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  • RETrace: simultaneous retrospective lineage tracing and methylation profiling of single cells.
    Genome Res. (IF 9.944) Pub Date : 2020-03-03
    Christopher Jen-Yue Wei,Kun Zhang

    Retrospective lineage tracing harnesses naturally occurring mutations in cells to elucidate single-cell development. Common single-cell phylogenetic fate mapping methods have utilized highly mutable microsatellite loci found within the human genome. Such methods were limited by the introduction of in vitro noise through polymerase slippage inherent in DNA amplification, which we characterized to be

    更新日期:2020-04-08
  • Noncoding regions underpin avian bill shape diversification at macroevolutionary scales
    Genome Res. (IF 9.944) Pub Date : 2020-04-08
    Leeban Yusuf; Matthew C. Heatley; Joseph P.G. Palmer; Henry J. Barton; Christopher R. Cooney; Toni I. Gossmann

    Recent progress has been made in identifying genomic regions implicated in trait evolution on a microevolutionary scale in many species, but whether these are relevant over macroevolutionary time remains unclear. Here, we directly address this fundamental question using bird beak shape, a key evolutionary innovation linked to patterns of resource use, divergence, and speciation, as a model trait. We

    更新日期:2020-04-08
  • Time course regulatory analysis based on paired expression and chromatin accessibility data
    Genome Res. (IF 9.944) Pub Date : 2020-03-18
    Zhana Duren; Xi Chen; Jingxue Xin; Yong Wang; Wing Hung Wong

    A time course experiment is a widely used design in the study of cellular processes such as differentiation or response to stimuli. In this paper, we propose time course regulatory analysis (TimeReg) as a method for the analysis of gene regulatory networks based on paired gene expression and chromatin accessibility data from a time course. TimeReg can be used to prioritize regulatory elements, to extract

    更新日期:2020-04-08
  • Transcriptome reconstruction and functional analysis of eukaryotic marine plankton communities via high-throughput metagenomics and metatranscriptomics
    Genome Res. (IF 9.944) Pub Date : 2020-03-23
    Alexey Vorobev; Marion Dupouy; Quentin Carradec; Tom O. Delmont; Anita Annamalé; Patrick Wincker; Eric Pelletier

    Large-scale metagenomic and metatranscriptomic data analyses are often restricted by their gene-centric approach, limiting the ability to understand organismal and community biology. De novo assembly of large and mosaic eukaryotic genomes from complex meta-omics data remains a challenging task, especially in comparison with more straightforward bacterial and archaeal systems. Here, we use a transcriptome

    更新日期:2020-04-08
  • Inhibition of transcription leads to rewiring of locus-specific chromatin proteomes
    Genome Res. (IF 9.944) Pub Date : 2020-03-18
    Deepani W. Poramba-Liyanage; Tessy Korthout; Christine E. Cucinotta; Ila van Kruijsbergen; Tibor van Welsem; Dris El Atmioui; Huib Ovaa; Toshio Tsukiyama; Fred van Leeuwen

    Transcription of a chromatin template involves the concerted interaction of many different proteins and protein complexes. Analyses of specific factors showed that these interactions change during stress and upon developmental switches. However, how the binding of multiple factors at any given locus is coordinated has been technically challenging to investigate. Here we used Epi-Decoder in yeast to

    更新日期:2020-04-08
  • Redundant and specific roles of cohesin STAG subunits in chromatin looping and transcriptional control
    Genome Res. (IF 9.944) Pub Date : 2020-04-06
    Valentina Casa; Macarena MorontaGines; Eduardo Gade Gusmao; Johan A. Slotman; Anne Zirkel; Natasa Josipovic; Oole Edwin; Wilfred F. J. van IJcken; Adriaan B. Houtsmuller; Argyris Papntonis; Kerstin S. Wendt

    Cohesin is a ring-shaped multiprotein complex that is crucial for 3D genome organization and transcriptional regulation during differentiation and development. It also confers sister chromatid cohesion and facilitates DNA damage repair. Besides its core subunits SMC3, SMC1A and RAD21, cohesin in somatic cells contains one of two orthologous STAG subunits, STAG1 or STAG2. How these variable subunits

    更新日期:2020-04-06
  • Rapid evolution of piRNA-mediated silencing of an invading transposable element was driven by abundant de novo mutations
    Genome Res. (IF 9.944) Pub Date : 2020-04-01
    Shuo Zhang; Beverly Pointer; Erin Kelleher

    The regulation of transposable element (TE) activity by small RNAs is a ubiquitous feature of germlines. However, despite the obvious benefits to the host in terms of ensuring the production of viable gametes and maintaining the integrity of the genomes they carry, it remains controversial whether TE regulation evolves adaptively. We examined the emergence and evolutionary dynamics of repressor alleles

