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https://www.readbyqxmd.com/read/28065650/network-dynamics-mediate-circadian-clock-plasticity
#1
Abdelhalim Azzi, Jennifer A Evans, Tanya Leise, Jihwan Myung, Toru Takumi, Alec J Davidson, Steven A Brown
A circadian clock governs most aspects of mammalian behavior. Although its properties are in part genetically determined, altered light-dark environment can change circadian period length through a mechanism requiring de novo DNA methylation. We show here that this mechanism is mediated not via cell-autonomous clock properties, but rather through altered networking within the suprachiasmatic nuclei (SCN), the circadian "master clock," which is DNA methylated in region-specific manner. DNA methylation is necessary to temporally reorganize circadian phasing among SCN neurons, which in turn changes the period length of the network as a whole...
January 2, 2017: Neuron
https://www.readbyqxmd.com/read/28057520/molecular-basis-for-the-regulation-of-the-circadian-clock-kinases-ck1%C3%AE-and-ck1%C3%AE%C2%B5
#2
REVIEW
Yu Yang, Tingting Xu, Yunfei Zhang, Ximing Qin
CK1δ and CK1ε are unique in the casein kinase 1 family and play critical roles in a number of physiological intracellular pathways. In particular, these kinases are involved in composing the mammalian circadian clock by phosphorylating core clock proteins. Considering that CK1δ/ε phosphorylate other key biological molecules, such as β-catenin and p53, understanding how the kinase activity is regulated would be greatly significant, since they are potential targets to develop pharmacological agents against cancer, pain, and circadian disorders...
January 3, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28051908/antimicrobial-capacity-of-the-freshwater-planarians-against-s-aureus-is-under-the-control-of-timeless
#3
Landry Laure Tsoumtsa, Cedric Torre, Virginie Trouplin, Benjamin Coiffard, Gregory Gimenez, Jean-Louis Mege, Eric Ghigo
Planarians, which are non-parasitic flatworms, are highly resistant to bacterial infections. To better understand the mechanisms underlying this resistance, we investigated the role of the circadian machinery in the anti-bacterial response of the freshwater planarian Schmidtea mediterranea. We identified Smed-Tim from S. mediterranea as a homolog of the mammalian clock gene Tim. We showed via RNA interference that Smed-Tim is required for the anti-microbial activities of Schmidtea mediterranea against Staphylococcus aureus infection during the light/dark cycle...
January 4, 2017: Virulence
https://www.readbyqxmd.com/read/28025148/circadian-clock-and-steroidogenic-related-gene-expression-profiles-in-mouse-leydig-cells-following-dexamethasone-stimulation
#4
Huatao Chen, Lei Gao, Yongjie Xiong, Dan Yang, Cuimei Li, Aihua Wang, Yaping Jin
Previous studies have shown that circadian clock genes are expressed in mammalian testes; however, it remains unclear if the expression patterns of these genes are cyclic. Furthermore, it is unknown whether Leydig cells, the primary androgen secreting cells in the testis, play a role in the rhythmicity of circadian clock and steroidogenic-related gene transcription. Here, we examine the circadian clock of mouse Leydig cells, and the link to steroidogenic-related gene transcription. We confirm, via sampling over a full circadian time (CT) period, a lack of circadian rhythmicity in mouse testes in comparison with the robust gene expression cycling of circadian clock genes in mouse livers...
December 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28017587/knockout-rescue-embryonic-stem-cell-derived-mouse-reveals-circadian-period-control-by-quality-and-quantity-of-cry1
#5
Koji L Ode, Hideki Ukai, Etsuo A Susaki, Ryohei Narumi, Katsuhiko Matsumoto, Junko Hara, Naoshi Koide, Takaya Abe, Masato T Kanemaki, Hiroshi Kiyonari, Hiroki R Ueda
To conduct comprehensive characterization of molecular properties in organisms, we established an efficient method to produce knockout (KO)-rescue mice within a single generation. We applied this method to produce 20 strains of almost completely embryonic stem cell (ESC)-derived mice ("ES mice") rescued with wild-type and mutant Cry1 gene under a Cry1(-/-):Cry2(-/-) background. A series of both phosphorylation-mimetic and non-phosphorylation-mimetic CRY1 mutants revealed that multisite phosphorylation of CRY1 can serve as a cumulative timer in the mammalian circadian clock...
