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  • United States  (7,197)
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  • American Association for the Advancement of Science (AAAS)  (9,247)
  • Nature Publishing Group (NPG)  (2,000)
  • University of California Press  (10)
  • Appalachian State University  (3)
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  • Bonn: Institute of Labor Economics (IZA)
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  • 1
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    Appalachian State University | Appalachian State University
    Publication Date: 2024-04-02
    Description: Published in 1977, Western North Carolina is a narrative history of the Southern Appalachian Mountains up to 1880. Ora Blackmun depicts the stories of native Cherokee and Sequoyah people and pioneers such as William Bartram, Daniel Boone, Bishops Spangenberg and Asbury, and Zeb Vance.
    Keywords: History ; United States ; State & Local ; South (al, Ar, Fl, Ga, Ky, La, Ms, Nc, Sc, Tn, Va, Wv) ; thema EDItEUR::N History and Archaeology::NH History::NHK History of the Americas
    Language: English
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  • 2
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    Appalachian State University | Appalachian State University
    Publication Date: 2024-04-02
    Description: Between the 1940s and 1970s, approxiately three million people left the Appalachian mountains in search of jobs in Midwest urban areas, such as Cincinnati, Chicago, and Detroit. Unfortunately, about a third of these people were forced into a life of long-term underclass dwellers. Struggling with questions of identity, rootlessness, and cultural negation, these people were given the name of “urban Appalachians.” Published in 1987, Too Few Tomorrows addresses some of the pressing questions regarding urban Appalachians and their story of migration to city life.
    Keywords: History ; United States ; State & Local ; South (al, Ar, Fl, Ga, Ky, La, Ms, Nc, Sc, Tn, Va, Wv) ; thema EDItEUR::N History and Archaeology::NH History::NHK History of the Americas
    Language: English
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  • 3
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    University of California Press | University of California Press
    Publication Date: 2023-02-02
    Description: For the first half of the twentieth century, no American industry boasted a more motley and prolific trade press than the movie business—a cutthroat landscape that set the stage for battle by ink. In 1930, Martin Quigley, publisher of Exhibitors Herald, conspired with Hollywood studios to eliminate all competing trade papers, yet this attempt and each one thereafter collapsed. Exploring the communities of exhibitors and creative workers that constituted key subscribers, Ink-Stained Hollywood tells the story of how a heterogeneous trade press triumphed by appealing to the foundational aspects of industry culture—taste, vanity, partisanship, and exclusivity. In captivating detail, Eric Hoyt chronicles the histories of well-known trade papers (Variety, Motion Picture Herald) alongside important yet forgotten publications (Film Spectator, Film Mercury, and Camera!), and challenges the canon of film periodicals, offering new interpretative frameworks for understanding print journalism’s relationship with the motion picture industry and its continued impact on creative industries today.
    Keywords: Social Science ; Media Studies ; History ; United States ; 20th Century ; Performing Arts ; Film ; History & Criticism ; bic Book Industry Communication::J Society & social sciences::JF Society & culture: general::JFD Media studies ; bic Book Industry Communication::H Humanities::HB History::HBJ Regional & national history::HBJK History of the Americas ; bic Book Industry Communication::A The arts::AP Film, TV & radio::APF Films, cinema::APFA Film theory & criticism
    Language: English
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  • 4
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    University of California Press
    Publication Date: 2024-03-28
    Description: While portrayals of immigrants and their descendants in France and throughout Europe often center on burning cars and radical Islam, Citizen Outsider: Children of North African Immigrants in France paints a different picture. Through fieldwork and interviews in Paris and its banlieues, Jean Beaman examines middle-class and upwardly mobile children of maghrébin, or North African immigrants. By showing how these individuals are denied cultural citizenship because of their North African origin, she puts to rest the notion of a French exceptionalism regarding cultural difference, race, and ethnicity and further centers race and ethnicity as crucial for understanding marginalization in French society.
    Keywords: islam ; race and ethnicity ; france ; north african ; second generation ; international migration ; cultural citizenship ; postcolonial ; racial project ; children of immigrants ; Banlieue ; French people ; Middle class ; Paris ; Social exclusion ; United States ; thema EDItEUR::J Society and Social Sciences ; thema EDItEUR::J Society and Social Sciences::JB Society and culture: general::JBF Social and ethical issues::JBFH Migration, immigration and emigration ; thema EDItEUR::5 Interest qualifiers::5P Relating to specific groups and cultures or social and cultural interests::5PB Relating to peoples: ethnic groups, indigenous peoples, cultures and other groupings of people::5PBC Relating to migrant groups / diaspora communities or peoples
    Language: English
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  • 5
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    Cornell University Press
    Publication Date: 2022-05-02
    Description: In Ruling Capital, Kevin P. Gallagher demonstrates how several emerging market and developing countries (EMDs) managed to reregulate cross-border financial flows in the wake of the global financial crisis, despite the political and economic difficulty of doing so at the national level. Gallagher also shows that some EMDs, particularly the BRICS coalition, were able to maintain or expand their sovereignty to regulate cross-border finance under global economic governance institutions. Gallagher combines econometric analysis with in-depth interviews with officials and interest groups in select emerging markets and policymakers at the International Monetary Fund, the World Trade Organization, and the G-20 to explain key characteristics of the global economy.
    Keywords: Economics ; finance ; monetary policy ; IMF ; WTO ; Brazil ; Capital (economics) ; Capital account ; Capital control ; Developed country ; Ecosystem Management Decision Support ; Exchange rate ; International Monetary Fund ; South Korea ; United States ; bic Book Industry Communication::K Economics, finance, business & management::KC Economics::KCP Political economy
    Language: English
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  • 6
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    University of California Press | University of California Press
    Publication Date: 2024-04-02
    Description: Los Angeles rose to significance in the first half of the twentieth century by way of its complex relationship to three rivers: the Los Angeles, the Owens, and the Colorado. The remarkable urban and suburban trajectory of southern California since then cannot be fully understood without reference to the ways in which each of these three river systems came to be connected to the future of the metropolitan region. This history of growth must be understood in full consideration of all three rivers and the challenges and opportunities they presented to those who would come to make Los Angeles a global power. Full of primary sources and original documents, Water and Los Angeles will be of interest to both students of Los Angeles and general readers interested in the origins of the city. “This is an invaluable new source book by two preeminent authorities on Los Angeles history.” -STEVEN P. ERIE, University of California, San Diego “Energized by a conviction of geography as destiny, this innovative docudrama of primary sources reveals the process whereby the Colorado River system propelled the urbanization of the American West. Water and Los Angeles constitutes a breakthrough fusion of environmental, engineering, urban, and political perspectives.” -KEVIN STARR, University of Southern California “This book offers an accessible, readable account of the importance of rivers to the development of modern Los Angeles.” -SARAH SCHRANK, Professor of History, California State University, Long Beach “Through a history of Los Angeles and the three rivers that helped to create it, this volume crosses several areas of scholarship to create an original and valuable contribution to research and teaching.” -NICOLAS G. ROSENTHAL, author of Reimagining Indian Country: Native American Migration and Identity in Twentieth-Century Los Angeles WILLIAM DEVERELL is Professor of History at the University of California and Director of the Huntington-USC Institute on California and the West. TOM SITTON is a curator emeritus of history from the Natural History Museum of Los Angeles County. Together, they are authors of California Progressive Revisited and Metropolis in the Making.
    Keywords: History ; United States ; General ; Nature ; General ; thema EDItEUR::N History and Archaeology::NH History::NHK History of the Americas ; thema EDItEUR::W Lifestyle, Hobbies and Leisure::WN Nature and the natural world: general interest
    Language: English
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  • 7
    Publication Date: 2022-04-29
    Description: The Dream Is Over tells the extraordinary story of the 1960 Master Plan for Higher Education in California, created by visionary University of California President Clark Kerr and his contemporaries. The Master Plan’s equality of opportunity policy brought college within reach of millions of American families for the first time and fashioned the world’s leading system of public research universities. The California idea became the leading model for higher education across the world and has had great influence in the rapid growth of universities in China and East Asia. Yet, remarkably, the political conditions supporting the California idea in California itself have evaporated. Universal access is faltering, public tuition is rising, the great research universities face new challenges, and educational participation in California, once the national leader, lags far behind. Can the social values embodied in Kerr’s vision be renewed?
    Keywords: equal opportunity ; clark kerr ; California ; China ; East Asia ; Higher education ; United States ; bic Book Industry Communication::J Society & social sciences::JN Education ; bic Book Industry Communication::J Society & social sciences::JN Education::JNA Philosophy & theory of education ; bic Book Industry Communication::J Society & social sciences::JN Education::JNB History of education
    Language: English
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  • 8
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    University of California Press
    Publication Date: 2024-03-29
    Description: How do the United States and France differ in laws and attitudes concerning discrimination at work? Franco-American scholar Marie Mercat-Bruns interviews prominent legal scholars to demonstrate how these two post-industrial democracies have adopted divergent strategies. Whereas employers in the United States and France rarely discriminate openly, deep systemic discrimination exists in both countries, each with a unique history of dealing with difference. Powerful and incisive, the book examines hot-button issues such as racial and religious bias, sexual harassment, gender discrimination, and equality for LGBT individuals, highlighting comparisons that will further discussions on social equality and fundamental human rights across borders.
    Keywords: employment ; european law ; french law ; discrimination ; american law ; law and legislation ; labor ; Anti-discrimination law ; Disability ; Disparate impact ; France ; United States ; thema EDItEUR::J Society and Social Sciences::JH Sociology and anthropology::JHB Sociology::JHBL Sociology: work and labour ; thema EDItEUR::L Law::LA Jurisprudence and general issues::LAM Comparative law ; thema EDItEUR::L Law::LA Jurisprudence and general issues::LAQ Law and society, sociology of law ; thema EDItEUR::L Law::LB International law
    Language: English
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  • 9
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    Cornell University Press
    Publication Date: 2024-03-29
    Description: Human rights advocates have long pressed for international institutions to prosecute crimes against humanity. With its global reach and mandate to investigate and prosecute some of the world's most severe crimes (genocide, war crimes, and crimes against humanity) the creation of the International Criminal Court in 2002 was hailed as a landmark event in the evolution of truly global society. Supporters argue that the ICC and other transnational tribunals will deter the commission of atrocities and contribute to global peace and stability, and they laud its independence and its potential to check the arbitrary use of power against the powerless. To better understand how international criminal courts function and determine their broader implications for global society, this book examines the factors that led to the creation and evolution of international criminal courts, the nature of the support for and opposition to such institutions, and how they function.
    Keywords: Political Science ; genocide ; war crimes ; crimes against humanity ; Cess ; Human rights ; International Criminal Court ; Rome Statute of the International Criminal Court ; United Nations ; United Nations Security Council ; United States ; thema EDItEUR::J Society and Social Sciences::JP Politics and government::JPS International relations::JPSN International institutions
    Language: English
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  • 10
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    University of California Press | University of California Press
    Publication Date: 2023-02-02
    Description: Chicago is home to one of the largest, most politically active Palestinian immigrant communities in the United States. For decades, secular nationalism held sway as the dominant political ideology, but since the 1990s, its structures have weakened and Islamic institutions have gained strength. Drawing on extensive fieldwork and interview data, Palestinian Chicago charts the origins of these changes and the multiple effects they have had on identity across religious, political, class, gender, and generational lines. The perspectives that emerge through this rich ethnography challenge prevailing understandings of secularity and religion, offering critical insight into current debates about immigration and national belonging.
    Keywords: Social Science ; Ethnic Studies ; General ; History ; Middle East ; Israel & Palestine ; History ; United States ; State & Local ; General ; bic Book Industry Communication::J Society & social sciences::JF Society & culture: general::JFS Social groups::JFSL Ethnic studies ; bic Book Industry Communication::H Humanities::HB History::HBJ Regional & national history::HBJF Asian history::HBJF1 Middle Eastern history ; bic Book Industry Communication::H Humanities::HB History::HBJ Regional & national history::HBJK History of the Americas
    Language: English
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  • 11
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    University of California Press
    Publication Date: 2024-03-29
    Description: Who are the dominant owners of US public debt? Is it widely held, or concentrated in the hands of a few? Does ownership of public debt give these bondholders power over our government? What do we make of the fact that foreign-owned debt has ballooned to nearly 50 percent today? Until now, we have not had any satisfactory answers to these questions. Public Debt, Inequality, and Power is the first comprehensive historical analysis of public debt ownership in the United States. It reveals that ownership of federal bonds has been increasingly concentrated in the hands of the 1 percent over the past three decades. Based on extensive and original research, Public Debt, Inequality, and Power will shock and enlighten.
    Keywords: economic history ; public debts ; government securities ; public finance ; National debt of the United States ; United States ; United States Treasury security ; thema EDItEUR::K Economics, Finance, Business and Management ; thema EDItEUR::K Economics, Finance, Business and Management::KC Economics ; thema EDItEUR::K Economics, Finance, Business and Management::KC Economics::KCZ Economic history
    Language: English
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  • 12
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    University of California Press
    Publication Date: 2024-04-02
    Description: China's relation to Taiwan has been in constant contention since the founding of the People's Republic of China in October 1949 and the creation of the defeated Kuomintang (KMT) exile regime on the island two months later. The islands autonomous sovereignty has continually been challenged, initially because of the KMT's insistence that it continue to represent not just Taiwan but all of China and later because Taiwan refused to cede sovereignty to the then-dominant power that had arisen on the other side of the Taiwan Strait. One thing that makes Taiwan so politically difficult and yet so intellectually fascinating is that it is not merely a security problem, but a ganglion of interrelated puzzles. The optimistic hope of the Ma Ying-jeou administration for a new era of peace and cooperation foundered on a landslide victory by the Democratic Progressive Party, which has made clear its intent to distance Taiwan from China's political embrace. The Taiwanese are now waiting with bated breath as the relationship tautens. Why did detente fail, and what chance does Taiwan have without it? Contributors to this volume focus on three aspects of the evolving quandary: nationalistic identity, social economy, and political strategy.
    Keywords: taishang ; taiwan strait ; 1992 consensus ; integration ; three links ; strategic ambiguity ; five no’s ; Beijing ; China ; Cross-Strait relations ; Kuomintang ; United States ; thema EDItEUR::N History and Archaeology::NH History ; thema EDItEUR::N History and Archaeology::NH History::NHF Asian history
    Language: English
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  • 13
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    Cornell University Press
    Publication Date: 2024-05-11
    Description: Most wars between countries end quickly and at relatively low cost. The few in which high-intensity fighting continues for years bring about a disproportionate amount of death and suffering. What separates these few unusually long and intense wars from the many conflicts that are far less destructive? In Logics of War, Alex Weisiger tests three explanations for a nation’s decision to go to war and continue fighting regardless of the costs. He combines sharp statistical analysis of interstate wars over the past two centuries with nine narrative case studies. He examines both well-known conflicts like World War II and the Persian Gulf War, as well as unfamiliar ones such as the 1864–1870 Paraguayan War (or the War of the Triple Alliance), which proportionally caused more deaths than any other war in modern history.