    更新日期:2020-04-03
  • Accurate and complete genomes from metagenomes
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    Lin-Xing Chen; Karthik Anantharaman; Alon Shaiber; A. Murat Eren; Jillian F. Banfield

    Genomes are an integral component of the biological information about an organism; thus, the more complete the genome, the more informative it is. Historically, bacterial and archaeal genomes were reconstructed from pure (monoclonal) cultures, and the first reported sequences were manually curated to completion. However, the bottleneck imposed by the requirement for isolates precluded genomic insights

    更新日期:2020-03-27
  • Comprehensive analysis of indels in whole-genome microsatellite regions and microsatellite instability across 21 cancer types
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    Akihiro Fujimoto; Masashi Fujita; Takanori Hasegawa; Jing Hao Wong; Kazuhiro Maejima; Aya Oku-Sasaki; Kaoru Nakano; Yuichi Shiraishi; Satoru Miyano; Go Yamamoto; Kiwamu Akagi; Seiya Imoto; Hidewaki Nakagawa

    Microsatellites are repeats of 1- to 6-bp units, and approximately 10 million microsatellites have been identified across the human genome. Microsatellites are vulnerable to DNA mismatch errors and have thus been used to detect cancers with mismatch repair deficiency. To reveal the mutational landscape of microsatellite repeat regions at the genome level, we analyzed approximately 20.1 billion microsatellites

    更新日期:2020-03-27
  • Alternative polyadenylation drives oncogenic gene expression in pancreatic ductal adenocarcinoma.
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    Swati Venkat,Arwen A Tisdale,Johann R Schwarz,Abdulrahman A Alahmari,H Carlo Maurer,Kenneth P Olive,Kevin H Eng,Michael E Feigin

    Alternative polyadenylation (APA) is a gene regulatory process that dictates mRNA 3'-UTR length, resulting in changes in mRNA stability and localization. APA is frequently disrupted in cancer and promotes tumorigenesis through altered expression of oncogenes and tumor suppressors. Pan-cancer analyses have revealed common APA events across the tumor landscape; however, little is known about tumor type-specific

    更新日期:2020-03-27
  • Identification of FMR1-regulated molecular networks in human neurodevelopment
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    Meng Li; Junha Shin; Ryan D. Risgaard; Molly J. Parries; Jianyi Wang; Deborah Chasman; Shuang Liu; Sushmita Roy; Anita Bhattacharyya; Xinyu Zhao

    RNA-binding proteins (RNA-BPs) play critical roles in development and disease to regulate gene expression. However, genome-wide identification of their targets in primary human cells has been challenging. Here, we applied a modified CLIP-seq strategy to identify genome-wide targets of the FMRP translational regulator 1 (FMR1), a brain-enriched RNA-BP, whose deficiency leads to Fragile X Syndrome (FXS)

    更新日期:2020-03-27
  • Genome-wide integrative analysis of circular RNA dysregulation and the corresponding circular RNA-microRNA-mRNA regulatory axes in autism.
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    Yen-Ju Chen,Chia-Ying Chen,Te-Lun Mai,Chih-Fan Chuang,Yu-Chen Chen,Sachin Kumar Gupta,Laising Yen,Yi-Da Wang,Trees-Juen Chuang

    Circular RNAs (circRNAs), a class of long noncoding RNAs, are known to be enriched in mammalian neural tissues. While a wide range of dysregulation of gene expression in autism spectrum disorder (ASD) have been reported, the role of circRNAs in ASD remains largely unknown. Here we performed genome-wide circRNA expression profiling in post-mortem brains from individuals with ASD and controls and identified

    更新日期:2020-03-27
  • Systems Genetics of the Drosophila Metabolome.
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    Shanshan Zhou,Fabio Morgante,Matthew Geisz,Junwu Ma,Robert Anholt,Trudy Mackay

    How effects of DNA sequence variants are transmitted through intermediate endophenotypes to modulate organismal traits remains a central question in quantitative genetics. This problem can be addressed through a systems approach in a population in which genetic polymorphisms, gene expression traits, metabolites and complex phenotypes can be evaluated on the same genotypes. Here, we focused on the metabolome

    更新日期:2020-03-27
  • Rearrangement of macronucleus chromosomes correspond to TAD-like structures of micronucleus chromosomes in Tetrahymena thermophila.
    Genome Res. (IF 9.944) Pub Date : 2020-03-12
    Zhengyu Luo,Tengfei Hu,Hong Jiang,Ruoyu Wang,Qianlan Xu,Simo Zhang,Jun Cao,Xiaoyuan Song

    The somatic macronucleus (MAC) and germline micronucleus (MIC) of Tetrahymena thermophila differ in chromosome numbers, sizes, functions, transcriptional activities, and cohesin complex location. However, the higher-order chromatin organization in T. thermophila is still largely unknown. Here, we explored the higher-order chromatin organization in the two distinct nuclei of T. thermophila using the