January 5, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28006027/evidence-for-weakened-intercellular-coupling-in-the-mammalian-circadian-clock-under-long-photoperiod
#6
M Renate Buijink, Assaf Almog, Charlotte B Wit, Ori Roethler, Anneke H O Olde Engberink, Johanna H Meijer, Diego Garlaschelli, Jos H T Rohling, Stephan Michel
For animals living in temperate latitudes, seasonal changes in day length are an important cue for adaptations of their physiology and behavior to the altered environmental conditions. The suprachiasmatic nucleus (SCN) is known as the central circadian clock in mammals, but may also play an important role in adaptations to different photoperiods. The SCN receives direct light input from the retina and is able to encode day-length by approximating the waveform of the electrical activity rhythm to the duration of daylight...
2016: PloS One
https://www.readbyqxmd.com/read/27992087/urokinase-type-plasminogen-activator-modulates-mammalian-circadian-clock-phase-regulation-in-tissue-type-plasminogen-activator-knockout-mice
#7
Joanna M Cooper, Ashutosh Rastogi, Jessica A Krizo, Eric M Mintz, Rebecca A Prosser
Glutamate phase shifts the circadian clock in the mammalian suprachiasmatic nucleus (SCN) by activating NMDA receptors. Tissue-type plasminogen activator (tPA) gates phase shifts by activating plasmin to generate m(ature)BDNF, which binds TrkB receptors allowing clock phase shifts. Here we investigate phase shifting in tPA knockout (tPA(-/-) ; B6.129S2-Plat(tm1Mlg) /J) mice, and identify urokinase-type plasminogen activator (uPA) as an additional circadian clock regulator. Behavioral activity rhythms in tPA(-/-) mice entrain to a light-dark (LD) cycle and phase shift in response to nocturnal light pulses with no apparent loss in sensitivity...
December 19, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27990019/transcriptional-architecture-of-the-mammalian-circadian-clock
#8
Joseph S Takahashi
Circadian clocks are endogenous oscillators that control 24-hour physiological and behavioural processes in organisms. These cell-autonomous clocks are composed of a transcription-translation-based autoregulatory feedback loop. With the development of next-generation sequencing approaches, biochemical and genomic insights into circadian function have recently come into focus. Genome-wide analyses of the clock transcriptional feedback loop have revealed a global circadian regulation of processes such as transcription factor occupancy, RNA polymerase II recruitment and initiation, nascent transcription, and chromatin remodelling...
December 19, 2016: Nature Reviews. Genetics
https://www.readbyqxmd.com/read/27942033/feedback-loops-of-the-mammalian-circadian-clock-constitute-repressilator
#9
J Patrick Pett, Anja Korenčič, Felix Wesener, Achim Kramer, Hanspeter Herzel
Mammals evolved an endogenous timing system to coordinate their physiology and behaviour to the 24h period of the solar day. While it is well accepted that circadian rhythms are generated by intracellular transcriptional feedback loops, it is still debated which network motifs are necessary and sufficient for generating self-sustained oscillations. Here, we systematically explore a data-based circadian oscillator model with multiple negative and positive feedback loops and identify a series of three subsequent inhibitions known as "repressilator" as a core element of the mammalian circadian oscillator...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27936378/genome-wide-identification-of-neuronal-activity-regulated-genes-in-drosophila
#10
Xiao Chen, Reazur Rahman, Fang Guo, Michael Rosbash
Activity-regulated genes (ARGs) are important for neuronal functions like long-term memory and are well-characterized in mammals but poorly studied in other model organisms like Drosophila. Here we stimulated fly neurons with different paradigms and identified ARGs using high-throughput sequencing from brains as well as from sorted neurons: they included a narrow set of circadian neurons as well as dopaminergic neurons. Surprisingly, many ARGs are specific to the stimulation paradigm and very specific to neuron type...
