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  • Animals  (7,845)
  • General Chemistry  (7,644)
  • Cell & Developmental Biology  (2,961)
  • Fisheries
  • 2005-2009  (5,020)
  • 1995-1999  (12,232)
  • 1945-1949  (1,246)
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  • 1
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    The impact generated on Sea Turtles by Fisheries in the Southwestern Atlantic Ocean (2009)
    WWF Programa Marino para Latinoamérica y el Caribe
    Details
    Publication Date: 2021-05-19
    Description: This document, which is directed at the fishing sector, researchers, conservationists and fishery administrators, was developed by researchers who are members of the Specialists Group for Marine Turtle Research and conservation in the Southwestern Atlantic Ocean (SWA) in response to the urgent need to evaluate the impact generated on sea turtles by fisheries. Historically, sea turtle conservation efforts have focused almost exclusively on the protection of nesting beaches. Nevertheless, over the last decade, research has proved incidental mortality as a result of fishing activities to be one of the greatest threats to these animals. This type of interaction is not only problematic for turtles, but also generates financial losses for fishermen and businesses. In spite of the efforts that are currently underway, researchers still do not have a detailed understanding of the impact that bycatch produces on sea turtle populations in the SWA. We have a long way to go before its effects can be minimized. Further research is needed regarding the biology and ecology of the various turtle species as well as the effective application of mitigation measures. The life cycles of sea turtles are long and complex. Turtles occupy various ecosystems (nesting beaches, coastal, neritic and oceanic zones, as well as pelagic and demersal areas) throughout their lifetimes, transcending various Exclusive Economic Zones and International Waters. The five species that inhabit the SWA region perform vast feeding and reproductive migrations, traveling through areas where many different fishing fleets operate. Therefore, sea turtles in the SWA interact with virtually all fisheries. These circumstances make it necessary to carry out biological, fishing related and conservation studies on a regional level. The efficiency of the existing international and national legal instruments has yet to be determined, in terms of their effectiveness in protecting sea turtles. In some cases, legislation that is specifically related to the interaction between fisheries and turtles does exist, such as those laws requiring the mandatory use of turtle excluding devices (TEDs). There are also explicit bans on sea turtle capture. Nevertheless, none of these regulations prevent sea turtle bycatch. Although some regional legal instruments are needed, these and the existing legislation will only be effective if they are accompanied by a broader range of permanent education and control measures, to achieve the commitment of all the parties involved. The ecosystem approach is gaining popularity among fishery administration organizations. Research and conservation efforts should also be moving in that direction. A regional and international effort is required in order to compile information regarding the bycatch produced by the various types of fisheries and fleets operating in the area. The enormous increase in fishing pressure that these fleets are exerting in this area has not been accompanied by an increase in information regarding the bycatch of species that have no commercial value. Pelagic longlining is one of the fishing methods, which must be most closely monitored, due to the high levels of bycatch that it produces, as well its ample distribution throughout the region, and the high level of fishing effort that it accounts for. Coastal trawlers and gillnetters must also be considered critical players, because they too produce a large rate of bycatch. These are the three types of fisheries that are most broadly distributed throughout the region, accounting for the majority of the fishing effort. Most of the institutions that work toward sea turtle conservation in the area have only begun to address the issue of bycatch over the last decade. This timeframe is reflected in the scope and quantity of the available publications, as well as the progress of activities directed at mitigating this problem. All of the institutions that have been mentioned in this report have made the gathering of information regarding interaction between sea turtles and fisheries one of their top priorities. Some institutions are even developing working programs for monitoring fisheries and testing mitigation measures. Many of these institutions have managed to develop adequate relationships with fishermen, ship owners and administrators. Nevertheless, limited access to funding is an obstacle to the development and testing of mitigation measures. The SWA network, which is a very valuable instrument that was created in 2003, has allowed the region’s institutions and researchers to exchange information and share their experience, in addition to lending each other support in carrying out joint activities, thus strengthening sea turtle conservation efforts. The capacity demonstrated so far by the region’s researchers and institutions, testifies to their ability to continue to make progress in knowledge generation and tests of bycatch mitigation measures.
    Description: Published
    Keywords: Fisheries ; Ecology ; Fishing gear ; Fisheries ; Ecology ; Fishing gear
    Repository Name: AquaDocs
    Type: Book
    Format: 71 pp
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  • 2
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    Boletín Estadístico Pesquero 2008 (2009)
    MGAP | DINARA
    Details
    Publication Date: 2021-01-30
    Description: A partir de la firma del Proyecto de Gestión Pesquera DINARA-FAO (UTF/URU/025/URU), en septiembre de 2007, se comenzó a conformar una Unidad de Economía Pesquera. Sus objetivos se focalizaron en fortalecer la capacidad de recolección y análisis estadístico de la información socio-económica del sector. En el 2008 esta Unidad compiló y realizó un análisis de la información comprendida entre los años 2002 y 2007, reanudando luego de varios años esta publicación histórica. La misma fue un éxito en todo sentido, especialmente para consulta de los diferentes actores del sector. La aceptación y receptividad que ha tenido dicha publicación nos motiva y obliga a continuar en esta línea, rumbo a la obtención de un producto de valor y utilidad, basado exclusivamente en información oficial nacional. Este año retomamos la serie anual poniendo nuevamente a disposición de todos información actualizada, completa y de calidad que estamos seguros será nuevamente de gran beneficio para el sector público como privado, así como de interés para el público en general.
    Description: Published
    Keywords: Fisheries ; Trade ; Fishery statistics ; Fisheries ; Trade
    Repository Name: AquaDocs
    Type: Book
    Format: 48
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  • 3
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    El impacto generado por las pesquerías en las tortugas marinas en el Océano Atlántico Sud Occidental (2009)
    WWF Programa Marino para Latinoamérica y el Caribe
    Details
    Publication Date: 2021-05-19
    Description: Este documento, dirigido al sector pesquero, investigadores, conservacionistas y administradores de las pesquerías, surge como respuesta de investigadores pertenecientes al Grupo de Especialistas en Investigación y Conservación de Tortugas Marinas en el Atlántico Sud Occidental (ASO) a la urgente necesidad de evaluar el impacto de las pesquerías sobre las tortugas marinas. Históricamente, los esfuerzos referidos a la conservación de las tortugas marinas se han dirigido casi exclusivamente a proteger las playas de anidación. Sin embargo en la última década se ha podido comprobar que una de las mayores amenazas es la mortalidad incidental causada por las pesquerías. Esta interacción no implica únicamente un problema para las tortugas, sino que también genera pérdidas económicas para los pescadores y las empresas.
    Description: This document, which is directed at the fishing sector, researchers, conservationists and fishery administrators, was developed by researchers who are members of the Specialists Group for Marine Turtle Research and Conservation in the Southwestern Atlantic Ocean (SWA) in response to the urgent need to evaluate the impact generated on sea turtles by fisheries. Historically, sea turtle conservation efforts have focused almost exclusively on the protection of nesting beaches. Nevertheless, over the last decade, research has proved incidental mortality as a result of fishing activities to be one of the greatest threats to these animals. This type of interaction is not only problematic for turtles, but also generates financial losses for fishermen and businesses.
    Description: Cont. fotografías
    Description: Published
    Description: Sea Turtle, keeping
    Keywords: Fisheries ; Ecology ; Fishing gear ; Fisheries ; Ecology ; Fishing gear
    Repository Name: AquaDocs
    Type: Book
    Format: 71
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  • 4
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    Un estudio de histamina en Dorado MAHI-MAHI Coryphaena hippurus y su relación con la calidad de producto de la pesca ecuatoriana (2009)
    INP (Ecuador)
    Details
    Publication Date: 2021-05-19
    Description: El presente trabajo llama la atención a las recientes epidemias de intoxicación histamínicas reportadas en los Estados Unidos, debido al consumo del dorado (Coryphaena hippurus) o Mahi-Mah, contaminado. Esto dió como resultado la prohición de las importaciones de esta especie, proveniente de varios países entre ellos el Ecuador, y siendo el dorado una especie de relativa importancia económica en este país, dicha prohibición ha preocupado al sector pesquero. Los estudios llevados a cabo muestran claramente la susceptibilidad de esta especie a desarrollar histamina. Esto se debe principalmente a la temperatura a la que está expuesta, pues la demora antes de enhielar el pescado es la etapa crítica. Los resultados muestran un aumento exponencial de los niveles de histamina, en ciertos casos después de tan solo 9 horas de almacenaje a temperaturas ambientales entre 25-30°C. Los niveles de histamina en pescado muestreado en el mercado local fueron tan altos como 250 mg/100g de muestra. Se demuestra que el problema se debe fundamentalmente al mal manejo de la captura por parte de la flota artesanal, y la subsecuente falta de infraestructura adecuada para conservarla, es decir, no se enfría el pescado. Sin embargo, el estudio muestra que una reducción de la temperatura del pescado de solo 15° menos, podría dar como resultado un producto de mayor calidad. En el presente trabajo se hacen recomendaciones para establecer un nivel máximo permitido para la exportación de 10 mg%, y se comparan dos métodos rápidos de análisis.
    Description: Published
    Keywords: Fisheries ; Histamines ; Quality control ; Fisheries
    Repository Name: AquaDocs
    Type: Journal Contribution
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  • 5
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    Un estudio de la factibilidad del uso de trampas para peces como un nuevo método de pesca en las Islas Galápagos (2009)
    INP (Ecuador)
    Details
    Publication Date: 2021-05-19
    Description: 153 experimental sets were made with stackable Antillean fish traps in depths of 5 to 30 m in the waters around the Galápagos Island (Ecuador), between Octobre and April 1983. 1,885 fish were caught of 18 species mainly of the families Pomadasyidae, Acanthuridae, Sparidae and Serranidae. The mean catch rate was 5,5 Kg per lift or 0,4 Kg.h-1, and the mean weight of the fish caught was 0,45 Kg. The optimum set duration was found to be between 2 and 18 hours (possibly indicating a high rate of escape). This study took place during the period of the ”El Niño”, when catches of fish in this area generally were low, and it is not known what effect this had. The catches were good compared with other shallow areas, but the fishes caught were mainly of medium quality. It is thought that significant increases in the quantity and quality of the catch could be obtained with commercial traps in deeper areas, but the efficient use of these would require new vessels and equipment, and the resulting increase in fishing effort could lead to overfishing of the most acceptable species of reef fish. Hence the development of fishery using fish traps is not recommended for Galápagos. A study of the biology of the fish caught was carried out. A bibliography of references on fish traps and their use was compiled and is included.
    Description: Published
    Keywords: Fisheries ; Trap fishing ; Fisheries ; Catch statistics ; Trap fishing
    Repository Name: AquaDocs
    Type: Journal Contribution
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  • 6
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    Rapport national sur l'état de l'environnement marin et côtier (2009)
    Details
    Publication Date: 2021-01-30
    Description: Le domaine maritime sénégalais s’étend de 18°00 N, -20°00 W, -16°30 E, 12°15 S ; la presqu’île du Cap-Vert située entre 14°30 N et 15°00 N le divise en deux zones aux caractéristiques topographiques distinctes. Au nord, le plateau continental est peu étendu vers le large et orienté Nord-Nord/Est. Au sud de la presqu’île, le plateau s’élargit et le talus continental est orienté nord-sud. L’embouchure du fleuve Sénégal au Sénégal au Nord de la presqu’île du Cap-Vert et celles de la Gambie et de la Casamance au Sud constituent également un trait marquant de cette région. Les travaux réalisés au Sénégal en océanographie ont montré : - l’existence de deux saisons marines aux caractéristiques très différentes qui se succèdent : une saison chaude de juillet à octobre et une saison froide de décembre à mai. Ces deux saisons sont séparées par des périodes de transition. Pendant la saison froide, les alizés (vent de secteur nord-ouest à nord-est) s’établissent et engendrent à la côte une résurgence d’eau profonde (upwelling) vers la surface ; - la mise en évidence de systèmes de grands courants aux caractéristiques différentes : le courant des Canaries et le contre courant équatorial ; - la description de trois grandes houles au large du Sénégal : o la houle de Nord-Nord ouest qui a lieu toute l’année o la houle de Sud-Sud ouest apparaissant pendant l’hivernage o la houle d’ouest possible aux environs du mois de novembre. Le littoral sénégalais représente une zone d’intérêt stratégique à la fois sur le plan démographique, économique et environnemental. Les milieux naturels, dans un état de conservation relativement préservé, produisent des ressources vitales pour les 11 millions d’habitants peuplant le Sénégal. L’économie nationale sénégalaise est très dépendante de ces ressources côtières et marines qui constituent les principales recettes en devises, qu’il s’agisse de pêche ou de tourisme. L’analyse de la situation et des tendances montre que la zone côtière fait l’objet de pressions diversifiées et de plus en plus lourdes. Ces pressions se traduisent souvent par des conflits d’intérêts entre les différents secteurs et par des impacts qui génèrent une dégradation de l’environnement et des conditions de vie des populations. Cette évolution risque ainsi de compromettre les potentialités de développement offertes par les 700 Km de littoral sénégalais. La pression démographique se développe préférentiellement sur la zone côtière qui accueille déjà près de 60% des habitants, notamment dans les centres urbains et les capitale, toutes situées en bord de mer, et qui continuent à recevoir des populations en provenance de l’intérieur, réfugiés climatiques ou économiques, ou simplement jeunesse attirée par les « lumières de la ville ». Cet exode, à l’origine de dysfonctionnements des systèmes de production ruraux qui manquent peu à peu de main d’oeuvre, contribue à son tour à générer des perturbations au niveau des centres urbains où la misère se substitue parfois à la pauvreté.