    更新日期:2020-03-27
  • Genomic loci susceptible to systematic sequencing bias in clinical whole genomes
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    Timothy M. Freeman; Genomics England Research Consortium; Dennis Wang; Jason Harris; John C. Ambrose; Prabhu Arumugam; Emma L. Baple; Marta Bleda; Freya Boardman-Pretty; Jeanne M. Boissiere; Christopher R. Boustred; Mark J. Caulfield; Georgia C. Chan; Clare E.H. Craig; Louise C. Daugherty; Anna de Burca; Andrew Devereau; Greg Elgar; Rebecca E. Foulger; Tom Fowler; Pedro Furió-Tarí; Joanne M. Hackett;

    Accurate massively parallel sequencing (MPS) of genetic variants is key to many areas of science and medicine, such as cataloging population genetic variation and diagnosing genetic diseases. Certain genomic positions can be prone to higher rates of systematic sequencing and alignment bias that limit accuracy, resulting in false positive variant calls. Current standard practices to differentiate between

    更新日期:2020-03-27
  • Human auditory ossicles as an alternative optimal source of ancient DNA.
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    Kendra Ann Sirak,Daniel Magalhaes Fernandes,Olivia Cheronet,Eadaoin Harney,Matthew Mah,Swapan Mallick,Nadin Rohland,Nicole Adamski,Nasreen Broomandkhoshbacht,Kimberly Callan,Francesca Candilio,Ann Marie Lawson,Kirsten Mandl,Jonas Oppenheimer,Kristin Stewardson,Fatma Zalzala,Alexandra Anders,Juraj Bartík,Alfredo Coppa,Tumen Dashtseveg,Sándor Évinger,Zdeněk Farkaš,Tamás Hajdu,Jamsranjav Bayarsaikhan

    DNA recovery from ancient human remains has revolutionized our ability to reconstruct the genetic landscape of the past. Ancient DNA research has benefited from the identification of skeletal elements, such as the cochlear part of the osseous inner ear, that provide optimal contexts for DNA preservation; however, the rich genetic information obtained from the cochlea must be counterbalanced against

    更新日期:2020-03-27
  • Assembly-free single-molecule sequencing recovers complete virus genomes from natural microbial communities.
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    John Beaulaurier,Elaine Luo,John M Eppley,Paul Den Uyl,Xiaoguang Dai,Andrew Burger,Daniel J Turner,Matthew Pendleton,Sissel Juul,Eoghan Harrington,Edward F DeLong

    Viruses are the most abundant biological entities on Earth and play key roles in host ecology, evolution, and horizontal gene transfer. Despite recent progress in viral metagenomics, the inherent genetic complexity of virus populations still poses technical difficulties for recovering complete virus genomes from natural assemblages. To address these challenges, we developed an assembly-free, single-molecule

    更新日期:2020-03-27
  • Analysis of Hi-C data using SIP effectively identifies loops in organisms from C. elegans to mammals.
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    M Jordan Rowley,Axel Poulet,Michael Nichols,Brianna Bixler,Adrian Sanborn,Elizabeth Brouhard,Karen Hermetz,Hannah Linsenbaum,Gyorgyi Csankovszki,Erez Lieberman Aiden,Victor G Corces

    Chromatin loops are a major component of 3D nuclear organization, visually apparent as intense point-to-point interactions in Hi-C maps. Identification of these loops is an important part of most Hi-C analyses. However current methods often miss visually evident CTCF loops in Hi-C datasets from mammals and they completely fail to identify high intensity loops in other organisms. We present Significant

    更新日期:2020-03-27
  • Dual threshold optimization and network inference reveal convergent evidence from TF binding locations and TF perturbation responses.
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    Yiming Kang,Nikhil R Patel,Christian Shively,Pamela Samantha Recio,Xuhua Chen,Bernd J Wranik,Griffin Kim,R Scott McIsaac,Rob Mitra,Michael R Brent

    A high-confidence map of the direct, functional targets of each transcription factor (TF) requires convergent evidence from independent sources. Two significant sources of evidence are TF binding locations and the transcriptional responses to direct TF perturbations. Systematic data sets of both types exist for yeast and human. Standard analysis of the genes whose regulatory DNA is bound by a TF, assayed

    更新日期:2020-03-27
  • An integrative view of the regulatory and transcriptional landscapes in mouse hematopoiesis
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    Guanjue Xiang; Cheryl A. Keller; Elisabeth Heuston; Belinda M. Giardine; Lin An; Alexander Q. Wixom; Amber Miller; April Cockburn; Michael E.G. Sauria; Kathryn Weaver; Jens Lichtenberg; Berthold Göttgens; Qunhua Li; David Bodine; Shaun Mahony; James Taylor; Gerd A. Blobel; Mitchell J. Weiss; Yong Cheng; Feng Yue; Jim Hughes; Douglas R. Higgs; Yu Zhang; Ross C. Hardison

