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genome integrity

Maxime Lamontagne, Jean-Christophe Bérubé, Ma'en Obeidat, Michael H Cho, Brian D Hobbs, Phuwanat Sakornsakolpat, Kim de Jong, H Marike Boezen, David Nickle, Ke Hao, Wim Timens, Maarten van den Berge, Philippe Joubert, Michel Laviolette, Don D Sin, Peter D Paré, Yohan Bossé
Causal genes of chronic obstructive pulmonary disease (COPD) remain elusive. The current study aims at integrating genome-wide association studies (GWAS) and lung expression quantitative loci (eQTL) data to map COPD candidate causal genes and gain biological insights into the recently discovered COPD susceptibility loci. Two complementary genomic datasets on COPD were studied. First, the lung eQTL dataset which included whole-genome gene expression and genotyping data from 1,038 individuals. Second, the largest COPD GWAS to date from the International COPD Genetics Consortium (ICGC) with 13,710 cases and 38,062 controls...
March 14, 2018: Human Molecular Genetics
Christos Dimitrakopoulos, Sravanth Kumar Hindupur, Luca Häfliger, Jonas Behr, Hesam Montazeri, Michael N Hall, Niko Beerenwinkel
Motivation: Several molecular events are known to be cancer-related, including genomic aberrations, hypermethylation of gene promoter regions, and differential expression of microRNAs. These aberration events are very heterogeneous across tumors and it is poorly understood how they affect the molecular makeup of the cell, including the transcriptome and proteome. Protein interaction networks can help decode the functional relationship between aberration events and changes in gene and protein expression...
March 14, 2018: Bioinformatics
Jiawei Wang, Bingjiao Yang, André Leier, Tatiana T Marquez-Lago, Morihiro Hayashida, Andrea Rocker, Zhang Yanju, Tatsuya Akutsu, Kuo-Chen Chou, Richard A Strugnell, Jiangning Song, Trevor Lithgow
Motivation: Many Gram-negative bacteria use type VI secretion systems (T6SS) to export effector proteins into adjacent target cells. These secreted effectors (T6SEs) play vital roles in the competitive survival in bacterial populations, as well as pathogenesis of bacteria. Although various computational analyses have been previously applied to identify effectors secreted by certain bacterial species, there is no universal method available to accurately predict T6SS effector proteins from the growing tide of bacterial genome sequence data...
March 14, 2018: Bioinformatics
Mohammad Hadi Karbalaie Niya, Hossein Keyvani, Fahimeh Safarnezhad Tameshkel, Mostafa Salehi-Vaziri, Sedigheh Teaghinezhad-S, Farah Bokharaei Salim, Seyed Hamid Reza Monavari, Davod Javanmard
Human papillomavirus (HPV) is a common viral infection worldwide associated with a variety of cancers. The integration of the HPV genome in these patients causes chromosomal instability and triggers carcinogenesis. The aim of this study was to investigate the HPV-16 genome physical status in four major cancers related to HPV infection. Formalin-fixed paraffin-embedded blocks from our previous projects on head and neck, colorectal, penile, and cervical cancers were collected, and HPV-16-positive specimens were used for further analysis...
March 13, 2018: Translational Oncology
Camilla Björkegren, Laura Baranello
Although our knowledge of chromatin organization has advanced significantly in recent years, much about the relationships between different features of genome architecture is still unknown. Folding of mammalian genomes into spatial domains is thought to depend on architectural proteins, other DNA-binding proteins, and different forms of RNA. In addition, emerging evidence points towards the possibility that the three-dimensional organisation of the genome is controlled by DNA topology. In this scenario, cohesin, CCCTC-binding factor (CTCF), transcription, DNA supercoiling, and topoisomerases are integrated to dictate different layers of genome organization, and the contribution of all four to gene control is an important direction of future studies...
March 16, 2018: International Journal of Molecular Sciences
R Cameron Coates, Benjamin P Bowen, Ernst Oberortner, Linda Thomashow, Michalis Hadjithomas, Zhiying Zhao, Jing Ke, Leslie Silva, Katherine Louie, Gaoyan Wang, David Robinson, Angela Tarver, Matthew Hamilton, Andrea Lubbe, Meghan Feltcher, Jeffery L Dangl, Amrita Pati, David Weller, Trent R Northen, Jan-Fang Cheng, Nigel J Mouncey, Samuel Deutsch, Yasuo Yoshikuni
Increasing availability of new genomes and putative biosynthetic gene clusters (BGCs) has extended the opportunity to access novel chemical diversity for agriculture, medicine, environmental and industrial purposes. However, functional characterization of BGCs through heterologous expression is limited because expression may require complex regulatory mechanisms, specific folding or activation. We developed an integrated workflow for BGC characterization that integrates pathway identification, modular design, DNA synthesis, assembly and characterization...