    Keywords: Political Science ; Adolf Hitler ; Argentina ; Germany ; Paraguay ; Unconditional surrender ; United States ; thema EDItEUR::J Society and Social Sciences::JW Warfare and defence::JWA Theory of warfare and military science
    Language: English
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  • 14
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    Appalachian State University | Appalachian State University
    Publication Date: 2024-04-02
    Description: This is a section from a larger work titled "Western North Carolina to 1880: Its Mountains and Its People." This part focuses on paintings by Elizabeth Cramer McClure that hang on the walls of a room in the original Historic Sherrill's Inn in Fairview, North Carolina. The inn, near Hickory Nut Gap, was a way-station for travelers during the 19th century and early 20th century. Present day, the inn was restored as a private home by Mr. and Mrs. G.K. McClure.
    Keywords: History ; United States ; State & Local ; South (al, Ar, Fl, Ga, Ky, La, Ms, Nc, Sc, Tn, Va, Wv) ; thema EDItEUR::N History and Archaeology::NH History::NHK History of the Americas
    Language: English
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  • 15
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    University of California Press
    Publication Date: 2024-03-29
    Description: We understand very little about the billions of dollars that flow throughout the world from migrants back to their home countries. In this rigorous and illuminating work, Matt Bakker, an economic sociologist, examines how these migrant remittances—the resources of some of the world’s least affluent people—have come to be seen in recent years as a fundamental contributor to development in the migrant‑sending states of the global south. This book analyzes how the connection between remittances and development was forged through the concrete political and intellectual practices of policy entrepreneurs within a variety of institutional settings, from national government agencies and international development organizations to nongovernmental policy foundations and think tanks.
    Keywords: international policy ; economic development ; sustainable development ; emigrant remittances ; migration ; Directo a México ; Financial institution ; Mexico ; Neoliberalism ; North America ; United States ; thema EDItEUR::K Economics, Finance, Business and Management ; thema EDItEUR::K Economics, Finance, Business and Management::KC Economics::KCL International economics ; thema EDItEUR::K Economics, Finance, Business and Management::KC Economics::KCM Development economics and emerging economies ; thema EDItEUR::K Economics, Finance, Business and Management::KC Economics::KCS Economic systems and structures
    Language: English
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  • 16
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    University of California Press
    Publication Date: 2024-03-23
    Description: Published on the occasion of the 2019 exhibition “Changing and Unchanging Things: Noguchi and Hasegawa in Postwar Japan,” The Saburo Hasegawa Reader encompasses a selection of writings by the Japanese artist, theorist, essayist, teacher, and curator Saburo Hasegawa (1908–1957), translated into English for the first time. Credited with introducing abstract art to Japan in the 1930s, Hasegawa also became influential as a lecturer on Japan and its aesthetic and philosophical traditions in New York and San Francisco before his premature death in 1957. A memorial volume, initiated by the Oakland Art Museum but left unpublished since the 1950s, as well as interviews from students at California College of Arts and Crafts, helps to establish Hasegawa as a thoughtful bridge between East and West and an engaging and thoughtful interpreter of classical and contemporary sources.
    Keywords: Saburo Hasegawa ; Isamu Noguchi ; Japan ; United States ; New York ; San Francisco ; abstract art ; transnationalism ; thema EDItEUR::A The Arts ; thema EDItEUR::N History and Archaeology::NH History::NHF Asian history
    Language: English
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  • 17
    Publication Date: 2016-01-20
    Description: Massive open online courses (MOOCs) are often characterized as remedies to educational disparities related to social class. Using data from 68 MOOCs offered by Harvard and MIT between 2012 and 2014, we found that course participants from the United States tended to live in more-affluent and better-educated neighborhoods than the average U.S. resident. Among those who did register for courses, students with greater socioeconomic resources were more likely to earn a certificate. Furthermore, these differences in MOOC access and completion were larger for adolescents and young adults, the traditional ages where people find on-ramps into science, technology, engineering, and mathematics (STEM) coursework and careers. Our findings raise concerns that MOOCs and similar approaches to online learning can exacerbate rather than reduce disparities in educational outcomes related to socioeconomic status.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hansen, John D -- Reich, Justin -- New York, N.Y. -- Science. 2015 Dec 4;350(6265):1245-8. doi: 10.1126/science.aab3782. Epub 2015 Dec 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard Graduate School of Education, Harvard University, Cambridge, MA 02138, USA. john_hansen@mail.harvard.edu. ; Office of Digital Learning, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26785488" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Career Choice ; Certification/*methods ; Education, Distance/*methods ; Engineering/education ; Humans ; Internet ; Learning ; Mathematics/education ; *Online Systems ; Science/education ; *Social Class ; Students ; Technology/education ; United States ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 18
    Publication Date: 2016-02-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Claiborne, Anne B -- English, Rebecca A -- Kahn, Jeffrey P -- 10002265/PHS HHS/ -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):668-70. doi: 10.1126/science.aaf3091. Epub 2016 Feb 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Medicine, U.S. National Academies of Sciences, Engineering, and Medicine, Washington, DC 20001, USA. aclaiborne@nas.edu. ; Institute of Medicine, U.S. National Academies of Sciences, Engineering, and Medicine, Washington, DC 20001, USA. ; Johns Hopkins Berman Institute of Bioethics, Johns Hopkins University, Baltimore, MD 21205, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26842937" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Ethics, Medical ; *Government Regulation ; Humans ; Mitochondrial Diseases/genetics/*prevention & control ; Mitochondrial Replacement Therapy/*ethics/*standards ; *Oocytes ; United States ; United States Food and Drug Administration ; *Zygote
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 19
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cohen, Jon -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):16-9. doi: 10.1126/science.351.6268.16.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721985" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomedical Research/*economics ; Communicable Disease Control/*economics ; Financial Management ; Humans ; National Institutes of Health (U.S.) ; United States ; Vaccines/*economics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 20
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shanahan, Jesse -- New York, N.Y. -- Science. 2016 Jan 22;351(6271):418. doi: 10.1126/science.351.6271.418.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jesse Shanahan is a master's student in astronomy at Wesleyan University in Middletown, Connecticut. Send your story to SciCareerEditor@aaas.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26798017" target="_blank"〉PubMed〈/a〉
    Keywords: Astronomy/*education ; *Career Mobility ; Disabled Persons/*psychology/statistics & numerical data ; Fear ; *Hostility ; Humans ; Male ; United States
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 21
    Publication Date: 2016-04-30
    Description: Noncoding variants play a central role in the genetics of complex traits, but we still lack a full understanding of the molecular pathways through which they act. We quantified the contribution of cis-acting genetic effects at all major stages of gene regulation from chromatin to proteins, in Yoruba lymphoblastoid cell lines (LCLs). About ~65% of expression quantitative trait loci (eQTLs) have primary effects on chromatin, whereas the remaining eQTLs are enriched in transcribed regions. Using a novel method, we also detected 2893 splicing QTLs, most of which have little or no effect on gene-level expression. These splicing QTLs are major contributors to complex traits, roughly on a par with variants that affect gene expression levels. Our study provides a comprehensive view of the mechanisms linking genetic variation to variation in human gene regulation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Yang I -- van de Geijn, Bryce -- Raj, Anil -- Knowles, David A -- Petti, Allegra A -- Golan, David -- Gilad, Yoav -- Pritchard, Jonathan K -- R01MH084703/MH/NIMH NIH HHS/ -- R01MH101825/MH/NIMH NIH HHS/ -- U01HG007036/HG/NHGRI NIH HHS/ -- U54CA149145/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):600-4. doi: 10.1126/science.aad9417. Epub 2016 Apr 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Stanford University, Stanford, CA, USA. ; Department of Human Genetics, University of Chicago, Chicago, IL, USA. ; Department of Computer Science, Stanford University, Stanford, CA, USA. Department of Radiology, Stanford University, Stanford, CA, USA. ; Genome Institute, Washington University in St. Louis, St. Louis, MO, USA. ; Department of Human Genetics, University of Chicago, Chicago, IL, USA. gilad@uchicago.edu pritch@stanford.edu. ; Department of Genetics, Stanford University, Stanford, CA, USA. Department of Biology, Stanford University, Stanford, CA, USA. Howard Hughes Medical Institute, Stanford University, Stanford, CA, USA. gilad@uchicago.edu pritch@stanford.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27126046" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Chromatin/metabolism ; *Gene Expression Regulation ; *Genetic Variation ; Genome-Wide Association Study ; Humans ; Immune System Diseases/*genetics ; Lymphocytes/immunology ; Phenotype ; Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; RNA Splicing/*genetics
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  • 22
    Publication Date: 2016-04-02
    Description: Global climate change is a major threat to biodiversity. Large-scale analyses have generally focused on the impacts of climate change on the geographic ranges of species and on phenology, the timing of ecological phenomena. We used long-term monitoring of the abundance of breeding birds across Europe and the United States to produce, for both regions, composite population indices for two groups of species: those for which climate suitability has been either improving or declining since 1980. The ratio of these composite indices, the climate impact indicator (CII), reflects the divergent fates of species favored or disadvantaged by climate change. The trend in CII is positive and similar in the two regions. On both continents, interspecific and spatial variation in population abundance trends are well predicted by climate suitability trends.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stephens, Philip A -- Mason, Lucy R -- Green, Rhys E -- Gregory, Richard D -- Sauer, John R -- Alison, Jamie -- Aunins, Ainars -- Brotons, Lluis -- Butchart, Stuart H M -- Campedelli, Tommaso -- Chodkiewicz, Tomasz -- Chylarecki, Przemyslaw -- Crowe, Olivia -- Elts, Jaanus -- Escandell, Virginia -- Foppen, Ruud P B -- Heldbjerg, Henning -- Herrando, Sergi -- Husby, Magne -- Jiguet, Frederic -- Lehikoinen, Aleksi -- Lindstrom, Ake -- Noble, David G -- Paquet, Jean-Yves -- Reif, Jiri -- Sattler, Thomas -- Szep, Tibor -- Teufelbauer, Norbert -- Trautmann, Sven -- van Strien, Arco J -- van Turnhout, Chris A M -- Vorisek, Petr -- Willis, Stephen G -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):84-7. doi: 10.1126/science.aac4858.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Conservation Ecology Group, School of Biological and Biomedical Sciences, Durham University, South Road, Durham DH1 3LE, UK. ; Royal Society for the Protection of Birds, Centre for Conservation Science, The Lodge, Sandy, Bedfordshire SG19 2DL, UK. ; Royal Society for the Protection of Birds, Centre for Conservation Science, The Lodge, Sandy, Bedfordshire SG19 2DL, UK. Conservation Science Group, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. ; United States Geological Survey, Patuxent Wildlife Research Center, 12100 Beech Forest Road, Laurel, MD 20708, USA. ; Institute of Integrative Biology, University of Liverpool, Crown Street, Liverpool L69 3BX, UK. ; Faculty of Biology, University of Latvia, Jelgavas iela 1, Riga, LV-1004, Latvia. ; Center for Mediterranean Forest Research, Centre Tecnologic Forestal de Catalunya, InForest JRU, Solsona 25280, Spain. REAF, Cerdanyola del Valles 08193, Catalonia, Spain. CSIC, Cerdanyola del Valles 08193, Catalonia, Spain. ; Conservation Science Group, Department of Zoology, University of Cambridge, Downing Street, Cambridge CB2 3EJ, UK. BirdLife International, The David Attenborough Building, Pembroke Street, Cambridge CB2 3QZ, UK. ; MITO2000 National Committee; c/o Dream Italia, Via Garibaldi 3, 52015, Pratovecchio-Stia, Arezzo, Italy. ; Ogolnopolskie Towarzystwo Ochrony Ptakow, Odrowaza 24,05-270 Marki, Poland. ; Museum and Institute of Zoology, Polish Academy of Sciences, Wilcza 64, 00-679 Warszawa, Poland. ; BirdWatch Ireland, Unit 20 Block D Bullford Business Campus, Kilcoole, County Wicklow, Ireland. ; Institute of Ecology and Earth Sciences, University of Tartu, Vanemuise Street 46, 51014 Tartu, Estonia. Estonian Ornithological Society, Veski 4, 51005 Tartu, Estonia. ; Sociedad Espanola de Ornitologia/BirdLife Melquiades Biencinto, 34, 28053 Madrid. Spain. ; European Bird Census Council, Post Office Box 6521, 6503 GA Nijmegen, Netherlands. Sovon Dutch Centre for Field Ornithology, Post Office Box 6521, 6503 GA Nijmegen, Netherlands. Department of Animal Ecology and Ecophysiology, Institute for Water and Wetland Research, Radboud University, Post Office Box 9010, 6500 GL Nijmegen, Netherlands. ; Dansk Ornitologisk Forening-BirdLife Denmark and University of Aarhus, Vesterbrogade 140, 1620 Kobenhavn V, Denmark. ; European Bird Census Council-Catalan Ornithological Institute, Natural History Museum of Barcelona, Placa Leonardo da Vinci 4-5, 08019 Barcelona, Catalonia, Spain. ; Section for Science, Nord University, 7600 Levanger, Norway. ; UMR7204 Sorbonne Universites-MNHN-CNRS-UPMC, CESCO, CRBPO, CP 135, 43 Rue Buffon, 75005 Paris, France. ; The Helsinki Lab of Ornithology, Finnish Museum of Natural History, Post Office Box 17, 00014 University of Helsinki, Finland. ; Biodiversity Unit, Department of Biology, Lund University, Ecology Building, S-223 62 Lund, Sweden. ; The British Trust for Ornithology, The Nunnery, Thetford, Norfolk IP24 2PU, UK. ; Natagora, Departement Etudes, Rue Nanon 98, B-5000 Namur, Belgium. ; Institute for Environmental Studies, Faculty of Science, Charles University in Prague, Czech Republic. Department of Zoology and Laboratory of Ornithology, Faculty of Science, Palacky University Olomouc, 17 Listopadu 50, 771 43 Olomouc, Czech Republic. ; Swiss Ornithological Institute, Seerose 1, 6204 Sempach, Switzerland. ; Institute of Environmental Sciences, University of Nyiregyhaza, Sostoi ut 31/b, 4400 Nyiregyhaza, Hungary. ; BirdLife Austria, Museumsplatz 1/10/8, A-1070 Vienna, Austria. ; Dachverband Deutscher Avifaunisten e.V. (Federation of German Avifaunists), An den Speichern 6, D-48157 Munster, Germany. ; Statistics Netherlands, Post Office Box 24500, 2490 HA The Hague, Netherlands. ; Sovon Dutch Centre for Field Ornithology, Post Office Box 6521, 6503 GA Nijmegen, Netherlands. Department of Animal Ecology and Ecophysiology, Institute for Water and Wetland Research, Radboud University, Post Office Box 9010, 6500 GL Nijmegen, Netherlands. ; Department of Zoology and Laboratory of Ornithology, Faculty of Science, Palacky University Olomouc, 17 Listopadu 50, 771 43 Olomouc, Czech Republic. Pan-European Common Bird Monitoring Scheme, Czech Society for Ornithology, Na Belidle 252/34, CZ-15000 Prague 5, Czech Republic.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034371" target="_blank"〉PubMed〈/a〉
    Keywords: Animal Migration ; Animals ; Biodiversity ; *Birds ; Breeding ; *Climate Change ; Ecological Parameter Monitoring ; Europe ; Population Dynamics ; United States
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Stone, Richard -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1138-40. doi: 10.1126/science.351.6278.1138.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26965605" target="_blank"〉PubMed〈/a〉
    Keywords: Computer Simulation ; *Explosions ; *Forensic Sciences ; Humans ; *Nuclear Weapons ; United States
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  • 24
    Publication Date: 2016-04-02
