ALBERT

Description: In den vergangenen zwei Jahren hat sich die Welt verändert und vermehrt beherrschen Krisen das Bild. Jahrzehntelange Gewissheiten gelten nicht mehr, Risiken und Unsicherheiten nehmen zu, die Herausforderungen werden immer komplexer und erfordern gleichzeitig immer schnelleres und konsequenteres Handeln.

Description: Seitdem Einweg-Plastikartikel wie Kunststofftüten und Strohhalme verboten wurden, sind Straßen und Strände sauberer geworden. Zudem wurde auch die öffentliche Diskussion über nachhaltigen Konsum intensiviert. Die Gesamtmenge an Kunststoff-Abfällen ließ sich mit "Plastikverboten" hingegen nicht signifikant reduzieren. Zu diesem Ergebnis kommt der vorliegende Polyproblem-Report der gemeinnützigen Röchling Stiftung und des Beratungshauses Wider Sense in Zusammenarbeit mit dem Wuppertal Institut. Die Autor*innen haben die Wirkung staatlicher Verbote von Einweg-Plastikprodukten unter die Lupe genommen und die Erfahrungen aus Deutschland, Kenia und Kalifornien analysiert.

Description: Within the Shaping Digitalisation project, we aim to highlight and discuss the opportunities that digitalisation can bring to Germany. In particular, we are discussing three stand-out areas where action is most needed to achieve ecological transformation: mobility, the circular economy, and agriculture and food. This report addresses the second area in need of action. Up until now, discussions on the circular economy have been limited to recycling and the re-use of materials. We must expand the scope of these discussions to include new, resource-efficient business models and the comprehensive transformation of value chains and industrial structures. Our analysis has found that digitalisation is indispensable for this transformation if used properly. We hope this report will provide the impetus needed to kick-start a climate- and resource-friendly industrial transformation in Germany. Here, we have incorporated the findings of our interdisciplinary workshop on "Shaping the Digital-Ecological Industrial Transformation - Business Models and Political Framework Conditions for Climate and Resource Protection" that was attended by experts from international research institutes, civil organizations, public authorities, and private companies.

Description: The introduction of a Digital Product Passport (DPP) is an opportunity to create a system that can store and share all relevant information throughout a product's life cycle. This would provide industry stakeholders, businesses, public authorities and consumers with a better understanding of the materials used in the product as well as their embodied environmental impact. With the COVID-19 pandemic, the Russian invasion of Ukraine and the cost-of-living crisis, now is a critical moment to transform our economic and business models, while also addressing the huge scale of material emissions. DPPs can be a pivotal policy instrument in this goal. Furthermore, DPPs can accelerate the twin green and digital transitions as part of EU efforts to deliver positive climate action and sustainable economies. In 2020, the European Commission (EC) adopted a new Circular Economy Action Plan (CEAP), which emphasised the need for circular economy initiatives to consider the entire life cycle of products, from the production of basic materials to end-of-life disposal. The Circular Economy Package published in March 2022 includes a proposal for an Ecodesign for Sustainable Products Regulation (ESPR), which builds upon the Ecodesign Directive that covers energy-related products. A DPP will form a key regulatory element of the ESPR by enhancing the traceability of products and their components. This will provide consumers and manufacturers with the information needed to make better informed choices by taking their environmental impact into consideration. As discussed in the report, there is widespread agreement amongst business leaders that a well-designed DPP could have both short- and longer-term benefits, improving access to reliable and comparable product sustainability information for businesses, consumers and policymakers. A well-designed DPP can unify information, making it more readily accessible to all actors in the supply chain. This will support businesses to ensure an effective transformation towards a decarbonised industry. It could also create incentives for companies to make their products more sustainable, as improving access to reliable and consistent information across supply chains will make it easier for customers to make comparisons.

Description: Die Dekarbonisierung der Mietwohnungsbestände ist zwingende Voraussetzung für die Einhaltung deutscher Klimaschutzziele. Hierzu ist eine schnelle und deutliche Verbesserung der Energieeffizienz unabdinglich. Aber: funktioniert der Markt für Energieeffizienz bei Mietwohnungen? Eine empirische Untersuchung auf dem Wuppertaler Mietwohnungsmarkt gibt Antworten darauf. Um die Sanierungsrate signifikant zu steigern, etwa durch eine höhere Zahlungsbereitschaft für Energieeffizienz, braucht es sowohl für Vermieter als auch für Mieter verbesserte Rahmenbedingungen.

Description: A main goal of this study - which also functions as deliverable 210078-D07 of the Circular Economy Beacons (CEB) project - is to evaluate currently available frameworks that measure and operationalise Circular Economy (CE), with a particular focus on the urban context. The regional focus lies on the Western Balkan region, which is at the centre of the project. Such "Urban Circularity Hotspot Frameworks" (UCHF) aim at providing decision support for policy makers, companies, citizens etc. regarding the transition to CE within cities. Based on the analysis of different frameworks, suggestions are derived regarding UCHF suitable for the specific characteristics of Western Balkan municipalities, i.e. a Circular Economy Beacons Urban Circularity Hotspot Framework (CEB-UCHF) ready for short-term implementation.

Description: Circular economy seems a vital enabler for sustainable use of natural resources which is also important for achieving the 2030 agenda for sustainable development goals. Therefore, a special session addressing issues of "sustainable solutions and remarkable practices in circular economy focusing materials downstream" was held at the 16th International Conference on Waste Management and Technology, where researchers and attendees worldwide were convened to share their experiences and visions. Presentations focusing on many key points such as new strategies, innovative technologies, management methods, and practical cases were discussed during the session. Accordingly, this article compiled all these distinctive presentations and gave insights into the pathway of circular economy towards the sustainable development goals. We summarized that the transition to circular economy can keep the value of resources and products at a high level and minimize waste production; the focus of governmental policies and plans with the involvement of public-private-partnership on 3Rs (reduce, reuse, and recycle) helps to improve the use of natural resources and take a step ahead to approach or achieve the sustainability.

Description: In Germany, the number of renewable energy prosumers has increased rapidly since 2000. However, the development of prosumers has faced and will continue to face various economic, social, and technological challenges, which have triggered the emergence of a number of innovative business models (BM). This paper enriches the empirical basis for prosumer-oriented BMs by investigating two BM innovations in Germany (P2P electricity trading and aggregation of small-size prosumers) drawing on business model and socio-technical transition theories. A mix of qualitative data collection methods, including document analysis and semi-structured expert interviews, was applied. We found that while both BMs can potentially address the challenges associated with renewable energy prosumer development in Germany, small-scale prosumers’ participation in both BMs has been limited so far. We identified various internal and external drivers and barriers for scaling up these BMs for prosumer development in Germany. Despite these barriers, both aggregation and centralized P2P targeting prosumers may potentially be also taken up by incumbent market actors such as utilities. Decentralized P2P on the other hand still faces significant internal and external barriers for upscaling. Based on the analysis, the paper provides policy recommendations with respect to the identified drivers and barriers. From a theoretical perspective, our findings provide further evidence to challenge the dichotomous understanding of niche actors and incumbents, the latter of which are often theorized to be resistant to radical innovations.

Description: How do recent changes in consumption in the wake of the COVID-19 pandemic affect the avoidance of packaging waste? How can an increase in packaging waste be countered and the previous trend towards unpackaged and reusable solutions be revived and promoted? To tackle these questions, we use a systemic approach that regards packaging as a network of interrelated interests of industry (manufacturing and logistics), trade (retail and catering), consumers and the waste management sector. To analyse this network, we applied three methods. First, we analysed secondary sources such as surveys. Second, we conducted semi-structured interviews with seven actors from industry, consumer education and waste management in May and June 2020. Third, we used the questions from the interview guideline to do an online survey among representatives of the public waste management industry.

Description: Die GLS Bank finanziert gezielt nachhaltige Projekte und Unternehmen in den Bereichen erneuerbare Energien, nachhaltige Wirtschaft, Ernährung, Wohnen, Bildung & Kultur, Soziales & Gesundheit. Eine zentrale Herausforderung ist es, die Nachhaltigkeitswirkung der Finanz- und Anlagestrategie robust zu quantifizieren und transparent darzustellen. Die GLS Bank hat sich zum Ziel gesetzt, die hierfür notwendigen Methoden und Daten zur Bewertung der Nachhaltigkeitswirkungen ihres Finanz- und Anlagenportfolios schrittweise weiterzuentwickeln, um eine richtungssichere Portfoliosteuerung und Kundenbetreuung zu unterstützen. Ziel des Projektes ist zunächst, das Emissionsgeschehen der finanzierten Wertschöpfungskette abzubilden (Scope 3), aber auch die eingesparten Emissionen als einen Beitrag zum Klimaschutz zu bewerten (Scope 4). Es werden die Scope 3 Emissionen der GLS Bank in den folgenden Finanz- und Anlagebereichen für das Berichtsjahr 2019 bilanziert: 1. Aktien- und Klimafonds; 2. Kredite; 3. Unternehmensbeteiligung. Scope 4 Emissionen werden in Form vermiedener Emissionen (Carbon Handprint) dabei ausschließlich für Bereiche bilanziert, in denen THG-Reduktionspotentiale richtungssicher abgeschätzt werden können. Im vorliegenden Bericht wird der Untersuchungsrahmen, die vom Wuppertal Institut entwickelte Methodik sowie Lösungsstrategien für die Überbrückung geringer Datenqualität/-verfügbarkeit beschrieben. Die Robustheit der Ergebnisse wird durch Prüfungsmethoden reflektiert und dem Leser somit eine Interpretationsunterstützung gegeben. In einem Ausblick werden Weiterentwicklungsbedarfe und -möglichkeiten skizziert, um schrittweise eine zunehmend robuste und wissenschaftliche fundierte Methodik und Datengrundlage zur Bewertung der Klimawirkung sowie weiterer Nachhaltigkeitswirkungen des Finanz- und Anlageportfolios der GLS Bank in Zusammenarbeit mit relevanten Stakeholdern zu etablieren.

Description: Damit sich die weltweit zunehmend ambitionierten Klimaschutzziele erreichen lassen, müssen auch im Industriesektor weitgehende Emissionsreduktionen innerhalb weniger Jahrzehnte realisiert werden. Expertinnen und Experten sind sich einig, dass dies nicht ohne den Umstieg von fossilen auf erneuerbare Energieträger und Rohmaterialien - sogenannte Feedstocks - umsetzbar ist. Im Zuge der verstärkten Nutzung dieser grünen Energieträger ist denkbar, dass sich deren Verfügbarkeit und Kosten zu immer wichtigeren Standortfaktoren für die Produktion industrieller Güter entwickeln werden. Dies könnte dazu führen, dass zukünftig Standorte mit kostengünstiger Verfügbarkeit von erneuerbaren Energien attraktiver gegenüber anderen Standorten werden und es dann zu Standortverlagerungen kommt - insbesondere im Bereich der energieintensiven Industrie. In dem vorliegenden Artikel greifen die Autoren diese möglichen Verlagerungen industrieller Produktion auf. In diesem Zusammenhang führen sie auch den Begriff "Renewables Pull" ein. Die in bestimmten Regionen der Welt kostengünstig und in großen Mengen verfügbaren erneuerbaren Energien könnten nach Ansicht der Autoren künftig eine Sogwirkung auslösen und bestimmte Teile der industriellen Produktion anziehen - auch Pull-Effekt genannt.

Description: The transition from today's "take, make, waste" economic paradigm to a circular economy requires a joint effort from actors on all levels: governments, business, and civil society. While companies are among the drivers of the circular transformation, they find it hard to achieve a circular economy on their own. Hence, cross-industry collaboration is one of the imperatives for scaling a circular economy. Against this background, econsense, together with Accenture and the Wuppertal Institute, launched its study "Germany's Transition to a Circular Economy - How to Unlock the Potential of Cross-Industry Collaboration". Based on a survey and expert interviews within the econsense community, the study finds that companies are yet to unlock the full potential of cross-industry collaboration. While two thirds of analysed industry collaborations have a high potential for scaling the circular economy, only 43 per cent of those already show a high degree of interaction. The study provides concrete guidance for companies to get started with circularity and identify the right partners for cross-industry collaboration. Specifically, the report recommends companies: 1) Understand what circularity is about and map it on their own operations and processes. 2) Understand the different circular business models and identify the ones relevant to each business. 3) Discover areas where collaboration can help to create the needed foundation and to execute circular actions.

