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Structural basis of substrate recognition and catalysis by fucosyltransferase 8 [Protein Structure and Folding]

Fucosylation of the innermost GlcNAc of N-glycans by fucosyltransferase 8 (FUT8) is an important step in the maturation of complex and hybrid N-glycans. This simple modification can dramatically affect the activities and half-lives of glycoproteins, effects that are relevant to understanding the invasiveness of some cancers, development of mAb therapeutics, and the etiology of a congenital glycosylation disorder. The acceptor substrate preferences of FUT8 are well-characterized and provide a framework for understanding N-glycan maturation in the Golgi; however, the structural basis of these substrate preferences and the mechanism through which catalysis is achieved remain unknown. Here we describe several structures of mouse and human FUT8 in the apo state and in complex with GDP, a mimic of the donor substrate, and with a glycopeptide acceptor substrate at 1.80–2.50 Å resolution. These structures provide insights into a unique conformational change associated with donor substrate binding, common strategies employed by fucosyltransferases to coordinate GDP, features that define acceptor substrate preferences, and a likely mechanism for enzyme catalysis. Together with molecular dynamics simulations, the structures also revealed how FUT8 dimerization plays an important role in defining the acceptor substrate-binding site. Collectively, this information significantly builds on our understanding of the core fucosylation process.




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ADAM10 and ADAM17 proteases mediate proinflammatory cytokine-induced and constitutive cleavage of endomucin from the endothelial surface [Membrane Biology]

Contact between inflammatory cells and endothelial cells (ECs) is a crucial step in vascular inflammation. Recently, we demonstrated that the cell-surface level of endomucin (EMCN), a heavily O-glycosylated single-transmembrane sialomucin, interferes with the interactions between inflammatory cells and ECs. We have also shown that, in response to an inflammatory stimulus, EMCN is cleared from the cell surface by an unknown mechanism. In this study, using adenovirus-mediated overexpression of a tagged EMCN in human umbilical vein ECs, we found that treatment with tumor necrosis factor α (TNF-α) or the strong oxidant pervanadate leads to loss of cell-surface EMCN and increases the levels of the C-terminal fragment of EMCN 3- to 4-fold. Furthermore, treatment with the broad-spectrum matrix metalloproteinase inhibitor batimastat (BB94) or inhibition of ADAM metallopeptidase domain 10 (ADAM10) and ADAM17 with two small-molecule inhibitors, GW280264X and GI254023X, or with siRNA significantly reduced basal and TNFα-induced cell-surface EMCN cleavage. Release of the C-terminal fragment of EMCN by TNF-α treatment was blocked by chemical inhibition of ADAM10 alone or in combination with ADAM17. These results indicate that cell-surface EMCN undergoes constitutive cleavage and that TNF-α treatment dramatically increases this cleavage, which is mediated predominantly by ADAM10 and ADAM17. As endothelial cell-surface EMCN attenuates leukocyte–EC interactions during inflammation, we propose that EMCN is a potential therapeutic target to manage vascular inflammation.




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Re: Covid-19: Brazil’s president rallies supporters against social distancing




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Re: Prognosis of unrecognised myocardial infarction determined by electrocardiography or cardiac magnetic resonance imaging: systematic review and meta-analysis




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A real opportunity to improve neurology services in England




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Rising drug prices drive US manufacturers’ revenues, analysis finds




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US drug makers have imposed big price rises for top selling drugs, study finds




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Prescribing sodium oxybate for narcolepsy




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“Impressive results” in stem cell treatment for multiple sclerosis




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Pay-to-Go Schemes and Other Noncoercive Return Programs: Is Scale Possible?

Noncoercive, pay-to-go, voluntary, assisted voluntary, and nonforced returns generally can offer paid travel and/or other financial incentive to encourage unauthorized immigrants to cooperate with immigration officials and leave host countries. A look at three key rationales for governments to choose pay-to-go and other returns.




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The Faltering U.S. Refugee Protection System: Legal and Policy Responses to Refugees, Asylum Seekers, and Others in Need of Protection

The U.S. refugee protection system, while generous in many respects, has become less robust over the last two decades. The unique and often diverse needs of emerging refugee populations have exposed severe limitations in the standard resettlement approach.This report examines U.S. legal and policy responses to those seeking protection and addresses the barriers, gaps, and opportunities that exist.




