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Replication Stress

Mariusz Papp, Piotr Gruca, Magdalena Lason-Tyburkiewicz, Paul Willner
Ketamine is the prototype of a new generation of antidepressant drugs, which is reported in clinical studies to be effective in treatment-resistant patients, with an effect that appears within hours and lasts for a few days. Chronic mild stress (CMS) is a well-established and widely used animal model of depression, in which anhedonia, anxiogenesis and cognitive dysfunction can be observed reliably. Studies using acute or brief ketamine treatment following withdrawal from CMS have replicated the clinical finding of a rapid onset of antidepressant action...
October 18, 2016: Behavioural Pharmacology
Jovan Nikolic, Ahmet Civas, Zoé Lama, Cécile Lagaudrière-Gesbert, Danielle Blondel
Stress granules (SGs) are membrane-less dynamic structures consisting of mRNA and protein aggregates that form rapidly in response to a wide range of environmental cellular stresses and viral infections. They act as storage sites for translationally silenced mRNAs under stress conditions. During viral infection, SG formation results in the modulation of innate antiviral immune responses, and several viruses have the ability to either promote or prevent SG assembly. Here, we show that rabies virus (RABV) induces SG formation in infected cells, as revealed by the detection of SG-marker proteins Ras GTPase-activating protein-binding protein 1 (G3BP1), T-cell intracellular antigen 1 (TIA-1) and poly(A)-binding protein (PABP) in the RNA granules formed during viral infection...
October 2016: PLoS Pathogens
Xiaojuan Huang, Jung-Ho Shin, Azul Pinochet-Barros, Tina T Su, John D Helmann
The Bacillus subtilis MntR metalloregulatory protein senses manganese, an essential element required for central metabolism, oxidative stress resistance and replication. An mntR null mutant is highly sensitive to Mn(II) intoxication, which is attributed in part to the constitutive expression of two importers: the proton-dependent NRAMP family transporter MntH and the ABC transporter MntABCD. Here, we show that an mntR null mutant is still sensitive to Mn(II) intoxication even if both of the import systems are absent...
October 17, 2016: Molecular Microbiology
Jyoti K Jha, Revathy Ramachandran, Dhruba K Chattoraj
The local separation of duplex DNA strands (strand opening) is necessary for initiating basic transactions on DNA such as transcription, replication, and homologous recombination. Strand opening is commonly a stage at which these processes are regulated. Many different mechanisms are used to open the DNA duplex, the details of which are of great current interest. In this review, we focus on a few well-studied cases of DNA replication origin opening in bacteria. In particular, we discuss the opening of origins that support the theta (θ) mode of replication, which is used by all chromosomal origins and many extra-chromosomal elements such as plasmids and phages...
2016: Frontiers in Molecular Biosciences
Hyun-Jin Kim, Jin-Young Min, Kyoung-Bok Min
OBJECTIVES: Central obesity plays a major role in the development of many chronic diseases, including cardiovascular disease and cancer. Chronic stress may be involved in the pathophysiology of central obesity. Although several large-scale genome-wide association studies have reported susceptibility genes for central adiposity, the effects of interactions between genes and psychosocial stress on central adiposity have rarely been examined. A recent study focusing on Caucasians discovered the novel gene early B-cell factor 1 (EBF1), which was associated with central obesity-related traits via interactions with stress levels...
September 2016: Journal of Preventive Medicine and Public Health, Yebang Ŭihakhoe Chi
Prabhaker Yadav, Ratnesh K Tripathi, Rajeev K Singh, Vindhya Mohindra
During the investigation of genes involved in the hypoxia tolerance, novel transcript, Replication Termination Factor 2 homologue (RTF2h), was found to be differentially expressed in brain of Clarias magur (previous name, C. batrachus) whose function was still undefined. Thus, present study was aimed to examine the transcriptional response of novel RTF2h gene, for its possible involvement in hypoxia tolerance in C. magur. Novel transcripts expressed under hypoxic stress were identified from ESTs obtained from SSH libraries of C...
October 14, 2016: Molecular Biology Reports
Getachew Tesfaye Beyene, Seetha V Balasingham, Stephan A Frye, Amine Namouchi, Håvard Homberset, Shewit Kalayou, Tahira Riaz, Tone Tønjum
Neisseria meningitidis (Nm) is a Gram-negative oral commensal that opportunistically can cause septicaemia and/or meningitis. Here, we overexpressed, purified and characterized the Nm DNA repair/recombination helicase RecG (RecGNm) and examined its role during genotoxic stress. RecGNm possessed ATP-dependent DNA binding and unwinding activities in vitro on a variety of DNA model substrates including a Holliday junction (HJ). Database searching of the Nm genomes identified 49 single nucleotide polymorphisms (SNPs) in the recGNm including 37 non-synonymous SNPs (nsSNPs), and 7 of the nsSNPs were located in the codons for conserved active site residues of RecGNm...
