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Mark Hedglin, Binod Pandey, Stephen J Benkovic
Translesion DNA synthesis (TLS) during S-phase uses specialized TLS DNA polymerases to replicate a DNA lesion, allowing stringent DNA synthesis to resume beyond the offending damage. Human TLS involves the conjugation of ubiquitin to PCNA clamps encircling damaged DNA and the role of this post-translational modification is under scrutiny. A widely-accepted model purports that ubiquitinated PCNA recruits TLS polymerases such as pol η to sites of DNA damage where they may also displace a blocked replicative polymerase...
October 22, 2016: ELife
Wenyan Xu, Daniel Kool, Derek K O'Flaherty, Ashley Keating, Lauralicia Sacre, Martin Egli, Anne Marietta Noronha, Christopher James Wilds, Linlin Zhao
DNA interstrand cross-links (ICLs) are cytotoxic DNA lesions derived from reactions of DNA with a number of anti-cancer reagents as well as endogenous bifunctional electrophiles. Deciphering the DNA repair mechanisms of ICLs is important for understanding the toxicity of DNA cross-linking agents and for the development of effective chemotherapies. Previous research has focused on ICLs cross-linked with the N7 and N2 atoms of guanine as well as those formed at the N6 atom of adenine; however, little is known about the mutagenicity of O6-dG-derived ICLs...
October 21, 2016: Chemical Research in Toxicology
Chantal Brosseau, Mohamed El Oirdi, Ayooluwa Adurogbangba, Xiaofang Ma, Peter Moffett
In plants, RNA silencing regulates gene expression through the action of Dicer-like (DCL) and Argonaute (AGO) proteins via micro RNAs and RNA-dependent DNA methylation (RdDM). In addition, RNA silencing functions as an anti-viral defense mechanism by targeting virus-derived double stranded RNA. Plants encode multiple AGO proteins with specialized functions, including AGO4-like proteins, which effect RdDM and AGO2, AGO5 and AGO1, which have antiviral activities. We show here that AGO4 is also required for defense against Plantago asiatica mosaic potexvirus (PlAMV), most likely independent of RdDM components such as DCL3, Pol IV and Pol V...
October 20, 2016: Molecular Plant-microbe Interactions: MPMI
Wenjun Zhang, Junfang Chen, Xiao Hong Pan, Jiafeng Zhang, Zhihong Guo, Yan Luo, Jiezhe Yang, Yan Xia, Lin He, Yun Xu, Ke Xu, Xiaobei Ding
OBJECTIVE: To investigate the HIV-1 molecular epidemiology among young people (18 to 25 years old) in Hangzhou. METHODS: Plasma samples from 262 newly diagnosed HIV-1 infected patients were collected between 2009 and 2013 from Hangzhou of Zhejiang province. HIV-1 nucleotide sequences of pol gene regions were amplified using a nested PCR method and sequenced. Phylogenetic and recombination analyses were used to determine the HIV-1 genotypes. RESULTS: Based on all sequences generated, the subtype/circulating recombinant forms (CRF) distribution was as follows: CRF01_AE (68...
October 20, 2016: AIDS Research and Human Retroviruses
Elizabeth Wolf, Joshua Herbeck, Stephen Van Rompaey, Mari M Kitahata, Katherine K Thomas, Gregory Pepper, Lisa Frenkel
HIV-1 incidence among youth, especially men who have sex with men (MSM), is increasing in the US. We aimed to better understand the patterns of adolescent HIV-1 acquisition, in order to help guide future prevention interventions. We conducted a study combining epidemiologic and HIV-1 pol sequence data from a retrospective cohort of HIV-infected adults and adolescents in Seattle, WA between 2000 and 2013. Adolescents were defined as 13-24 years of age at the time of first HIV-1 care. Maximum-likelihood phylogenetic trees were reconstructed to identify putative viral transmission clusters of two or more individuals, followed by multivariable regression tests of associations between clustering and demographic and clinical parameters...
October 20, 2016: AIDS Research and Human Retroviruses
Natalya M Gashnikova, Darya P Zyryanova, Ekaterina M Astakhova, Vladimir V Ivlev, Maria P Gashnikova, Natalya V Moskaleva, Sergey S Aikin, Tatyana N Bulatova, Sergey V Pustylnikov, Evgeny F Bocharov, Aleksey V Totmenin
Kemerovo Oblast (KO) has had the highest rate of HIV spread in Russia since 2011. The aim of this work was to study the genetic variation of HIV-1 in Kemerovo Oblast. Blood was sampled from a total of 91 HIV-positive antiretroviral-therapy-naïve individuals in 2013 (38) and 2015 (53). HIV-1 subtypes, pol gene drug resistance mutations, and viral tropism were analyzed. In 2013-2015, the prevalence of HIV-1 subtype A decreased in KO from 60.5 to 7.5 %. The samples collected in 2015 from the patients with newly diagnosed HIV demonstrate the current dominance of HIV-1 CRF63_02A1 (71...
