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https://www.readbyqxmd.com/read/29227248/salt-inducible-kinase-3-regulates-the-mammalian-circadian-clock-by-destabilizing-per2-protein
#1
Naoto Hayasaka, Arisa Hirano, Yuka Miyoshi, Isao T Tokuda, Hikari Yoshitane, Junichiro Matsuda, Yoshitaka Fukada
Salt-inducible kinase 3 (SIK3) plays a crucial role in various aspects of metabolism. In the course of investigating metabolic defects in Sik3-deficient mice (Sik3-/-), we observed that circadian rhythmicity of the metabolisms was phase-delayed. Sik3-/- mice also exhibited other circadian abnormalities, including lengthening of the period, impaired entrainment to the light-dark cycle, phase variation in locomotor activities, and aberrant physiological rhythms. Ex vivosuprachiasmatic nucleus slices from Sik3-/- mice exhibited destabilized and desynchronized molecular rhythms among individual neurons...
December 11, 2017: ELife
https://www.readbyqxmd.com/read/29216180/the-ink4a-arf-locus-operates-as-a-regulator-of-the-circadian-clock-modulating-ras-activity
#2
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/29215003/rhythmic-potassium-transport-regulates-the-circadian-clock-in-human-red-blood-cells
#3
Erin A Henslee, Priya Crosby, Stephen J Kitcatt, Jack S W Parry, Andrea Bernardini, Rula G Abdallat, Gabriella Braun, Henry O Fatoyinbo, Esther J Harrison, Rachel S Edgar, Kai F Hoettges, Akhilesh B Reddy, Rita I Jabr, Malcolm von Schantz, John S O'Neill, Fatima H Labeed
Circadian rhythms organize many aspects of cell biology and physiology to a daily temporal program that depends on clock gene expression cycles in most mammalian cell types. However, circadian rhythms are also observed in isolated mammalian red blood cells (RBCs), which lack nuclei, suggesting the existence of post-translational cellular clock mechanisms in these cells. Here we show using electrophysiological and pharmacological approaches that human RBCs display circadian regulation of membrane conductance and cytoplasmic conductivity that depends on the cycling of cytoplasmic K+ levels...
December 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/29163208/circadian-alterations-in-a-murine-model-of-hypothalamic-glioma
#4
José M Duhart, Lucila Brocardo, Carlos S Caldart, Luciano Marpegan, Diego A Golombek
The mammalian circadian system is controlled by a central oscillator located in the suprachiasmatic nuclei (SCN) of the hypothalamus, in which glia appears to play a prominent role. Gliomas originate from glial cells and are the primary brain tumors with the highest incidence and mortality. Optic pathway/hypothalamic gliomas account for 4-7% of all pediatric intracranial tumors. Given the anatomical location, which compromises both the circadian pacemaker and its photic input pathway, we decided to study whether the presence of gliomas in the hypothalamic region could alter circadian behavioral outputs...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29161870/modeling-transcriptional-co-regulation-of-mammalian-circadian-clock
#5
Yanqin Wang, Xin Ni, Jie Yan, Ling Yang
The circadian clock is a self-sustaining oscillator that has a period of about 24 hours at the molecular level. The oscillator is a transcription-translation feedback loop system composed of several genes. In this paper, a scalar nonlinear differential equation with two delays, modeling the transcriptional co-regulation in mammalian circadian clock, is proposed and analyzed. Sufficient conditions are established for the asymptotic stability of the unique nontrivial positive equilibrium point of the model by studying an exponential polynomial characteristic equation with delay-dependent coefficients...
October 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/29152229/ticking-time-bombs-connections-between-circadian-clocks-and-cancer
#6
REVIEW
Katja A Lamia
Connections between mammalian circadian and cell division cycles have been postulated since the early 20th century, and epidemiological and genetic studies have linked disruption of circadian clock function to increased risk of several types of cancer. In the past decade, it has become clear that circadian clock components influence cell growth and transformation in a cell-autonomous manner. Furthermore, several molecular mechanistic connections have been described in which clock proteins participate in sensing DNA damage, modulating DNA repair, and influencing the ubiquitination and degradation of key players in oncogenesis (c-MYC) and tumor suppression (p53)...
