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Pallavi Lamba, Lauren E Foley, Patrick Emery
Light is one of the chief environmental cues that reset circadian clocks. In Drosophila , CRYPTOCHROME (CRY) mediates acute photic resetting of circadian clocks by promoting the degradation of TIMELESS (TIM) in a cell-autonomous manner. Thus, even circadian oscillators in peripheral organs can independently perceive light in Drosophila However, there is substantial evidence for non-autonomous mechanisms of circadian photoreception in the brain. We have previously shown that the Morning (M) and Evening (E) oscillators are critical light-sensing neurons that cooperate to shift the phase of circadian behavior in response to light input...
June 6, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Mary Anna Venneri, Valeria Hasenmajer, Daniela Fiore, Emilia Sbardella, Riccardo Pofi, Chiara Graziadio, Daniele Gianfrilli, Claudia Pivonello, Mariarosaria Negri, Fabio Naro, Ashley B Grossman, Andrea Lenzi, Rosario Pivonello, Andrea M Isidori
Context: Adrenal insufficiency (AI) requires life-long glucocorticoid replacement. Conventional therapies fail to mimic the endogenous cortisol circadian rhythm. Clock genes are essential components of the molecular machinery controlling an organ's circadian function and are influenced by glucocorticoids. However, clock gene expression has never been investigated in AI patients. Objective: To evaluate the effect of the timing of glucocorticoid administration on circadian gene expression in peripheral blood mononuclear cells (PBMCs) of AI patients from the DREAM trial...
May 25, 2018: Journal of Clinical Endocrinology and Metabolism
Áron Szabó, Christian Papin, David Cornu, Elisabeth Chélot, Zoltán Lipinszki, Andor Udvardy, Virginie Redeker, Ugo Mayor, François Rouyer
Circadian clocks have evolved as time-measuring molecular devices to help organisms adapt their physiology to daily changes in light and temperature. Transcriptional oscillations account for a large fraction of rhythmic protein abundance. However, cycling of various posttranslational modifications, such as ubiquitylation, also contributes to shape the rhythmic protein landscape. In this study, we used an in vivo ubiquitin labeling assay to investigate the circadian ubiquitylated proteome of Drosophila melanogaster...
May 22, 2018: Cell Reports
Maite Ogueta, Roger C Hardie, Ralf Stanewsky
The daily light-dark cycles represent a key signal for synchronizing circadian clocks. Both insects and mammals possess dedicated "circadian" photoreceptors but also utilize the visual system for clock resetting. In Drosophila, circadian clock resetting is achieved by the blue-light photoreceptor cryptochrome (CRY), which is expressed within subsets of the brain clock neurons. In addition, rhodopsin-expressing photoreceptor cells contribute to light synchronization. Light resets the molecular clock by CRY-dependent degradation of the clock protein Timeless (TIM), although in specific subsets of key circadian pacemaker neurons, including the small ventral lateral neurons (s-LNvs), TIM and Period (PER) oscillations can be synchronized by light independent of CRY and canonical visual Rhodopsin phototransduction...
April 30, 2018: Current Biology: CB
Kalliopi Keramida, Nikolaos Kouris
No abstract text is available yet for this article.
May 12, 2018: Hellenic Journal of Cardiology: HJC, Hellēnikē Kardiologikē Epitheōrēsē
John S Torday
Biology has remained descriptive since its formalization by Linnaeus in the 18th Century. Dobzhansky has challenged us to think mechanistically by stating that 'Nothing in Biology makes sense except in the light of evolution', but NeoDarwinian evolution remains untestable or refutable. The physicist Bohm has encouraged us to recognize that our perception of 'reality' is mediated by our evolved, subjective senses, though there is a coherent Implicate Order just out of reach. Only recently has a novel understanding of physiologic evolution based on cell-cell communication for embryonic development and phylogeny offered the opportunity to mechanistically merge Quantum Mechanics with Evolutionary Biology...
May 2, 2018: Progress in Biophysics and Molecular Biology
Sin Ho Kweon, Jongbin Lee, Chunghun Lim, Joonho Choe
Post-translational control is a crucial mechanism for circadian timekeeping. Evolutionarily conserved kinases and phosphatases have been implicated in circadian phosphorylation and degradation of clock-relevant proteins, which sustain high-amplitude rhythms with 24 hr periodicity in animal behaviors and physiology. Here, we report a novel clock function of the heterodimeric Ca2+ /calmodulin-dependent phosphatase calcineurin and its regulator sarah ( sra ) in Drosophila Genomic deletion of the sra locus dampened circadian locomotor activity rhythms in free-running constant dark after entrainment in light-dark cycles...
