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  • 1
    Publication Date: 2019-07-12
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: German
    Type: contributiontoperiodical , doc-type:contributionToPeriodical
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  • 2
    Publication Date: 2019-07-24
    Description: The Global Stocktake (GST) takes a central role within the architecture of the Paris Agreement, with many hoping that it will become a catalyst for increased mitigation ambition. This paper outlines four governance functions for an ideal GST: pacemaker, ensurer of accountability, driver of ambition and provider of guidance and signal. The GST can set the pace of progress by stimulating and synchronizing policy processes across governance levels. It can ensure accountability of Parties through transparency and public information sharing. Ambition can be enhanced through benchmarks for action and transformative learning. By reiterating and refining the long term visions, it can echo and amplify the guidance and signal provided by the Paris Agreement. The paper further outlines preconditions for the effective performance of these functions. Process-related conditions include: a public appraisal of inputs; a facilitative format that can develop specific recommendations; high-level endorsement to amplify the message and effectively inform national climate policy agendas; and an appropriate schedule, especially with respect to the transparency framework. Underlying information provided by Parties complemented with other (scientific) sources needs to enable benchmark setting for collective climate action, to allow for transparent assessments of the state of emissions and progress of a low-carbon transformation. The information also needs to be politically relevant and concrete enough to trigger enhancement of ambition. We conclude that meeting these conditions would enable an ideal GST and maximize its catalytic effect.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: English
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  • 3
    Publication Date: 2019-11-06
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: English
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  • 4
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    Berlin : Wissenschaftlicher Beirat der Bundesregierung Globale Umweltveränderungen
    Publication Date: 2019-10-25
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: German
    Type: report , doc-type:report
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  • 5
    Publication Date: 2019-07-12
    Description: Sustainable Development Goals and the Paris Agreement stand as milestone diplomatic achievements. However, immense discrepancies between political commitments and governmental action remain. Combined national climate commitments fall far short of the Paris Agreement's 1.5/2°C targets. Similar political ambition gaps persist across various areas of sustainable development. Many therefore argue that actions by nonstate actors, such as businesses and investors, cities and regions, and nongovernmental organizations (NGOs), are crucial. These voices have resonated across the United Nations (UN) system, leading to growing recognition, promotion, and mobilization of such actions in ever greater numbers. This article investigates optimistic arguments about nonstate engagement, namely: (a) "the more the better"; (b) "everybody wins"; (c) "everyone does their part"; and (d) "more brings more." However, these optimistic arguments may not be matched in practice due to governance risks. The current emphasis on quantifiable impacts may lead to the under-appreciation of variegated social, economic, and environmental impacts. Claims that everybody stands to benefit may easily be contradicted by outcomes that are not in line with priorities and needs in developing countries. Despite the seeming depoliticization of the role of nonstate actors in implementation, actions may still lead to politically contentious outcomes. Finally, nonstate climate and sustainability actions may not be self-reinforcing but may heavily depend on supporting mechanisms. The article concludes with governance risk-reduction strategies that can be combined to maximize nonstate potential in sustainable and climate-resilient transformations.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: English
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  • 6
    Publication Date: 2019-05-17
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: English
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  • 7
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    Wuppertal : Wuppertal Institut für Klima, Umwelt, Energie
    Publication Date: 2021-04-06
    Description: On 26 January 2019, the Commission on Growth, Structural Change and Employment recommended that no more coal-fired power plants would be operated in Germany by 2038 at the latest. In this paper the Wuppertal Institute comments on the results of the Commission and makes recommendations for the current necessary steps for the climate and innovation policy in Europe, Germany and North Rhine-Westphalia.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: English
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  • 8
    Publication Date: 2019-07-12
    Description: Obwohl viele der aktuellen Herausforderungen im Bereich der Energieversorgung eine internationale Dimension haben bzw. nur international gelöst werden können, ist die internationale Energiepolitik bis heute ein weitgehend ungesteuerter Politikbereich. Im letzten Jahrzehnt entwickelten sich zwar neue globale Kooperationsstrukturen und Initiativen, der Weg zu einer multilateralen, globalen Governance-Struktur, die zentrale Impulse für die gemeinsame Etablierung international geltender Normen und Regeln geben könnte, ist aber noch weit. Der Artikel führt in die aktuellen Entwicklungen ein und diskutiert die verbleibenden Herausforderungen.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: German
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  • 9
    Publication Date: 2019-12-16
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: German
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  • 10
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    Wuppertal : Wuppertal Institut für Klima, Umwelt, Energie
    Publication Date: 2020-01-27
    Description: Digitalisation is in full swing and it is changing and influencing the world of the 21st century as no other dynamics of change has done before. Dealing with its impacts and at the same time shaping digitalisation itself is therefore a core task for achieving a globally sustainable transformation (German Advisory Council on Global Change - WGBU, 2019). But which direction should digitalisation take to ensure that it makes e ective contributions to globally sustainable development? And what is the specific approach needed to steer digitalisation in the right direction?
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: English
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  • 11
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    Wuppertal : Wuppertal Institute for Climate, Environment and Energy
    Publication Date: 2021-04-20
    Description: The new mechanism under Article 6.4 of the Paris Agreement is to be supervised by a body designated by the Conference of the Parties serving as the Meeting of the Parties to the Paris Agreement (CMA). However, so far there is no clarity what role exactly the supervisory body (Body) is to play. Against this background, this JIKO Policy Paper analyses different governance options for Art. 6.4. The paper first reflects the objectives of the new mechanism and on what the role of the mechanism as a whole should be. The paper then summarises what has already been agreed on the functioning of the mechanism and elaborates what steps will be needed to generate transferrable emission reductions under the Article 6.4 mechanism. On this basis, the paper develops criteria for how to decide what role the Body should have, and then discusses what role the Body and the other actors that are involved in the mechanism could have in each of the steps of the activity cycle.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: English
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  • 12
    Publication Date: 2019-07-12
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: German
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  • 13
    Publication Date: 2021-08-06
    Description: Before linking emissions trading systems, there should be a good understanding of the expected economic implications: How could linking affect the development of the common allowance price, the development of emissions or industrial production, capital flows or liquidity? Answering these questions requires a multitude of data and assumptions and therefore usually the use of economic models. This report gives an overview of various economic models that are suitable for assessing the economic effects of linking. It analyses the economic indicators relevant for the assessment of the effects of linking, formulates requirements for economic models to answer this question, discusses the advantages and disadvantages of different modelling approaches and gives an assessment of which models are suitable in principle for the assessment of linking. Five models were selected for a more detailed description: E3ME, GEM-E3, PACE, POLES, and TIMES-MARKAL.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: English
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  • 14
    Publication Date: 2019-12-12
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: German
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  • 15
    Publication Date: 2021-08-06
    Description: The implementation of energy efficiency improvement actions not only yields energy and greenhouse gas emission savings, but also leads to other multiple impacts such as air pollution reductions and subsequent health and eco-system effects, resource impacts, economic effects on labour markets, aggregate demand and energy prices or on energy security. While many of these impacts have been studied in previous research, this work quantifies them in one consistent framework based on a common underlying bottom-up funded energy efficiency scenario across the EU. These scenario data are used to quantify multiple impacts by energy efficiency improvement action and for all EU28 member states using existing approaches and partially further developing methodologies. Where possible, impacts are integrated into cost-benefit analyses. We find that with a conservative estimate, multiple impacts sum up to a size of at least 50% of energy cost savings, with substantial impacts coming from e.g., air pollution, energy poverty reduction and economic impacts.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
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  • 16
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    Essen : Klartext-Verlag
    Publication Date: 2019-07-16
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: German
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  • 17
    Publication Date: 2019-05-17
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: English
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  • 18
    Publication Date: 2021-04-20
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: English
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  • 19
    Publication Date: 2021-05-18
    Description: The need for sustainable energy management at the municipal level is growing, in order to meet EU climate goals. Multiple initiatives have been launched to support municipalities in energy planning and strategy development process. Despite available support, research shows mixed results about implementation of plans and strategies. This research paper analyses what targets municipalities set, how they monitor implementation of their sustainable energy action plans (SEAPs) and searches for the most important factors that have enabled or hindered the implementation of local SEAPs at Latvia. The article shows that, in some cases, there is evidence that SEAP development is a project-based activity, supported by external experts. From municipal personnel point of view, it is a project that ends with approved SEAP, but not a part of their future daily routine. Eventually implementation of the plan is difficult, because municipalities lack experience in daily management of energy data, distribution of responsibilities and implementation of procedures. Municipalities also tend to exclude important stakeholders in their SEAPs, like, private sector, household sector and transport sector, which lead to lower targets and lower achievements in GHG reduction.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
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  • 20
    Publication Date: 2021-04-20
    Description: With the adoption of Article 6 of the Paris Agreement, former debates about generating carbon credits on the basis of national policies have resurged. National policies have not been eligible as project activities under the Kyoto Protocol's flexible mechanisms. The Paris Agreement opens the possibility for such policy crediting but also provides an entirely new context: Universal participation, ambitious long-term targets and nationally defined contributions (NDCs) that are to be made more ambitious over time. As this paper shows, these changes in the framework conditions add an additional layer of complexity to policy-based cooperation. The paper explores the potential for policy-based cooperation by first briefly presenting the regulatory basis provided by the Paris Agreement before outlining a prototype for policy-based cooperation and its key challenges.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
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  • 21
    Publication Date: 2021-04-20
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: English
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  • 22
    Publication Date: 2021-04-20
    Description: The Paris Agreement requires mitigation contributions from all Parties. Therefore, the determination of additionality of activities under the market mechanisms of its Article 6 will need to be revisited. This paper provides recommendations on how to operationalize additionality under Article 6. We first review generic definitions of additionality and current approaches for testing of additionality before discussing under which conditions additionality testing of specific activities or policies is still necessary under the new context of the Paris Agreement, that is, in order to prevent increases of global emissions. We argue that the possibility of "hot air" generation under nationally-determined contributions (NDCs) requires an independent check of the NDC's ambition. If the NDC of the transferring country does contain "hot air", or if the transferred emission reductions are not covered by the NDC, a dedicated additionality test should be required. While additionality tests of projects and programmes could continue to be done through investment analysis, for policy instruments new approaches are required. They should be differentiated according to type of policy instrument. For regulation, we suggest calculating the resulting pay-back period for technology users. If the regulation generates investments exceeding a payback period threshold, it could be deemed additional. Similarly, carbon pricing policies that generate a carbon price exceeding a threshold could qualify; for trading schemes an absence of over-allocation needs to be shown. The threshold should be differentiated according to country categories and rise over time.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
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  • 23
    Publication Date: 2022-02-18
    Description: Combating climate change requires a fundamental simultaneous transformation of various sectoral systems that are key to the functioning of our economies and societies, such as energy, industry, transport, housing, and agriculture. This report by the COP21 RIPPLES project examines sector-specific challenges to decarbonisation and what contribution international governance could make to overcoming these challenges. Taking a sectoral perspective, the report identifies the key governance challenges that exist internationally towards the deep transformations required, and specifies the resulting key governance functions to be fulfilled by means of international cooperation/international institutions. To this end, the report first clarifies a number of key concepts, including international (climate) governance, international and transnational institutions, institutional complexes and poly-centricity. It then derives a number of functions that international institutions can fulfil from the relevant literature: providing guidance and signals, setting rules, providing transparency and accountability, providing capacity building, technology and finance, and facilitating knowledge and learning. This is the basis for an investigation into the key governance challenges and the potential of international governance in 14 key sectoral systems.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: English
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  • 24
    Publication Date: 2022-02-18
    Description: In der öffentlichen Diskussion rücken die Konsequenzen der notwenigen Klimaschutzmaßnahmen sowie damit verbundene Kosten in den Fokus und entfalten ihre Sprengkraft. Ökologische, ökonomische und soziale Nachhaltigkeit werden zunehmend gegeneinander in Stellung gebracht. Häufig wird Klimaschutz gegen Wohlstand, wirtschaftliche Entwicklung und Arbeitsplätze ausgespielt. Mit der von der Friedrich-Ebert-Stiftung beim Wuppertal Institut in Auftrag gegebenen Studie entlarven die Autorinnen und Autoren "unheilige Allianzen", verbreitete Mythen und interessensgesteuerte Desinformation. Anhand von zehn konkreten Fragestellungen liefern sie eine faktenbasierte Analyse und zeigen, dass eine zukunftsorientierte Energie- und Klimapolitik im Einklang mit Wohlstand und sozialem Fortschritt sehr wohl möglich ist.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: German
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  • 25
    Publication Date: 2022-02-18
    Description: Before introducing an emissions trading system, jurisdictions have to consider the ex-isting energy and climate policy framework. This report seeks to analyse and evaluate non-ETS climate policy instruments, such as carbon taxes or green certificate trading schemes, regarding their suitability to serve as a basis for establishing emission trading systems. There is a general assessment of prototypical policy instruments. Besides, the report contains insights from case studies in India and Mexico. The report is meant to inform ETS development by showing how existing policy instruments could contribute to this process and by illustrating how non-ETS policy instruments could coexist with an emissions trading system, allowing for an effective policy mix.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
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  • 26
    Publication Date: 2022-02-18
    Description: Theoretical advances suggest that international governance in general and the Paris Agreement in particular provide a strong signal guiding sociotechnical systems toward decarbonization. We assess this signal and its effects empirically, by examining the struggle of competing narratives as present in the communications of leading US fossil fuel industry associations and companies. The results are then discussed in the context of the national and international climate and energy policy debates in a study period from late 2014 until the announcement of withdrawal from the Paris Agreement in June 2017. We find that the Paris Agreement has institutionalized a narrative paradigm that is surprisingly resilient. While the election of Donald Trump and his climate and energy policy led to a narrative shift in the coal industry, the oil and gas industry remained conspicuously silent in its immediate response and maintained its narrative strategies despite its alignment with the Paris Agreement.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
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  • 27
    Publication Date: 2022-02-18
    Description: The study analyses the country background, emissions trends, ongoing activities and barriers relating to the implementation of the Nationally Determined Contribution (NDC) of Ethiopia under the UNFCCC. A special emphasis is laid on further mitigation potentials in the fields of agriculture, forestry and low-emission transport.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
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  • 28
    Publication Date: 2022-02-18
    Description: Der heutige energetische Sanierungsbedarf des Gebäudebestands in Deutschland ist ein über Jahrzehnte qua irregeleiteter Auslegung produzierter. Inzwischen hat der technische Fortschritt erreicht, was zu erwarten war: Das Null-Energie-Haus, sogar das Plus-Energie-Haus sind heute möglich geworden. Beide sind auch "wirtschaftlich" - sofern man neu baut. Und selbstverständlich nur bei einem geklärten Verständnis von "wirtschaftlich", insbesondere im anstehenden Gebäude-Energie-Gesetz (GEG).
