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https://www.readbyqxmd.com/read/29324865/association-of-circadian-rhythm-genes-arntl-bmal1-and-clock-with-multiple-sclerosis
#1
Polona Lavtar, Gorazd Rudolf, Aleš Maver, Alenka Hodžić, Nada Starčević Čizmarević, Maja Živković, Saša Šega Jazbec, Zalika Klemenc Ketiš, Miljenko Kapović, Evica Dinčić, Ranko Raičević, Juraj Sepčić, Luca Lovrečić, Aleksandra Stanković, Smiljana Ristić, Borut Peterlin
Prevalence of multiple sclerosis varies with geographic latitude. We hypothesized that this fact might be partially associated with the influence of latitude on circadian rhythm and consequently that genetic variability of key circadian rhythm regulators, ARNTL and CLOCK genes, might contribute to the risk for multiple sclerosis. Our aim was to analyse selected polymorphisms of ARNTL and CLOCK, and their association with multiple sclerosis. A total of 900 Caucasian patients and 1024 healthy controls were compared for genetic signature at 8 SNPs, 4 for each of both genes...
2018: PloS One
https://www.readbyqxmd.com/read/29316442/circadian-clocks-and-upr-new-twists-as-the-story-unfolds
#2
Nikolay B Milev, David Gatfield
Circadian clocks help control the unfolded protein response (UPR). In a recent issue of Nature Cell Biology, Bu et al. (2017) show that the interaction is reciprocal, with miRNA-211 providing a signal from the UPR to the clock component BMAL1, affecting circadian timing, global translational control, and cancer cell survival.
January 8, 2018: Developmental Cell
https://www.readbyqxmd.com/read/29305918/circadian-modification-network-of-a-core-clock-driver-bmal1-to-harmonize-physiology-from-brain-to-peripheral-tissues
#3
Teruya Tamaru, Ken Takamatsu
Circadian clocks dictate various physiological functions by brain SCN (a central clock) -orchestrating the temporal harmony of peripheral clocks of tissues/organs in the whole body, with adaptability to environments by resetting their timings. Dysfunction of this circadian adaptation system (CAS) occasionally causes/exacerbates diseases. CAS is based on cell-autonomous molecular clocks, which oscillate via a core transcriptional/translational feedback loop with clock genes/proteins, e.g., BMAL1: CLOCK circadian transcription driver and CRY1/2 and PER1/2 suppressors, and is modulated by various regulatory loops including clock protein modifications...
January 3, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29300726/regulation-of-circadian-clock-transcriptional-output-by-clock-bmal1
#4
Alexandra J Trott, Jerome S Menet
The mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of 15% of the transcriptome and control the daily regulation of biological functions. The recent characterization of CLOCK:BMAL1 cistrome revealed that although CLOCK:BMAL1 binds synchronously to all of its target genes, its transcriptional output is highly heterogeneous. By performing a meta-analysis of several independent genome-wide datasets, we found that the binding of other transcription factors at CLOCK:BMAL1 enhancers likely contribute to the heterogeneity of CLOCK:BMAL1 transcriptional output...
January 4, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29276151/bmal1-deficiency-contributes-to-mandibular-dysplasia-by-upregulating-mmp3
#5
Jiajia Zhao, Xin Zhou, Qingming Tang, Ran Yu, Shaoling Yu, Yanlin Long, Cen Cao, Jun Han, Anbing Shi, Jeremy J Mao, Xiong Chen, Lili Chen
Skeletal mandibular hypoplasia (SMH), one of the common types of craniofacial deformities, seriously affects appearance, chewing, pronunciation, and breathing. Moreover, SMH is prone to inducing obstructive sleep apnea syndrome. We found that brain and muscle ARNT-like 1 (BMAL1), the core component of the molecular circadian oscillator, was significantly decreased in mandibles of juvenile SMH patients. Accordingly, SMH was observed in circadian-rhythm-disrupted or BMAL1-deficient mice. RNA sequencing and protein chip analyses suggested that matrix metallopeptidase 3 (MMP3) is the potential target of BMAL1...
December 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29258993/circadian-clocks-from-stem-cells-to-tissue-homeostasis-and-regeneration
#6
REVIEW
Pieterjan Dierickx, Linda W Van Laake, Niels Geijsen
The circadian clock is an evolutionarily conserved timekeeper that adapts body physiology to diurnal cycles of around 24 h by influencing a wide variety of processes such as sleep-to-wake transitions, feeding and fasting patterns, body temperature, and hormone regulation. The molecular clock machinery comprises a pathway that is driven by rhythmic docking of the transcription factors BMAL1 and CLOCK on clock-controlled output genes, which results in tissue-specific oscillatory gene expression programs. Genetic as well as environmental perturbation of the circadian clock has been implicated in various diseases ranging from sleep to metabolic disorders and cancer development...
