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A tension-mediated glycocalyx-integrin feedback loop promotes mesenchymal-like glioblastoma
Barnes, J. Matthew,Kaushik, Shelly,Bainer, Russell O.,Sa, Jason K.,Woods, Elliot C.,Kai, FuiBoon,Przybyla, Laralynne,Lee, Mijeong,Lee, Hye Won,Tung, Jason C.,Maller, Ori,Barrett, Alexander S.,Lu, Kan Nature Publishing Group 2018 Nature cell biology Vol.20 No.10
Evaluating the contribution of rare variants to type 2 diabetes and related traits using pedigrees
Jun, Goo,Manning, Alisa,Almeida, Marcio,Zawistowski, Matthew,Wood, Andrew R.,Teslovich, Tanya M.,Fuchsberger, Christian,Feng, Shuang,Cingolani, Pablo,Gaulton, Kyle J.,Dyer, Thomas,Blackwell, Thomas W. National Academy of Sciences 2018 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.115 No.2
<P>A major challenge in evaluating the contribution of rare variants to complex disease is identifying enough copies of the rare alleles to permit informative statistical analysis. To investigate the contribution of rare variants to the risk of type 2 diabetes (T2D) and related traits, we performed deep whole-genome analysis of 1,034 members of 20 large Mexican-American families with high prevalence of T2D. If rare variants of large effect accounted for much of the diabetes risk in these families, our experiment was powered to detect association. Using gene expression data on 21,677 transcripts for 643 pedigree members, we identified evidence for large-effect rare-variant c/s-expression quantitative trait loci that could not be detected in population studies, validating our approach. Flowever, we did not identify any rare variants of large effect associated with T2D, or the related traits of fasting glucose and insulin, suggesting that large-effect rare variants account for only a modest fraction of the genetic risk of these traits in this sample of families. Reliable identification of large-effect rare variants will require larger samples of extended pedigrees or different study designs that further enrich for such variants.</P>
Extracellular vesicle-based therapeutics: natural versus engineered targeting and trafficking
Daniel E. Murphy,Olivier G. de Jong,Maarten Brouwer,Matthew J. Wood,Grégory Lavieu,Raymond M. Schiffelers,Pieter Vader 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
Extracellular vesicles (EVs) are increasingly being recognized as mediators of intercellular signaling via the delivery of effector molecules. Interestingly, certain types of EVs are also capable of inducing therapeutic responses. For these reasons, the therapeutic potential of EVs is a topic of intense research, both in the context of drug delivery and regenerative medicine. However, to fully utilize EVs for therapeutic purposes, an improved understanding of the mechanisms by which they function would be highly advantageous. Here, the current state of knowledge regarding the cellular uptake and trafficking of EVs is reviewed, along with a consideration of how these pathways potentially influence the functions of therapeutic EVs. Furthermore, the natural cell-targeting abilities, biodistribution profiles, and pharmacokinetics of exogenously administered EVs, along with the components responsible for these features are discussed. An overview of the potential clinical applications and preclinical examples of their successful use is also provided. Finally, examples of EV modifications that have successfully been employed to improve their therapeutic characteristics receive a particular focus. We suggest that, in addition to investigation of EV cell targeting and routes of uptake, future research into the routes of intracellular trafficking in recipient cells is required to optimally utilize EVs for therapeutic purposes.