March 15, 2018: Journal of Industrial Microbiology & Biotechnology
Suhong Xiao, Ying-Sheng Tang, Praveen Kusumanchi, Sally P Stabler, Ying Zhang, Asok C Antony
Background: Epidemiologic and in vitro studies suggest independent linkages between poor folate and/or vitamin B-12 nutrition, genomic human papillomavirus (HPV) type 16 viral integration, and cancer. However, there is no direct evidence in vivo to support the causative role of poor folate nutrition in HPV16 integration into the cellular genome. Objective: We tested the hypothesis that folate deficiency enables the integration of HPV16 into the genome of HPV16-harboring keratinocytes, and could thereby influence earlier transformation of these cells to cancer in an animal model...
March 1, 2018: Journal of Nutrition
Zhong Ni, Xiting Wang, Tianchen Zhang, Linlin Li, Jianxue Li
Small cell lung cancer (SCLC) is the subtype of lung cancer with the highest degree of malignancy and the lowest degree of differentiation. The purpose of this study was to investigate the molecular mechanisms of SCLC using bioinformatics analysis, and to provide new ideas for the early diagnosis and targeted therapy of SCLC. Microarray data were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) in SCLC were compared with the normal lung samples and identified. Gene Ontology (GO) function and pathway analysis of DEGs was performed through the DAVID database...
April 2018: Experimental and Therapeutic Medicine
Guillermo de Anda-Jáuregui, Kai Guo, Brett A McGregor, Junguk Hur
The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs)...
2018: Frontiers in Physiology
Jingxiao Wang, Xinjie Yang, Haibo Han, Limin Wang, Weiqian Bao, Shanshan Wang, Robert M Hoffman, Meng Yang, Hui Qi, Chao An, Kaiwen Hu
Objective: Triple-negative breast cancer (TNBC) is highly invasive and metastatic, which is in urgent need of transformative therapeutics. Tubeimu (TBM), the rhizome of Bolbostemma paniculatum (Maxim.) Franquet, is one of the Chinese medicinal herbs used for breast diseases since the ancient times. The present study evaluated the efficacy, especially the anti-metastatic effects of the dichloromethane extract of Tubeimu (ETBM) on TNBC orthotopic mouse models and cell lines. Methods: We applied real-time imaging on florescent orthotopic TNBC mice model and tested cell migration and invasion abilities with MDA-MB-231 cell line...
February 2018: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
Kathleen A Calzone, Jean Jenkins, Stacey Culp, Laurie Badzek
BACKGROUND: The Precision Medicine Initiative will accelerate genomic discoveries that improve health care, necessitating a genomic competent workforce. PURPOSE: This study assessed leadership team (administrator/educator) year-long interventions to improve registered nurses' (RNs) capacity to integrate genomics into practice. METHODS: We examined genomic competency outcomes in 8,150 RNs. DISCUSSION: Awareness and intention to learn more increased compared with controls...
November 13, 2017: Nursing Outlook
Nelly Olova, Felix Krueger, Simon Andrews, David Oxley, Rebecca V Berrens, Miguel R Branco, Wolf Reik
BACKGROUND: Whole-genome bisulfite sequencing (WGBS) is becoming an increasingly accessible technique, used widely for both fundamental and disease-oriented research. Library preparation methods benefit from a variety of available kits, polymerases and bisulfite conversion protocols. Although some steps in the procedure, such as PCR amplification, are known to introduce biases, a systematic evaluation of biases in WGBS strategies is missing. RESULTS: We perform a comparative analysis of several commonly used pre- and post-bisulfite WGBS library preparation protocols for their performance and quality of sequencing outputs...
March 15, 2018: Genome Biology
Eric W Malone, Joshuah S Perkin, Brian M Leckie, Matthew A Kulp, Carla R Hurt, Donald M Walker
Extirpated organisms are reintroduced into their former ranges worldwide to combat species declines and biodiversity losses. The growing field of reintroduction biology provides guiding principles for reestablishing populations, though criticisms remain regarding limited integration of initial planning, modeling frameworks, interdisciplinary collaborations, and multi-species approaches. We used an interdisciplinary, multi-species, quantitative framework to plan reintroductions of three fish species into Abrams Creek, Great Smoky Mountains National Park, USA...