2016: PloS One
Asish K Ghosh, Rahul Rai, Kitae E Park, Mesut Eren, Toshio Miyata, Lisa D Wilsbacher, Douglas E Vaughan
Doxorubicin, an anthracycline antibiotic, is a commonly used anticancer drug. In spite of its widespread usage, its therapeutic effect is limited by its cardiotoxicity. On the cellular level, Doxorubicin-induced cardiotoxicity manifests as stress induced premature senescence. Previously, we demonstrated that plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of serine proteases, is an important biomarker and regulator of cellular senescence and aging. Here, we tested the hypothesis that pharmacological inhibition of cellular PAI-1 protects against stress- and aging-induced cellular senescence and delineated the molecular basis of protective action of PAI-1 inhibition...
October 6, 2016: Oncotarget
Julian D Ford, Andres R Schneeberger, Irina Komarovskaya, Kristina Muenzenmaier, Dorothy Castille, Lewis A Opler, Bruce Link
A new clinician rating measure, the Symptoms of Trauma Scale (SOTS) was administered to adult psychiatric outpatients (46 men, 47 women) with severe mental illness (SMI) who reported a history of trauma exposure and were recently discharged from inpatient psychiatric treatment. SOTS composite severity scores for DSM-IV and DSM-5 posttraumatic stress disorder (PTSD), complex PTSD (cPTSD), and total PTSD/cPTSD severity had acceptable internal consistency reliability. SOTS scores' construct and convergent validity was supported by correlations with self-report measures of childhood and adult trauma history, and PTSD, dissociation, and anger symptoms...
October 12, 2016: Journal of Trauma & Dissociation
Adam D LaMotte, Casey T Taft, Robin P Weatherill, Melynda D Casement, Suzannah K Creech, William P Milberg, Catherine B Fortier, Regina E McGlinchey
Objective: This study investigated sleep problems and physical pain as moderators of the relationship between PTSD symptoms and aggression among returning veterans. Prior research has demonstrated associations between PTSD symptoms and aggression, but little work has sought to identify moderators of this relationship. Sleep problems and physical pain are both common clinical problems among veterans and have theoretical links to aggression. Method: Participants were 103 returning service members and veterans recruited from the greater Boston area and enrolled in the VA Translational Research Center for Traumatic Brain Injury (TBI) and Stress Disorders (TRACTS)...
August 15, 2016: Psychological Trauma: Theory, Research, Practice and Policy
Grasiella Angelina Andriani, Vinnycius Pereira Almeida, Francesca Faggioli, Maurizio Mauro, Wanxia Li Tsai, Laura Santambrogio, Alexander Maslov, Massimo Gadina, Judith Campisi, Jan Vijg, Cristina Montagna
Age-related accumulation of ploidy changes is associated with decreased expression of genes controlling chromosome segregation and cohesin functions. To determine the consequences of whole chromosome instability (W-CIN) we down-regulated the spindle assembly checkpoint component BUB1 and the mitotic cohesin SMC1A, and used four-color-interphase-FISH coupled with BrdU incorporation and analyses of senescence features to reveal the fate of W-CIN cells. We observed significant correlations between levels of not-diploid cells and senescence-associated features (SAFs)...
October 12, 2016: Scientific Reports
Hossein Ramshini, Tahere Mirzazadeh, Mohsen Esmaeilzadeh Moghaddam, Reza Amiri
A primary concern of modern plant breeding is that genetic diversity has decreased during the past century. This study set out to explore changes in genetic variation during 84 years of breeding by investigating the germination-related traits, inter-simple sequence repeat (ISSR) fingerprinting and osmotic stress tolerance of 30 Iranian wheat (Triticum aestivum L.) cultivars. Seeds were planted under control and osmotic stress (-2, -4 and -6 bar) in three replications. The ISSR experiment was carried out using 32 different primers...
July 2016: Physiology and Molecular Biology of Plants: An International Journal of Functional Plant Biology
Holly Stevens, Ashley B Williams, W Matthew Michael
To better understand how the cellular response to DNA replication stress is regulated during embryonic development, we and others have established the early C. elegans embryo as a model system to study this important problem. As is the case in most eukaryotic cell types, the replication stress response is controlled by the ATR kinase in early worm embryos. In this report we use RNAi to systematically characterize ATR pathway components for roles in promoting cell cycle delay during a replication stress response, and we find that these genetic requirements vary, depending on the source of stress...