    Description: The dynamic properties of foldamers, synthetic molecules that mimic folded biomolecules, have mainly been explored in free solution. We report on the design, synthesis, and conformational behavior of photoresponsive foldamers bound in a phospholipid bilayer akin to a biological membrane phase. These molecules contain a chromophore, which can be switched between two configurations by different wavelengths of light, attached to a helical synthetic peptide that both promotes membrane insertion and communicates conformational change along its length. Light-induced structural changes in the chromophore are translated into global conformational changes, which are detected by monitoring the solid-state (19)F nuclear magnetic resonance signals of a remote fluorine-containing residue located 1 to 2 nanometers away. The behavior of the foldamers in the membrane phase is similar to that of analogous compounds in organic solvents.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉De Poli, Matteo -- Zawodny, Wojciech -- Quinonero, Ophelie -- Lorch, Mark -- Webb, Simon J -- Clayden, Jonathan -- New York, N.Y. -- Science. 2016 Apr 29;352(6285):575-80. doi: 10.1126/science.aad8352. Epub 2016 Mar 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Chemistry, University of Manchester, Manchester M13 9PL, UK. ; Department of Chemistry, University of Hull, Hull HU6 7RX, UK. ; School of Chemistry, University of Manchester, Manchester M13 9PL, UK. Manchester Institute of Biotechnology, University of Manchester, Manchester M1 7DN, UK. ; School of Chemistry, University of Bristol, Bristol BS8 1TS, UK. j.clayden@bristol.ac.uk.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27033546" target="_blank"〉PubMed〈/a〉
    Keywords: Light ; Lipid Bilayers/*chemistry ; Magnetic Resonance Spectroscopy ; Peptides/*chemistry/radiation effects ; Phosphatidylcholines/*chemistry/radiation effects ; Phospholipids/*chemistry/radiation effects ; Photochemical Processes ; Protein Conformation ; Protein Folding
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  • 25
    Publication Date: 2016-01-28
    Description: Hydroxymethylcytosine, well described in DNA, occurs also in RNA. Here, we show that hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet in Drosophila. We map the transcriptome-wide hydroxymethylation landscape, revealing hydroxymethylcytosine in the transcripts of many genes, notably in coding sequences, and identify consensus sites for hydroxymethylation. We found that RNA hydroxymethylation can favor mRNA translation. Tet and hydroxymethylated RNA are found to be most abundant in the Drosophila brain, and Tet-deficient fruitflies suffer impaired brain development, accompanied by decreased RNA hydroxymethylation. This study highlights the distribution, localization, and function of cytosine hydroxymethylation and identifies central roles for this modification in Drosophila.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Delatte, Benjamin -- Wang, Fei -- Ngoc, Long Vo -- Collignon, Evelyne -- Bonvin, Elise -- Deplus, Rachel -- Calonne, Emilie -- Hassabi, Bouchra -- Putmans, Pascale -- Awe, Stephan -- Wetzel, Collin -- Kreher, Judith -- Soin, Romuald -- Creppe, Catherine -- Limbach, Patrick A -- Gueydan, Cyril -- Kruys, Veronique -- Brehm, Alexander -- Minakhina, Svetlana -- Defrance, Matthieu -- Steward, Ruth -- Fuks, Francois -- R01 GM089992/GM/NIGMS NIH HHS/ -- T32 CA117846/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):282-5. doi: 10.1126/science.aac5253.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Universite Libre de Bruxelles (ULB), Brussels, Belgium. ; Waksman Institute, Department of Molecular Biology and Biochemistry, Cancer Institute of New Jersey, Rutgers University, Piscataway, NJ, USA. ; Laboratory of Molecular Biology of the Gene, Faculty of Sciences, Universite Libre de Bruxelles, Gosselies, Belgium. ; Institut fur Molekularbiologie und Tumorforschung, Philipps-Universitat Marburg, Marburg, Germany. ; Department of Chemistry, University of Cincinnati, Cincinnati, OH, USA. ; Laboratory of Cancer Epigenetics, Faculty of Medicine, ULB Cancer Research Center (U-CRC), Universite Libre de Bruxelles (ULB), Brussels, Belgium. ffuks@ulb.ac.be.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816380" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain/*abnormalities/metabolism ; Cell Line ; Cytosine/*analogs & derivatives/metabolism ; Dioxygenases/genetics/metabolism ; Drosophila melanogaster/genetics/*growth & development/metabolism ; Methylation ; RNA, Messenger/genetics/*metabolism ; Transcriptome
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  • 26
    Publication Date: 2016-01-28
    Description: Genes encoding human beta-type globin undergo a developmental switch from embryonic to fetal to adult-type expression. Mutations in the adult form cause inherited hemoglobinopathies or globin disorders, including sickle cell disease and thalassemia. Some experimental results have suggested that these diseases could be treated by induction of fetal-type hemoglobin (HbF). However, the mechanisms that repress HbF in adults remain unclear. We found that the LRF/ZBTB7A transcription factor occupies fetal gamma-globin genes and maintains the nucleosome density necessary for gamma-globin gene silencing in adults, and that LRF confers its repressive activity through a NuRD repressor complex independent of the fetal globin repressor BCL11A. Our study may provide additional opportunities for therapeutic targeting in the treatment of hemoglobinopathies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778394/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778394/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Masuda, Takeshi -- Wang, Xin -- Maeda, Manami -- Canver, Matthew C -- Sher, Falak -- Funnell, Alister P W -- Fisher, Chris -- Suciu, Maria -- Martyn, Gabriella E -- Norton, Laura J -- Zhu, Catherine -- Kurita, Ryo -- Nakamura, Yukio -- Xu, Jian -- Higgs, Douglas R -- Crossley, Merlin -- Bauer, Daniel E -- Orkin, Stuart H -- Kharchenko, Peter V -- Maeda, Takahiro -- R01 AI084905/AI/NIAID NIH HHS/ -- R01 HL032259/HL/NHLBI NIH HHS/ -- R56 DK105001/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):285-9. doi: 10.1126/science.aad3312.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA. ; Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. ; School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, Australia. ; Medical Research Council, Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK. ; Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki, Japan. ; Cell Engineering Division, RIKEN BioResource Center, Tsukuba, Ibaraki, Japan. Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan. ; Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Children's Research Institute, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. ; Division of Hematology/Oncology, Boston Children's Hospital, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Stem Cell Institute, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Howard Hughes Medical Institute, Boston, MA 02115, USA. ; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA. peter.kharchenko@post.harvard.edu tmaeda@partners.org. ; Division of Hematology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. peter.kharchenko@post.harvard.edu tmaeda@partners.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816381" target="_blank"〉PubMed〈/a〉
    Keywords: Anemia, Sickle Cell/genetics ; Animals ; Carrier Proteins/genetics/*metabolism ; Cell Line ; Chromatin/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Erythroblasts/cytology ; Erythropoiesis/genetics ; Fetal Hemoglobin/*genetics ; *Gene Silencing ; Humans ; Mice ; Mice, Knockout ; Nuclear Proteins/genetics/*metabolism ; Repressor Proteins/genetics/*metabolism ; Sequence Deletion ; Thalassemia/genetics ; Transcription Factors/genetics/*metabolism ; gamma-Globins/*genetics
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  • 27
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McNutt, Marcia -- New York, N.Y. -- Science. 2016 Feb 12;351(6274):641. doi: 10.1126/science.aaf4014. Epub 2016 Feb 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Marcia McNutt Editor-in-Chief Science Journals.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912832" target="_blank"〉PubMed〈/a〉
    Keywords: Corrosion ; Federal Government ; Humans ; Michigan ; *Public Health ; Safety/*economics ; Trust ; United States ; United States Environmental Protection Agency ; Water Supply/*economics
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  • 28
    Publication Date: 2016-02-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fahlgren, Noah -- Bart, Rebecca -- Herrera-Estrella, Luis -- Rellan-Alvarez, Ruben -- Chitwood, Daniel H -- Dinneny, Jose R -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):824. doi: 10.1126/science.351.6275.824-a. Epub 2016 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Donald Danforth Plant Science Center, St. Louis, MO 63132, USA. ; Nacional de Genomica para la Biodiversidad, Irapuato, 36821, Mexico. ; Donald Danforth Plant Science Center, St. Louis, MO 63132, USA. jdinneny@carnegiescience.edu dchitwood@danforthcenter.org. ; Carnegie Institution for Science, Stanford, CA 94305, USA. jdinneny@carnegiescience.edu dchitwood@danforthcenter.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912883" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Food, Genetically Modified/*adverse effects ; Genetic Engineering/*utilization ; Health ; Humans ; Plants, Genetically Modified/*adverse effects/genetics ; United States ; Zea mays/genetics
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  • 29
    Publication Date: 2016-01-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2016 Jan 8;351(6269):115. doi: 10.1126/science.351.6269.115.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26744390" target="_blank"〉PubMed〈/a〉
    Keywords: Female ; Financing, Organized/*statistics & numerical data ; Humans ; Research Personnel ; Research Support as Topic/*statistics & numerical data ; *Sexism ; United States ; *Women, Working
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mervis, Jeffrey -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):10-1. doi: 10.1126/science.351.6268.10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉With reporting from Science's news staff.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721980" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics ; Budgets ; Humans ; National Institutes of Health (U.S.)/*economics ; *Research Support as Topic ; United States ; United States National Aeronautics and Space Administration/economics
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Underwood, Emily -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):277-8. doi: 10.1126/science.352.6283.277.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081045" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Brain ; *Datasets as Topic ; European Union ; Humans ; International Cooperation ; Neurosciences/*trends ; United States
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  • 32
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Varmus, Harold -- New York, N.Y. -- Science. 2016 Apr 8;352(6282):123. doi: 10.1126/science.aaf7301.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harold Varmus is the Lewis Thomas University Professor at the Meyer Cancer Center, Weill Cornell Medicine, New York, NY; Senior Associate Member of the New York Genome Center, New York, NY; and former director of the U.S. National Cancer Institute. varmus@med.cornell.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27124426" target="_blank"〉PubMed〈/a〉
    Keywords: Federal Government ; Humans ; Information Dissemination ; *Leadership ; Medical Oncology/economics/*trends ; Neoplasms/diagnosis/drug therapy/prevention & control ; United States
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  • 33
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fu, He -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):486. doi: 10.1126/science.352.6284.486.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉He Fu is a Ph.D. candidate in the Department of Microbiology at the University of Illinois, Urbana-Champaign. For more on life and careers, visit sciencecareers.org. Send your story to SciCareerEditor@aaas.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102487" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Choice ; China ; *International Educational Exchange ; Microbiology/*education ; United States
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  • 34
    Publication Date: 2016-02-27
    Description: Ebola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated after proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Misasi, John -- Gilman, Morgan S A -- Kanekiyo, Masaru -- Gui, Miao -- Cagigi, Alberto -- Mulangu, Sabue -- Corti, Davide -- Ledgerwood, Julie E -- Lanzavecchia, Antonio -- Cunningham, James -- Muyembe-Tamfun, Jean Jacques -- Baxa, Ulrich -- Graham, Barney S -- Xiang, Ye -- Sullivan, Nancy J -- McLellan, Jason S -- 5K08AI079381/AI/NIAID NIH HHS/ -- HHSN261200800001E/PHS HHS/ -- T32GM008704/GM/NIGMS NIH HHS/ -- Intramural NIH HHS/ -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1343-6. doi: 10.1126/science.aad6117. Epub 2016 Feb 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. Division of Infectious Diseases, Boston Children's Hospital, Boston, MA 02215, USA. ; Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. ; Centre for Infectious Diseases Research, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084 China. ; Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. ; Institute for Research in Biomedicine, Universita della Svizzera Italiana, CH-6500 Bellinzona, Switzerland. Institute of Microbiology, ETH Zurich, CH-8093 Zurich, Switzerland. ; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. ; National Institute for Biomedical Research, National Laboratory of Public Health, Kinshasa B.P. 1197, Democratic Republic of the Congo. ; Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA. ; Centre for Infectious Diseases Research, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084 China. njsull@mail.nih.gov yxiang@mail.tsinghua.edu.cn. ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. njsull@mail.nih.gov yxiang@mail.tsinghua.edu.cn.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26917592" target="_blank"〉PubMed〈/a〉
    Keywords: Antibodies, Monoclonal/*chemistry/immunology ; Antibodies, Neutralizing/*chemistry/immunology ; Antibodies, Viral/*chemistry/immunology ; Cathepsins/chemistry ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Ebolavirus/*immunology ; Hemorrhagic Fever, Ebola/immunology/*prevention & control ; Humans ; Protein Conformation ; Proteolysis ; Viral Envelope Proteins/chemistry/*immunology
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  • 35
    Publication Date: 2016-02-26
    Description: With functions that range from cell envelope structure to signal transduction and transport, lipoproteins constitute 2 to 3% of bacterial genomes and play critical roles in bacterial physiology, pathogenicity, and antibiotic resistance. Lipoproteins are synthesized with a signal peptide securing them to the cytoplasmic membrane with the lipoprotein domain in the periplasm or outside the cell. Posttranslational processing requires a signal peptidase II (LspA) that removes the signal peptide. Here, we report the crystal structure of LspA from Pseudomonas aeruginosa complexed with the antimicrobial globomycin at 2.8 angstrom resolution. Mutagenesis studies identify LspA as an aspartyl peptidase. In an example of molecular mimicry, globomycin appears to inhibit by acting as a noncleavable peptide that sterically blocks the active site. This structure should inform rational antibiotic drug discovery.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vogeley, Lutz -- El Arnaout, Toufic -- Bailey, Jonathan -- Stansfeld, Phillip J -- Boland, Coilin -- Caffrey, Martin -- BB/I019855/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):876-80. doi: 10.1126/science.aad3747.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Medicine and School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland. ; Department of Biochemistry, University of Oxford, South Parks Road, Oxford, UK. ; School of Medicine and School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland. martin.caffrey@tcd.ie.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912896" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Anti-Bacterial Agents/*chemistry/pharmacology ; Aspartic Acid Endopeptidases/*antagonists & inhibitors/*chemistry/genetics ; Bacterial Proteins/*antagonists & inhibitors/*chemistry/genetics ; Catalytic Domain ; Conserved Sequence ; Crystallography, X-Ray ; Mutagenesis ; Peptides/*chemistry/pharmacology ; Protein Conformation ; Protein Processing, Post-Translational ; Pseudomonas aeruginosa/*enzymology ; Substrate Specificity
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  • 36
    Publication Date: 2016-01-09
    Description: Splicing of precursor messenger RNA is accomplished by a dynamic megacomplex known as the spliceosome. Assembly of a functional spliceosome requires a preassembled U4/U6.U5 tri-snRNP complex, which comprises the U5 small nuclear ribonucleoprotein (snRNP), the U4 and U6 small nuclear RNA (snRNA) duplex, and a number of protein factors. Here we report the three-dimensional structure of a Saccharomyces cerevisiae U4/U6.U5 tri-snRNP at an overall resolution of 3.8 angstroms by single-particle electron cryomicroscopy. The local resolution for the core regions of the tri-snRNP reaches 3.0 to 3.5 angstroms, allowing construction of a refined atomic model. Our structure contains U5 snRNA, the extensively base-paired U4/U6 snRNA, and 30 proteins including Prp8 and Snu114, which amount to 8495 amino acids and 263 nucleotides with a combined molecular mass of ~1 megadalton. The catalytic nucleotide U80 from U6 snRNA exists in an inactive conformation, stabilized by its base-pairing interactions with U4 snRNA and protected by Prp3. Pre-messenger RNA is bound in the tri-snRNP through base-pairing interactions with U6 snRNA and loop I of U5 snRNA. This structure, together with that of the spliceosome, reveals the molecular choreography of the snRNAs in the activation process of the spliceosomal ribozyme.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wan, Ruixue -- Yan, Chuangye -- Bai, Rui -- Wang, Lin -- Huang, Min -- Wong, Catherine C L -- Shi, Yigong -- New York, N.Y. -- Science. 2016 Jan 29;351(6272):466-75. doi: 10.1126/science.aad6466. Epub 2016 Jan 7.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Ministry of Education Key Laboratory of Protein Science, Tsinghua-Peking Joint Center for Life Sciences, Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China. ; National Center for Protein Science Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26743623" target="_blank"〉PubMed〈/a〉