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: German
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  • 29
    Publication Date: 2022-02-18
    Description: In spite of differences in energy policies and supply, Japan and Germany have to master similar challenges: To reorganize the energy supply system towards - in the long term - being reliable, affordable, low in risks and resource use, and climate-neutral. At the same time, the ecological modernization should maintain or even strengthen international competitiveness. To better address these challenges, a bi-national expert council has been established between the two high-tech countries in 2016 - the GJETC. The aim of the GJETC is to show that despite different starting points, a national energy transition can be more successful, if both countries learn from their strengths and also weaknesses, to avoid the latter. If the implementation of an energy transition in the two countries is socially and economically sound and advances technology innovation and deployment, it may not only double success, but can also serve as blue prints for other countries, especially due to learning from similarities and differences. For example: Why is per capita energy consumption higher in transport in Germany, but energy intensity higher in Japan's building sector? How can variable renewable energies be integrated in an efficient energy system at lowest costs? The Council meets twice a year, holds stakeholder dialogues and outreach events, and prepares policy papers on strategic topics of mutual interest. Four comprehensive studies, each in cooperation of a German and a Japanese research institute, have been the basis for 15 joint key recommendations during the 1st phase. The 2nd phase to 2020 will study the role of hydrogen and digitalisation for the energy transition, as well as other topics. The paper presents the findings and recommendations of the GJETC of the first phase 2016-18 as well as first results of the second phase. It also reviews the setup of the GJETC and the way it works, to assess if and how it can serve as a role model of bilateral cooperation on the energy transition.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
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  • 30
    Publication Date: 2022-02-18
    Description: Derzeit befindet sich der zweite Entwurf zum Gebäudeenergiegesetz (GEG) des Bundeswirtschaftsministeriums und Bundesbauressorts zur Vereinheitlichung des Energieeinsparrechts für Gebäude in den Ressorts in der Abstimmung. Doch der Entwurf fällt weit hinter dem aktuellen klimapolitischen Aufbruch der Großen Koalition zurück und die Vorgaben der Europäischen Union erfüllt er nicht.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
    Language: German
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  • 31
    Publication Date: 2022-02-18
    Description: While the Paris Agreement (PA) has enshrined ambitious long-term objectives, the current level of action of the Parties to the Agreement falls far short of this ambition, as is recognised in the very COP decision adopting the Agreement. The Global Stocktake (GST) established in Art. 14 of the PA is a key element to address this problem. Its purpose is to review the implementation of the PA and to assess the progress made towards the collectively agreed goals. The aim of this report is to develop recommendations on how to maximise the potential impact of the GST. The report starts from a perspective of what the GST could ideally do, irrespective of decisions already taken under the UNFCCC and other political constraints. In the second step, the report takes these limitations into account and suggests ways for how to nonetheless work towards the desired outcome.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
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  • 32
    Publication Date: 2022-02-18
    Description: Ein wachsender Teil der Gesellschaft sehnt sich beim Konsum zunehmend nach Vertrauenswürdigkeit und Individualität. Zwei Aspekte, die viele Konsumentinnen und Konsumenten im Massenmarkt vermissen. Das Konzept "Prosumieren", vorangetrieben von zivilgesellschaftlichen Initiativen wie urbanen Gemeinschaftsgärten, Foodsharing oder Repair-Cafés, bietet die Möglichkeit zu Partizipation und Empowerment der Verbraucherinnen und Verbrauchern, die damit nicht mehr nur einfache Konsumentinnen/Konsumenten sind, sondern zu Prosumentinnen/Prosumenten werden. Die vorliegenden Handlungsempfehlungen richten sich vorrangig an die Verbraucherpolitik, doch betreffen sie auch etliche andere Ressorts, wie etwa Bildung und Verkehr. Ihr Ziel ist es, der Verbraucherpolitik die Bandbreite an Prosumptionsformen in den Feldern Ernährung und Bekleidung aufzuzeigen und ihr so einen Überblick zu verschaffen. Zugleich wird jedoch für ausgewählte Modelle im Detail auf die aktuellen praktischen Hürden sowie die Möglichkeiten eingegangen, diese abzubauen und das nachhaltige Prosumieren zu fördern. Schließlich wurde ein kurzer Leitfaden zur Bewertung der Nachhaltigkeitspotentiale von Prosumptionsmodellen erstellt, an dem sich die Verbraucherpolitik bei der Bewertung neuer Prosumptionsinitiativen, welche sich aktuell rasant verbreiten und immer neue Formen hervorbringen, orientieren kann.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
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  • 33
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    Stockholm : European Council for an Energy Efficient Economy
    Publication Date: 2022-02-18
    Description: The emission reduction potential of energy efficiency and energy supply in buildings is estimated in various energy and climate action plans, scenarios, and potential analyses. But the third pillar of sustainability - sufficiency - is neglected in most studies.The increasing demand of space per person in the residential sector is a trend in most European countries. Its implication on energy use, demand for resources like land, building material, equipment, and waste production is enormous. Next to the ecological impact, the distribution of space has social and societal effects. Thus, sufficiency policies in the building sector complementing efficiency and energy policy are needed for a sustainable development of the European building stock. But how can a sufficiency potential in the building sector be estimated? How much space and equipment is needed for a decent living and how much is too much? The paper proposes four areas of sufficiency in buildings: space, design and construction, equipment, and use. It presents a set of indicators, a quantitative estimate of energy savings from reduced per capita floor area, and visualises the sufficiency potential in European countries in an experimental approach. The final discussion focuses on the question: What does this mean for policy making?
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  • 34
    Publication Date: 2022-02-18
    Description: Much mitigation-related governance activity is evident in a range of sectoral systems, and regarding particular governance functions. However, there is a tendency for this activity to relate to the easiest functions to address, such as "learning and knowledge building", or to take place in somewhat limited "niches". Across all sectoral systems examined, the gap between identified governance needs and what is currently supplied is most serious in terms of the critical function of setting rules to facilitate collective action. A lack of "guidance and signal" is also evident, particularly in the finance, extractive industries, energy-intensive industries, and buildings sectoral systems. Of the sectoral systems examined, the power sector appears the most advanced in covering the main international governance functions required of it. Nevertheless, it still falls short in achieving critical governance functions necessary for sufficient decarbonisation. Significantly, while the signal is strong and clear for the phase-in of renewable energy, it is either vague or absent when it comes to the phase-out of fossil fuel-generated electricity. The same lack of signal that certain high-carbon activities need actively to be phased out is also evident in financial, fossil-fuel extractive industry and transport-related sectors. More effective mitigation action will need greater co-ordination or orchestration effort, sometimes led by the UNFCCC, but also from the bodies such as the G20, as well as existing (or potentially new) sector-level institutions. The EU needs to re-consider what it means to provide climate leadership in an increasingly "polycentric" governance landscape.
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  • 35
    Publication Date: 2022-02-18
    Description: Article 6 of the Paris Agreement establishes three approaches for countries to cooperate with each other in implementing their climate protection contributions. However, Article 6 sketches out only some basic contours; the details are to be filled in by further negotiations. This article surveys the views countries have submitted so far in order to identify the main issues at stake, points of controvery and convergence and possible ways forward. The submissions reveal some sharp differences in opinions on key issues such as the scope of the new mechanisms, how to operationalise the Article 6 requirement to increase ambition, whether to have international provisions on the promotion of sustainable development, and how to protect environmental integrity in the use of Article 6. The article concludes with a number of recommendations on how to address these controversies.
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  • 36
    Publication Date: 2022-02-18
    Description: Relevante Fragen rund um die Möglichkeiten und Erfordernisse der Reduzierung und Beendigung der Kohleverstromung werden seit mehreren Jahren diskutiert. Dabei sind eine Fülle von Strategien, Analysen und Argumenten entwickelt worden, wie die Reduzierung und Beendigung der energetischen Nutzung von Kohle auf der Zeitachse umgesetzt und strukturpolitisch flankiert werden könnte. Der vorliegende "Kohle-Reader" greift die vorliegenden Analysen auf und gibt einen Überblick über den Diskussionsstand. Er soll über Fakten und Zusammenhänge informieren, das Für und Wider für einzelne Handlungsoptionen benennen und dazu den jeweiligen wissenschaftlichen Hintergrund aufzeigen. Er hat den Anspruch wissenschaftlich-neutral zu sein und er soll in Sprache und Darstellung prägnant und für die nicht zuvor im Detail mit den Themen befassten Leserinnen und Leser gut verständlich sein, ohne unzulässig zu verkürzen oder zuzuspitzen.
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  • 37
    Publication Date: 2022-02-18
    Description: Relevant aspects of the options and requirements for reducing and phasing out coal-fired power generation have been under debate for several years. This process has produced a range of strategies, analyses and arguments, outlining how coal use in the energy sector could be reduced and phased out in the planned time frame, and determining structural policy measures suitable to support this. This Coal Report studies the existing analyses and provides an overview of the state of debate. It is intended to provide information on facts and contexts, present the advantages and disadvantages of individual courses of action, and reveal the respective scientific backgrounds. It strives to take a scientific and independent approach, and present facts in concise language, making it easy to follow for readers who are not experts in the field, without excessive abridgements or provocative statements.
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  • 38
    Publication Date: 2022-02-18
    Description: Improvements in energy efficiency have numerous impacts additional to energy and greenhouse gas savings. This paper presents key findings and policy recommendations of the COMBI project ("Calculating and Operationalising the Multiple Benefits of Energy Efficiency in Europe"). This project aimed at quantifying the energy and non-energy impacts that a realisation of the EU energy efficiency potential would have in 2030. It covered the most relevant technical energy efficiency improvement actions in buildings, transport and industry. Quantified impacts include reduced air pollution (and its effects on human health, eco-systems), improved social welfare (health, productivity), saved biotic and abiotic resources, effects on the energy system and energy security, and the economy (employment, GDP, public budgets and energy/EU-ETS prices). The paper shows that a more ambitious energy efficiency policy in Europe would lead to substantial impacts: overall, in 2030 alone, monetized multiple impacts (MI) would amount to 61 bn Euros per year in 2030, i.e. corresponding to approx. 50% of energy cost savings (131 bn Euros). Consequently, the conservative CBA approach of COMBI yields that including MI quantifications to energy efficiency impact assessments would increase the benefit side by at least 50-70%. As this analysis excludes numerous impacts that could either not be quantified or monetized or where any double-counting potential exists, actual benefits may be much larger. Based on these findings, the paper formulates several recommendations for EU policy making: (1) the inclusion of MI into the assessment of policy instruments and scenarios, (2) the need of reliable MI quantifications for policy design and target setting, (3) the use of MI for encouraging inter-departmental and cross-sectoral cooperation in policy making to pursue common goals, and (4) the importance of MI evaluations for their communication and promotion to decision-makers, stakeholders, investors and the general public.
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  • 39
    Publication Date: 2022-02-18
    Description: Each year, approximately one-third of the food produced for human consumption is lost or wasted worldwide. The waste of resources used for this food has significant environmental impacts in terms of land and water use as well as greenhouse gas emissions. Consequently, one of the targets of the UN sustainable development goals is to halve per capita global food waste at the retail and consumer levels and reduce food losses along production and supply chains by 2030. However, sufficient knowledge about the suitability of instruments for food waste prevention is still lacking. The purpose of this paper is therefore threefold: first, it outlines the generation and causes of food losses and waste. Second, it discusses good practices from different countries, such as laws to reduce food waste, voluntary agreements, awareness campaigns and results from behavioural economics. Finally, based on these findings, this paper identifies barriers to as well as requirements for the implementation of effective and efficient instruments.
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  • 40
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    Stockholm : European Council for an Energy Efficient Economy
    Publication Date: 2022-02-18
    Description: "400,000 new homes per year are needed in German cities." This figure has been cited repeatedly in political discussions, media, and statements of different groups for a couple of years now. Living space is needed to mitigate the (further) inordinate increase of rents in some cities and regions and to ease finding appropriate flats at affordable prices for low- and medium-income households. But how to activate investors and the real estate market? Having the triangle of sustainability in mind with its ecologic, social and economic cornerstones the discussion - metaphorically spoken - currently pulls the three corners: Which should have the highest priority? The economically driven most favourable solution is lowering the requirements for new buildings such as the energy performance to make building cheaper. The social perspective prefers an increase of public social housing investments regardless of efficiency standards. And the ecological side argues that a high performance is needed to reach energy and climate targets in the buildings sector. Starting at this point of discussion, firstly, the paper reflects the assumptions behind the numbers of new homes needed against a sufficiency background. Secondly, it presents current changes in German building policies: a new legislation for energy supply and efficiency is currently in preparation. It discusses the potential to integrate sufficiency aspects in building policies, focussing specifically on the new regulation, financial incentives, and energy advice. The paper analyses if and to what extent it is likely to balance the three cornerstones of sustainability by integrating sufficiency aspects into efficiency policies. Household experiences with prepayment meters are used as an example to illustrate the potential for tapping efficiency and sufficiency potentials in low-income households considering social, economic, and ecological aspects. Based on the identified (in)consistencies, thirdly, it suggests further development in German policies to make better use of synergies between the ecologic, social and economic demands on buildings.
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  • 41
    Publication Date: 2022-02-18
    Description: Nach jahrzehntelangen, erfolgreichen Reduktionen der CO2-Emissionen in der Industrie, ist der Trend in den letzten Jahren wieder rückläufig geworden: seit 2014 sind die Emissionen wieder angestiegen (UBA 2019). Um die deutschen Klimaziele zu erreichen ist es daher notwendig, die Anstrengungen zu verstärken und intensiver als in der Vergangenheit Innovationen für den Klimaschutz voranzutreiben: Neue Produkte und Geschäftsmodelle sowie neue Herstellungsverfahren zu entwickeln, mit denen sich Treibhausgasemissionen reduzieren lassen. Um die deutschen Klimaziele für 2030 einzuhalten, werden hierfür gerade auch (inkrementelle) Effizienzsteigerungen nötig sein - diese werden jedoch nicht ausreichend sein. Innovationen müssen auch einen disruptiven Wandel von Strukturen und Geschäftsmodellen erwirken. Disruptive Innovationen und industrielle Konversionsprozesse bergen jedoch hohe Risiken für die etablierte Industrie. Hier stellt sich also die Frage, wie eine auf Klimaschutz ausgerichtete Innovationspolitik gestaltet werden muss, um einerseits die notwendigen CO2-Einsparungen zu ermöglichen und andererseits die Leistungfähigkeit der deutschen Industrie zu befördern? Vor diesem Hintergrund widmet sich diese Studie zwei zentralen Fragestellungen: Wie laufen Klimaschutz-Innovationsprozesse ab? Wie können Klimaschutz-Innovationen befördert werden? Basierend auf einer konzeptionellen Klassifizierung von Klimaschutz-Innovationen, wurden eine Reihe von existierenden Klimaschutz-Innovationen, gerade aus der energieintensiven Industrie analysiert. Vier Fallbeispiele aus verschiedenen Sektoren (Aluminiumherstellung und -verarbeitung, Herstellung neuer Kraftstoffe sowie der Verzinkung) und verschiedenen Innovationstypen werden in der Studie ausführlich beschrieben. Dabei zeigt sich, dass sich Unternehmen nicht nur an aktuellen Rahmenbedingungen orientieren, sondern Innovationen - sowohl inkrementeller wie auch radikaler Natur- im Bereich Klimaschutz auch unter der Annahme dynamischer Entwicklungen von sich verstärkenden Klimaschutzrahmenbedingungen vorantreiben. Darüber hinaus waren an allen untersuchten Fällen auch externe Promotoren unterstützend tätig. Daher wurden die möglichen Rollen von Klimaschutz-Promotoren mit unterschiedlichen regionalen und inhaltlichen Schwerpunkten gezielt analysiert.