December 19, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29234010/loss-of-the-molecular-clock-in-myeloid-cells-exacerbates-t-cell-mediated-cns-autoimmune-disease
#7
Caroline E Sutton, Conor M Finlay, Mathilde Raverdeau, James O Early, Joseph DeCourcey, Zbigniew Zaslona, Luke A J O'Neill, Kingston H G Mills, Annie M Curtis
The transcription factor BMAL1 is a core component of the molecular clock, regulating biological pathways that drive 24 h (circadian) rhythms in behaviour and physiology. The molecular clock has a profound influence on innate immune function, and circadian disruption is linked with increased incidence of multiple sclerosis (MS). However, the mechanisms underlying this association are unknown. Here we show that BMAL1 and time-of-day regulate the accumulation and activation of various immune cells in a CNS autoimmune disease model, experimental autoimmune encephalomyelitis (EAE)...
December 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29230015/a-perk-mir-211-axis-suppresses-circadian-regulators-and-protein-synthesis-to-promote-cancer-cell-survival
#8
Yiwen Bu, Akihiro Yoshida, Nilesh Chitnis, Brian J Altman, Feven Tameire, Amanda Oran, Victoria Gennaro, Kent E Armeson, Steven B McMahon, Gerald B Wertheim, Chi V Dang, Davide Ruggero, Constantinos Koumenis, Serge Y Fuchs, J Alan Diehl
The unfolded protein response (UPR) is a stress-activated signalling pathway that regulates cell proliferation, metabolism and survival. The circadian clock coordinates metabolism and signal transduction with light/dark cycles. We explore how UPR signalling interfaces with the circadian clock. UPR activation induces a 10 h phase shift in circadian oscillations through induction of miR-211, a PERK-inducible microRNA that transiently suppresses both Bmal1 and Clock, core circadian regulators. Molecular investigation reveals that miR-211 directly regulates Bmal1 and Clock via distinct mechanisms...
December 11, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29219947/dendritic-cell-nuclear-protein-1-regulates-melatonin-biosynthesis-by-binding-to-bmal1-and-inhibiting-the-transcription-of-n-acetyltransferase-in-c6-cells
#9
Dong Chen, Yi-Pei Li, Yan-Xia Yu, Tian Zhou, Chao Liu, Er-Kang Fei, Feng Gao, Chen-Chen Mu, Hai-Gang Ren, Guang-Hui Wang
Dendritic cell nuclear protein-1 (DCNP1) is a protein associated with major depression. In the brains of depression patients, DCNP1 is up-regulated. However, how DCNP1 participates in the pathogenesis of major depression remains unknown. In this study, we first transfected HEK293 cells with EGFP-DCNP1 and demonstrated that the full-length DCNP1 protein was localized in the nucleus, and RRK (the residues 117-119) composed its nuclear localization signal (NLS). An RRK-deletion form of DCNP1 (DCNP1ΔRRK) and truncated form (DCNP11-116), each lacking the RRK residues, did not show the specific nuclear localization like full-length DCNP1 in the cells...
December 7, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29219623/usual-normalization-strategies-for-gene-expression-studies-impair-the-detection-and-analysis-of-circadian-patterns
#10
Diego de Siqueira Figueredo, Mayara Rodrigues Barbosa, Daniel Gomes Coimbra, José Luiz Araújo Dos Santos, Ellyda Fernanda Lopes Costa, Bruna Del Vechio Koike, Magna Suzana Alexandre Moreira, Tiago Gomes de Andrade
Recent studies have shown that transcriptomes from different tissues present circadian oscillations. Therefore, the endogenous variation of total RNA should be considered as a potential bias in circadian studies of gene expression. However, normalization strategies generally include the equalization of total RNA concentration between samples prior to cDNA synthesis. Moreover, endogenous housekeeping genes (HKGs) frequently used for data normalization may exhibit circadian variation and distort experimental results if not detected or considered...