    Keywords: Catalysis ; Cryoelectron Microscopy ; Nucleic Acid Conformation ; Protein Conformation ; RNA Precursors/chemistry ; *RNA Splicing ; RNA, Messenger/chemistry ; RNA, Small Nuclear/*chemistry/ultrastructure ; Ribonucleoprotein, U4-U6 Small Nuclear/*chemistry/ultrastructure ; Ribonucleoprotein, U5 Small Nuclear/*chemistry/ultrastructure ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/ultrastructure ; Spliceosomes/*chemistry/ultrastructure
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  • 37
    Publication Date: 2016-04-16
    Description: Drug resistance compromises control of malaria. Here, we show that resistance to a commonly used antimalarial medication, atovaquone, is apparently unable to spread. Atovaquone pressure selects parasites with mutations in cytochrome b, a respiratory protein with low but essential activity in the mammalian blood phase of the parasite life cycle. Resistance mutations rescue parasites from the drug but later prove lethal in the mosquito phase, where parasites require full respiration. Unable to respire efficiently, resistant parasites fail to complete mosquito development, arresting their life cycle. Because cytochrome b is encoded by the maternally inherited parasite mitochondrion, even outcrossing with wild-type strains cannot facilitate spread of resistance. Lack of transmission suggests that resistance will be unable to spread in the field, greatly enhancing the utility of atovaquone in malaria control.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goodman, Christopher D -- Siregar, Josephine E -- Mollard, Vanessa -- Vega-Rodriguez, Joel -- Syafruddin, Din -- Matsuoka, Hiroyuki -- Matsuzaki, Motomichi -- Toyama, Tomoko -- Sturm, Angelika -- Cozijnsen, Anton -- Jacobs-Lorena, Marcelo -- Kita, Kiyoshi -- Marzuki, Sangkot -- McFadden, Geoffrey I -- AI031478/AI/NIAID NIH HHS/ -- RR00052/RR/NCRR NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 15;352(6283):349-53. doi: 10.1126/science.aad9279.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of BioSciences, University of Melbourne, Melbourne, VIC 3010, Australia. gim@unimelb.edu.au deang@unimelb.edu.au. ; School of BioSciences, University of Melbourne, Melbourne, VIC 3010, Australia. Eijkman Institute for Molecular Biology, JI Diponegoro no. 69, Jakarta, 10430, Indonesia. Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ; School of BioSciences, University of Melbourne, Melbourne, VIC 3010, Australia. ; Johns Hopkins University Bloomberg School of Public Health, Department of Molecular Microbiology and Immunology, Malaria Research Institute, Baltimore, MD 21205, USA. ; Eijkman Institute for Molecular Biology, JI Diponegoro no. 69, Jakarta, 10430, Indonesia. Department of Parasitology, Faculty of Medicine, Hasanuddin University, Jalan Perintis Kemerdekaan Km10, Makassar 90245, Indonesia. ; Division of Medical Zoology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan. ; Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. ; Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. School of Tropical Medicine and Global Health, Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan. ; Eijkman Institute for Molecular Biology, JI Diponegoro no. 69, Jakarta, 10430, Indonesia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27081071" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anopheles/*parasitology ; Antimalarials/*pharmacology/therapeutic use ; Atovaquone/*pharmacology/therapeutic use ; Cell Line ; Cytochromes b/*genetics ; Drug Resistance/*genetics ; Genes, Mitochondrial/genetics ; Humans ; Life Cycle Stages/drug effects/genetics ; Malaria/drug therapy/*parasitology/transmission ; Male ; Mice ; Mitochondria/*genetics ; Mutation ; Plasmodium berghei/*drug effects/genetics/growth & development ; Selection, Genetic
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  • 38
    Publication Date: 2016-02-26
    Description: The U4/U6.U5 triple small nuclear ribonucleoprotein (tri-snRNP) is a major spliceosome building block. We obtained a three-dimensional structure of the 1.8-megadalton human tri-snRNP at a resolution of 7 angstroms using single-particle cryo-electron microscopy (cryo-EM). We fit all known high-resolution structures of tri-snRNP components into the EM density map and validated them by protein cross-linking. Our model reveals how the spatial organization of Brr2 RNA helicase prevents premature U4/U6 RNA unwinding in isolated human tri-snRNPs and how the ubiquitin C-terminal hydrolase-like protein Sad1 likely tethers the helicase Brr2 to its preactivation position. Comparison of our model with cryo-EM three-dimensional structures of the Saccharomyces cerevisiae tri-snRNP and Schizosaccharomyces pombe spliceosome indicates that Brr2 undergoes a marked conformational change during spliceosome activation, and that the scaffolding protein Prp8 is also rearranged to accommodate the spliceosome's catalytic RNA network.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Agafonov, Dmitry E -- Kastner, Berthold -- Dybkov, Olexandr -- Hofele, Romina V -- Liu, Wen-Ti -- Urlaub, Henning -- Luhrmann, Reinhard -- Stark, Holger -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1416-20. doi: 10.1126/science.aad2085. Epub 2016 Feb 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. Bioanalytics Group, Institute for Clinical Chemistry, University Medical Center Gottingen, D-37075 Gottingen, Germany. ; Department of 3D Electron Cryomicroscopy, Georg-August Universitat Gottingen, D-37077 Gottingen, Germany. Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. ; Bioanalytical Mass Spectrometry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. Bioanalytics Group, Institute for Clinical Chemistry, University Medical Center Gottingen, D-37075 Gottingen, Germany. reinhard.luehrmann@mpi-bpc.mpg.de hstark1@gwdg.de henning.urlaub@mpibpc.mpg.de. ; Department of Cellular Biochemistry, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. reinhard.luehrmann@mpi-bpc.mpg.de hstark1@gwdg.de henning.urlaub@mpibpc.mpg.de. ; Department of 3D Electron Cryomicroscopy, Georg-August Universitat Gottingen, D-37077 Gottingen, Germany. Department of Structural Dynamics, Max Planck Institute for Biophysical Chemistry, D-37077 Gottingen, Germany. reinhard.luehrmann@mpi-bpc.mpg.de hstark1@gwdg.de henning.urlaub@mpibpc.mpg.de.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26912367" target="_blank"〉PubMed〈/a〉
    Keywords: Cryoelectron Microscopy ; Crystallography, X-Ray ; DEAD-box RNA Helicases/chemistry ; Enzyme Activation ; HeLa Cells ; Humans ; Models, Molecular ; Peptide Elongation Factors/chemistry ; Protein Conformation ; RNA Helicases/chemistry ; RNA-Binding Proteins/chemistry ; Ribonucleoprotein, U4-U6 Small Nuclear/*chemistry ; Ribonucleoprotein, U5 Small Nuclear/*chemistry ; Ribonucleoproteins, Small Nuclear/chemistry ; Saccharomyces cerevisiae Proteins/chemistry ; Schizosaccharomyces/metabolism ; Ubiquitin Thiolesterase/chemistry
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  • 39
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-28
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Alberts, Bruce -- New York, N.Y. -- Science. 2016 Jan 15;351(6270):207. doi: 10.1126/science.aaf2001.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Bruce Alberts is the Chancellor's Leadership Chair in Biochemistry and Biophysics for Science and Education at the University of California, San Francisco, CA, and emeritus editor-in-chief of Science. Bruce.Alberts@ucsf.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816352" target="_blank"〉PubMed〈/a〉
    Keywords: *Career Choice ; *Faculty ; Humans ; Leadership ; Policy Making ; *Power (Psychology) ; Schools/*manpower/trends ; Teaching/*manpower/methods/trends ; United States
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  • 40
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pennisi, Elizabeth -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):394-5. doi: 10.1126/science.352.6284.394. Epub 2016 Apr 21.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102455" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Evolution, Molecular ; Foundations ; Genes ; Genetic Research/*economics ; Great Britain ; Humans ; *Research Support as Topic ; *Selection, Genetic ; Sweden ; United States
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  • 41
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Blum, Arlene -- New York, N.Y. -- Science. 2016 Mar 11;351(6278):1117. doi: 10.1126/science.aaf5468. Epub 2016 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Arlene Blum is founder and executive director of the Green Science Policy Institute, Berkeley, CA. arlene@GreenSciencePolicy.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26965592" target="_blank"〉PubMed〈/a〉
    Keywords: Consumer Product Safety/*legislation & jurisprudence ; Health ; Household Products/*toxicity ; Humans ; Manufactured Materials/*toxicity ; United States
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  • 42
    Publication Date: 2016-02-04
    Description: Bacterial adaptive immunity and genome engineering involving the CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) protein Cas9 begin with RNA-guided DNA unwinding to form an RNA-DNA hybrid and a displaced DNA strand inside the protein. The role of this R-loop structure in positioning each DNA strand for cleavage by the two Cas9 nuclease domains is unknown. We determine molecular structures of the catalytically active Streptococcus pyogenes Cas9 R-loop that show the displaced DNA strand located near the RuvC nuclease domain active site. These protein-DNA interactions, in turn, position the HNH nuclease domain adjacent to the target DNA strand cleavage site in a conformation essential for concerted DNA cutting. Cas9 bends the DNA helix by 30 degrees , providing the structural distortion needed for R-loop formation.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Fuguo -- Taylor, David W -- Chen, Janice S -- Kornfeld, Jack E -- Zhou, Kaihong -- Thompson, Aubri J -- Nogales, Eva -- Doudna, Jennifer A -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Feb 19;351(6275):867-71. doi: 10.1126/science.aad8282. Epub 2016 Jan 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA. ; Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. ; Department of Chemistry, University of California, Berkeley, CA 94720, USA. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA. Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. doudna@berkeley.edu enogales@lbl.gov. ; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. California Institute for Quantitative Biosciences, University of California, Berkeley, CA 94720, USA. Howard Hughes Medical Institute, University of California, Berkeley, CA 94720, USA. Department of Chemistry, University of California, Berkeley, CA 94720, USA. Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. doudna@berkeley.edu enogales@lbl.gov.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26841432" target="_blank"〉PubMed〈/a〉
    Keywords: *CRISPR-Cas Systems ; Catalytic Domain ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Crystallography, X-Ray ; DNA/*chemistry ; *DNA Cleavage ; Endonucleases/*chemistry/ultrastructure ; Genetic Engineering ; Genome ; Nucleic Acid Conformation ; Protein Conformation ; RNA/chemistry ; RNA, Guide ; Streptococcus pyogenes/*enzymology
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  • 43
    Publication Date: 2016-03-26
    Description: Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germline-targeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naive B cells bind germline-targeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. Using deep mutational scanning and multitarget optimization, we developed a germline-targeting immunogen (eOD-GT8) for diverse VRC01-class bnAbs. We then used the immunogen to isolate VRC01-class precursor naive B cells from HIV-uninfected donors. Frequencies of true VRC01-class precursors, their structures, and their eOD-GT8 affinities support this immunogen as a candidate human vaccine prime. These methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872700/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4872700/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jardine, Joseph G -- Kulp, Daniel W -- Havenar-Daughton, Colin -- Sarkar, Anita -- Briney, Bryan -- Sok, Devin -- Sesterhenn, Fabian -- Ereno-Orbea, June -- Kalyuzhniy, Oleksandr -- Deresa, Isaiah -- Hu, Xiaozhen -- Spencer, Skye -- Jones, Meaghan -- Georgeson, Erik -- Adachi, Yumiko -- Kubitz, Michael -- deCamp, Allan C -- Julien, Jean-Philippe -- Wilson, Ian A -- Burton, Dennis R -- Crotty, Shane -- Schief, William R -- P01 AI094419/AI/NIAID NIH HHS/ -- P01 AI110657/AI/NIAID NIH HHS/ -- P41GM103393/GM/NIGMS NIH HHS/ -- R01 AI084817/AI/NIAID NIH HHS/ -- UM1 AI100663/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2016 Mar 25;351(6280):1458-63. doi: 10.1126/science.aad9195.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Program in Molecular Structure and Function, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 0A4, Canada. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Vaccine and Infectious Disease Division, Statistical Center for HIV/AIDS Research and Prevention (SCHARP), Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Program in Molecular Structure and Function, Hospital for Sick Children Research Institute, Toronto, Ontario M5G 0A4, Canada. Departments of Biochemistry and Immunology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. ; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA. ; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. Division of Infectious Diseases, Department of Medicine, University of California San Diego School of Medicine, La Jolla, CA, USA. schief@scripps.edu shane@lji.org. ; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA. IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA. Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA. Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02129, USA. schief@scripps.edu shane@lji.org.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27013733" target="_blank"〉PubMed〈/a〉
    Keywords: AIDS Vaccines/*immunology ; Amino Acid Sequence ; Antibodies, Monoclonal/chemistry/*immunology/isolation & purification ; Antibodies, Neutralizing/chemistry/*immunology/isolation & purification ; Antibody Affinity ; B-Lymphocytes/immunology ; Cell Separation ; Combinatorial Chemistry Techniques ; Epitopes, B-Lymphocyte/chemistry/genetics/*immunology ; Germ Cells/*immunology ; HIV Antibodies/chemistry/*immunology/isolation & purification ; HIV-1/*immunology ; Humans ; Molecular Sequence Data ; Mutation ; Peptide Library ; Precursor Cells, B-Lymphoid/*immunology ; Protein Conformation
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2016 Jan 1;351(6268):14. doi: 10.1126/science.351.6268.14.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26721983" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Databases, Genetic/*economics ; Financial Support ; Human Genome Project/*economics ; Humans ; Models, Animal ; National Human Genome Research Institute (U.S.)/*economics ; United States
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Richmond, Geraldine -- New York, N.Y. -- Science. 2016 Jan 29;351(6272):427. doi: 10.1126/science.aaf2869. Epub 2016 Jan 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Geraldine Richmond is president of AAAS and Presidential Chair in Science and professor in the Department of Chemistry and Biochemistry at the University of Oregon, Eugene, OR. richmond@oregon.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26823402" target="_blank"〉PubMed〈/a〉
    Keywords: Africa ; Asia ; *Food Supply ; Humans ; *Internationality ; United States ; *Water Supply
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  • 46
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-04-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- New York, N.Y. -- Science. 2016 Apr 1;352(6281):20. doi: 10.1126/science.352.6281.20.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27034352" target="_blank"〉PubMed〈/a〉
    Keywords: Awards and Prizes ; Biomedical Research/*economics ; *Financing, Government ; National Institute of General Medical Sciences (U.S.) ; United States
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  • 47
    Publication Date: 2016-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kaiser, Jocelyn -- Couzin-Frankel, Jennifer -- New York, N.Y. -- Science. 2016 Jan 22;351(6271):325-6. doi: 10.1126/science.351.6271.325.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26797992" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*organization & administration ; Federal Government ; Humans ; Neoplasms/*therapy ; Policy ; United States
    Print ISSN: 0036-8075
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    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 48
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 2016-03-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roman, Joe -- Kraska, James -- New York, N.Y. -- Science. 2016 Mar 18;351(6279):1258-60. doi: 10.1126/science.aad4247.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gund Institute for Ecological Economics, University of Vermont, Burlington, VT 05405, USA. jroman@uvm.edu. ; Stockton Center for the Study of International Law, U.S. Naval War College, Newport, RI 02841, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26989232" target="_blank"〉PubMed〈/a〉