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  • 42
    Publication Date: 2022-02-18
    Description: The study analyses the country background, emissions trends, ongoing activities and barriers relating to the implementation of the Nationally Determined Contribution (NDC) of the Islamic Republic of Iran under the UNFCCC. A special emphasis is laid on further mitigation potentials in the fields of demand-side efficiency through energy-price reform, upstream oil and gas efficiency (with an emphasis on gas flaring) and a sustainable energy mix (with an emphasis on renewable energies).
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  • 43
    Publication Date: 2022-02-18
    Description: Today more than 45 % of all energy-related CO2 emissions come from burning coal. Thus, reducing CO2 emissions from coal use is a necessity for reaching the targets of the Paris Agreement. This will not only pose challenges for coal consumers (restructuring of the energy system), but also for countries whose economy is strongly depending on the production of coal. This paper examines the role of coal in three countries, which are or were in recent years among the top coal exporters: Indonesia, Colombia and Vietnam. Understanding challenges and possible transition pathways in these countries will help to develop global strategies to reduce CO2 emissions from coal in the short to mid-term.
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  • 44
    Publication Date: 2022-02-18
    Description: The twenty-third Conference of the Parties (COP-23) of the United Nations Framework Convention on Climate Change (UNFCCC) was held in Bonn on 6-17 November 2017, under the presidency of Fiji. COP-23 focused, in particular, on developing rules to implement the 2015 Paris Agreement and on raising ambition for climate protection. Since this was the first "Oceanic" COP, special attention was given to supporting the countries of the Global South in their efforts to reduce emissions, adapt to climate change, and deal with the unavoidable impacts of climate change. This article summarizes the main developments and results of COP-23.
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  • 45
    Publication Date: 2022-02-18
    Description: With the "Energiewende", the German term for the transformation of the national energy system, the German government pursues ambitious goals, primarily but not only to reflect the climate change challenge and to react to the risks associated with the use of nuclear power plants. After launching the energy concept in mid-2011, which describes the "Energiewende" goals, Germany was perceived as an international pioneer in energy transition for many years and has been acknowledged for its braveness to combine ambitious greenhouse gas (GHG) mitigation targets with a phase out program for nuclear power plants. In this context, this article asks where Germany’s energy transition currently stands, what is planned next and how far the set targets have been achieved or where more action is required to stick to this pathway.
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  • 46
    Publication Date: 2022-02-18
    Description: Last year's conference of the global climate change regime took place from 2 until 15 December 2018 in Katowice, Poland. The conference had two main objectives: operationalising the Paris Agreement by adopting detailed rules for its implementation, and starting the process of strengthening Parties' climate protection contributions. This article covers the negotiations on these two sets of issues and also includes a discussion of other recent climate activities by Parties and non-Party actors. Success of the negotiations in Katowice was far from assured, but in the end COP24 concluded with the adoption of the "Katowice Climate Package" setting out detailed guidelines on how to implement its various elements. However, the conference fell short on the first objective, none of the major emitting countries was ready to step up its climate ambition. The most important aspect of the Katowice outcome is therefore that it has brought the wrangling about implementation procedures to a close, making way for the true task at hand: the strengthening of national and international activities to protect the climate and the implementation of the existing pledges. Arguably, a key factor that has been slowing down climate policy is the power of entrenched interests. The article therefore concludes with a reflection on how such barriers to climate action may be overcome and what role future COPs may play in this regard.
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  • 47
    Publication Date: 2022-02-18
    Description: Article 6 of the Paris Agreement establishes mechanisms for Parties to "pursue voluntary cooperation in the implementation of their nationally determined contributions to allow for higher ambition in their mitigation and adaptation actions [...]" (Article 6.1). I. e. the mechanisms are explicitly designed to foster higher ambition. However, without additional guidance and rules, the economic incentives of carbon markets may work against increasing host country ambition. For example, setting ambitious NDC targets may directly reduce the amount of mitigation outcomes that go beyond the NDC target and that a host country can transfer abroad. The report presents four options on how the risks can be ad-dressed and ambition can be increased: (1) Strengthening reporting, transparency and comparability; (2) Reconciling the design of the Article 6.4 mechanism with ambition raising of host countries; (3) Supporting the host country to raise ambition through the Article 6.4 mechanism; (4) Fostering the acquiring country to raise ambition through the Article 6.4 mechanism. These options are assessed and recommendations are provided on how they could be implemented.
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  • 48
    Publication Date: 2022-02-18
    Description: Article 6.4 of the Paris Agreement establishes a new mechanism for Parties to cooperate in achieving their nationally determined contributions (NDCs). One key innovation of the Article 6.4 mechanism is its objective to "deliver an overall mitigation in global emissions" (Art. 6.4(d)). This report develops recommendations on how to implement this objective. A key difficulty lies in the fact that even basics of how the mechanism is supposed to function have so far not been clarified by the Parties. The report therefore first sketches out what has so far been agreed and discussed on the mechanism’s activity cycle. Second, as the concept of overall mitigation has so far also not been clearly defined by Parties, the report derives a working definition from the language that was agreed in the Paris Agreement. In the next step, the report provides a survey of the options to achieve overall mitigation that have so far been discussed in the relevant literature and in the Article 6 negotiations. Many of these options were developed in the context of the Kyoto mechanisms. The report therefore discusses to what extent the options are also applicable under the Paris Agreement or whether adjustments need to be made. In the following, the options that are applicable under the Agreement are assessed on the basis of a number of criteria. The report concludes with a summary of the main findings and recommendations.
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  • 49
    Publication Date: 2022-02-18
    Description: This report explores the future role of the voluntary carbon market and its potential to contribute to raising the ambition of climate policy. For this purpose, desk research was complemented by interviews with voluntary carbon market representatives. The report finds that the current roles of the voluntary market are set to change fundamentally due to the Paris Agreement. For the future of the voluntary market as an investor, three roles were identified, each of which is associated with specific challenges: The market may maintain its current role of buyer of carbon neutrality credits, it may become a supporter of NDC implementation, or it may become a driver of ambition. With regard to the future role of private certification standards, the Paris Agreement may hold the possibility of using such standards in the context of compliance activities. Overall, the findings indicate that the voluntary market has some potential to contribute to ambition raising. Whether this potential will actually be unlocked depends on how the concept of ambition raising will be operationalized under the Paris Agreement and to what degree it can be integrated into the voluntary market's activities and business models.
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  • 50
    Publication Date: 2022-02-18
    Description: Das Kreislaufwirtschaftsgesetz (KrWG) verlangt mit Bezug auf das Abfallvermeidungsprogramm (AVP) die Benennung zweckmäßiger Maßstäbe für Abfallvermeidungsmaßnahmen (AVM), anhand derer die Fortschritte bei der Entkopplung der mit der Abfallerzeugung verbundenen Auswirkungen auf Mensch und Umwelt vom Wirtschaftswachstum erfasst werden können. Das AVP benennt mögliche Indikatoren, allerdings ist unklar, inwieweit diese das Entstehen von Abfällen darstellen oder die Effekte von AVM abbilden können. Mögliche Bewertungsmaßstäbe für die Messung des Abfallvermeidungserfolges wurden analysiert, auf ihre Eignung geprüft und ein Set an Indikatoren erarbeitet, um eine kontinuierliche Messung des Erfolges von AVM zu ermöglichen.
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  • 51
    Publication Date: 2022-05-06
    Description: Europa braucht eine neue Fortschrittsvision. Eine Energiewende hat dieses Potenzial. Sie kann der "Europäischen Idee" einen zukunftsorientierten Inhalt geben. Das Ziel für 2050 ist klar: ein Europa ohne fossile und nukleare Energie! Das ist keine Utopie. Studien, Beschlüsse der EU und einiger Mitgliedsländer belegen, dass diese Vision machbar und mit vielen Vorteilen verbunden ist: mehr Jobs, mehr Versorgungssicherheit, weniger vorzeitige Todesfälle durch Luftverschmutzung, Abbau von Ressourcenkonflikten, sinkende Energiekosten. Neue grüne Leitmärkte für erneuerbare Energien und Ressourceneffizienz entstehen. Eine europäische Energiewende erfordert eine Allianz, idealerweise angefeuert durch die Nachbarn Frankreich und Deutschland. Viele hoffen auf Deutschland als Treiber von Atom- und Kohleausstieg. Aber "revolutionäre Ziele" zu beschließen ist nicht genug: Sie endlich umzusetzen - darauf warten Deutschland und Europa. Dieses Buch zeigt, welche konkreten Schritte diese Fortschrittsvision voranbringen werden.
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  • 52
    Publication Date: 2022-01-20
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  • 53
    Publication Date: 2022-01-20
    Keywords: ddc:320
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  • 54
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    Wuppertal : Wuppertal Institut für Klima, Umwelt, Energie
    Publication Date: 2022-11-09
    Description: Am 26. Januar 2019 hat die Kommission "Wachstum, Strukturwandel und Beschäftigung" beschlossen, dass in Deutschland bis spätestens 2038 keine Kohlekraftwerke mehr betrieben werden sollen. Das Wuppertal Institut nimmt in diesem Papier Stellung zu den Ergebnissen der Kommission und gibt Empfehlungen für die nun notwendigen Schritte für die Klima- und Innovationspolitik in Europa, Deutschland und Nordrhein-Westfalen.
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  • 55
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    Wuppertal : Wuppertal Institut für Klima, Umwelt, Energie
    Publication Date: 2022-11-10
    Description: Europe needs a new vision of progress. An energy transition has this potential. It can give the "European idea" a future-oriented content. The goal for 2050 is clear: a Europe without fossil and nuclear energy! This is not a utopia. Studies, resolutions of the EU and some member states prove that this vision is feasible and has many advantages: more jobs, more security of supply, fewer premature deaths due to air pollution, reduction of resource conflicts, falling energy costs. New green lead markets for renewable energies and resource efficiency are emerging. A European energy transition requires an alliance, ideally fuelled by neighbours France and Germany. Many are hoping for Germany as a driver of nuclear and coal phase-out. But deciding on "revolutionary goals" is not enough: finally implementing them is what Germany and Europe are waiting for. This report shows which concrete steps can advance this vision of progress.
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  • 56
    Publication Date: 2022-11-10
    Description: Dieses Wuppertal Paper dient dazu, a) die mögliche Klimaschutzwirkung eines CO2-Preises zu analysieren, allein und im Gesamtpaket von Instrumenten zum Klimaschutz, b) die Möglichkeiten der Mittelverwendung zu analysieren und zu bewerten, c) dadurch den Dschungel der Argumente und Motivationen in den bestehenden Vorschlägen zu lichten und d) aus der Analyse ein Modell zu skizzieren, das den Anforderungen von Klimaschutz und sozialer Gerechtigkeit sowie Erhalt der Wettbewerbsfähigkeit am besten gerecht wird und damit der Bundesregierung als Anregung bei der Entscheidung über Einführung und Ausgestaltung eines CO2-Preises dienen kann. In dem Papier werden diese Fragen anhand von neun Thesen mit einem abschließenden Fazit ergründet. Daraus wird deutlich: Ein CO2-Preis kann sektorale Ziele und Instrumente nicht ersetzen. Seine volle Wirkung kann er nur entfalten, wenn er komplementär zu sektorspezifischen Klimaschutzinstrumenten eingeführt wird. Nur wenn für diese Instrumente ein guter Teil der Einnahmen aus der CO2-Steuer eingesetzt wird, sind die Klimaziele erreichbar. Die Ziele werden dadurch mit weitaus geringerem CO2-Preis bei gleichzeitig höheren Kostenentlastungen für Verbraucherinnen und Verbraucher, Unternehmen und sogar die öffentlichen Haushalte erreichbar, als wenn die Politik allein auf einen CO2-Preis setzen würde.
