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https://www.readbyqxmd.com/read/28525736/a-flick-of-the-tail-keeps-the-circadian-clock-in-line
#1
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
#2
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
#3
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
#4
Yoshiaki Onishi, Tatsunosuke Tomita, Ryoji Kurita
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 hypo-methylated, respectively and that 5-aza-2'-deoxycytidine (aza-dC) not only enhanced PER2 gene expression but also PER2 oscillation within 24 hours in RPMI8402 cells...
May 9, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28483667/effect-of-brain-derived-neurotrophic-factor-bdnf-on-hepatocyte-metabolism
#5
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
#6
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
#7
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
#8
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...
April 28, 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
#9
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
https://www.readbyqxmd.com/read/28452286/clock-gene-expression-in-the-suprachiasmatic-nucleus-of-hibernating-arctic-ground-squirrels
#10
Tomoko Ikeno, Cory T Williams, C Loren Buck, Brian M Barnes, Lily Yan
Most organisms have a circadian system, entrained to daily light-dark cycles, that regulates 24-h rhythms of physiology and behavior. It is unclear, however, how circadian systems function in animals that exhibit seasonal metabolic suppression, particularly when this coincides with the long-term absence of a day-night cycle. The arctic ground squirrel, Urocytellus parryii, is a medium-sized, semi-fossorial rodent that appears above-ground daily during its short active season in spring and summer before re-entering a constantly dark burrow for 6 to 9 months of hibernation...
April 1, 2017: Journal of Biological Rhythms
https://www.readbyqxmd.com/read/28440811/evaluation-of-circadian-phenotypes-utilizing-fibroblasts-from-patients-with-circadian-rhythm-sleep-disorders
#11
A Hida, Y Ohsawa, S Kitamura, K Nakazaki, N Ayabe, Y Motomura, K Matsui, M Kobayashi, A Usui, Y Inoue, H Kusanagi, Y Kamei, K Mishima
We evaluated the circadian phenotypes of patients with delayed sleep-wake phase disorder (DSWPD) and non-24-hour sleep-wake rhythm disorder (N24SWD), two different circadian rhythm sleep disorders (CRSDs) by measuring clock gene expression rhythms in fibroblast cells derived from individual patients. Bmal1-luciferase (Bmal1-luc) expression rhythms were measured in the primary fibroblast cells derived from skin biopsy samples of patients with DSWPD and N24SWD, as well as control subjects. The period length of the Bmal1-luc rhythm (in vitro period) was distributed normally and was 22...
April 25, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28432873/conditional-deletion-of-bmal1-accentuates-microvascular-and-macrovascular-injury
#12
Ashay D Bhatwadekar, Eleni Beli, Yanpeng Diao, Jonathan Chen, Qianyi Luo, Alpha Alex, Sergio Caballero, James M Dominguez, Tatiana E Salazar, Julia V Busik, Mark S Segal, Maria B Grant
The brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein (BMAL)-1 constitutes a major transcriptional regulator of the circadian clock. Here, we explored the impact of conditional deletion of Bmal1 in endothelium and hematopoietic cells in murine models of microvascular and macrovascular injury. We used two models of Bmal1(fx/fx);Tek-Cre mice, a retinal ischemia/reperfusion model and a neointimal hyperplasia model of the femoral artery. Eyes were enumerated for acellular capillaries and were stained for oxidative damage markers using nitrotyrosine immunohistochemistry...
June 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28423013/mapping-the-co-localization-of-the-circadian-proteins-per2-and-bmal1-with-enkephalin-and-substance-p-throughout-the-rodent-forebrain
#13
Ariana Frederick, Jory Goldsmith, Nuria de Zavalia, Shimon Amir
Despite rhythmic expression of clock genes being found throughout the central nervous system, very little is known about their function outside of the suprachiasmatic nucleus. Determining the pattern of clock gene expression across neuronal subpopulations is a key step in understanding their regulation and how they may influence the functions of various brain structures. Using immunofluorescence and confocal microscopy, we quantified the co-expression of the clock proteins BMAL1 and PER2 with two neuropeptides, Substance P (SubP) and Enkephalin (Enk), expressed in distinct neuronal populations throughout the forebrain...
2017: PloS One
https://www.readbyqxmd.com/read/28421530/time-of-day-dependent-neuronal-injury-after-ischemic-stroke-implication-of-circadian-clock-transcriptional-factor-bmal1-and-survival-kinase-akt
#14
Mustafa Caglar Beker, Berrak Caglayan, Esra Yalcin, Ahmet Burak Caglayan, Seyma Turkseven, Busra Gurel, Taha Kelestemur, Elif Sertel, Zafer Sahin, Selim Kutlu, Ulkan Kilic, Ahmet Tarik Baykal, Ertugrul Kilic
Occurrence of stroke cases displays a time-of-day variation in human. However, the mechanism linking circadian rhythm to the internal response mechanisms against pathophysiological events after ischemic stroke remained largely unknown. To this end, temporal changes in the susceptibility to ischemia/reperfusion (I/R) injury were investigated in mice in which the ischemic stroke induced at four different Zeitgeber time points with 6-h intervals (ZT0, ZT6, ZT12, and ZT18). Besides infarct volume and brain swelling, neuronal survival, apoptosis, ischemia, and circadian rhythm related proteins were examined using immunohistochemistry, Western blot, planar surface immune assay, and liquid chromatography-mass spectrometry tools...