December 9, 2016: ELife
https://www.readbyqxmd.com/read/27929128/extraordinary-behavioral-entrainment-following-circadian-rhythm-bifurcation-in-mice
#11
Elizabeth M Harrison, Thijs J Walbeek, Jonathan Sun, Jeremy Johnson, Qays Poonawala, Michael R Gorman
The mammalian circadian timing system uses light to synchronize endogenously generated rhythms with the environmental day. Entrainment to schedules that deviate significantly from 24 h (T24) has been viewed as unlikely because the circadian pacemaker appears capable only of small, incremental responses to brief light exposures. Challenging this view, we demonstrate that simple manipulations of light alone induce extreme plasticity in the circadian system of mice. Firstly, exposure to dim nocturnal illumination (<0...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27926536/a-minimal-titration-model-of-the-mammalian-dynamical-heat-shock-response
#12
Aude Sivéry, Emmanuel Courtade, Quentin Thommen
Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response (HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular chaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms, having stress-induced activation and feedback regulations with multiple partners, the HSR is still incompletely understood. In this context, we propose a minimal molecular model for the gene regulatory network of the HSR that reproduces quantitatively different heat shock experiments both on heat shock factor 1 (HSF1) and HSPs activities...
December 7, 2016: Physical Biology
https://www.readbyqxmd.com/read/27922612/the-intricate-dance-of-post-translational-modifications-in-the-rhythm-of-life
#13
REVIEW
Arisa Hirano, Ying-Hui Fu, Louis J Ptáček
Endogenous biological rhythms with approximately 24-h periodicity are generated by the circadian clock, in which clock genes coordinate with one another and form a transcriptional-translational negative feedback loop. The precision of the circadian clock is further regulated by multiple post-translational modifications (PTMs), including phosphorylation, ubiquitination, acetylation and SUMOylation. Here, we review current understanding of the regulatory mechanisms of the core clock proteins by PTMs in the mammalian circadian clock...
December 6, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27922611/genetic-and-epigenomic-mechanisms-of-mammalian-circadian-transcription
#14
REVIEW
Romeo Papazyan, Yuxiang Zhang, Mitchell A Lazar
The mammalian molecular clock comprises a complex network of transcriptional programs that integrates environmental signals with physiological pathways in a tissue-specific manner. Emerging technologies are extending knowledge of basic clock features by uncovering their underlying molecular mechanisms, thus setting the stage for a 'systems' view of the molecular clock. Here we discuss how recent data from genome-wide genetic and epigenetic studies have informed the understanding of clock function. In addition to its importance in human physiology and disease, the clock mechanism provides an ideal model to assess general principles of dynamic transcription regulation in vivo...
December 6, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27916729/enkephalin-and-neuropeptide-y-interaction-in-the-intergeniculate-leaflet-network-a-part-of-the-mammalian-biological-clock
#15
K Palus, L Chrobok, M Kepczynski, M H Lewandowski
The intergeniculate leaflet (IGL) is a flat thalamic nucleus implicated in the modulation of circadian rhythmicity. In rat, two main GABAergic subpopulations can be distinguished in the IGL: neurons synthesizing neuropeptide Y (NPY), which directly innervates the suprachiasmatic nuclei, and enkephalinergic cells, which connect contralaterally located leaflets. The aim of this study was to evaluate possible effects of inner IGL neurotransmitters on the spontaneous and synaptic activity of IGL neurons. The data presented in this article provide evidence that enkephalin, and not NPY, could act upon the majority of IGL neurons...