Description: Digitalisation is taking place at a fast pace in all European countries and it is transforming the economies, societies, communication, jobs and the necessary skills for the workplace and everyday life. The Covid-19 pandemic is also accelerating digitalisation at many levels. To address the great challenges resulting from this, the European Commission has launched the Green Deal, a long-term transformation strategy towards an innovative and sustainable society. Three important initiatives under the Green Deal are the New Circular Economy Action Plan, the Biodiversity Strategy for 2030 and the Zero Pollution Action Plan. The various strategies and action plans draw up a large portfolio of measures, instruments and milestones that are always linked to digital technologies. Ideally, these are eco-innovative and sustainable and contribute to improving living conditions in Europe. The EIO Biennial Report 2020, which looks at a different topic every two years, considers digitalisation a major opportunity to accelerate the transition to a circular Europe. In the current report, the authors provide an overview of eco-innovation trends, illustrated by digital technology and policy practices that can further drive the circular economy.

Description: Auf dem Weg zu einer ressourceneffizienten Gesellschaft bedarf es richtiger Rahmenbedingungen, Informationen und Handlungsalternativen. Eine Möglichkeit, diese Voraussetzungen zu schaffen, ist ein kommunales Zero-Waste-Konzept. Zero Waste lässt sich übersetzen mit "Null Abfall, null Verschwendung" und verfolgt das Ziel, möglichst wenig Abfall zu produzieren sowie effizient und sparsam mit Ressourcen umzugehen. Ein solches Konzept wie in Kiel ist die Basis für eine Zertifizierung als Zero Waste City, eine Auszeichnung, die der europäische Verein Zero Waste Europe vergibt. 2007 wurde die italienische Gemeinde Capannori zur ersten Zero Waste City in Europa erklärt, seitdem sind knapp 400 europäische Gemeinden dieser Bewegung gefolgt.

Description: Öffentliche Mittel für die Unterstützung von Unternehmen sollten bestenfalls so eingesetzt werden, dass sie eine möglichst große, nachhaltige Wirkung haben und mit einem gesellschaftlichen Nutzen verbunden sind. Das kann unmittelbar erfolgen, in dem die konkrete Förderung an bestimmte Vorgaben gebunden wird, wie etwa den Ausbau von zukunftsfähigen Infrastrukturen. Es besteht jedoch auch die Möglichkeit, die Risikoabsicherung von Unternehmen - beispielsweise über Bürgschaften oder andere geeignete Finanzierungskonditionen - an der Nachhaltigkeitsperformance der Unternehmen auszurichten. Der vorliegende vierstufige Leitfaden, den der WWF Deutschland und das Wuppertal Institut entwickelt haben, dient als Grundlage für die zielorientiertere Vergabe von Mitteln und deren praktische Umsetzung. Er baut auf der von der Europäischen Union entwickelten "Taxonomie" für nachhaltige Investitionen auf. Darin enthalten sind Grenzwerte, welche die Nachhaltigkeitsperformance wirtschaftlicher Aktivitäten definieren. Auf diese Weise lässt sich filtern, ob ein wirtschaftliches Vorhaben zukunftsfähig ist. Hierbei unterstützt der "Entscheidungsbaum" des Leitfadens die Anwendung der EU-Taxonomie als Regelwerk.

Description: Diese Kurzstudie ist Teil des Verbundvorhabens "Circular Economy als Innovationsmotor für eine klimaneutrale und ressourceneffiziente Wirtschaft (CEWI)" der Stiftung 2°, dem WWF Deutschland und dem Wuppertal Institut und hat zum Ziel, die Potenziale des Gebäudesektors und der dazugehörigen Wertschöpfung im Hinblick auf die Umsetzung von zirkulären Ansätzen zu analysieren und den Beitrag zur Ressourceneinsparung und dem Klimaschutz zu bewerten. Das Ergebnis dieser Kurzstudie leitet sich aus einem intensiven Bewertungsprozess verschiedener Maßnahmen-Cluster ab und besteht aus sechs Handlungsfeldern, die ein Potenzial für den Ausbau von Klimaneutralität und Ressourceneffizienz im Gebäudesektor aufweisen. Diese Handlungsfelder bilden die Grundlage für den weiteren Projektverlauf von CEWI, in dem Industrieakteure in Workshops gemeinsam Pilotprojekte modellieren werden.

Description: Diese Kurzstudie ist Teil des Verbundvorhabens "Circular Economy als Innovationsmotor für eine klimaneutrale und ressourceneffiziente Wirtschaft (CEWI)" der Stiftung 2°, dem WWF Deutschland und dem Wuppertal Institut und hat zum Ziel, die Potenziale des Automobilsektors und der dazugehörigen Wertschöpfung im Hinblick auf die Umsetzung von zirkulären Ansätzen zu analysieren und den Beitrag zur Ressourceneinsparung und dem Klimaschutz zu bewerten. Das Ergebnis dieser Kurzstudie leitet sich aus einem intensiven Bewertungsprozess verschiedener Maßnahmen-Cluster ab und besteht aus sechs Handlungsfeldern, die ein Potenzial für den Ausbau von Klimaneutralität und Ressourceneffizienz im Automobilsektor aufweisen. Diese Handlungsfelder bilden die Grundlage für den weiteren Projektverlauf von CEWI, in dem Akteure aus der Praxis in Workshops gemeinsam Pilotprojekte modellieren werden.

Description: Die Wirtschaftsförderung Region Stuttgart GmbH (WRS) unterstützt die Transformation der Region Stuttgart in Richtung Nachhaltigkeit und sieht die Bioökonomie als eine wichtige Strategie zu diesem Zweck. Die WRS hat das Wuppertal Institut mit dieser Kurzstudie mit dem Fokus auf die industrielle Bioökonomie beauftragt, um eine Informationsgrundlage für die Spezifikation weiterer Aktivitäten der WRS im Kontext der Bioökonomie zu schaffen. Die Studie gibt einen Überblick über definitorische Ansätze und Diskurslinien der Bioökonomie. Sie fasst Einschätzungen des deutschen Bioökonomierates zu Marktpotenzialen der Bioökonomie in verschiedenen Branchen zusammen, die u.a. für Automobil, Biotechnologie und IKT als gut eingeschätzt werden. Anschließend umreißt die Studie die Innovationsansätze Biomimikry und Biointelligenz. Für den Ansatz Biointelligenz zur biologischen Transformation der industriellen Wertschöpfung werden die in Studien von Dritten identifizierten Marktpotenziale der Biointelligenz zusammengefasst, u.a. in den Bereichen Unterstützungssysteme, Produktionssysteme/-technologien und Baumaterialien. Darüber hinaus stellt die Studie Schnittstellen relevanter Landesstrategien in Baden-Württemberg zu Bioökonomiethemen dar, die synergetisch genutzt werden könnten. Ergänzend gibt die Studie einen Überblick über die Akteurslandschaft in Baden-Württemberg. Der Überblick basiert insbesondere auf dem Bioökonomie Kompetenzatlas wissenschaftlicher Akteure, der von der Landeskoordinierungsstelle an der Universität Hohenheim herausgegeben wird, sowie einer Akteursanalyse aus dem Projekt "Bioökonomie in Baden-Württemberg", das am KIT durch das ITAS durchgeführt wurde und durch die BIOPRO Baden-Württemberg GmbH unterstützt wurde. Auf Basis dieser Informationssammlung entwirft die Studie weiterführende Fragen in Bezug auf mögliche weitere Aktivitäten der WRS im Kontext der Bioökonomie, u.a. die mögliche Nutzung von Innovationsansätzen aus dem Bereich der Living Lab und Reallaborforschung.

Description: Two thirds of today's world trade is based on global value chains and supply networks. Purely regional supply chains have become less important in recent decades. The effects of these globalised structures are manifold. On the one hand, they promote employment and generate prosperity. On the other hand, they are beset by extreme social, ecological and economic imbalances. The COVID-19 pandemic has demonstrated the fragility of existing supply chain systems. The lockdown continues to disrupt complex supply chains and many problems of existing production and consumption continue to worsen. COVID-19 is one example of the crises that can shake globally networked supply chains in the short term. Other crises, such as climate change, develop more insidiously and are less immediately recognisable. Different as they are, such crises have one thing in common: they highlight the vulnerability of global social and economic structures and illustrate the impact of global trade on the regions and people of the world. This is precisely where global sustainability strategy comes in - it aims to fundamentally reduce differences and inequalities in opportunities and quality of life. The COVID-19 pandemic has forced the entire world into upheaval, creating an opportunity to make sustainability a central political resilience strategy. In the wake of the Corona pandemic, the discussion about resilient communities has flared up. In order to guarantee supply in the face of such crises, these should be more strongly regional and circular in their economic approach and global and sustainable in their perspective. The aim should be sustainable, transparent, non-exploitative supply chains that guarantee the security of supply to cover basic needs and public services despite sudden changes and crises. This discussion paper draws a future scenario of globally cooperative, circular regional economies that fundamentally reduce global inequalities in opportunities and quality of life, while at the same time permanently preserving the natural foundations of life.

Description: Immer mehr Unternehmen verkünden, klimaneutral sein zu wollen und zahlreiche Firmen bieten bereits klimaneutrale Produkte oder Dienstleistungen an: Von der klimaneutralen Paketzustellung bis zur Flugreise. Doch was bedeuten die Neutralitätsziele der Unternehmen genau? Ist das gesetzte Ziel ambitioniert? Und welche Rolle spielt Offsetting, also der Ankauf von Klimaschutzzertifikaten und deren Anrechnung auf das eigene Klimaschutzziel? Die hinter den verkündeten Zielen stehenden Ansätze sind häufig nur schwer nachvollziehbar. Vor diesem Hintergrund gibt der vorliegende Zukunftsimpuls zehn Empfehlungen für die Festlegung und Umsetzung von Neutralitätszielen. Die Autorinnen und Autoren sprechen sich dabei unter anderem für die Nutzung einer robusten Datenbasis als Grundlage für Neutralitätsziele aus, betonen die Bedeutung einer transparenten Kommunikation und zeigen auf, welche Rolle Offsetting spielen sollte. So sollten angekaufte Klimaschutz-Zertifikate einen möglichst begrenzten Beitrag zur Zielerfüllung leisen und ausschließlich zum Ausgleich von Emissionen genutzt werden, die nicht reduziert oder vermieden werden können. Insgesamt sollten Neutralitätsziele nicht zum alleinigen Kriterium für ambitionierten Klimaschutz von Unternehmen gemacht werden, sie stellen vielmehr ein Baustein einer weitaus umfassenderen unternehmerischen Klimaschutzstrategie dar.

Description: With increasing world population and an unsettling resource scarcity in the back, sustainble consumption has moved to the foreground of political, economical and social discussions. One major school-of-thought is Circular Economy (CE), an approach summarizing various sustainable consumption activites under one roof. However, quantitative studies on the consumer are rare, yet crucial for a transfer from linear to circular consumption. This dissertation adds to literature by providing pioneer insights into consumer behavior in CE as an overarching concept, instead limiting research on singular subconcepts. Namely, four consumer activities are studied: recycling, upcycling, renting and sharing. In order to identify relevant insights for both academics and practitioners in CE, the research question ("what drives participation in CE?") is broken down into sub-hypotheses, which are addressed by three empirical studies. Using the SOR-Model (adaption Belk 1975) as overarching logic, the three studies deal with (1) the consumer (and their motivation) and situational stimuli (both (2) offline and (3) online). Respectively, three data sets are consulted to assess the sub-hypotheses and to identify overarching insights on how to accelerate consumer participation in CE, The research methodology employed ranges from a structured equation model (SEM), a random allocation field experiment during Fashion Week in Berlin to a discrete-choice model with best-worst scaling. The dissertation succeeds in revealing that (1) different activities in CE can be summarized in one latent variable, proving CE as a wholesome concept in consumer-related activities; that (2) Trust has a leveraging effect on participation in CE activities. Further, Trust can be enhanced offline via face-to-face interaction and online via third-party online attributes.; and that (3) experience in CE activities affects perception of online attributes, implying the need for adapted measures when dealing with CE-unexperienced consumers as compared to consumers with prior experience in CE activities.