October 19, 2016: Archives of Virology
Robert L Dilley, Priyanka Verma, Nam Woo Cho, Harrison D Winters, Anne R Wondisford, Roger A Greenberg
Homology-directed DNA repair is essential for genome maintenance through templated DNA synthesis. Alternative lengthening of telomeres (ALT) necessitates homology-directed DNA repair to maintain telomeres in about 10-15% of human cancers. How DNA damage induces assembly and execution of a DNA replication complex (break-induced replisome) at telomeres or elsewhere in the mammalian genome is poorly understood. Here we define break-induced telomere synthesis and demonstrate that it utilizes a specialized replisome, which underlies ALT telomere maintenance...
October 19, 2016: Nature
Jeannette Pols
This article is a written version of the lecture for the IPONS conference in Stockholm. The article starts from the claim that there is no such thing as technology, only different variations of technologies. These technologies, plural, all have their specific workings that we can only learn about by studying these empirically, by analysing the relations between people and their technologies. These relations are always unpredictable, as it is not given beforehand what values the participants pursue. Studying and understanding the workings of healthcare technology is a crucial task for nursing studies, as nurses are often key actors in making these devices work...
October 18, 2016: Nursing Philosophy: An International Journal for Healthcare Professionals
T Hertz, M G Logan, M Rolland, C A Magaret, C Rademeyer, A Fiore-Gartland, P T Edlefsen, A DeCamp, H Ahmed, N Ngandu, B B Larsen, N Frahm, J Marais, R Thebus, D Geraghty, J Hural, L Corey, J Kublin, G Gray, M J McElrath, J I Mullins, P B Gilbert, C Williamson
INTRODUCTION: The Merck Adenovirus-5 Gag/Pol/Nef HIV-1 subtype-B vaccine evaluated in predominately subtype B epidemic regions (Step Study), while not preventing infection, exerted vaccine-induced immune pressure on HIV-1 breakthrough infections. Here we investigated if the same vaccine exerted immune pressure when tested in the Phambili Phase 2b study in a subtype C epidemic. MATERIALS AND METHODS: A sieve analysis, which compares breakthrough viruses from placebo and vaccine arms, was performed on 277 near full-length genomes generated from 23 vaccine and 20 placebo recipients...
October 15, 2016: Vaccine
Vasily M Studitsky, Ekaterina V Nizovtseva, Alexey K Shaytan, Donal S Luse
Packaging of DNA into chromatin affects all processes on DNA. Nucleosomes present a strong barrier to transcription, raising important questions about the nature and the mechanisms of overcoming the barrier. Recently it was shown that DNA sequence, DNA-histone interactions and backtracking by RNA polymerase II (Pol II) all contribute to formation of the barrier. After partial uncoiling of nucleosomal DNA from histone octamer by Pol II and backtracking of the enzyme, nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state...
2016: Biochemistry & Molecular Biology Journal
Geert-Jan Will, Eveline A Crone, Pol A C van Lier, Berna Güroğlu
Childhood peer acceptance is associated with high levels of prosocial behavior and advanced perspective taking skills. Yet, the neurobiological mechanisms underlying these associations have not been studied. This functional magnetic resonance imaging study examined the neural correlates of sharing decisions in a group of adolescents who had a stable accepted status (n = 27) and a group who had a chronic rejected status (n = 19) across six elementary school grades. Both groups of adolescents played three allocation games in which they could share money with strangers with varying costs and profits to them and the other person...
October 17, 2016: Developmental Science
Colin M Venner, Immaculate Nankya, Fred Kyeyune, Korey Demers, Cynthia Kwok, Pai-Lien Chen, Sandra Rwambuya, Marshall Munjoma, Tsungai Chipato, Josaphat Byamugisha, Barbara Van Der Pol, Peter Mugyenyi, Robert A Salata, Charles S Morrison, Eric J Arts
INTRODUCTION: Long-term natural history cohorts of HIV-1 in the absence of treatment provide the best measure of virulence by different viral subtypes. METHODS: Newly HIV infected Ugandan and Zimbabwean women (N=303) were recruited and monitored for clinical, social, behavioral, immunological and viral parameters for 3 to 9.5years. RESULTS: Ugandan and Zimbabwean women infected with HIV-1 subtype C had 2.5-fold slower rates of CD4 T-cell declines and higher frequencies of long-term non-progression than those infected with subtype A or D (GEE model, P<0...
October 12, 2016: EBioMedicine
Karoline Rodrigues Campos, Maria Gisele Gonçalves, Adele Caterino-de-Araujo
Changes in retrovirus acquisition/transmission behaviors have been reported in Brazil, with a concerning increase in HIV-1 infected individuals aged 15 to 39 years. In São Paulo, HIV-1/HTLV-1 and HIV-1/HTLV-2 coinfections have been associated with intravenous drug use and failure to detect HTLV-1/2 with immunosuppression and the use of active antiretroviral therapy (HAART). Negative results for HTLV serologic [western blotting (WB)] and molecular [real-time PCR pol (qPCR)] confirmatory assays have been reported, whereas the best sensitivity has been found for INNO-LIA (LIA)...