March 15, 2018: Global Change Biology
Margarita Villar, Lourdes Mateos-Hernandez, Jose de la Fuente
BACKGROUND: Why an autoimmune disease that is the main cause of the acute neuromuscular paralysis worldwide has not yet a well-characterized cause or an effective treatment? The existence of different clinical variants for the Guillain-Barré syndrome (GBS) coupled with the fact that a high number of pathogens can cause an infection that sometimes, but not always, precedes the development of the syndrome, confers a high degree of uncertainty for both prognosis and treatment. In the post-genomic era, the development of omics technologies for the high-throughput analysis of biological molecules is allowing the characterization of biological systems in a degree of depth unimaginable before...
March 14, 2018: Current Medicinal Chemistry
Beatriz Silva Lima, Mafalda Ascensão Videira
Since the human genome decoding, understanding and identification of genetic disturbances behind many diseases, including cancer, are intensively increasing. Scientific and technological advances in this area trigger the search for therapeutic (curative) approaches targeting the correction of gene disturbances. Gene therapy medicinal products (GTMPs) emerge in this context, bringing new challenges for their characterization. Compared to small molecules, biodistribution is fundamental to identifying target organs and anticipating safety and efficacy, may be integrated into safety and pharmacology studies, and may eventually be anticipated based on specificities of vectors and constructs...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
Natthakan Thongon, Chiara Zucal, Vito Giuseppe D'Agostino, Toma Tebaldi, Silvia Ravera, Federica Zamporlini, Francesco Piacente, Ruxanda Moschoi, Nadia Raffaelli, Alessandro Quattrone, Alessio Nencioni, Jean-Francois Peyron, Alessandro Provenzani
Background: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance. Methods: We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, and by exploiting an integrated approach based on genetic, biochemical, and genome wide analyses, we annotated the drug resistance mechanisms...
2018: Cancer & Metabolism
Changguo Ma, Chunjie Gu, Yongxia Huo, Xiaoyan Li, Xiong-Jian Luo
Genome-wide association studies (GWAS) have identified more than 100 loci that show robust association with schizophrenia risk. However, due to the complexity of linkage disequilibrium and gene regulatory, it is challenging to pinpoint the causal genes at the risk loci and translate the genetic findings from GWAS into disease mechanism and clinical treatment. Here we systematically predicted the plausible candidate causal genes for schizophrenia at genome-wide level. We utilized different approaches and strategies to predict causal genes for schizophrenia, including Sherlock, SMR, DAPPLE, Prix Fixe, NetWAS, and DEPICT...
March 15, 2018: Translational Psychiatry
Carin K Ingemarsdotter, Jingwei Zeng, Ziqi Long, Andrew M L Lever, Julia C Kenyon
BACKGROUND: NSC260594, a quinolinium derivative from the NCI diversity set II compound library, was previously identified in a target-based assay as an inhibitor of the interaction between the HIV-1 (ψ) stem-loop 3 (SL3) RNA and Gag. This compound was shown to exhibit potent antiviral activity. Here, the effects of this compound on individual stages of the viral lifecycle were examined by qRT-PCR, ELISA and Western blot, to see if its actions were specific to the viral packaging stage...
March 14, 2018: Retrovirology
Christina Maria Franck, Jens Westermann, Aurélien Boisson-Dernier
Plant cells are surrounded by cell walls protecting them from a myriad of environmental challenges. For successful habitat adaptation, extracellular cues are perceived at the cell wall and relayed to downstream signaling constituents to mediate dynamic cell wall remodeling and adapted intracellular responses. Plant malectin-like receptor kinases, also known as Catharanthus roseus receptor-like kinase 1-like proteins (CrRLK1Ls), take part in these perception and relay processes. CrRLK1Ls are involved in many different plant functions...
March 14, 2018: Annual Review of Plant Biology
Ilia Korvigo, Andrey Afanasyev, Nikolay Romashchenko, Mikhail Skoblov
Many automatic classifiers were introduced to aid inference of phenotypical effects of uncategorised nsSNVs (nonsynonymous Single Nucleotide Variations) in theoretical and medical applications. Lately, several meta-estimators have been proposed that combine different predictors, such as PolyPhen and SIFT, to integrate more information in a single score. Although many advances have been made in feature design and machine learning algorithms used, the shortage of high-quality reference data along with the bias towards intensively studied in vitro models call for improved generalisation ability in order to further increase classification accuracy and handle records with insufficient data...
2018: PloS One
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