    Keywords: *Bays ; *Conservation of Natural Resources ; Cuba ; Diplomacy ; United States
    Print ISSN: 0036-8075
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  • 49
    Publication Date: 2016-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Check Hayden, Erika -- England -- Nature. 2016 Apr 28;532(7600):424-5. doi: 10.1038/532424a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27121817" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics/legislation & jurisprudence/*trends ; *Federal Government ; Financing, Government/economics/legislation & jurisprudence ; Humans ; Immunotherapy/economics ; Information Dissemination ; Leadership ; Neoplasms/economics/genetics/immunology/*therapy ; *Private Sector/economics ; *Public-Private Sector Partnerships/economics ; United States
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  • 50
    Publication Date: 2016-01-28
    Description: Adeno-associated virus (AAV) vectors are currently the leading candidates for virus-based gene therapies because of their broad tissue tropism, non-pathogenic nature and low immunogenicity. They have been successfully used in clinical trials to treat hereditary diseases such as haemophilia B (ref. 2), and have been approved for treatment of lipoprotein lipase deficiency in Europe. Considerable efforts have been made to engineer AAV variants with novel and biomedically valuable cell tropisms to allow efficacious systemic administration, yet basic aspects of AAV cellular entry are still poorly understood. In particular, the protein receptor(s) required for AAV entry after cell attachment remains unknown. Here we use an unbiased genetic screen to identify proteins essential for AAV serotype 2 (AAV2) infection in a haploid human cell line. The most significantly enriched gene of the screen encodes a previously uncharacterized type I transmembrane protein, KIAA0319L (denoted hereafter as AAV receptor (AAVR)). We characterize AAVR as a protein capable of rapid endocytosis from the plasma membrane and trafficking to the trans-Golgi network. We show that AAVR directly binds to AAV2 particles, and that anti-AAVR antibodies efficiently block AAV2 infection. Moreover, genetic ablation of AAVR renders a wide range of mammalian cell types highly resistant to AAV2 infection. Notably, AAVR serves as a critical host factor for all tested AAV serotypes. The importance of AAVR for in vivo gene delivery is further highlighted by the robust resistance of Aavr(-/-) (also known as Au040320(-/-) and Kiaa0319l(-/-)) mice to AAV infection. Collectively, our data indicate that AAVR is a universal receptor involved in AAV infection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pillay, S -- Meyer, N L -- Puschnik, A S -- Davulcu, O -- Diep, J -- Ishikawa, Y -- Jae, L T -- Wosen, J E -- Nagamine, C M -- Chapman, M S -- Carette, J E -- DP2 AI104557/AI/NIAID NIH HHS/ -- R01 GM066875/GM/NIGMS NIH HHS/ -- U19 AI109662/AI/NIAID NIH HHS/ -- England -- Nature. 2016 Feb 4;530(7588):108-12. doi: 10.1038/nature16465. Epub 2016 Jan 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Stanford, California 94305, USA. ; Department of Biochemistry and Molecular Biology, School of Medicine, Oregon Health &Science University, 3181 Sam Jackson Park Road, Portland, Oregon 97239-3098, USA. ; Shriners Hospital for Children, 3101 Sam Jackson Park Road, Portland, Oregon 97239, USA. ; Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Netherlands. ; Department of Comparative Medicine, Stanford University School of Medicine, 287 Campus Drive, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26814968" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antibodies/immunology/pharmacology ; Cell Line ; Dependovirus/classification/drug effects/*physiology ; Endocytosis/drug effects ; Female ; Gene Deletion ; Genetic Therapy/methods ; Host Specificity ; Humans ; Male ; Mice ; Parvoviridae Infections/*metabolism/*virology ; Receptors, Cell Surface/antagonists & inhibitors/deficiency/genetics/*metabolism ; Receptors, Virus/antagonists & inhibitors/deficiency/genetics/*metabolism ; *Viral Tropism/drug effects ; Virus Internalization/drug effects ; trans-Golgi Network/drug effects
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  • 51
    Publication Date: 2016-01-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cheng, Frank -- England -- Nature. 2016 Jan 14;529(7585):156. doi: 10.1038/529156e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Calgary, Alberta, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26762447" target="_blank"〉PubMed〈/a〉
    Keywords: Chemical Hazard Release/*prevention & control ; Equipment Safety ; *Materials Testing ; Oil and Gas Industry/*instrumentation/methods ; United States
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    Nature Publishing Group (NPG)
    Publication Date: 2016-01-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Jan 28;529(7587):437-8. doi: 10.1038/529437b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26819007" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; China ; Cities ; Congo ; Conservation of Natural Resources/*legislation & jurisprudence ; Ecosystem ; Great Britain ; *Parks, Recreational/legislation & jurisprudence ; Pleasure ; Uganda ; United States ; *Wilderness
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  • 53
    Publication Date: 2016-03-05
    Description: HKU1 is a human betacoronavirus that causes mild yet prevalent respiratory disease, and is related to the zoonotic SARS and MERS betacoronaviruses, which have high fatality rates and pandemic potential. Cell tropism and host range is determined in part by the coronavirus spike (S) protein, which binds cellular receptors and mediates membrane fusion. As the largest known class I fusion protein, its size and extensive glycosylation have hindered structural studies of the full ectodomain, thus preventing a molecular understanding of its function and limiting development of effective interventions. Here we present the 4.0 A resolution structure of the trimeric HKU1 S protein determined using single-particle cryo-electron microscopy. In the pre-fusion conformation, the receptor-binding subunits, S1, rest above the fusion-mediating subunits, S2, preventing their conformational rearrangement. Surprisingly, the S1 C-terminal domains are interdigitated and form extensive quaternary interactions that occlude surfaces known in other coronaviruses to bind protein receptors. These features, along with the location of the two protease sites known to be important for coronavirus entry, provide a structural basis to support a model of membrane fusion mediated by progressive S protein destabilization through receptor binding and proteolytic cleavage. These studies should also serve as a foundation for the structure-based design of betacoronavirus vaccine immunogens.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860016/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860016/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kirchdoerfer, Robert N -- Cottrell, Christopher A -- Wang, Nianshuang -- Pallesen, Jesper -- Yassine, Hadi M -- Turner, Hannah L -- Corbett, Kizzmekia S -- Graham, Barney S -- McLellan, Jason S -- Ward, Andrew B -- R56 AI118016/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2016 Mar 3;531(7592):118-21. doi: 10.1038/nature17200.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Integrative Structural and Computational Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA. ; Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755, USA. ; Viral Pathogenesis Laboratory, National Institute of Allergy and Infectious Diseases, Building 40, Room 2502, 40 Convent Drive, Bethesda, Maryland 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26935699" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Line ; Coronavirus/*chemistry/*ultrastructure ; Cryoelectron Microscopy ; Humans ; Membrane Fusion ; Models, Molecular ; Protein Binding ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Tertiary ; Protein Subunits/chemistry/metabolism ; Proteolysis ; Receptors, Virus/metabolism ; Spike Glycoprotein, Coronavirus/*chemistry/metabolism/*ultrastructure ; Viral Vaccines/chemistry/immunology ; Virus Internalization
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Feb 18;530(7590):253-4. doi: 10.1038/530253b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26887453" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*economics/*trends ; Child ; *Federal Government ; *Goals ; Humans ; Immunotherapy ; Information Dissemination ; Neoplasms/*therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; United States
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  • 55
    Publication Date: 2016-04-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nardone, Roland M -- MacLeod, Roderick A F -- Capes-Davis, Amanda -- England -- Nature. 2016 Apr 21;532(7599):313.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27127813" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line, Tumor ; DNA Contamination ; Databases, Factual ; *Disease Models, Animal ; Guidelines as Topic ; Heterografts/*standards ; Humans ; National Cancer Institute (U.S.) ; Neoplasms/*pathology ; Quality Control ; Reproducibility of Results ; United States ; Xenograft Model Antitumor Assays/*standards
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  • 56
    Publication Date: 2016-02-09
    Description: The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions. S also contains the principal antigenic determinants and is the target of neutralizing antibodies. Here we present the structure of a mouse coronavirus S trimer ectodomain determined at 4.0 A resolution by single particle cryo-electron microscopy. It reveals the metastable pre-fusion architecture of S and highlights key interactions stabilizing it. The structure shares a common core with paramyxovirus F proteins, implicating mechanistic similarities and an evolutionary connection between these viral fusion proteins. The accessibility of the highly conserved fusion peptide at the periphery of the trimer indicates potential vaccinology strategies to elicit broadly neutralizing antibodies against coronaviruses. Finally, comparison with crystal structures of human coronavirus S domains allows rationalization of the molecular basis for species specificity based on the use of spatially contiguous but distinct domains.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Walls, Alexandra C -- Tortorici, M Alejandra -- Bosch, Berend-Jan -- Frenz, Brandon -- Rottier, Peter J M -- DiMaio, Frank -- Rey, Felix A -- Veesler, David -- GM103310/GM/NIGMS NIH HHS/ -- T32GM008268/GM/NIGMS NIH HHS/ -- England -- Nature. 2016 Mar 3;531(7592):114-7. doi: 10.1038/nature16988. Epub 2016 Feb 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA. ; Institut Pasteur, Unite de Virologie Structurale, 75015 Paris, France. ; CNRS UMR 3569 Virologie, 75015 Paris, France. ; Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26855426" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Antibodies, Neutralizing/immunology ; Cell Line ; Coronavirus Infections/immunology/virology ; *Cryoelectron Microscopy ; Drosophila melanogaster ; Mice ; Models, Molecular ; Molecular Sequence Data ; Murine hepatitis virus/*chemistry/immunology/*ultrastructure ; Protein Multimerization ; Protein Structure, Tertiary ; Spike Glycoprotein, Coronavirus/*chemistry/immunology/*ultrastructure ; Viral Vaccines/chemistry/immunology ; Virus Internalization
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 May 11;533(7602):146. doi: 10.1038/533146a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27172009" target="_blank"〉PubMed〈/a〉
    Keywords: Device Approval/legislation & jurisprudence ; Drug Approval/legislation & jurisprudence ; Electronic Cigarettes/*adverse effects/utilization ; Humans ; Industry/legislation & jurisprudence ; Nicotine/administration & dosage/adverse effects/analysis ; Research Personnel ; Smoking/epidemiology/mortality/*prevention & control ; Tobacco Products/adverse effects/utilization ; United States ; United States Food and Drug Administration/*legislation & jurisprudence
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  • 58
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Roth, Alvin E -- England -- Nature. 2016 Apr 14;532(7598):178. doi: 10.1038/532178a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stanford University, California, USA. He shared the 2012 Nobel Memorial Prize in Economic Sciences with Lloyd Shapley.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075091" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Economics/*history ; Female ; *Game Theory ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Marketing/history ; Marriage/psychology ; Mathematics/*history ; Nobel Prize ; United States
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  • 59
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-14
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 May 11;533(7602):145. doi: 10.1038/533145a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27172008" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Anxiety ; Biomedical Research/*trends ; Breast Feeding/*adverse effects ; Clinical Trials as Topic/ethics/methods ; Female ; Humans ; Infant ; Infant, Newborn ; Milk, Human/*chemistry/*metabolism ; Mothers/psychology ; Pharmaceutical Preparations/*administration & dosage/*metabolism ; Risk Assessment ; Safety ; *Uncertainty ; United States ; United States Food and Drug Administration
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  • 60
    Publication Date: 2016-03-05
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lauer, Michael -- Valantine, Hannah -- Collins, Francis S -- England -- Nature. 2016 Mar 3;531(7592):35. doi: 10.1038/531035b.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Institutes of Health, Bethesda, Maryland, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26935689" target="_blank"〉PubMed〈/a〉
    Keywords: Congresses as Topic ; *National Institutes of Health (U.S.)/economics/organization & administration ; *Organizational Policy ; Sexual Harassment/*prevention & control/statistics & numerical data ; United States ; Workplace
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  • 61
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-07
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 May 5;533(7601):7. doi: 10.1038/533007a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27146996" target="_blank"〉PubMed〈/a〉
    Keywords: Americas ; *Bone and Bones/metabolism ; Burial/ethics/*legislation & jurisprudence ; Dissent and Disputes/*legislation & jurisprudence ; *Federal Government ; Genome, Human/genetics ; Genomics ; History, Ancient ; Human Migration/history ; Humans ; Indians, North American/classification/genetics/*legislation & jurisprudence ; Indians, South American/classification/genetics/legislation & jurisprudence ; *Phylogeny ; Research Personnel/*legislation & jurisprudence ; United States ; Washington
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  • 62
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2016 Feb 4;530(7588):17. doi: 10.1038/530017a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26842036" target="_blank"〉PubMed〈/a〉
    Keywords: Attention/drug effects ; Cognition Disorders/*complications/*drug therapy/psychology ; Depression/*complications/drug therapy/*psychology ; *Drug Discovery ; *Drug Industry/legislation & jurisprudence ; Humans ; Memory/drug effects ; Schizophrenia/drug therapy ; United States ; United States Food and Drug Administration/legislation & jurisprudence
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  • 63
    Publication Date: 2016-03-24
    Description: (beta-)Arrestins are important regulators of G-protein-coupled receptors (GPCRs). They bind to active, phosphorylated GPCRs and thereby shut off 'classical' signalling to G proteins, trigger internalization of GPCRs via interaction with the clathrin machinery and mediate signalling via 'non-classical' pathways. In addition to two visual arrestins that bind to rod and cone photoreceptors (termed arrestin1 and arrestin4), there are only two (non-visual) beta-arrestin proteins (beta-arrestin1 and beta-arrestin2, also termed arrestin2 and arrestin3), which regulate hundreds of different (non-visual) GPCRs. Binding of these proteins to GPCRs usually requires the active form of the receptors plus their phosphorylation by G-protein-coupled receptor kinases (GRKs). The binding of receptors or their carboxy terminus as well as certain truncations induce active conformations of (beta-)arrestins that have recently been solved by X-ray crystallography. Here we investigate both the interaction of beta-arrestin with GPCRs, and the beta-arrestin conformational changes in real time and in living human cells, using a series of fluorescence resonance energy transfer (FRET)-based beta-arrestin2 biosensors. We observe receptor-specific patterns of conformational changes in beta-arrestin2 that occur rapidly after the receptor-beta-arrestin2 interaction. After agonist removal, these changes persist for longer than the direct receptor interaction. Our data indicate a rapid, receptor-type-specific, two-step binding and activation process between GPCRs and beta-arrestins. They further indicate that beta-arrestins remain active after dissociation from receptors, allowing them to remain at the cell surface and presumably signal independently. Thus, GPCRs trigger a rapid, receptor-specific activation/deactivation cycle of beta-arrestins, which permits their active signalling.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nuber, Susanne -- Zabel, Ulrike -- Lorenz, Kristina -- Nuber, Andreas -- Milligan, Graeme -- Tobin, Andrew B -- Lohse, Martin J -- Hoffmann, Carsten -- 1 R01 DA038882/DA/NIDA NIH HHS/ -- BB/K019864/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2016 Mar 31;531(7596):661-4. doi: 10.1038/nature17198. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Pharmacology and Toxicology, University of Wurzburg, Versbacher Str. 9, 97078 Wurzburg, Germany. ; Rudolf Virchow Center, University of Wurzburg, Versbacher Str. 9, 97078 Wurzburg, Germany. ; Comprehensive Heart Failure Center, University of Wurzburg, Versbacher Str. 9, 97078 Wurzburg, Germany. ; Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK. ; MRC Toxicology Unit, University of Leicester, Hodgkin Building, Lancaster Road, Leicester LE1 9HN, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007855" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/chemistry/*metabolism ; Biosensing Techniques ; Cattle ; Cell Line ; Cell Membrane/metabolism ; Cell Survival ; Crystallography, X-Ray ; Fluorescence Resonance Energy Transfer ; Humans ; Kinetics ; Models, Molecular ; Protein Binding ; Protein Conformation ; Receptors, G-Protein-Coupled/chemistry/*metabolism ; Signal Transduction ; Substrate Specificity ; Time Factors