Description: Industrial demand response can play an important part in balancing the intermittent production from a growing share of renewable energies in electricity markets. This paper analyses the role of aggregators - intermediaries between participants and power markets - in facilitating industrial demand response. Based on the results from semi-structured interviews with German demand response aggregators, as well as a wider stakeholder online survey, we examine the role of aggregators in overcoming barriers to industrial demand response. We find that a central role for aggregators is to raise awareness for the potentials of demand response, as well as to support implementation by engaging key actors in industrial companies. Moreover, we develop a taxonomy that helps analyse how the different functional roles of aggregators create economic value. We find that there is considerable heterogeneity in the kind of services that aggregators offer, many of which do create significant economic value. However, some of the functional roles that aggregators currently fill may become obsolete once market barriers to demand response are reduced or knowledge on demand response becomes more diffused.

Description: The study sheds light on the background of the prevention of plastic waste from packaging and disposable products by explaining the need for action, the environmental impacts and risks to human health. Experiences of the members of the PREVENT Waste Alliance and their partners in the prevention of plastic waste by multi-actor partnerships are presented by means of 17 best practice examples. Finally, the study gives recommendations for the reduction of plastic waste and the further work of the PREVENT Waste Alliance. These include success factors for waste prevention, necessary next steps and conclusions regarding the necessary political framework conditions.

Description: Die beiden mächtigsten Energiekonzerne in Deutschland fusionieren wechselseitig ihre Geschäftsfelder. Das Ergebnis wird eine bisher nie dagewesene Marktbeherrschung im Energiesektor darstellen. Die beiden Autoren beleuchten den Deal und kritisieren die Untätigkeit sämtlicher Aufsichtsbehörden.

Description: Prepaid-Stromzähler sind in Deutschland noch selten, bieten jedoch zukünftig einen interessanten Markt. Vor allem kleinere Anbieter, aber auch erste Regionalversorger kombinieren die Megatrends Digitalisierung und Energiewende und kreieren daraus neue Dienstleistungen. Zusammen mit IT-Firmen entwickeln sie daraus neue Geschäftsideen, die auch hinsichtlich sozialer Aspekte hohen Anforderungen genügen. Der Rollout von Smart Metering-Lösungen eröffnet zukünftig noch größere Chancen, durch Echtzeit-Datenerfassung den Energieverbrauch und damit auch Einsparpotenziale transparent zu machen. Hochaufgelöste Daten ermöglichen innovative Dienstleistungen und bringen die Kundenbeziehung auf eine neue Ebene.

Description: Mehr als sechs Millionen Tonnen Kunststoffabfälle fallen in Deutschland jährlich an, nur etwas weniger als die Hälfte kann werk- und rohstofflich genutzt werden, der Rest wird verbrannt. Gerade gemischte Kunststoffarten erschweren das Recycling. Hier bietet sich das chemische Recycling (Pyrolyse) an. Bei diesem Verfahren werden die Stoffe durch hohe Temperaturen zersetzt und in kleinere Moleküle aufgespalten. Diese lassen sich im Sinne der Kreislaufwirtschaft in neue Kunststoffe oder chemische Grundstoffe überführen. Die Schätzungen gehen von bis zu zwei Millionen Tonnen Kunststoffabfall jährlich aus, der auf diese Weise wiederverwendet werden könnte. Das vorliegende Diskussionspapier zeigt, dass Pyrolyse von gemischten Kunststoffabfällen die chemische Industrie sowie die Abfallwirtschaft klimafreundlicher gestalten kann. Im Papier geht das Autorenteam auf die Potenziale und Entwicklungsperspektiven für Nordrhein-Westfalen ein mit dem Ziel, wissenschaftliche Grundlagen für Investitionsentscheidungen und Projektentwicklung im Sinne der Kreislaufwirtschaft zu schaffen.

Description: Die Emscher-Lippe Region ist seit vielen Jahren von einer intensiven wirtschaftlichen Transformation geprägt. Die fortschreitende De-Industrialisierung bzw. die Neuorientierung der Industrie nach dem Wegfall der Kohle- und Stahlindustrie stellt regionale Entscheidungsträger vor große Herausforderungen, wenn es darum geht, der hohen Arbeitslosenquote zu begegnen, Beschäftigungsquoten zu sichern, mit der prekären Finanzsituation in den kommunalen Haushalten umzugehen und den Wirtschaftsstandort zu stabilisieren und neu aufzustellen. Der Strukturwandel der Region ist mit Schließung der letzten Steinkohle-Zeche Ende 2018 nicht abgeschlossen, sondern geht mit dem Kohleausstieg im Energiesektor in eine zweite Phase. Dies sollte auch als Chance verstanden werden, den Wirtschaftsstandort Emscher-Lippe mit seinen energiereichen Industrien innovativ neu zu gestalten und die Region sowohl energetisch, als auch stofflich von der Nutzung fossiler Träger abzukoppeln. Eine wichtige Säule der regionalen Wirtschaftsförderung besteht darin, strategische Netzwerke und regionale Wertschöpfungsketten zu stärken, um die in der Region ansässigen (mittelständischen) Unternehmen zu unterstützen und den Strukturwandel innerhalb der dominierenden Industrien aus den Bereichen Energieerzeugung und chemischer Industrie zu begleiten. Die vorliegende Studie bereitet auf, welche Bedeutung die Wasserstoffwirtschaft in der Emscher-Lippe Region in diesem Zusammenhang derzeit spielt und zukünftig spielen könnte.

Description: Die Europäische Union (EU) hat erkannt, dass das Ziel der Klimaneutralität bis 2050 ein zentraler Innovations- und Wachstumsmotor für Industrie und Wirtschaft in der EU sein kann. Neben großen Chancen stellt dies die europäische Wirtschaft und überwiegend die besonders emissionsintensiven sowie im international starkem Wettbewerb stehenden Grundstoffindustrien auch vor erhebliche Herausforderungen. Eine integrierte Klima- und Industriestrategie ist für den Klimaschutz von zentraler Bedeutung, da auf die Produktion von Stahl, Zement, Grundstoffchemikalien, Glas, Papier und anderen Materialien in der EU und weltweit rund 20 Prozent der gesamten Treibhausgasemissionen entfallen. Auch in einer treibhausgasneutralen Zukunft kann auf diese Materialien nicht verzichten werden. Zugleich ist die emissionsfreie Herstellung der Materialien technologisch sowie mit Blick auf die dafür erforderlichen Infrastrukturen besonders herausfordernd. Dies gilt vor allem für die Frage woher die hohen benötigten Mengen an grüner Energie - insbesondere Strom und Wasserstoff - zu wettbewerbsfähigen Preisen kommen sollen. Analysen zeigen, dass trotz erheblicher Kosten bei der Prozessumstellung die Kosten der Transformation der Grundstoffindustrie für die Gesellschaft insgesamt tragbar sind. Denn bezogen auf die Endprodukte betragen die Mehrkosten meist nur wenige Prozentpunkte; die Preise von Rohstahl oder Zement dagegen würden sich zwischen einem Drittel und 100 Prozent verteuern. Da fast alle Grundstoffhersteller in starker Weltmarktkonkurrenz stehen, können sie die Investitionen in eine klimaneutrale Produktion und die benötigten Energieinfrastrukturen aber nicht ohne Unterstützung tragen. Das vorliegende Papier skizziert ein integriertes Klima-Industriepolitikpaket, das der EU ermöglichen kann, die bestehende technologische Führung in vielen dieser Industrien zielgerichtet zum Aufbau einer treibhausgasneutralen Grundstoffindustrie zu nutzen.

Description: The concept Material Input per Service Unit (MIPS) was developed 20 years ago as a measure for the overall natural resource use of products and services. The material intensity analysis is used to calculate the material footprint of any economic activities in production and consumption. Environmental assessment has developed extensive databases for life cycle inventories, which can additionally be adopted for material intensity analysis. Based on practical experience in measuring material footprints on the micro level, this paper presents the current state of research and methodology development: it shows the international discussions on the importance of accounting methodologies to measure progress in resource efficiency. The MIPS approach is presented and its micro level application for assessing value chains, supporting business management, and operationalizing sustainability strategies is discussed. Linkages to output-oriented Life Cycle Assessment as well as to Material Flow Analysis (MFA) at the macro level are pointed out. Finally we come to the conclusion that the MIPS approach provides relevant knowledge on resource and energy input at the micro level for fact-based decision-making in science, policy, business, and consumption.

Description: Increasing concerns regarding the world's natural resources and sustainability continue to be a major issue for global development. As a result several political initiatives and strategies for green or resource-efficient growth both on national and international levels have been proposed. A core element of these initiatives is the promotion of an increase of resource or material productivity. This dissertation examines material productivity developments in the OECD and BRICS countries between 1980 and 2008. By applying the concept of convergence stemming from economic growth theory to material productivity the analysis provides insights into both aspects: material productivity developments in general as well as potentials for accelerated improvements in material productivity which consequently may allow a reduction of material use globally.The results of the convergence analysis underline the importance of policy-making with regard to technology and innovation policy enabling the production of resource-efficient products and services as well as technology transfer and diffusion.​

Description: In globalen Energieszenarien spielt die Windenergie eine wichtige Rolle für den zukünftigen Strommix. Die Technologie hat sich bewährt und die Windbranche entwickelt sich zu einer reifen Industrie. Während der bisherige Ausbau der Windenergie stark von deutschen und europäischen Unternehmen bestimmt wurde, sind nun chinesische und amerikanische Unternehmen auf dem Weltmarkt weitgehend führend. Das vorliegende Buch untersucht daher maßgebende Erfolgsfaktoren der deutschen Windbranche auf dem internationalen Markt und konzentriert sich auf zwei Bereiche: Zum einen wird die Anwendbarkeit der Erfolgsfaktorenforschung - ein Konzept aus dem strategischen Management - einer kritischen Prüfung unterzogen. Zum anderen werden in einer qualitativen Analyse Erfolgsfaktoren diskutiert, die für die vergleichsweise junge Branche wichtig sind. Entscheidend ist es demnach, Lösungen, Strategien oder Technologieentwicklungen aus anderen Branchen zu transferieren (Transferkompetenz) und eine gemeinsame Technologieentwicklung in der Wertschöpfungskette (Joint Development) zu etablieren.

Description: Die systematisch-intentionale Förderung von innovativen Unternehmensgründungen aus Universitäten und Forschungseinrichtungen bedarf einer ergänzenden Neuausrichtung, will sie sich zukünftig als noch legitimierter und effizienter erweisen. Dabei wird im Rahmen einer integrativen Gründungs- und Innovationsförderung aus Universitäten und Forschungseinrichtungen eine Programmatik entworfen, die sich insbesondere in Prototypen komplexer Zukunftsinnovationen manifestiert.

Description: Aufgrund der Reform des Erneuerbare-Energien-Gesetzes soll die Förderhöhe für Strom aus Photovoltaik-Freiflächenanlagen nun wettbewerblich über Ausschreibungen ermittelt werden. Dafür muss eine entsprechende Rechtsverordnung geschaffen werden. Für die Eckpunkte eines solchen Ausschreibungsdesigns hat das Bundeswirtschaftsministerium eine öffentliche Konsultation in Gang gesetzt, zu der auch das Wuppertal Institut zusammen mit dem Fraunhofer-Institut für Solare Energiesysteme ISE und weiteren Unterstützern eine Stellungnahme abgegeben haben. Ihre Empfehlung ist, die Ressourcen-/bzw. Landnutzung von PV-Freiflächenanlagen als wesentliches Kriterium in die Förderung einzubeziehen. Vor dem Hintergrund eines erhöhten Nutzungsdrucks auf den ländlichen Raum weisen sie darauf hin, dass ihr angestrebter Ausbau zu ökonomischen, ökologischen, politischen und gesellschaftlichen Konfliktkonstellationen führen könnte. Zugleich machen sie deutlich, dass es zur herkömmlichen Technologie eine Alternative, die Agrophotovoltaik-Freiflächentechnologie gibt, ein Anbausystem zur Produktion von landwirtschaftlichen Gütern unterhalb von PV-Modulen. Sie ermöglicht die simultane Erzeugung von PV-Strom und die Produktion von Nahrungsmitteln. Folgerichtig wird empfohlen, nicht die PV-Anlagen, sondern Freiflächen-Technologien zum Gegenstand der geplanten Pilotausschreibungen zu machen. Die Ausweitung herkömmlicher Anlagen sollte sich auf unterdurchschnittlich fruchtbare Ackerflächen beschränken.