April 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28421465/the-role-of-the-molecular-clock-in-skeletal-muscle-and-what-it-is-teaching-us-about-muscle-bone-crosstalk
#15
REVIEW
Lance A Riley, Karyn A Esser
PURPOSE OF REVIEW: This review summarizes what has been learned about the interaction between skeletal muscle and bone from mouse models in which BMAL1, a core molecular clock protein has been deleted. Additionally, we highlight several genes which change following loss of BMAL1. The protein products from these genes are secreted from muscle and have a known effect on bone homeostasis. RECENT FINDINGS: Circadian rhythms have been implicated in regulating systems homeostasis through a series of transcriptional-translational feedback loops termed the molecular clock...
April 18, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28416676/dissociation-of-per1-and-bmal1-circadian-rhythms-in-the-suprachiasmatic-nucleus-in-parallel-with-behavioral-outputs
#16
Daisuke Ono, Sato Honma, Yoshihiro Nakajima, Shigeru Kuroda, Ryosuke Enoki, Ken-Ichi Honma
The temporal order of physiology and behavior in mammals is primarily regulated by the circadian pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). Taking advantage of bioluminescence reporters, we monitored the circadian rhythms of the expression of clock genes Per1 and Bmal1 in the SCN of freely moving mice and found that the rate of phase shifts induced by a single light pulse was different in the two rhythms. The Per1-luc rhythm was phase-delayed instantaneously by the light presented at the subjective evening in parallel with the activity onset of behavioral rhythm, whereas the Bmal1-ELuc rhythm was phase-delayed gradually, similar to the activity offset...
May 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28414715/transcriptional-regulatory-logic-of-the-diurnal-cycle-in-the-mouse-liver
#17
Jonathan Aryeh Sobel, Irina Krier, Teemu Andersin, Sunil Raghav, Donatella Canella, Federica Gilardi, Alexandra Styliani Kalantzi, Guillaume Rey, Benjamin Weger, Frédéric Gachon, Matteo Dal Peraro, Nouria Hernandez, Ueli Schibler, Bart Deplancke, Felix Naef
Many organisms exhibit temporal rhythms in gene expression that propel diurnal cycles in physiology. In the liver of mammals, these rhythms are controlled by transcription-translation feedback loops of the core circadian clock and by feeding-fasting cycles. To better understand the regulatory interplay between the circadian clock and feeding rhythms, we mapped DNase I hypersensitive sites (DHSs) in the mouse liver during a diurnal cycle. The intensity of DNase I cleavages cycled at a substantial fraction of all DHSs, suggesting that DHSs harbor regulatory elements that control rhythmic transcription...
April 2017: PLoS Biology
https://www.readbyqxmd.com/read/28412365/vaccinia-related-kinase-3-vrk3-sets-the-circadian-period-and-amplitude-by-affecting-the-subcellular-localization-of-clock-proteins-in-mammalian-cells
#18
Nayoung Park, Jieun Song, Seongsu Jeong, Thanh Thi Tran, Hyuk Wan Ko, Eun Young Kim
In the eukaryotic circadian clock machinery, negative feedback repression of CLOCK (CLK) and BMAL1 transcriptional activity by PERIOD (PER) and CRYPTOCHROME (CRY) underlies the basis for 24 h rhythmic gene expression. Thus, precise regulation of the time-dependent nuclear entry of circadian repressors is crucial to generating normal circadian rhythms. Here, we sought to identify novel kinase(s) that regulate nuclear entry of mammalian CRY1 (mCRY1) with an unbiased screening using red fluorescent protein (RFP)-tagged human kinome expression plasmids in mammalian cells...
April 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28401936/bmal1-links-the-circadian-clock-to-viral-airway-pathology-and-asthma-phenotypes
#19
A Ehlers, W Xie, E Agapov, S Brown, D Steinberg, R Tidwell, G Sajol, R Schutz, R Weaver, H Yu, M Castro, L B Bacharier, X Wang, M J Holtzman, J A Haspel
Patients with asthma experience circadian variations in their symptoms. However it remains unclear how specific aspects of this common airway disease relate to clock genes, which are critical to the generation of circadian rhythms in mammals. Here, we used a viral model of acute and chronic airway disease to examine how circadian clock disruption affects asthmatic lung phenotypes. Deletion of the core clock gene bmal1 or environmental disruption of circadian function by jet lag exacerbated acute viral bronchiolitis caused by Sendai virus (SeV) and influenza A virus in mice...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28393157/structural-modeling-of-the-ahr-arnt-complex-in-the-bhlh-pasa-pasb-region-elucidates-the-key-determinants-of-dimerization
#20
Dario Corrada, Michael S Denison, Laura Bonati
Elucidation of the dimerization process of the aryl hydrocarbon receptor (AhR) with the AhR nuclear translocator (ARNT) is crucial for understanding the mechanisms underlying the functional activity of AhR, including mediation of the toxicity of environmental contaminants. In this work, for the first time a structural model of the AhR:ARNT dimer encompassing the entire bHLH-PASA-PASB domain region is proposed. It is developed by using a template-based modeling approach, relying on the recently available crystallographic structures of two dimers of homologous systems in the bHLH-PAS family of proteins: the CLOCK:BMAL1 and the HIF2α:ARNT heterodimers...
May 2, 2017: Molecular BioSystems
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