    Description: Les besoins en matériaux de construction consécutifs à cette évolution démographique entraînent des prélèvements massifs de sable sur les plages qui ont à leur tour des conséquences négatives sur l’érosion et la protection du littoral. La fragilisation des cordons dunaires augmente ainsi les risques d’inondations des terres, la ville de Saint Louis étant particulièrement vulnérable à cet égard. Les besoins en développement ont conduit à la réalisation d’infrastructures le long du littoral. Ces constructions, qui tiennent trop rarement compte des contraintes environnementales, ont entraîné des répercussions structurelles sur l’équilibre de la zone côtière. Ainsi, les barrages anti-sel, tel le barrage de Diama sur le fleuve Sénégal, ont entraîné des répercussions sur le fonctionnement de certains écosystèmes côtiers. En condamnant les influences des apports d’eau douce ils appauvrissent les milieux situés en aval, stérilisant peu à peu des zones riches en ressources ainsi que les économies et les cultures qui en dépendent. Le ralentissement des courants et la baisse de salinité en amont du barrage favorisent l’apparition de certaines plantes envahissantes, telles que la bilharziose ou le paludisme. Les effectifs de poissons dépendant de milieux à salinité variable sont directement affectés, expliquant par exemple une chute de près de 70% des captures dans le bas delta du Sénégal. Les besoins du développement se traduisent également par l’amélioration ou la création d’axes routiers qui, dans la majorité des cas, longent la zone côtière. Ces ouvrages entraînent des impacts directs sur l’environnement, tels la destruction des mangroves là où les routes barrent l’écoulement des marées (exemple de la route Samba Dia – Djifère. Les systèmes de production traditionnels sont en règle générale peu préparés à faire face à des circuits de commercialisation organisés à une échelle régionale ou internationale, où à des technologies plus performantes, et éprouvent des difficultés à maintenir un contrôle sur leur terroir. Faute de pouvoir opérer une métamorphose rapide de leur système de production, le risque existe de voir peu à peu disparaître des savoir-faire d’une grande valeur dans la gestion même de ces territoires et de leurs ressources et , plus généralement, des cultures qui leur sont associées. Le développement industriel exerce des impacts potentiels ou réels de grande magnitude sur la zone côtière et marine. Les secteurs les plus significatifs à cet égard sont le tourisme et les hydrocarbures. Concernant le premier, les infrastructures, principalement orientées vers le tourisme balnéaire, sont en grande majorité installées à proximité directe de la zone côtière. L’absence quasi généralisée d’études d’impacts approfondies et indépendantes a conduit à de nombreux échecs. Ainsi, la plupart des projets ont été pensés et réalisés sans tenir suffisamment compte des contextes socio-économiques, culturels et environnementaux dans lesquels ils s’insèrent. Certaines réalisations ont été planifiées sur des secteurs soumis à une forte érosion littorale, compromettant de façon irrémédiable non seulement les investissements mais l’utilisation ultérieure du site, comme cela s’est produit sur les plages au sud immédiat du Cap Skirring. Les questions relatives à la disponibilité en eau douce qui se posent de façon cruciale dans le Saloum par exemple, à la gestion des déchets et des eaux usées ne sont que rarement prises en considération de façon structurelle et durable, conduisant à la dégradation de l’environnement ou à des conflits avec les communautés locales qui nuisent à la qualité même du tourisme. L’exploration et l’exploitation des ressources en hydrocarbures représentent aussi un secteur d’intérêt stratégique avec une généralisation des prospections. Si la découverte de gisement d’intérêt commercial représente une opportunité majeure pour l’économie nationale, elle soulève néanmoins un certain nombre de questions au regard de l’environnement. En effet les des puits. Parmi ces risques nous pouvons citer les impacts des études sismiques sur les organismes marins, notamment poissons et cétacés, le rejet de fluides toxiques et déblais de forage, le déversement des eaux de production et les pollutions aiguës dues à des accidents intervenant pendant le forage, le stockage ou le transport. Le Sénégal en ce moment, en est au stade de la prospection. Toutefois, pour ce qui concerne le transport d’hydrocarbures, plus de 90 000 0000 de tonnes d’hydrocarbures transitent par les côtes sénégalaises. Les modèles de dérive des nappes élaborés par la Compagnie pétrolière Woodside en relation avec le champ de Chinguetti, actuellement en cours de production au large de la Mauritanie, montrent des probabilités d’impact sur les côtes allant du golfe d’Arguin jusqu’à Dakar, en cas d’accident. La surexploitation des ressources halieutiques constitue également un problème au niveau de l’environnement marin et côtier. En effet, si une partie de la fluctuation des biomasses peut s’expliquer par les changements du régime des upwellings, la baisse des captures s’explique par un effort de pêche excessif, que ce soit dans le sous-secteur industriel ou artisanal. A cette surcapacité vient s’ajouter la présence de flottes illicites non déclarées et non réglementées. L’utilisation de certains engins ou pratiques de pêche contribue à aggraver la situation : la pêche crevettière est à l’origine de prises accidentelles qui représentent jusqu’à 85 % du total des captures, incluant des espèces protégées comme les tortues marines, et qui sont rejetés à la mer . Les chaluts de fonds, qui vont pêcher jusqu’à 800 m de profondeur, ainsi que les dragues à coquillages entraînant des dégâts structurels sur les écosystèmes De plus l’influence des marchés à l’exportation exerce des pressions sélectives sur certaines espèces, les espèces démersales de poissons, céphalopodes étant les plus recherchées sur le marché. Les changements climatiques ont également des impacts négatifs sur l’environnement marin et côtier. On sait que l’élévation du niveau marin aura des répercussions directes sur les installations humaines littorales ainsi que sur les écosystèmes insulaires et côtiers. Des zones de mangroves entières qui ne disposent pas des conditions écologiques pour s’adapter peuvent disparaître, entraînant des risques accrus d’érosion et d’inondation. Ces mêmes risques se multiplient avec la fréquence accrue des épisodes météorologiques exceptionnels tels que les ondes de tempêtes capables de drosser les pirogues à la côte ou de provoquer la rupture de cordons dunaires. On sait par ailleurs que le réchauffement de la température des mers influe négativement sur la productivité des océans et la dynamique des courants tels que le courant profond originaire de l’antarctique et qui exporte vers le Sénégal et les autres pays de la sousrégion des sels nutritifs présents dans les upwellings. On observe également une diminution de la puissance des alizés qui pourrait avoir des répercussions directes sur la force des upwellings et donc sur la productivité des pêcheries et du milieu marin en général. La stratégie de réponse proposée combine une protection des zones côtières importantes et un reboisement des dunes littorales dans les secteurs de la côte nord et de la Flèche de Sangomar particulièrement menacés. L’évaluation économique de cette stratégie montre qu’elle est coûteuse mais nettement en deçà de la valeur économique des terres qu’elle sera amenée à protéger. Des efforts complémentaires devront cependant être faits pour évaluer le coût d’autres solutions de protection telles que le nourissement artificiel des plages. Par ailleurs, la stratégie envisagée ne répondant qu’à l’un des impacts des changements climatiques, à savoir les inondations, toute une série de mesures dites d’accompagnement ont été suggérées qui visent à diminuer la vulnérabilité en gérant mieux les ressources présentes dans la zone côtière, en développant les techniques de récupération des sols salés et en prenant des mesures législatives et institutionnelles appropriées. Enfin, il est très important de souligner que ces différentes mesures ne devraient être envisagées que dans un cadre plus global de gestion intégrée des zones côtières, seul à même d’assurer la participation de l’ensemble des acteurs concernés, l’éducation, la recherche et l’information environnementales mais aussi la cohérences et le suivi des mesures.
    Description: Ministère de l'Environnement, de la Protection de la Nature, des Bassins de Rétention et des Lacs Artificiels, Dakar (Sénégal)
    Description: Published
    Description: écosystéme marin; technique de pêche; filet; érosion côtière; pollution; pêche; flore; environnement; migration; pêcheur; oiseau d'eau; tortue marine; lamantin; requin; mammifére marin; réglementation; mangrove; écosystème; estuaire; delta
    Keywords: Deltas ; Ecosystems ; Marine environment ; Aquatic birds ; Fishermen ; Fisheries ; Mangroves ; Coastal erosion ; Flora ; Fishing nets ; Deltas ; Ecosystems ; Mangroves ; Coastal erosion ; Marine environment ; Marine mammals ; Shark fisheries ; Turtle fisheries ; Aquatic birds ; Fishermen ; Migrations ; Flora ; Fisheries ; Marine pollution ; Fishing nets ; Climatic changes
    Repository Name: AquaDocs
    Type: Report , Non-Refereed
    Format: 1456859 bytes
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    Format: 71
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  • 7
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    From Farming to Fishing: Marine Resource Conservation (2009)
    Western Indian Ocean Marine Science Association
    Details
    Publication Date: 2021-05-19
    Description: This paper examines the arrival of a new group of fishermen on the Kenyan coast and what this has meant for the state of fishery resources. It reviews four subject areas: access and the number of fishermen; the fishermen’s identity; the choice of fishing gear; and the fishing grounds selected. Data were collected from a small number of fishing households in the villages of Uyombo and Takaungu in Kilifi District, using mainly qualitative research methods. Local households on the Kenyan coast face increasing pressure on land as well as on marine resources. The declining economic situation and greater pressure on land have made people turn to fishing as an income-generating activity. This group of fishermen is referred to as the ‘new’ generation of fishermen as they have been involved in fishing for only one or two generations (including the current one) in contrast to the ‘old’ generation from families who have been fishing or in fishingrelated activities for much longer. The old generation of fishermen and their households have also diversified their incomes, with many fishing households turning to farming, for example, with women and grown-up children involved in various activities. The new generation of fishermen, mainly of the Mijikenda population group, has often been blamed for the loss of traditional access regulations and for using harmful fishing gear. This paper discusses the new generation of fishermen and their identity as they perceive it and relates this to employment generation as a policy measure for marine conservation.
