, Kir4.1 expression is reduced in diabetes; however, the interplay of TNF-α, Kir4.1, and clock genes in Müller cells remains unknown. We hypothesize that the Kir4...
May 1, 2017: Investigative Ophthalmology & Visual Science
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