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https://www.readbyqxmd.com/read/27923151/a-novel-role-for-the-kr%C3%A3-ppel-like-factor-14-on-macrophage-inflammatory-response-and-atherosclerosis-development
#1
Xiao Wei, Ruomei Yang, Chengpan Wang, Xun Jian, Ling Li, Hua Liu, Gangyi Yang, Zhiyong Li
Genome-wide association studies have shown that Krüppel-like factor 14 (KLF14) is associated with both Type 2 diabetes mellitus and lipid metabolism. However, its role in chronic inflammatory responses and the pathogenesis of atherosclerosis remains unknown. The present study was designed to investigate both in vivo and in vitro the impact of KLF14 on chronic inflammatory responses and atherosclerosis. ApoE KO mice, a well-established animal model of atherosclerosis, had higher expressions of KLF14 in aorta tissues than that in C57BL/6 J mice when fed the high-fat diet (HFD) or standard chow diet...
November 14, 2016: Cardiovascular Pathology: the Official Journal of the Society for Cardiovascular Pathology
https://www.readbyqxmd.com/read/27923117/examining-topological-domain-influence-on-enhancer-function
#2
Robert A Beagrie, Ana Pombo
Enhancers regulate the expression of target genes across large genomic distances, but it is unclear how recently discovered topological domains affect this regulation. Reporting in this issue of Developmental Cell, Symmons et al. (2016) show that the endogenous Shh topological domain promotes functional interactions between Shh and its remote enhancer.
December 5, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27923068/gene-expression-correlates-with-the-number-of-herpes-viral-genomes-initiating-infection-in-single-cells
#3
Efrat M Cohen, Oren Kobiler
Viral gene expression varies significantly among genetically identical cells. The sources of these variations are not well understood and have been suggested to involve both deterministic host differences and stochastic viral host interactions. For herpesviruses, only a limited number of incoming viral genomes initiate expression and replication in each infected cell. To elucidate the effect of this limited number of productively infecting genomes on viral gene expression in single cells, we constructed a set of fluorescence-expressing genetically tagged herpes recombinants...
December 6, 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27923066/somatic-genomics-and-clinical-features-of-lung-adenocarcinoma-a-retrospective-study
#4
Jianxin Shi, Xing Hua, Bin Zhu, Sarangan Ravichandran, Mingyi Wang, Cu Nguyen, Seth A Brodie, Alessandro Palleschi, Marco Alloisio, Gianluca Pariscenti, Kristine Jones, Weiyin Zhou, Aaron J Bouk, Joseph Boland, Belynda Hicks, Adam Risch, Hunter Bennett, Brian T Luke, Lei Song, Jubao Duan, Pengyuan Liu, Takashi Kohno, Qingrong Chen, Daoud Meerzaman, Crystal Marconett, Ite Laird-Offringa, Ian Mills, Neil E Caporaso, Mitchell H Gail, Angela C Pesatori, Dario Consonni, Pier Alberto Bertazzi, Stephen J Chanock, Maria Teresa Landi
BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histologic subtype of lung cancer and has a high risk of distant metastasis at every disease stage. We aimed to characterize the genomic landscape of LUAD and identify mutation signatures associated with tumor progression. METHODS AND FINDINGS: We performed an integrative genomic analysis, incorporating whole exome sequencing (WES), determination of DNA copy number and DNA methylation, and transcriptome sequencing for 101 LUAD samples from the Environment And Genetics in Lung cancer Etiology (EAGLE) study...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923063/control-of-gene-expression-by-rna-binding-protein-action-on-alternative-translation-initiation-sites
#5
Angela Re, Levi Waldron, Alessandro Quattrone
Transcript levels do not faithfully predict protein levels, due to post-transcriptional regulation of gene expression mediated by RNA binding proteins (RBPs) and non-coding RNAs. We developed a multivariate linear regression model integrating RBP levels and predicted RBP-mRNA regulatory interactions from matched transcript and protein datasets. RBPs significantly improved the accuracy in predicting protein abundance of a portion of the total modeled mRNAs in three panels of tissues and cells and for different methods employed in the detection of mRNA and protein...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27923053/different-evolutionary-paths-to-complexity-for-small-and-large-populations-of-digital-organisms
#6
Thomas LaBar, Christoph Adami
A major aim of evolutionary biology is to explain the respective roles of adaptive versus non-adaptive changes in the evolution of complexity. While selection is certainly responsible for the spread and maintenance of complex phenotypes, this does not automatically imply that strong selection enhances the chance for the emergence of novel traits, that is, the origination of complexity. Population size is one parameter that alters the relative importance of adaptive and non-adaptive processes: as population size decreases, selection weakens and genetic drift grows in importance...