Description: There are a variety of economic and ecological benefits to increased resource efficiency. Social, institutional and technical innovations can all contribute towards efficiency increases. Companies face different hurdles in fostering such innovation. Small and medium-sized companies are subject to specific constraints that may prevent them from benefiting from innovation-induced resource efficiency improvements. Qualitative interviews were conducted among German small and medium-sized enterprises (SMEs) and intermediaries to identify barriers for resource efficiency innovations and to elaborate a policy mix at the federal level that could help SMEs to overcome these. We found five major barriers to resource efficiency innovations in German SMEs, comprising deficits in innovation culture, inter-firm cooperation along the value chain, finance, awareness and take-up of government funds. We propose a distinct policy mix as a response to this situation. The policy mix comprises the interlocking and synergistic elements of government funding schemes, innovation agents and innovation laboratories.

Description: Although there are already some qualification offers available for enterprises to support resource efficiency innovations, the high potentials that can be identified especially for small and medium sized enterprises (SMEs) have not been activated until now. As successful change lies in the hands of humans, the main aim of vocational education has to be the promotion of organisational and cultural changes in the enterprises. As there is already a small but increasing number of enterprises that perform very well in resource efficiency innovations one question arises: What are typical characteristics of those enterprises? Leaning on a good-practice approach, the project "ResourceCulture" is going to prove or falsify the hypothesis that enterprises being successful with resource efficiency innovations have a specific culture of trust, which substantially contributes to innovation processes, or even initially enables them. Detailed empirical field research will light up which correlations between resource efficiency, innovation and cultures of trust can be found and will offer important aspects for the improvement of management instruments and qualification concepts for workplace training. The project seizes qualification needs that were likewise mentioned by enterprises and consultants, regarding the implementation of resource efficiency. This article - based on first empirical field research results - derives preliminary indications for the design of the qualification module for the target groups resource efficiency consultants and managers. On this basis and in order to implement "ResourceCulture" conceptual and methodological starting points for workplace training are outlined.

Description: Die Krisen der internationalen Finanzmärkte waren 1998 noch nicht Realität, Atomkraft galt in Deutschland unter der Regierung Kohl immer noch als Zukunftsoption für die kommenden Jahrzehnte und für eine Bundespolitik in Richtung Energiewende war weit und breit kein gesellschaftlicher Konsens in Sicht. Dennoch gab es schon vor der Energiewende Projekte, die sich der Steigerung der Energieeffizienz verschrieben hatten. Mit kombinierten Einspar- und Solarkraftwerken, die an Schulen mit finanzieller Bürgerbeteiligungen entstehen, sollte der Weg zu einer umweltverträglichen Energieversorgung für vier Schulen in Nordrhein-Westfalen eingeschlagen werden. Wie der vorliegende Projektbericht zeigt, konnten die Ziele des Vorhabens erreicht werden: Steigerung der Endenergieeffizienz, verstärkte Nutzung erneuerbarer Energien und der Einsatz dezentraler Kraft-Wärme-Kopplung.

Description: The food and agricultural sector will face numerous challenges in the next decades, arising from changing global production and consumption patterns, which currently go along with high resource use, causing ecological and socio-economic impacts. The aim of this paper is to illustrate and evaluate the practical applicability of the Hot Spot Analysis methodology in the context of supply chain management in companies. The HSA is a method to identify social and ecological problems along the entire life cycle of a product. Special emphasis is put on a customized implementation in the value chain beef of McDonald's Germany. The HSA of McDonald's beef value chain shows that the main ecological problems arise in the phase of raw material extraction, whereas the main social problems can be identified in the phase of slaughtering. Finally, the paper shows potentials and shortcomings of such a customized application and how the results can be implemented in the sustainability management of a company.

Description: Critical metals are in great demand by the electrical and electronics industry, so waste electrical and eletronic equipment represents a significant source of secondary raw materials. Owing to low recycling rates and the concomitant supply risks associated with critical metals, the closure of the material cycles is highly relevant to the German economy. Losses of these metals occur from collection until their material recovery, along the entire disposal chain of waste electrical and electronic equipment. This paper develops planning criteria for the design of collection groups to achieve higher recovery amounts of such metals. The aim is to clarify what amounts of metals exist, both product-specific and on the market, how the dismantling of the products is constructed and how collection groups can be arranged with planning criteria oriented towards resource conservation. The analysis is a snapshot using the example of indium and selected products. A procedure is presented and findings identified which are transferable to various critical metals and to waste electrical and electronic equipment. The results show that grouping of products according to resource amounts and the dismantling effort enables forward-looking and resource-efficient planning of the treatment of every single collection group.

Description: This paper reflects the socio-economic power of renewable energy production cooperatives for a wider energy system transformation in Germany. Energy cooperatives have turned into important supporters of renewable and decentralised energy structures, due to their strong growth since the year 2006, their participation in local renewable energy projects and their democratic awareness. The cooperative form of coordinating local renewable energy projects applies to a decentralised energy system that is managed by many smaller firms - a system concept that is preferred by the majority of German citizens. However, there is not enough knowledge to understand to what extent this organisational form is able to unify a broad group of actors in promoting a renewable energy system (societal power) and to gather capital for elaborating renewable energy supply structures (economic power). The reflection is based on an empirical assessment of all energy cooperatives that were registered in Germany before 31st December 2013. Their growth dynamic and their business approaches are discussed. A special focus lies on renewable energy production cooperatives. The study presents the development of their members, their capital, their profit and loss, as well as their investment intensity over a timeframe of three years (2010-2012). The socio-economic potential of renewable energy production cooperatives for supporting a renewable energy system is discussed against the background of empirical results.

Description: Die elektrische Energieversorgung von Kommunen wird nach einer Privatisierungswelle Ende der 1990er Jahren mehr und mehr wieder in kommunale Hand zurückgeholt und Kommunen entdecken Chancen und Möglichkeiten, die sich dadurch ergeben. In Nordhessen ist ein Trend der Rekommunalisierung erkennbar durch die Neugründung von Stadt- und Gemeindewerken zur Elektrizitätsversorgung oder deren Weiterentwicklung. Dieser Prozess wird unter anderem durch die Städtische Werke Aktiengesellschaft, Kassel angetrieben, die als Partner die Kommunen insbesondere beim Rückkauf der Stromnetze, der Gründung von eigenen Stadtwerken und dem Vertrieb von Energieprodukten unterstützen. Gleichzeitig ist seit Mitte Dezember 2013 der Energieversorger E.ON Mitte AG von den nordhessischen und südniedersächsischen Landkreisen (zurück)gekauft und als Energie aus der Mitte GmbH & Co. KG (EAM) wieder in kommunaler Hand. Vor dem Hintergrund dieser Entwicklungen untersucht die vorliegende Arbeit den Prozess der Rekommunalisierung der Energieversorgung in Nordhessen und beschreibt die damit verbundenen Herausforderungen für die Kommunen. Am Beispiel von drei Kommunalwerken in Nordhessen wird die Fragestellung untersucht, wie der Prozess der Rekommunalisierung gestaltet werden kann und welche Teilprozesse wie Netzrückkauf, Vertrieb und Erzeugung mit welchen Herausforderungen verbunden sind. Auch die Frage, welche Bedeutung die Rekommunalisierung von E.ON Mitte AG hat, wird untersucht. Um möglichst viel Wissen über die Rekommunalisierungsvorgänge von beteiligten Personen zu erlangen, wurde das Erhebungsverfahren der leitfadengestützten Experteninterviews ausgewählt. Die Auswertung der erhobenen Daten erfolgte mit der Methodik Grounded Theory.

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cressey, Daniel -- England -- Nature. 2014 Apr 10;508(7495):159. doi: 10.1038/508159a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24717487" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cressey, Daniel -- England -- Nature. 2014 Mar 6;507(7490):18. doi: 10.1038/507018a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24598618" target="_blank"〉PubMed〈/a〉

Description: The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a post-fusion state. As the sole viral antigen on the HIV-1 virion surface, Env is both the target of neutralizing antibodies and a focus of vaccine efforts. Here we report the structure at 3.5 A resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22. This structure reveals the pre-fusion conformation of gp41, indicates rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition. Pre-fusion gp41 encircles amino- and carboxy-terminal strands of gp120 with four helices that form a membrane-proximal collar, fastened by insertion of a fusion peptide-proximal methionine into a gp41-tryptophan clasp. Spike rearrangements required for entry involve opening the clasp and expelling the termini. N-linked glycosylation and sequence-variable regions cover the pre-fusion closed spike; we used chronic cohorts to map the prevalence and location of effective HIV-1-neutralizing responses, which were distinguished by their recognition of N-linked glycan and tolerance for epitope-sequence variation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348022/" 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/PMC4348022/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pancera, Marie -- Zhou, Tongqing -- Druz, Aliaksandr -- Georgiev, Ivelin S -- Soto, Cinque -- Gorman, Jason -- Huang, Jinghe -- Acharya, Priyamvada -- Chuang, Gwo-Yu -- Ofek, Gilad -- Stewart-Jones, Guillaume B E -- Stuckey, Jonathan -- Bailer, Robert T -- Joyce, M Gordon -- Louder, Mark K -- Tumba, Nancy -- Yang, Yongping -- Zhang, Baoshan -- Cohen, Myron S -- Haynes, Barton F -- Mascola, John R -- Morris, Lynn -- Munro, James B -- Blanchard, Scott C -- Mothes, Walther -- Connors, Mark -- Kwong, Peter D -- AI0678501/AI/NIAID NIH HHS/ -- AI100645/AI/NIAID NIH HHS/ -- P01 GM056550/GM/NIGMS NIH HHS/ -- P01-GM56550/GM/NIGMS NIH HHS/ -- P30 AI050410/AI/NIAID NIH HHS/ -- R01 GM098859/GM/NIGMS NIH HHS/ -- R01-GM098859/GM/NIGMS NIH HHS/ -- R21 AI100696/AI/NIAID NIH HHS/ -- R21-AI100696/AI/NIAID NIH HHS/ -- UL1 TR000142/TR/NCATS NIH HHS/ -- UM1 AI100645/AI/NIAID NIH HHS/ -- ZIA AI005023-13/Intramural NIH HHS/ -- ZIA AI005024-13/Intramural NIH HHS/ -- England -- Nature. 2014 Oct 23;514(7523):455-61. doi: 10.1038/nature13808. Epub 2014 Oct 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. ; Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Sandringham, Johannesburg 2131, South Africa. ; Departments of Medicine, Epidemiology, Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics and Immunology, Duke University School of Medicine, and the Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, North Carolina 27710, USA. ; 1] Center for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service (NHLS), Sandringham, Johannesburg 2131, South Africa [2] University of the Witwatersrand, Braamfontein, Johannesburg 2000, South Africa [3] Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban 4041, South Africa. ; Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut 06536, USA. ; Department of Physiology and Biophysics, Weill Cornell Medical College of Cornell University, New York, New York 10021, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25296255" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jones, Nicola -- England -- Nature. 2014 Feb 6;506(7486):16-7. doi: 10.1038/506016a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499897" target="_blank"〉PubMed〈/a〉