2016: PloS One
Panagiotis Kotsantis, Lara Marques Silva, Sarah Irmscher, Rebecca M Jones, Lisa Folkes, Natalia Gromak, Eva Petermann
Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRAS(V12) promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRAS(V12), elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage...
October 11, 2016: Nature Communications
Xue-Jiao Chang, Chao-Qun Zheng, Yu-Wei Wang, Chuang Meng, Xiao-Lu Xie, Hai-Peng Liu
Gradually increasing atmospheric CO2 partial pressure (pCO2) has caused an imbalance in carbonate chemistry and resulted in decreased seawater pH in marine ecosystems, termed seawater acidification. Anthropogenic seawater acidification is postulated to affect the physiology of many marine calcifying organisms. To understand the possible effects of seawater acidification on the proteomic responses of a marine crustacean brine shrimp (Artemia sinica) three groups of cysts were hatched and further raised in seawater at different pH levels (8...
October 7, 2016: Fish & Shellfish Immunology
Amine Namouchi, Marta Gómez-Muñoz, Stephan A Frye, Line Victoria Moen, Torbjørn Rognes, Tone Tønjum, Seetha V Balasingham
BACKGROUND: As an intracellular human pathogen, Mycobacterium tuberculosis (Mtb) is facing multiple stressful stimuli inside the macrophage and the granuloma. Understanding Mtb responses to stress is essential to identify new virulence factors and pathways that play a role in the survival of the tubercle bacillus. The main goal of this study was to map the regulatory networks of differentially expressed (DE) transcripts in Mtb upon various forms of genotoxic stress. We exposed Mtb cells to oxidative (H2O2 or paraquat), nitrosative (DETA/NO), or alkylation (MNNG) stress or mitomycin C, inducing double-strand breaks in the DNA...
October 10, 2016: BMC Genomics
Andrea R Ashbaugh, Stephanie Houle-Johnson, Christophe Herbert, Wissam El-Hage, Alain Brunet
The purpose of this study is to assess the psychometric properties of a French version of the Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), a self-report measure of posttraumatic stress disorder (PTSD) symptoms, and to further validate the existing English version of the measure. Undergraduate students (n = 838 English, n = 262 French) completed the PCL-5 as well as other self-report symptom measures of PTSD and depression online. Both the English and French versions PCL-5 total scores demonstrated excellent internal consistency (English: α = ...
2016: PloS One
Thomas E Bass, Jessica W Luzwick, Gina Kavanaugh, Clinton Carroll, Huzefa Dungrawala, Gloria G Glick, Michael D Feldkamp, Reid Putney, Walter J Chazin, David Cortez
The ATR checkpoint kinase coordinates cellular responses to DNA replication stress. Budding yeast contain three activators of Mec1 (the ATR orthologue); however, only TOPBP1 is known to activate ATR in vertebrates. We identified ETAA1 as a replication stress response protein in two proteomic screens. ETAA1-deficient cells accumulate double-strand breaks, sister chromatid exchanges, and other hallmarks of genome instability. They are also hypersensitive to replication stress and have increased frequencies of replication fork collapse...
October 10, 2016: Nature Cell Biology
Peter Haahr, Saskia Hoffmann, Maxim A X Tollenaere, Teresa Ho, Luis Ignacio Toledo, Matthias Mann, Simon Bekker-Jensen, Markus Räschle, Niels Mailand
Activation of the ATR kinase following perturbations to DNA replication relies on a complex mechanism involving ATR recruitment to RPA-coated single-stranded DNA via its binding partner ATRIP and stimulation of ATR kinase activity by TopBP1. Here, we discovered an independent ATR activation pathway in vertebrates, mediated by the uncharacterized protein ETAA1 (Ewing's tumour-associated antigen 1). Human ETAA1 accumulates at DNA damage sites via dual RPA-binding motifs and promotes replication fork progression and integrity, ATR signalling and cell survival after genotoxic insults...
October 10, 2016: Nature Cell Biology
Yanping Han, Haihong Fang, Lei Liu, Dongsheng Zhou
Y. pestis exhibits dramatically different traits of pathogenicity and transmission, albeit their close genetic relationship with its ancestor-Y. pseudotuberculosis, a self-limiting gastroenteric pathogen. Y. pestis is evolved into a deadly pathogen and transmitted to mammals and/or human beings by infected flea biting or directly contacting with the infected animals. Various kinds of environmental changes are implicated into its complex life cycle and pathogenesis. Dynamic regulation of gene expression is critical for environmental adaptation or survival, primarily reflected by genetic regulation mediated by transcriptional factors and small regulatory RNAs at the transcriptional and posttranscriptional level, respectively...
2016: Advances in Experimental Medicine and Biology
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