2017: F1000Research
https://www.readbyqxmd.com/read/29152136/postnatal-calpain-inhibition-elicits-cerebellar-cell-death-and-motor-dysfunction
#7
Junyao Li, Sanjuan Yang, Guoqi Zhu
Calpain-1 deletion elicits neurodevelopmental disorders, such as ataxia. However, the function of calpain in postnatal neurodevelopment and its mechanisms remain unknown. In this study, we revealed that postnatal intraperitoneal injection of various calpain inhibitors attenuated cerebellar cytosolic calpain activity. Moreover, postnatal application of calpeptin (2 mg/kg) apparently reduced spectrin breakdown, promoted suprachiasmatic nucleus circadian oscillatory protein (SCOP) accumulation in cerebellar tissue...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29149024/the-role-of-the-mammalian-prion-protein-in-the-control-of-sleep
#8
REVIEW
Amber Roguski, Andrew C Gill
Sleep disruption is a prevalent clinical feature in many neurodegenerative disorders, including human prion diseases where it can be the defining dysfunction, as in the case of the "eponymous" fatal familial insomnia, or an early-stage symptom as in certain types of Creutzfeldt-Jakob disease. It is important to establish the role of the cellular prion protein (PrP(C)), the key molecule involved in prion pathogenesis, within the sleep-wake system in order to understand fully the mechanisms underlying its contribution to both healthy circadian rhythmicity and sleep dysfunction during disease...
November 17, 2017: Pathogens
https://www.readbyqxmd.com/read/29139560/the-mammalian-circadian-clock-exhibits-chronic-ethanol-tolerance-and-withdrawal-induced-glutamate-hypersensitivity-accompanied-by-changes-in-glutamate-and-trkb-receptor-proteins
#9
Jonathan H Lindsay, Rebecca A Prosser
BACKGROUND: Alcohol tolerance and withdrawal-induced effects are criteria for alcohol use disorders listed by the DSM-V. Although tolerance and withdrawal have been studied over many decades, there is still uncertainty regarding mechanistic distinctions that characterize these different forms of ethanol (EtOH)-induced plasticity. Previously, we demonstrated that the suprachiasmatic nucleus (SCN) circadian clock develops both acute and rapid tolerance to EtOH inhibition of glutamate-induced circadian phase shifts...
November 15, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/29117554/downregulation-of-the-apelinergic-axis-accelerates-aging-whereas-its-systemic-restoration-improves-the-mammalian-healthspan
#10
Rahul Rai, Asish K Ghosh, Mesut Eren, Alexander R Mackie, Daniel C Levine, So-Youn Kim, Jonathan Cedernaes, Veronica Ramirez, Daniele Procissi, Layton H Smith, Teresa K Woodruff, Joseph Bass, Douglas E Vaughan
Aging drives the occurrence of numerous diseases, including cardiovascular disease (CVD). Recent studies indicate that blood from young mice reduces age-associated pathologies. However, the "anti-aging" factors in juvenile circulation remain poorly identified. Here, we characterize the role of the apelinergic axis in mammalian aging and identify apelin as an anti-aging factor. The expression of apelin (apln) and its receptor (aplnr) exhibits an age-dependent decline in multiple organs. Reduced apln signaling perturbs organismal homeostasis; mice harboring genetic deficiency of aplnr or apln exhibit enhanced cardiovascular, renal, and reproductive aging...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29117548/multiplexing-visual-signals-in-the-suprachiasmatic-nuclei
#11
Adam R Stinchcombe, Joshua W Mouland, Kwoon Y Wong, Robert J Lucas, Daniel B Forger
The suprachiasmatic nuclei (SCN), the site of the mammalian circadian (daily) pacemaker, contains thousands of interconnected neurons, some of which receive direct retinal input. Here, we study the fast (<1 s) responses of SCN neurons to visual stimuli with a large-scale mathematical model tracking the ionic currents and voltage of all SCN neurons. We reconstruct the SCN network connectivity and reject 99.99% of theoretically possible SCN networks by requiring that the model reproduces experimentally determined receptive fields of SCN neurons...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29113166/expression-of-circadian-clock-genes-in-human-colorectal-adenoma-and-carcinoma
#12
Tomoyuki Momma, Hirokazu Okayama, Masaru Saitou, Hidekazu Sugeno, Nobuhiro Yoshimoto, Yuji Takebayashi, Shinji Ohki, Seiichi Takenoshita