Description: Autophagy, the process by which proteins and organelles are sequestered in double-membrane structures called autophagosomes and delivered to lysosomes for degradation, is critical in diseases such as cancer and neurodegeneration. Much of our understanding of this process has emerged from analysis of bulk cytoplasmic autophagy, but our understanding of how specific cargo, including organelles, proteins or intracellular pathogens, are targeted for selective autophagy is limited. Here we use quantitative proteomics to identify a cohort of novel and known autophagosome-enriched proteins in human cells, including cargo receptors. Like known cargo receptors, nuclear receptor coactivator 4 (NCOA4) was highly enriched in autophagosomes, and associated with ATG8 proteins that recruit cargo-receptor complexes into autophagosomes. Unbiased identification of NCOA4-associated proteins revealed ferritin heavy and light chains, components of an iron-filled cage structure that protects cells from reactive iron species but is degraded via autophagy to release iron through an unknown mechanism. We found that delivery of ferritin to lysosomes required NCOA4, and an inability of NCOA4-deficient cells to degrade ferritin led to decreased bioavailable intracellular iron. This work identifies NCOA4 as a selective cargo receptor for autophagic turnover of ferritin (ferritinophagy), which is critical for iron homeostasis, and provides a resource for further dissection of autophagosomal cargo-receptor connectivity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180099/" 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/PMC4180099/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mancias, Joseph D -- Wang, Xiaoxu -- Gygi, Steven P -- Harper, J Wade -- Kimmelman, Alec C -- GM070565/GM/NIGMS NIH HHS/ -- GM095567/GM/NIGMS NIH HHS/ -- P50 CA127003/CA/NCI NIH HHS/ -- R01 CA157490/CA/NCI NIH HHS/ -- R01 GM070565/GM/NIGMS NIH HHS/ -- R01 GM095567/GM/NIGMS NIH HHS/ -- R01CA157490/CA/NCI NIH HHS/ -- England -- Nature. 2014 May 1;509(7498):105-9. doi: 10.1038/nature13148. Epub 2014 Mar 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA [2] Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA [3] Harvard Radiation Oncology Program, Boston, Massachusetts 02115, USA [4] Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. ; Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. ; Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24695223" target="_blank"〉PubMed〈/a〉

Description: The neutralizing antibody response to influenza virus is dominated by antibodies that bind to the globular head of haemagglutinin, which undergoes a continuous antigenic drift, necessitating the re-formulation of influenza vaccines on an annual basis. Recently, several laboratories have described a new class of rare influenza-neutralizing antibodies that target a conserved site in the haemagglutinin stem. Most of these antibodies use the heavy-chain variable region VH1-69 gene, and structural data demonstrate that they bind to the haemagglutinin stem through conserved heavy-chain complementarity determining region (HCDR) residues. However, the VH1-69 antibodies are highly mutated and are produced by some but not all individuals, suggesting that several somatic mutations may be required for their development. To address this, here we characterize 197 anti-stem antibodies from a single donor, reconstruct the developmental pathways of several VH1-69 clones and identify two key elements that are required for the initial development of most VH1-69 antibodies: a polymorphic germline-encoded phenylalanine at position 54 and a conserved tyrosine at position 98 in HCDR3. Strikingly, in most cases a single proline to alanine mutation at position 52a in HCDR2 is sufficient to confer high affinity binding to the selecting H1 antigen, consistent with rapid affinity maturation. Surprisingly, additional favourable mutations continue to accumulate, increasing the breadth of reactivity and making both the initial mutations and phenylalanine at position 54 functionally redundant. These results define VH1-69 allele polymorphism, rearrangement of the VDJ gene segments and single somatic mutations as the three requirements for generating broadly neutralizing VH1-69 antibodies and reveal an unexpected redundancy in the affinity maturation process.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Pappas, Leontios -- Foglierini, Mathilde -- Piccoli, Luca -- Kallewaard, Nicole L -- Turrini, Filippo -- Silacci, Chiara -- Fernandez-Rodriguez, Blanca -- Agatic, Gloria -- Giacchetto-Sasselli, Isabella -- Pellicciotta, Gabriele -- Sallusto, Federica -- Zhu, Qing -- Vicenzi, Elisa -- Corti, Davide -- Lanzavecchia, Antonio -- U19 AI-057266/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Dec 18;516(7531):418-22. doi: 10.1038/nature13764. Epub 2014 Oct 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Insitute for Research in Biomedicine, Universita della Svizzera Italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland. ; Department of Infectious Diseases and Vaccines MedImmune LLC, One MedImmune Way, Gaithersburg, Maryland 20878, USA. ; Viral Pathogens and Biosafety Unit, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. ; Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland. ; Unit of Preventive Medicine, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy. ; 1] Insitute for Research in Biomedicine, Universita della Svizzera Italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland [2] Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland [3]. ; 1] Insitute for Research in Biomedicine, Universita della Svizzera Italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland [2] Insitute for Microbiology, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25296253" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mallapaty, Smriti -- England -- Nature. 2014 Feb 20;506(7488):279. doi: 10.1038/506279a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24553222" target="_blank"〉PubMed〈/a〉

Description: Genome instability is central to ageing, cancer and other diseases. It is not only proteins involved in DNA replication or the DNA damage response (DDR) that are important for maintaining genome integrity: from yeast to higher eukaryotes, mutations in genes involved in pre-mRNA splicing and in the biogenesis and export of messenger ribonucleoprotein (mRNP) also induce DNA damage and genome instability. This instability is frequently mediated by R-loops formed by DNA-RNA hybrids and a displaced single-stranded DNA. Here we show that the human TREX-2 complex, which is involved in mRNP biogenesis and export, prevents genome instability as determined by the accumulation of gamma-H2AX (Ser-139 phosphorylated histone H2AX) and 53BP1 foci and single-cell electrophoresis in cells depleted of the TREX-2 subunits PCID2, GANP and DSS1. We show that the BRCA2 repair factor, which binds to DSS1, also associates with PCID2 in the cell. The use of an enhanced green fluorescent protein-tagged hybrid-binding domain of RNase H1 and the S9.6 antibody did not detect R-loops in TREX-2-depleted cells, but did detect the accumulation of R-loops in BRCA2-depleted cells. The results indicate that R-loops are frequently formed in cells and that BRCA2 is required for their processing. This link between BRCA2 and RNA-mediated genome instability indicates that R-loops may be a chief source of replication stress and cancer-associated instability.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhatia, Vaibhav -- Barroso, Sonia I -- Garcia-Rubio, Maria L -- Tumini, Emanuela -- Herrera-Moyano, Emilia -- Aguilera, Andres -- England -- Nature. 2014 Jul 17;511(7509):362-5. doi: 10.1038/nature13374. Epub 2014 Jun 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centro Andaluz de Biologia Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla, Avenida Americo Vespucio s/n, 41092 Seville, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24896180" target="_blank"〉PubMed〈/a〉

Description: Targeted genome editing by artificial nucleases has brought the goal of site-specific transgene integration and gene correction within the reach of gene therapy. However, its application to long-term repopulating haematopoietic stem cells (HSCs) has remained elusive. Here we show that poor permissiveness to gene transfer and limited proficiency of the homology-directed DNA repair pathway constrain gene targeting in human HSCs. By tailoring delivery platforms and culture conditions we overcame these barriers and provide stringent evidence of targeted integration in human HSCs by long-term multilineage repopulation of transplanted mice. We demonstrate the therapeutic potential of our strategy by targeting a corrective complementary DNA into the IL2RG gene of HSCs from healthy donors and a subject with X-linked severe combined immunodeficiency (SCID-X1). Gene-edited HSCs sustained normal haematopoiesis and gave rise to functional lymphoid cells that possess a selective growth advantage over those carrying disruptive IL2RG mutations. These results open up new avenues for treating SCID-X1 and other diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4082311/" 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/PMC4082311/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Genovese, Pietro -- Schiroli, Giulia -- Escobar, Giulia -- Di Tomaso, Tiziano -- Firrito, Claudia -- Calabria, Andrea -- Moi, Davide -- Mazzieri, Roberta -- Bonini, Chiara -- Holmes, Michael C -- Gregory, Philip D -- van der Burg, Mirjam -- Gentner, Bernhard -- Montini, Eugenio -- Lombardo, Angelo -- Naldini, Luigi -- 249845/European Research Council/International -- TGT11D02/Telethon/Italy -- England -- Nature. 2014 Jun 12;510(7504):235-40. doi: 10.1038/nature13420. Epub 2014 May 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉TIGET, San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy. ; 1] TIGET, San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy [2] Vita Salute San Raffaele University, 20132 Milan, Italy. ; 1] TIGET, San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy [2] The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Queensland 4102, Australia. ; Experimental Hematology Unit, San Raffaele Scientific Institute, 20132 Milan, Italy. ; Sangamo BioSciences Inc., Richmond, California 94804, USA. ; Department of Immunology Erasmus MC, University Medical Center, 3015 Rotterdam, The Netherlands. ; 1] TIGET, San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scientific Institute, 20132 Milan, Italy [2] Vita Salute San Raffaele University, 20132 Milan, Italy [3].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24870228" target="_blank"〉PubMed〈/a〉

Description: The TRIM37 (also known as MUL) gene is located in the 17q23 chromosomal region, which is amplified in up to approximately 40% of breast cancers. TRIM37 contains a RING finger domain, a hallmark of E3 ubiquitin ligases, but its protein substrate(s) is unknown. Here we report that TRIM37 mono-ubiquitinates histone H2A, a chromatin modification associated with transcriptional repression. We find that in human breast cancer cell lines containing amplified 17q23, TRIM37 is upregulated and, reciprocally, the major H2A ubiquitin ligase RNF2 (also known as RING1B) is downregulated. Genome-wide chromatin immunoprecipitation (ChIP)-chip experiments in 17q23-amplified breast cancer cells identified many genes, including multiple tumour suppressors, whose promoters were bound by TRIM37 and enriched for ubiquitinated H2A. However, unlike RNF2, which is a subunit of polycomb repressive complex 1 (PRC1), we find that TRIM37 associates with polycomb repressive complex 2 (PRC2). TRIM37, PRC2 and PRC1 are co-bound to specific target genes, resulting in their transcriptional silencing. RNA-interference-mediated knockdown of TRIM37 results in loss of ubiquitinated H2A, dissociation of PRC1 and PRC2 from target promoters, and transcriptional reactivation of silenced genes. Knockdown of TRIM37 in human breast cancer cells containing amplified 17q23 substantially decreases tumour growth in mouse xenografts. Conversely, ectopic expression of TRIM37 renders non-transformed cells tumorigenic. Collectively, our results reveal TRIM37 as an oncogenic H2A ubiquitin ligase that is overexpressed in a subset of breast cancers and promotes transformation by facilitating silencing of tumour suppressors and other genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269325/" 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/PMC4269325/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhatnagar, Sanchita -- Gazin, Claude -- Chamberlain, Lynn -- Ou, Jianhong -- Zhu, Xiaochun -- Tushir, Jogender S -- Virbasius, Ching-Man -- Lin, Ling -- Zhu, Lihua J -- Wajapeyee, Narendra -- Green, Michael R -- R01 GM033977/GM/NIGMS NIH HHS/ -- R01GM033977/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Dec 4;516(7529):116-20. doi: 10.1038/nature13955. Epub 2014 Nov 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA [2] Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. ; CEA/DSV/iRCM/LEFG, Genopole G2, and Universite Paris Diderot, 91057 Evry, France. ; Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. ; Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut 06877, USA. ; 1] Programs in Gene Function and Expression and Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA [2] Program in Bioinformatics and Integrative Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA. ; Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470042" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Van Noorden, Richard -- England -- Nature. 2014 Feb 6;506(7486):17. doi: 10.1038/506017a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24499898" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2014 Oct 2;514(7520):6. doi: 10.1038/514006a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25279880" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mansell, Warren -- Carey, Timothy A -- England -- Nature. 2014 Sep 11;513(7517):172. doi: 10.1038/513172e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Manchester, UK. ; Centre for Remote Health, Alice Springs, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25209790" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhutta, Zulfiqar Ahmed -- England -- Nature. 2014 Jul 17;511(7509):285-7. doi: 10.1038/511285a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center of Excellence in Women and Child Health at the Aga Khan University in Karachi, Pakistan, and co-director of the Sick Kids Center for Global Child Health in Toronto, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25030151" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Geraedts, Joep -- England -- Nature. 2014 Jun 19;510(7505):340. doi: 10.1038/510340d.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Maastricht University, the Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24943949" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crooks, Richard M -- England -- Nature. 2014 Jan 9;505(7482):165-6. doi: 10.1038/505165a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712-1224, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24402276" target="_blank"〉PubMed〈/a〉