October 17, 2016: AIDS Research and Human Retroviruses
Laurent Alric, Caroline Besson, Nathanael Lapidus, Juliette Jeannel, Jean-Marie Michot, Patrice Cacoub, Danielle Canioni, Stanislas Pol, Frédéric Davi, Pascaline Rabiega, Loic Ysebaert, Delphine Bonnet, Olivier Hermine
: Hepatitis C virus (HCV) infection is associated with lymphoproliferative disorders and B-cell non-Hodgkin lymphomas (B-NHLs). Evaluation of the efficacy and safety profiles of different antiviral therapies in HCV patients with B-NHL is warranted. METHODS: First, we evaluated the sustained virologic response (SVR) and safety of Peg-interferon-alpha (Peg-IFN) + ribavirin +/- first protease inhibitors (PI1s) therapy in 61 HCV patients with B-NHL enrolled in a nationwide observational survey compared with 94 matched HCV-infected controls without B-NHL...
2016: PloS One
Carmen Brankaer, Pol Ghesquière, Anke De Wel, Ann Swillen, Bert De Smedt
Cross-syndrome comparisons offer an important window onto understanding heterogeneity in mathematical learning disabilities or dyscalculia. The present study therefore investigated symbolic numerical magnitude processing in two genetic syndromes that are both characterized by mathematical learning disabilities: Turner syndrome and 22q11.2 deletion syndrome (22q11DS). We further verified whether the phenotypic outcomes of these syndromes emerged from the same or different cognitive processes and therefore examined whether numerical impairments were related to working memory deficits, often observed in these syndromes...
October 17, 2016: Developmental Science
Emma Cunningham, Yuen-Ting Chan, Adamma Aghaizu, David F Bibby, Gary Murphy, Jennifer Tosswill, Ross J Harris, Richard Myers, Nigel Field, Valerie Delpech, Patricia A Cane, O Noel Gill, Jean L Mbisa
OBJECTIVES: To determine the prevalence of inferred low-frequency HIV-1 transmitted drug resistance (TDR) in MSM in the UK and its predicted effect on first-line therapy. METHODS: The HIV-1 pol gene was amplified from 442 newly diagnosed MSM identified as likely recently infected by serological avidity testing in 2011-13. The PCR products were sequenced by next-generation sequencing with a mutation frequency threshold of >2% and TDR mutations defined according to the 2009 WHO surveillance drug resistance mutations list...
October 14, 2016: Journal of Antimicrobial Chemotherapy
Naotaka Nakazawa, Aneesh R Sathe, G V Shivashankar, Michael P Sheetz
Substrate rigidity affects many physiological processes through mechanochemical signals from focal adhesion (FA) complexes that subsequently modulate gene expression. We find that shuttling of the LIM domain (domain discovered in the proteins, Lin11, Isl-1, and Mec-3) protein four-and-a-half LIM domains 2 (FHL2) between FAs and the nucleus depends on matrix mechanics. In particular, on soft surfaces or after the loss of force, FHL2 moves from FAs into the nucleus and concentrates at RNA polymerase (Pol) II sites, where it acts as a transcriptional cofactor, causing an increase in p21 gene expression that will inhibit growth on soft surfaces...
October 14, 2016: Proceedings of the National Academy of Sciences of the United States of America
Prakasha Gowda, Thomas E Spratt
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent tobacco carcinogen that forms mutagenic DNA adducts including O(6)-methyl-2'-deoxyguanosine (O(6)-Me-dG), O(6)-[4-(3-pyridyl)-4-oxobut-1-yl]-dG (O6-POB-dG), O(2)-methylthymidine (O(2)-Me-dT), and O(2)-POB-dT. We evaluated the ability of human DNA polymerase ν to bypass this damage to evaluate the structural constraints on substrates for pol ν and to evaluate if there is kinetic evidence suggesting the in vivo activity of pol ν on tobacco-induced DNA damage...
October 14, 2016: Chemical Research in Toxicology
Pol Cirujeda, Yashin Dicente Cid, Henning Muller, Daniel Rubin, Todd A Aguilera, Billy W Loo, Maximilian Diehn, Xavier Binefa, Adrien Depeursinge
This paper proposes a novel imaging biomarker of lung cancer relapse from 3-D texture analysis of CT images. Three-dimensional morphological nodular tissue properties are described in terms of 3-D Riesz-wavelets. The responses of the latter are aggregated within nodular regions by means of feature covariances, which leverage rich intra- and inter- variations of the feature space dimensions. When compared to the classical use of the average for feature aggregation, feature covariances preserve spatial co-variations between features...
July 18, 2016: IEEE Transactions on Medical Imaging
Margarita Kovaleva, Valery Pilipchuk, Leonid Manevitch
The present work follows our previous study dealing with a new type of synchronization in a system of two weakly coupled generalized van der Pol-Duffing autogenerators. The essence of the effect revealed is that the synchronized oscillations are not stationary but accompanied by the most intensive energy exchange between the oscillators. The phase shift between the generators remains constant most of the time, except for vanishingly small transitional intervals. The current analysis deals with a generalized model in order to clarify the frequency detuning effect...
September 2016: Physical Review. E
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