December 8, 2017: Chronobiology International
https://www.readbyqxmd.com/read/29217191/tnf-%C3%AE-induces-expression-of-the-circadian-clock-gene-bmal1-via-dual-calcium-dependent-pathways-in-rheumatoid-synovial-cells
#11
Kohsuke Yoshida, Ayako Nakai, Kenta Kaneshiro, Naonori Hashimoto, Kohjin Suzuki, Koto Uchida, Teppei Hashimoto, Yoshiko Kawasaki, Koji Tateishi, Natsuko Nakagawa, Nao Shibanuma, Yoshitada Sakai, Akira Hashiramoto
Tumor necrosis factor (TNF)-α is responsible for expressions of several clock genes and affects joint symptoms of rheumatoid arthritis (RA) with diurnal fluctuation. We tried to determine the mechanism involved in over-expression of Bmal1, induced by TNF-α, in primary cultured rheumatoid synovial cells. Cells were incubated with intra-cellular Ca2+ chelator BAPTA-AM, calcineurin inhibitor FK506 and p300/CBP (CREB binding protein) inhibitor C646, respectively, or transfected with p300 and CBP small interfering RNA (siRNA) before stimulation with TNF-α...
December 4, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29216180/the-ink4a-arf-locus-operates-as-a-regulator-of-the-circadian-clock-modulating-ras-activity
#12
Rukeia El-Athman, Nikolai N Genov, Jeannine Mazuch, Kaiyang Zhang, Yong Yu, Luise Fuhr, Mónica Abreu, Yin Li, Thomas Wallach, Achim Kramer, Clemens A Schmitt, Angela Relógio
The mammalian circadian clock and the cell cycle are two major biological oscillators whose coupling influences cell fate decisions. In the present study, we use a model-driven experimental approach to investigate the interplay between clock and cell cycle components and the dysregulatory effects of RAS on this coupled system. In particular, we focus on the Ink4a/Arf locus as one of the bridging clock-cell cycle elements. Upon perturbations by the rat sarcoma viral oncogene (RAS), differential effects on the circadian phenotype were observed in wild-type and Ink4a/Arf knock-out mouse embryonic fibroblasts (MEFs), which could be reproduced by our modelling simulations and correlated with opposing cell cycle fate decisions...
December 2017: PLoS Biology
https://www.readbyqxmd.com/read/29193800/suppression-of-circadian-secretion-of-glucagon-like-peptide-1-by-the-saturated-fatty-acid-palmitate
#13
A Martchenko, R H Oh, S E Wheeler, P Gurges, J A Chalmers, P L Brubaker
AIM: Glucagon-like peptide-1 is an incretin hormone secreted by the intestinal L-cell with a circadian rhythm that parallels expression of the core clock gene, Bmal1. Although feeding rats a high-fat/high-sucrose Western diet impairs rhythmic glucagon-like peptide-1 release, the mechanisms underlying this effect remain unclear. Therefore, the aim of the present study was to determine the pathway(s) by which the saturated fat, palmitate, a major component of the Western diet, impairs circadian glucagon-like peptide-1 secretion...
November 29, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29191941/genetic-deletion-of-the-circadian-clock-transcription-factor-bmal1-and-chronic-alcohol-consumption-differentially-alter-hepatic-glycogen-in-mice
#14
Uduak S Udoh, Jennifer A Valcin, Telisha M Swain, Ashley N Filiano, Karen L Gamble, Martin E Young, Shannon M Bailey
Multiple metabolic pathways exhibit time-of-day dependent rhythms that are controlled by the molecular circadian clock. We have shown that chronic alcohol is capable of altering the molecular clock and diurnal oscillations in several elements of hepatic glycogen metabolism. Herein, we sought to determine whether genetic disruption of the hepatocyte clock differentially impacts hepatic glycogen content in chronic alcohol-fed mice. Male hepatocyte-specific BMAL1 knockout (HBK) and littermate controls were fed control or alcohol-containing diets for 5 weeks to alter hepatic glycogen content...