May 3, 2018: Genetics
Alan K Davis, Joseph P Barsuglia, Rafael Lancelotta, Robert M Grant, Elise Renn
BACKGROUND/AIM: 5-Methoxy- N,N-dimethyltryptamine (5-MeO-DMT) is a psychoactive compound found in several plants and in high concentrations in Bufo alvarius toad venom. Synthetic, toad, and plant-sourced 5-MeO-DMT are used for spiritual and recreational purposes and may have psychotherapeutic effects. However, the use of 5-MeO-DMT is not well understood. Therefore, we examined patterns of use, motivations for consumption, subjective effects, and potential benefits and consequences associated with 5-MeO-DMT use...
April 1, 2018: Journal of Psychopharmacology
Katherina Beck, Anna Hovhanyan, Pamela Menegazzi, Charlotte Helfrich-Förster, Thomas Raabe
Endogenous molecular circadian clocks drive daily rhythmic changes at the cellular, physiological, and behavioral level for adaptation to and anticipation of environmental signals. The core molecular system consists of autoregulatory feedback loops, where clock proteins inhibit their own transcription. A complex and not fully understood interplay of regulatory proteins influences activity, localization and stability of clock proteins to set the pace of the clock. This study focuses on the molecular function of Ribosomal S6 Kinase (RSK) in the Drosophila melanogaster circadian clock...
2018: Frontiers in Molecular Neuroscience
Andrew E Christie, Andy Yu, Micah G Pascual, Vittoria Roncalli, Matthew C Cieslak, Amanda N Warner, Tess J Lameyer, Meredith E Stanhope, Patsy S Dickinson, J Joe Hull
Essentially all organisms exhibit recurring patterns of physiology/behavior that oscillate with a period of ~24-h and are synchronized to the solar day. Crustaceans are no exception, with robust circadian rhythms having been documented in many members of this arthropod subphylum. However, little is known about the molecular underpinnings of their circadian rhythmicity. Moreover, the location of the crustacean central clock has not been firmly established, although both the brain and eyestalk ganglia have been hypothesized as loci...
April 11, 2018: Marine Genomics
Deniz Top, Jenna L O'Neil, Gregory E Merz, Kritika Dusad, Brian R Crane, Michael W Young
In the Drosophila circadian clock, Period (PER) and Timeless (TIM) proteins inhibit Clock-mediated transcription of per and tim genes until PER is degraded by Doubletime/CK1 (DBT)-mediated phosphorylation, establishing a negative feedback loop. Multiple regulatory delays within this feedback loop ensure ~24 hr periodicity. Of these delays, the mechanisms that regulate delayed PER degradation (and Clock reactivation) remain unclear. Here we show that phosphorylation of certain DBT target sites within a central region of PER affect PER inhibition of Clock and the stability of the PER/TIM complex...
April 3, 2018: ELife
D Lipsker
This is a short reflection about bedside reasoning in clinical medicine, emphasizing the importance of distinguishing between causes and mechanisms of diseases. All complex/sporadic diseases result from interactions between a genetic predisposition and environmental factors. The main disease mechanisms resulting in clinical signs involve inflammation, insult of vessels or nerves, pharmacological or hormonal dysfunction, altered metabolism and overload, tumoral proliferations, intrinsic dysfunction, malformation and traumatism...
March 31, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
Changfan Lin, Deniz Top, Craig C Manahan, Michael W Young, Brian R Crane
Cryptochromes (CRYs) entrain the circadian clocks of plants and animals to light. Irradiation of the Drosophila cryptochrome (dCRY) causes reduction of an oxidized flavin cofactor by a chain of conserved tryptophan (Trp) residues. However, it is unclear how redox chemistry within the Trp chain couples to dCRY-mediated signaling. Here, we show that substitutions of four key Trp residues to redox-active tyrosine and redox-inactive phenylalanine tune the light sensitivity of dCRY photoreduction, conformational activation, cellular stability, and targeted degradation of the clock protein timeless (TIM)...