    Description: Published
    Description: Artisanal fisheries;household survey; income diversification; marine conservation,
    Keywords: Fisheries ; Fishery resources ; Fisheries ; Fishery resources
    Repository Name: AquaDocs
    Type: Journal Contribution
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  • 8
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    Plan directeur de développement forestier pêche et aquaculture continentales (2009)
    Details
    Publication Date: 2021-05-19
    Description: FAO, Rome (Italie);Ministère du Développement et de l'Hydraulique, Dakar (Sénégal)
    Description: Published
    Description: Plan de développement; fôret; pêche; milieu continental; aquaculture; pisciculture ; bilan ; facteur climatique; facteur hydrologique ; facteur socio économique; population rurale; ressources naturelles; poisson d'eau douce; ressources naturelles; gestion de l'environnement; technique de pêche; commercialisation ; consommation; projet de développement
    Keywords: Natural resources ; Fisheries ; Aquaculture ; Marketing ; Development projects ; Forests ; Climatic data ; Hydrology ; Inland water environment ; Aquatic environment ; Development potential ; Fisheries ; Aquaculture ; Marketing ; Development projects ; Fish consumption ; Hydrology ; Inland water environment ; Aquatic environment ; Forests ; Socioeconomic aspects ; Climatic data ; Natural resources ; Freshwater
    Repository Name: AquaDocs
    Type: Book
    Format: 412144 bytes
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  • 9
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    Coots use hatch order to learn to recognize and reject conspecific brood parasitic chicks (2009)
    Nature Publishing Group (NPG)
    Details
    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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    Reprogramming towards pluripotency requires AID-dependent DNA demethylation (2009)
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    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
    Print ISSN: 0028-0836
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    The sequence and de novo assembly of the giant panda genome (2009)
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    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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    Phylogenies reveal new interpretation of speciation and the Red Queen (2009)
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    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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    A structural explanation for the binding of endocytic dileucine motifs by the AP2 complex (2009)
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    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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    No bull: genes for better milk (2009)
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    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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    Two types of dopamine neuron distinctly convey positive and negative motivational signals (2009)
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    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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    Costing the earth (2009)
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    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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    Frequent inactivation of A20 in B-cell lymphomas (2009)
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    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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    A magnificence to share (2009)
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    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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    Pore architecture and ion sites in acid-sensing ion channels and P2X receptors (2009)
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    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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    A fly by any other name (2009)
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    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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    Zc3h12a is an RNase essential for controlling immune responses by regulating mRNA decay (2009)
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    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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    NOAA chief ready to tackle climate (2009)
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    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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    Linking the p53 tumour suppressor pathway to somatic cell reprogramming (2009)
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    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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    Adaptive immune features of natural killer cells (2009)
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    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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    Lab hazard (2009)
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    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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    Synthetic biology: The yin and yang of nature (2009)
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    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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    Elite and stochastic models for induced pluripotent stem cell generation (2009)
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    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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    HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses (2009)
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    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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    Long-range oncogenic activation of Igh-c-myc translocations by the Igh 3' regulatory region (2009)
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    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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    Malaria: The gatekeeper revealed (2009)
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    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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    Stably maintained dendritic spines are associated with lifelong memories (2009)
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    Details
    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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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Ancient ivory figurine deserves a more thoughtful label (2009)
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    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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    Crystal structure of the ATP-gated P2X(4) ion channel in the closed state (2009)
    Nature Publishing Group (NPG)
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    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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    Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz (2009)
    Nature Publishing Group (NPG)
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    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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    Polar science: bid for freely accessible biodiversity archive (2009)
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    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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    Bidirectional plasticity in fast-spiking GABA circuits by visual experience (2009)
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    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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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Obituary: Daniel Carleton Gajdusek (1923-2008) (2009)
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    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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    CBP/p300-mediated acetylation of histone H3 on lysine 56 (2009)
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    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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    Riboflavin kinase couples TNF receptor 1 to NADPH oxidase (2009)
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    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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    Predicting new molecular targets for known drugs (2009)
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    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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    Mitochondrial gene replacement in primate offspring and embryonic stem cells (2009)
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    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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    Rational design of a structural and functional nitric oxide reductase (2009)
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    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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    Journal club. A systems biologist ponders how disparate ideas can sometimes come together beautifully (2009)
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    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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    Forcing cells to change lineages (2009)
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    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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    CCR3 is a target for age-related macular degeneration diagnosis and therapy (2009)
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    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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    MicroRNA-mediated switching of chromatin-remodelling complexes in neural development (2009)
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    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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    Darwin's bridge between microevolution and macroevolution (2009)
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    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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    Directed transdifferentiation of mouse mesoderm to heart tissue by defined factors (2009)
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    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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    Cancer: When restriction is good (2009)
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    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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    Discovery of dual function acridones as a new antimalarial chemotype (2009)
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    Details
    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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    Neurotransmission selectively regulates synapse formation in parallel circuits in vivo (2009)
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    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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    Distinct sensory representations of wind and near-field sound in the Drosophila brain (2009)
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    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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    Asymptomatic deer excrete infectious prions in faeces (2009)
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    Publication Date: 2009-09-11
    Description: Infectious prion diseases-scrapie of sheep and chronic wasting disease (CWD) of several species in the deer family-are transmitted naturally within affected host populations. Although several possible sources of contagion have been identified in excretions and secretions from symptomatic animals, the biological importance of these sources in sustaining epidemics remains unclear. Here we show that asymptomatic CWD-infected mule deer (Odocoileus hemionus) excrete CWD prions in their faeces long before they develop clinical signs of prion disease. Intracerebral inoculation of irradiated deer faeces into transgenic mice overexpressing cervid prion protein (PrP) revealed infectivity in 14 of 15 faecal samples collected from five deer at 7-11 months before the onset of neurological disease. Although prion concentrations in deer faeces were considerably lower than in brain tissue from the same deer collected at the end of the disease, the estimated total infectious dose excreted in faeces by an infected deer over the disease course may approximate the total contained in a brain. Prolonged faecal prion excretion by infected deer provides a plausible natural mechanism that might explain the high incidence and efficient horizontal transmission of CWD within deer herds, as well as prion transmission among other susceptible cervids.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3186440/" 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/PMC3186440/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tamguney, Gultekin -- Miller, Michael W -- Wolfe, Lisa L -- Sirochman, Tracey M -- Glidden, David V -- Palmer, Christina -- Lemus, Azucena -- DeArmond, Stephen J -- Prusiner, Stanley B -- AG02132/AG/NIA NIH HHS/ -- P01 AG002132/AG/NIA NIH HHS/ -- P01 AG002132-26/AG/NIA NIH HHS/ -- P01 AG002132-29/AG/NIA NIH HHS/ -- England -- Nature. 2009 Sep 24;461(7263):529-32. doi: 10.1038/nature08289. Epub 2009 Sep 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute for Neurodegenerative Diseases, 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/19741608" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Oral ; Animals ; Biological Assay ; Brain/metabolism ; Deer/*metabolism ; Feces/*chemistry ; Injections, Intraventricular ; Mice ; Mice, Transgenic ; PrPSc Proteins/isolation & purification/*metabolism/*pathogenicity/radiation ; effects ; Time Factors ; Wasting Disease, Chronic/*metabolism/*transmission
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    Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila (2009)
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    Publication Date: 2009-12-04