Description: Fertilization occurs when sperm and egg recognize each other and fuse to form a new, genetically distinct organism. The molecular basis of sperm-egg recognition is unknown, but is likely to require interactions between receptor proteins displayed on their surface. Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. Here we identify folate receptor 4 (Folr4) as the receptor for Izumo1 on the mouse egg, and propose to rename it Juno. We show that the Izumo1-Juno interaction is conserved within several mammalian species, including humans. Female mice lacking Juno are infertile and Juno-deficient eggs do not fuse with normal sperm. Rapid shedding of Juno from the oolemma after fertilization suggests a mechanism for the membrane block to polyspermy, ensuring eggs normally fuse with just a single sperm. Our discovery of an essential receptor pair at the nexus of conception provides opportunities for the rational development of new fertility treatments and contraceptives.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998876/" 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/PMC3998876/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bianchi, Enrica -- Doe, Brendan -- Goulding, David -- Wright, Gavin J -- 098051/Wellcome Trust/United Kingdom -- England -- Nature. 2014 Apr 24;508(7497):483-7. doi: 10.1038/nature13203. Epub 2014 Apr 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. ; Mouse Production Team, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK. ; Electron and Advanced Light Microscopy Suite, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24739963" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Crous, Casparus J -- England -- Nature. 2014 Sep 4;513(7516):7. doi: 10.1038/513007a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25186869" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bianco, Paolo -- Cattaneo, Elena -- De Luca, Michele -- Pani, Luca -- England -- Nature. 2014 Feb 27;506(7489):434. doi: 10.1038/506434c.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Sapienza University of Rome, Italy. ; University of Milan, Italy. ; University of Modena and Reggio Emilia, Modena, Italy. ; Italian Medicines Agency (AIFA), Rome, Italy.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24572414" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Biller-Andorno, Nikola -- England -- Nature. 2014 Jul 10;511(7508):155. doi: 10.1038/511155a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25008510" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Biba, Erin -- England -- Nature. 2014 Nov 20;515(7527):S124-5. doi: 10.1038/515S124a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25407711" target="_blank"〉PubMed〈/a〉

Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bollen, Mathieu -- England -- Nature. 2015 Jan 1;517(7532):29-30. doi: 10.1038/nature14080. Epub 2014 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Biosignaling and Therapeutics, Department of Cellular and Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25487157" target="_blank"〉PubMed〈/a〉

Description: Endocytosis is required for internalization of micronutrients and turnover of membrane components. Endophilin has been assigned as a component of clathrin-mediated endocytosis. Here we show in mammalian cells that endophilin marks and controls a fast-acting tubulovesicular endocytic pathway that is independent of AP2 and clathrin, activated upon ligand binding to cargo receptors, inhibited by inhibitors of dynamin, Rac, phosphatidylinositol-3-OH kinase, PAK1 and actin polymerization, and activated upon Cdc42 inhibition. This pathway is prominent at the leading edges of cells where phosphatidylinositol-3,4-bisphosphate-produced by the dephosphorylation of phosphatidylinositol-3,4,5-triphosphate by SHIP1 and SHIP2-recruits lamellipodin, which in turn engages endophilin. This pathway mediates the ligand-triggered uptake of several G-protein-coupled receptors such as alpha2a- and beta1-adrenergic, dopaminergic D3 and D4 receptors and muscarinic acetylcholine receptor 4, the receptor tyrosine kinases EGFR, HGFR, VEGFR, PDGFR, NGFR and IGF1R, as well as interleukin-2 receptor. We call this new endocytic route fast endophilin-mediated endocytosis (FEME).〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Boucrot, Emmanuel -- Ferreira, Antonio P A -- Almeida-Souza, Leonardo -- Debard, Sylvain -- Vallis, Yvonne -- Howard, Gillian -- Bertot, Laetitia -- Sauvonnet, Nathalie -- McMahon, Harvey T -- U105178805/Medical Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- England -- Nature. 2015 Jan 22;517(7535):460-5. doi: 10.1038/nature14067. Epub 2014 Dec 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK [2] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK. ; MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. ; 1] Institute of Structural and Molecular Biology, University College London &Birkbeck College, London WC1E 6BT, UK [2] Department of Biology, Ecole Normale Superieure de Cachan, 94235 Cachan, France. ; Institut Pasteur, Unite de Pathogenie Moleculaire Microbienne, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25517094" target="_blank"〉PubMed〈/a〉

Description: The kinetochore is the crucial apparatus regulating chromosome segregation in mitosis and meiosis. Particularly in meiosis I, unlike in mitosis, sister kinetochores are captured by microtubules emanating from the same spindle pole (mono-orientation) and centromeric cohesion mediated by cohesin is protected in the following anaphase. Although meiotic kinetochore factors have been identified only in budding and fission yeasts, these molecules and their functions are thought to have diverged earlier. Therefore, a conserved mechanism for meiotic kinetochore regulation remains elusive. Here we have identified in mouse a meiosis-specific kinetochore factor that we termed MEIKIN, which functions in meiosis I but not in meiosis II or mitosis. MEIKIN plays a crucial role in both mono-orientation and centromeric cohesion protection, partly by stabilizing the localization of the cohesin protector shugoshin. These functions are mediated mainly by the activity of Polo-like kinase PLK1, which is enriched to kinetochores in a MEIKIN-dependent manner. Our integrative analysis indicates that the long-awaited key regulator of meiotic kinetochore function is Meikin, which is conserved from yeasts to humans.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jihye -- Ishiguro, Kei-ichiro -- Nambu, Aya -- Akiyoshi, Bungo -- Yokobayashi, Shihori -- Kagami, Ayano -- Ishiguro, Tadashi -- Pendas, Alberto M -- Takeda, Naoki -- Sakakibara, Yogo -- Kitajima, Tomoya S -- Tanno, Yuji -- Sakuno, Takeshi -- Watanabe, Yoshinori -- England -- Nature. 2015 Jan 22;517(7535):466-71. doi: 10.1038/nature14097. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Chromosome Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1Yayoi, Tokyo 113-0032, Japan. ; Instituto de Biologia Molecular y Celular del Cancer (CSIC-USAL), 37007 Salamanca, Spain. ; Center for Animal Resources and Development, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 Japan. ; Laboratory for Chromosome Segregation, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533956" target="_blank"〉PubMed〈/a〉

Description: Members of the dynein family, consisting of cytoplasmic and axonemal isoforms, are motors that move towards the minus ends of microtubules. Cytoplasmic dynein-1 (dynein-1) plays roles in mitosis and cellular cargo transport, and is implicated in viral infections and neurodegenerative diseases. Cytoplasmic dynein-2 (dynein-2) performs intraflagellar transport and is associated with human skeletal ciliopathies. Dyneins share a conserved motor domain that couples cycles of ATP hydrolysis with conformational changes to produce movement. Here we present the crystal structure of the human cytoplasmic dynein-2 motor bound to the ATP-hydrolysis transition state analogue ADP.vanadate. The structure reveals a closure of the motor's ring of six AAA+ domains (ATPases associated with various cellular activites: AAA1-AAA6). This induces a steric clash with the linker, the key element for the generation of movement, driving it into a conformation that is primed to produce force. Ring closure also changes the interface between the stalk and buttress coiled-coil extensions of the motor domain. This drives helix sliding in the stalk which causes the microtubule binding domain at its tip to release from the microtubule. Our structure answers the key questions of how ATP hydrolysis leads to linker remodelling and microtubule affinity regulation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336856/" 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/PMC4336856/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schmidt, Helgo -- Zalyte, Ruta -- Urnavicius, Linas -- Carter, Andrew P -- 100387/Wellcome Trust/United Kingdom -- MC_UP_A025_1011/Medical Research Council/United Kingdom -- WT100387/Wellcome Trust/United Kingdom -- England -- Nature. 2015 Feb 19;518(7539):435-8. doi: 10.1038/nature14023. Epub 2014 Dec 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council Laboratory of Molecular Biology, Division of Structural Studies, Francis Crick Avenue, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25470043" target="_blank"〉PubMed〈/a〉

Description: The gastrointestinal tracts of mammals are colonized by hundreds of microbial species that contribute to health, including colonization resistance against intestinal pathogens. Many antibiotics destroy intestinal microbial communities and increase susceptibility to intestinal pathogens. Among these, Clostridium difficile, a major cause of antibiotic-induced diarrhoea, greatly increases morbidity and mortality in hospitalized patients. Which intestinal bacteria provide resistance to C. difficile infection and their in vivo inhibitory mechanisms remain unclear. Here we correlate loss of specific bacterial taxa with development of infection, by treating mice with different antibiotics that result in distinct microbiota changes and lead to varied susceptibility to C. difficile. Mathematical modelling augmented by analyses of the microbiota of hospitalized patients identifies resistance-associated bacteria common to mice and humans. Using these platforms, we determine that Clostridium scindens, a bile acid 7alpha-dehydroxylating intestinal bacterium, is associated with resistance to C. difficile infection and, upon administration, enhances resistance to infection in a secondary bile acid dependent fashion. Using a workflow involving mouse models, clinical studies, metagenomic analyses, and mathematical modelling, we identify a probiotic candidate that corrects a clinically relevant microbiome deficiency. These findings have implications for the rational design of targeted antimicrobials as well as microbiome-based diagnostics and therapeutics for individuals at risk of C. difficile infection.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4354891/" 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/PMC4354891/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buffie, Charlie G -- Bucci, Vanni -- Stein, Richard R -- McKenney, Peter T -- Ling, Lilan -- Gobourne, Asia -- No, Daniel -- Liu, Hui -- Kinnebrew, Melissa -- Viale, Agnes -- Littmann, Eric -- van den Brink, Marcel R M -- Jenq, Robert R -- Taur, Ying -- Sander, Chris -- Cross, Justin R -- Toussaint, Nora C -- Xavier, Joao B -- Pamer, Eric G -- AI95706/AI/NIAID NIH HHS/ -- DP2 OD008440/OD/NIH HHS/ -- DP2OD008440/OD/NIH HHS/ -- K23 AI095398/AI/NIAID NIH HHS/ -- P01 CA023766/CA/NCI NIH HHS/ -- P30 CA008748/CA/NCI NIH HHS/ -- R01 AI042135/AI/NIAID NIH HHS/ -- R01 AI095706/AI/NIAID NIH HHS/ -- R01 AI42135/AI/NIAID NIH HHS/ -- T32 CA009149/CA/NCI NIH HHS/ -- T32 GM007739/GM/NIGMS NIH HHS/ -- T32GM07739/GM/NIGMS NIH HHS/ -- U54 CA148967/CA/NCI NIH HHS/ -- England -- Nature. 2015 Jan 8;517(7533):205-8. doi: 10.1038/nature13828. Epub 2014 Oct 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2] Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; 1] Computational Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA [2] Department of Biology, University of Massachusetts Dartmouth, North Dartmouth, Massachusetts 02747, USA. ; Computational Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA. ; Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; Donald B. and Catherine C. Marron Cancer Metabolism Center, Sloan-Kettering Institute, New York, New York 10065, USA. ; Genomics Core Laboratory, Sloan-Kettering Institute, New York, New York 10065, USA. ; 1] Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2] Immunology Program, Sloan-Kettering Institute, New York, New York 10065, USA. ; Bone Marrow Transplant Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA. ; 1] Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2] Computational Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA. ; 1] Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [2] Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA [3] Immunology Program, Sloan-Kettering Institute, New York, New York 10065, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25337874" target="_blank"〉PubMed〈/a〉