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  • 64
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Callaway, Ewen -- England -- Nature. 2016 Apr 14;532(7598):159-60. doi: 10.1038/nature.2016.19714.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075075" target="_blank"〉PubMed〈/a〉
    Keywords: Financing, Organized/economics/*legislation & jurisprudence/*organization & ; administration ; Great Britain ; Laboratories/*economics ; National Institutes of Health (U.S.)/legislation & jurisprudence ; Research Personnel/*economics ; United States
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  • 65
    Publication Date: 2016-03-31
    Description: Colonic epithelial cells are covered by thick inner and outer mucus layers. The inner mucus layer is free of commensal microbiota, which contributes to the maintenance of gut homeostasis. In the small intestine, molecules critical for prevention of bacterial invasion into epithelia such as Paneth-cell-derived anti-microbial peptides and regenerating islet-derived 3 (RegIII) family proteins have been identified. Although there are mucus layers providing physical barriers against the large number of microbiota present in the large intestine, the mechanisms that separate bacteria and colonic epithelia are not fully elucidated. Here we show that Ly6/PLAUR domain containing 8 (Lypd8) protein prevents flagellated microbiota invading the colonic epithelia in mice. Lypd8, selectively expressed in epithelial cells at the uppermost layer of the large intestinal gland, was secreted into the lumen and bound flagellated bacteria including Proteus mirabilis. In the absence of Lypd8, bacteria were present in the inner mucus layer and many flagellated bacteria invaded epithelia. Lypd8(-/-) mice were highly sensitive to intestinal inflammation induced by dextran sulfate sodium (DSS). Antibiotic elimination of Gram-negative flagellated bacteria restored the bacterial-free state of the inner mucus layer and ameliorated DSS-induced intestinal inflammation in Lypd8(-/-) mice. Lypd8 bound to flagella and suppressed motility of flagellated bacteria. Thus, Lypd8 mediates segregation of intestinal bacteria and epithelial cells in the colon to preserve intestinal homeostasis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Okumura, Ryu -- Kurakawa, Takashi -- Nakano, Takashi -- Kayama, Hisako -- Kinoshita, Makoto -- Motooka, Daisuke -- Gotoh, Kazuyoshi -- Kimura, Taishi -- Kamiyama, Naganori -- Kusu, Takashi -- Ueda, Yoshiyasu -- Wu, Hong -- Iijima, Hideki -- Barman, Soumik -- Osawa, Hideki -- Matsuno, Hiroshi -- Nishimura, Junichi -- Ohba, Yusuke -- Nakamura, Shota -- Iida, Tetsuya -- Yamamoto, Masahiro -- Umemoto, Eiji -- Sano, Koichi -- Takeda, Kiyoshi -- England -- Nature. 2016 Apr 7;532(7597):117-21. doi: 10.1038/nature17406. Epub 2016 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan. ; Core Research for Evolutional Science and Technology, Japan Agency for Medical Research and Development, Tokyo 100-0004, Japan. ; Department of Microbiology and Infection Control, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan. ; Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan. ; Department of Bacteriology, Okayama University Graduate School of Medicine, Okayama 700-8558, Japan. ; Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. ; Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan. ; Department of Cell Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan. ; Department of Bacterial Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan. ; Laboratory of Immunoparasitology, Research Institute for Microbial Diseases, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27027293" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Adhesion ; Caco-2 Cells ; Cell Line ; Colitis/chemically induced/drug therapy/genetics ; Colon/*microbiology ; Dextran Sulfate ; Epithelium/*microbiology ; Female ; *Flagella ; GPI-Linked Proteins/deficiency/genetics/*metabolism/secretion ; Gram-Negative Bacteria/drug effects/metabolism/pathogenicity/*physiology ; Homeostasis ; Humans ; Inflammation/chemically induced/drug therapy/genetics ; Intestinal Mucosa/cytology/metabolism/*microbiology/secretion ; Male ; Mice ; Proteus mirabilis/drug effects/metabolism/pathogenicity ; Symbiosis
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  • 66
    Publication Date: 2016-03-24
    Description: Arrestins are cytosolic proteins that regulate G-protein-coupled receptor (GPCR) desensitization, internalization, trafficking and signalling. Arrestin recruitment uncouples GPCRs from heterotrimeric G proteins, and targets the proteins for internalization via clathrin-coated pits. Arrestins also function as ligand-regulated scaffolds that recruit multiple non-G-protein effectors into GPCR-based 'signalsomes'. Although the dominant function(s) of arrestins vary between receptors, the mechanism whereby different GPCRs specify these divergent functions is unclear. Using a panel of intramolecular fluorescein arsenical hairpin (FlAsH) bioluminescence resonance energy transfer (BRET) reporters to monitor conformational changes in beta-arrestin2, here we show that GPCRs impose distinctive arrestin 'conformational signatures' that reflect the stability of the receptor-arrestin complex and role of beta-arrestin2 in activating or dampening downstream signalling events. The predictive value of these signatures extends to structurally distinct ligands activating the same GPCR, such that the innate properties of the ligand are reflected as changes in beta-arrestin2 conformation. Our findings demonstrate that information about ligand-receptor conformation is encoded within the population average beta-arrestin2 conformation, and provide insight into how different GPCRs can use a common effector for different purposes. This approach may have application in the characterization and development of functionally selective GPCR ligands and in identifying factors that dictate arrestin conformation and function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lee, Mi-Hye -- Appleton, Kathryn M -- Strungs, Erik G -- Kwon, Joshua Y -- Morinelli, Thomas A -- Peterson, Yuri K -- Laporte, Stephane A -- Luttrell, Louis M -- DK055524/DK/NIDDK NIH HHS/ -- GM095497/GM/NIGMS NIH HHS/ -- MOP-74603/Canadian Institutes of Health Research/Canada -- R01 DK055524/DK/NIDDK NIH HHS/ -- R01 GM095497/GM/NIGMS NIH HHS/ -- RR027777/RR/NCRR NIH HHS/ -- S10 RR027777/RR/NCRR NIH HHS/ -- England -- Nature. 2016 Mar 31;531(7596):665-8. doi: 10.1038/nature17154. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA. ; Department of Pharmaceutical &Biomedical Sciences, College of Pharmacy, Medical University of South Carolina, Charleston, South Carolina 29425, USA. ; Department of Medicine, McGill University Health Center Research Institute, McGill University, Quebec H4A 3J1, Canada. ; Pharmacology and Therapeutics, McGill University, Quebec H3G 1Y6, Canada. ; Anatomy and Cell Biology, McGill University, Quebec H3A 0C7, Canada. ; Research Service of the Ralph H. Johnson Veterans Affairs Medical Center, Charleston, South Carolina 29401, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007854" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/*chemistry/*metabolism ; Enzyme Activation ; HEK293 Cells ; Humans ; Ligands ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Protein Conformation ; Protein Transport ; Rats ; Receptors, G-Protein-Coupled/chemistry/*metabolism ; *Signal Transduction
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  • 67
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Apr 14;532(7598):147-8. doi: 10.1038/532147b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075057" target="_blank"〉PubMed〈/a〉
    Keywords: Financing, Organized/*legislation & jurisprudence/*organization & administration ; National Institute of Allergy and Infectious Diseases (U.S.) ; *Research Personnel/economics/psychology ; Surveys and Questionnaires ; United States
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  • 68
    Publication Date: 2016-04-30
    Description: As climate change unfolds, weather systems in the United States have been shifting in patterns that vary across regions and seasons. Climate science research typically assesses these changes by examining individual weather indicators, such as temperature or precipitation, in isolation, and averaging their values across the spatial surface. As a result, little is known about population exposure to changes in weather and how people experience and evaluate these changes considered together. Here we show that in the United States from 1974 to 2013, the weather conditions experienced by the vast majority of the population improved. Using previous research on how weather affects local population growth to develop an index of people's weather preferences, we find that 80% of Americans live in counties that are experiencing more pleasant weather than they did four decades ago. Virtually all Americans are now experiencing the much milder winters that they typically prefer, and these mild winters have not been offset by markedly more uncomfortable summers or other negative changes. Climate change models predict that this trend is temporary, however, because US summers will eventually warm more than winters. Under a scenario in which greenhouse gas emissions proceed at an unabated rate (Representative Concentration Pathway 8.5), we estimate that 88% of the US public will experience weather at the end of the century that is less preferable than weather in the recent past. Our results have implications for the public's understanding of the climate change problem, which is shaped in part by experiences with local weather. Whereas weather patterns in recent decades have served as a poor source of motivation for Americans to demand a policy response to climate change, public concern may rise once people's everyday experiences of climate change effects start to become less pleasant.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Egan, Patrick J -- Mullin, Megan -- England -- Nature. 2016 Apr 21;532(7599):357-60.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27127821" target="_blank"〉PubMed〈/a〉
    Keywords: Climate Change/*statistics & numerical data ; *Forecasting ; Global Warming/statistics & numerical data ; Greenhouse Effect/statistics & numerical data ; Humidity ; Motivation ; *Public Opinion ; Rain ; Seasons ; Temperature ; Time Factors ; United States ; *Weather
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  • 69
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Eisenstein, Michael -- England -- Nature. 2016 May 5;533(7601):S20-1. doi: 10.1038/533S20a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27144604" target="_blank"〉PubMed〈/a〉
    Keywords: Federal Government ; Financing, Government/economics/statistics & numerical data ; Great Britain ; Humans ; Inventions/economics ; Investments/*economics/statistics & numerical data ; National Institutes of Health (U.S.)/economics ; Patents as Topic ; Research/*economics/statistics & numerical data ; Research Support as Topic/economics/statistics & numerical data ; United States
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  • 70
    Publication Date: 2016-04-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lewis, Simon L -- England -- Nature. 2016 Apr 21;532(7599):283. doi: 10.1038/532283a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27111605" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Environmental Policy/*legislation & jurisprudence ; Global Warming/*legislation & jurisprudence/*prevention & control ; Human Activities/legislation & jurisprudence ; *International Cooperation ; Islands ; Paris ; *Politics ; *Temperature ; United States
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  • 71
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Mar 10;531(7593):140. doi: 10.1038/531140a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26961620" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CRISPR-Cas Systems/*genetics ; Directed Molecular Evolution/methods ; Dual Use Research/ethics/legislation & jurisprudence ; Embryo Research/ethics ; *Genetic Engineering/ethics/legislation & jurisprudence/trends ; Genome, Human/genetics ; Genomics/ethics/trends ; Germ-Line Mutation/ethics/genetics ; Government Regulation ; Humans ; Public Opinion ; Risk Assessment ; *Security Measures/legislation & jurisprudence ; United States
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  • 72
    Publication Date: 2016-02-11
    Description: The enteric nervous system (ENS) is the largest component of the autonomic nervous system, with neuron numbers surpassing those present in the spinal cord. The ENS has been called the 'second brain' given its autonomy, remarkable neurotransmitter diversity and complex cytoarchitecture. Defects in ENS development are responsible for many human disorders including Hirschsprung disease (HSCR). HSCR is caused by the developmental failure of ENS progenitors to migrate into the gastrointestinal tract, particularly the distal colon. Human ENS development remains poorly understood owing to the lack of an easily accessible model system. Here we demonstrate the efficient derivation and isolation of ENS progenitors from human pluripotent stem (PS) cells, and their further differentiation into functional enteric neurons. ENS precursors derived in vitro are capable of targeted migration in the developing chick embryo and extensive colonization of the adult mouse colon. The in vivo engraftment and migration of human PS-cell-derived ENS precursors rescue disease-related mortality in HSCR mice (Ednrb(s-l/s-l)), although the mechanism of action remains unclear. Finally, EDNRB-null mutant ENS precursors enable modelling of HSCR-related migration defects, and the identification of pepstatin A as a candidate therapeutic target. Our study establishes the first, to our knowledge, human PS-cell-based platform for the study of human ENS development, and presents cell- and drug-based strategies for the treatment of HSCR.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846424/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4846424/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Fattahi, Faranak -- Steinbeck, Julius A -- Kriks, Sonja -- Tchieu, Jason -- Zimmer, Bastian -- Kishinevsky, Sarah -- Zeltner, Nadja -- Mica, Yvonne -- El-Nachef, Wael -- Zhao, Huiyong -- de Stanchina, Elisa -- Gershon, Michael D -- Grikscheit, Tracy C -- Chen, Shuibing -- Studer, Lorenz -- DP2 DK098093-01/DK/NIDDK NIH HHS/ -- NS15547/NS/NINDS NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R01 NS015547/NS/NINDS NIH HHS/ -- England -- Nature. 2016 Mar 3;531(7592):105-9. doi: 10.1038/nature16951. Epub 2016 Feb 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Center for Stem Cell Biology, New York, New York 10065, USA. ; Developmental Biology Program, Sloan-Kettering Institute for Cancer Research, New York, New York 10065, USA. ; Weill Graduate School of Medical Sciences of Cornell University, New York, New York 10065, USA. ; Molecular Pharmacology Program, New York, New York 10065, USA. ; Department of Pathology and Cell Biology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA. ; Children's Hospital Los Angeles, Pediatric Surgery, Los Angeles, California 90027, USA. ; Department of Surgery, Weill Medical College of Cornell University, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26863197" target="_blank"〉PubMed〈/a〉
    Keywords: Aging ; Animals ; Cell Differentiation ; Cell Line ; *Cell Lineage ; Cell Movement ; Cell Separation ; *Cell- and Tissue-Based Therapy/methods ; Chick Embryo ; Colon/drug effects/pathology ; Disease Models, Animal ; Drug Discovery/*methods ; Enteric Nervous System/*pathology ; Female ; Gastrointestinal Tract/drug effects/pathology ; Hirschsprung Disease/*drug therapy/*pathology/therapy ; Humans ; Male ; Mice ; Neurons/drug effects/*pathology ; Pepstatins/metabolism ; Pluripotent Stem Cells/pathology ; Receptor, Endothelin B/metabolism ; Signal Transduction
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  • 73
    Publication Date: 2016-04-14
