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Sonisilpa Mohapatra, James C Weisshaar
The organization of the chromosomal DNA and ribosomes in living Escherichia coli is compared under two growth conditions: "fast" (50-min doubling time) and "slow" (147-min doubling time). Superresolution fluorescence microscopy reveals strong DNA-ribosome segregation in both cases. In both fast and slow growth, free ribosomal subunits evidently must circulate between the nucleoid (where they initiate co-transcriptional translation) and ribosome-rich regions (where most translation occurs)...
August 14, 2018: Molecular Microbiology
Susan Elaine Greni, Bruna Demari-Silva, Tatiane Marques Porangaba de Oliveira, Lincoln Suesdek, Gabriel Zorello Laporta, Maria Anice Mureb Sallum
Nyssorhynchus strodei (Root) is an understudied species of potential epidemiological importance, having been found naturally infected in Brazil with Plasmodium falciparum Welch, Plasmodium vivax Grassi & Feletti, and Plasmodium malariae Feletti & Grassi. It belongs to the strodei subgroup that includes Nyssorhynchus albertoi (Unti), Nyssorhynchus arthuri (Unti), Nyssorhynchus rondoni (Neiva & Pinto), Nyssorhynchus striatus (Sant'Ana & Sallum), and three unnamed species, Nyssorhynchus arthuri B, Nyssorhynchus arthuri C, and Nyssorhynchus arthuri D...
August 10, 2018: Journal of Medical Entomology
Anna M Varizhuk, Anna D Protopopova, Vladimir B Tsvetkov, Nikolay A Barinov, Victor V Podgorsky, Maria V Tankevich, Maria A Vlasenok, Vyacheslav V Severov, Igor P Smirnov, Evgeniy V Dubrovin, Dmitry V Klinov, Galina E Pozmogova
We examined the assembly of DNA G-quadruplexes (G4s) into higher-order structures using atomic force microscopy, optical and electrophoretic methods, NMR spectroscopy and molecular modeling. Our results suggest that parallel blunt-ended G4s with single-nucleotide or modified loops may form different types of multimers, ranging from stacks of intramolecular structures and/or interlocked dimers and trimers to wires. Decreasing the annealing rate and increasing salt or oligonucleotide concentrations shifted the equilibrium from intramolecular G4s to higher-order structures...
August 11, 2018: Nucleic Acids Research
Honorata Czapinska, Monika Kowalska, Evelina Zagorskaite, Elena Manakova, Anton Slyvka, Shuang-Yong Xu, Virginijus Siksnys, Giedrius Sasnauskas, Matthias Bochtler
Escherichia coli McrA (EcoKMcrA) acts as a methylcytosine and hydroxymethylcytosine dependent restriction endonuclease. We present a biochemical characterization of EcoKMcrA that includes the first demonstration of its endonuclease activity, small angle X-ray scattering (SAXS) data, and a crystal structure of the enzyme in the absence of DNA. Our data indicate that EcoKMcrA dimerizes via the anticipated C-terminal HNH domains, which together form a single DNA binding site. The N-terminal domains are not homologous to SRA domains, do not interact with each other, and have separate DNA binding sites...
August 10, 2018: Nucleic Acids Research
Mohammed Jaber, Christian Ewelt, Johannes Wölfer, Benjamin Brokinkel, Christian Thomas, Martin Hasselblatt, Oliver Grauer, Walter Stummer
BACKGROUND: Approximately 20% of low-grade gliomas (LGG) display visible protoporphyrin fluorescence during surgery after 5-aminolevulinic acid (5-ALA) administration. OBJECTIVE: To determine if fluorescence represents a prognostic marker in LGG. METHODS: Seventy-four consecutive patients with LGG (World Health Organization 2016) were operated on with 5-ALA. Fluorescent tissue was specifically biopsied. Tumor size, age, Karnofsky index, contrast-enhancement, fluorescence, and molecular factors (IDH1/IDH2-mutations, Ki67/MIB1 Index, 1p19q codeletions, ATRX, EGFR, p53 expression, and O6-methylguanine DNA methyltransferase promotor methylation), were related to progression-free survival (PFS), malignant transformation-free survival (MTFS) and overall survival (OS)...