    Thousands of epigenomic data sets have been generated in the past decade, but it is difficult for researchers to effectively use all the data relevant to their projects. Systematic integrative analysis can help meet this need, and the VISION project was established for validated systematic integration of epigenomic data in hematopoiesis. Here, we systematically integrated extensive data recording epigenetic

    更新日期:2020-03-27
  • Gene expression networks in the Drosophila Genetic Reference Panel.
    Genome Res. (IF 9.944) Pub Date : 2020-03-06
    Logan J Everett,Wen Huang,Shanshan Zhou,Mary Anna Carbone,Richard F Lyman,Gunjan H Arya,Matthew S Geisz,Junwu Ma,Fabio Morgante,Genevieve St Armour,Lavanya Turlapati,Robert R H Anholt,Trudy Mackay

    A major challenge in modern biology is to understand how naturally occurring variation in DNA sequences affects complex organismal traits through networks of intermediate molecular phenotypes. This question is best addressed in a genetic mapping population in which all molecular polymorphisms are known and for which molecular endophenotypes and complex traits are assessed on the same genotypes. Here

    更新日期:2020-03-27
  • Integrated annotations and analyses of small RNA–producing loci from 47 diverse plants
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    Alice Lunardon; Nathan R. Johnson; Emily Hagerott; Tamia Phifer; Seth Polydore; Ceyda Coruh; Michael J. Axtell

    Plant endogenous small RNAs (sRNAs) are important regulators of gene expression. There are two broad categories of plant sRNAs: microRNAs (miRNAs) and endogenous short interfering RNAs (siRNAs). MicroRNA loci are relatively well-annotated but compose only a small minority of the total sRNA pool; siRNA locus annotations have lagged far behind. Here, we used a large data set of published and newly generated

    更新日期:2020-03-27
  • Corrigendum: Convergent recombination cessation between mating-type genes and centromeres in selfing anther-smut fungi
    Genome Res. (IF 9.944) Pub Date : 2020-03-01
    Fantin Carpentier; Ricardo C. Rodríguez de la Vega; Sara Branco; Alodie Snirc; Marco A. Coelho; Michael E. Hood; Tatiana Giraud

    Genome Research 29: 944–953 (2019)

    更新日期:2020-03-27
  • T-Cell Immunity against the Hepatitis C Virus: A Persistent Research Priority in an Era of Highly Effective Therapy
    Genome Res. (IF 9.944) Pub Date : 2020-03-23
    Stephanie Smith; Jonathan R. Honegger; Christopher Walker

    Approximately 70% of acute hepatitis C virus (HCV) infections become chronic, indicating that the virus is exceptionally well adapted to persist in humans with otherwise normal immune function. Robust, lifelong replication of this small RNA virus does not require a generalized failure of immunity. HCV effectively subverts innate and adaptive host defenses while leaving immunity against other viruses

    更新日期:2020-03-26
  • Neural Substrates and Circuits of Drug Addiction
    Genome Res. (IF 9.944) Pub Date : 2020-03-23
    Matthew W. Feltenstein; Ronald E. See; Rita A. Fuchs

    Drug addiction is a chronic relapsing disorder, and a significant amount of research has been devoted to understand the factors that contribute to the development, loss of control, and persistence of compulsive addictive behaviors. In this review, we provide an overview of various theories of addiction to drugs of abuse and the neurobiology involved in elements of the addiction cycle. Specific focus

    更新日期:2020-03-26
  • H7N9 Influenza Virus in China
    Genome Res. (IF 9.944) Pub Date : 2020-03-23
    Chengjun Li; Hualan Chen

    In early 2013, human infections caused by a novel H7N9 avian influenza virus (AIV) were first reported in China; these infections caused severe disease and death. The virus was initially low pathogenic to poultry, enabling it to spread widely in different provinces, especially in live poultry markets. Importantly, the H7N9 low pathogenic AIVs (LPAIVs) evolved into highly pathogenic AIVs (HPAIVs) in

    更新日期:2020-03-26
  • Genetic Vulnerability to Opioid Addiction
    Genome Res. (IF 9.944) Pub Date : 2020-03-23
    Brian Reed; Mary Jeanne Kreek

    Opioid addiction, also referred to as opioid use disorder, continues to be a devastating problem throughout the world. Familial relation and twin studies have revealed opioid addiction, like other addictive diseases, to be profoundly influenced by genetics. Genetics studies of opioid addiction have affirmed the importance of genetics contributors in susceptibility to develop opioid addiction, and also

    更新日期:2020-03-26
  • Equine Influenza
    Genome Res. (IF 9.944) Pub Date : 2020-03-09
    Thomas M. Chambers