December 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27923049/expression-of-lncrnas-in-low-grade-gliomas-and-glioblastoma-multiforme-an-in-silico-analysis
#7
Brian J Reon, Jordan Anaya, Ying Zhang, James Mandell, Benjamin Purow, Roger Abounader, Anindya Dutta
BACKGROUND: Each year, over 16,000 patients die from malignant brain cancer in the US. Long noncoding RNAs (lncRNAs) have recently been shown to play critical roles in regulating neurogenesis and brain tumor progression. To better understand the role of lncRNAs in brain cancer, we performed a global analysis to identify and characterize all annotated and novel lncRNAs in both grade II and III gliomas as well as grade IV glioblastomas (glioblastoma multiforme [GBM]). METHODS AND FINDINGS: We determined the expression of all lncRNAs in over 650 brain cancer and 70 normal brain tissue RNA sequencing datasets from The Cancer Genome Atlas (TCGA) and other publicly available datasets...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923047/precision-cancer-diagnostics-tracking-genomic-evolution-in-clinical-trials
#8
Francisco Beca, Andrew H Beck
In a Perspective, Francisco Beca and Andrew Beck discuss Charles Swanton and colleagues' accompanying Research Article on somatic mutations in patients with inflammatory breast cancer treated in a Phase II clinical trial.
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923045/tumor-evolution-in-two-patients-with-basal-like-breast-cancer-a-retrospective-genomics-study-of-multiple-metastases
#9
Katherine A Hoadley, Marni B Siegel, Krishna L Kanchi, Christopher A Miller, Li Ding, Wei Zhao, Xiaping He, Joel S Parker, Michael C Wendl, Robert S Fulton, Ryan T Demeter, Richard K Wilson, Lisa A Carey, Charles M Perou, Elaine R Mardis
BACKGROUND: Metastasis is the main cause of cancer patient deaths and remains a poorly characterized process. It is still unclear when in tumor progression the ability to metastasize arises and whether this ability is inherent to the primary tumor or is acquired well after primary tumor formation. Next-generation sequencing and analytical methods to define clonal heterogeneity provide a means for identifying genetic events and the temporal relationships between these events in the primary and metastatic tumors within an individual...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923043/clonal-evolutionary-analysis-during-her2-blockade-in-her2-positive-inflammatory-breast-cancer-a-phase-ii-open-label-clinical-trial-of-afatinib-vinorelbine
#10
Gerald Goh, Ramona Schmid, Kelly Guiver, Wichit Arpornwirat, Imjai Chitapanarux, Vinod Ganju, Seock-Ah Im, Sung-Bae Kim, Arunee Dechaphunkul, Jedzada Maneechavakajorn, Neil Spector, Thomas Yau, Mehdi Afrit, Slim Ben Ahmed, Stephen R Johnston, Neil Gibson, Martina Uttenreuther-Fischer, Javier Herrero, Charles Swanton
BACKGROUND: Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923042/sequencing-strategies-to-guide-decision-making-in-cancer-treatment
#11
James T Topham, Marco A Marra
In a Perspective, James Topham and Marco Marra discuss progress in the use of genomic information to guide cancer treatment.