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Improving Immigrants' Employment Prospects through Work-Focused Language Instruction

This report describes the range of policies available to improve immigrants’ economic integration through language acquisition, especially those focused on getting immigrants into jobs or moving into higher-paying jobs. It assesses promising models and practices from Europe and North America.




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Andrews: We’ve never been approached for registration - Chairman says staff hurt by Fearon tragedy; ministry moving to certify 17 facilities

Declaring it has been “pained” by the Jodian Fearon situation, the embattled Andrews Memorial Hospital (AMH) is speaking out, saying it has never been approached for or rejected efforts at registration or certification since it began operating 76...




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Five-year INDECOM Act inertia - Williams, Golding still want prosecutorial powers for commission; DPP, Chuck, cops not sold on idea

Almost five years ago, lawmakers on a bipartisan committee of Parliament agreed unanimously to amend the law to give the Independent Commission of Investigations (INDECOM) the power to arrest and prosecute cops. That proposed amendment, which was...




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A Demographic Profile of Black Caribbean Immigrants in the United States

Immigration from the Caribbean to the United States is a relatively recent phenomenon, beginning largely after 1965. This report provides a demographic profile of the 1.7 million Caribbean immigrants in the United States: their geographic settlement, education and workforce characteristics, earnings, modes of entry, and more.




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Patterns and Predictors of School Readiness and Early Childhood Success among Young Children in Black Immigrant Families

Using a nationally representative U.S. birth-cohort study, this report examines levels of school readiness among young children by race/ethnicity and nativity. The authors identify the contextual factors — such as family circumstances, parenting practices, and enrollment in center-based child care — that encourage early school success.




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GAP wants to delay capital projects at local airports

The operator Jamaica’s two largest airports wants to scrap or delay non-essential capital projects. It forms part of a wider halt of capital projects by the Grupo Aeroportuario del Pacífico – which translate to Pacific Airport Group, or GAP –...




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Water disruptions in Linstead, Constant Spring and Denham Town

The National Water Commission (NWC) says a loss in power supply forced the shutdown of the Dinthill facility today, leaving some northern St Catherine communities without water.  The affected communities are: Linstead,...




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What is prayer?

Mothers are often well-known for their ‘power prayers’ that agree with Heaven to shift circumstances in their families. On this Mother’s Day, we bless them for their love and sacrifice! And now more than ever, we want to make sure that our prayers...




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Prioritizing Integration

This book takes stock of the impact of the crisis on immigrant integration in Europe and the United States. It assesses where immigrants have lost ground, using evidence such as levels of funding for educational programs, employment rates, trends toward protectionism, public opinion, and levels of discrimination.




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Hoja de ruta para la participación de las diásporas en el desarrollo: Un manual para políticos y profesionales de los países de origen y de acogida

Este manual ofrece a los formuladores de políticas y especialistas una guía accesible y práctica sobre las iniciativas gubernamentales referentes a la diáspora. Este manual contiene un menú, seleccionado cuidadosamente, de opciones normativas y programáticas viables basadas en experiencias reales en distintas partes del mundo.




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Comment associer les diasporas au développement: Manuel a l’usage des decideurs et praticiens dans les pays d’origine et d’accueil

Ce manuel pratique et simple d’utilisation à l’usage des décideurs et des praticiens fait le point des mesures les plus récentes prises par les pouvoirs publics en direction des diasporas. La question qui se pose aux responsables politiques n’est pas tant de savoir si les diasporas peuvent être utiles à leur pays d’origine, mais comment elles le sont et quels types de politiques et de programmes publics sont à même de favoriser ces relations.




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Developing a Road Map for Engaging Diasporas in Development: A Handbook for Policymakers and Practitioners in Home and Host Countries

This practical handbook highlights policies and programs that can magnify the resources, both human and financial, that emigrants and their descendants contribute to development. It gives concrete examples of policies and programs that have been effective, and pulls out both useful lessons and common challenges associated with the topics at hand.




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How Can Talent Abroad Induce Development at Home? Towards a Pragmatic Diaspora Agenda

This edited volume develops a pragmatic approach to the engagement of highly skilled members of the diaspora for the benefit of their countries of origin. The book, edited by a World Bank senior economist, is based on empirical work in middle-income and high-income economies.