August 9, 2018: Neurosurgery
Thuy-Ai T Nguyen, Sara A Grimm, Pierre R Bushel, Jianying Li, Yuanyuan Li, Brian D Bennett, Christopher A Lavender, James M Ward, David C Fargo, Carl W Anderson, Leping Li, Michael A Resnick, Daniel Menendez
p53 transcriptional networks are well-characterized in many organisms. However, a global understanding of requirements for in vivo p53 interactions with DNA and relationships with transcription across human biological systems in response to various p53 activating situations remains limited. Using a common analysis pipeline, we analyzed 41 data sets from genome-wide ChIP-seq studies of which 16 have associated gene expression data, including our recent primary data with normal human lymphocytes. The resulting extensive analysis, accessible at p53 BAER hub via the UCSC browser, provides a robust platform to characterize p53 binding throughout the human genome including direct influence on gene expression and underlying mechanisms...
August 10, 2018: Nucleic Acids Research
Felicity C Fitzgerald, Edouard Lhomme, Kathryn Harris, Julia Kenny, Ronan Doyle, Cissy Kityo, Liam B Shaw, George Abongomera, Victor Musiime, Adrian Cook, Julianne R Brown, Anthony Brooks, Ellen Owen-Powell, Diana M Gibb, Andrew J Prendergast, A Sarah Walker, Rodolphe Thiebaut, Nigel Klein
Objective: Immune activation is associated with morbidity/mortality in HIV-infection despite antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children. Methods: Nineteen markers of immune activation/inflammation were measured over 96 weeks in HIV-infected Ugandan children in CHAPAS-3 (ISRCTN69078957) and HIV-uninfected age-matched controls. Microbial translocation was assessed using molecular techniques including next-generation sequencing...
August 11, 2018: Journal of Infectious Diseases
Anne-Laure Le Gac, Clément Lafon-Placette, Didier Chauveau, Vincent Segura, Alain Delaunay, Régis Fichot, Nicolas Marron, Isabelle Le Jan, Alain Berthelot, Guillaume Bodineau, Jean-Charles Bastien, Franck Brignolas, Stéphane Maury
Trees have a long lifespan and must continually adapt to environmental pressures, notably in the context of climate change. Epigenetic mechanisms are doubtless involved in phenotypic plasticity and in stress memory; however, little evidence of the role of epigenetic processes is available for trees growing in fields. Here, we analyzed the possible involvement of epigenetic mechanisms in the winter-dormant shoot apical meristem of Populus × euramericana clones in memory of the growing conditions faced during the vegetative period...
August 9, 2018: Journal of Experimental Botany
Henry C Olson, Luther Davis, Kostantin Kiianitsa, Kevin J Khoo, Yilun Liu, Theo A Knijnenburg, Nancy Maizels
RECQ5 (RECQL5) is one of several human helicases that dissociates RAD51-DNA filaments. The gene that encodes RECQ5 is frequently amplified in human tumors, but it is not known whether amplification correlates with increased gene expression, or how increased RECQ5 levels affect DNA repair at nicks and double-strand breaks. Here, we address these questions. We show that RECQ5 gene amplification correlates with increased gene expression in human tumors, by in silico analysis of over 9000 individual tumors representing 32 tumor types in the TCGA dataset...
August 13, 2018: Nucleic Acids Research
Conghui Liu, Yan Zhang, Yuwei Ren, Hengchao Wang, Shuqu Li, Fan Jiang, Lijuan Yin, Xi Qiao, Guojie Zhang, Wanqiang Qian, Bo Liu, Wei Fan
Background: The golden apple snail (Pomacea canaliculata) is a fresh water snail listed among the top-100 worst invasive species worldwide and a noted agricultural and quarantine pest that causes great economic losses. It is characterized by fast growth, strong stress tolerance, a high reproduction rate, and adaptation to a broad range of environments. Results: Here, we used long-read sequencing to produce a 440-Mb high-quality, chromosome-level assembly of the P...
