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https://www.readbyqxmd.com/read/27915231/predominant-role-of-dna-polymerase-eta-and-p53-dependent-translesion-synthesis-in-the-survival-of-ultraviolet-irradiated-human-cells
#1
Leticia K Lerner, Guilherme Francisco, Daniela T Soltys, Clarissa R R Rocha, Annabel Quinet, Alexandre T Vessoni, Ligia P Castro, Taynah I P David, Silvina O Bustos, Bryan E Strauss, Vanesa Gottifredi, Anne Stary, Alain Sarasin, Roger Chammas, Carlos F M Menck
Genome lesions trigger biological responses that help cells manage damaged DNA, improving cell survival. Pol eta is a translesion synthesis (TLS) polymerase that bypasses lesions that block replicative polymerases, avoiding continued stalling of replication forks, which could lead to cell death. p53 also plays an important role in preventing cell death after ultraviolet (UV) light exposure. Intriguingly, we show that p53 does so by favoring translesion DNA synthesis by pol eta. In fact, the p53-dependent induction of pol eta in normal and DNA repair-deficient XP-C human cells after UV exposure has a protective effect on cell survival after challenging UV exposures, which was absent in p53- and Pol H-silenced cells...
December 2, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27806931/the-mechanism-of-ros-regulation-of-antibiotic-resistance-and-antimicrobial-lethality
#2
Ma Lina, Mi Hongfei, Xue Yunxin, Wang Dai, Zhao Xilin
Misuse and overuse of antibiotics have led to serious resistance problems that pose a grave threat to human health. How to solve the increasing antibiotic resistance problem is a huge challenge. Besides the traditional strategy of developing novel antimicrobial agents, exploring ways to enhance the lethal activity of antibiotics currently available is another feasible approach to fight against resistance. Recent studies showed that ROS plays an important role in regulating both antibiotic resistance and antimicrobial lethality...
October 20, 2016: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/27800635/screening-of-genotoxicity-and-mutagenicity-in-extractable-organics-from-oil-sands-process-affected-water
#3
Nikolas C Zetouni, Arno G Siraki, Michael Weinfeld, Alberto Dos Santos Pereira, Jonathan W Martin
Large volumes of oil sands process-affected water (OSPW) are produced by the oil sands surface mining industry during hot-water extraction of the bitumen. It is well documented that the acid extractable organics (AEOs) in OSPW, a highly complex mixture of acidic and polar neutral substances, are acutely toxic, but few studies have examined the genotoxicity or mutagenicity of this mixture. Here, the in vitro SOS-Chromotest and Ames tests (TA98 and TA100 strains) were used to evaluate genotoxicity and mutagenicity for whole OSPW-AEOs in the presence and absence of biotransformation by rat S9 liver enzymes...
November 1, 2016: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/27790613/sending-out-an-sos-mitochondria-as-a-signaling-hub
#4
REVIEW
Iryna Bohovych, Oleh Khalimonchuk
Normal cellular physiology is critically dependent on numerous mitochondrial activities including energy conversion, cofactor and precursor metabolite synthesis, and regulation of ion and redox homeostasis. Advances in mitochondrial research during the last two decades provide solid evidence that these organelles are deeply integrated with the rest of the cell and multiple mechanisms are in place to monitor and communicate functional states of mitochondria. In many cases, however, the exact molecular nature of various mitochondria-to-cell communication pathways is only beginning to emerge...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27766091/molecular-interaction-and-cellular-location-of-reca-and-chew-proteins-in-salmonella-enterica-during-sos-response-and-their-implication-in-swarming
#5
Oihane Irazoki, Jesús Aranda, Timo Zimmermann, Susana Campoy, Jordi Barbé
In addition to its role in DNA damage repair and recombination, the RecA protein, through its interaction with CheW, is involved in swarming motility, a form of flagella-dependent movement across surfaces. In order to better understand how SOS response modulates swarming, in this work the location of RecA and CheW proteins within the swarming cells has been studied by using super-resolution microscopy. Further, and after in silico docking studies, the specific RecA and CheW regions associated with the RecA-CheW interaction have also been confirmed by site-directed mutagenesis and immunoprecipitation techniques...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27759504/sexual-pain-disorders-in-spanish-women-drug-users
#6
Francisco Javier Del Río, Francisco Cabello-Santamaría, Marina A Cabello-García, Jerónimo Aragón-Vela
BACKGROUND: The impact of pain in sexuality, couple relationships and the quality of life is very well known. OBJECTIVES: The relationship between substance abuse and the presence of sexual pain disorder is assessed, together with anxiety and sexual attitudes . METHOD: Two samples were selected. One sample for women with a history of substance abuse (n = 129), and another one of women nonconsumers (n = 129). The Golombok Rust Inventory of Sexual Satisfaction (GRISS), the Sexual Opinion Survey (SOS) and the State Trait Anxiety Inventory (STAI) questionnaires were used...