    Horses are the third major mammalian species, along with humans and swine, long known to be subject to acute upper respiratory disease from influenza A virus infection. The viruses responsible are subtype H7N7, which is believed extinct, and H3N8, which circulates worldwide. The equine influenza lineages are clearly divergent from avian influenza lineages of the same subtypes. Their genetic evolution

    更新日期:2020-03-26
  • Antivirals Targeting the Neuraminidase
    Genome Res. (IF 9.944) Pub Date : 2020-03-09
    Larisa Gubareva; Teena Mohan

    The neuraminidase (NA) of influenza A and B viruses plays a distinct role in viral replication and has a highly conserved catalytic site. Numerous sialic (neuraminic) acid analogs that competitively bind to the NA active site and potently inhibit enzyme activity have been synthesized and tested. Four NA inhibitors are now licensed in various parts of the world (zanamivir, oseltamivir, peramivir, and

    更新日期:2020-03-26
  • Systems Biological Analysis of Immune Response to Influenza Vaccination
    Genome Res. (IF 9.944) Pub Date : 2020-03-09
    Mario Cortese; Amy C. Sherman; Nadine G. Rouphael; Bali Pulendran

    The last decade has witnessed tremendous progress in immunology and vaccinology, owing to several scientific and technological breakthroughs. Systems vaccinology is a field that has emerged at the forefront of vaccine research and development and provides a unique way to probe immune responses to vaccination in humans. The goals of systems vaccinology are to use systems-based approaches to define signatures

    更新日期:2020-03-26
  • Non-Hodgkin Lymphomas: Malignancies Arising from Mature B Cells
    Genome Res. (IF 9.944) Pub Date : 2020-03-09
    Jennifer Shingleton; Jie Wang; Carolyn Baloh; Tushar Dave; Nicholas Davis; Lanie Happ; Othmane Jadi; Rachel Kositsky; Xiang Li; Cassandra Love; Razvan Panea; Qiu Qin; Anupama Reddy; Naina Singhi; Eileen Smith; Devang Thakkar; Sandeep S. Dave

    Non-Hodgkin lymphomas (NHLs) are a diverse group of entities, both clinically and molecularly. Here, we review the evolution of classification schemes in B-cell lymphoma, noting the now standard WHO classification system that is based on immune cell-of-origin and molecular phenotypes. We review how lymphomas arise throughout the B-cell development process as well as the molecular and clinical features

    更新日期:2020-03-26
  • Family-Based Designs that Disentangle Inherited Factors from Pre- and Postnatal Environmental Exposures: In Vitro Fertilization, Discordant Sibling Pairs, Maternal versus Paternal Comparisons, and Adoption Designs
    Genome Res. (IF 9.944) Pub Date : 2020-03-09
    Anita Thapar; Frances Rice

    Identifying environmental risk and protective exposures that have causal effects on health is an important scientific goal. Many environmental exposures are nonrandomly allocated and influenced by dispositional factors including inherited ones. We review family-based designs that can separate the influence of environmental exposures from inherited influences shared between parent and offspring. We

    更新日期:2020-03-26
  • HCV Assembly and Egress via Modifications in Host Lipid Metabolic Systems
    Genome Res. (IF 9.944) Pub Date : 2020-03-02
    Kunitada Shimotohno

    Hepatitis C virus (HCV) proliferates by hijacking the host lipid machinery. In vitro replication systems revealed many aspects of the virus life cycle; in particular, viral utilization of host lipid metabolism during HCV proliferation. HCV interacts with lipid droplets (LDs) before starting the process of virus capsid formation at the lipid-rich endoplasmic reticulum (ER) membrane compartment. HCV

    更新日期:2020-03-26
  • Integrating Family-Based and Mendelian Randomization Designs
    Genome Res. (IF 9.944) Pub Date : 2020-03-02
    Liang-Dar Hwang; Neil M. Davies; Nicole M. Warrington; David M. Evans

    Most Mendelian randomization (MR) studies published in the literature to date have involved analyses of unrelated, putatively independent sets of individuals. However, estimates obtained from these sorts of studies are subject to a range of biases including dynastic effects, assortative mating, residual population stratification, and horizontal pleiotropy. The inclusion of related individuals in MR

    更新日期:2020-03-26
  • Influenza Polymerase Inhibitors: Mechanisms of Action and Resistance
    Genome Res. (IF 9.944) Pub Date : 2020-03-02
    Emi Takashita

    The influenza virus RNA-dependent RNA polymerase is highly conserved among influenza A, B, C, and D viruses. It comprises three subunits: polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), and polymerase acidic protein (PA) in influenza A and B viruses or polymerase 3 protein (P3) in influenza C and D viruses. Because this polymerase is essential for influenza virus replication, it

    更新日期:2020-03-26
  • H5 Influenza Viruses in Egypt
    Genome Res. (IF 9.944) Pub Date : 2020-03-02
    Rabeh El-Shesheny; Ahmed Kandeil; Ahmed Mostafa; Mohamed A. Ali; Richard J. Webby