    Description: Dietary restriction extends healthy lifespan in diverse organisms and reduces fecundity. It is widely assumed to induce adaptive reallocation of nutrients from reproduction to somatic maintenance, aiding survival of food shortages in nature. If this were the case, long life under dietary restriction and high fecundity under full feeding would be mutually exclusive, through competition for the same limiting nutrients. Here we report a test of this idea in which we identified the nutrients producing the responses of lifespan and fecundity to dietary restriction in Drosophila. Adding essential amino acids to the dietary restriction condition increased fecundity and decreased lifespan, similar to the effects of full feeding, with other nutrients having little or no effect. However, methionine alone was necessary and sufficient to increase fecundity as much as did full feeding, but without reducing lifespan. Reallocation of nutrients therefore does not explain the responses to dietary restriction. Lifespan was decreased by the addition of amino acids, with an interaction between methionine and other essential amino acids having a key role. Hence, an imbalance in dietary amino acids away from the ratio optimal for reproduction shortens lifespan during full feeding and limits fecundity during dietary restriction. Reduced activity of the insulin/insulin-like growth factor signalling pathway extends lifespan in diverse organisms, and we find that it also protects against the shortening of lifespan with full feeding. In other organisms, including mammals, it may be possible to obtain the benefits to lifespan of dietary restriction without incurring a reduction in fecundity, through a suitable balance of nutrients in the diet.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2798000/" 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/PMC2798000/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grandison, Richard C -- Piper, Matthew D W -- Partridge, Linda -- 081394/Wellcome Trust/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Dec 24;462(7276):1061-4. doi: 10.1038/nature08619. Epub 2009 Dec 2.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institute of Healthy Ageing, Department of Genetics Evolution and Environment, University College London, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19956092" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acids/*metabolism ; Animals ; *Diet ; Drosophila melanogaster/metabolism/*physiology ; Female ; Insulin/metabolism ; Longevity/*physiology ; Methionine/metabolism ; Oviposition/physiology ; Random Allocation ; Signal Transduction
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    Archaeology: Origins of the female image (2009)
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    Publication Date: 2009-05-16
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mellars, Paul -- England -- Nature. 2009 May 14;459(7244):176-7. doi: 10.1038/459176a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19444200" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Archaeology ; Female ; Germany ; History, Ancient ; Horns/chemistry ; Humans ; Sculpture/*history ; Sex Characteristics ; Symbolism
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    Journal club. A geneticist views two theories of X-chromosome inactivation in a broad context (2009)
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    Publication Date: 2009-03-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khalil, Ahmad M -- England -- Nature. 2009 Mar 19;458(7236):263. doi: 10.1038/458263f.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Harvard Medical School, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19295563" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Female ; *Models, Genetic ; RNA Interference ; RNA, Long Noncoding ; RNA, Untranslated/*genetics ; Ribonuclease III/deficiency ; X Chromosome Inactivation/*genetics
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    Journal club. A physiologist notes the similarities between animal and plant electricity (2009)
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    Publication Date: 2009-03-06
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tammaro, Paolo -- England -- Nature. 2009 Mar 5;458(7234):11. doi: 10.1038/458011e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University of Manchester, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19262629" target="_blank"〉PubMed〈/a〉
    Keywords: Amino Acid Substitution ; Animals ; Arabidopsis/cytology/genetics/metabolism ; Arabidopsis Proteins/*chemistry/genetics/*metabolism ; Chloride Channels/*chemistry/genetics/*metabolism ; Chlorides/*metabolism ; Humans ; Ion Transport ; Nitrates/*metabolism
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    Developmental biology: Birth of the blood cell (2009)
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    Publication Date: 2009-02-13
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2766277/" 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/PMC2766277/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yoshimoto, Momoko -- Yoder, Mervin C -- R01 AI080759/AI/NIAID NIH HHS/ -- R01 AI080759-01/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Feb 12;457(7231):801-3. doi: 10.1038/457801a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19212393" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Cells/*cytology ; Embryo, Mammalian/cytology/embryology ; Hemangioblasts/*cytology ; Hematopoietic Stem Cells/cytology ; Mice
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    Vision: New light on allergy receptor (2009)
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    Publication Date: 2009-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Grant, Maria -- England -- Nature. 2009 Jul 9;460(7252):182-3. doi: 10.1038/460182a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587753" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chemokine CCL11/antagonists & inhibitors/metabolism ; Chemokine CCL24/antagonists & inhibitors/metabolism ; Chemokines, CC/antagonists & inhibitors/metabolism ; Choroid/blood supply/cytology/metabolism ; Choroidal Neovascularization/diagnosis/metabolism ; Humans ; Hypersensitivity/metabolism ; Inflammation ; Macular Degeneration/diagnosis/*metabolism/therapy ; Mice ; Receptors, CCR3/antagonists & inhibitors/immunology/*metabolism ; Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism
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    Cheater-resistance is not futile (2009)
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    Publication Date: 2009-10-02
    Description: Cooperative social systems are susceptible to cheating by individuals that reap the benefits of cooperation without incurring the costs. There are various theoretical mechanisms for the repression of cheating and many have been tested experimentally. One possibility that has not been tested rigorously is the evolution of mutations that confer resistance to cheating. Here we show that the presence of a cheater in a population of randomly mutated social amoebae can select for cheater-resistance. Furthermore, we show that this cheater-resistance can be a noble strategy because the resister strain does not necessarily exploit other strains. Thus, the evolution of resisters may be instrumental in preserving cooperative behaviour in the face of cheating.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Khare, Anupama -- Santorelli, Lorenzo A -- Strassmann, Joan E -- Queller, David C -- Kuspa, Adam -- Shaulsky, Gad -- England -- Nature. 2009 Oct 15;461(7266):980-2. doi: 10.1038/nature08472. Epub 2009 Sep 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19794414" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cooperative Behavior ; Dictyostelium/genetics/*physiology ; Evolution, Molecular ; Genes, Protozoan/genetics ; *Models, Biological ; Mutation/genetics ; Protozoan Proteins/genetics/metabolism ; *Social Behavior ; Spores, Protozoan/physiology
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    Recall of learned information may rely on taking drug again (2009)
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    Publication Date: 2009-01-30
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Young, Alice M -- Colpaert, Francis C -- England -- Nature. 2009 Jan 29;457(7229):533. doi: 10.1038/457533a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19177109" target="_blank"〉PubMed〈/a〉
    Keywords: Amphetamines/*administration & dosage/adverse effects/*pharmacology ; Animals ; *Biomedical Enhancement ; Cognition/*drug effects/physiology ; *Health ; Humans ; Mental Recall/*drug effects/*physiology
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    Sex determination: Birds do it with a Z gene (2009)
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    Publication Date: 2009-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Graves, Jennifer A Marshall -- England -- Nature. 2009 Sep 10;461(7261):177-8. doi: 10.1038/461177a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741690" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Chick Embryo ; Chickens/*genetics/*physiology ; Disorders of Sex Development ; Evolution, Molecular ; Female ; Gene Dosage/genetics ; Humans ; Male ; Models, Genetic ; Ovary/embryology/metabolism ; RNA Interference ; SOX9 Transcription Factor/genetics/metabolism ; Sex Chromosomes/*genetics ; *Sex Determination Processes ; Testis/embryology/metabolism ; Transcription Factors/deficiency/*genetics/*metabolism
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    Being human: love: neuroscience reveals all (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-01-09
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Young, Larry J -- England -- Nature. 2009 Jan 8;457(7226):148. doi: 10.1038/457148a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322, USA. lyoun03@emory.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19129828" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arvicolinae/genetics/physiology ; Dopamine/metabolism ; Female ; Humans ; *Love ; Male ; Maternal Behavior/physiology ; Oxytocin/*metabolism ; Pair Bond ; Paternal Behavior ; Receptors, Vasopressin/genetics/metabolism ; Sexual Behavior/drug effects/physiology ; Vasopressins/*metabolism
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    Journal club. A molecular cardiologist looks into getting to the heart of his inner fish (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-08-29
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Riley, Paul -- England -- Nature. 2009 Aug 27;460(7259):1061. doi: 10.1038/4601061e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉University College London.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19713895" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cardiovascular Diseases/therapy ; Fishes/*physiology ; Mice ; Myocardium/*cytology ; Neuregulin-1/*pharmacology ; Regeneration/*drug effects ; Salamandridae/physiology
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    JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin (2009)
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    Publication Date: 2009-09-29
    Description: Activation of Janus kinase 2 (JAK2) by chromosomal translocations or point mutations is a frequent event in haematological malignancies. JAK2 is a non-receptor tyrosine kinase that regulates several cellular processes by inducing cytoplasmic signalling cascades. Here we show that human JAK2 is present in the nucleus of haematopoietic cells and directly phosphorylates Tyr 41 (Y41) on histone H3. Heterochromatin protein 1alpha (HP1alpha), but not HP1beta, specifically binds to this region of H3 through its chromo-shadow domain. Phosphorylation of H3Y41 by JAK2 prevents this binding. Inhibition of JAK2 activity in human leukaemic cells decreases both the expression of the haematopoietic oncogene lmo2 and the phosphorylation of H3Y41 at its promoter, while simultaneously increasing the binding of HP1alpha at the same site. Tauhese results identify a previously unrecognized nuclear role for JAK2 in the phosphorylation of H3Y41 and reveal a direct mechanistic link between two genes, jak2 and lmo2, involved in normal haematopoiesis and leukaemia.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3785147/" 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/PMC3785147/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dawson, Mark A -- Bannister, Andrew J -- Gottgens, Berthold -- Foster, Samuel D -- Bartke, Till -- Green, Anthony R -- Kouzarides, Tony -- 089957/Wellcome Trust/United Kingdom -- 12765/Cancer Research UK/United Kingdom -- G0800784/Medical Research Council/United Kingdom -- MC_UP_1102/2/Medical Research Council/United Kingdom -- Cancer Research UK/United Kingdom -- Medical Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Oct 8;461(7265):819-22. doi: 10.1038/nature08448. Epub 2009 Sep 27.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Cambridge Institute for Medical Research and Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 0XY, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19783980" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptor Proteins, Signal Transducing ; Animals ; Binding Sites ; Cell Line ; Cell Nucleus/enzymology ; Chromatin/chemistry/*metabolism ; Chromosomal Proteins, Non-Histone/*metabolism ; DNA-Binding Proteins/genetics ; Gene Expression Regulation, Neoplastic ; Hematopoiesis/genetics ; Hematopoietic Stem Cells/cytology/enzymology ; Histones/chemistry/genetics/*metabolism ; Humans ; Janus Kinase 2/antagonists & inhibitors/*metabolism ; LIM Domain Proteins ; Leukemia/enzymology/genetics/metabolism/pathology ; Metalloproteins/genetics ; Mice ; Oncogenes/genetics ; Phosphorylation ; Promoter Regions, Genetic/genetics ; Protein Binding ; Proto-Oncogene Proteins ; Signal Transduction ; Tyrosine/metabolism
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    Biomaterials (2009)
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    Publication Date: 2009-11-27
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Daw, Rosamund -- Tonzani, Stefano -- England -- Nature. 2009 Nov 26;462(7272):425. doi: 10.1038/462425a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19940911" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biocompatible Materials/chemistry/metabolism/therapeutic use ; *Biomedical Research/trends ; Humans
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    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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    Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules (2009)
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    Publication Date: 2009-09-11
    Description: It is widely accepted that tissue differentiation and morphogenesis in multicellular organisms are regulated by tightly controlled concentration gradients of morphogens. How exactly these gradients are formed, however, remains unclear. Here we show that Fgf8 morphogen gradients in living zebrafish embryos are established and maintained by two essential factors: fast, free diffusion of single molecules away from the source through extracellular space, and a sink function of the receiving cells, regulated by receptor-mediated endocytosis. Evidence is provided by directly examining single molecules of Fgf8 in living tissue by fluorescence correlation spectroscopy, quantifying their local mobility and concentration with high precision. By changing the degree of uptake of Fgf8 into its target cells, we are able to alter the shape of the Fgf8 gradient. Our results demonstrate that a freely diffusing morphogen can set up concentration gradients in a complex multicellular tissue by a simple source-sink mechanism.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Shuizi Rachel -- Burkhardt, Markus -- Nowak, Matthias -- Ries, Jonas -- Petrasek, Zdenek -- Scholpp, Steffen -- Schwille, Petra -- Brand, Michael -- England -- Nature. 2009 Sep 24;461(7263):533-6. doi: 10.1038/nature08391. Epub 2009 Sep 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Genetics, Biotechnology Center, TUD, Tatzberg 47-49, 01307 Dresden, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741606" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Diffusion ; Embryo, Nonmammalian/*cytology/embryology/*metabolism ; *Endocytosis ; Extracellular Space/metabolism ; Fibroblast Growth Factors/genetics/*metabolism ; Gastrulation ; Green Fluorescent Proteins/genetics/metabolism ; Models, Biological ; Morphogenesis/*physiology ; Receptors, Fibroblast Growth Factor/metabolism ; Zebrafish/*embryology/*metabolism ; Zebrafish Proteins/genetics/*metabolism