August 9, 2018: GigaScience
Karlijn A C Meeks, Peter Henneman, Andrea Venema, Juliet Addo, Silver Bahendeka, Tom Burr, Ina Danquah, Cecilia Galbete, Marcel M A M Mannens, Frank P Mockenhaupt, Ellis Owusu-Dabo, Charles N Rotimi, Matthias B Schulze, Liam Smeeth, Joachim Spranger, Mohammad H Zafarmand, Adebowale Adeyemo, Charles Agyemang
Background: Type 2 diabetes (T2D) results from a complex interplay between genetics and the environment. Several epigenome-wide association studies (EWAS) have found DNA methylation loci associated with T2D in European populations. However, data from African populations are lacking. We undertook the first EWAS for T2D among sub-Saharan Africans, aiming at identifying ubiquitous and novel DNA methylation loci associated with T2D. Methods: The Illumina 450k DNA-methylation array was used on whole blood samples of 713 Ghanaian participants (256 with T2D, 457 controls) from the cross-sectional Research on Obesity and Diabetes among African Migrants (RODAM) study...
August 10, 2018: International Journal of Epidemiology
Jun Chen, Jingna Xun, Junyang Yang, Yongjia Ji, Li Liu, Tangkai Qi, Zhenyan Wang, Renfang Zhang, Yinzhong Shen, Rosalie Ponte, Vikram Mehraj, Jean-Pierre Routy, Hongzhou Lu
Background: Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme that metabolises tryptophan to immunosuppressive kynurenines. We investigated whether IDO activity is associated with the size of HIV reservoirs. Methods: In this cross-sectional study, total HIV DNA in PBMCs from 127 HIV-infected patients receiving antiretroviral therapy (ART) was quantified. Tryptophan and kynurenine concentrations, as well as microbial translocation markers were measured in plasma samples...
August 10, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Feng Li, Fujun Jin, Yiliang Wang, Danlin Zheng, Junwei Liu, Zhen Zhang, Rongze Wang, Dong Dong, Kai Zheng, Yifei Wang
Heat shock protein 90 (Hsp90) has been identified as an essential host factor for the infection and replication of several viruses, including HSV-1. Recent works have clearly shown that Hsp90 plays a role in the early stages of HSV-1 infection, including nuclear import and DNA replication. However, the role of Hsp90 in the late stages of HSV-1 infection remains unclear. In this study, we found that Hsp90 was up-regulated during late viral infection. Treatment with the Hsp90 inhibitor AT-533 significantly decreased the intracellular and extracellular virus titer, and strongly inhibited nucleocapsid egress from the nucleus...
August 10, 2018: Journal of Biochemistry
Liming Ouyang, Petter Holland, Hongzhong Lu, David Bergenholm, Jens Nielsen
The S. cerevisiae transcription factor (TF) Stb5 is known to be involved in regulating NADPH generation. We explored its role by combining DNA binding studies with transcriptome analysis at four environmental conditions that were selected to cover a range of different metabolic states. Using ChIP-exo, DNA binding targets of Stb5 were found to confirm many previously proposed binding targets, in particular genes encoding enzymes involved in NADPH generation and the pentose-phosphate (PP) pathway. Transcriptome analysis of an STB5 deletion strain revealed transcriptional changes in direct regulation targets of Stb5, including several PP pathway genes as well as additional novel regulatory targets, but interestingly not including the proposed PP pathway flux controlling enzyme Zwf1...
August 9, 2018: FEMS Yeast Research
Tim Künne, Yifan Zhu, Fausia da Silva, Nico Konstantinides, Rebecca E McKenzie, Ryan N Jackson, Stan Jj Brouns
Prokaryotes use primed CRISPR adaptation to update their memory bank of spacers against invading genetic elements that have escaped CRISPR interference through mutations in their protospacer target site. We previously observed a trend that nucleotide-dependent mismatches between crRNA and the protospacer strongly influence the efficiency of primed CRISPR adaptation. Here we show that guanine-substitutions in the target strand of the protospacer are highly detrimental to CRISPR interference and interference-dependent priming, while cytosine-substitutions are more readily tolerated...