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27923030/patient-derived-induced-pluripotent-stem-cells-in-cancer-research-and-precision-oncology
#12
Eirini P Papapetrou
Together with recent advances in the processing and culture of human tissue, bioengineering, xenotransplantation and genome editing, Induced pluripotent stem cells (iPSCs) present a range of new opportunities for the study of human cancer. Here we discuss the main advantages and limitations of iPSC modeling, and how the method intersects with other patient-derived models of cancer, such as organoids, organs-on-chips and patient-derived xenografts (PDXs). We highlight the opportunities that iPSC models can provide beyond those offered by existing systems and animal models and present current challenges and crucial areas for future improvements toward wider adoption of this technology...
December 6, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27922817/ischemic-stroke-patients-are-biologically-older-than-their-chronological-age
#13
Carolina Soriano-Tárraga, Eva Giralt-Steinhauer, Marina Mola-Caminal, Rosa M Vivanco-Hidalgo, Angel Ois, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Sergi Sayols-Baixeras, Roberto Elosua, Jaume Roquer, Jordi Jiménez-Conde
Ischemic stroke is associated with aging. It is possible to predict chronological age by measuring age-related changes in DNA methylation from multiple CpG sites across the genome, known as biological age. The difference between biological age and actual chronological age would indicate an individual's level of aging. Our aim was to determine the biological age of ischemic stroke patients and compare their aging with controls of the same chronological age. A total of 123 individuals, 41 controls and 82 patients with ischemic stroke were paired by chronological age, ranging from 39 to 82 years...
August 25, 2016: Aging
https://www.readbyqxmd.com/read/27922636/dna-methylation-and-substance-use-risk-a-prospective-genome-wide-study-spanning-gestation-to-adolescence
#14
C A M Cecil, E Walton, R G Smith, E Viding, E J McCrory, C L Relton, M Suderman, J-B Pingault, W McArdle, T R Gaunt, J Mill, E D Barker
Epigenetic processes have been implicated in addiction; yet, it remains unclear whether these represent a risk factor and/or a consequence of substance use. Here, we believe we conducted the first genome-wide, longitudinal study to investigate whether DNA methylation patterns in early life prospectively associate with substance use in adolescence. The sample comprised of 244 youth (51% female) from the Avon Longitudinal Study of Parents and Children (ALSPAC), with repeated assessments of DNA methylation (Illumina 450k array; cord blood at birth, whole blood at age 7) and substance use (tobacco, alcohol and cannabis use; age 14-18)...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27922628/a-chromosome-level-genome-assembly-of-the-asian-arowana-scleropages-formosus
#15
Jia Li, Chao Bian, Yinchang Hu, Xidong Mu, Xueyan Shen, Vydianathan Ravi, Inna S Kuznetsova, Ying Sun, Xinxin You, Ying Qiu, Xinhui Zhang, Hui Yu, Yu Huang, Pao Xu, Ruobo Gu, Junmin Xu, László Orbán, Byrappa Venkatesh, Qiong Shi
Asian arowana (Scleropages formosus), an ancient teleost belonging to the Order Osteoglossomorpha, has been a valuable ornamental fish with some varieties. However, its biological studies and breeding germplasm have been remarkably limited by the lack of a reference genome. To solve these problems, here we report high-quality genome sequences of three common varieties of Asian arowana (the golden, red and green arowana). We firstly generated a chromosome-level genome assembly of the golden arowana, on basis of the genetic linkage map constructed with the restriction site-associated DNA sequencing (RAD-seq)...