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    Role of Jhdm2a in regulating metabolic gene expression and obesity resistance (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-02-06
    Description: Recent studies indicate that the methylation state of histones can be dynamically regulated by histone methyltransferases and demethylases. The H3K9-specific demethylase Jhdm2a (also known as Jmjd1a and Kdm3a) has an important role in nuclear hormone receptor-mediated gene activation and male germ cell development. Through disruption of the Jhdm2a gene in mice, here we demonstrate that Jhdm2a is critically important in regulating the expression of metabolic genes. The loss of Jhdm2a function results in obesity and hyperlipidemia in mice. We provide evidence that the loss of Jhdm2a function disrupts beta-adrenergic-stimulated glycerol release and oxygen consumption in brown fat, and decreases fat oxidation and glycerol release in skeletal muscles. We show that Jhdm2a expression is induced by beta-adrenergic stimulation, and that Jhdm2a directly regulates peroxisome proliferator-activated receptor alpha (Ppara) and Ucp1 expression. Furthermore, we demonstrate that beta-adrenergic activation-induced binding of Jhdm2a to the PPAR responsive element (PPRE) of the Ucp1 gene not only decreases levels of H3K9me2 (dimethylation of lysine 9 of histone H3) at the PPRE, but also facilitates the recruitment of Ppargamma and Rxralpha and their co-activators Pgc1alpha (also known as Ppargc1a), CBP/p300 (Crebbp) and Src1 (Ncoa1) to the PPRE. Our studies thus demonstrate an essential role for Jhdm2a in regulating metabolic gene expression and normal weight control in mice.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085783/" 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/PMC4085783/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tateishi, Keisuke -- Okada, Yuki -- Kallin, Eric M -- Zhang, Yi -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Apr 9;458(7239):757-61. doi: 10.1038/nature07777. Epub 2009 Feb 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7295, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19194461" target="_blank"〉PubMed〈/a〉
    Keywords: Adipose Tissue, Brown/metabolism ; Animals ; Cells, Cultured ; Energy Metabolism/*physiology ; Gene Expression Profiling ; *Gene Expression Regulation ; Glycerol/metabolism ; Ion Channels/metabolism ; Jumonji Domain-Containing Histone Demethylases ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondrial Proteins/metabolism ; Muscle, Skeletal/metabolism ; Obesity/*metabolism ; Oxidation-Reduction ; Oxidoreductases, N-Demethylating/*genetics/*metabolism ; Phenotype ; Receptors, Adrenergic, beta/metabolism
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    Animal-health facility in Germany leads the way for Europe (2009)
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    Publication Date: 2009-04-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mettenleiter, Thomas C -- England -- Nature. 2009 Apr 2;458(7238):571. doi: 10.1038/458571d.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19340058" target="_blank"〉PubMed〈/a〉
    Keywords: *Academies and Institutes/standards ; Animal Welfare/standards ; Animals ; *Animals, Laboratory ; Biomedical Research ; Germany ; Housing, Animal/*standards/*trends
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    Formyl peptide receptor-like proteins are a novel family of vomeronasal chemosensors (2009)
    Nature Publishing Group (NPG)
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    Publication Date: 2009-04-24
    Description: Mammals rely heavily on olfaction to interact adequately with each other and with their environment. They make use of seven-transmembrane G-protein-coupled receptors to identify odorants and pheromones. These receptors are present on dendrites of olfactory sensory neurons located in the main olfactory or vomeronasal sensory epithelia, and pertain to the odorant, trace amine-associated receptor and vomeronasal type 1 (ref. 4) or 2 (refs 5-7) receptor superfamilies. Whether these four sensor classes represent the complete olfactory molecular repertoire used by mammals to make sense of the outside world is unknown. Here we report the expression of formyl peptide receptor-related genes by vomeronasal sensory neurons, in multiple mammalian species. Similar to the four known olfactory receptor gene classes, these genes encode seven-transmembrane proteins, and are characterized by monogenic transcription and a punctate expression pattern in the sensory neuroepithelium. In vitro expression of mouse formyl peptide receptor-like 1, 3, 4, 6 and 7 provides sensitivity to disease/inflammation-related ligands. Establishing an in situ approach that combines whole-mount vomeronasal preparations with dendritic calcium imaging in the intact neuroepithelium, we show neuronal responses to the same molecules, which therefore represent a new class of vomeronasal agonists. Taken together, these results suggest that formyl peptide receptor-like proteins have an olfactory function associated with the identification of pathogens, or of pathogenic states.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Riviere, Stephane -- Challet, Ludivine -- Fluegge, Daniela -- Spehr, Marc -- Rodriguez, Ivan -- England -- Nature. 2009 May 28;459(7246):574-7. doi: 10.1038/nature08029.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology and Animal Biology, and National Center of Competence Frontiers in Genetics, University of Geneva, 1205 Geneva, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19387439" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium Signaling ; Cell Line ; Dendrites/drug effects/metabolism ; *Disease ; Gene Expression Profiling ; Humans ; Inflammation/pathology ; Ligands ; Mice ; Olfactory Perception/drug effects/*physiology ; Olfactory Receptor Neurons/cytology/drug effects/*metabolism ; Organ Specificity ; Receptors, Formyl Peptide/genetics/*metabolism ; Smell/drug effects/*physiology ; Vomeronasal Organ/*cytology/drug effects/physiology
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    Behaviour: Flies on film (2009)
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    Publication Date: 2009-12-04
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchen, Lizzie -- England -- Nature. 2009 Dec 3;462(7273):562-4. doi: 10.1038/462562a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19956235" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior/physiology ; *Behavior, Animal ; Behavioral Research/*instrumentation/methods ; Drosophila melanogaster/*physiology ; Female ; Humans ; Male ; Software ; Video Recording/instrumentation/methods
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    VEGFR1-activity-independent metastasis formation (2009)
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    Publication Date: 2009-09-18
    Description: Molecules such as vascular endothelial growth factor (VEGF) or placental growth factor-critical regulators of tumour angiogenesis-are also thought to mobilize into blood circulation bone marrow-derived cells (BMDCs), which may subsequently be recruited to tumours and facilitate tumour growth and metastasis. A study has suggested that BMDCs form 'metastatic niches' in lungs before arrival of cancer cells, and showed that pharmacological inhibition of VEGF receptor 1 (VEGFR1, also known as Flt1)-cognate receptor for VEGF and placental growth factor-prevented BMDC infiltration in lungs and 'metastatic niche' formation. Here we report that blockade of VEGFR1 activity does not affect the rate of spontaneous metastasis formation in a clinically relevant and widely used preclinical model. Therefore, alternative pathways probably mediate the priming of tissues for metastasis.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3065241/" 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/PMC3065241/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dawson, Michelle R -- Duda, Dan G -- Fukumura, Dai -- Jain, Rakesh K -- P01 CA080124/CA/NCI NIH HHS/ -- P01 CA080124-05/CA/NCI NIH HHS/ -- P01 CA080124-06A2/CA/NCI NIH HHS/ -- P01 CA080124-07/CA/NCI NIH HHS/ -- P01 CA080124-08/CA/NCI NIH HHS/ -- P01 CA080124-09/CA/NCI NIH HHS/ -- R01 CA085140/CA/NCI NIH HHS/ -- R01 CA085140-06/CA/NCI NIH HHS/ -- R01 CA085140-07/CA/NCI NIH HHS/ -- R01 CA085140-08/CA/NCI NIH HHS/ -- R01 CA085140-09/CA/NCI NIH HHS/ -- R01 CA096915/CA/NCI NIH HHS/ -- R01 CA096915-04/CA/NCI NIH HHS/ -- R01 CA096915-05/CA/NCI NIH HHS/ -- R01 CA096915-06A1/CA/NCI NIH HHS/ -- R01 CA096915-07/CA/NCI NIH HHS/ -- R01 CA096915-08/CA/NCI NIH HHS/ -- R01 CA115767/CA/NCI NIH HHS/ -- R01 CA115767-01A1/CA/NCI NIH HHS/ -- R01 CA115767-02/CA/NCI NIH HHS/ -- R01 CA115767-03/CA/NCI NIH HHS/ -- R01 CA115767-04/CA/NCI NIH HHS/ -- R01 CA126642/CA/NCI NIH HHS/ -- R01 CA126642-01A1/CA/NCI NIH HHS/ -- R01 CA126642-02/CA/NCI NIH HHS/ -- R24 CA085140/CA/NCI NIH HHS/ -- R24 CA085140-05/CA/NCI NIH HHS/ -- T32 CA073479/CA/NCI NIH HHS/ -- T32 CA073479-08/CA/NCI NIH HHS/ -- T32 CA073479-09/CA/NCI NIH HHS/ -- T32 CA073479-10/CA/NCI NIH HHS/ -- T32 CA073479-11/CA/NCI NIH HHS/ -- T32 CA073479-12/CA/NCI NIH HHS/ -- England -- Nature. 2009 Sep 17;461(7262):E4; discussion E5. doi: 10.1038/nature08254.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Steele Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19759568" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bone Marrow Cells/cytology ; Cell Movement ; Lung/pathology ; Lung Neoplasms/*secondary ; Mice ; Mice, Inbred C57BL ; Neoplasm Transplantation ; Neoplasms/*pathology ; Vascular Endothelial Growth Factor Receptor-1/*antagonists & ; inhibitors/deficiency/*metabolism
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    Direct reprogramming of human neural stem cells by OCT4 (2009)
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    Publication Date: 2009-09-01
    Description: Induced pluripotent stem (iPS) cells have been generated from mouse and human somatic cells by ectopic expression of four transcription factors (OCT4 (also called POU5F1), SOX2, c-Myc and KLF4). We previously reported that Oct4 alone is sufficient to reprogram directly adult mouse neural stem cells to iPS cells. Here we report the generation of one-factor human iPS cells from human fetal neural stem cells (one-factor (1F) human NiPS cells) by ectopic expression of OCT4 alone. One-factor human NiPS cells resemble human embryonic stem cells in global gene expression profiles, epigenetic status, as well as pluripotency in vitro and in vivo. These findings demonstrate that the transcription factor OCT4 is sufficient to reprogram human neural stem cells to pluripotency. One-factor iPS cell generation will advance the field further towards understanding reprogramming and generating patient-specific pluripotent stem cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Jeong Beom -- Greber, Boris -- Arauzo-Bravo, Marcos J -- Meyer, Johann -- Park, Kook In -- Zaehres, Holm -- Scholer, Hans R -- England -- Nature. 2009 Oct 1;461(7264):649-3. doi: 10.1038/nature08436.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Max Planck Institute for Molecular Biomedicine, Department of Cell and Developmental Biology, Rontgenstrasse 20, 48149 Munster, NRW, Germany.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19718018" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biomarkers/analysis ; *Cell Dedifferentiation ; Cell Differentiation ; Cell Line ; *Cellular Reprogramming ; DNA Methylation ; Embryonic Stem Cells/cytology/metabolism ; Epigenesis, Genetic ; Fetus/*cytology ; Gene Expression Profiling ; Germ Layers/cytology/metabolism ; Humans ; Mice ; Neurons/*cytology/metabolism ; Octamer Transcription Factor-3/genetics/*metabolism ; Pluripotent Stem Cells/*cytology/*metabolism
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    Specific synapses develop preferentially among sister excitatory neurons in the neocortex (2009)
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    Publication Date: 2009-02-11
    Description: Neurons in the mammalian neocortex are organized into functional columns. Within a column, highly specific synaptic connections are formed to ensure that similar physiological properties are shared by neuron ensembles spanning from the pia to the white matter. Recent studies indicate that synaptic connectivity in the neocortex is sparse and highly specific to allow even adjacent neurons to convey information independently. How this fine-scale microcircuit is constructed to create a functional columnar architecture at the level of individual neurons largely remains a mystery. Here we investigate whether radial clones of excitatory neurons arising from the same mother cell in the developing neocortex serve as a substrate for the formation of this highly specific microcircuit. We labelled ontogenetic radial clones of excitatory neurons in the mouse neocortex by in utero intraventricular injection of enhanced green fluorescent protein (EGFP)-expressing retroviruses around the onset of the peak phase of neocortical neurogenesis. Multiple-electrode whole-cell recordings were performed to probe synapse formation among these EGFP-labelled sister excitatory neurons in radial clones and the adjacent non-siblings during postnatal stages. We found that radially aligned sister excitatory neurons have a propensity for developing unidirectional chemical synapses with each other rather than with neighbouring non-siblings. Moreover, these synaptic connections display the same interlaminar directional preference as those observed in the mature neocortex. These results indicate that specific microcircuits develop preferentially within ontogenetic radial clones of excitatory neurons in the developing neocortex and contribute to the emergence of functional columnar microarchitectures in the mature neocortex.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2727717/" 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/PMC2727717/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yu, Yong-Chun -- Bultje, Ronald S -- Wang, Xiaoqun -- Shi, Song-Hai -- AS5274/Autism Speaks/ -- R01 DA024681/DA/NIDA NIH HHS/ -- R01 DA024681-01A1/DA/NIDA NIH HHS/ -- R21 MH083624/MH/NIMH NIH HHS/ -- R21 MH083624-01/MH/NIMH NIH HHS/ -- England -- Nature. 2009 Mar 26;458(7237):501-4. doi: 10.1038/nature07722. Epub 2009 Feb 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Biology Program, Memorial Sloan Kettering Cancer Centre, 1275 York Avenue, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19204731" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Lineage ; Clone Cells/cytology ; Mice ; Neocortex/anatomy & histology/*cytology ; Neurons/*cytology/*metabolism ; Synapses/*metabolism