    Description: Circadian clocks are fundamental to the biology of most eukaryotes, coordinating behaviour and physiology to resonate with the environmental cycle of day and night through complex networks of clock-controlled genes. A fundamental knowledge gap exists, however, between circadian gene expression cycles and the biochemical mechanisms that ultimately facilitate circadian regulation of cell biology. Here we report circadian rhythms in the intracellular concentration of magnesium ions, [Mg(2+)]i, which act as a cell-autonomous timekeeping component to determine key clock properties both in a human cell line and in a unicellular alga that diverged from each other more than 1 billion years ago. Given the essential role of Mg(2+) as a cofactor for ATP, a functional consequence of [Mg(2+)]i oscillations is dynamic regulation of cellular energy expenditure over the daily cycle. Mechanistically, we find that these rhythms provide bilateral feedback linking rhythmic metabolism to clock-controlled gene expression. The global regulation of nucleotide triphosphate turnover by intracellular Mg(2+) availability has potential to impact upon many of the cell's more than 600 MgATP-dependent enzymes and every cellular system where MgNTP hydrolysis becomes rate limiting. Indeed, we find that circadian control of translation by mTOR is regulated through [Mg(2+)]i oscillations. It will now be important to identify which additional biological processes are subject to this form of regulation in tissues of multicellular organisms such as plants and humans, in the context of health and disease.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Feeney, Kevin A -- Hansen, Louise L -- Putker, Marrit -- Olivares-Yanez, Consuelo -- Day, Jason -- Eades, Lorna J -- Larrondo, Luis F -- Hoyle, Nathaniel P -- O'Neill, John S -- van Ooijen, Gerben -- 093734/Z/10/Z/Wellcome Trust/United Kingdom -- MC_UP_1201/4/Medical Research Council/United Kingdom -- England -- Nature. 2016 Apr 21;532(7599):375-9. doi: 10.1038/nature17407. Epub 2016 Apr 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉MRC Laboratory for Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK. ; School of Biological Sciences, University of Edinburgh, Max Born Crescent, Edinburgh EH9 3BF, UK. ; Millennium Nucleus for Fungal Integrative and Synthetic Biology, Departamento de Genetica Molecular y Microbiologia, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Casilla 114-D, Santiago, Chile. ; Department of Earth Sciences, University of Cambridge, Downing Street, Cambridge CB2 3EQ, UK. ; School of Chemistry, University of Edinburgh, David Brewster Road, Edinburgh EH9 3FJ, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27074515" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Cell Line ; Chlorophyta/cytology/metabolism ; Circadian Clocks/genetics/*physiology ; Circadian Rhythm/genetics/*physiology ; *Energy Metabolism ; Feedback, Physiological ; Gene Expression Regulation ; Humans ; Intracellular Space/metabolism ; Magnesium/*metabolism ; Male ; Mice ; TOR Serine-Threonine Kinases/metabolism ; Time Factors
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  • 74
    Publication Date: 2016-04-15
    Description: Accurate modelling and prediction of the local to continental-scale hydroclimate response to global warming is essential given the strong impact of hydroclimate on ecosystem functioning, crop yields, water resources, and economic security. However, uncertainty in hydroclimate projections remains large, in part due to the short length of instrumental measurements available with which to assess climate models. Here we present a spatial reconstruction of hydroclimate variability over the past twelve centuries across the Northern Hemisphere derived from a network of 196 at least millennium-long proxy records. We use this reconstruction to place recent hydrological changes and future precipitation scenarios in a long-term context of spatially resolved and temporally persistent hydroclimate patterns. We find a larger percentage of land area with relatively wetter conditions in the ninth to eleventh and the twentieth centuries, whereas drier conditions are more widespread between the twelfth and nineteenth centuries. Our reconstruction reveals that prominent seesaw patterns of alternating moisture regimes observed in instrumental data across the Mediterranean, western USA, and China have operated consistently over the past twelve centuries. Using an updated compilation of 128 temperature proxy records, we assess the relationship between the reconstructed centennial-scale Northern Hemisphere hydroclimate and temperature variability. Even though dry and wet conditions occurred over extensive areas under both warm and cold climate regimes, a statistically significant co-variability of hydroclimate and temperature is evident for particular regions. We compare the reconstructed hydroclimate anomalies with coupled atmosphere-ocean general circulation model simulations and find reasonable agreement during pre-industrial times. However, the intensification of the twentieth-century-mean hydroclimate anomalies in the simulations, as compared to previous centuries, is not supported by our new multi-proxy reconstruction. This finding suggests that much work remains before we can model hydroclimate variability accurately, and highlights the importance of using palaeoclimate data to place recent and predicted hydroclimate changes in a millennium-long context.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ljungqvist, Fredrik Charpentier -- Krusic, Paul J -- Sundqvist, Hanna S -- Zorita, Eduardo -- Brattstrom, Gudrun -- Frank, David -- England -- Nature. 2016 Apr 7;532(7597):94-8. doi: 10.1038/nature17418.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of History, Stockholm University, SE-10691 Stockholm, Sweden. ; Centre for Medieval Studies, Stockholm University, SE-10691 Stockholm, Sweden. ; Bolin Centre for Climate Research, Stockholm University, SE-10691 Stockholm, Sweden. ; Navarino Environmental Observatory, GR-24001 Messinia, Greece. ; Department of Physical Geography, Stockholm University, SE-10691 Stockholm, Sweden. ; Helmholtz-Zentrum Geesthacht, Institute for Coastal Research, DE-21502 Geesthacht, Germany. ; Department of Mathematics, Stockholm University, SE-10691 Stockholm, Sweden. ; Swiss Federal Research Institute WSL, CH-8903 Birmensdorf, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078569" target="_blank"〉PubMed〈/a〉
    Keywords: Atmosphere ; China ; *Climate ; Climate Change/*statistics & numerical data ; Ecosystem ; Geographic Mapping ; Geologic Sediments/chemistry ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Medieval ; Hydrology ; Ice/analysis ; Mediterranean Region ; Models, Theoretical ; *Rain ; Soil/chemistry ; Spatio-Temporal Analysis ; Temperature ; Trees/anatomy & histology/growth & development ; Uncertainty ; United States
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  • 75
    Publication Date: 2016-01-08
    Description: Influenza pandemics occur unpredictably when zoonotic influenza viruses with novel antigenicity acquire the ability to transmit amongst humans. Host range breaches are limited by incompatibilities between avian virus components and the human host. Barriers include receptor preference, virion stability and poor activity of the avian virus RNA-dependent RNA polymerase in human cells. Mutants of the heterotrimeric viral polymerase components, particularly PB2 protein, are selected during mammalian adaptation, but their mode of action is unknown. We show that a species-specific difference in host protein ANP32A accounts for the suboptimal function of avian virus polymerase in mammalian cells. Avian ANP32A possesses an additional 33 amino acids between the leucine-rich repeats and carboxy-terminal low-complexity acidic region domains. In mammalian cells, avian ANP32A rescued the suboptimal function of avian virus polymerase to levels similar to mammalian-adapted polymerase. Deletion of the avian-specific sequence from chicken ANP32A abrogated this activity, whereas its insertion into human ANP32A, or closely related ANP32B, supported avian virus polymerase function. Substitutions, such as PB2(E627K), were rapidly selected upon infection of humans with avian H5N1 or H7N9 influenza viruses, adapting the viral polymerase for the shorter mammalian ANP32A. Thus ANP32A represents an essential host partner co-opted to support influenza virus replication and is a candidate host target for novel antivirals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710677/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710677/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Long, Jason S -- Giotis, Efstathios S -- Moncorge, Olivier -- Frise, Rebecca -- Mistry, Bhakti -- James, Joe -- Morisson, Mireille -- Iqbal, Munir -- Vignal, Alain -- Skinner, Michael A -- Barclay, Wendy S -- 087039/Z/08/Z/Wellcome Trust/United Kingdom -- BB/K002465/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBS/E/I/00001708/Biotechnology and Biological Sciences Research Council/United Kingdom -- G0600006/Medical Research Council/United Kingdom -- England -- Nature. 2016 Jan 7;529(7584):101-4. doi: 10.1038/nature16474.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Section of Virology, Department of Medicine, Imperial College London, St Mary's Campus, London W2 1PG, UK. ; Centre d'etudes d'agents Pathogenes et Biotechnologies pour la Sante (CPBS), FRE 3689, CNRS-UM, 34293 Montpellier, France. ; Avian Viral Diseases Programme, The Pirbright Institute, Ash Road, Pirbright, Woking GU24 0NF, UK. ; UMR INRA/Genetique Physiologie et Systemes d'Elevage, INRA, 31326 Castanet-Tolosan, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26738596" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Sequence ; Animals ; Avian Proteins/*chemistry/deficiency/*metabolism ; Cell Line ; Chickens/virology ; Cricetinae ; Cricetulus ; Dogs ; Evolution, Molecular ; Gene Expression Regulation, Viral ; Gene Knockdown Techniques ; *Host Specificity ; Humans ; Influenza A Virus, H5N1 Subtype/enzymology/genetics/physiology ; Influenza A Virus, H7N9 Subtype/enzymology/genetics/physiology ; Influenza A virus/*enzymology/genetics/physiology ; Intracellular Signaling Peptides and Proteins/*chemistry/deficiency/*metabolism ; RNA Replicase/genetics/*metabolism ; Species Specificity ; Transcription, Genetic ; Viral Proteins/genetics/*metabolism ; Virus Replication
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  • 76
    Publication Date: 2016-01-21
    Description: Cellular immunity against viral infection and tumour cells depends on antigen presentation by major histocompatibility complex class I (MHC I) molecules. Intracellular antigenic peptides are transported into the endoplasmic reticulum by the transporter associated with antigen processing (TAP) and then loaded onto the nascent MHC I molecules, which are exported to the cell surface and present peptides to the immune system. Cytotoxic T lymphocytes recognize non-self peptides and program the infected or malignant cells for apoptosis. Defects in TAP account for immunodeficiency and tumour development. To escape immune surveillance, some viruses have evolved strategies either to downregulate TAP expression or directly inhibit TAP activity. So far, neither the architecture of TAP nor the mechanism of viral inhibition has been elucidated at the structural level. Here we describe the cryo-electron microscopy structure of human TAP in complex with its inhibitor ICP47, a small protein produced by the herpes simplex virus I. Here we show that the 12 transmembrane helices and 2 cytosolic nucleotide-binding domains of the transporter adopt an inward-facing conformation with the two nucleotide-binding domains separated. The viral inhibitor ICP47 forms a long helical hairpin, which plugs the translocation pathway of TAP from the cytoplasmic side. Association of ICP47 precludes substrate binding and prevents nucleotide-binding domain closure necessary for ATP hydrolysis. This work illustrates a striking example of immune evasion by persistent viruses. By blocking viral antigens from entering the endoplasmic reticulum, herpes simplex virus is hidden from cytotoxic T lymphocytes, which may contribute to establishing a lifelong infection in the host.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Oldham, Michael L -- Hite, Richard K -- Steffen, Alanna M -- Damko, Ermelinda -- Li, Zongli -- Walz, Thomas -- Chen, Jue -- Howard Hughes Medical Institute/ -- England -- Nature. 2016 Jan 28;529(7587):537-40. doi: 10.1038/nature16506. Epub 2016 Jan 20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Rockefeller University, 1230 York Avenue, New York, New York 10065, USA. ; Howard Hughes Medical Institute, 4000 Jones Bridge Road, Chevy Chase, Maryland 20815, USA. ; Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26789246" target="_blank"〉PubMed〈/a〉
    Keywords: ATP-Binding Cassette Transporters/antagonists & ; inhibitors/chemistry/*metabolism/*ultrastructure ; Amino Acid Sequence ; Antigens, Viral/immunology/metabolism ; *Cryoelectron Microscopy ; Endoplasmic Reticulum/metabolism ; Herpesvirus 1, Human/chemistry/*immunology/metabolism/ultrastructure ; Immediate-Early Proteins/chemistry/*metabolism/*ultrastructure ; *Immune Evasion ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Conformation
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  • 77
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winston, Patrick Henry -- England -- Nature. 2016 Feb 18;530(7590):282. doi: 10.1038/530282a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Massachusetts Institute of Technology, Cambridge, Massachusetts, USA. He was a graduate student of Marvin Minsky's in the 1960s, and thereafter an admiring friend and colleague.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26887486" target="_blank"〉PubMed〈/a〉
    Keywords: Artificial Intelligence/*history ; Child ; History, 20th Century ; History, 21st Century ; Humans ; Microscopy, Confocal/history ; Neural Networks (Computer) ; Robotics/history ; Software/history ; United States
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  • 78
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Witze, Alexandra -- England -- Nature. 2016 Apr 7;532(7597):17. doi: 10.1038/532017a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078544" target="_blank"〉PubMed〈/a〉
    Keywords: Aircraft ; Arctic Regions ; Climate Change/statistics & numerical data ; Ecosystem ; Environmental Monitoring/*instrumentation/*methods ; Geographic Mapping ; Ice Cover ; Satellite Communications ; *Snow ; United States ; United States National Aeronautics and Space Administration ; Water Supply/*statistics & numerical data
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  • 79
    Publication Date: 2016-01-26
    Description: Intracellular aggregation of the human amyloid protein alpha-synuclein is causally linked to Parkinson's disease. While the isolated protein is intrinsically disordered, its native structure in mammalian cells is not known. Here we use nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy to derive atomic-resolution insights into the structure and dynamics of alpha-synuclein in different mammalian cell types. We show that the disordered nature of monomeric alpha-synuclein is stably preserved in non-neuronal and neuronal cells. Under physiological cell conditions, alpha-synuclein is amino-terminally acetylated and adopts conformations that are more compact than when in buffer, with residues of the aggregation-prone non-amyloid-beta component (NAC) region shielded from exposure to the cytoplasm, which presumably counteracts spontaneous aggregation. These results establish that different types of crowded intracellular environments do not inherently promote alpha-synuclein oligomerization and, more generally, that intrinsic structural disorder is sustainable in mammalian cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Theillet, Francois-Xavier -- Binolfi, Andres -- Bekei, Beata -- Martorana, Andrea -- Rose, Honor May -- Stuiver, Marchel -- Verzini, Silvia -- Lorenz, Dorothea -- van Rossum, Marleen -- Goldfarb, Daniella -- Selenko, Philipp -- England -- Nature. 2016 Feb 4;530(7588):45-50. doi: 10.1038/nature16531. Epub 2016 Jan 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉In-Cell NMR Laboratory, Department of NMR-supported Structural Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rossle Strasse 10, 13125 Berlin, Germany. ; Department of Chemical Physics, Weizmann Institute of Science, Rehovot 76100, Israel. ; Department of Molecular Physiology and Cell Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Robert-Rossle Strasse 10, 13125 Berlin, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26808899" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Cell Line ; Cytoplasm/chemistry/metabolism ; Electron Spin Resonance Spectroscopy ; HeLa Cells ; Humans ; Intracellular Space/*chemistry/*metabolism ; Neurons/cytology/metabolism ; Nuclear Magnetic Resonance, Biomolecular ; Protein Conformation ; alpha-Synuclein/*chemistry/*metabolism
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  • 80
    Publication Date: 2016-03-24
