New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Opportunism and persistence in milk production in the Brazilian Amazonia

In Amazonia milk production is considered as an opportunity to improve the viability of small farms because of the double function of milk and calf pro­duction, which is promoted by the high forage potential resulting from the hot and humid climate. However, dairy production does not depend on fodder only, the challenge is more complex. This paper describes how the local milk supply chain and the context restrict the productivity and innovation process in the dairy sector. It also outlines short-term development possibilities. We implemented a new method that combined three complementary approaches in order to understand better the complexity of dairy production in Amazonia. These approaches were based on i) a farm typology carried out during two dif­ferent periods to build farm trajectories, ii) a retrospective analysis to describe changes and persistence in the involved factors, and iii) a supply chain analysis based on secondary data and information collected from key informants. The obtained results completed the significant knowledge gathered by researchers over the past ten years. The typology revealed the frequent and sudden changes in farm strategies, with two main trends: opportunism and persistence in relation to management practices, especially animal reproduction, feeding, and dairy product marketing. The latter highly depends on the capacity of local dairy fac­tories to build a trusting relationship with the farmers. However, this partnership is difficult to set up because of transportation constraints, insufficient access to the market, and national production norms. This context explains the frequent creation / closing out of dairy factories. This is why many farmers center their production on calves and consider milk as a by-product. Others, however, keep up producing milk and calves for cultural reasons, looking out for alternatives to milk marketing. Three scenarios have been developed: i) intensification, ii) increase in the local demand, and iii) demanding environmental policies

Le bassin laitier en Amazonie brésilienne, situation actuelle et perspectives d’évolution.

National audienceBrazil has reached France and Germany in the world hierarchy of dairy producers, and should very soon overtake them. As for beef production, in less than 10 years Brazil has become the second world producer and the first exporter. The expansion of dairy production depends on the construction of the Amazonian dairy basin. Milk comes from small family-run farms characterized by extensive herd and grassland management. Moreover, the processes of intensification, considered as a stake to improve the economic and environmental sustainability of livestock farms, appear still very limited to individual opportunities. For ten years, dairy production has been modified by the construction of dairy basins, due to the installation of regional and national dairy industries with larger capacities of tranformation. Questions have arose on the evolution of dairy farms and the processes of intensification : which is the current situation of these livestock farming systems, and what are their evolutions? For their reflections, the authors used the results of ten years of research, conduced in the state of Pará, about the characteristics of dairy farms and milk basins. The authors explain the development of dairy production in the Amazon region during the last decade and the installation of the milk basins. From three contrasted agricultural borders, they also present the characteristics of the dairy farms linked with one type of milk basin as well as the perpectives for their evolutions. The authors conclude by the progressive intensification that will occur in the future on dairy farms, with the development of national and international dairy industries. Other evolutions are to be considered : the increasing demand to improve work conditions of the farmers and the development of agroforestry systems.Le Brésil a rejoint la France et l’Allemagne dans la hiérarchie mondiale des producteurs laitiers et devrait très prochainement les dépasser. Comme pour la viande bovine où le Brésil est devenu en moins de 10 ans le second producteur mondial et le premier exportateur, l’expansion de la production laitière repose en partie sur la construction du bassin laitier amazonien. La production de lait provient d’exploitations familiales extensives quant à la conduite des troupeaux et des surfaces. En outre, les processus d’intensification, pourtant un enjeu pour améliorer la viabilité économique et environnementale de ces fermes, apparaissent encore très limités à des opportunités individuelles. Depuis une dizaine d’années, la filière laitière est soumise à de profondes modifications avec la structuration de bassins laitiers qui se traduisent par l’installation d’industries régionales, puis nationales, qui mettent en place des laiteries de capacité toujours plus grande. Cependant l’Amazonie est aussi marquée par la disparité d’organisation des filières, avec la vente informelle et les petites laiteries familiales. Avec le fort développement de la production laitière, des questions se posent sur l’évolution des systèmes laitiers et des processus d’intensification : quelle est la situation actuelle des exploitations commercialisant du lait et vers où vont-elles ? Les auteurs basent leurs réflexions sur les résultats de recherches menées depuis plus de 10 ans sur les systèmes d’élevage laitier et les filières laitières dans l’état du Pará. Les résultats présentent le fort développement de la production laitière au cours de la dernière décennie et les processus de mise en place des bassins laitiers. A partir de trois frontières agricoles contrastées, ils montrent également les caractéristiques des élevages et les organisations des filières laitières ainsi que les perspectives d’évolution. Les auteurs concluent sur l’intensification progressive dans les années à venir des élevages, notamment poussée par le développement des industries laitières de portée nationale et internationale. D’autres évolutions sont à prévoir : une demande de plus en plus forte exprimée sur l’amélioration des conditions de travail et de vie, une forte progression de l’agroforesterie

Sterol and ecdysteroids profiles of Serratula tinctoria (L.) : plant and cell cultures producing steroids

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Native oxide limited cross-plane thermal transport in suspended silicon membranes revealed by scanning thermal microscopy

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Scanning thermal microscopy and nanoscale heat transfer

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