April 10, 2018: Proceedings of the National Academy of Sciences of the United States of America
Thomas Foth, Jette Lange, Kylie Smith
Mainstream nursing history often positions itself in opposition to philosophy and many nursing historians are reticent of theorizing. In the quest to illuminate the lives of nurses and women current historical approaches are driven by reformist aspirations but are based on the conception that nursing or caring is basically good and the timelessness of universal values. This has the effect of essentialising political categories of identity such as class, race and gender. This kind of history is about affirmation rather than friction and about the conservation of memory and musealization...
March 24, 2018: Nursing Philosophy: An International Journal for Healthcare Professionals
Chantal Beatrice Magne Nde, Gloria Casas Gimeno, Maria Docanto, Kevin C Knower, Morag J Young, Jakob Buehn, Edris Sayed, Colin D Clyne
Activation of estrogen receptor α (ERα) stimulates cell division and tumor growth by modulating the expression of ERα target genes. This activation involves the recruitment of specific proteins with activities that are still not fully understood. Timeless, the human homolog of the Drosophila gene involved in circadian rhythm, was previously shown to be a strong predictor of tamoxifen relapse, and is involved in genomic stability and cell cycle control. In this study, we investigated the interplay between Timeless and ERα, and showed that human Timeless is an ERα coactivator...
May 11, 2018: Journal of Molecular Biology
Yiran Ao, Qin Zhao, Kai Yang, Gang Zheng, Xiaoqing Lv, Xiaoli Su
Clock genes are the core of the circadian rhythms in the human body and are important in regulating normal physiological functions. To date, research has indicated that the clock gene, period circadian clock 2 ( PER2 ), is downregulated in numerous types of cancer, and that it is associated with cancer occurrence and progression via the regulation of various downstream cell cycle genes. However, it remains unclear whether the decreased expression of PER2 influences the expression of other clock genes in cancer cells...
April 2018: Oncology Letters
Riikka Tapanainen, Darren J Parker, Maaria Kankare
To function properly, organisms must adjust their physiology, behavior and metabolism in response to a suite of varying environmental conditions. One of the central regulators of these changes is organisms' internal circadian clock, and recent evidence has suggested that the clock genes are also important in the regulation of seasonal adjustments. In particular, thermosensitive splicing of the core clock gene timeless in a cosmopolitan fly, Drosophila melanogaster , has implicated this gene to be involved in thermal adaptation...
March 28, 2018: G3: Genes—Genomes—Genetics
Ana Filošević, Sabina Al-Samarai, Rozi Andretić Waldowski
Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila ...
2018: Frontiers in Molecular Neuroscience
Yue Ma, Yongchuang Wang, Donghua Xie, Yue Gu, Haimin Zhang, Guozhong Wang, Yunxia Zhang, Huijun Zhao, Po Keung Wong
Excessive uptake of nitrite has been proven to be detrimental to the ecological system and human health. Hence, there is a rising requirement for constructing effective electrochemical sensors to precisely monitor the level of nitrite. In this work, NiFe-layered double hydroxide nanosheet arrays (NiFe-LDH NSAs) have been successfully fabricated on a carbon cloth (CC) substrate via a facile one-pot hydrothermal route. By integrating the collective merits of macroporous CC and NiFe-LDH NSAs such as superior electrical conductivity, striking synergistic effect between the dual active components, enlarged electrochemically active surface area, unique three-dimensional hierarchical porous network characteristics, and fast charge transport and ion diffusion, the proposed NiFe-LDH NSAs/CC architecture can be served as a self-supporting sensor toward nitrite detection...
February 21, 2018: ACS Applied Materials & Interfaces
Shumaila Noreen, Mirko Pegoraro, Faisal Nouroz, Eran Tauber, Charalambos P Kyriacou
The level of rescue of clock function in genetically arrhythmic Drosophila melanogaster hosts using interspecific clock gene transformation was used to study the putative intermolecular coevolution between interacting clock proteins. Among them PER and TIM are the two important negative regulators of the circadian clock feedback loop. We transformed either the D. pseudoobscura per or tim transgenes into the corresponding arrhythmic D. melanogaster mutant (per01 or tim01) and observed >50% rhythmicity but the period of activity rhythm was either longer (D...
March 30, 2018: Gene
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