    For almost a decade, Egypt has been endemic for highly pathogenic avian influenza (HPAI) A(H5N1) viruses. In addition to being catastrophic for poultry production, A(H5N1) has also caused 359 human infections in the country (∼40% of global cases), with 120 being fatal. From 2017, A(H5N1) viruses have been gradually replaced by HPAI A(H5N8) viruses seeded from Southeast Asia through Europe; no human

    更新日期:2020-03-26
  • Mouse Models of Myeloid Malignancies
    Genome Res. (IF 9.944) Pub Date : 2020-02-18
    Faisal Basheer; George Vassiliou

    Mouse models of human myeloid malignancies support the detailed and focused investigation of selected driver mutations and represent powerful tools in the study of these diseases. Carefully developed murine models can closely recapitulate human myeloid malignancies in vivo, enabling the interrogation of a number of aspects of these diseases including their preclinical course, interactions with the

    更新日期:2020-03-26
  • Influenza Therapeutics in Clinical Practice—Challenges and Recent Advances
    Genome Res. (IF 9.944) Pub Date : 2020-02-10
    John H. Beigel; Frederick G. Hayden

    In the last few years, several new direct-acting influenza antivirals have been licensed, and others have advanced in clinical development. The increasing diversity of antiviral classes should allow an adequate public health response should a resistant virus to one agent or class widely circulate. One new antiviral, baloxavir marboxil, has been approved in the United States for treatment of influenza

    更新日期:2020-03-26
  • Epigenetic Mechanisms in Leukemias and Lymphomas
    Genome Res. (IF 9.944) Pub Date : 2020-02-03
    Cihangir Duy; Wendy Béguelin; Ari Melnick

    Although we are just beginning to understand the mechanisms that regulate the epigenome, aberrant epigenetic programming has already emerged as a hallmark of hematologic malignancies including acute myeloid leukemia (AML) and B-cell lymphomas. Although these diseases arise from the hematopoietic system, the epigenetic mechanisms that drive these malignancies are quite different. Yet, in all of these

    更新日期:2020-03-26
  • The Role of the Central Amygdala in Alcohol Dependence
    Genome Res. (IF 9.944) Pub Date : 2020-01-27
    Marisa Roberto; Dean Kirson; Sophia Khom

    Alcohol dependence is a chronically relapsing disorder characterized by compulsive drug-seeking and drug-taking, loss of control in limiting intake, and the emergence of a withdrawal syndrome in the absence of the drug. Accumulating evidence suggests an important role for synaptic transmission in the central nucleus of the amygdala (CeA) in mediating alcohol-related behaviors and neuroadaptive mechanisms

    更新日期:2020-03-26
  • Influenza Vaccine Effectiveness: New Insights and Challenges
    Genome Res. (IF 9.944) Pub Date : 2020-01-27
    Huong Q. McLean; Edward A. Belongia

    Methods for assessing influenza vaccine efficacy and effectiveness have evolved over six decades. Randomized trials remain the gold standard for licensure, but observational studies are needed for annual assessment of vaccine effectiveness (VE). The test-negative design (TND) has become the de facto standard for these field studies. Patients who seek medical care with acute respiratory illness are

    更新日期:2020-03-26
  • Swine Influenza A Viruses and the Tangled Relationship with Humans
    Genome Res. (IF 9.944) Pub Date : 2020-01-27
    Tavis K. Anderson; Jennifer Chang; Zebulun W. Arendsee; Divya Venkatesh; Carine K. Souza; J. Brian Kimble; Nicola S. Lewis; C. Todd Davis; Amy L. Vincent

    Influenza A viruses (IAVs) are the causative agents of one of the most important viral respiratory diseases in pigs and humans. Human and swine IAV are prone to interspecies transmission, leading to regular incursions from human to pig and vice versa. This bidirectional transmission of IAV has heavily influenced the evolutionary history of IAV in both species. Transmission of distinct human seasonal

    更新日期:2020-03-26
  • The Structure, Function, and Pathobiology of the Influenza A and B Virus Ion Channels
    Genome Res. (IF 9.944) Pub Date : 2020-01-27
    Robert A. Lamb

    Influenza A virus AM2 protein is an integral membrane protein that is an ion channel (also known as a viroporin). The channel has 24 extracellular residues, 19 residues that span the membrane once and acts as both the channel pore and also the membrane anchoring domain, and a 54-residue cytoplasmic tail. The M2 protein has four identical chains linked via two disulfide bonds that form a four-helix

    更新日期:2020-03-26
  • Normal Hematopoiesis Is a Balancing Act of Self-Renewal and Regeneration
    Genome Res. (IF 9.944) Pub Date : 2020-01-27
    Oakley C. Olson; Yoon-A Kang; Emmanuelle Passegué