October 19, 2016: Substance Use & Misuse
https://www.readbyqxmd.com/read/27736765/sorting-out-antibiotics-mechanisms-of-action-a-double-fluorescent-protein-reporter-for-high-throughput-screening-of-ribosome-and-dna-biosynthesis-inhibitors
#7
Ilya A Osterman, Ekaterina S Komarova, Dmitry I Shiryaev, Ilya A Korniltsev, Irina M Khven, Dmitry A Lukyanov, Vadim N Tashlitsky, Marina V Serebryakova, Olga V Efremenkova, Yan A Ivanenkov, Alexey A Bogdanov, Petr V Sergiev, Olga A Dontsova
In order to accelerate drug discovery, a simple, reliable, and cost-effective system for high-throughput identification of a potential antibiotic mechanism of action is required. To facilitate such screening of new antibiotics, we created a double-reporter system for not only antimicrobial activity detection but also simultaneous sorting of potential antimicrobials into those that cause ribosome stalling and those that induce the SOS response due to DNA damage. In this reporter system, the red fluorescent protein gene rfp was placed under the control of the SOS-inducible sulA promoter...
December 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27721142/defibrotide-for-the-management-of-sinusoidal-obstruction-syndrome-in-patients-who-undergo-haemopoietic-stem-cell-transplantation
#8
John Coutsouvelis, Sharon Avery, Michael Dooley, Carl Kirkpatrick, Andrew Spencer
Sinusoidal obstruction syndrome, previously known as veno-occlusive disease (VOD/SOS), is a complication in patients undergoing haemopoietic stem cell transplantation (HSCT). Severe VOD/SOS, including progression to multi-organ failure, has resulted in a mortality of greater than 80%. Defibrotide's varying pharmacological actions, particularly on endothelial cells, make it is a useful agent to consider for prophylaxis and treatment of VOD/SOS. Barriers to its routine use include the high acquisition cost and the fact that neither the oral or parenteral formulations are licensed products in many countries at this time...
September 30, 2016: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/27708387/plant-growth-promoting-rhizobacteria-dietzia-natronolimnaea-modulates-the-expression-of-stress-responsive-genes-providing-protection-of-wheat-from-salinity-stress
#9
Nidhi Bharti, Shiv Shanker Pandey, Deepti Barnawal, Vikas Kumar Patel, Alok Kalra
Plant growth promoting rhizobacteria (PGPR) hold promising future for sustainable agriculture. Here, we demonstrate a carotenoid producing halotolerant PGPR Dietzia natronolimnaea STR1 protecting wheat plants from salt stress by modulating the transcriptional machinery responsible for salinity tolerance in plants. The expression studies confirmed the involvement of ABA-signalling cascade, as TaABARE and TaOPR1 were upregulated in PGPR inoculated plants leading to induction of TaMYB and TaWRKY expression followed by stimulation of expression of a plethora of stress related genes...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27706829/lateral-gene-transfer-bacterial-genome-evolution-and-the-anthropocene
#10
Michael R Gillings
Lateral gene transfer (LGT) has significantly influenced bacterial evolution since the origins of life. It helped bacteria generate flexible, mosaic genomes and enables individual cells to rapidly acquire adaptive phenotypes. In turn, this allowed bacteria to mount strong defenses against human attempts to control their growth. The widespread dissemination of genes conferring resistance to antimicrobial agents has precipitated a crisis for modern medicine. Our actions can promote increased rates of LGT and also provide selective forces to fix such events in bacterial populations...
October 5, 2016: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/27698085/intracellular-d-serine-accumulation-promotes-genetic-diversity-via-modulated-induction-of-reca-in-enterohemorrhagic-escherichia-coli
#11
James P R Connolly, Andrew J Roe
: We recently discovered that exposure of enterohemorrhagic Escherichia coli (EHEC) to d-serine resulted in accumulation of this unusual amino acid, induction of the SOS regulon, and downregulation of the type III secretion system that is essential for efficient colonization of the host. Here, we have investigated the physiological relevance of this elevated SOS response, which is of particular interest given the presence of Stx toxin-carrying lysogenic prophages on the EHEC chromosome that are activated during the SOS response...