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    Cytoplasmic functions of the tumour suppressor p53 (2009)
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    Publication Date: 2009-05-02
    Description: The principal tumour-suppressor protein, p53, accumulates in cells in response to DNA damage, oncogene activation and other stresses. It acts as a nuclear transcription factor that transactivates genes involved in apoptosis, cell cycle regulation and numerous other processes. An emerging area of research unravels additional activities of p53 in the cytoplasm, where it triggers apoptosis and inhibits autophagy. These previously unknown functions contribute to the mission of p53 as a tumour suppressor.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814168/" 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/PMC2814168/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Green, Douglas R -- Kroemer, Guido -- P01 CA069381/CA/NCI NIH HHS/ -- P01 CA069381-140010/CA/NCI NIH HHS/ -- R01 AI040646/AI/NIAID NIH HHS/ -- R01 AI040646-14/AI/NIAID NIH HHS/ -- R01 AI044828/AI/NIAID NIH HHS/ -- R01 AI044828-12/AI/NIAID NIH HHS/ -- R01 AI047891/AI/NIAID NIH HHS/ -- R01 AI047891-11/AI/NIAID NIH HHS/ -- R37 GM052735/GM/NIGMS NIH HHS/ -- R37 GM052735-19/GM/NIGMS NIH HHS/ -- England -- Nature. 2009 Apr 30;458(7242):1127-30. doi: 10.1038/nature07986.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. douglas.green@stjude.org〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19407794" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Apoptosis ; Autophagy ; Cell Nucleus/metabolism ; Cytoplasm/*metabolism ; Humans ; Mitochondria/metabolism ; Neoplasms/metabolism/pathology ; Transcription, Genetic ; Tumor Suppressor Protein p53/genetics/*metabolism
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    Requirement for NF-kappaB signalling in a mouse model of lung adenocarcinoma (2009)
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    Publication Date: 2009-10-23
    Description: NF-kappaB transcription factors function as crucial regulators of inflammatory and immune responses as well as of cell survival. They have also been implicated in cellular transformation and tumorigenesis. However, despite extensive biochemical characterization of NF-kappaB signalling during the past twenty years, the requirement for NF-kappaB in tumour development in vivo, particularly in solid tumours, is not completely understood. Here we show that the NF-kappaB pathway is required for the development of tumours in a mouse model of lung adenocarcinoma. Concomitant loss of p53 (also known as Trp53) and expression of oncogenic Kras(G12D) resulted in NF-kappaB activation in primary mouse embryonic fibroblasts. Conversely, in lung tumour cell lines expressing Kras(G12D) and lacking p53, p53 restoration led to NF-kappaB inhibition. Furthermore, the inhibition of NF-kappaB signalling induced apoptosis in p53-null lung cancer cell lines. Inhibition of the pathway in lung tumours in vivo, from the time of tumour initiation or after tumour progression, resulted in significantly reduced tumour development. Together, these results indicate a critical function for NF-kappaB signalling in lung tumour development and, further, that this requirement depends on p53 status. These findings also provide support for the development of NF-kappaB inhibitory drugs as targeted therapies for the treatment of patients with defined mutations in Kras and p53.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780341/" 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/PMC2780341/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Meylan, Etienne -- Dooley, Alison L -- Feldser, David M -- Shen, Lynn -- Turk, Erin -- Ouyang, Chensi -- Jacks, Tyler -- P30 CA014051/CA/NCI NIH HHS/ -- P30 CA014051-37/CA/NCI NIH HHS/ -- P30 CA014051-38/CA/NCI NIH HHS/ -- P30-CA14051/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Nov 5;462(7269):104-7. doi: 10.1038/nature08462. Epub 2009 Oct 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Koch Institute for Integrative Cancer Research, and Department of Biology, and Howard Hughes Medical Institute, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19847165" target="_blank"〉PubMed〈/a〉
    Keywords: Adenocarcinoma/*metabolism/*pathology ; Animals ; Apoptosis ; Carcinoma, Non-Small-Cell Lung/metabolism/pathology ; Cell Line ; Cell Line, Tumor ; Cell Survival ; Cells, Cultured ; DNA/metabolism ; *Disease Models, Animal ; Fibroblasts ; Genes, p53/genetics ; Humans ; Lung Neoplasms/*metabolism/*pathology ; Mice ; NF-kappa B/antagonists & inhibitors/*metabolism ; Oncogene Protein p21(ras)/genetics/metabolism ; *Signal Transduction ; Transcription Factor RelA/metabolism ; Tumor Suppressor Protein p53/deficiency/genetics/metabolism
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    Clustering of InsP3 receptors by InsP3 retunes their regulation by InsP3 and Ca2+ (2009)
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    Publication Date: 2009-04-07
    Description: The versatility of Ca2+ signals derives from their spatio-temporal organization. For Ca2+ signals initiated by inositol-1,4,5-trisphosphate (InsP3), this requires local interactions between InsP3 receptors (InsP3Rs) mediated by their rapid stimulation and slower inhibition by cytosolic Ca2+. This allows hierarchical recruitment of Ca2+ release events as the InsP3 concentration increases. Single InsP3Rs respond first, then clustered InsP3Rs open together giving a local 'Ca2+ puff', and as puffs become more frequent they ignite regenerative Ca2+ waves. Using nuclear patch-clamp recording, here we demonstrate that InsP3Rs are initially randomly distributed with an estimated separation of 1 m. Low concentrations of InsP3 cause InsP3Rs to aggregate rapidly and reversibly into small clusters of about four closely associated InsP3Rs. At resting cytosolic [Ca2+], clustered InsP3Rs open independently, but with lower open probability, shorter open time, and less InsP3 sensitivity than lone InsP3Rs. Increasing cytosolic [Ca2+] reverses the inhibition caused by clustering, InsP3R gating becomes coupled, and the duration of multiple openings is prolonged. Clustering both exposes InsP3Rs to local Ca2+ rises and increases the effects of Ca2+. Dynamic regulation of clustering by InsP3 retunes InsP3R sensitivity to InsP3 and Ca2+, facilitating hierarchical recruitment of the elementary events that underlie all InsP3-evoked Ca2+ signals.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2702691/" 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/PMC2702691/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Taufiq-Ur-Rahman -- Skupin, Alexander -- Falcke, Martin -- Taylor, Colin W -- 085295/Wellcome Trust/United Kingdom -- BBE0046601/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 Apr 2;458(7238):655-9. doi: 10.1038/nature07763.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology, Tennis Court Road, Cambridge CB2 1PD, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19348050" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Calcium/*metabolism ; *Calcium Signaling ; Cell Line ; Cytosol/metabolism ; Inositol 1,4,5-Trisphosphate/*metabolism ; Inositol 1,4,5-Trisphosphate Receptors/*metabolism ; Ion Channel Gating ; Patch-Clamp Techniques ; Protein Transport ; Rats
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    US agriculture research gets priority plan (2009)
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    Publication Date: 2009-10-02
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buchen, Lizzie -- England -- Nature. 2009 Oct 1;461(7264):580. doi: 10.1038/461580a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19794466" target="_blank"〉PubMed〈/a〉
    Keywords: Agriculture/*organization & administration/*trends ; Animals ; Research/*trends ; United States ; United States Department of Agriculture/*organization & administration
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    Cell biology: Sent by the scent of death (2009)
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    Publication Date: 2009-09-11
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Gregory, Christopher -- England -- Nature. 2009 Sep 10;461(7261):181-2. doi: 10.1038/461181a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19741694" target="_blank"〉PubMed〈/a〉
    Keywords: Adenosine Triphosphate/*metabolism/secretion ; Animals ; Apoptosis/*physiology ; Chemotactic Factors/metabolism/secretion ; Chemotaxis/drug effects ; Culture Media, Conditioned/metabolism/pharmacology ; Humans ; Macrophages/cytology/drug effects/metabolism ; Mice ; Monocytes/cytology/drug effects/metabolism ; Phagocytes/*cytology/drug effects/metabolism ; Phagocytosis/drug effects/*physiology ; Receptors, Purinergic P2/metabolism ; Receptors, Purinergic P2Y2 ; *Signal Transduction/drug effects ; Thymus Gland/*cytology ; Uridine Triphosphate/*metabolism/secretion
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    Malaria: Evolution in vector control (2009)
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    Publication Date: 2009-11-20
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Michalakis, Yannis -- Renaud, Francois -- England -- Nature. 2009 Nov 19;462(7271):298-300. doi: 10.1038/462298a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19924207" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Culicidae/microbiology/parasitology/*physiology ; Fungi/physiology ; Humans ; Insect Control ; Insect Vectors/microbiology/*physiology ; Insecticides ; *Malaria/parasitology/physiopathology/prevention & control/transmission ; Mutation ; Plasmodium/genetics/*physiology
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    Crystal structure of an avian influenza polymerase PA(N) reveals an endonuclease active site (2009)
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    Publication Date: 2009-02-06
    Description: The heterotrimeric influenza virus polymerase, containing the PA, PB1 and PB2 proteins, catalyses viral RNA replication and transcription in the nucleus of infected cells. PB1 holds the polymerase active site and reportedly harbours endonuclease activity, whereas PB2 is responsible for cap binding. The PA amino terminus is understood to be the major functional part of the PA protein and has been implicated in several roles, including endonuclease and protease activities as well as viral RNA/complementary RNA promoter binding. Here we report the 2.2 angstrom (A) crystal structure of the N-terminal 197 residues of PA, termed PA(N), from an avian influenza H5N1 virus. The PA(N) structure has an alpha/beta architecture and reveals a bound magnesium ion coordinated by a motif similar to the (P)DX(N)(D/E)XK motif characteristic of many endonucleases. Structural comparisons and mutagenesis analysis of the motif identified in PA(N) provide further evidence that PA(N) holds an endonuclease active site. Furthermore, functional analysis with in vivo ribonucleoprotein reconstitution and direct in vitro endonuclease assays strongly suggest that PA(N) holds the endonuclease active site and has critical roles in endonuclease activity of the influenza virus polymerase, rather than PB1. The high conservation of this endonuclease active site among influenza strains indicates that PA(N) is an important target for the design of new anti-influenza therapeutics.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yuan, Puwei -- Bartlam, Mark -- Lou, Zhiyong -- Chen, Shoudeng -- Zhou, Jie -- He, Xiaojing -- Lv, Zongyang -- Ge, Ruowen -- Li, Xuemei -- Deng, Tao -- Fodor, Ervin -- Rao, Zihe -- Liu, Yingfang -- G0700848/Medical Research Council/United Kingdom -- England -- Nature. 2009 Apr 16;458(7240):909-13. doi: 10.1038/nature07720. Epub 2009 Feb 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19194458" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Birds/virology ; Catalytic Domain ; Crystallography, X-Ray ; Endonucleases/*chemistry/genetics/*metabolism ; Influenza A Virus, H5N1 Subtype/*enzymology ; Influenza in Birds/*virology ; Models, Molecular ; Protein Subunits/chemistry/genetics/metabolism ; RNA Replicase/*chemistry/genetics/*metabolism ; Viral Proteins/*chemistry/genetics/*metabolism
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    Cell biology: The not-so-odd couple (2009)
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    Publication Date: 2009-07-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Millar, Sarah E -- England -- Nature. 2009 Jul 2;460(7251):44-5. doi: 10.1038/460044a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571874" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Choristoma/genetics/metabolism/pathology ; Chromatin/genetics ; DNA Helicases/metabolism ; Humans ; Nuclear Proteins/metabolism ; *Signal Transduction ; Telomerase/*metabolism ; Transcription Factors/metabolism ; Wnt Proteins/genetics/*metabolism ; Xenopus laevis/embryology/metabolism ; beta Catenin/deficiency/genetics/*metabolism
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    CtIP-BRCA1 modulates the choice of DNA double-strand-break repair pathway throughout the cell cycle (2009)
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    Publication Date: 2009-04-10
    Description: The repair of DNA double-strand breaks (DSBs) is tightly regulated during the cell cycle. In G1 phase, the absence of a sister chromatid means that repair of DSBs occurs through non-homologous end-joining or microhomology-mediated end-joining (MMEJ). These pathways often involve loss of DNA sequences at the break site and are therefore error-prone. In late S and G2 phases, even though DNA end-joining pathways remain functional, there is an increase in repair of DSBs by homologous recombination, which is mostly error-free. Consequently, the relative contribution of these different pathways to DSB repair in the cell cycle has a large influence on the maintenance of genetic integrity. It has remained unknown how DSBs are directed for repair by different, potentially competing, repair pathways. Here we identify a role for CtIP (also known as RBBP8) in this process in the avian B-cell line DT40. We establish that CtIP is required not only for repair of DSBs by homologous recombination in S/G2 phase but also for MMEJ in G1. The function of CtIP in homologous recombination, but not MMEJ, is dependent on the phosphorylation of serine residue 327 and recruitment of BRCA1. Cells expressing CtIP protein that cannot be phosphorylated at serine 327 are specifically defective in homologous recombination and have a decreased level of single-stranded DNA after DNA damage, whereas MMEJ remains unaffected. Our data support a model in which phosphorylation of serine 327 of CtIP as cells enter S phase and the recruitment of BRCA1 functions as a molecular switch to shift the balance of DSB repair from error-prone DNA end-joining to error-free homologous recombination.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857324/" 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/PMC2857324/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yun, Maximina H -- Hiom, Kevin -- MC_U105184300/Medical Research Council/United Kingdom -- U.1051.03.005(78826)/Medical Research Council/United Kingdom -- England -- Nature. 2009 May 21;459(7245):460-3. doi: 10.1038/nature07955. Epub 2009 Apr 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19357644" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Avian Proteins/*metabolism ; B-Lymphocytes/cytology/metabolism ; BRCA1 Protein/*metabolism ; Carrier Proteins/genetics/*metabolism ; *Cell Cycle ; Cell Line ; Chickens ; Cisplatin/pharmacology ; *DNA Breaks, Double-Stranded/radiation effects ; DNA Repair/genetics/*physiology ; G1 Phase ; G2 Phase ; Humans ; Nuclear Proteins/genetics/*metabolism ; Phosphorylation ; Phosphoserine/metabolism ; Recombination, Genetic/genetics ; S Phase ; X-Rays