December 2, 2016: Neuroscience
https://www.readbyqxmd.com/read/27909716/aberrant-timeless-expression-is-associated-with-poor-clinical-survival-and-lymph-node-metastasis-in-early-stage-cervical-carcinoma
#16
Weijing Zhang, Weiling He, Yongjie Shi, Jing Zhao, Sailan Liu, Fengxiang Zhang, Jiarui Yang, Chuanmiao Xie, Yanna Zhang
TIMELESS is a highly conserved protein required for the maintenance of normal mammalian circadian oscillations and for controlling cellular metabolism and proliferation. Recently, TIMELESS was implicated in the tumorigenesis of certain cancers. However, little is known on TIMELESS protein expression and its potential as a prognostic factor in cervical cancer. Here, we investigate TIMELESS expression pattern and its clinicopathological significance in early-stage cervical carcinoma. TIMELESS mRNA and protein expression was evaluated by real-time PCR and western blot analysis in cervical cancer cell lines, a normal cervical cell line, as well as in six pairs of surgically removed cervical cancer and adjacent normal cervical tissues...
January 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/27892932/reciprocal-regulation-of-carbon-monoxide-metabolism-and-the-circadian-clock
#17
Roman Klemz, Silke Reischl, Thomas Wallach, Nicole Witte, Karsten Jürchott, Sabrina Klemz, Veronika Lang, Stephan Lorenzen, Miriam Knauer, Steffi Heidenreich, Min Xu, Jürgen A Ripperger, Michael Schupp, Ralf Stanewsky, Achim Kramer
Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a wide range of physiological, metabolic and behavioral processes. Feedback of metabolic signals, such as redox state, NAD(+)/NADH and AMP/ADP ratios, or heme, modulate circadian rhythms and thereby optimize energy utilization across the 24-h cycle. We show that rhythmic heme degradation, which generates the signaling molecule carbon monoxide (CO), is required for normal circadian rhythms as well as circadian metabolic outputs. CO suppresses circadian transcription by attenuating CLOCK-BMAL1 binding to target promoters...
November 28, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27885007/circadian-physiology-of-metabolism
#18
REVIEW
Satchidananda Panda
A majority of mammalian genes exhibit daily fluctuations in expression levels, making circadian expression rhythms the largest known regulatory network in normal physiology. Cell-autonomous circadian clocks interact with daily light-dark and feeding-fasting cycles to generate approximately 24-hour oscillations in the function of thousands of genes. Circadian expression of secreted molecules and signaling components transmits timing information between cells and tissues. Such intra- and intercellular daily rhythms optimize physiology both by managing energy use and by temporally segregating incompatible processes...
November 25, 2016: Science
https://www.readbyqxmd.com/read/27879349/ncam1-polysialylation-the-prion-protein-s-elusive-reason-for-being
#19
REVIEW
Mohadeseh Mehrabian, Herbert Hildebrandt, Gerold Schmitt-Ulms
Much confusion surrounds the physiological function of the cellular prion protein (PrP(C)). It is, however, anticipated that knowledge of its function will shed light on its contribution to neurodegenerative diseases and suggest ways to interfere with the cellular toxicity central to them. Consequently, efforts to elucidate its function have been all but exhaustive. Building on earlier work that uncovered the evolutionary descent of the prion founder gene from an ancestral ZIP zinc transporter, we recently investigated a possible role of PrP(C) in a morphogenetic program referred to as epithelial-to-mesenchymal transition (EMT)...
December 2016: ASN Neuro
https://www.readbyqxmd.com/read/27879317/correlated-evolution-between-ck1%C3%AE-protein-and-the-serine-rich-motif-contributes-to-regulating-the-mammalian-circadian-clock
#20
Lijuan Xing, Yang An, Guangsen Shi, Jie Yan, Pancheng Xie, Zhipeng Qu, Zhihui Zhang, Zhiwei Liu, Dejing Pan, Ying Xu
Understanding the mechanism underlying the physiological divergence of species is a long-standing issue in evolutionary biology. The circadian clock is a highly conserved system existing in almost all organisms that regulates a wide range of physiological and behavioral events to adapt to the day-night cycle. Here, the interactions between hCK1ϵ/δ/DBT (Drosophila ortholog of CK1δ/ϵ) and serine-rich (SR) motifs from hPER2 (ortholog of Drosophila per) were reconstructed in a Drosophila circadian system. The results indicated that in Drosophila, the SR mutant form hPER2(S662G) does not recapitulate the mouse or human mutant phenotype...
January 6, 2017: Journal of Biological Chemistry
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