    The hematopoietic system is highly organized to maintain its functional integrity and to meet lifelong organismal demands. Hematopoietic stem cells (HSCs) must balance self-renewal with differentiation and the regeneration of the blood system. It is a complex balancing act between these competing HSC functions. Although highly quiescent at steady state, HSCs become activated in response to inflammatory

    更新日期:2020-03-26
  • Influenza Reverse Genetics—Historical Perspective
    Genome Res. (IF 9.944) Pub Date : 2020-01-21
    Gabriele Neumann

    The generation of wild-type, mutant, and reassortant influenza viruses from viral cDNAs (reverse genetics) is now a basic molecular virology technique in many influenza virus laboratories. Here, I describe the original RNA polymerase I reverse genetics system and the modifications that have been developed in past years. Together, these technologies have made possible many advances in basic and applied

    更新日期:2020-03-26
  • Pathobiological Origins and Evolutionary History of Highly Pathogenic Avian Influenza Viruses
    Genome Res. (IF 9.944) Pub Date : 2020-01-21
    Dong-Hun Lee; Miria Ferreira Criado; David E. Swayne

    High-pathogenicity avian influenza (HPAI) viruses have arisen from low-pathogenicity avian influenza (LPAI) viruses via changes in the hemagglutinin proteolytic cleavage site, which include mutation of multiple nonbasic to basic amino acids, duplication of basic amino acids, or recombination with insertion of cellular or viral amino acids. Between 1959 and 2019, a total of 42 natural, independent H5

    更新日期:2020-03-26
  • The Epidemiology, Virology, and Pathogenicity of Human Infections with Avian Influenza Viruses
    Genome Res. (IF 9.944) Pub Date : 2020-01-21
    Dayan Wang; Wenfei Zhu; Lei Yang; Yuelong Shu

    Influenza is a global challenge, and future pandemics of influenza are inevitable. One of the lessons learned from past pandemics is that all pandemic influenza viruses characterized to date possess viral genes originating from avian influenza viruses (AIVs). During the past decades, a wide range of AIVs have overcome the species barrier and infected humans with different clinical manifestations ranging

    更新日期:2020-03-26
  • Opioid-Induced Molecular and Cellular Plasticity of Ventral Tegmental Area Dopamine Neurons
    Genome Res. (IF 9.944) Pub Date : 2020-01-21
    Marie A. Doyle; Michelle S. Mazei-Robison

    Opioid drugs are highly valued as potent analgesics; however, there are significant risks associated with long-term use because of their abuse liability. Opioids cause changes in ventral tegmental area (VTA) gene expression and cell activity that have been linked to addiction-related behaviors in rodent models. Here, we focus on VTA dopamine (DA) neurons and review the cellular, structural, and synaptic

    更新日期:2020-03-26
  • Interferon-Free Hepatitis C Virus Therapy
    Genome Res. (IF 9.944) Pub Date : 2020-01-21
    Jean-Michel Pawlotsky

    Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with ∼71 million chronically infected individuals worldwide. Treatment of patients with HCV-related liver disease has advanced considerably thanks to the development of new direct-acting antiviral drugs that are now administered as highly potent, safe, and well-tolerated combinations with a high barrier to resistance. International

    更新日期:2020-03-26
  • Influenza Vaccines Delivered in Early Childhood Could Turn Antigenic Sin into Antigenic Blessings
    Genome Res. (IF 9.944) Pub Date : 2020-01-21
    Michael Worobey; Stanley Plotkin; Scott E. Hensley

    Substantial evidence has accumulated that “original antigenic sin” is a central factor shaping immune responses against influenza viruses. Here, we argue that this propensity of initial influenza virus exposure to establish a lifelong immunological imprint presents a remarkable opportunity: Immunization of infants prior to their initial, natural viral exposure could circumvent narrow immunological

    更新日期:2020-03-26
  • Metabolic Role of PTEN in Insulin Signaling and Resistance
    Genome Res. (IF 9.944) Pub Date : 2020-01-21
    Yu Zhe Li; Antonio Di Cristofano; Minna Woo

    Phosphatase and tensin homolog (PTEN) is most prominently known for its function in tumorigenesis. However, a metabolic role of PTEN is emerging as a result of its altered expression in type 2 diabetes (T2D), which results in impaired insulin signaling and promotion of insulin resistance during the pathogenesis of T2D. PTEN functions in regulating insulin signaling across different organs have been

    更新日期:2020-03-26
  • Psychostimulant-Induced Adaptations in Nucleus Accumbens Glutamatergic Transmission
    Genome Res. (IF 9.944) Pub Date : 2020-01-21
    William J. Wright; Yan Dong

    Carrying different aspects of emotional and motivational signals, glutamatergic synaptic projections from multiple limbic and paralimbic brain regions converge to the nucleus accumbens (NAc), in which these arousing signals are processed and prioritized for behavioral output. In animal models of drug addiction, some key drug-induced alterations at NAc glutamatergic synapses underlie important cellular