Circadian rhythms are fundamental biological systems in most organisms. Epidemiological and animal studies have demonstrated that disruption of circadian rhythms is linked to tumor progression and mammalian tumorigenesis. However, the clinical significance of in situ clock gene expression in precancerous and cancerous colorectal lesions remains unknown. The present study aimed to investigate mRNA transcript levels of circadian clock genes within human colorectal cancer and adenoma tissue sections. Using in situ hybridization, the expression of key clock genes, including period circadian protein homolog (Per) 1 and 2, cryptochrome 1 (Cry1), circadian locomoter output cycles protein kaput (Clock), brain and muscle ARNT-like protein 1 (Bmal1) and casein kinase 1ε (CK1ε) were retrospectively examined in 51 cases of colorectal carcinoma and 10 cases of adenoma...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29099263/dosing-time-dependent-in-vitro-pharmacodynamics-of-everolimus-despite-a-defective-circadian-clock
#13
Yuan Zhang, Sylvie Giacchetti, Alexandre Parouchev, Eva Hadadi, Xiaomei Li, Robert Dallmann, Helena Xandri-Monje, Lucie Portier, Rene Adam, Françis Lévi, Sandrine Dulong, Yunhua Chang
Everolimus (EV), a rapamycin analogue mTOR inhibitor, is used in the clinic to treat Estrogen positive (ER(+)) breast cancer in order to avoid the resistance to hormonotherapy. Here, we investigated whether EV efficacy varied according to administration timing by using the ER(+) breast cancer cell line MCF-7 as model system. Our results showed that instead of apoptosis, EV induced a G0/G1 phase blockage of MCF-7 cells. Following serum shock, MCF-7 cells displayed a statistically significant 24h rhythm of mammalian target of Rapamycin (mTOR) activity, but perturbed circadian clock genes oscillations...
November 3, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29095827/co-option-of-the-bzip-transcription-factor-vrille-as-the-activator-of-doublesex1-in-environmental-sex-determination-of-the-crustacean-daphnia-magna
#14
Nur Syafiqah Mohamad Ishak, Quang Dang Nong, Tomoaki Matsuura, Yasuhiko Kato, Hajime Watanabe
Divergence of upstream regulatory pathways of the transcription factor Doublesex (Dsx) serves as a basis for evolution of sex-determining mechanisms in animals. However, little is known about the regulation of Dsx in environmental sex determination. In the crustacean Daphnia magna, environmental sex determination is implemented by male-specific expression of the Dsx ortholog, Dsx1. Transcriptional regulation of Dsx1 comprises at least three phases during embryogenesis: non-sex-specific initiation, male-specific up-regulation, and its maintenance...
November 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29070825/melanopsin-a-canonical-light-receptor-mediates-thermal-activation-of-clock-genes
#15
Maria Nathália Moraes, Leonardo Vinícius Monteiro de Assis, Keila Karoline Magalhães-Marques, Maristela Oliveira Poletini, Leonardo Henrique Ribeiro Graciani de Lima, Ana Maria de Lauro Castrucci
Melanopsin (OPN4) is a photo-pigment found in a small subset of intrinsically photosensitive ganglion cells (ipRGCs) of the mammalian retina. These cells play a role in synchronizing the central circadian pacemaker to the astronomical day by conveying information about ambient light to the hypothalamic suprachiasmatic nucleus, the site of the master clock. We evaluated the effect of a heat stimulus (39.5 °C) on clock gene (Per1 and Bmal1) expression in cultured murine Melan-a melanocytes synchronized by medium changes, and in B16-F10 melanoma cells, in the presence of the selective OPN4 antagonist AA92593, or after OPN4 knockdown by small interfering RNA (siRNA)...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29059507/the-non-visual-opsins-eighteen-in-the-ancestor-of-vertebrates-astonishing-increase-in-ray-finned-fish-and-loss-in-amniotes
#16
Felix Emile Gastonguay Beaudry, Tom W Iwanicki, Bertha Ruth Zelada Mariluz, Sylvain Darnet, Henner Brinkmann, Patricia Schneider, John Stewart Taylor
Non-visual opsins were discovered in the early 1990s. These genes play roles in circadian rhythm in mammals, seasonal reproduction in birds, light avoidance in amphibian larvae, and neural development in fish. However, the interpretation of such studies and the success of future work are compromised by the fact that non-visual opsin repertoires have not been properly characterized in any of these lineages. Here, we show that non-visual opsins from tetrapods and ray-finned fish are distributed among 18 monophyletic subfamilies...
