51 research outputs found
The choline transporter Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial function
Genetic factors contribute to the risk of thrombotic diseases. Recent genome wide association studies have identified genetic loci including SLC44A2 which may regulate thrombosis. Here we show that Slc44a2 controls platelet activation and thrombosis by regulating mitochondrial energetics. We find that Slc44a2 null mice (Slc44a2(KO)) have increased bleeding times and delayed thrombosis compared to wild-type (Slc44a2(WT)) controls. Platelets from Slc44a2(KO) mice have impaired activation in response to thrombin. We discover that Slc44a2 mediates choline transport into mitochondria, where choline metabolism leads to an increase in mitochondrial oxygen consumption and ATP production. Platelets lacking Slc44a2 contain less ATP at rest, release less ATP when activated, and have an activation defect that can be rescued by exogenous ADP. Taken together, our data suggest that mitochondria require choline for maximum function, demonstrate the importance of mitochondrial metabolism to platelet activation, and reveal a mechanism by which Slc44a2 influences thrombosis
Advances in Global and Local Helioseismology: an Introductory Review
Helioseismology studies the structure and dynamics of the Sun's interior by
observing oscillations on the surface. These studies provide information about
the physical processes that control the evolution and magnetic activity of the
Sun. In recent years, helioseismology has made substantial progress towards the
understanding of the physics of solar oscillations and the physical processes
inside the Sun, thanks to observational, theoretical and modeling efforts. In
addition to the global seismology of the Sun based on measurements of global
oscillation modes, a new field of local helioseismology, which studies
oscillation travel times and local frequency shifts, has been developed. It is
capable of providing 3D images of the subsurface structures and flows. The
basic principles, recent advances and perspectives of global and local
helioseismology are reviewed in this article.Comment: 86 pages, 46 figures; "Pulsation of the Sun and Stars", Lecture Notes
in Physics, Vol. 832, Rozelot, Jean-Pierre; Neiner, Coralie (Eds.), 201
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
Human Genome Variation 2006: emerging views on structural variation and large-scale SNP analysis
The Eighth Annual Human Genome Variation Meeting Was Held In September 2006 In The Hong Kong Special Administrative Region, China. The Meeting Highlighted Recent Advances In Characterization Of Genetic Variation, Including Genome-Wide Association Studies And Structural Variation. © 2007 Nature Publishing Group.link_to_subscribed_fulltex
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