December 6, 2016: Scientific Data
https://www.readbyqxmd.com/read/27922611/genetic-and-epigenomic-mechanisms-of-mammalian-circadian-transcription
#16
REVIEW
Romeo Papazyan, Yuxiang Zhang, Mitchell A Lazar
The mammalian molecular clock comprises a complex network of transcriptional programs that integrates environmental signals with physiological pathways in a tissue-specific manner. Emerging technologies are extending knowledge of basic clock features by uncovering their underlying molecular mechanisms, thus setting the stage for a 'systems' view of the molecular clock. Here we discuss how recent data from genome-wide genetic and epigenetic studies have informed the understanding of clock function. In addition to its importance in human physiology and disease, the clock mechanism provides an ideal model to assess general principles of dynamic transcription regulation in vivo...
December 6, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27922606/otto-a-new-strategy-to-extract-mental-disease-relevant-combinations-of-gwas-hits-from-individuals
#17
H Ehrenreich, M Mitjans, S Van der Auwera, T P Centeno, M Begemann, H J Grabe, S Bonn, K-A Nave
Despite high heritability of schizophrenia, genome-wide association studies (GWAS) have not yet revealed distinct combinations of single-nucleotide polymorphisms (SNPs), relevant for mental disease-related, quantifiable behavioral phenotypes. Here we propose an individual-based model to use genome-wide significant markers for extracting first genetic signatures of such behavioral continua. 'OTTO' (old Germanic=heritage) marks an individual characterized by a prominent phenotype and a particular load of phenotype-associated risk SNPs derived from GWAS that likely contributed to the development of his personal mental illness...
December 6, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27922604/common-variants-on-2p16-1-6p22-1-and-10q24-32-are-associated-with-schizophrenia-in-han-chinese-population
#18
H Yu, H Yan, J Li, Z Li, X Zhang, Y Ma, L Mei, C Liu, L Cai, Q Wang, F Zhang, N Iwata, M Ikeda, L Wang, T Lu, M Li, H Xu, X Wu, B Liu, J Yang, K Li, L Lv, X Ma, C Wang, L Li, F Yang, T Jiang, Y Shi, T Li, D Zhang, W Yue
Many schizophrenia susceptibility loci have been identified through genome-wide association studies (GWASs) in European populations. However, until recently, schizophrenia GWASs in non-European populations were limited to small sample sizes and have yielded few loci associated with schizophrenia. To identify genetic risk variations for schizophrenia in the Han Chinese population, we performed a two-stage GWAS of schizophrenia comprising 4384 cases and 5770 controls, followed by independent replications of 13 single-nucleotide polymorphisms in an additional 4339 schizophrenia cases and 7043 controls of Han Chinese ancestry...
December 6, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27922601/the-effect-of-extrinsic-mortality-on-genome-size-evolution-in-prokaryotes
#19
Piotr Bentkowski, Cock van Oosterhout, Ben Ashby, Thomas Mock
Mortality has a significant role in prokaryotic ecology and evolution, yet the impact of variations in extrinsic mortality on prokaryotic genome evolution has received little attention. We used both mathematical and agent-based models to reveal how variations in extrinsic mortality affect prokaryotic genome evolution. Our results suggest that the genome size of bacteria increases with increased mortality. A high extrinsic mortality increases the pool of free resources and shortens life expectancy, which selects for faster reproduction, a phenotype we called 'scramblers'...
December 6, 2016: ISME Journal
https://www.readbyqxmd.com/read/27922600/vibrio-crassostreae-a-benign-oyster-colonizer-turned-into-a-pathogen-after-plasmid-acquisition
#20
Maxime Bruto, Adèle James, Bruno Petton, Yannick Labreuche, Sabine Chenivesse, Marianne Alunno-Bruscia, Martin F Polz, Frédérique Le Roux
Vibrios are frequently associated with oyster mortality; however whether they are the primary causative agent or secondary opportunistic colonizers is not well understood. Here we combine analysis of natural infection dynamics, population genomics and molecular genetics to ask (i) to what extent oysters are passively colonized by Vibrio population present in the surrounding water, (ii) how populations turn over during pathogenicity events and (iii) what genetic factors are responsible for pathogenicity. We identified several populations of Vibrio preferentially associated with oyster tissues...
December 6, 2016: ISME Journal
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