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Migration of Health Workers: The WHO Code of Practice and the Global Economic Crisis

This edited volume from the World Health Organization (WHO), which includes chapters written by MPI researchers, examines country-level responses to the international movement of health-care workers, both before and after adoption of the WHO’s Global Code of Practice on the International Recruitment of Health Personnel.




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Communicating More for Less: Using Translation and Interpretation Technology to Serve Limited English Proficient Individuals

This report provides an overview of several commonly used translation and interpretation technologies. It aims to assist language access practitioners in understanding and identifying which systems would best meet their agency’s language access needs.




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Proactive Engagement: Two Strategies for Providing Language Access in Workforce Development Services

This interactive language access webinar, one in a series offered by the Migration Policy Institute's National Center on Immigrant Integration Policy, examines how New York and Illinois have broken down some of these barriers to proactively engage LEP communities to obtain workforce services.




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Proactive Engagement: Two Strategies for Providing Language Access in Workforce Development Services

This webinar examines how New York and Illinois have proactively engaged Limited English Proficient (LEP) communities to obtain workforce services.




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LEP Workers & Access to Workforce Services: Perspectives on Current Barriers to Access and Prospects for Improvements Under WIA Reauthorization

In this webinar, experts discuss barriers immigrant and LEP individuals face in accessing the WIA system, how a revitalized WIA could address these barriers, and the extent to which the current Senate Health, Education, Labor, and Pensions (HELP) Committee's WIA reauthorization proposal addresses these barriers.




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Limited English Proficient Individuals in the United States: Number, Share, Growth, and Linguistic Diversity

The number of U.S. residents deemed Limited English Proficient (LEP) has increased substantially in recent decades, consistent with the growth of the U.S. foreign-born population. This brief offers analysis on the number, share, growth, and linguistic diversity of LEP individuals in the United States from 1990 to 2010 at the national, state, and metropolitan-area levels.




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Genetically engineered 'Magneto' protein remotely controls brain and behaviour

“Badass” new method uses a magnetised protein to activate brain cells rapidly, reversibly, and non-invasively

Researchers in the United States have developed a new method for controlling the brain circuits associated with complex animal behaviours, using genetic engineering to create a magnetised protein that activates specific groups of nerve cells from a distance.

Understanding how the brain generates behaviour is one of the ultimate goals of neuroscience – and one of its most difficult questions. In recent years, researchers have developed a number of methods that enable them to remotely control specified groups of neurons and to probe the workings of neuronal circuits.

Related: Remote control of brain activity with heated nanoparticles

Related: Researchers read and write brain activity with light

Continue reading...




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Stem cells from schizophrenics produce fewer neurons

New research shows that a genetic mutation associated with schizophrenia alters the process of cellular differentiation, disturbing the balance of neurons and glia in the brain

Stem cells obtained from patients with schizophrenia carry a genetic mutation that alters the ratio of the different type of nerve cells they produce, according to a new study by researchers in Japan. The findings, published today in the journal Translational Psychiatry, suggest that abnormal neural differentiation may contribute to the disease, such that fewer neurons and more non-neuronal cells are generated during the earliest stages of brain development.

Schizophrenia is a debilitating mental illness that affects about 1 in 100 people. It is known to be highly heritable, but is genetically complex: so far, researchers have identified over 100 rare genetic variations and dozens of mutations associated with increased risk of developing the disease.

Related: Brain’s immune cells hyperactive in schizophrenia

Related: Turning urine into brain cells | Mo Costandi

Continue reading...




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[ Politics ] Open Question : Should President Trump continue to have manufacturing sent to China???




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[ Singles & Dating ] Open Question : Is it seen as wrong for women to be protective of themselves, and not reliant on a male protector?




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[ Languages ] Open Question : Improve to listen English.?

I'm a Japanese,struggling to catch English. Exa: V/B, we don't have the similar sound of V. so both sounds B. Can native English speakers always hear the difference of B/V even in France,Spanish or other Europe language?




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Memo: Prior COVID-19 diagnosis 'permanently disqualifying' for U.S. military service

Military Entrance Processing Stations won't process individuals who have had COVID-19 for military service, even if they've fully recovered from the virus, the Pentagon confirmed this week.