    Keywords: ddc:320
    Repository Name: Wuppertal Institut für Klima, Umwelt, Energie
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  • 57
    Publication Date: 2009-12-18
    Description: Avian brood parasites and their hosts provide model systems for investigating links between recognition, learning, and their fitness consequences. One major evolutionary puzzle has continued to capture the attention of naturalists for centuries: why do hosts of brood parasites generally fail to recognize parasitic offspring after they have hatched from the egg, even when the host and parasitic chicks differ to almost comic degrees? One prominent theory to explain this pattern proposes that the costs of mistakenly learning to recognize the wrong offspring make recognition maladaptive. Here we show that American coots, Fulica americana, can recognize and reject parasitic chicks in their brood by using learned cues, despite the fact that the hosts and the brood parasites are of the same species. A series of chick cross-fostering experiments confirm that coots use first-hatched chicks in a brood as referents to learn to recognize their own chicks and then discriminate against later-hatched parasitic chicks in the same brood. When experimentally provided with the wrong reference chicks, coots can be induced to discriminate against their own offspring, confirming that the learning errors proposed by theory can exist. However, learning based on hatching order is reliable in naturally parasitized coot nests because host eggs hatch predictably ahead of parasite eggs. Conversely, a lack of reliable information may help to explain why the evolution of chick recognition is not more common in hosts of most interspecific brood parasites.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shizuka, Daizaburo -- Lyon, Bruce E -- England -- Nature. 2010 Jan 14;463(7278):223-6. doi: 10.1038/nature08655. Epub 2009 Dec 16.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ecology and Evolutionary Biology, University of California, Santa Cruz, California 95064, USA. shizuka@biology.ucsc.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20016486" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Birds/*parasitology/*physiology ; British Columbia ; Cues ; Discrimination Learning/*physiology ; Feeding Behavior/physiology ; Genetic Fitness ; Nesting Behavior/*physiology ; Ovum/growth & development ; Pattern Recognition, Visual/physiology ; Survival Rate ; Time Factors ; Wetlands
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  • 58
    Publication Date: 2009-12-23
    Description: Reprogramming of somatic cell nuclei to yield induced pluripotent stem (iPS) cells makes possible derivation of patient-specific stem cells for regenerative medicine. However, iPS cell generation is asynchronous and slow (2-3 weeks), the frequency is low (〈0.1%), and DNA demethylation constitutes a bottleneck. To determine regulatory mechanisms involved in reprogramming, we generated interspecies heterokaryons (fused mouse embryonic stem (ES) cells and human fibroblasts) that induce reprogramming synchronously, frequently and fast. Here we show that reprogramming towards pluripotency in single heterokaryons is initiated without cell division or DNA replication, rapidly (1 day) and efficiently (70%). Short interfering RNA (siRNA)-mediated knockdown showed that activation-induced cytidine deaminase (AID, also known as AICDA) is required for promoter demethylation and induction of OCT4 (also known as POU5F1) and NANOG gene expression. AID protein bound silent methylated OCT4 and NANOG promoters in fibroblasts, but not active demethylated promoters in ES cells. These data provide new evidence that mammalian AID is required for active DNA demethylation and initiation of nuclear reprogramming towards pluripotency in human somatic cells.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906123/" 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/PMC2906123/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhutani, Nidhi -- Brady, Jennifer J -- Damian, Mara -- Sacco, Alessandra -- Corbel, Stephane Y -- Blau, Helen M -- AG009521/AG/NIA NIH HHS/ -- AG024987/AG/NIA NIH HHS/ -- AI007328/AI/NIAID NIH HHS/ -- R01 AG009521/AG/NIA NIH HHS/ -- R01 AG009521-25/AG/NIA NIH HHS/ -- R01 AG024987/AG/NIA NIH HHS/ -- R01 AG024987-05/AG/NIA NIH HHS/ -- T32 AI007328/AI/NIAID NIH HHS/ -- U01 HL100397/HL/NHLBI NIH HHS/ -- England -- Nature. 2010 Feb 25;463(7284):1042-7. doi: 10.1038/nature08752.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Baxter Laboratory for Stem Cell Biology, Institute for Stem Cell Biology and Regenerative Medicine, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305-5175, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20027182" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Division ; Cell Fusion ; Cell Line ; Cells, Cultured ; Cellular Reprogramming/genetics/*physiology ; Chromatin Immunoprecipitation ; Cytidine Deaminase/deficiency/genetics/*metabolism ; DNA/chemistry/genetics/metabolism ; *DNA Methylation ; DNA Replication ; Embryonic Stem Cells/cytology/metabolism ; Fibroblasts/cytology/metabolism ; Gene Expression Regulation ; Gene Knockdown Techniques ; Homeodomain Proteins/genetics ; Humans ; Induced Pluripotent Stem Cells/*cytology/enzymology/*metabolism ; Lung/cytology/embryology ; Mice ; Models, Biological ; Octamer Transcription Factor-3/genetics ; Promoter Regions, Genetic/genetics ; Time Factors
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  • 59
    Publication Date: 2009-12-17
    Description: Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951497/" 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/PMC3951497/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Li, Ruiqiang -- Fan, Wei -- Tian, Geng -- Zhu, Hongmei -- He, Lin -- Cai, Jing -- Huang, Quanfei -- Cai, Qingle -- Li, Bo -- Bai, Yinqi -- Zhang, Zhihe -- Zhang, Yaping -- Wang, Wen -- Li, Jun -- Wei, Fuwen -- Li, Heng -- Jian, Min -- Li, Jianwen -- Zhang, Zhaolei -- Nielsen, Rasmus -- Li, Dawei -- Gu, Wanjun -- Yang, Zhentao -- Xuan, Zhaoling -- Ryder, Oliver A -- Leung, Frederick Chi-Ching -- Zhou, Yan -- Cao, Jianjun -- Sun, Xiao -- Fu, Yonggui -- Fang, Xiaodong -- Guo, Xiaosen -- Wang, Bo -- Hou, Rong -- Shen, Fujun -- Mu, Bo -- Ni, Peixiang -- Lin, Runmao -- Qian, Wubin -- Wang, Guodong -- Yu, Chang -- Nie, Wenhui -- Wang, Jinhuan -- Wu, Zhigang -- Liang, Huiqing -- Min, Jiumeng -- Wu, Qi -- Cheng, Shifeng -- Ruan, Jue -- Wang, Mingwei -- Shi, Zhongbin -- Wen, Ming -- Liu, Binghang -- Ren, Xiaoli -- Zheng, Huisong -- Dong, Dong -- Cook, Kathleen -- Shan, Gao -- Zhang, Hao -- Kosiol, Carolin -- Xie, Xueying -- Lu, Zuhong -- Zheng, Hancheng -- Li, Yingrui -- Steiner, Cynthia C -- Lam, Tommy Tsan-Yuk -- Lin, Siyuan -- Zhang, Qinghui -- Li, Guoqing -- Tian, Jing -- Gong, Timing -- Liu, Hongde -- Zhang, Dejin -- Fang, Lin -- Ye, Chen -- Zhang, Juanbin -- Hu, Wenbo -- Xu, Anlong -- Ren, Yuanyuan -- Zhang, Guojie -- Bruford, Michael W -- Li, Qibin -- Ma, Lijia -- Guo, Yiran -- An, Na -- Hu, Yujie -- Zheng, Yang -- Shi, Yongyong -- Li, Zhiqiang -- Liu, Qing -- Chen, Yanling -- Zhao, Jing -- Qu, Ning -- Zhao, Shancen -- Tian, Feng -- Wang, Xiaoling -- Wang, Haiyin -- Xu, Lizhi -- Liu, Xiao -- Vinar, Tomas -- Wang, Yajun -- Lam, Tak-Wah -- Yiu, Siu-Ming -- Liu, Shiping -- Zhang, Hemin -- Li, Desheng -- Huang, Yan -- Wang, Xia -- Yang, Guohua -- Jiang, Zhi -- Wang, Junyi -- Qin, Nan -- Li, Li -- Li, Jingxiang -- Bolund, Lars -- Kristiansen, Karsten -- Wong, Gane Ka-Shu -- Olson, Maynard -- Zhang, Xiuqing -- Li, Songgang -- Yang, Huanming -- Wang, Jian -- Wang, Jun -- R01 HG003229/HG/NHGRI NIH HHS/ -- R01 HG003229-05/HG/NHGRI NIH HHS/ -- England -- Nature. 2010 Jan 21;463(7279):311-7. doi: 10.1038/nature08696. Epub 2009 Dec 13.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉BGI-Shenzhen, Shenzhen 518083, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010809" target="_blank"〉PubMed〈/a〉
    Keywords: Algorithms ; Animals ; China ; Conserved Sequence/genetics ; Contig Mapping ; Diet/veterinary ; Dogs ; Evolution, Molecular ; Female ; Fertility/genetics/physiology ; Genome/*genetics ; *Genomics ; Heterozygote ; Humans ; Multigene Family/genetics ; Polymorphism, Single Nucleotide/genetics ; Receptors, G-Protein-Coupled/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Synteny/genetics ; Ursidae/classification/*genetics/physiology
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  • 60
    Publication Date: 2009-12-17
    Description: The Red Queen describes a view of nature in which species continually evolve but do not become better adapted. It is one of the more distinctive metaphors of evolutionary biology, but no test of its claim that speciation occurs at a constant rate has ever been made against competing models that can predict virtually identical outcomes, nor has any mechanism been proposed that could cause the constant-rate phenomenon. Here we use 101 phylogenies of animal, plant and fungal taxa to test the constant-rate claim against four competing models. Phylogenetic branch lengths record the amount of time or evolutionary change between successive events of speciation. The models predict the distribution of these lengths by specifying how factors combine to bring about speciation, or by describing how rates of speciation vary throughout a tree. We find that the hypotheses that speciation follows the accumulation of many small events that act either multiplicatively or additively found support in 8% and none of the trees, respectively. A further 8% of trees hinted that the probability of speciation changes according to the amount of divergence from the ancestral species, and 6% suggested speciation rates vary among taxa. By comparison, 78% of the trees fit the simplest model in which new species emerge from single events, each rare but individually sufficient to cause speciation. This model predicts a constant rate of speciation, and provides a new interpretation of the Red Queen: the metaphor of species losing a race against a deteriorating environment is replaced by a view linking speciation to rare stochastic events that cause reproductive isolation. Attempts to understand species-radiations or why some groups have more or fewer species should look to the size of the catalogue of potential causes of speciation shared by a group of closely related organisms rather than to how those causes combine.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Venditti, Chris -- Meade, Andrew -- Pagel, Mark -- England -- Nature. 2010 Jan 21;463(7279):349-52. doi: 10.1038/nature08630. Epub 2009 Dec 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉School of Biological Sciences, University of Reading, Reading, Berkshire, RG6 6BX, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010607" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Animals ; *Genetic Speciation ; *Models, Biological ; *Phylogeny ; Selection, Genetic ; Stochastic Processes
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  • 61
    Publication Date: 2009-01-14
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4340503/" 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/PMC4340503/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kelly, Bernard T -- McCoy, Airlie J -- Spate, Kira -- Miller, Sharon E -- Evans, Philip R -- Honing, Stefan -- Owen, David J -- 090909/Wellcome Trust/United Kingdom -- MC_U105178845/Medical Research Council/United Kingdom -- England -- Nature. 2008 Dec 18;456(7224):976-79. doi: 10.1038/nature07422.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19140243" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Protein Complex 2/*chemistry/genetics/*metabolism ; Amino Acid Motifs ; Animals ; Antigens, CD4/*chemistry/*metabolism ; Binding Sites ; Conserved Sequence ; *Endocytosis ; Humans ; Leucine/*metabolism ; Mice ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Subunits/chemistry/genetics/metabolism ; Rats
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  • 62
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2009 Jan 22;457(7228):369. doi: 10.1038/457369a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19158758" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Breeding/economics/*methods ; Cattle/*genetics ; Dairying/economics/*methods ; Female ; Internationality ; Male ; Milk/*secretion/*standards ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide/genetics ; United States ; United States Department of Agriculture
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  • 63
    Publication Date: 2009-05-19
    Description: Midbrain dopamine neurons are activated by reward or sensory stimuli predicting reward. These excitatory responses increase as the reward value increases. This response property has led to a hypothesis that dopamine neurons encode value-related signals and are inhibited by aversive events. Here we show that this is true only for a subset of dopamine neurons. We recorded the activity of dopamine neurons in monkeys (Macaca mulatta) during a Pavlovian procedure with appetitive and aversive outcomes (liquid rewards and airpuffs directed at the face, respectively). We found that some dopamine neurons were excited by reward-predicting stimuli and inhibited by airpuff-predicting stimuli, as the value hypothesis predicts. However, a greater number of dopamine neurons were excited by both of these stimuli, inconsistent with the hypothesis. Some dopamine neurons were also excited by both rewards and airpuffs themselves, especially when they were unpredictable. Neurons excited by the airpuff-predicting stimuli were located more dorsolaterally in the substantia nigra pars compacta, whereas neurons inhibited by the stimuli were located more ventromedially, some in the ventral tegmental area. A similar anatomical difference was observed for their responses to actual airpuffs. These findings suggest that different groups of dopamine neurons convey motivational signals in distinct manners.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2739096/" 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/PMC2739096/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsumoto, Masayuki -- Hikosaka, Okihide -- Z01 EY000415-05/Intramural NIH HHS/ -- England -- Nature. 2009 Jun 11;459(7248):837-41. doi: 10.1038/nature08028. Epub 2009 May 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Sensorimotor Research, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-4435, USA. matsumotom@nei.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19448610" target="_blank"〉PubMed〈/a〉
    Keywords: Air ; Animals ; Appetitive Behavior/physiology ; Conditioning, Classical/physiology ; Dopamine/*metabolism ; Macaca mulatta/*physiology ; Models, Neurological ; *Motivation ; Neurons/*physiology ; Reward
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  • 64
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    Nature Publishing Group (NPG)
    Publication Date: 2009-11-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sukhdev, Pavan -- England -- Nature. 2009 Nov 19;462(7271):277. doi: 10.1038/462277a. Epub 2009 Nov 15.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Economics of Ecosystems and Biodiversity (TEEB) project, United Nations Campus, Hermann-Ehlers-Strasse 10, 53113 Bonn, Germany. teeb@unep-teeb.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19915547" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; *Conservation of Natural Resources ; Fresh Water ; Government ; Humans ; Poverty
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  • 65
    Publication Date: 2009-05-05
    Description: A20 is a negative regulator of the NF-kappaB pathway and was initially identified as being rapidly induced after tumour-necrosis factor-alpha stimulation. It has a pivotal role in regulation of the immune response and prevents excessive activation of NF-kappaB in response to a variety of external stimuli; recent genetic studies have disclosed putative associations of polymorphic A20 (also called TNFAIP3) alleles with autoimmune disease risk. However, the involvement of A20 in the development of human cancers is unknown. Here we show, using a genome-wide analysis of genetic lesions in 238 B-cell lymphomas, that A20 is a common genetic target in B-lineage lymphomas. A20 is frequently inactivated by somatic mutations and/or deletions in mucosa-associated tissue lymphoma (18 out of 87; 21.8%) and Hodgkin's lymphoma of nodular sclerosis histology (5 out of 15; 33.3%), and, to a lesser extent, in other B-lineage lymphomas. When re-expressed in a lymphoma-derived cell line with no functional A20 alleles, wild-type A20, but not mutant A20, resulted in suppression of cell growth and induction of apoptosis, accompanied by downregulation of NF-kappaB activation. The A20-deficient cells stably generated tumours in immunodeficient mice, whereas the tumorigenicity was effectively suppressed by re-expression of A20. In A20-deficient cells, suppression of both cell growth and NF-kappaB activity due to re-expression of A20 depended, at least partly, on cell-surface-receptor signalling, including the tumour-necrosis factor receptor. Considering the physiological function of A20 in the negative modulation of NF-kappaB activation induced by multiple upstream stimuli, our findings indicate that uncontrolled signalling of NF-kappaB caused by loss of A20 function is involved in the pathogenesis of subsets of B-lineage lymphomas.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kato, Motohiro -- Sanada, Masashi -- Kato, Itaru -- Sato, Yasuharu -- Takita, Junko -- Takeuchi, Kengo -- Niwa, Akira -- Chen, Yuyan -- Nakazaki, Kumi -- Nomoto, Junko -- Asakura, Yoshitaka -- Muto, Satsuki -- Tamura, Azusa -- Iio, Mitsuru -- Akatsuka, Yoshiki -- Hayashi, Yasuhide -- Mori, Hiraku -- Igarashi, Takashi -- Kurokawa, Mineo -- Chiba, Shigeru -- Mori, Shigeo -- Ishikawa, Yuichi -- Okamoto, Koji -- Tobinai, Kensei -- Nakagama, Hitoshi -- Nakahata, Tatsutoshi -- Yoshino, Tadashi -- Kobayashi, Yukio -- Ogawa, Seishi -- England -- Nature. 2009 Jun 4;459(7247):712-6. doi: 10.1038/nature07969. Epub 2009 May 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cancer Genomics Project, Department of Pediatrics, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19412163" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/physiology ; Cell Line ; Cysteine Endopeptidases/*genetics/*metabolism ; DNA-Binding Proteins ; Gene Expression ; *Gene Silencing ; Genome/genetics ; Humans ; Intracellular Signaling Peptides and Proteins/*genetics/*metabolism ; Lymphoma, B-Cell/*genetics/*physiopathology ; Mice ; NF-kappa B/genetics/metabolism ; Nuclear Proteins/*genetics/*metabolism