    更新日期:2020-03-26
  • Original Antigenic Sin: How Original? How Sinful?
    Genome Res. (IF 9.944) Pub Date : 2020-01-21
    Jonathan W. Yewdell; Jefferson J.S. Santos

    We review the phenomenon of “original antigenic sin” (OAS) in antibody responses to influenza A virus (IAV) infection or vaccination. OAS refers to the preferential induction of antibodies with higher affinity to priming versus boosting immunogens. We emphasize its mechanistic basis and origins in the basic immunobiology of B-cell responses to myriad immunogens. We tabulate 23 studies in animals and

    更新日期:2020-03-26
  • A Brain on Cannabinoids: The Role of Dopamine Release in Reward Seeking and Addiction
    Genome Res. (IF 9.944) Pub Date : 2020-01-21
    Kate Z. Peters; Erik B. Oleson; Joseph F. Cheer

    Cannabis sativa, like all known drugs of abuse, leads to increased dopamine activation within the mesolimbic pathway. Consequent dopamine release within terminal regions of the striatum is a powerful mediator of reward and reinforcement and patterned dopamine release is critical for associative learning processes that are fundamentally involved in addiction. The endocannabinoid system modulates dopamine

    更新日期:2020-03-26
  • Human Susceptibility to Influenza Infection and Severe Disease
    Genome Res. (IF 9.944) Pub Date : 2020-01-21
    Robert C. Mettelman; Paul G. Thomas

    Influenza viruses are a persistent threat to global human health. Increased susceptibility to infection and the risk factors associated with progression to severe influenza-related disease are determined by a multitude of viral, host, and environmental conditions. Decades of epidemiologic research have broadly defined high-risk groups, while new genomic association studies have identified specific

    更新日期:2020-03-26
  • Growth Factors and Alcohol Use Disorder
    Genome Res. (IF 9.944) Pub Date : 2020-01-21
    Mirit Liran; Nofar Rahamim; Dorit Ron; Segev Barak

    Neurotrophic growth factors were originally characterized for their support in neuronal differentiation, outgrowth, and survival during development. However, it has been acknowledged that they also play a vital role in the adult brain. Abnormalities in growth factors have been implicated in a variety of neurological and psychiatric disorders, including alcohol use disorder (AUD). This work focuses

    更新日期:2020-03-26
  • Discovery of the PTEN Tumor Suppressor and Its Connection to the PI3K and AKT Oncogenes
    Genome Res. (IF 9.944) Pub Date : 2020-01-13
    Ramon Parsons

    PTEN (phosphatase and tensin homolog on chromosome 10) was discovered over 20 years ago in 1997 and linked to the phosphatidylinositol 3-kinase (PI3K) and AKT oncogenes the following year. The discovery of PTEN emerged from the linked concepts of oncogenes and tumor suppressor genes that cause and prevent cancer and the fields of tumor viruses and human cancer genetics from which these two concepts

    更新日期:2020-03-26
  • Medications Development for Treatment of Opioid Use Disorder
    Genome Res. (IF 9.944) Pub Date : 2020-01-13
    E. Andrew Townsend; S. Stevens Negus; Matthew L. Banks

    This review describes methods for preclinical evaluation of candidate medications to treat opioid use disorder (OUD). The review is founded on the propositions that (1) drug self-administration procedures provide the most direct method for assessment of medication effectiveness, (2) procedures that assess choice between opioid and nondrug reinforcers are especially useful, and (3) states of opioid

    更新日期:2020-03-26
  • Impact of Genetics on Mature Lymphoid Leukemias and Lymphomas
    Genome Res. (IF 9.944) Pub Date : 2020-01-13
    Nathanael G. Bailey; Kojo S.J. Elenitoba-Johnson

    Recurrent genetic aberrations have long been recognized in mature lymphoid leukemias and lymphomas. As conventional karyotypic and molecular cloning techniques evolved in the 1970s and 1980s, multiple cytogenetic aberrations were identified in lymphomas, often balanced translocations that juxtaposed oncogenes to the immunoglobulin (IG) or T-cell receptor (TR) loci, leading to dysregulation. However

    更新日期:2020-03-26
  • Posttranslational Regulation and Conformational Plasticity of PTEN
    Genome Res. (IF 9.944) Pub Date : 2020-01-13
    Larissa Kotelevets; Barbara Trifault; Eric Chastre; Mark G.H. Scott

    Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor that is frequently down-modulated in human cancer. PTEN inhibits the phosphatidylinositol 3-phosphate kinase (PI3K)/AKT pathway through its lipid phosphatase activity. Multiple PI3K/AKT-independent actions of PTEN, protein-phosphatase activities and functions within the nucleus have also been described. PTEN, therefore

    更新日期:2020-03-26
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