November 30, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29186676/the-circadian-clock-regulates-adipogenesis-by-a-per3-crosstalk-pathway-to-klf15
#15
Abhishek Aggarwal, Maria José Costa, Belén Rivero-Gutiérrez, Lijuan Ji, Stefanie L Morgan, Brian J Feldman
The generation of new adipocytes from precursor cells (adipogenesis) has implications for systemic metabolism and is a commonly used model for studying the process of cell differentiation in vitro. Previous studies from us and others suggested that the peripheral circadian clock can influence adipogenesis in vitro, but the mechanisms driving this activity and the relevance for adipogenesis in vivo are unknown. Here we reveal that mouse adipocyte precursor cells (APCs) contain a circadian clock that oscillates in vivo...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29176713/rapid-resetting-of-human-peripheral-clocks-by-phototherapy-during-simulated-night-shift-work
#16
Marc Cuesta, Philippe Boudreau, Nicolas Cermakian, Diane B Boivin
A majority of night shift workers have their circadian rhythms misaligned to their atypical schedule. While bright light exposure at night is known to reset the human central circadian clock, the behavior of peripheral clocks under conditions of shift work is more elusive. The aim of the present study was to quantify the resetting effects of bright light exposure on both central (plasma cortisol and melatonin) and peripheral clocks markers (clock gene expression in peripheral blood mononuclear cells, PBMCs) in subjects living at night...
November 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29172799/prognostic-significance-of-downregulated-bmal1-and-upregulated-ki-67-proteins-in-nasopharyngeal-carcinoma
#17
Q Y He, F Jin, Y Y Li, W L Wu, J H Long, X L Luo, X Y Gong, X X Chen, T Bi, Z L Li, B Qu, H Jiang, P X Zhang
This study assessed the prognostic value of BMAL1 and Ki-67 expression in patients with nasopharyngeal carcinoma. Level of BMAL1 mRNA was assessed in tissue specimens from 36 nasopharyngeal carcinomas and 20 nasopharyngeal chronic inflammations using quantitative reverse transcriptase-polymerase chain reaction. Expression of BMAL1 and Ki-67 proteins was analyzed immunohistochemically in 90 paired nasopharyngeal carcinoma and distant normal tissues. The Kaplan-Meier curves and the Log-rank test were used to calculate prognostic significance stratified by BMAL1 and Ki67 protein expression and the COX regression model was to analyze the multivariate prognosis...
November 27, 2017: Chronobiology International
https://www.readbyqxmd.com/read/29172740/the-choroid-plexus-harbors-a-circadian-oscillator-modulated-by-estrogens
#18
Telma Quintela, Tânia Albuquerque, Gabriella Lundkvist, Andrea Carmine Belin, Daniela Talhada, Isabel Gonçalves, Eva Carro, Cecília R A Santos
The suprachiasmatic nucleus (SCN) of the hypothalamus is considered the master circadian oscillator in mammals. However, extra-SCN structures in the brain also display daily rhythms. Recently, we have demonstrated that the choroid plexus (CP) expresses core clock genes that are subjected to circadian regulation in a sex-dependent manner. By using CP explants cultured from female knock-in mice carrying the Period-luciferase transgene, we show that CP exhibits endogenous circadian rhythms of PERIOD2::LUCIFERASE expression...
November 27, 2017: Chronobiology International
https://www.readbyqxmd.com/read/29165002/adrenal-dependent-and-independent-stress-induced-per1-mrna-in-hypothalamic-paraventricular-nucleus-and-prefrontal-cortex-of-male-and-female-rats
#19
Lauren E Chun, Jenny Christensen, Elizabeth R Woodruff, Sarah J Morton, Laura R Hinds, Robert L Spencer
Oscillating clock gene expression gives rise to a molecular clock that is present not only in the body's master circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN), but also in extra-SCN brain regions. These extra-SCN molecular clocks depend on the SCN for entrainment to a light:dark cycle. The SCN has limited neural efferents, so it may entrain extra-SCN molecular clocks through its well-established circadian control of glucocorticoid hormone secretion. Glucocorticoids can regulate the normal rhythmic expression of clock genes in some extra-SCN tissues...
November 22, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/29164122/changes-in-expression-of-the-clock-gene-in-obstructive-sleep-apnea-syndrome-patients-are-not-reverted-by-continuous-positive-airway-pressure-treatment
#20
Susana Moreira, Raquel Rodrigues, André B Barros, Nadja Pejanovic, Ana Neves-Costa, Dora Pedroso, Cláudia Pereira, Dina Fernandes, João Valença Rodrigues, Cristina Barbara, Luís Ferreira Moita
Purpose: Metabolic syndrome and cardiovascular disease are strongly associated with obstructive sleep apnea syndrome (OSAS), which causes substantial changes to normal circadian physiological functions, including metabolic pathways. Because core clock genes are known to be modulated by sleep/vigilance cycles, we asked whether the expression level of mRNA coding for clock genes is altered in non-treated OSAS patients and if it can be corrected by standard continuous positive airway pressure (CPAP) treatment...
2017: Frontiers in Medicine
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