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A Precarious Position: The Labor Market Integration of New Immigrants in Spain

This report assesses how new immigrants to Spain fare in the country's labor market, evaluating the conditions under which they are able to find employment, and their progress out of unskilled work into middle-skilled jobs. The report is part of a series of six case studies on labor market outcomes among immigrants to European Union countries.




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A Work in Progress: Prospects for Upward Mobility Among New Immigrants in Germany

This report analyzes the labor market integration of newcomers to Germany, who tend to have different national origins and higher levels of education than earlier waves of migrants. These new immigrants have had varying levels of success in finding employment and transitioning into higher-skilled jobs.




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Building an Integration System: Policies to Support Immigrants’ Progression in the Czech Labor Market

This report presents an overview of Czech integration policies, with a special focus on economic integration. It focuses on policies designed to support migrants’ incorporation in the Czech labor market, and assesses the extent to which these policies facilitate migrants’ upward mobility into more skilled work.




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Better Work for Immigrants: Tackling Joblessness and Stunted Progression in the European Union

This day-long conference in Brussels, co-sponsored by the International Labour Office and the European Commision’s Directorate-General for Employment, Social Affairs, and Inclusion, focuses on the dynamics by which migrants get stuck in low-skilled work, and the role of training and employment services in helping them progress in their occupations.




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Better Work for Immigrants: Tackling Joblessness and Stunted Progression in the European Union

A day-long conference in Brussels, co-sponsored by the International Labour Office and the European Commision’s Directorate-General for Employment, Social Affairs, and Inclusion, where panelists discuss the dynamics by which migrants get stuck in low-skilled work, and the role of training and employment services in helping them progress in their occupations. The conference concludes a project and series of reports prepared on the Labor Market Integration of New Arrivals in Europe




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It is Time for Federal Agencies to Do More to Improve the Provision of Language Access Services

Whether driven by pragmatism, local laws, or federal civil-rights provisions, state and local governments and agencies across the United States increasingly have designed and implemented language access services (i.e. translation and interpretation) in response to growing Limited English Proficient populations. This commentary argues it is time for the federal government to follow suit.




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Weaknesses in the Visa Waiver Program

Testimony of Susan Ginsburg, then Director of MPI's Mobility and Security Program, before the Senate Judiciary Committee Subcommittee on Terrorism, Technology, and Homeland Security.




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Prospects for Comprehensive Immigration Reform

Testimony of Doris Meissner, Director of MPI's U.S. Immigration Policy Program, before the Senate Judiciary Committee Subcommittee on Immigration, Border Security, and Citizenship, at its hearing: "Comprehensive Immigration Reform in 2009, Can We Do It and How?" 




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Securing the Border: Building on the Progress Made

Testimony of Doris Meissner, Director of MPI's U.S. Immigration Policy Program, before the Senate Homeland Security and Governmental Affairs Committee.




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Border Security: Measuring the Progress and Addressing the Challenges

Testimony of Doris Meissner, Senior Fellow and Director, U.S. Immigration Policy Program, before the Committee on Homeland Security and Governmental Affairs, U.S. Senate.




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The Executive Proclamation Designating the Organ Mountains-Desert Peaks a National Monument: Implications for Border Security

Testimony of Marc R. Rosenblum, Deputy Director, U.S. Immigration Program, before the House Committee on Homeland Security Subcommittee on Oversight and Management Efficiency.




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A Review of the Department of Homeland Security’s Policies and Procedures for the Apprehension, Detention, and Release of Non-Citizens Unlawfully Present in the United States

Letter submitted by Marc R. Rosenblum, Deputy Director, U.S. Immigration Program, at the request of the Minority Staff of the House Oversight and Government Reform Committee for the February 25, 2015 joint subcommittee hearing reviewing apprehension, detention, and release policies regarding unauthorized immigrants.




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An Examination of the Administration's Central American Minors Refugee/Parole Program

Testimony of Doris Meissner, Director of MPI's U.S. Immigration Policy Program, before the Senate Judiciary Committee's Subcommittee on Immigration and the National Interest regarding the Central American Minors Refugee/Parole Program that began in December 2014.




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Senate Judiciary Testimony on Immigration Enforcement Priorities and Use of Prosecutorial Discretion

Testimony of Marc Rosenblum before the Senate Judiciary Committee for the December 2, 2015 hearing on priorities for immigration enforcement and the use of prosecutorial discretion.