29,117 research outputs found

    The progressive ankyloses protein ANK facilitates clathrin- and adaptor-mediated membrane traffic at the trans-Golgi network-to-endosome interface.

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    This is a pre-copyedited, author-produced version of an article accepted for publication in Human molecular genetics following peer review. The version of record Wenke Seifert, York Posor, Peter Schu, Gudrun Stenbeck, Stefan Mundlos, Sabine Klaassen, Peter Nürnberg, Volker Haucke, Uwe Kornak, Jirko Kühnisch, The progressive ankylosis protein ANK facilitates clathrin- and adaptor-mediated membrane traffic at the trans-Golgi network-to-endosome interface, Human Molecular Genetics, Volume 25, Issue 17, 1 September 2016, Pages 3836–3848, is available online at: https://doi.org/10.1093/hmg/ddw23

    Fashion Culture: Worn In New York

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    On Tuesday, October 30, 2018, New York Times bestselling author Emily Spivack presented Worn in New York, a contemporary cultural history of well-loved clothes and the people who wore them. Contributors in and out of the public eye share personal, wild, poignant, funny stories about the clothes that are part of their New York lives. A book signing followed the presentation

    York County History - Accession 68 - M30 (42)

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    The York County History collection consists of a brief summary of York County, SC history from its settlement in 1750 to the Great Depression in the 1930s. The author is unknown.https://digitalcommons.winthrop.edu/manuscriptcollection_findingaids/1119/thumbnail.jp

    Edith L. Fisch, First Female Law Professor in New York State

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    Edith Fisch, author of the treatise Fisch on New York Evidence, was the first female law professor in New York State when she began teaching at New York Law School in 1962. She was also the first woman to earn the J.S.D. degree at Columbia University Law School and the first person ever to earn all degrees awarded by the law school, receiving her LL.B. in 1948, her LL.M. in 1949, and her J.S.D. in 1950. Professor Fisch served as president of the New York Women\u27s Bar Association from 1970 to 1971. Her accomplishments are all the more significant because Professor Fisch had contracted polio at the age of 12 and was confined to a wheelchair for the rest of her life.https://digitalcommons.nyls.edu/firsts/1007/thumbnail.jp

    Edith L. Fisch, Associate Professor, 1962-1965. President, New York Women\u27s Bar Association, 1970-1971.

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    Edith L. Fisch, Associate Professor, 1962-1965. Professor Fisch served as president of the New York Women\u27s Bar Association from 1970 to 1971. She was the author of the treatise Fisch on New York Evidence and was the first female law professor in New York State when she began teaching at New York Law School in 1962. She was also the first woman to earn the J.S.D. degree at Columbia University Law School and the first person ever to earn all degrees awarded by the law school, receiving her LL.B. in 1948, her LL.M. in 1949, and her J.S.D. in 1950. Her accomplishments are all the more significant because Professor Fisch had contracted polio at the age of 12 and was confined to a wheelchair for the rest of her life.https://digitalcommons.nyls.edu/bar_leaders/1003/thumbnail.jp

    York County History Collection - Accession 1446 - M709 (765)

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    The York County History Collection consists of a brief history of York County from 1750s-1930s titled, “York County” by an unknown author and two pamphlets titled, “The Background of The History of York County, South Carolina: A Radio Address at WBT Charlotte, N.C., July 21, 1933, in the series of the South Carolina Economic Council” by Albert M. Grist of York, South Carolina.https://digitalcommons.winthrop.edu/manuscriptcollection_findingaids/2433/thumbnail.jp

    28th Annual Faculty Author Celebration & Awards

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    The 28th Annual Faculty Author Celebration & Awards honored New York Medical College faculty for their research published during the 2020 calendar year. On Wednesday, December 15th at 4pm the Health Sciences Library and New York Medical College leadership announced the Faculty Author Award recipients. The awards honored authors in a variety of categories considering engagement, distribution, and the influence of their publications. It was a prolific year for New York Medical College faculty, who published more than 800 citations in 2020. During this celebration, we heard from college leadership and authors across departments as they discussed their work and their experiences publishing during this significant year in research

    Räumlich-zeitliche Kontrolle der Clathrin-vermittelten Endozytose durch PI3K C2α und Phosphatidylinositol-3,4-bisphosphat