November 2017: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/29059248/clock-dependent-and-system-driven-oscillators-interact-in-the-suprachiasmatic-nuclei-to-pace-mammalian-circadian-rhythms
#17
Karine Abitbol, Ségolène Debiesse, François Molino, Pietro Mesirca, Isabelle Bidaud, Yoichi Minami, Matteo E Mangoni, Kazuhiro Yagita, Patrice Mollard, Xavier Bonnefont
Circadian clocks drive biological rhythms with a period of approximately 24 hours and keep in time with the outside world through daily resetting by environmental cues. While this external entrainment has been extensively investigated in the suprachiasmatic nuclei (SCN), the role of internal systemic rhythms, including daily fluctuations in core temperature or circulating hormones remains debated. Here, we show that lactating mice, which exhibit dampened systemic rhythms, possess normal molecular clockwork but impaired rhythms in both heat shock response gene expression and electrophysiological output in their SCN...
2017: PloS One
https://www.readbyqxmd.com/read/29044737/chronic-bmy7378-treatment-alters-behavioral-circadian-rhythms
#18
Jhenkruthi Vijaya Shankara, Angélique Orr, Richelle Mychasiuk, Michael C Antle
The mammalian circadian clock is synchronized to the day : night cycle by light. Serotonin modulates the circadian effects of light, with agonists inhibiting response to light and antagonists enhancing responses to light. A special class of serotonergic compounds, the mixed 5-HT1A agonist/antagonists, potentiates light-induced phase advances by up to 400% when administered acutely. In this study, we examine the effects of one of these mixed 5-HT1A agonist/antagonists, BMY7378, when administered chronically...
October 17, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28986235/alpha-synuclein-epigenetics-mitochondria-metabolism-calcium-traffic-circadian-dysfunction-in-parkinson-s-disease-an-integrated-strategy-for-management
#19
REVIEW
Oliver T Phillipson
The motor deficits which characterise the sporadic form of Parkinson's disease arise from age-related loss of a subset of dopamine neurons in the substantia nigra. Although motor symptoms respond to dopamine replacement therapies, the underlying disease process remains. This review details some features of the progressive molecular pathology and proposes deployment of a combination of nutrients: R-lipoic acid, acetyl-l-carnitine, ubiquinol, melatonin (or receptor agonists) and vitamin D3, with the collective potential to slow progression of these features...
November 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28978916/the-innate-immune-cell-response-to-bacterial-infection-in-larval-zebrafish-is-light-regulated
#20
Lucia Y Du, Hannah Darroch, Pramuk Keerthisinghe, Elina Ashimbayeva, Jonathan W Astin, Kathryn E Crosier, Philip S Crosier, Guy Warman, James Cheeseman, Christopher J Hall
The circadian clock, which evolved to help organisms harmonize physiological responses to external conditions (such as the light/dark cycle, LD), is emerging as an important regulator of the immune response to infection. Gaining a complete understanding of how the circadian clock influences the immune cell response requires animal models that permit direct observation of these processes within an intact host. Here, we investigated the use of larval zebrafish, a powerful live imaging system, as a new model to study the impact of a fundamental zeitgeber, light, on the innate immune cell response to infection...
October 4, 2017: Scientific Reports
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