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  • 66
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    Nature Publishing Group (NPG)
    Publication Date: 2009-04-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉England -- Nature. 2009 Apr 16;458(7240):808. doi: 10.1038/458808a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19369979" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antarctic Regions ; *Ecosystem ; International Cooperation/*legislation & jurisprudence ; Travel/*legislation & jurisprudence
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  • 67
    Publication Date: 2009-07-31
    Description: Acid-sensing ion channels are proton-activated, sodium-selective channels composed of three subunits, and are members of the superfamily of epithelial sodium channels, mechanosensitive and FMRF-amide peptide-gated ion channels. These ubiquitous eukaryotic ion channels have essential roles in biological activities as diverse as sodium homeostasis, taste and pain. Despite their crucial roles in biology and their unusual trimeric subunit stoichiometry, there is little knowledge of the structural and chemical principles underlying their ion channel architecture and ion-binding sites. Here we present the structure of a functional acid-sensing ion channel in a desensitized state at 3 A resolution, the location and composition of the approximately 8 A 'thick' desensitization gate, and the trigonal antiprism coordination of caesium ions bound in the extracellular vestibule. Comparison of the acid-sensing ion channel structure with the ATP-gated P2X(4) receptor reveals similarity in pore architecture and aqueous vestibules, suggesting that there are unanticipated yet common structural and mechanistic principles.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2845979/" 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/PMC2845979/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gonzales, Eric B -- Kawate, Toshimitsu -- Gouaux, Eric -- F32 GM083615/GM/NIGMS NIH HHS/ -- F32 GM083615-01/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 30;460(7255):599-604. doi: 10.1038/nature08218.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Portland, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19641589" target="_blank"〉PubMed〈/a〉
    Keywords: Acid Sensing Ion Channels ; Animals ; Binding Sites ; CHO Cells ; Cell Line ; Cesium/metabolism ; Chickens/*physiology ; Cricetinae ; Cricetulus ; Crystallization ; Humans ; Ions/metabolism ; *Models, Molecular ; Nerve Tissue Proteins/*chemistry ; Protein Structure, Tertiary ; Receptors, Purinergic P2/*chemistry ; Receptors, Purinergic P2X ; Sodium Channels/*chemistry ; Zebrafish/*physiology
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  • 68
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    Nature Publishing Group (NPG)
    Publication Date: 2009-01-23
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- England -- Nature. 2009 Jan 22;457(7228):368. doi: 10.1038/457368a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19158757" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Drosophila/*classification ; Drosophila melanogaster/classification ; Species Specificity ; *Terminology as Topic
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  • 69
    Publication Date: 2009-03-27
    Description: Toll-like receptors (TLRs) recognize microbial components, and evoke inflammation and immune responses. TLR stimulation activates complex gene expression networks that regulate the magnitude and duration of the immune reaction. Here we identify the TLR-inducible gene Zc3h12a as an immune response modifier that has an essential role in preventing immune disorders. Zc3h12a-deficient mice suffered from severe anaemia, and most died within 12 weeks. Zc3h12a(-/-) mice also showed augmented serum immunoglobulin levels and autoantibody production, together with a greatly increased number of plasma cells, as well as infiltration of plasma cells to the lung. Most Zc3h12a(-/-) splenic T cells showed effector/memory characteristics and produced interferon-gamma in response to T-cell receptor stimulation. Macrophages from Zc3h12a(-/-) mice showed highly increased production of interleukin (IL)-6 and IL-12p40 (also known as IL12b), but not TNF, in response to TLR ligands. Although the activation of TLR signalling pathways was normal, Il6 messenger RNA decay was severely impaired in Zc3h12a(-/-) macrophages. Overexpression of Zc3h12a accelerated Il6 mRNA degradation via its 3'-untranslated region (UTR), and destabilized RNAs with 3'-UTRs for genes including Il6, Il12p40 and the calcitonin receptor gene Calcr. Zc3h12a contains a putative amino-terminal nuclease domain, and the expressed protein had RNase activity, consistent with a role in the decay of Il6 mRNA. Together, these results indicate that Zc3h12a is an essential RNase that prevents immune disorders by directly controlling the stability of a set of inflammatory genes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Matsushita, Kazufumi -- Takeuchi, Osamu -- Standley, Daron M -- Kumagai, Yutaro -- Kawagoe, Tatsukata -- Miyake, Tohru -- Satoh, Takashi -- Kato, Hiroki -- Tsujimura, Tohru -- Nakamura, Haruki -- Akira, Shizuo -- P01 AI070167/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Apr 30;458(7242):1185-90. doi: 10.1038/nature07924. Epub 2009 Mar 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Host Defense, WPI Immunology Frontier Research Center, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19322177" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics/metabolism ; Anemia/complications/genetics ; Animals ; Autoantibodies/blood/immunology ; Autoimmune Diseases/complications/immunology ; Cell Line ; Cytokines/biosynthesis/genetics ; Fetal Diseases/immunology ; Humans ; Immunity/*genetics/*immunology ; Inflammation Mediators/metabolism ; Interleukin-6/genetics ; Macrophages, Peritoneal/immunology/metabolism ; Mice ; Plasma Cells/cytology ; *RNA Stability ; Ribonucleases/deficiency/genetics/*metabolism ; T-Lymphocytes/immunology
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  • 70
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    Nature Publishing Group (NPG)
    Publication Date: 2009-04-01
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dalton, Rex -- Witze, Alexandra -- England -- Nature. 2009 Mar 26;458(7237):396. doi: 10.1038/458396a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19334300" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Ecosystem ; *Greenhouse Effect ; History, 20th Century ; History, 21st Century ; Leadership ; Marine Biology ; United States ; United States Government Agencies/*organization & administration
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  • 71
    Publication Date: 2009-08-12
    Description: Reprogramming somatic cells to induced pluripotent stem (iPS) cells has been accomplished by expressing pluripotency factors and oncogenes, but the low frequency and tendency to induce malignant transformation compromise the clinical utility of this powerful approach. We address both issues by investigating the mechanisms limiting reprogramming efficiency in somatic cells. Here we show that reprogramming factors can activate the p53 (also known as Trp53 in mice, TP53 in humans) pathway. Reducing signalling to p53 by expressing a mutated version of one of its negative regulators, by deleting or knocking down p53 or its target gene, p21 (also known as Cdkn1a), or by antagonizing reprogramming-induced apoptosis in mouse fibroblasts increases reprogramming efficiency. Notably, decreasing p53 protein levels enabled fibroblasts to give rise to iPS cells capable of generating germline-transmitting chimaeric mice using only Oct4 (also known as Pou5f1) and Sox2. Furthermore, silencing of p53 significantly increased the reprogramming efficiency of human somatic cells. These results provide insights into reprogramming mechanisms and suggest new routes to more efficient reprogramming while minimizing the use of oncogenes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735889/" 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/PMC2735889/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawamura, Teruhisa -- Suzuki, Jotaro -- Wang, Yunyuan V -- Menendez, Sergio -- Morera, Laura Batlle -- Raya, Angel -- Wahl, Geoffrey M -- Izpisua Belmonte, Juan Carlos -- 5 R01 CA061449/CA/NCI NIH HHS/ -- 5 R01 CA100845/CA/NCI NIH HHS/ -- R01 CA061449/CA/NCI NIH HHS/ -- R01 CA061449-30/CA/NCI NIH HHS/ -- R01 CA100845/CA/NCI NIH HHS/ -- R01 CA100845-05/CA/NCI NIH HHS/ -- R33 HL088293/HL/NHLBI NIH HHS/ -- R33 HL088293-03/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Aug 27;460(7259):1140-4. doi: 10.1038/nature08311. Epub 2009 Aug 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19668186" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cells, Cultured ; Cellular Reprogramming/*physiology ; Cyclin-Dependent Kinase Inhibitor p21/deficiency/genetics/metabolism ; Down-Regulation ; Embryo, Mammalian/cytology ; Female ; Fibroblasts/cytology/metabolism ; Humans ; Keratinocytes ; Male ; Mice ; Mice, Inbred C57BL ; Pluripotent Stem Cells/*cytology/*metabolism ; Tumor Suppressor Protein p53/deficiency/genetics/*metabolism
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  • 72
    Publication Date: 2009-01-13
    Description: In an adaptive immune response, naive T cells proliferate during infection and generate long-lived memory cells that undergo secondary expansion after a repeat encounter with the same pathogen. Although natural killer (NK) cells have traditionally been classified as cells of the innate immune system, they share many similarities with cytotoxic T lymphocytes. We use a mouse model of cytomegalovirus infection to show that, like T cells, NK cells bearing the virus-specific Ly49H receptor proliferate 100-fold in the spleen and 1,000-fold in the liver after infection. After a contraction phase, Ly49H-positive NK cells reside in lymphoid and non-lymphoid organs for several months. These self-renewing 'memory' NK cells rapidly degranulate and produce cytokines on reactivation. Adoptive transfer of these NK cells into naive animals followed by viral challenge results in a robust secondary expansion and protective immunity. These findings reveal properties of NK cells that were previously attributed only to cells of the adaptive immune system.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2674434/" 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/PMC2674434/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sun, Joseph C -- Beilke, Joshua N -- Lanier, Lewis L -- AI068129/AI/NIAID NIH HHS/ -- R01 AI068129/AI/NIAID NIH HHS/ -- R01 AI068129-09/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Jan 29;457(7229):557-61. doi: 10.1038/nature07665. Epub 2009 Jan 11.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, California 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19136945" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing/deficiency/genetics ; Adoptive Transfer ; Animals ; Cell Proliferation ; Immunologic Memory/*immunology ; Killer Cells, Natural/*cytology/*immunology ; Lymphoid Tissue/immunology ; Mice ; Mice, Congenic ; Mice, Inbred C57BL ; *Models, Immunological ; Muromegalovirus/immunology/physiology ; Phenotype ; T-Lymphocytes, Cytotoxic/immunology
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  • 73
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dance, Amber -- England -- Nature. 2009 Apr 2;458(7238):664-5. doi: 10.1038/nj7238-664a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19444985" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Laboratory/immunology ; Asthma/immunology ; Hypersensitivity/epidemiology/*immunology ; Occupational Diseases/epidemiology/*etiology/mortality ; *Occupational Exposure/statistics & numerical data ; *Research Personnel
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  • 74
    Publication Date: 2009-01-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gore, Jeff -- van Oudenaarden, Alexander -- K99 GM085279/GM/NIGMS NIH HHS/ -- R00 GM085279/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Jan 15;457(7227):271-2. doi: 10.1038/457271a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19148089" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biological Clocks/*physiology ; Circadian Rhythm/*physiology ; Escherichia coli ; *Feedback, Physiological ; Gene Expression Regulation/*genetics ; Genes, Synthetic/*genetics ; Genetic Engineering ; *Models, Biological
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  • 75
    Publication Date: 2009-07-03
    Description: Induced pluripotent stem cells offer unprecedented potential for disease research, drug screening, toxicology and regenerative medicine. However, the process of reprogramming is inefficient and often incomplete. Here I consider reasons for bottlenecks in induced pluripotent stem cell generation, and propose a model in which most or all cells have the potential to become pluripotent.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yamanaka, Shinya -- England -- Nature. 2009 Jul 2;460(7251):49-52. doi: 10.1038/nature08180.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto 606-8507, Japan. yamanaka@cira.kyoto-u.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571877" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Lineage ; *Cellular Reprogramming/genetics ; Epigenesis, Genetic ; Humans ; Mice ; *Models, Biological ; Pluripotent Stem Cells/*cytology/metabolism ; Stochastic Processes ; Transduction, Genetic
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  • 76
    Publication Date: 2009-11-06
    Description: The activation of innate immune responses by nucleic acids is crucial to protective and pathological immunities and is mediated by the transmembrane Toll-like receptors (TLRs) and cytosolic receptors. However, it remains unknown whether a mechanism exists that integrates these nucleic-acid-sensing systems. Here we show that high-mobility group box (HMGB) proteins 1, 2 and 3 function as universal sentinels for nucleic acids. HMGBs bind to all immunogenic nucleic acids examined with a correlation between affinity and immunogenic potential. Hmgb1(-/-) and Hmgb2(-/-) mouse cells are defective in type-I interferon and inflammatory cytokine induction by DNA or RNA targeted to activate the cytosolic nucleic-acid-sensing receptors; cells in which the expression of all three HMGBs is suppressed show a more profound defect, accompanied by impaired activation of the transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor (NF)-kappaB. The absence of HMGBs also severely impairs the activation of TLR3, TLR7 and TLR9 by their cognate nucleic acids. Our results therefore indicate a hierarchy in the nucleic-acid-mediated activation of immune responses, wherein the selective activation of nucleic-acid-sensing receptors is contingent on the more promiscuous sensing of nucleic acids by HMGBs. These findings may have implications for understanding the evolution of the innate immune system and for the treatment of immunological disorders.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yanai, Hideyuki -- Ban, Tatsuma -- Wang, ZhiChao -- Choi, Myoung Kwon -- Kawamura, Takeshi -- Negishi, Hideo -- Nakasato, Makoto -- Lu, Yan -- Hangai, Sho -- Koshiba, Ryuji -- Savitsky, David -- Ronfani, Lorenza -- Akira, Shizuo -- Bianchi, Marco E -- Honda, Kenya -- Tamura, Tomohiko -- Kodama, Tatsuhiko -- Taniguchi, Tadatsugu -- England -- Nature. 2009 Nov 5;462(7269):99-103. doi: 10.1038/nature08512.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19890330" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cytosol/immunology ; DNA/immunology ; HMGB Proteins/deficiency/genetics/*immunology/*metabolism ; HMGB1 Protein/deficiency/genetics/immunology/metabolism ; HMGB2 Protein/deficiency/genetics/immunology/metabolism ; Immunity, Innate/*immunology ; Interferon Regulatory Factor-3/metabolism ; Mice ; Mice, Inbred C57BL ; Models, Immunological ; NF-kappa B/metabolism ; Nucleic Acids/*immunology ; Nucleotides/chemistry/immunology/metabolism ; RNA/immunology ; Signal Transduction ; Toll-Like Receptors/immunology ; Virus Diseases/immunology/virology