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    Phosphoinositides (PIs) are rare lipids of the cytoplasmic leaflet of eukaryotic membranes. They serve as spatiotemporal signposts directing proteins to distinct subcellular compartments or membrane domains and thereby contribute to defining membrane identity. Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] is most abundant at the plasma membrane where it regulates signaling, ion channels, actin dynamics, and clathrin-mediated endocytosis (CME). The nucleation and assembly of clathrin-coated pits (CCPs) depends on PI(4,5)P2. After membrane fission, PI(4,5)P2 hydrolysis triggers vesicle uncoating and newly formed vesicles fuse with the early endosomal compartment. Endosomes are highly enriched in phosphatidylinositol-3-phosphate [PI(3)P] and maintenance and functionality of these organelles both require PI(3)P. However, the mechanism of PI conversion on the endocytic route from a PI(4,5)P2 to a PI(3)P enriched membrane is still enigmatic. Here, we show that phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] is a novel lipid regulator of CME that is required for the maturation of CCPs. Cells depleted of PI(3,4)P2 by means of the PI(3,4)P2-specific 4-phosphatase INPP4B display endocytic defects characterized by long-lived CCPs. This effect is different from PI(4,5)P2-controlled initiation of CCP formation and demonstrates a dual lipid requirement for the sequential generation of PI(4,5)P2 and PI(3,4)P2 during CME. We further identify the clathrin-associated class II phosphatidylinositol-3-kinase, PI3K C2α, as the enzyme that synthesizes PI(3,4)P2 at CCPs. RNA interference-mediated depletion of PI3K C2α phenocopies effects seen in cells enzymatically depleted of PI(3,4)P2 and results in a partial loss of PI(3,4)P2 from the plasma membrane. Detailed characterization suggested a late maturation defect of CCPs preceding dynamin-mediated fission. A comprehensive analysis of endocytic proteins revealed the PX-BAR domain protein sorting nexin 9 (SNX9) as an effector of PI(3,4)P2. The recruitment of SNX9 to CCPs arrested at a late stage due to dynamin2-depletion strictly depends on both PI3K C2α and PI(3,4)P2. Furthermore, depletion of SNX9 and its close homolog SNX18 causes endocytic defects akin to loss of PI3K C2α that cannot be rescued by PI-binding deficient mutants of SNX9. Taken together, these observations identify a novel lipid requirement in CME and suggest a continuous mechanism for PI conversion along the endocytic route. Instead of de novo formation of PI(3)P on early endosomes, endocytic vesicle formation is coupled to PI(3,4)P2 synthesis. The phosphatase INPP4A, an effector of the early endosomal GTPase Rab5, would directly generate PI(3)P on membranes en route to early endosomes. These findings establish a novel role of PI(3,4)P2 as a product of a class II PI3K in a central cell physiological process and thus significantly advance our understanding of membrane traffic, the roles of class II PI3Ks, and the physiological importance of PI(3,4)P2.Phosphoinositide (PIs) sind seltene Lipide der zytoplasmatischen Seite eukaryo-tischer Membranen, die als räumliche und zeitliche Orientierungspunkte für Proteine dienen. Dadurch definieren PIs wesentlich die Identität distinkter zellulärer Membranen. Phosphatidylinositol-4,5-bisphosphat [PI(4,5)P2] ist in der Plasmamembran (PM) konzentriert und dort von essentieller Bedeutung für verschiedene Prozesse, darunter die Clathrin- vermittelte Endozytose (CME). Für die Nukleation und Assemblierung Clathrin- ummantelter Membranvertiefungen (CCPs) ist PI(4,5)P2 unverzichtbar. Nach der Abschnürung wird PI(4,5)P2 hydrolysiert und das Vesikel fusioniert mit dem frühen endosomalen Kompartiment. In Endosomen ist Phosphatidy- linositol-3-phosphat [PI(3)P] die dominierende PI Spezies und für die Funktion dieser Organellen unabdingbar. Jedoch ist der Mechanismus der PI Konversion auf der endozytischen Route, die Umwandlung einer PI(4,5)P2- zu einer PI(3)P-reichen Membran, bisher nur unzureichend verstanden. In der vorliegenden Arbeit etablieren wir Phosphatidyl¬inositol-3,4-bisphosphat [PI(3,4)P2] als neuen Lipidregulator der CME, der für die Reifung der CCPs von Bedeutung ist. Mittels der PI(3,4)P2-spezifischen 4-Phosphatase INPP4B von PI(3,4)P2 depletierte Zellen zeigen einen endozytischen Defekt, der durch langlebige CCPs charakterisiert ist. Dieser Effekt unterscheidet sich von der PI(4,5)P2-kontrollierten Initiation der CCP Bildung und zeigt ein Erfordernis der sequentiellen Generierung von PI(4,5)P2 und PI(3,4)P2 auf. Weiterhin identifizieren wir die Clathrin-assoziierte Klasse II Phosphatidylinositol-3-Kinase (PI3K), PI3K C2α, als das Enzym, das PI(3,4)P2 an CCPs synthetisiert. Die RNA Interferenz-vermittelte Depletion von PI3K C2α führte zu einer Phänokopie der Effekte, die in PI(3,4)P2-defizienten Zellen auftraten und zu einem partiellen Verlust PI(3,4)P2s von der PM. Detaillierte Untersuchungen deuteten auf einen späten, jedoch vor der Membranfission liegenden, Maturierungsdefekt von CCPs hin. Eine Analyse endozytischer Proteine zeigte das PX-BAR-Domänen Protein sorting nexin 9 (SNX9) als Effektor von PI(3,4)P2 auf. Die Rekrutierung von SNX9 zu arretierten Spätstadium-CCPs in Dynamin2-depletierten Zellen ist strikt von PI3K C2α und PI(3,4)P2 abhängig. Weiterhin führen die Depletion von SNX9 und dessen eng verwandtem Protein SNX18 zu einem dem in PI3K C2α-depletierten Zellen ähnlichen endozytischen Defekt, der nicht von PI-Bindungs-defizienten Mutanten von SNX9 kompensiert werden kann. Diese Daten identifizieren ein neues Lipid- Erfordernis in der CME und legen einen kontinuierlichen Mechanismus der PI Konversion nahe. Anstatt der de novo Bildung von PI(3)P in frühen Endosomen findet PI(3,4)P2-Synthese während der Vesikelbildung statt. Die Phosphatase INPP4A, ein Effektor der früh-endosomalen GTPase Rab5, könnte PI(3)P direkt auf endozytischen Vesikeln generieren, bevor diese mit dem frühen endosomalen Kompartiment fusionieren. Diese Ergebnisse etablieren eine neue Rolle von PI(3,4)P2 als Produkt einer Klasse II PI3K in einem zentralen zellphysiologischen Prozess und tragen daher signifikant zu unserem Verständnis des Membranverkehrs, der Rollen der Klasse II PI3Ks und der physiologischen Bedeutung von PI(3,4)P2 bei

    Segregation in New York, London and Tokyo

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    Since the 1980s, the workforce in New York, London and Tokyo has been professionalizing with an increasing share of high income earners. While measures of segregation have stabilized, spatial inequality has increased due to gentrification of inner-city neighborhoods and suburbanization of poverty.Urbanis

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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