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    Journal club. A biologist looks at the effect of a dynamic nuclear environment on gene expression (2009)
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    Publication Date: 2009-07-03
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉De, Subhajyoti -- England -- Nature. 2009 Jul 2;460(7251):15. doi: 10.1038/460015e.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Medical Research Council, Cambridge, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19571840" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Nucleus/*genetics ; Chromatin Assembly and Disassembly/genetics ; *Gene Expression Regulation/genetics ; Gene Expression Regulation, Developmental/genetics ; Genes, Homeobox/genetics
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    A safe operating space for humanity (2009)
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    Publication Date: 2009-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rockstrom, Johan -- Steffen, Will -- Noone, Kevin -- Persson, Asa -- Chapin, F Stuart 3rd -- Lambin, Eric F -- Lenton, Timothy M -- Scheffer, Marten -- Folke, Carl -- Schellnhuber, Hans Joachim -- Nykvist, Bjorn -- de Wit, Cynthia A -- Hughes, Terry -- van der Leeuw, Sander -- Rodhe, Henning -- Sorlin, Sverker -- Snyder, Peter K -- Costanza, Robert -- Svedin, Uno -- Falkenmark, Malin -- Karlberg, Louise -- Corell, Robert W -- Fabry, Victoria J -- Hansen, James -- Walker, Brian -- Liverman, Diana -- Richardson, Katherine -- Crutzen, Paul -- Foley, Jonathan A -- England -- Nature. 2009 Sep 24;461(7263):472-5. doi: 10.1038/461472a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Stockholm Resilience Centre, Stockholm University, Kraftriket 2B, 10691 Stockholm, Sweden.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779433" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Biodiversity ; Civilization ; Conservation of Natural Resources/*methods/trends ; *Earth (Planet) ; Ecology/*methods/*trends ; *Ecosystem ; Extinction, Biological ; Fossils ; Green Chemistry Technology/*methods/trends ; Greenhouse Effect ; History, 20th Century ; History, 21st Century ; History, Ancient ; *Human Activities/history ; Humans ; Nitrogen/metabolism ; Phosphorus/metabolism
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    Bacteria hijack integrin-linked kinase to stabilize focal adhesions and block cell detachment (2009)
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    Publication Date: 2009-06-03
    Description: The rapid turnover and exfoliation of mucosal epithelial cells provides an innate defence system against bacterial infection. Nevertheless, many pathogenic bacteria, including Shigella, are able to surmount exfoliation and colonize the epithelium efficiently. Here we show that the Shigella flexneri effector OspE (consisting of OspE1 and OspE2 proteins), which is highly conserved among enteropathogenic Escherichia coli, enterohaemorrhagic E. coli, Citrobacter rodentium and Salmonella strains, reinforces host cell adherence to the basement membrane by interacting with integrin-linked kinase (ILK). The number of focal adhesions was augmented along with membrane fraction ILK by ILK-OspE binding. The interaction between ILK and OspE increased cell surface levels of 1 integrin and suppressed phosphorylation of focal adhesion kinase and paxillin, which are required for rapid turnover of focal adhesion in cell motility. Nocodazole-washout-induced focal adhesion disassembly was blocked by expression of OspE. Polarized epithelial cells infected with a Shigella mutant lacking the ospE gene underwent more rapid cell detachment than cells infected with wild-type Shigella. Infection of guinea pig colons with Shigella corroborated the pivotal role of the OspE-ILK interaction in suppressing epithelial detachment, increasing bacterial cell-to-cell spreading, and promoting bacterial colonization. These results indicate that Shigella sustain their infectious foothold by using special tactics to prevent detachment of infected cells.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Minsoo -- Ogawa, Michinaga -- Fujita, Yukihiro -- Yoshikawa, Yuko -- Nagai, Takeshi -- Koyama, Tomohiro -- Nagai, Shinya -- Lange, Anika -- Fassler, Reinhard -- Sasakawa, Chihiro -- England -- Nature. 2009 May 28;459(7246):578-82. doi: 10.1038/nature07952.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Infectious Disease Control, International Research Center for Infectious Diseases, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19489119" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD29/metabolism ; Bacterial Outer Membrane Proteins/genetics/metabolism ; Cell Adhesion/drug effects/*physiology ; Cell Polarity ; Colon/microbiology ; Epithelial Cells/cytology/microbiology ; Focal Adhesions/drug effects/*physiology ; Guinea Pigs ; HeLa Cells ; Humans ; Mice ; Nocodazole/pharmacology ; Phosphorylation ; Protein Binding ; Protein-Serine-Threonine Kinases/*metabolism ; Shigella flexneri/pathogenicity/*physiology ; Virulence Factors/deficiency/genetics/metabolism
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    A newly discovered protein export machine in malaria parasites (2009)
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    Publication Date: 2009-06-19
    Description: Several hundred malaria parasite proteins are exported beyond an encasing vacuole and into the cytosol of the host erythrocyte, a process that is central to the virulence and viability of the causative Plasmodium species. The trafficking machinery responsible for this export is unknown. Here we identify in Plasmodium falciparum a translocon of exported proteins (PTEX), which is located in the vacuole membrane. The PTEX complex is ATP-powered, and comprises heat shock protein 101 (HSP101; a ClpA/B-like ATPase from the AAA+ superfamily, of a type commonly associated with protein translocons), a novel protein termed PTEX150 and a known parasite protein, exported protein 2 (EXP2). EXP2 is the potential channel, as it is the membrane-associated component of the core PTEX complex. Two other proteins, a new protein PTEX88 and thioredoxin 2 (TRX2), were also identified as PTEX components. As a common portal for numerous crucial processes, this translocon offers a new avenue for therapeutic intervention.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725363/" 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/PMC2725363/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Koning-Ward, Tania F -- Gilson, Paul R -- Boddey, Justin A -- Rug, Melanie -- Smith, Brian J -- Papenfuss, Anthony T -- Sanders, Paul R -- Lundie, Rachel J -- Maier, Alexander G -- Cowman, Alan F -- Crabb, Brendan S -- R01 AI044008-11/AI/NIAID NIH HHS/ -- R01 AI44008/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jun 18;459(7249):945-9. doi: 10.1038/nature08104.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉The Walter & Eliza Hall Institute of Medical Research, Melbourne 3052, Australia.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19536257" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Animals, Genetically Modified ; Malaria, Falciparum/*parasitology ; Models, Biological ; Multiprotein Complexes/*chemistry/*metabolism ; Plasmodium falciparum/*metabolism ; Protein Binding ; Protein Transport ; Protozoan Proteins/*metabolism
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    The role of DNA shape in protein-DNA recognition (2009)
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    Publication Date: 2009-10-30
    Description: The recognition of specific DNA sequences by proteins is thought to depend on two types of mechanism: one that involves the formation of hydrogen bonds with specific bases, primarily in the major groove, and one involving sequence-dependent deformations of the DNA helix. By comprehensively analysing the three-dimensional structures of protein-DNA complexes, here we show that the binding of arginine residues to narrow minor grooves is a widely used mode for protein-DNA recognition. This readout mechanism exploits the phenomenon that narrow minor grooves strongly enhance the negative electrostatic potential of the DNA. The nucleosome core particle offers a prominent example of this effect. Minor-groove narrowing is often associated with the presence of A-tracts, AT-rich sequences that exclude the flexible TpA step. These findings indicate that the ability to detect local variations in DNA shape and electrostatic potential is a general mechanism that enables proteins to use information in the minor groove, which otherwise offers few opportunities for the formation of base-specific hydrogen bonds, to achieve DNA-binding specificity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2793086/" 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/PMC2793086/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rohs, Remo -- West, Sean M -- Sosinsky, Alona -- Liu, Peng -- Mann, Richard S -- Honig, Barry -- GM54510/GM/NIGMS NIH HHS/ -- R01 GM030518/GM/NIGMS NIH HHS/ -- U54 CA121852/CA/NCI NIH HHS/ -- U54 CA121852-05/CA/NCI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Oct 29;461(7268):1248-53. doi: 10.1038/nature08473.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Center for Computational Biology and Bioinformatics, Department of Biochemistry and Molecular Biophysics, Columbia University, 1130 Saint Nicholas Avenue, New York, New York 10032, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19865164" target="_blank"〉PubMed〈/a〉
    Keywords: AT Rich Sequence/genetics ; Animals ; Arginine/metabolism ; Base Sequence ; DNA/*chemistry/genetics/*metabolism ; DNA-Binding Proteins/chemistry/*metabolism ; Databases, Factual ; Hydrogen Bonding ; Lysine ; *Nucleic Acid Conformation ; Nucleosomes/chemistry/metabolism ; Protein Binding ; Saccharomyces cerevisiae ; Static Electricity
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    Global patterns of speciation and diversity (2009)
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    Publication Date: 2009-07-17
    Description: In recent years, strikingly consistent patterns of biodiversity have been identified over space, time, organism type and geographical region. A neutral theory (assuming no environmental selection or organismal interactions) has been shown to predict many patterns of ecological biodiversity. This theory is based on a mechanism by which new species arise similarly to point mutations in a population without sexual reproduction. Here we report the simulation of populations with sexual reproduction, mutation and dispersal. We found simulated time dependence of speciation rates, species-area relationships and species abundance distributions consistent with the behaviours found in nature. From our results, we predict steady speciation rates, more species in one-dimensional environments than two-dimensional environments, three scaling regimes of species-area relationships and lognormal distributions of species abundance with an excess of rare species and a tail that may be approximated by Fisher's logarithmic series. These are consistent with dependences reported for, among others, global birds and flowering plants, marine invertebrate fossils, ray-finned fishes, British birds and moths, North American songbirds, mammal fossils from Kansas and Panamanian shrubs. Quantitative comparisons of specific cases are remarkably successful. Our biodiversity results provide additional evidence that species diversity arises without specific physical barriers. This is similar to heavy traffic flows, where traffic jams can form even without accidents or barriers.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Aguiar, M A M -- Baranger, M -- Baptestini, E M -- Kaufman, L -- Bar-Yam, Y -- England -- Nature. 2009 Jul 16;460(7253):384-7. doi: 10.1038/nature08168.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉New England Complex Systems Institute, Cambridge, Massachusetts 02138, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19606148" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biodiversity ; Disorders of Sex Development ; Extinction, Biological ; *Genetic Speciation ; Genotype ; Haploidy ; Models, Biological ; Mutation/genetics ; Population Dynamics ; Reproduction/genetics/*physiology ; Sexual Behavior, Animal ; Time Factors
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    Is REST a regulator of pluripotency? (2009)
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    Publication Date: 2009-02-27
    Description: Establishment and maintenance of the pluripotent state of ESCs is a key issue in stem cell biology and regenerative medicine, and consequently identification of transcription factors that regulate ESC pluripotency is an important goal. Singh et al. claim that the transcriptional repressor REST is such a regulator and that a 50% reduction of REST in ESCs leads to activation of a specific microRNA, miR-21, and that this subsequently results in loss of pluripotency markers and a reciprocal gain in some lineage-specific differentiation markers. In contrast, we show that, in haplodeficient Rest(+/-) ESCs, we detected no change in pluripotency markers, no precocious expression of differentiated neuronal markers and no interaction of REST with miR-21. It is vital that identification of factors that regulate pluripotency is based on robust, consistent data, and the contrast in data reported here undermines the claim by Singh et al. that REST is such a regulator.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buckley, Noel J -- Johnson, Rory -- Sun, Yuh-Man -- Stanton, Lawrence W -- England -- Nature. 2009 Feb 26;457(7233):E5-6; discussion E7. doi: 10.1038/nature07784.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉King's College London, Institute of Psychiatry, Centre for the Cellular Basis of Behaviour, James Black Centre, 125 Coldharbour Lane, London SE5 9NU, UK. noel.buckley@iop.kcl.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19242418" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Embryonic Stem Cells/*cytology/*metabolism ; Gene Knockdown Techniques ; Mice ; MicroRNAs/genetics/metabolism ; Pluripotent Stem Cells/*cytology/*metabolism ; Polymerase Chain Reaction ; Repressor Proteins/genetics/*metabolism ; Reproducibility of Results
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    Darwin's last laugh (2009)
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    Publication Date: 2009-07-10
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉de Waal, Frans B M -- England -- Nature. 2009 Jul 9;460(7252):175. doi: 10.1038/460175a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Living Links Center, Emory University, 954 N. Gatewood Road, Atlanta, Georgia 30322, USA. dewaal@emory.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19587747" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Behavior, Animal/physiology ; *Biological Evolution ; Cognition/*physiology ; Humans ; Laughter ; Phylogeny ; Selection, Genetic
