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排序方式: 共有10000条查询结果,搜索用时 11 毫秒
991.
OG Pybus MA Suchard P Lemey FJ Bernardin A Rambaut FW Crawford RR Gray N Arinaminpathy SL Stramer MP Busch EL Delwart 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(37):15066-15071
We introduce a conceptual bridge between the previously unlinked fields of phylogenetics and mathematical spatial ecology, which enables the spatial parameters of an emerging epidemic to be directly estimated from sampled pathogen genome sequences. By using phylogenetic history to correct for spatial autocorrelation, we illustrate how a fundamental spatial variable, the diffusion coefficient, can be estimated using robust nonparametric statistics, and how heterogeneity in dispersal can be readily quantified. We apply this framework to the spread of the West Nile virus across North America, an important recent instance of spatial invasion by an emerging infectious disease. We demonstrate that the dispersal of West Nile virus is greater and far more variable than previously measured, such that its dissemination was critically determined by rare, long-range movements that are unlikely to be discerned during field observations. Our results indicate that, by ignoring this heterogeneity, previous models of the epidemic have substantially overestimated its basic reproductive number. More generally, our approach demonstrates that easily obtainable genetic data can be used to measure the spatial dynamics of natural populations that are otherwise difficult or costly to quantify. 相似文献
992.
AJ Geall A Verma GR Otten CA Shaw A Hekele K Banerjee Y Cu CW Beard LA Brito T Krucker DT O'Hagan M Singh PW Mason NM Valiante PR Dormitzer SW Barnett R Rappuoli JB Ulmer CW Mandl 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(36):14604-14609
Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted. 相似文献
993.
Laure Ségurel Emma E. Thompson Timothée Flutre Jessica Lovstad Aarti Venkat Susan W. Margulis Jill Moyse Steve Ross Kathryn Gamble Guy Sella Carole Ober Molly Przeworski 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(45):18493-18498
The ABO histo-blood group, the critical determinant of transfusion incompatibility, was the first genetic polymorphism discovered in humans. Remarkably, ABO antigens are also polymorphic in many other primates, with the same two amino acid changes responsible for A and B specificity in all species sequenced to date. Whether this recurrence of A and B antigens is the result of an ancient polymorphism maintained across species or due to numerous, more recent instances of convergent evolution has been debated for decades, with a current consensus in support of convergent evolution. We show instead that genetic variation data in humans and gibbons as well as in Old World monkeys are inconsistent with a model of convergent evolution and support the hypothesis of an ancient, multiallelic polymorphism of which some alleles are shared by descent among species. These results demonstrate that the A and B blood groups result from a trans-species polymorphism among distantly related species and has remained under balancing selection for tens of millions of years—to date, the only such example in hominoids and Old World monkeys outside of the major histocompatibility complex. 相似文献
994.
Christos Pliotas Richard Ward Emma Branigan Akiko Rasmussen Gregor Hagelueken Hexian Huang Susan S. Black Ian R. Booth Olav Schiemann James H. Naismith 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(40):E2675-E2682
The heptameric mechanosensitive channel of small conductance (MscS) provides a critical function in Escherichia coli where it opens in response to increased bilayer tension. Three approaches have defined different closed and open structures of the channel, resulting in mutually incompatible models of gating. We have attached spin labels to cysteine mutants on key secondary structural elements specifically chosen to discriminate between the competing models. The resulting pulsed electron–electron double resonance (PELDOR) spectra matched predicted distance distributions for the open crystal structure of MscS. The fit for the predictions by structural models of MscS derived by other techniques was not convincing. The assignment of MscS as open in detergent by PELDOR was unexpected but is supported by two crystal structures of spin-labeled MscS. PELDOR is therefore shown to be a powerful experimental tool to interrogate the conformation of transmembrane regions of integral membrane proteins. 相似文献
995.
Selective inhibition of CD4+ T-cell cytokine production and autoimmunity by BET protein and c-Myc inhibitors 总被引:1,自引:0,他引:1
996.
997.
Itamar Harel Yoshiro Maezawa Roi Avraham Ariel Rinon Hsiao-Yen Ma Joe W. Cross Noam Leviatan Julius Hegesh Achira Roy Jasmine Jacob-Hirsch Gideon Rechavi Jaime Carvajal Shubha Tole Chrissa Kioussi Susan Quaggin Eldad Tzahor 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(46):18839-18844
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