December 15, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27698081/the-small-rna-gcvb-promotes-mutagenic-break-repair-by-opposing-the-membrane-stress-response
#12
Brittany Barreto, Elizabeth Rogers, Jun Xia, Ryan L Frisch, Megan Richters, Devon M Fitzgerald, Susan M Rosenberg
: Microbes and human cells possess mechanisms of mutagenesis activated by stress responses. Stress-inducible mutagenesis mechanisms may provide important models for mutagenesis that drives host-pathogen interactions, antibiotic resistance, and possibly much of evolution generally. In Escherichia coli, repair of DNA double-strand breaks is switched to a mutagenic mode, using error-prone DNA polymerases, via the SOS DNA damage and general (σ(S)) stress responses. We investigated small RNA (sRNA) clients of Hfq, an RNA chaperone that promotes mutagenic break repair (MBR), and found that GcvB promotes MBR by allowing a robust σ(S) response, achieved via opposing the membrane stress (σ(E)) response...
December 15, 2016: Journal of Bacteriology
https://www.readbyqxmd.com/read/27694055/comparative-assessment-of-cardiac-activity-and-dna-damage-in-haemocytes-of-the-mediterranean-mussel-mytilus-galloprovincialis-in-exposure-to-tributyltin-chloride
#13
Rajko Martinović, Stoimir Kolarević, Margareta Kračun-Kolarević, Jovana Kostić, Sandra Jokanović, Zoran Gačić, Danijela Joksimović, Mirko Đurović, Zoran Kljajić, Branka Vuković-Gačić
This study gives an insight in sensitivity of heart rate (Hr) of Mytilus galloprovincialis as a physiological biomarker. Impact of tributyltin chloride (TBT-Cl) on Hr was studied in parallel with evaluation of mutagenic, genotoxic and cytotoxic potential of TBT-Cl (10, 100 and 1000μg/L) within 96h treatment in static conditions. Mutagenic potential was assessed by SOS/umuC assay while genotoxicity was assessed in haemocytes of M. galloprovincialis by using the comet assay and the micronucleus test. Benzo(a)pyrene (B(a)P) was used as a positive control...
September 27, 2016: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/27687175/dna-damage-responses-and-stress-resistance-concepts-from-bacterial-sos-to-metazoan-immunity
#14
Ashley B Williams, Björn Schumacher
The critical need for species preservation has driven the evolution of mechanisms that integrate stress signals from both exogenous and endogenous sources. Past research has been largely focused on cell-autonomous stress responses; however, recently their systemic outcomes within an organism and their implications at the ecological and species levels have emerged. Maintenance of species depends on the high fidelity transmission of the genome over infinite generations; thus, many pathways exist to monitor and restore the integrity of the genome and to coordinate DNA repair with other cellular processes, such as cell division and growth...
September 26, 2016: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/27683177/liver-microvascular-injury-and-thrombocytopenia-of-antibody-calicheamicin-conjugates-in-cynomolgus-monkeys-mechanism-and-monitoring
#15
Magali Guffroy, Hadi Falahatpisheh, Kathleen Biddle, John Kreeger, Leslie Obert, Karen Walters, Richard Goldstein, Germaine Boucher, Tim Coskran, William Reagan, Danielle Sullivan, Chunli Huang, Sharon A Sokolowski, Richard Giovanelli, Hans-Peter Gerber, Martin B Finkelstein, Nasir K Khan
PURPOSE: Adverse reactions reported in patients treated with antibody-calicheamicin conjugates such as gemtuzumab ozogamicin (GO, Mylotarg®) and inotuzumab ozogamicin (IO) include thrombocytopenia and sinusoidal obstruction syndrome (SOS). The objective of this experimental work was to investigate the mechanism for thrombocytopenia, characterize the liver injury and identify potential safety biomarkers. EXPERIMENTAL DESIGN: Cynomolgus monkeys were dosed intravenously at 6 mg/m2/dose once every 3 weeks with a non-binding antibody-calicheamicin conjugate (PF-0259) containing the same linker-payload as GO and IO...
