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Aging and diseases generally result from tissue inability to maintain homeostasis through adaptation. The adult heart is particularly vulnerable to disequilibrium in homeostasis because its regenerative abilities are limited. Here, we report that MLIP (muscle enriched A-type lamin-interacting protein), a unique protein of unknown function, is required for proper cardiac adaptation. Mlip−/− mice exhibited normal cardiac function despite myocardial metabolic abnormalities and cardiac-specific overactivation of Akt/mTOR pathways. Cardiac-specific MLIP overexpression led to an inhibition of Akt/mTOR, providing evidence of a direct impact of MLIP on these key signaling pathways. Mlip−/− hearts showed an impaired capacity to adapt to stress (isoproterenol-induced hypertrophy), likely because of deregulated Akt/mTOR activity. Genome-wide association studies showed a genetic association between Mlip and early response to cardiac stress, supporting the role of MLIP in cardiac adaptation. Together, these results revealed that MLIP is required for normal myocardial adaptation to stress through integrated regulation of the Akt/mTOR pathways.  相似文献   
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The present paper aims at reviewing general knowledge of large European perialpine lakes as provided by sediment studies, and at outlining the contribution, from several lines of evidence, of modern paleolimnology in both interpreting past lake ecological evolution and forecasting lake responses to future human impacts. A literature survey mainly based on papers published in international journals indexed on ISI-Wos and Scopus from 1975 to April 2017 has been conducted on the 20 perialpine lakes with zmax?≥?100 m and lake area?≥?10 km2, and on 4 shallower perialpine lakes representing hotspots of extensive neo- and paleo-limnological research. By pinpointing temporal and spatial differences in paleolimnological studies conducted in the Alpine countries, the review identifies knowledge gaps in the perialpine area, and shows how sediment-based reconstructions represent a powerful tool, in mutual support with limnological surveys, to help predicting future scenarios through the “past-forward” principle, which consists in reconstructing past lake responses to conditions comparable to those to come. The most recent methodological developments of sediment studies show the potential to cope with the increasing ecosystem variability induced by climate change, and to produce innovative and crucial information for tuning future management and sustainable use of Alpine waters.  相似文献   
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Changes in the composition and size structure of cladoceran remains collected in sediment traps (ST) were compared at a monthly time-resolution to the changes in the cladoceran source communities in order to assess the effects of production, sedimentation and taphonomic processes on the composition, completeness of time series and size structure of cladoceran remains in a large deep monomictic subalpine lake. Cladoceran remains collected in the ST globally reflected seasonal changes in the composition of the source community for the dominant taxa (Daphnia sp., Eubosmina spp. and. D. brachyurum) but failed in capturing accurately the seasonal changes in the abundance of the least abundant species, B. longirostris. Using allometric relationships, the average body size of the organisms that produced the remains retrieved in the ST could be reconstructed. Although the cladoceran average body size estimated from trap remains was always smaller than that of the source communities, temporal changes in the average body size of the dominant taxa in the source community were captured by trap samples. Our results showed that, in this deep subalpine lake, cladoceran remains production, sedimentation and taphonomic processes within the water column did not alter the compositional fidelity of remains at seasonal and annual time scales for the dominant taxa. Results did not show any significant over-representation of Bosmina and subsequent under-representation of Daphnia in contrast to previous studies on small and flat lakes. Our results suggest that the frequently observed under-estimation of Daphnia in fossil assemblages could be a consequence of the mesh size used when processing sediment core samples rather than of varying magnitude of degradation processes between small or flat lakes and deep lakes. Finally, our results support the use of the size of cladoceran remains within paleo-ecological studies to assess past changes in the size structure of the source communities.  相似文献   
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The French National Institute of Ecology and Environment (INEE) aims at fostering pluridisciplinarity in Environmental Science and, for that purpose, funds ex muros research groups (GDR) on thematic topics. Trophic ecology has been identified as a scientific field in ecology that would greatly benefit from such networking activity, as being profoundly scattered. This has motivated the seeding of a GDR, entitled “GRET”. The contours of the GRET's action, and its ability to fill these gaps within trophic ecology at the French national scale, will depend on the causes of this relative scattering. This study relied on a nationally broadcasted poll aiming at characterizing the field of trophic ecology in France. Amongst all the unique individuals that fulfilled the poll, over 300 belonged at least partly to the field of trophic ecology. The sample included all French public research institutes and career stages. Three main disruptions within the community of scientist in trophic ecology were identified. The first highlighted the lack of interfaces between microbial and trophic ecology. The second evidenced that research questions were strongly linked to single study fields or ecosystem type. Last, research activities are still quite restricted to the ecosystem boundaries. All three rupture points limit the conceptual and applied progression in the field of trophic ecology. Here we show that most of the disruptions within French Trophic Ecology are culturally inherited, rather than motivated by scientific reasons or justified by socio-economic stakes. Comparison with the current literature confirms that these disruptions are not necessarily typical of the French research landscape, but instead echo the general weaknesses of the international research in ecology. Thereby, communication and networking actions within and toward the community of trophic ecologists, as planned within the GRET's objectives, should contribute to fill these gaps, by reintegrating microbes within trophic concepts and setting the seeds for trans- and meta-ecosystemic research opportunities. Once the community of trophic ecologists is aware of the scientific benefit in pushing its boundaries forwards, turning words and good intentions into concrete research projects will depend on the opportunities to obtain research funding.  相似文献   
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Recent experimental and clinical retrospective studies support the view that reduction of brain cholesterol protects against Alzheimer's disease (AD). However, genetic and pharmacological evidence indicates that low brain cholesterol leads to neurodegeneration. This apparent contradiction prompted us to analyze the role of neuronal cholesterol in amyloid peptide generation in experimental systems that closely resemble physiological and pathological situations. We show that, in the hippocampus of control human and transgenic mice, only a small pool of endogenous APP and its beta-secretase, BACE 1, are found in the same membrane environment. Much higher levels of BACE 1-APP colocalization is found in hippocampal membranes from AD patients or in rodent hippocampal neurons with a moderate reduction of membrane cholesterol. Their increased colocalization is associated with elevated production of amyloid peptide. These results suggest that loss of neuronal membrane cholesterol contributes to excessive amyloidogenesis in AD and pave the way for the identification of the cause of cholesterol loss and for the development of specific therapeutic strategies.  相似文献   
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