    Description: Endoplasmic reticulum (ER) stress is a major contributor to inflammatory diseases, such as Crohn disease and type 2 diabetes. ER stress induces the unfolded protein response, which involves activation of three transmembrane receptors, ATF6, PERK and IRE1alpha. Once activated, IRE1alpha recruits TRAF2 to the ER membrane to initiate inflammatory responses via the NF-kappaB pathway. Inflammation is commonly triggered when pattern recognition receptors (PRRs), such as Toll-like receptors or nucleotide-binding oligomerization domain (NOD)-like receptors, detect tissue damage or microbial infection. However, it is not clear which PRRs have a major role in inducing inflammation during ER stress. Here we show that NOD1 and NOD2, two members of the NOD-like receptor family of PRRs, are important mediators of ER-stress-induced inflammation in mouse and human cells. The ER stress inducers thapsigargin and dithiothreitol trigger production of the pro-inflammatory cytokine IL-6 in a NOD1/2-dependent fashion. Inflammation and IL-6 production triggered by infection with Brucella abortus, which induces ER stress by injecting the type IV secretion system effector protein VceC into host cells, is TRAF2, NOD1/2 and RIP2-dependent and can be reduced by treatment with the ER stress inhibitor tauroursodeoxycholate or an IRE1alpha kinase inhibitor. The association of NOD1 and NOD2 with pro-inflammatory responses induced by the IRE1alpha/TRAF2 signalling pathway provides a novel link between innate immunity and ER-stress-induced inflammation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869892/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869892/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keestra-Gounder, A Marijke -- Byndloss, Mariana X -- Seyffert, Nubia -- Young, Briana M -- Chavez-Arroyo, Alfredo -- Tsai, April Y -- Cevallos, Stephanie A -- Winter, Maria G -- Pham, Oanh H -- Tiffany, Connor R -- de Jong, Maarten F -- Kerrinnes, Tobias -- Ravindran, Resmi -- Luciw, Paul A -- McSorley, Stephen J -- Baumler, Andreas J -- Tsolis, Renee M -- AI044170/AI/NIAID NIH HHS/ -- AI076246/AI/NIAID NIH HHS/ -- AI076278/AI/NIAID NIH HHS/ -- AI096528/AI/NIAID NIH HHS/ -- AI109799/AI/NIAID NIH HHS/ -- AI112258/AI/NIAID NIH HHS/ -- AI117303/AI/NIAID NIH HHS/ -- GM056765/GM/NIGMS NIH HHS/ -- R01 AI044170/AI/NIAID NIH HHS/ -- R01 AI076246/AI/NIAID NIH HHS/ -- R01 AI076278/AI/NIAID NIH HHS/ -- R01 AI096528/AI/NIAID NIH HHS/ -- R01 AI109799/AI/NIAID NIH HHS/ -- R21 AI112258/AI/NIAID NIH HHS/ -- R21 AI117303/AI/NIAID NIH HHS/ -- R25 GM056765/GM/NIGMS NIH HHS/ -- England -- Nature. 2016 Apr 21;532(7599):394-7. doi: 10.1038/nature17631. Epub 2016 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave, Davis, California 95616, USA. ; Center for Comparative Medicine, Schools of Medicine and Veterinary Medicine, University of California at Davis, One Shields Ave, Davis, California 95616, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27007849" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacterial Outer Membrane Proteins/metabolism ; Brucella abortus/immunology/pathogenicity ; Cell Line ; Dithiothreitol/pharmacology ; Endoplasmic Reticulum/drug effects/pathology ; *Endoplasmic Reticulum Stress/drug effects ; Endoribonucleases/antagonists & inhibitors ; Female ; Humans ; Immunity, Innate ; Inflammation/chemically induced/*metabolism ; Interleukin-6/biosynthesis ; Male ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; Nod1 Signaling Adaptor Protein/immunology/*metabolism ; Nod2 Signaling Adaptor Protein/immunology/*metabolism ; Protein-Serine-Threonine Kinases/antagonists & inhibitors ; Receptors, Pattern Recognition/metabolism ; *Signal Transduction/drug effects ; TNF Receptor-Associated Factor 2/metabolism ; Taurochenodeoxycholic Acid/pharmacology ; Thapsigargin/pharmacology ; Unfolded Protein Response/drug effects
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  • 81
    Publication Date: 2016-03-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cressey, Daniel -- England -- Nature. 2016 Mar 10;531(7593):152. doi: 10.1038/531152a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26961636" target="_blank"〉PubMed〈/a〉
    Keywords: *Biological Evolution ; *Climate Change ; Conservation of Natural Resources/*methods ; Ecology/*methods ; *Plants ; Research ; *Seed Bank ; Seeds/*growth & development ; United States
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  • 82
    Publication Date: 2016-02-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2016 Feb 11;530(7589):142. doi: 10.1038/nature.2016.19290.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26863962" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Embryo Research/*legislation & jurisprudence ; Extrachromosomal Inheritance/genetics ; Female ; Follow-Up Studies ; Genetic Therapy/*legislation & jurisprudence/*methods ; Great Britain ; Haplorhini/genetics ; Heredity/genetics/physiology ; Humans ; Male ; Mitochondrial Diseases/genetics/*prevention & control ; Mitochondrial Replacement Therapy/adverse effects/*legislation & ; jurisprudence/*methods ; Mutation/genetics ; *Patient Safety ; Sex Factors ; United States ; United States Food and Drug Administration/legislation & jurisprudence
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  • 83
    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reardon, Sara -- England -- Nature. 2016 Mar 31;531(7596):560. doi: 10.1038/531560a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029280" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adolescent Behavior/*drug effects/physiology/*psychology ; Child ; *Clinical Trials as Topic/economics ; Decision Making ; Gonadotropin-Releasing Hormone/agonists ; Humans ; National Institutes of Health (U.S.)/economics ; Puberty/*drug effects/*physiology/psychology ; Time Factors ; Transgender Persons/*psychology ; Treatment Outcome ; United States
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  • 84
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kogleck, Larissa -- England -- Nature. 2016 Mar 17;531(7594):S102-3. doi: 10.1038/531S102a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26982019" target="_blank"〉PubMed〈/a〉
    Keywords: China ; Cooperative Behavior ; Great Britain ; Italy ; Japan ; Journal Impact Factor ; Research/economics/*organization & administration/standards/*statistics & ; numerical data ; Switzerland ; United States
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  • 85
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Feb 18;530(7590):253. doi: 10.1038/530253a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26887454" target="_blank"〉PubMed〈/a〉
    Keywords: Aircraft/*instrumentation/*legislation & jurisprudence/standards ; Global Warming/*legislation & jurisprudence/*prevention & control ; Internationality ; United States ; United States Environmental Protection Agency/*legislation & jurisprudence
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  • 86
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    Nature Publishing Group (NPG)
    Publication Date: 2016-02-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Feb 4;530(7588):6. doi: 10.1038/530006a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26842020" target="_blank"〉PubMed〈/a〉
    Keywords: Ecology/*economics/*legislation & jurisprudence ; Environmental Policy/*legislation & jurisprudence ; Politics ; Research Support as Topic/*economics/*legislation & jurisprudence ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 87
    Publication Date: 2016-03-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kuzma, Jennifer -- England -- Nature. 2016 Mar 10;531(7593):165-7. doi: 10.1038/531165a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genetic Engineering and Society Center at North Carolina State University, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26961641" target="_blank"〉PubMed〈/a〉
    Keywords: CRISPR-Cas Systems/genetics ; Crops, Agricultural/genetics ; *Dissent and Disputes ; Genetic Engineering/*legislation & jurisprudence ; *Government Regulation ; *Policy Making ; United States ; United States Department of Agriculture/legislation & jurisprudence ; United States Environmental Protection Agency/legislation & jurisprudence ; United States Food and Drug Administration/legislation & jurisprudence
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 88
    Publication Date: 2016-04-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Waltz, Emily -- England -- Nature. 2016 Apr 21;532(7599):293. doi: 10.1038/nature.2016.19754.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27111611" target="_blank"〉PubMed〈/a〉
    Keywords: Agaricus/enzymology/*genetics ; CRISPR-Cas Systems/*genetics ; Catechol Oxidase/genetics/metabolism ; Crops, Agricultural/economics/enzymology/genetics ; Food, Genetically Modified ; Gene Deletion ; Genetic Engineering/economics/*legislation & jurisprudence ; Patents as Topic ; United States ; United States Department of Agriculture/*legislation & jurisprudence
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 89
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ward, Alyssa -- Baldwin, Thomas O -- Antin, Parker B -- England -- Nature. 2016 Apr 14;532(7598):177. doi: 10.1038/532177d.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ; University of California, Riverside, USA. ; University of Arizona, Tucson, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075087" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Confounding Factors (Epidemiology) ; *Learning ; Mice ; Mice, Transgenic/genetics ; National Institutes of Health (U.S.)/economics ; Reproducibility of Results ; Research/*standards ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 90
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wapner, Jessica -- England -- Nature. 2016 May 5;533(7601):S13-5. doi: 10.1038/533S13a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27144603" target="_blank"〉PubMed〈/a〉
    Keywords: Industry/*economics ; Inventions/*economics ; Licensure/economics/legislation & jurisprudence ; Patents as Topic/legislation & jurisprudence ; Science/*economics ; *Technology Transfer ; United States ; Universities/*economics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 91
    Publication Date: 2016-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nowogrodzki, Anna -- England -- Nature. 2016 Mar 31;531(7596):561. doi: 10.1038/nature.2016.19599.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27029258" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Specimen Banks/*economics/trends ; Climate Change ; Financing, Government/*economics/trends ; Financing, Organized/economics ; Museums ; Research Support as Topic/*economics/trends ; Time Factors ; United States ; United States Government Agencies/economics/trends
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 92
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    Nature Publishing Group (NPG)
    Publication Date: 2016-04-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2016 Apr 28;532(7600):414. doi: 10.1038/532414a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27121803" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/economics/manpower/*organization & administration/*trends ; *Federal Government ; Humans ; International Cooperation ; National Cancer Institute (U.S.) ; Neoplasms/*therapy ; Research Personnel/organization & administration ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 93
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2016 Apr 7;532(7597):13-4. doi: 10.1038/532013a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27078541" target="_blank"〉PubMed〈/a〉
    Keywords: Emigrants and Immigrants/legislation & jurisprudence/psychology ; Emigration and Immigration/*legislation & jurisprudence ; *Fear ; Internationality ; Islam/*psychology ; *Politics ; Research Personnel/*psychology ; Science/*manpower/standards ; *Uncertainty ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 94
    Publication Date: 2016-04-15
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2016 Apr 14;532(7598):158-9. doi: 10.1038/532158a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27075074" target="_blank"〉PubMed〈/a〉
    Keywords: CRISPR-Cas Systems/*genetics ; Crops, Agricultural/*genetics ; Food, Genetically Modified ; Genetic Engineering/*legislation & jurisprudence/*trends ; *Government Regulation ; Internationality ; Plant Breeding/legislation & jurisprudence/methods ; United States ; United States Department of Agriculture/legislation & jurisprudence
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 95
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ledford, Heidi -- England -- Nature. 2016 Mar 10;531(7593):149. doi: 10.1038/531149a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26961633" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; CRISPR-Cas Systems/*genetics ; Europe ; Humans ; Patents as Topic/*legislation & jurisprudence ; Time Factors ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 96
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-12
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Savage, Neil -- England -- Nature. 2016 May 11;533(7602):S56-8. doi: 10.1038/533S56a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27167391" target="_blank"〉PubMed〈/a〉
    Keywords: Access to Information ; Competitive Behavior ; *Cooperative Behavior ; Drug Discovery/economics/manpower/*methods/*organization & administration ; Drug Industry/economics/manpower/*methods/*organization & administration ; *Efficiency, Organizational ; Humans ; *Information Dissemination ; Public-Private Sector Partnerships/organization & administration ; Time Factors ; United States ; United States Food and Drug Administration
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 97
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    Nature Publishing Group (NPG)
    Publication Date: 2016-05-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Savage, Neil -- England -- Nature. 2016 May 5;533(7601):S10-2. doi: 10.1038/533S10a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27144602" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Science Disciplines/economics ; Entrepreneurship/*economics/*organization & administration/statistics & numerical ; data/trends ; Europe ; Humans ; Inventions/economics/statistics & numerical data ; Investments/economics ; Laboratories/economics/organization & administration ; Licensure/economics ; Marketing/economics ; Patents as Topic ; Private Sector/economics/organization & administration/statistics & numerical ; data/trends ; Research/*economics/organization & administration ; Technology Transfer ; United States ; Universities/economics/organization & administration ; Vaccines/economics
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 98
    Publication Date: 2016-02-13
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Baker, Monya -- England -- Nature. 2016 Feb 11;530(7589):141. doi: 10.1038/nature.2016.19269.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26863961" target="_blank"〉PubMed〈/a〉
    Keywords: Biomedical Research/*standards ; *Biotechnology ; Drug Industry ; *Open Access Publishing ; Reproducibility of Results ; *Uncertainty ; United States
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 99
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    Nature Publishing Group (NPG)
    Publication Date: 2016-03-18
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Macilwain, Colin -- England -- Nature. 2016 Mar 17;531(7594):277. doi: 10.1038/531277a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26983505" target="_blank"〉PubMed〈/a〉
    Keywords: *Democracy ; Europe ; *Politics ; *Research Personnel/psychology ; Social Change ; United States
    Print ISSN: 0028-0836
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 100
    Publication Date: 2015-06-25
    Description: In response to DNA damage, tissue homoeostasis is ensured by protein networks promoting DNA repair, cell cycle arrest or apoptosis. DNA damage response signalling pathways coordinate these processes, partly by propagating gene-expression-modulating signals. DNA damage influences not only the abundance of messenger RNAs, but also their coding information through alternative splicing. Here we show that transcription-blocking DNA lesions promote chromatin displacement of late-stage spliceosomes and initiate a positive feedback loop centred on the signalling kinase ATM. We propose that initial spliceosome displacement and subsequent R-loop formation is triggered by pausing of RNA polymerase at DNA lesions. In turn, R-loops activate ATM, which signals to impede spliceosome organization further and augment ultraviolet-irradiation-triggered alternative splicing at the genome-wide level. Our findings define R-loop-dependent ATM activation by transcription-blocking lesions as an important event in the DNA damage response of non-replicating cells, and highlight a key role for spliceosome displacement in this process.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501432/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4501432/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tresini, Maria -- Warmerdam, Daniel O -- Kolovos, Petros -- Snijder, Loes -- Vrouwe, Mischa G -- Demmers, Jeroen A A -- van IJcken, Wilfred F J -- Grosveld, Frank G -- Medema, Rene H -- Hoeijmakers, Jan H J -- Mullenders, Leon H F -- Vermeulen, Wim -- Marteijn, Jurgen A -- 10-0594/Worldwide Cancer Research/United Kingdom -- 233424/European Research Council/International -- 340988/European Research Council/International -- P01 AG017242/AG/NIA NIH HHS/ -- England -- Nature. 2015 Jul 2;523(7558):53-8. doi: 10.1038/nature14512. Epub 2015 Jun 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Genetics, Cancer Genomics Netherlands, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands. ; Division of Cell Biology, Netherlands Cancer Institute, Amsterdam, 1066 CX, The Netherlands. ; Department of Cell Biology, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands. ; Department of Human Genetics, Leiden University Medical Center, Leiden, 2333 ZC, The Netherlands. ; Erasmus MC Proteomics Center, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands. ; Erasmus Center for Biomics, Erasmus University Medical Center, Rotterdam, 3015 CN, The Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26106861" target="_blank"〉PubMed〈/a〉
    Keywords: Alternative Splicing/physiology ; Ataxia Telangiectasia Mutated Proteins/*metabolism ; Cell Line ; Chromatin/metabolism ; DNA Damage/*physiology ; DNA-Directed RNA Polymerases/metabolism ; Enzyme Activation ; Humans ; *Signal Transduction ; Spliceosomes/*metabolism ; Ultraviolet Rays
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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