Description: Intracellular ISG15 is an interferon (IFN)-alpha/beta-inducible ubiquitin-like modifier which can covalently bind other proteins in a process called ISGylation; it is an effector of IFN-alpha/beta-dependent antiviral immunity in mice. We previously published a study describing humans with inherited ISG15 deficiency but without unusually severe viral diseases. We showed that these patients were prone to mycobacterial disease and that human ISG15 was non-redundant as an extracellular IFN-gamma-inducing molecule. We show here that ISG15-deficient patients also display unanticipated cellular, immunological and clinical signs of enhanced IFN-alpha/beta immunity, reminiscent of the Mendelian autoinflammatory interferonopathies Aicardi-Goutieres syndrome and spondyloenchondrodysplasia. We further show that an absence of intracellular ISG15 in the patients' cells prevents the accumulation of USP18, a potent negative regulator of IFN-alpha/beta signalling, resulting in the enhancement and amplification of IFN-alpha/beta responses. Human ISG15, therefore, is not only redundant for antiviral immunity, but is a key negative regulator of IFN-alpha/beta immunity. In humans, intracellular ISG15 is IFN-alpha/beta-inducible not to serve as a substrate for ISGylation-dependent antiviral immunity, but to ensure USP18-dependent regulation of IFN-alpha/beta and prevention of IFN-alpha/beta-dependent autoinflammation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303590/" 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/PMC4303590/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zhang, Xianqin -- Bogunovic, Dusan -- Payelle-Brogard, Beatrice -- Francois-Newton, Veronique -- Speer, Scott D -- Yuan, Chao -- Volpi, Stefano -- Li, Zhi -- Sanal, Ozden -- Mansouri, Davood -- Tezcan, Ilhan -- Rice, Gillian I -- Chen, Chunyuan -- Mansouri, Nahal -- Mahdaviani, Seyed Alireza -- Itan, Yuval -- Boisson, Bertrand -- Okada, Satoshi -- Zeng, Lu -- Wang, Xing -- Jiang, Hui -- Liu, Wenqiang -- Han, Tiantian -- Liu, Delin -- Ma, Tao -- Wang, Bo -- Liu, Mugen -- Liu, Jing-Yu -- Wang, Qing K -- Yalnizoglu, Dilek -- Radoshevich, Lilliana -- Uze, Gilles -- Gros, Philippe -- Rozenberg, Flore -- Zhang, Shen-Ying -- Jouanguy, Emmanuelle -- Bustamante, Jacinta -- Garcia-Sastre, Adolfo -- Abel, Laurent -- Lebon, Pierre -- Notarangelo, Luigi D -- Crow, Yanick J -- Boisson-Dupuis, Stephanie -- Casanova, Jean-Laurent -- Pellegrini, Sandra -- 1P01AI076210-01A1/AI/NIAID NIH HHS/ -- 309449/European Research Council/International -- 8UL1TR000043/TR/NCATS NIH HHS/ -- P01 AI076210/AI/NIAID NIH HHS/ -- P01 AI090935/AI/NIAID NIH HHS/ -- P01AI090935/AI/NIAID NIH HHS/ -- R00 AI106942/AI/NIAID NIH HHS/ -- R00AI106942-02/AI/NIAID NIH HHS/ -- R01 AI035237/AI/NIAID NIH HHS/ -- R37 AI095983/AI/NIAID NIH HHS/ -- R37AI095983/AI/NIAID NIH HHS/ -- U19 AI083025/AI/NIAID NIH HHS/ -- U19AI083025/AI/NIAID NIH HHS/ -- UL1 TR000043/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jan 1;517(7532):89-93. doi: 10.1038/nature13801. Epub 2014 Oct 12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China. ; 1] St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York 10065, USA [2] Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; Institut Pasteur, Cytokine Signaling Unit, CNRS URA 1961, 75724 Paris, France. ; 1] Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA [2] Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA [3] Microbiology Training Area, Graduate School of Biomedical Sciences of Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; 1] Division of Immunology, Children's Hospital Boston, Boston, Massachusetts 02115, USA [2] Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132 Genoa, Italy. ; Immunology Division and Pediatric Neurology Department, Hacettepe University Children's Hospital, 06100 Ankara, Turkey. ; Division of Infectious Diseases and Clinical Immunology, Pediatric Respiratory Diseases Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, 4739 Teheran, Iran. ; Manchester Academic Health Science Centre, University of Manchester, Genetic Medicine, Manchester, M13 9NT, UK. ; Department of Pediatrics, Third Xiangya Hospital, Central South University, Changsha 410013, China. ; St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York 10065, USA. ; BGI-Shenzhen, Shenzhen 518083, China. ; Sangzhi County People's Hospital, Sangzhi 427100, China. ; Genetics Laboratory, Hubei Maternal and Child Health Hospital, Wuhan, Hubei 430070, China. ; 1] Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China [2] Center for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. ; Institut Pasteur, Bacteria-Cell Interactions Unit, 75724 Paris, France. ; CNRS UMR5235, Montpellier II University, Place Eugene Bataillon, 34095 Montpellier, France. ; Department of Biochemistry, McGill University, Montreal, QC H3A 0G4, Canada. ; Paris Descartes University, 75006 Paris, France. ; 1] Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, France [2] Paris Descartes University, Imagine Institute, 75015 Paris, France. ; 1] Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, France [2] Paris Descartes University, Imagine Institute, 75015 Paris, France [3] Center for the Study of Primary Immunodeficiencies, Necker Hospital for Sick Children, 75015 Paris, France. ; 1] Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA [2] Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA [3] Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA. ; 1] St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York 10065, USA [2] Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, France [3] Paris Descartes University, Imagine Institute, 75015 Paris, France. ; Division of Immunology, Children's Hospital Boston, Boston, Massachusetts 02115, USA. ; 1] Manchester Academic Health Science Centre, University of Manchester, Genetic Medicine, Manchester, M13 9NT, UK [2] Paris Descartes University, Imagine Institute, 75015 Paris, France [3] INSERM UMR 1163, Laboratory of Neurogenetics and Neuroinflammation, Imagine Institute, 75006 Paris, France. ; 1] Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, 75015 Paris, France [2] Paris Descartes University, Imagine Institute, 75015 Paris, France [3] Howard Hughes Medical Institute, New York, New York 10065, USA [4] Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children, 75015 Paris, France [5]. ; 1] Institut Pasteur, Cytokine Signaling Unit, CNRS URA 1961, 75724 Paris, France [2].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25307056" target="_blank"〉PubMed〈/a〉

Description: The widespread reorganization of cellular architecture in mitosis is achieved through extensive protein phosphorylation, driven by the coordinated activation of a mitotic kinase network and repression of counteracting phosphatases. Phosphatase activity must subsequently be restored to promote mitotic exit. Although Cdc14 phosphatase drives this reversal in budding yeast, protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) activities have each been independently linked to mitotic exit control in other eukaryotes. Here we describe a mitotic phosphatase relay in which PP1 reactivation is required for the reactivation of both PP2A-B55 and PP2A-B56 to coordinate mitotic progression and exit in fission yeast. The staged recruitment of PP1 (the Dis2 isoform) to the regulatory subunits of the PP2A-B55 and PP2A-B56 (B55 also known as Pab1; B56 also known as Par1) holoenzymes sequentially activates each phosphatase. The pathway is blocked in early mitosis because the Cdk1-cyclin B kinase (Cdk1 also known as Cdc2) inhibits PP1 activity, but declining cyclin B levels later in mitosis permit PP1 to auto-reactivate. PP1 first reactivates PP2A-B55; this enables PP2A-B55 in turn to promote the reactivation of PP2A-B56 by dephosphorylating a PP1-docking site in PP2A-B56, thereby promoting the recruitment of PP1. PP1 recruitment to human, mitotic PP2A-B56 holoenzymes and the sequences of these conserved PP1-docking motifs suggest that PP1 regulates PP2A-B55 and PP2A-B56 activities in a variety of signalling contexts throughout eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338534/" 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/PMC4338534/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grallert, Agnes -- Boke, Elvan -- Hagting, Anja -- Hodgson, Ben -- Connolly, Yvonne -- Griffiths, John R -- Smith, Duncan L -- Pines, Jonathon -- Hagan, Iain M -- 092096/Wellcome Trust/United Kingdom -- A13678/Cancer Research UK/United Kingdom -- A16406/Cancer Research UK/United Kingdom -- C147/A16406/Cancer Research UK/United Kingdom -- C29/A13678/Cancer Research UK/United Kingdom -- England -- Nature. 2015 Jan 1;517(7532):94-8. doi: 10.1038/nature14019. Epub 2014 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cell Division Group, CRUK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. ; The Gurdon Institute, Tennis Court Road, University of Cambridge, Cambridge, CB2 1QN, UK. ; Biological Mass Spectrometry, CRUK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25487150" target="_blank"〉PubMed〈/a〉

Description: Broadly, tissue regeneration is achieved in two ways: by proliferation of common differentiated cells and/or by deployment of specialized stem/progenitor cells. Which of these pathways applies is both organ- and injury-specific. Current models in the lung posit that epithelial repair can be attributed to cells expressing mature lineage markers. By contrast, here we define the regenerative role of previously uncharacterized, rare lineage-negative epithelial stem/progenitor (LNEP) cells present within normal distal lung. Quiescent LNEPs activate a DeltaNp63 (a p63 splice variant) and cytokeratin 5 remodelling program after influenza or bleomycin injury in mice. Activated cells proliferate and migrate widely to occupy heavily injured areas depleted of mature lineages, at which point they differentiate towards mature epithelium. Lineage tracing revealed scant contribution of pre-existing mature epithelial cells in such repair, whereas orthotopic transplantation of LNEPs, isolated by a definitive surface profile identified through single-cell sequencing, directly demonstrated the proliferative capacity and multipotency of this population. LNEPs require Notch signalling to activate the DeltaNp63 and cytokeratin 5 program, and subsequent Notch blockade promotes an alveolar cell fate. Persistent Notch signalling after injury led to parenchymal 'micro-honeycombing' (alveolar cysts), indicative of failed regeneration. Lungs from patients with fibrosis show analogous honeycomb cysts with evidence of hyperactive Notch signalling. Our findings indicate that distinct stem/progenitor cell pools repopulate injured tissue depending on the extent of the injury, and the outcomes of regeneration or fibrosis may depend in part on the dynamics of LNEP Notch signalling.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312207/" 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/PMC4312207/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Vaughan, Andrew E -- Brumwell, Alexis N -- Xi, Ying -- Gotts, Jeffrey E -- Brownfield, Doug G -- Treutlein, Barbara -- Tan, Kevin -- Tan, Victor -- Liu, Feng Chun -- Looney, Mark R -- Matthay, Michael A -- Rock, Jason R -- Chapman, Harold A -- F32 HL117600-01/HL/NHLBI NIH HHS/ -- R01 HL44712/HL/NHLBI NIH HHS/ -- U01 HL099995/HL/NHLBI NIH HHS/ -- U01 HL099999/HL/NHLBI NIH HHS/ -- U01 HL111054/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jan 29;517(7536):621-5. doi: 10.1038/nature14112. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Cardiovascular Research Institute, University of California, San Francisco (UCSF), San Francisco, California 94143, USA. ; Department of Biochemistry, Stanford University School of Medicine and Howard Hughes Medical Institute, Stanford, California 94305, USA. ; Max Planck Institute for Evolutionary Anthropology, Department of Evolutionary Genetics, Deutscher Platz 6, 04103 Leipzig, Germany. ; Department of Anatomy, School of Medicine, University of California, San Francisco (UCSF), San Francisco, California 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533958" target="_blank"〉PubMed〈/a〉

Description: Despite three decades of successful, predominantly phenotype-driven discovery of the genetic causes of monogenic disorders, up to half of children with severe developmental disorders of probable genetic origin remain without a genetic diagnosis. Particularly challenging are those disorders rare enough to have eluded recognition as a discrete clinical entity, those with highly variable clinical manifestations, and those that are difficult to distinguish from other, very similar, disorders. Here we demonstrate the power of using an unbiased genotype-driven approach to identify subsets of patients with similar disorders. By studying 1,133 children with severe, undiagnosed developmental disorders, and their parents, using a combination of exome sequencing and array-based detection of chromosomal rearrangements, we discovered 12 novel genes associated with developmental disorders. These newly implicated genes increase by 10% (from 28% to 31%) the proportion of children that could be diagnosed. Clustering of missense mutations in six of these newly implicated genes suggests that normal development is being perturbed by an activating or dominant-negative mechanism. Our findings demonstrate the value of adopting a comprehensive strategy, both genome-wide and nationwide, to elucidate the underlying causes of rare genetic disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Deciphering Developmental Disorders Study -- 098395/Wellcome Trust/United Kingdom -- 100140/Wellcome Trust/United Kingdom -- CZD/16/6/Chief Scientist Office/United Kingdom -- WT098051/Wellcome Trust/United Kingdom -- Department of Health/United Kingdom -- England -- Nature. 2015 Mar 12;519(7542):223-8. doi: 10.1038/nature14135. Epub 2014 Dec 24.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25533962" target="_blank"〉PubMed〈/a〉