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  • 77
    Publication Date: 2009-12-17
    Description: B-cell malignancies, such as human Burkitt's lymphoma, often contain translocations that link c-myc or other proto-oncogenes to the immunoglobulin heavy chain locus (IgH, encoded by Igh). The nature of elements that activate oncogenes within such translocations has been a long-standing question. Translocations within Igh involve DNA double-strand breaks initiated either by the RAG1/2 endonuclease during variable, diversity and joining gene segment (V(D)J) recombination, or by activation-induced cytidine deaminase (AID, also known as AICDA) during class switch recombination (CSR). V(D)J recombination in progenitor B (pro-B) cells assembles Igh variable region exons upstream of mu constant region (Cmu) exons, which are the first of several sets of C(H) exons ('C(H) genes') within a C(H) locus that span several hundred kilobases (kb). In mature B cells, CSR deletes Cmu and replaces it with a downstream C(H) gene. An intronic enhancer (iEmu) between the variable region exons and Cmu promotes V(D)J recombination in developing B cells. Furthermore, the Igh 3' regulatory region (Igh3'RR) lies downstream of the C(H) locus and modulates CSR by long-range transcriptional enhancement of C(H) genes. Transgenic mice bearing iEmu or Igh3'RR sequences fused to c-myc are predisposed to B lymphomas, demonstrating that such elements can confer oncogenic c-myc expression. However, in many B-cell lymphomas, Igh-c-myc translocations delete iEmu and place c-myc up to 200 kb upstream of the Igh3'RR. Here we address the oncogenic role of the Igh3'RR by inactivating it in two distinct mouse models for B-cell lymphoma with Igh-c-myc translocations. We show that the Igh3'RR is dispensable for pro-B-cell lymphomas with V(D)J recombination-initiated translocations, but is required for peripheral B-cell lymphomas with CSR-associated translocations. As the Igh3'RR is not required for CSR-associated Igh breaks or Igh-c-myc translocations in peripheral B-cell lymphoma progenitors, we conclude that this regulatory region confers oncogenic activity by long-range and developmental stage-specific activation of translocated c-myc genes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2802177/" 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/PMC2802177/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gostissa, Monica -- Yan, Catherine T -- Bianco, Julia M -- Cogne, Michel -- Pinaud, Eric -- Alt, Frederick W -- CA92625/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Dec 10;462(7274):803-7. doi: 10.1038/nature08633.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20010689" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/*genetics ; Alleles ; Animals ; Cells, Cultured ; Chromosome Breakpoints ; Gene Rearrangement, B-Lymphocyte/*genetics ; Genes, Immunoglobulin Heavy Chain/*genetics ; Genes, myc/*genetics ; Immunoglobulin Class Switching/genetics ; Lymphoma, B-Cell/*genetics/pathology ; Mice ; Mice, Transgenic ; Regulatory Sequences, Nucleic Acid/*genetics ; Translocation, Genetic/*genetics
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  • 78
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    Nature Publishing Group (NPG)
    Publication Date: 2009-06-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reiff, Sarah B -- Striepen, Boris -- England -- Nature. 2009 Jun 18;459(7249):918-9. doi: 10.1038/459918a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536248" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Humans ; Malaria, Falciparum/drug therapy/*parasitology ; Models, Biological ; Plasmodium falciparum/*metabolism ; Protein Binding ; Protein Transport ; Protozoan Proteins/antagonists & inhibitors/*metabolism ; Vacuoles/metabolism/parasitology
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  • 79
    Publication Date: 2009-12-01
    Description: Changes in synaptic connections are considered essential for learning and memory formation. However, it is unknown how neural circuits undergo continuous synaptic changes during learning while maintaining lifelong memories. Here we show, by following postsynaptic dendritic spines over time in the mouse cortex, that learning and novel sensory experience lead to spine formation and elimination by a protracted process. The extent of spine remodelling correlates with behavioural improvement after learning, suggesting a crucial role of synaptic structural plasticity in memory formation. Importantly, a small fraction of new spines induced by novel experience, together with most spines formed early during development and surviving experience-dependent elimination, are preserved and provide a structural basis for memory retention throughout the entire life of an animal. These studies indicate that learning and daily sensory experience leave minute but permanent marks on cortical connections and suggest that lifelong memories are stored in largely stably connected synaptic networks.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4724802/" 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/PMC4724802/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yang, Guang -- Pan, Feng -- Gan, Wen-Biao -- R01 NS047325/NS/NINDS NIH HHS/ -- England -- Nature. 2009 Dec 17;462(7275):920-4. doi: 10.1038/nature08577. Epub 2009 Nov 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Molecular Neurobiology Program, The Helen and Martin Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, Department of Physiology and Neuroscience, New York University School of Medicine, New York, New York 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19946265" target="_blank"〉PubMed〈/a〉
    Keywords: Aging/physiology ; Animals ; Dendritic Spines/metabolism/*physiology ; Forelimb/physiology ; Memory/*physiology ; Mice ; Motor Cortex/cytology/physiology ; Motor Skills/physiology ; Neuronal Plasticity/physiology ; Pyramidal Cells/metabolism ; Synapses/*metabolism ; Time Factors
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  • 80
    Publication Date: 2009-06-19
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McDonnell, Anna -- England -- Nature. 2009 Jun 18;459(7249):909. doi: 10.1038/459909b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536241" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; Fertility ; History, Ancient ; Humans ; Pregnancy ; Sculpture/*history
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  • 81
    Publication Date: 2009-07-31
    Description: P2X receptors are cation-selective ion channels gated by extracellular ATP, and are implicated in diverse physiological processes, from synaptic transmission to inflammation to the sensing of taste and pain. Because P2X receptors are not related to other ion channel proteins of known structure, there is at present no molecular foundation for mechanisms of ligand-gating, allosteric modulation and ion permeation. Here we present crystal structures of the zebrafish P2X(4) receptor in its closed, resting state. The chalice-shaped, trimeric receptor is knit together by subunit-subunit contacts implicated in ion channel gating and receptor assembly. Extracellular domains, rich in beta-strands, have large acidic patches that may attract cations, through fenestrations, to vestibules near the ion channel. In the transmembrane pore, the 'gate' is defined by an approximately 8 A slab of protein. We define the location of three non-canonical, intersubunit ATP-binding sites, and suggest that ATP binding promotes subunit rearrangement and ion channel opening.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2720809/" 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/PMC2720809/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kawate, Toshimitsu -- Michel, Jennifer Carlisle -- Birdsong, William T -- Gouaux, Eric -- U54 GM075026/GM/NIGMS NIH HHS/ -- U54 GM075026-04/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 30;460(7255):592-8. doi: 10.1038/nature08198.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vollum Institute, Oregon Health and Science University, 3181 Southwest Sam Jackson Park Road, Oregon 97239, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19641588" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/metabolism ; Animals ; Binding Sites ; Cell Line ; Crystallography, X-Ray ; Gadolinium/metabolism ; Humans ; Ion Channels/antagonists & inhibitors/*chemistry ; Membrane Proteins/chemistry ; *Models, Molecular ; Protein Binding ; Protein Folding ; Protein Structure, Tertiary ; Purinergic P2 Receptor Antagonists ; Receptors, Purinergic P2/*chemistry ; Receptors, Purinergic P2X4 ; Zebrafish/*physiology ; Zebrafish Proteins/antagonists & inhibitors/*chemistry
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  • 82
    Publication Date: 2009-07-25
    Description: African primates are naturally infected with over 40 different simian immunodeficiency viruses (SIVs), two of which have crossed the species barrier and generated human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2). Unlike the human viruses, however, SIVs do not generally cause acquired immunodeficiency syndrome (AIDS) in their natural hosts. Here we show that SIVcpz, the immediate precursor of HIV-1, is pathogenic in free-ranging chimpanzees. By following 94 members of two habituated chimpanzee communities in Gombe National Park, Tanzania, for over 9 years, we found a 10- to 16-fold higher age-corrected death hazard for SIVcpz-infected (n = 17) compared to uninfected (n = 77) chimpanzees. We also found that SIVcpz-infected females were less likely to give birth and had a higher infant mortality rate than uninfected females. Immunohistochemistry and in situ hybridization of post-mortem spleen and lymph node samples from three infected and two uninfected chimpanzees revealed significant CD4(+) T-cell depletion in all infected individuals, with evidence of high viral replication and extensive follicular dendritic cell virus trapping in one of them. One female, who died within 3 years of acquiring SIVcpz, had histopathological findings consistent with end-stage AIDS. These results indicate that SIVcpz, like HIV-1, is associated with progressive CD4(+) T-cell loss, lymphatic tissue destruction and premature death. These findings challenge the prevailing view that all natural SIV infections are non-pathogenic and suggest that SIVcpz has a substantial negative impact on the health, reproduction and lifespan of chimpanzees in the wild.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2872475/" 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/PMC2872475/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keele, Brandon F -- Jones, James Holland -- Terio, Karen A -- Estes, Jacob D -- Rudicell, Rebecca S -- Wilson, Michael L -- Li, Yingying -- Learn, Gerald H -- Beasley, T Mark -- Schumacher-Stankey, Joann -- Wroblewski, Emily -- Mosser, Anna -- Raphael, Jane -- Kamenya, Shadrack -- Lonsdorf, Elizabeth V -- Travis, Dominic A -- Mlengeya, Titus -- Kinsel, Michael J -- Else, James G -- Silvestri, Guido -- Goodall, Jane -- Sharp, Paul M -- Shaw, George M -- Pusey, Anne E -- Hahn, Beatrice H -- HHSN266200400088C/PHS HHS/ -- P30 AI 27767/AI/NIAID NIH HHS/ -- P30 AI027767/AI/NIAID NIH HHS/ -- P30 AI027767-21A17134/AI/NIAID NIH HHS/ -- R01 AI058715/AI/NIAID NIH HHS/ -- R01 AI058715-06A1/AI/NIAID NIH HHS/ -- R01 AI50529/AI/NIAID NIH HHS/ -- R01 AI58715/AI/NIAID NIH HHS/ -- R37 AI050529/AI/NIAID NIH HHS/ -- R37 AI050529-06A1/AI/NIAID NIH HHS/ -- RR-00165/RR/NCRR NIH HHS/ -- T32 GM008111/GM/NIGMS NIH HHS/ -- U19 AI067854/AI/NIAID NIH HHS/ -- U19 AI067854-059010/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 23;460(7254):515-9. doi: 10.1038/nature08200.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19626114" target="_blank"〉PubMed〈/a〉
    Keywords: Acquired Immunodeficiency Syndrome/pathology ; Africa ; Animals ; Animals, Wild ; CD4-Positive T-Lymphocytes/immunology ; Female ; Humans ; Male ; Molecular Sequence Data ; Pan troglodytes/*virology ; Prevalence ; Simian Acquired Immunodeficiency ; Syndrome/epidemiology/immunology/*mortality/*pathology ; Simian Immunodeficiency Virus/*physiology
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  • 83
    Publication Date: 2009-04-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Danis, Bruno -- Griffiths, Huw -- England -- Nature. 2009 Apr 16;458(7240):830. doi: 10.1038/458830b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19370008" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antarctic Regions ; *Archives ; *Biodiversity ; Databases, Factual ; *Internet ; *Marine Biology ; Oceans and Seas
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  • 84
    Publication Date: 2009-11-13
    Description: Experience-dependent plasticity in the brain requires balanced excitation-inhibition. How individual circuit elements contribute to plasticity outcome in complex neocortical networks remains unknown. Here we report an intracellular analysis of ocular dominance plasticity-the loss of acuity and cortical responsiveness for an eye deprived of vision in early life. Unlike the typical progressive loss of pyramidal-cell bias, direct recording from fast-spiking cells in vivo reveals a counterintuitive initial shift towards the occluded eye followed by a late preference for the open eye, consistent with a spike-timing-dependent plasticity rule for these inhibitory neurons. Intracellular pharmacology confirms a dynamic switch of GABA (gamma-aminobutyric acid) impact to pyramidal cells following deprivation in juvenile mice only. Together these results suggest that the bidirectional recruitment of an initially binocular GABA circuit may contribute to experience-dependent plasticity in the developing visual cortex.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yazaki-Sugiyama, Yoko -- Kang, Siu -- Cateau, Hideyuki -- Fukai, Tomoki -- Hensch, Takao K -- England -- Nature. 2009 Nov 12;462(7270):218-21. doi: 10.1038/nature08485.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CREST, JST, Toyonaka, Osaka 560-0082, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19907494" target="_blank"〉PubMed〈/a〉
    Keywords: Action Potentials/*physiology ; Aging/physiology ; Animals ; Dominance, Ocular/*physiology ; Interneurons/metabolism ; Mice ; Mice, Inbred C57BL ; Models, Neurological ; Neuronal Plasticity/*physiology ; Neurons/*metabolism ; Photic Stimulation ; Pyramidal Cells/metabolism ; Receptors, GABA/metabolism ; Visual Cortex/cytology/physiology ; Visual Pathways/physiology ; Visual Perception/*physiology ; gamma-Aminobutyric Acid/*metabolism
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  • 85
    Publication Date: 2009-02-25
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Goudsmit, Jaap -- England -- Nature. 2009 Jan 22;457(7228):394. doi: 10.1038/457394a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Jaap Goudsmit is in the Research and Development Department of Crucell Holland, PO Box 2048, Leiden, 2301 CA, the Netherlands, and in the Academic Medical Center of the University of Amsterdam. j.goudsmit@crucell.com.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19158783" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; History, 20th Century ; History, 21st Century ; Humans ; Nobel Prize ; Prion Diseases/*history/transmission ; Prions/chemistry/*history/metabolism
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  • 86
    Publication Date: 2009-03-10
    Description: Acetylation within the globular core domain of histone H3 on lysine 56 (H3K56) has recently been shown to have a critical role in packaging DNA into chromatin following DNA replication and repair in budding yeast. However, the function or occurrence of this specific histone mark has not been studied in multicellular eukaryotes, mainly because the Rtt109 enzyme that is known to mediate acetylation of H3K56 (H3K56ac) is fungal-specific. Here we demonstrate that the histone acetyl transferase CBP (also known as Nejire) in flies and CBP and p300 (Ep300) in humans acetylate H3K56, whereas Drosophila Sir2 and human SIRT1 and SIRT2 deacetylate H3K56ac. The histone chaperones ASF1A in humans and Asf1 in Drosophila are required for acetylation of H3K56 in vivo, whereas the histone chaperone CAF-1 (chromatin assembly factor 1) in humans and Caf1 in Drosophila are required for the incorporation of histones bearing this mark into chromatin. We show that, in response to DNA damage, histones bearing acetylated K56 are assembled into chromatin in Drosophila and human cells, forming foci that colocalize with sites of DNA repair. Furthermore, acetylation of H3K56 is increased in multiple types of cancer, correlating with increased levels of ASF1A in these tumours. Our identification of multiple proteins regulating the levels of H3K56 acetylation in metazoans will allow future studies of this critical and unique histone modification that couples chromatin assembly to DNA synthesis, cell proliferation and cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2756583/" 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/PMC2756583/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Das, Chandrima -- Lucia, M Scott -- Hansen, Kirk C -- Tyler, Jessica K -- CA95641/CA/NCI NIH HHS/ -- GM64475/GM/NIGMS NIH HHS/ -- R01 CA095641/CA/NCI NIH HHS/ -- R01 CA095641-07/CA/NCI NIH HHS/ -- R01 GM064475/GM/NIGMS NIH HHS/ -- R01 GM064475-07/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 May 7;459(7243):113-7. doi: 10.1038/nature07861. Epub 2009 Mar 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, PO Box 6511, Aurora Colorado 80045, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19270680" target="_blank"〉PubMed〈/a〉