August 11, 2018: Nucleic Acids Research
Mitsuru Sasaki-Honda, Tatsuya Jonouchi, Meni Arai, Akitsu Hotta, Satomi Mitsuhashi, Ichizo Nishino, Ryoichi Matsuda, Hidetoshi Sakurai
DUX4, the causative gene of facioscapulohumeral muscular dystrophy (FSHD), is ectopically expressed in the skeletal muscle cells of FSHD patients because of chromatin relaxation at 4q35. The diminished heterochromatic state at 4q35 is caused by either large genome contractions (FSHD1) or mutations in genes encoding chromatin regulators, such as SMCHD1 (FSHD2). However, the mechanism by which DUX4 expression is regulated remains largely unknown. Here, using a myocyte model developed from patient-derived induced pluripotent stem cells (iPSCs), we determined that DUX4 expression was increased by oxidative stress (OS), a common environmental stress in skeletal muscle, in both FSHD1 and FSHD2 myocytes...
August 9, 2018: Human Molecular Genetics
Sneha Munshi, Soundhararajan Gopi, Gitanjali Asampille, Sandhyaa Subramanian, Luis A Campos, Hanudatta S Atreya, Athi N Naganathan
DNA-binding protein domains (DBDs) sample diverse conformations in equilibrium facilitating the search and recognition of specific sites on DNA over millions of energetically degenerate competing sites. We hypothesize that DBDs have co-evolved to sense and exploit the strong electric potential from the array of negatively charged phosphate groups on DNA. We test our hypothesis by employing the intrinsically disordered DBD of cytidine repressor (CytR) as a model system. CytR displays a graded increase in structure, stability and folding rate on increasing the osmolarity of the solution that mimics the non-specific screening by DNA phosphates...
August 11, 2018: Nucleic Acids Research
Néstor García-Rodríguez, Ronald P Wong, Helle D Ulrich
Replication of damaged DNA is challenging because lesions in the replication template frequently interfere with an orderly progression of the replisome. In this situation, complete duplication of the genome is ensured by the action of DNA damage bypass pathways effecting either translesion synthesis by specialized, damage-tolerant DNA polymerases or a recombination-like mechanism called template switching (TS). Here we report that budding yeast Pif1, a helicase known to be involved in the resolution of complex DNA structures as well as the maturation of Okazaki fragments during replication, contributes to DNA damage bypass...
August 10, 2018: Nucleic Acids Research
Maria Fernanda de Moura Leão, Jonathaline Apollo Duarte, Patrícia Dutra Sauzen, Jacqueline da Costa Escobar Piccoli, Luís Flávio Souza de Oliveira, Michel Mansur Machado
Hypertension, a chronic non-transmissible multifactorial condition, it is highly frequent in Brazil, affecting about 32.5% of the population over 25 years of age. It is characterized by the sustained increase in systolic and diastolic blood pressure levels above 140 mmHg and 90 mmHg, respectively. It is the major aggravating factor in cardiovascular complications and the appearance of other comorbidities. Aiming to promote greater adherence to treatment and improve the population's access to basic medicament, in 2004 the Federal Government created the Programa Farmácia Popular do Brasil (PFPB); partnership with private institutions that provides the population with medicament to control hypertension, free of charge or subsidized at up to 90% of the value...
August 9, 2018: Environmental Toxicology and Pharmacology
Akhilesh Kumar Shukla, Hamidullah, Manoj Kumar Shrivash, Vishwa Deepak Tripathi, Rituraj Konwar, Jyoti Pandey
The present study demonstrates the identification of N-hydroxycinnamamide derivatives and their anticancer potential against human triple-negative breast cancer cell line MDA-MB‑231, MCF-7 and non-malignant origin cell line, HEK-293 (human embryonic kidney). MTT assay was studied with HEK-293 cell line. Anticancer potential of the N-hydroxycinnamamide derivatives were compared with marked drug Tamoxifen through in vitro study. The compound numbers 3b and 3h exhibit most potent activity against antagonistic breast cancer cells (MDA-MB-231) with IC50 13μM and 5μM respectively...
August 11, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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