September 28, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27682515/non-steroidal-anti-inflammatory-drugs-and-risk-of-heart-failure-in-four-european-countries-nested-case-control-study
#16
Andrea Arfè, Lorenza Scotti, Cristina Varas-Lorenzo, Federica Nicotra, Antonella Zambon, Bianca Kollhorst, Tania Schink, Edeltraut Garbe, Ron Herings, Huub Straatman, René Schade, Marco Villa, Silvia Lucchi, Vera Valkhoff, Silvana Romio, Frantz Thiessard, Martijn Schuemie, Antoine Pariente, Miriam Sturkenboom, Giovanni Corrao
OBJECTIVES:  To investigate the cardiovascular safety of non-steroidal anti-inflammatory drugs (NSAIDs) and estimate the risk of hospital admission for heart failure with use of individual NSAIDs. DESIGN:  Nested case-control study. SETTING:  Five population based healthcare databases from four European countries (the Netherlands, Italy, Germany, and the United Kingdom). PARTICIPANTS:  Adult individuals (age ≥18 years) who started NSAID treatment in 2000-10...
September 28, 2016: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/27681346/the-effect-of-20-hydroxyecdysone-on-the-susceptibility-of-escherichia-coli-to-different-antibiotics
#17
G Smirnova, K Bezmaternykh, O N Oktyabrsky
AIMS: The aim of this study was to investigate the influence of 20-hydroxyecdysone (20E) on the susceptibility of growing Escherichia coli to antibiotics. METHODS AND RESULTS: Susceptibility of E. coli to antibiotics in the presence of 20E was estimated by determination of the colony-forming ability and the specific growth rate. Pretreatment with 20E decreased the bactericidal effect of ciprofloxacin (0·3 and 3·0 μg ml(-1) ), streptomycin (10 and 40 μg ml(-1) ) and kanamycin (10 μg ml(-1) ) and increased the bactericidal action of 0·03 μg ml(-1) ciprofloxacin...
December 2016: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/27639198/low-doses-of-gamma-radiation-induce-sos-response-and-increase-mutation-frequency-in-escherichia-coli-and-salmonella-typhimurium-cells
#18
Alexander Bolsunovsky, Tatiana Frolova, Dmitry Dementyev, Olga Sinitsyna
This study addresses use of two bacterial test systems (the Ames test and the SOS chromotest) to estimate the effects of low doses of γ-radiation. The most substantial increases in induction of SOS response and mutation frequencies were observed in the first 24h of exposure to γ-radiation as compared to the cells in the exposure-free control. Gamma-radiation also impaired growth and survival of S. typhimurium cells in the first 24h. The effects were attenuated at lower exposure doses and at longer exposure times...
September 14, 2016: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/27623410/gene-expression-variability-underlies-adaptive-resistance-in-phenotypically-heterogeneous-bacterial-populations
#19
Keesha E Erickson, Peter B Otoupal, Anushree Chatterjee
The root cause of the antibiotic resistance crisis is the ability of bacteria to evolve resistance to a multitude of antibiotics and other environmental toxins. The regulation of adaptation is difficult to pinpoint due to extensive phenotypic heterogeneity arising during evolution. Here, we investigate the mechanisms underlying general bacterial adaptation by evolving wild-type Escherichia coli populations to dissimilar chemical toxins. We demonstrate the presence of extensive inter- and intrapopulation phenotypic heterogeneity across adapted populations in multiple traits, including minimum inhibitory concentration, growth rate, and lag time...
November 13, 2015: ACS Infectious Diseases
https://www.readbyqxmd.com/read/27620482/dna-targeting-as-a-likely-mechanism-underlying-the-antibacterial-activity-of-synthetic-bis-indole-antibiotics
#20
Timothy J Opperman, Steven M Kwasny, Jessica Bo Li, Mark A Lewis, Daniel Aiello, John D Williams, Norton P Peet, Donald T Moir, Terry L Bowlin, Eric C Long
We previously reported the synthesis and biological activity of a series of cationic bis-indoles with potent, broad-spectrum antibacterial properties. Here, we describe mechanism of action studies to test the hypothesis that these compounds bind to DNA and that this target plays an important role in their antibacterial outcome. The results reported here indicate that the bis-indoles bind selectively to DNA at A/T-rich sites, which is correlated with the inhibition of DNA and RNA synthesis in representative Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) organisms...
December 2016: Antimicrobial Agents and Chemotherapy
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