    Keywords: Acetylation ; Animals ; Cell Cycle Proteins/metabolism ; Cell Line ; Chromosomal Proteins, Non-Histone/metabolism ; DNA Damage/physiology ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*enzymology ; HeLa Cells ; Histone Deacetylases/metabolism ; Histones/*metabolism ; Humans ; Lysine/*metabolism ; Molecular Chaperones/metabolism ; Retinoblastoma-Binding Protein 4 ; Sirtuin 1 ; Sirtuin 2 ; Sirtuins/metabolism ; p300-CBP Transcription Factors/*metabolism
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  • 87
    Publication Date: 2009-07-31
    Description: Reactive oxygen species (ROS) produced by NADPH oxidase function as defence and signalling molecules related to innate immunity and various cellular responses. The activation of NADPH oxidase in response to plasma membrane receptor activation depends on the phosphorylation of cytoplasmic oxidase subunits, their translocation to membranes and the assembly of all NADPH oxidase components. Tumour necrosis factor (TNF) is a prominent stimulus of ROS production, but the molecular mechanisms by which TNF activates NADPH oxidase are poorly understood. Here we identify riboflavin kinase (RFK, formerly known as flavokinase) as a previously unrecognized TNF-receptor-1 (TNFR1)-binding protein that physically and functionally couples TNFR1 to NADPH oxidase. In mouse and human cells, RFK binds to both the TNFR1-death domain and to p22(phox), the common subunit of NADPH oxidase isoforms. RFK-mediated bridging of TNFR1 and p22(phox) is a prerequisite for TNF-induced but not for Toll-like-receptor-induced ROS production. Exogenous flavin mononucleotide or FAD was able to substitute fully for TNF stimulation of NADPH oxidase in RFK-deficient cells. RFK is rate-limiting in the synthesis of FAD, an essential prosthetic group of NADPH oxidase. The results suggest that TNF, through the activation of RFK, enhances the incorporation of FAD in NADPH oxidase enzymes, a critical step for the assembly and activation of NADPH oxidase.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yazdanpanah, Benjamin -- Wiegmann, Katja -- Tchikov, Vladimir -- Krut, Oleg -- Pongratz, Carola -- Schramm, Michael -- Kleinridders, Andre -- Wunderlich, Thomas -- Kashkar, Hamid -- Utermohlen, Olaf -- Bruning, Jens C -- Schutze, Stefan -- Kronke, Martin -- England -- Nature. 2009 Aug 27;460(7259):1159-63. doi: 10.1038/nature08206. Epub 2009 Jul 29.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Cologne, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19641494" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Line ; Cytochrome b Group/metabolism ; Enzyme Activation ; Fibroblasts ; Flavin Mononucleotide/metabolism ; Flavin-Adenine Dinucleotide/biosynthesis/metabolism ; HeLa Cells ; Humans ; Isoenzymes/chemistry/metabolism ; Membrane Glycoproteins/metabolism ; Mice ; NADH, NADPH Oxidoreductases/metabolism ; NADPH Oxidase/chemistry/*metabolism ; Phosphotransferases (Alcohol Group Acceptor)/deficiency/genetics/*metabolism ; Protein Binding ; Protein Structure, Tertiary ; Reactive Oxygen Species/metabolism ; Receptors, Tumor Necrosis Factor, Type I/chemistry/*metabolism
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  • 88
    Publication Date: 2009-11-03
    Description: Although drugs are intended to be selective, at least some bind to several physiological targets, explaining side effects and efficacy. Because many drug-target combinations exist, it would be useful to explore possible interactions computationally. Here we compared 3,665 US Food and Drug Administration (FDA)-approved and investigational drugs against hundreds of targets, defining each target by its ligands. Chemical similarities between drugs and ligand sets predicted thousands of unanticipated associations. Thirty were tested experimentally, including the antagonism of the beta(1) receptor by the transporter inhibitor Prozac, the inhibition of the 5-hydroxytryptamine (5-HT) transporter by the ion channel drug Vadilex, and antagonism of the histamine H(4) receptor by the enzyme inhibitor Rescriptor. Overall, 23 new drug-target associations were confirmed, five of which were potent (〈100 nM). The physiological relevance of one, the drug N,N-dimethyltryptamine (DMT) on serotonergic receptors, was confirmed in a knockout mouse. The chemical similarity approach is systematic and comprehensive, and may suggest side-effects and new indications for many drugs.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784146/" 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/PMC2784146/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Keiser, Michael J -- Setola, Vincent -- Irwin, John J -- Laggner, Christian -- Abbas, Atheir I -- Hufeisen, Sandra J -- Jensen, Niels H -- Kuijer, Michael B -- Matos, Roberto C -- Tran, Thuy B -- Whaley, Ryan -- Glennon, Richard A -- Hert, Jerome -- Thomas, Kelan L H -- Edwards, Douglas D -- Shoichet, Brian K -- Roth, Bryan L -- R01 DA017204/DA/NIDA NIH HHS/ -- R01 DA017204-04/DA/NIDA NIH HHS/ -- R01 DA017204-05/DA/NIDA NIH HHS/ -- R01 MH061887/MH/NIMH NIH HHS/ -- R01 MH061887-09/MH/NIMH NIH HHS/ -- R01 MH061887-10/MH/NIMH NIH HHS/ -- U19 MH082441/MH/NIMH NIH HHS/ -- U19 MH082441-01/MH/NIMH NIH HHS/ -- U19 MH082441-010001/MH/NIMH NIH HHS/ -- U19 MH082441-019002/MH/NIMH NIH HHS/ -- U19 MH082441-019003/MH/NIMH NIH HHS/ -- U19 MH082441-02/MH/NIMH NIH HHS/ -- U19 MH082441-020001/MH/NIMH NIH HHS/ -- U19 MH082441-029002/MH/NIMH NIH HHS/ -- U19 MH082441-03/MH/NIMH NIH HHS/ -- U19 MH082441-030001/MH/NIMH NIH HHS/ -- U19 MH082441-039002/MH/NIMH NIH HHS/ -- England -- Nature. 2009 Nov 12;462(7270):175-81. doi: 10.1038/nature08506. Epub 2009 Nov 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmaceutical Chemistry, University of California San Francisco, 1700 4th Street, San Francisco, California 94143-2550, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19881490" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Computational Biology ; Databases, Factual ; Drug Evaluation, Preclinical/*methods ; Drug-Related Side Effects and Adverse Reactions ; Humans ; Ligands ; Mice ; Mice, Knockout ; Off-Label Use ; Pharmaceutical Preparations/*metabolism ; Receptors, Serotonin/metabolism ; *Substrate Specificity ; United States ; United States Food and Drug Administration
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  • 89
    Publication Date: 2009-08-28
    Description: Mitochondria are found in all eukaryotic cells and contain their own genome (mitochondrial DNA or mtDNA). Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin. Mutations in mtDNA contribute to a diverse range of currently incurable human diseases and disorders. To establish preclinical models for new therapeutic approaches, we demonstrate here that the mitochondrial genome can be efficiently replaced in mature non-human primate oocytes (Macaca mulatta) by spindle-chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilization, embryo development and produced healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infants born so far originated from the spindle donors whereas mtDNA came from the cytoplast donors. No contribution of spindle donor mtDNA was detected in offspring. Spindle replacement is shown here as an efficient protocol replacing the full complement of mitochondria in newly generated embryonic stem cell lines. This approach may offer a reproductive option to prevent mtDNA disease transmission in affected families.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2774772/" 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/PMC2774772/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tachibana, Masahito -- Sparman, Michelle -- Sritanaudomchai, Hathaitip -- Ma, Hong -- Clepper, Lisa -- Woodward, Joy -- Li, Ying -- Ramsey, Cathy -- Kolotushkina, Olena -- Mitalipov, Shoukhrat -- P01 HD047675/HD/NICHD NIH HHS/ -- P01 HD047675-01A17045/HD/NICHD NIH HHS/ -- P01 HD047675-04/HD/NICHD NIH HHS/ -- P51 RR000163/RR/NCRR NIH HHS/ -- P51 RR000163-486766/RR/NCRR NIH HHS/ -- P51 RR000163-486775/RR/NCRR NIH HHS/ -- P51 RR000163-486819/RR/NCRR NIH HHS/ -- P51 RR000163-496038/RR/NCRR NIH HHS/ -- P51 RR000163-496045/RR/NCRR NIH HHS/ -- P51 RR000163-496074/RR/NCRR NIH HHS/ -- P51 RR000163-496133/RR/NCRR NIH HHS/ -- P51 RR000163-496134/RR/NCRR NIH HHS/ -- P51 RR000163-496136/RR/NCRR NIH HHS/ -- P51 RR000163-496137/RR/NCRR NIH HHS/ -- R01 HD057121/HD/NICHD NIH HHS/ -- R01 HD057121-01A2/HD/NICHD NIH HHS/ -- R01 NS044330/NS/NINDS NIH HHS/ -- R01 NS044330-05/NS/NINDS NIH HHS/ -- R24 RR013632/RR/NCRR NIH HHS/ -- R24 RR013632-10/RR/NCRR NIH HHS/ -- England -- Nature. 2009 Sep 17;461(7262):367-72. doi: 10.1038/nature08368. Epub 2009 Aug 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Oregon National Primate Research Center, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19710649" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Nucleus/genetics ; DNA, Mitochondrial/analysis/*genetics ; Embryo Transfer ; Embryonic Stem Cells/*cytology/*metabolism/transplantation ; Female ; Fertilization in Vitro ; Genes, Mitochondrial/*genetics ; Genome, Mitochondrial/*genetics ; Macaca mulatta/embryology/*genetics ; Male ; Meiosis ; Mitochondrial Diseases/genetics/prevention & control ; Mutation ; Oocytes/cytology/metabolism ; Pregnancy ; *Reproductive Techniques, Assisted
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  • 90
    Publication Date: 2009-11-27
    Description: Protein design provides a rigorous test of our knowledge about proteins and allows the creation of novel enzymes for biotechnological applications. Whereas progress has been made in designing proteins that mimic native proteins structurally, it is more difficult to design functional proteins. In comparison to recent successes in designing non-metalloproteins, it is even more challenging to rationally design metalloproteins that reproduce both the structure and function of native metalloenzymes. This is because protein metal-binding sites are much more varied than non-metal-containing sites, in terms of different metal ion oxidation states, preferred geometry and metal ion ligand donor sets. Because of their variability, it has been difficult to predict metal-binding site properties in silico, as many of the parameters, such as force fields, are ill-defined. Therefore, the successful design of a structural and functional metalloprotein would greatly advance the field of protein design and our understanding of enzymes. Here we report a successful, rational design of a structural and functional model of a metalloprotein, nitric oxide reductase (NOR), by introducing three histidines and one glutamate, predicted as ligands in the active site of NOR, into the distal pocket of myoglobin. A crystal structure of the designed protein confirms that the minimized computer model contains a haem/non-haem Fe(B) centre that is remarkably similar to that in the crystal structure. This designed protein also exhibits NO reduction activity, and so models both the structure and function of NOR, offering insight that the active site glutamate is required for both iron binding and activity. These results show that structural and functional metalloproteins can be rationally designed in silico.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297211/" 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/PMC4297211/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yeung, Natasha -- Lin, Ying-Wu -- Gao, Yi-Gui -- Zhao, Xuan -- Russell, Brandy S -- Lei, Lanyu -- Miner, Kyle D -- Robinson, Howard -- Lu, Yi -- GM062211/GM/NIGMS NIH HHS/ -- R01 GM062211/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Dec 24;462(7276):1079-82. doi: 10.1038/nature08620. Epub 2009 Nov 25.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940850" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Crystallization ; Iron/metabolism ; Models, Molecular ; Myoglobin/chemistry ; Nitric Oxide/metabolism ; Oxidoreductases/*chemical synthesis/*chemistry/metabolism ; Protein Binding ; Protein Structure, Tertiary
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  • 91
    Publication Date: 2009-08-08
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kell, Douglas -- England -- Nature. 2009 Aug 6;460(7256):669. doi: 10.1038/460669e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The University of Manchester, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19661875" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Brain Chemistry ; Creutzfeldt-Jakob Syndrome/metabolism ; Ferritins/metabolism ; Humans ; Hydroxyl Radical/metabolism ; Iron/chemistry/*metabolism ; PrPSc Proteins/*metabolism ; Prion Diseases/*metabolism ; Scrapie/metabolism ; Systems Biology
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  • 92
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    Nature Publishing Group (NPG)
    Publication Date: 2009-12-04
    Description: The ability to produce stem cells by induced pluripotency (iPS reprogramming) has rekindled an interest in earlier studies showing that transcription factors can directly convert specialized cells from one lineage to another. Lineage reprogramming has become a powerful tool to study cell fate choice during differentiation, akin to inducing mutations for the discovery of gene functions. The lessons learnt provide a rubric for how cells may be manipulated for therapeutic purposes.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graf, Thomas -- Enver, Tariq -- MC_U137973817/Medical Research Council/United Kingdom -- England -- Nature. 2009 Dec 3;462(7273):587-94. doi: 10.1038/nature08533.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Genomic Regulation and ICREA, 08003 Barcelona, Spain. thomas.graf@crg.es〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19956253" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Differentiation ; Cell Lineage/*physiology ; Cellular Reprogramming/*genetics ; *Gene Expression Regulation, Developmental ; Gene Regulatory Networks/physiology ; Humans ; Pluripotent Stem Cells/cytology/*metabolism ; Transcription Factors/*metabolism
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  • 93
    Publication Date: 2009-06-16
    Description: Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularisation (CNV). Here we show that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in choroidal neovascular endothelial cells in humans with AMD, and that despite the expression of its ligands eotaxin-1, -2 and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor A (VEGF-A) neutralization, which is in clinical use at present, and, unlike VEGF-A blockade, is not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712122/" 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/PMC2712122/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takeda, Atsunobu -- Baffi, Judit Z -- Kleinman, Mark E -- Cho, Won Gil -- Nozaki, Miho -- Yamada, Kiyoshi -- Kaneko, Hiroki -- Albuquerque, Romulo J C -- Dridi, Sami -- Saito, Kuniharu -- Raisler, Brian J -- Budd, Steven J -- Geisen, Pete -- Munitz, Ariel -- Ambati, Balamurali K -- Green, Martha G -- Ishibashi, Tatsuro -- Wright, John D -- Humbles, Alison A -- Gerard, Craig J -- Ogura, Yuichiro -- Pan, Yuzhen -- Smith, Justine R -- Grisanti, Salvatore -- Hartnett, M Elizabeth -- Rothenberg, Marc E -- Ambati, Jayakrishna -- AI039759/AI/NIAID NIH HHS/ -- AI45898/AI/NIAID NIH HHS/ -- DK076893/DK/NIDDK NIH HHS/ -- EY010572/EY/NEI NIH HHS/ -- EY015130/EY/NEI NIH HHS/ -- EY015422/EY/NEI NIH HHS/ -- EY017011/EY/NEI NIH HHS/ -- EY017182/EY/NEI NIH HHS/ -- EY017950/EY/NEI NIH HHS/ -- EY018350/EY/NEI NIH HHS/ -- EY018836/EY/NEI NIH HHS/ -- R01 DK076893/DK/NIDDK NIH HHS/ -- R01 EY015422/EY/NEI NIH HHS/ -- R01 EY015422-04/EY/NEI NIH HHS/ -- R01 EY018350/EY/NEI NIH HHS/ -- R01 EY018350-02/EY/NEI NIH HHS/ -- R01 EY018836/EY/NEI NIH HHS/ -- R01 EY018836-02/EY/NEI NIH HHS/ -- England -- Nature. 2009 Jul 9;460(7252):225-30. doi: 10.1038/nature08151. Epub 2009 Jun 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Ophthalmology & Visual Science, University of Kentucky, Lexington, Kentucky 40506, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19525930" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Chemokine CCL11/antagonists & inhibitors/metabolism ; Chemokine CCL24/antagonists & inhibitors/metabolism ; Chemokines, CC/antagonists & inhibitors/metabolism ; Choroid/blood supply/cytology/metabolism ; Choroidal Neovascularization/diagnosis/metabolism ; Disease Models, Animal ; Endothelial Cells/cytology/metabolism ; Humans ; Inflammation ; Leukocytes ; Ligands ; Macular Degeneration/*diagnosis/metabolism/*therapy ; Mice ; Mice, Inbred C57BL ; Quantum Dots ; Receptors, CCR3/analysis/*antagonists & ; inhibitors/genetics/immunology/*metabolism ; Retina/drug effects/pathology ; Vascular Endothelial Growth Factor A/antagonists & inhibitors/immunology
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  • 94
    Publication Date: 2009-06-30