Description: Human immunodeficiency virus type 1 (HIV-1) assembly proceeds in two stages. First, the 55 kilodalton viral Gag polyprotein assembles into a hexameric protein lattice at the plasma membrane of the infected cell, inducing budding and release of an immature particle. Second, Gag is cleaved by the viral protease, leading to internal rearrangement of the virus into the mature, infectious form. Immature and mature HIV-1 particles are heterogeneous in size and morphology, preventing high-resolution analysis of their protein arrangement in situ by conventional structural biology methods. Here we apply cryo-electron tomography and sub-tomogram averaging methods to resolve the structure of the capsid lattice within intact immature HIV-1 particles at subnanometre resolution, allowing unambiguous positioning of all alpha-helices. The resulting model reveals tertiary and quaternary structural interactions that mediate HIV-1 assembly. Strikingly, these interactions differ from those predicted by the current model based on in vitro-assembled arrays of Gag-derived proteins from Mason-Pfizer monkey virus. To validate this difference, we solve the structure of the capsid lattice within intact immature Mason-Pfizer monkey virus particles. Comparison with the immature HIV-1 structure reveals that retroviral capsid proteins, while having conserved tertiary structures, adopt different quaternary arrangements during virus assembly. The approach demonstrated here should be applicable to determine structures of other proteins at subnanometre resolution within heterogeneous environments.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schur, Florian K M -- Hagen, Wim J H -- Rumlova, Michaela -- Ruml, Tomas -- Muller, Barbara -- Krausslich, Hans-Georg -- Briggs, John A G -- England -- Nature. 2015 Jan 22;517(7535):505-8. doi: 10.1038/nature13838. Epub 2014 Nov 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany [2] Molecular Medicine Partnership Unit, European Molecular Biology Laboratory/Universitatsklinikum Heidelberg, Heidelberg, Germany. ; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, 69117 Heidelberg, Germany. ; 1] Institute of Organic Chemistry and Biochemistry (IOCB), Academy of Sciences of the Czech Republic, v.v.i., IOCB &Gilead Research Center, Flemingovo nam. 2, 166 10 Prague, Czech Republic [2] Department of Biotechnology, Institute of Chemical Technology, Prague, Technicka 5, 166 28, Prague, Czech Republic. ; Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague, Technicka 5, 166 28, Prague, Czech Republic. ; 1] Molecular Medicine Partnership Unit, European Molecular Biology Laboratory/Universitatsklinikum Heidelberg, Heidelberg, Germany [2] Department of Infectious Diseases, Virology, Universitatsklinikum Heidelberg, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25363765" target="_blank"〉PubMed〈/a〉

Description: Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (〈/=50 years in males and 〈/=60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol 〉 190 mg dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4319990/" 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/PMC4319990/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Do, Ron -- Stitziel, Nathan O -- Won, Hong-Hee -- Jorgensen, Anders Berg -- Duga, Stefano -- Angelica Merlini, Pier -- Kiezun, Adam -- Farrall, Martin -- Goel, Anuj -- Zuk, Or -- Guella, Illaria -- Asselta, Rosanna -- Lange, Leslie A -- Peloso, Gina M -- Auer, Paul L -- NHLBI Exome Sequencing Project -- Girelli, Domenico -- Martinelli, Nicola -- Farlow, Deborah N -- DePristo, Mark A -- Roberts, Robert -- Stewart, Alexander F R -- Saleheen, Danish -- Danesh, John -- Epstein, Stephen E -- Sivapalaratnam, Suthesh -- Hovingh, G Kees -- Kastelein, John J -- Samani, Nilesh J -- Schunkert, Heribert -- Erdmann, Jeanette -- Shah, Svati H -- Kraus, William E -- Davies, Robert -- Nikpay, Majid -- Johansen, Christopher T -- Wang, Jian -- Hegele, Robert A -- Hechter, Eliana -- Marz, Winfried -- Kleber, Marcus E -- Huang, Jie -- Johnson, Andrew D -- Li, Mingyao -- Burke, Greg L -- Gross, Myron -- Liu, Yongmei -- Assimes, Themistocles L -- Heiss, Gerardo -- Lange, Ethan M -- Folsom, Aaron R -- Taylor, Herman A -- Olivieri, Oliviero -- Hamsten, Anders -- Clarke, Robert -- Reilly, Dermot F -- Yin, Wu -- Rivas, Manuel A -- Donnelly, Peter -- Rossouw, Jacques E -- Psaty, Bruce M -- Herrington, David M -- Wilson, James G -- Rich, Stephen S -- Bamshad, Michael J -- Tracy, Russell P -- Cupples, L Adrienne -- Rader, Daniel J -- Reilly, Muredach P -- Spertus, John A -- Cresci, Sharon -- Hartiala, Jaana -- Tang, W H Wilson -- Hazen, Stanley L -- Allayee, Hooman -- Reiner, Alex P -- Carlson, Christopher S -- Kooperberg, Charles -- Jackson, Rebecca D -- Boerwinkle, Eric -- Lander, Eric S -- Schwartz, Stephen M -- Siscovick, David S -- McPherson, Ruth -- Tybjaerg-Hansen, Anne -- Abecasis, Goncalo R -- Watkins, Hugh -- Nickerson, Deborah A -- Ardissino, Diego -- Sunyaev, Shamil R -- O'Donnell, Christopher J -- Altshuler, David -- Gabriel, Stacey -- Kathiresan, Sekar -- 090532/Wellcome Trust/United Kingdom -- 095552/Wellcome Trust/United Kingdom -- 5U54HG003067-11/HG/NHGRI NIH HHS/ -- G-0907/Parkinson's UK/United Kingdom -- K08 HL114642/HL/NHLBI NIH HHS/ -- K08HL114642/HL/NHLBI NIH HHS/ -- P01 HL076491/HL/NHLBI NIH HHS/ -- P01 HL098055/HL/NHLBI NIH HHS/ -- R01 HL107816/HL/NHLBI NIH HHS/ -- R01HL107816/HL/NHLBI NIH HHS/ -- RC2 HL-102923/HL/NHLBI NIH HHS/ -- RC2 HL-102924/HL/NHLBI NIH HHS/ -- RC2 HL-102925/HL/NHLBI NIH HHS/ -- RC2 HL-102926/HL/NHLBI NIH HHS/ -- RC2 HL-103010/HL/NHLBI NIH HHS/ -- T32 HL007208/HL/NHLBI NIH HHS/ -- T32HL00720/HL/NHLBI NIH HHS/ -- T32HL007604/HL/NHLBI NIH HHS/ -- UL1 TR000439/TR/NCATS NIH HHS/ -- Canadian Institutes of Health Research/Canada -- England -- Nature. 2015 Feb 5;518(7537):102-6. doi: 10.1038/nature13917. Epub 2014 Dec 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [2] Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [3] Department of Medicine, Harvard Medical School, Boston, Massachusetts 02114, USA. [4] Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; 1] Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA. [2] Division of Statistical Genomics, Washington University School of Medicine, St Louis, Missouri 63110, USA. ; Department of Clinical Biochemistry KB3011, Section for Molecular Genetics, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Copenhagen 1165, Denmark. ; Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Universita degli Studi di Milano, Milano 20122, Italy. ; Division of Cardiology, Ospedale Niguarda, Milano 20162, Italy. ; Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. ; Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2J, UK. ; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. ; University of Verona School of Medicine, Department of Medicine, Verona 37129, Italy. ; John &Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada. ; Department of Public Health and Primary Care, University of Cambridge, Cambridge CB2 1TN, UK. ; MedStar Health Research Institute, Cardiovascular Research Institute, Hyattsville, Maryland 20782, USA. ; Department of Vascular Medicine, Academic Medical Center, Amsterdam 1105 AZ, The Netherlands. ; Department of Cardiovascular Sciences, University of Leicester, and Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester LE3 9QP, UK. ; DZHK (German Research Centre for Cardiovascular Research), Munich Heart Alliance, Deutsches Herzzentrum Munchen, Technische Universitat Munchen, Berlin 13347, Germany. ; Medizinische Klinik II, University of Lubeck, Lubeck 23562, Germany. ; 1] Center for Human Genetics, Duke University, Durham, North Carolina 27708, USA. [2] Department of Cardiology and Center for Genomic Medicine, Duke University School of Medicine, Durham, North Carolina 27708, USA. ; Department of Cardiology and Center for Genomic Medicine, Duke University School of Medicine, Durham, North Carolina 27708, USA. ; Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4W7, Canada. ; Department of Biochemistry, Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada. ; 1] Department of Biochemistry, Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada. [2] Department of Medicine, Schulich School of Medicine and Dentistry, Robarts Research Institute, University of Western Ontario, London, Ontario N6A 3K7, Canada. ; 1] Medical Faculty Mannheim, Mannheim Institute of Public Health, Social and Preventive Medicine, Heidelberg University, Ludolf Krehl Strasse 7-11, Mannheim D-68167, Germany. [2] Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz 8036, Austria. [3] Synlab Academy, Mannheim 68259, Germany. ; Medical Faculty Mannheim, Mannheim Institute of Public Health, Social and Preventive Medicine, Heidelberg University, Ludolf Krehl Strasse 7-11, Mannheim D-68167, Germany. ; The National Heart, Lung, Blood Institute's Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; National Heart, Lung, and Blood Institute Center for Population Studies, The Framingham Heart Study, Framingham, Massachusetts 01702, USA. ; Department of Biostatistics and Epidemiology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Department of Epidemiology, University of Alabama-Birmingham, Birmingham, Alabama 35233, USA. ; Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA. ; School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27106, USA. ; Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; 1] Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599, USA. [2] Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599, USA. ; Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota 55455, USA. ; University of Mississippi Medical Center, Jackson, Mississippi 39216, USA. ; Atherosclerosis Research Unit, Department of Medicine, and Center for Molecular Medicine, Karolinska Institutet, Stockholm 171 77, Sweden. ; Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford OX1 2JD, UK. ; Merck Sharp &Dohme Corporation, Rahway, New Jersey 08889, USA. ; The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK. ; 1] The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK. [2] Department of Statistics, University of Oxford, Oxford OX1 2JD, UK. ; National Heart, Lung, and Blood Institute, Bethesda, Maryland 20824, USA. ; 1] Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington 98195, USA. [2] Group Health Research Institute, Group Health Cooperative, Seattle, Washington 98101, USA. ; Section on Cardiology, and Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina 27106, USA. ; Jackson Heart Study, University of Mississippi Medical Center, Jackson State University, Jackson, Mississippi 39217, USA. ; Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia 22904, USA. ; 1] Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA. [2] Seattle Children's Hospital, Seattle, Washington 98105, USA. [3] Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; Department of Biochemistry, University of Vermont, Burlington, Vermont 05405, USA. ; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA. ; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. ; St Luke's Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, Missouri 64111, USA. ; 1] Cardiovascular Division, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA. [2] Department of Genetics, Washington University in St Louis, Missouri 63130, USA. ; Department of Preventive Medicine and Institute for Genetic Medicine, University of Southern California Keck School of Medicine, Los Angeles, California 90033, USA. ; Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio 44195, USA. ; 1] Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. [2] Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA. ; Ohio State University, Columbus, Ohio 43210, USA. ; Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas 77030, USA. ; 1] Department of Epidemiology, University of Washington, Seattle, Washington 98195, USA. [2] Department of Medicine, School of Medicine, University of Washington, Seattle, Washington 98195, USA. ; 1] Department of Clinical Biochemistry KB3011, Section for Molecular Genetics, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Copenhagen 1165, Denmark. [2] Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Kobenhavn N, Denmark. ; Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Missouri 48109, USA. ; 1] Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2J, UK. [2] The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX1 2JD, UK. ; Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA. ; Department of Cardiology, Parma Hospital, Parma 43100, Italy. ; 1] Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA. [2] Division of Genetics, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. ; 1] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. [2] Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25487149" target="_blank"〉PubMed〈/a〉