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    Viruses manipulate the marine environment (2009)
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    Publication Date: 2009-05-16
    Description: Marine viruses affect Bacteria, Archaea and eukaryotic organisms and are major components of the marine food web. Most studies have focused on their role as predators and parasites, but many of the interactions between marine viruses and their hosts are much more complicated. A series of recent studies has shown that viruses have the ability to manipulate the life histories and evolution of their hosts in remarkable ways, challenging our understanding of this almost invisible world.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Rohwer, Forest -- Thurber, Rebecca Vega -- England -- Nature. 2009 May 14;459(7244):207-12. doi: 10.1038/nature08060.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biology, San Diego State University, San Diego, California 92182, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19444207" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Ecosystem ; *Marine Biology ; Transduction, Genetic ; *Virus Physiological Phenomena ; *Viruses/genetics
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    DNA demethylation in hormone-induced transcriptional derepression (2009)
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    Publication Date: 2009-10-16
    Description: Epigenetic modifications at the histone level affect gene regulation in response to extracellular signals. However, regulated epigenetic modifications at the DNA level, especially active DNA demethylation, in gene activation are not well understood. Here we report that DNA methylation/demethylation is hormonally switched to control transcription of the cytochrome p450 27B1 (CYP27B1) gene. Reflecting vitamin-D-mediated transrepression of the CYP27B1 gene by the negative vitamin D response element (nVDRE), methylation of CpG sites ((5m)CpG) is induced by vitamin D in this gene promoter. Conversely, treatment with parathyroid hormone, a hormone known to activate the CYP27B1 gene, induces active demethylation of the (5m)CpG sites in this promoter. Biochemical purification of a complex associated with the nVDRE-binding protein (VDIR, also known as TCF3) identified two DNA methyltransferases, DNMT1 and DNMT3B, for methylation of CpG sites, as well as a DNA glycosylase, MBD4 (ref. 10). Protein-kinase-C-phosphorylated MBD4 by parathyroid hormone stimulation promotes incision of methylated DNA through glycosylase activity, and a base-excision repair process seems to complete DNA demethylation in the MBD4-bound promoter. Such parathyroid-hormone-induced DNA demethylation and subsequent transcriptional derepression are impaired in Mbd4(-/-) mice. Thus, the present findings suggest that methylation switching at the DNA level contributes to the hormonal control of transcription.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Mi-Sun -- Kondo, Takeshi -- Takada, Ichiro -- Youn, Min-Young -- Yamamoto, Yoko -- Takahashi, Sayuri -- Matsumoto, Takahiro -- Fujiyama, Sally -- Shirode, Yuko -- Yamaoka, Ikuko -- Kitagawa, Hirochika -- Takeyama, Ken-ichi -- Shibuya, Hiroshi -- Ohtake, Fumiaki -- Kato, Shigeaki -- England -- Nature. 2009 Oct 15;461(7266):1007-12. doi: 10.1038/nature08456.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉ERATO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchisi, Saitama 332-0012, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829383" target="_blank"〉PubMed〈/a〉
    Keywords: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics ; Animals ; Cell Line ; CpG Islands/genetics ; DNA (Cytosine-5-)-Methyltransferase/metabolism ; DNA Glycosylases/metabolism ; DNA Methylation/*drug effects ; Down-Regulation/drug effects ; Endodeoxyribonucleases/deficiency/genetics ; Mice ; Parathyroid Hormone/*pharmacology ; Phosphorylation ; Protein Kinase C/metabolism ; Response Elements/genetics ; Transcription, Genetic/*drug effects ; Vitamin D/pharmacology
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    A surface transporter family conveys the trypanosome differentiation signal (2009)
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    Publication Date: 2009-05-16
    Description: Microbial pathogens use environmental cues to trigger the developmental events needed to infect mammalian hosts or transmit to disease vectors. The parasites causing African sleeping sickness respond to citrate or cis-aconitate (CCA) to initiate life-cycle development when transmitted to their tsetse fly vector. This requires hypersensitization of the parasites to CCA by exposure to low temperature, conditions encountered after tsetse fly feeding at dusk or dawn. Here we identify a carboxylate-transporter family, PAD (proteins associated with differentiation), required for perception of this differentiation signal. Consistent with predictions for the response of trypanosomes to CCA, PAD proteins are expressed on the surface of the transmission-competent 'stumpy-form' parasites in the bloodstream, and at least one member is thermoregulated, showing elevated expression and surface access at low temperature. Moreover, RNA-interference-mediated ablation of PAD expression diminishes CCA-induced differentiation and eliminates CCA hypersensitivity under cold-shock conditions. As well as being molecular transducers of the differentiation signal in these parasites, PAD proteins provide the first example of a surface marker able to discriminate the transmission stage of trypanosomes in their mammalian host.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2685892/" 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/PMC2685892/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dean, Samuel -- Marchetti, Rosa -- Kirk, Kiaran -- Matthews, Keith R -- 073358/Wellcome Trust/United Kingdom -- 082555/Wellcome Trust/United Kingdom -- BB/E012442/1/Biotechnology and Biological Sciences Research Council/United Kingdom -- Biotechnology and Biological Sciences Research Council/United Kingdom -- Wellcome Trust/United Kingdom -- England -- Nature. 2009 May 14;459(7244):213-7. doi: 10.1038/nature07997.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Immunity, Infection and Evolution, Institute for Immunology and Infection Research, School of Biological Sciences, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19444208" target="_blank"〉PubMed〈/a〉
    Keywords: Aconitic Acid/analogs & derivatives/metabolism ; Animals ; Cell Differentiation ; Citric Acid/metabolism ; Gene Expression Regulation, Developmental ; Insect Vectors/parasitology ; Oocytes ; Protozoan Proteins/genetics/*metabolism ; RNA Interference ; RNA, Messenger/genetics/metabolism ; RNA, Protozoan/genetics/metabolism ; Temperature ; Trypanosoma brucei brucei/cytology/genetics/*growth & development/*metabolism ; Trypanosomiasis, African/parasitology ; Tsetse Flies/parasitology ; Xenopus laevis
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    The Beagle in a bottle (2009)
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    Publication Date: 2009-02-13
    Description: Why infer evolution when you can watch it happen in real time? This is the basic premise of using populations of fast-replicating microorganisms in test tubes to study evolution. The approach, known as experimental evolution, has provided a way of testing many of the key hypotheses that arose from the modern evolutionary synthesis. However, details of the unnatural histories of microorganisms in test tubes can be extrapolated only so far. Potential future directions for the approach include studying microbial evolution for its own sake under the most natural conditions possible in the test tube, and testing some qualitative theories of genome evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buckling, Angus -- Craig Maclean, R -- Brockhurst, Michael A -- Colegrave, Nick -- England -- Nature. 2009 Feb 12;457(7231):824-9. doi: 10.1038/nature07892.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Zoology, University of Oxford, Oxford OX1 3PS, UK. angus.buckling@zoo.ox.ac.uk〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19212400" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Bacteria/genetics/growth & development/virology ; Bacterial Physiological Phenomena ; *Biodiversity ; *Biological Evolution ; *Selection, Genetic
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    Developmental biology: A bad boy comes good (2009)
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    Publication Date: 2009-09-26
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Theopold, Ulrich -- England -- Nature. 2009 Sep 24;461(7263):486-7. doi: 10.1038/461486a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19779443" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Blood Cells/cytology/metabolism ; *Cell Differentiation ; Drosophila melanogaster/*cytology/growth & development/*metabolism ; *Hematopoiesis ; Hematopoietic Stem Cells/*cytology/*metabolism ; Humans ; Immune System/cytology ; Larva/cytology/metabolism ; Reactive Oxygen Species/*metabolism ; Signal Transduction
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    Physical chemistry: How to improve your image (2009)
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    Publication Date: 2009-04-11
    Description: 〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730462/" 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/PMC2730462/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Therien, Michael J -- R01 CA115229/CA/NCI NIH HHS/ -- R01 CA115229-04/CA/NCI NIH HHS/ -- England -- Nature. 2009 Apr 9;458(7239):716-7. doi: 10.1038/458716b.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19360076" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Coloring Agents/chemistry/*metabolism ; Microscopy, Fluorescence, Multiphoton/*methods
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    The origin and evolution of arthropods (2009)
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    Publication Date: 2009-02-13
    Description: The past two decades have witnessed profound changes in our understanding of the evolution of arthropods. Many of these insights derive from the adoption of molecular methods by systematists and developmental biologists, prompting a radical reordering of the relationships among extant arthropod classes and their closest non-arthropod relatives, and shedding light on the developmental basis for the origins of key characteristics. A complementary source of data is the discovery of fossils from several spectacular Cambrian faunas. These fossils form well-characterized groupings, making the broad pattern of Cambrian arthropod systematics increasingly consensual.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Budd, Graham E -- Telford, Maximilian J -- England -- Nature. 2009 Feb 12;457(7231):812-7. doi: 10.1038/nature07890.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Earth Sciences, Uppsala University, Villavagen 16, Uppsala SE-752 36, Sweden. graham.budd@pal.uu.se〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19212398" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arthropods/anatomy & histology/*classification/*physiology ; *Biological Evolution ; Fossils ; Phylogeny
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    Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis (2009)
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    Publication Date: 2009-01-06
    Description: Metastatic progression depends on genetic alterations intrinsic to cancer cells as well as the inflammatory microenvironment of advanced tumours. To understand how cancer cells affect the inflammatory microenvironment, we conducted a biochemical screen for macrophage-activating factors secreted by metastatic carcinomas. Here we show that, among the cell lines screened, Lewis lung carcinoma (LLC) were the most potent macrophage activators leading to production of interleukin-6 (IL-6) and tumour-necrosis factor-alpha (TNF-alpha) through activation of the Toll-like receptor (TLR) family members TLR2 and TLR6. Both TNF-alpha and TLR2 were found to be required for LLC metastasis. Biochemical purification of LLC-conditioned medium (LCM) led to identification of the extracellular matrix proteoglycan versican, which is upregulated in many human tumours including lung cancer, as a macrophage activator that acts through TLR2 and its co-receptors TLR6 and CD14. By activating TLR2:TLR6 complexes and inducing TNF-alpha secretion by myeloid cells, versican strongly enhances LLC metastatic growth. These results explain how advanced cancer cells usurp components of the host innate immune system, including bone-marrow-derived myeloid progenitors, to generate an inflammatory microenvironment hospitable for metastatic growth.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746432/" 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/PMC2746432/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kim, Sunhwa -- Takahashi, Hiroyuki -- Lin, Wan-Wan -- Descargues, Pascal -- Grivennikov, Sergei -- Kim, Youngjun -- Luo, Jun-Li -- Karin, Michael -- R01 CA118165/CA/NCI NIH HHS/ -- R01 CA118165-02/CA/NCI NIH HHS/ -- R01 CA132586/CA/NCI NIH HHS/ -- R01 ES006376/ES/NIEHS NIH HHS/ -- R01 ES006376-14/ES/NIEHS NIH HHS/ -- T32 CA121938/CA/NCI NIH HHS/ -- England -- Nature. 2009 Jan 1;457(7225):102-6. doi: 10.1038/nature07623.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19122641" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antigens, CD14/metabolism ; Carcinoma, Lewis Lung/*metabolism/pathology/secretion ; Culture Media, Conditioned/metabolism/pharmacology ; Culture Media, Serum-Free/metabolism ; Interleukin-6/metabolism/secretion ; Liver Neoplasms/secondary ; Lung Neoplasms/metabolism/pathology/secondary ; *Macrophage Activation ; Macrophages/*metabolism/secretion ; Mice ; Mice, Inbred C57BL ; *Neoplasm Metastasis/pathology ; Neoplasm Transplantation ; Toll-Like Receptor 2/agonists/*metabolism ; Toll-Like Receptor 6/metabolism ; Tumor Necrosis Factor-alpha/metabolism/secretion ; Versicans/metabolism/pharmacology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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    Climate change: Beyond the CO(2) connection (2009)
    Nature Publishing Group (NPG)
    Details
    Publication Date: 2009-09-17
    Description: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Zahn, Rainer -- England -- Nature. 2009 Jul 16;460(7253):335-6. doi: 10.1038/460335a.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Institucio Catalana de Recerca i Estudis Avancats (ICREA), Institut de Ciencia i Tecnologia Ambientals and Departmento de Geologia, Universitat Autonoma de Barcelona, Bellaterra E-08193, Spain. rainer.zahn@uab.cat.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19606136" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Antarctic Regions ; Atlantic Ocean ; Atmosphere/chemistry ; Carbon Dioxide/metabolism ; *Climate ; Geologic Sediments/microbiology ; History, Ancient ; Ice Cover ; Indian Ocean ; Seawater/chemistry ; *Temperature ; *Water Movements
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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