    Description: One of the most distinctive steps in the development of the vertebrate nervous system occurs at mitotic exit when cells lose multipotency and begin to develop stable connections that will persist for a lifetime. This transition is accompanied by a switch in ATP-dependent chromatin-remodelling mechanisms that appears to coincide with the final mitotic division of neurons. This switch involves the exchange of the BAF53a (also known as ACTL6a) and BAF45a (PHF10) subunits within Swi/Snf-like neural-progenitor-specific BAF (npBAF) complexes for the homologous BAF53b (ACTL6b) and BAF45b (DPF1) subunits within neuron-specific BAF (nBAF) complexes in post-mitotic neurons. The subunits of the npBAF complex are essential for neural-progenitor proliferation, and mice with reduced dosage for the genes encoding its subunits have defects in neural-tube closure similar to those in human spina bifida, one of the most serious congenital birth defects. In contrast, BAF53b and the nBAF complex are essential for an evolutionarily conserved program of post-mitotic neural development and dendritic morphogenesis. Here we show that this essential transition is mediated by repression of BAF53a by miR-9* and miR-124. We find that BAF53a repression is mediated by sequences in the 3' untranslated region corresponding to the recognition sites for miR-9* and miR-124, which are selectively expressed in post-mitotic neurons. Mutation of these sites led to persistent expression of BAF53a and defective activity-dependent dendritic outgrowth in neurons. In addition, overexpression of miR-9* and miR-124 in neural progenitors caused reduced proliferation. Previous studies have indicated that miR-9* and miR-124 are repressed by the repressor-element-1-silencing transcription factor (REST, also known as NRSF). Indeed, expression of REST in post-mitotic neurons led to derepression of BAF53a, indicating that REST-mediated repression of microRNAs directs the essential switch of chromatin regulatory complexes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2921580/" 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/PMC2921580/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoo, Andrew S -- Staahl, Brett T -- Chen, Lei -- Crabtree, Gerald R -- 2 T32 HD007249/HD/NICHD NIH HHS/ -- AI060037/AI/NIAID NIH HHS/ -- HD55391/HD/NICHD NIH HHS/ -- NS046789/NS/NINDS NIH HHS/ -- R01 HD055391/HD/NICHD NIH HHS/ -- R01 NS046789/NS/NINDS NIH HHS/ -- R01 NS046789-08/NS/NINDS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 30;460(7255):642-6. doi: 10.1038/nature08139. Epub 2009 Jun 28.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, and Department of Developmental Biology, Stanford University, Stanford, California 94305, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19561591" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/metabolism ; Actins/genetics/metabolism ; Animals ; CHO Cells ; Cell Line ; Chromatin Assembly and Disassembly/genetics/*physiology ; Chromosomal Proteins, Non-Histone/genetics/metabolism ; Cricetinae ; Cricetulus ; DNA-Binding Proteins/genetics/metabolism ; Dendrites/physiology ; *Gene Expression Regulation, Developmental ; Mice ; Mice, Transgenic ; MicroRNAs/*metabolism ; Mitosis ; Nervous System/cytology/*embryology ; Neurons/cytology ; Repressor Proteins/metabolism ; Stem Cells/metabolism
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  • 95
    Publication Date: 2009-02-13
    Description: Evolutionary biologists have long sought to understand the relationship between microevolution (adaptation), which can be observed both in nature and in the laboratory, and macroevolution (speciation and the origin of the divisions of the taxonomic hierarchy above the species level, and the development of complex organs), which cannot be witnessed because it occurs over intervals that far exceed the human lifespan. The connection between these processes is also a major source of conflict between science and religious belief. Biologists often forget that Charles Darwin offered a way of resolving this issue, and his proposal is ripe for re-evaluation in the light of recent research.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Reznick, David N -- Ricklefs, Robert E -- England -- Nature. 2009 Feb 12;457(7231):837-42. doi: 10.1038/nature07894.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, University of California, Riverside, California 92521, USA. gupy@ucr.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19212402" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological ; Animals ; *Biological Evolution ; Extinction, Biological ; Genetic Speciation
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  • 96
    Publication Date: 2009-04-28
    Description: Heart disease is the leading cause of mortality and morbidity in the western world. The heart has little regenerative capacity after damage, leading to much interest in understanding the factors required to produce new cardiac myocytes. Despite a robust understanding of the molecular networks regulating cardiac differentiation, no single transcription factor or combination of factors has been shown to activate the cardiac gene program de novo in mammalian cells or tissues. Here we define the minimal requirements for transdifferentiation of mouse mesoderm to cardiac myocytes. We show that two cardiac transcription factors, Gata4 and Tbx5, and a cardiac-specific subunit of BAF chromatin-remodelling complexes, Baf60c (also called Smarcd3), can direct ectopic differentiation of mouse mesoderm into beating cardiomyocytes, including the normally non-cardiogenic posterior mesoderm and the extraembryonic mesoderm of the amnion. Gata4 with Baf60c initiated ectopic cardiac gene expression. Addition of Tbx5 allowed differentiation into contracting cardiomyocytes and repression of non-cardiac mesodermal genes. Baf60c was essential for the ectopic cardiogenic activity of Gata4 and Tbx5, partly by permitting binding of Gata4 to cardiac genes, indicating a novel instructive role for BAF complexes in tissue-specific regulation. The combined function of these factors establishes a robust mechanism for controlling cellular differentiation, and may allow reprogramming of new cardiomyocytes for regenerative purposes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728356/" 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/PMC2728356/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Takeuchi, Jun K -- Bruneau, Benoit G -- C06 RR018928/RR/NCRR NIH HHS/ -- R01 HL085860/HL/NHLBI NIH HHS/ -- R01 HL085860-01/HL/NHLBI NIH HHS/ -- R01HL085860/HL/NHLBI NIH HHS/ -- England -- Nature. 2009 Jun 4;459(7247):708-11. doi: 10.1038/nature08039. Epub 2009 Apr 26.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA. takeuchi.j.ab@m.titech.ac.jp〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396158" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Cell Differentiation ; Cell Transdifferentiation ; Chromosomal Proteins, Non-Histone ; Embryo, Mammalian ; GATA4 Transcription Factor/metabolism ; Gene Expression Regulation, Developmental ; Heart/*embryology ; Mesoderm/cytology/*embryology ; Mice ; Muscle Proteins ; Myocytes, Cardiac/*cytology/metabolism ; T-Box Domain Proteins/metabolism
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  • 97
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    Unknown
    Nature Publishing Group (NPG)
    Publication Date: 2009-04-11
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822621/" 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/PMC2822621/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brunet, Anne -- R01 AG031198/AG/NIA NIH HHS/ -- R01 AG031198-01A1/AG/NIA NIH HHS/ -- England -- Nature. 2009 Apr 9;458(7239):713-4. doi: 10.1038/458713a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19360073" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis/physiology ; *Caloric Restriction ; Humans ; Insulin/physiology ; Neoplasms/*diet therapy ; Phosphatidylinositol 3-Kinases/metabolism ; Signal Transduction/physiology ; Tumor Cells, Cultured
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  • 98
    Publication Date: 2009-04-10
    Description: Preventing and delaying the emergence of drug resistance is an essential goal of antimalarial drug development. Monotherapy and highly mutable drug targets have each facilitated resistance, and both are undesirable in effective long-term strategies against multi-drug-resistant malaria. Haem remains an immutable and vulnerable target, because it is not parasite-encoded and its detoxification during haemoglobin degradation, critical to parasite survival, can be subverted by drug-haem interaction as in the case of quinolines and many other drugs. Here we describe a new antimalarial chemotype that combines the haem-targeting character of acridones, together with a chemosensitizing component that counteracts resistance to quinoline antimalarial drugs. Beyond the essential intrinsic characteristics common to deserving candidate antimalarials (high potency in vitro against pan-sensitive and multi-drug-resistant Plasmodium falciparum, efficacy and safety in vivo after oral administration, inexpensive synthesis and favourable physicochemical properties), our initial lead, T3.5 (3-chloro-6-(2-diethylamino-ethoxy)-10-(2-diethylamino-ethyl)-acridone), demonstrates unique synergistic properties. In addition to 'verapamil-like' chemosensitization to chloroquine and amodiaquine against quinoline-resistant parasites, T3.5 also results in an apparently mechanistically distinct synergism with quinine and with piperaquine. This synergy, evident in both quinoline-sensitive and quinoline-resistant parasites, has been demonstrated both in vitro and in vivo. In summary, this innovative acridone design merges intrinsic potency and resistance-counteracting functions in one molecule, and represents a new strategy to expand, enhance and sustain effective antimalarial drug combinations.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kelly, Jane X -- Smilkstein, Martin J -- Brun, Reto -- Wittlin, Sergio -- Cooper, Roland A -- Lane, Kristin D -- Janowsky, Aaron -- Johnson, Robert A -- Dodean, Rozalia A -- Winter, Rolf -- Hinrichs, David J -- Riscoe, Michael K -- England -- Nature. 2009 May 14;459(7244):270-3. doi: 10.1038/nature07937. Epub 2009 Apr 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Portland Veterans Affairs Medical Centre, Portland, Oregon 97239, USA. kellyja@ohsu.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19357645" target="_blank"〉PubMed〈/a〉
    Keywords: Acridones/analysis/metabolism/*pharmacology ; Animals ; Antimalarials/analysis/metabolism/*pharmacology ; *Drug Discovery ; Drug Resistance/drug effects ; Drug Synergism ; Heme/antagonists & inhibitors/metabolism ; Membrane Transport Proteins/genetics/metabolism ; Mutation/genetics ; Plasmodium falciparum/*drug effects/genetics/growth & development/metabolism ; Plasmodium yoelii/drug effects ; Protozoan Proteins/genetics/metabolism ; Quinine/pharmacology ; Quinolines/pharmacology ; Trophozoites/metabolism ; Verapamil/pharmacology
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  • 99
    Publication Date: 2009-08-21
    Description: Activity is thought to guide the patterning of synaptic connections in the developing nervous system. Specifically, differences in the activity of converging inputs are thought to cause the elimination of synapses from less active inputs and increase connectivity with more active inputs. Here we present findings that challenge the generality of this notion and offer a new view of the role of activity in synapse development. To imbalance neurotransmission from different sets of inputs in vivo, we generated transgenic mice in which ON but not OFF types of bipolar cells in the retina express tetanus toxin (TeNT). During development, retinal ganglion cells (RGCs) select between ON and OFF bipolar cell inputs (ON or OFF RGCs) or establish a similar number of synapses with both on separate dendritic arborizations (ON-OFF RGCs). In TeNT retinas, ON RGCs correctly selected the silenced ON bipolar cell inputs over the transmitting OFF bipolar cells, but were connected with them through fewer synapses at maturity. Time-lapse imaging revealed that this was caused by a reduced rate of synapse formation rather than an increase in synapse elimination. Similarly, TeNT-expressing ON bipolar cell axons generated fewer presynaptic active zones. The remaining active zones often recruited multiple, instead of single, synaptic ribbons. ON-OFF RGCs in TeNT mice maintained convergence of ON and OFF bipolar cells inputs and had fewer synapses on their ON arbor without changes to OFF arbor synapses. Our results reveal an unexpected and remarkably selective role for activity in circuit development in vivo, regulating synapse formation but not elimination, affecting synapse number but not dendritic or axonal patterning, and mediating independently the refinement of connections from parallel (ON and OFF) processing streams even where they converge onto the same postsynaptic cell.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746695/" 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/PMC2746695/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kerschensteiner, Daniel -- Morgan, Josh L -- Parker, Edward D -- Lewis, Renate M -- Wong, Rachel O L -- EY01730/EY/NEI NIH HHS/ -- EY10699/EY/NEI NIH HHS/ -- R01 EY010699/EY/NEI NIH HHS/ -- R01 EY010699-16/EY/NEI NIH HHS/ -- T32 EY07031/EY/NEI NIH HHS/ -- England -- Nature. 2009 Aug 20;460(7258):1016-20. doi: 10.1038/nature08236.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA. KerschensteinerD@vision.wustl.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19693082" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Axons/metabolism ; Dendrites/metabolism ; Female ; Glutamic Acid/metabolism ; Male ; Mice ; Mice, Transgenic ; Receptors, Kainic Acid/genetics/metabolism ; Retinal Bipolar Cells/cytology/metabolism ; Retinal Ganglion Cells/cytology/metabolism ; Synapses/*metabolism ; Synaptic Transmission/*physiology ; Tetanus Toxin/genetics/metabolism
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  • 100
    Publication Date: 2009-03-13
    Description: Behavioural responses to wind are thought to have a critical role in controlling the dispersal and population genetics of wild Drosophila species, as well as their navigation in flight, but their underlying neurobiological basis is unknown. We show that Drosophila melanogaster, like wild-caught Drosophila strains, exhibits robust wind-induced suppression of locomotion in response to air currents delivered at speeds normally encountered in nature. Here we identify wind-sensitive neurons in Johnston's organ, an antennal mechanosensory structure previously implicated in near-field sound detection (reviewed in refs 5 and 6). Using enhancer trap lines targeted to different subsets of Johnston's organ neurons, and a genetically encoded calcium indicator, we show that wind and near-field sound (courtship song) activate distinct populations of Johnston's organ neurons, which project to different regions of the antennal and mechanosensory motor centre in the central brain. Selective genetic ablation of wind-sensitive Johnston's organ neurons in the antenna abolishes wind-induced suppression of locomotion behaviour, without impairing hearing. Moreover, different neuronal subsets within the wind-sensitive population respond to different directions of arista deflection caused by air flow and project to different regions of the antennal and mechanosensory motor centre, providing a rudimentary map of wind direction in the brain. Importantly, sound- and wind-sensitive Johnston's organ neurons exhibit different intrinsic response properties: the former are phasically activated by small, bi-directional, displacements of the aristae, whereas the latter are tonically activated by unidirectional, static deflections of larger magnitude. These different intrinsic properties are well suited to the detection of oscillatory pulses of near-field sound and laminar air flow, respectively. These data identify wind-sensitive neurons in Johnston's organ, a structure that has been primarily associated with hearing, and reveal how the brain can distinguish different types of air particle movements using a common sensory organ.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2755041/" 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/PMC2755041/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yorozu, Suzuko -- Wong, Allan -- Fischer, Brian J -- Dankert, Heiko -- Kernan, Maurice J -- Kamikouchi, Azusa -- Ito, Kei -- Anderson, David J -- R01 DC002780/DC/NIDCD NIH HHS/ -- T32 GM007737/GM/NIGMS NIH HHS/ -- T32 GM007737-30/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Mar 12;458(7235):201-5. doi: 10.1038/nature07843.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Biology 216-76, California Institute of Technology, Pasadena, California 91125, USA. yorozu@caltech.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19279637" target="_blank"〉PubMed〈/a〉
    Keywords: *Air Movements ; Animals ; Auditory Perception/*physiology ; Behavior, Animal/physiology ; Drosophila melanogaster/*physiology ; Electrophysiological Phenomena/physiology ; Mechanoreceptors/physiology ; Sensory Receptor Cells/*physiology
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