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941.
Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major 总被引:14,自引:0,他引:14
Darrah PA Patel DT De Luca PM Lindsay RW Davey DF Flynn BJ Hoff ST Andersen P Reed SG Morris SL Roederer M Seder RA 《Nature medicine》2007,13(7):843-850
CD4+ T cells have a crucial role in mediating protection against a variety of pathogens through production of specific cytokines. However, substantial heterogeneity in CD4+ T-cell cytokine responses has limited the ability to define an immune correlate of protection after vaccination. Here, using multiparameter flow cytometry to assess the immune responses after immunization, we show that the degree of protection against Leishmania major infection in mice is predicted by the frequency of CD4+ T cells simultaneously producing interferon-gamma, interleukin-2 and tumor necrosis factor. Notably, multifunctional effector cells generated by all vaccines tested are unique in their capacity to produce high amounts of interferon-gamma. These data show that the quality of a CD4+ T-cell cytokine response can be a crucial determinant in whether a vaccine is protective, and may provide a new and useful prospective immune correlate of protection for vaccines based on T-helper type 1 (TH1) cells. 相似文献
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Ian M. Ware Michael E. Van Nuland Jennifer A. Schweitzer Zamin Yang Christopher W. Schadt Lindsay C. Sidak‐Loftis Nathan E. Stone Joseph D. Busch David M. Wagner Joseph K. Bailey 《Global Change Biology》2019,25(4):1514-1528
We examined the hypothesis that climate‐driven evolution of plant traits will influence associated soil microbiomes and ecosystem function across the landscape. Using a foundation tree species, Populus angustifolia, observational and common garden approaches, and a base population genetic collection that spans 17 river systems in the western United States, from AZ to MT, we show that (a) as mean annual temperature (MAT) increases, genetic and phenotypic variation for bud break phenology decline; (b) soil microbiomes, soil nitrogen (N), and soil carbon (C) vary in response to MAT and conditioning by trees; and (c) with losses of genetic variation due to warming, population‐level regulation of community and ecosystem functions strengthen. These results demonstrate a relationship between the potential evolutionary response of populations and subsequent shifts in ecosystem function along a large temperature gradient. 相似文献
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Shamina M. Rangwala Katharine D’Aquino Yue-Mei Zhang Lindsay Bader Wilson Edwards Songmao Zheng Annette Eckardt Ann Lacombe Rebecca Pick Veronica Moreno Lijuan Kang Wenying Jian Eric Arnoult Martin Case Celia Jenkinson Ellen Chi Ronald V. Swanson Paul Kievit James N. Leonard 《Cell metabolism》2019,29(4):837-843.e5
946.
James S.V. Lally Sarani Ghoshal Danielle K. DePeralta Omeed Moaven Lan Wei Ricard Masia Derek J. Erstad Naoto Fujiwara Vivian Leong Vanessa P. Houde Alexander E. Anagnostopoulos Alice Wang Lindsay A. Broadfield Rebecca J. Ford Robert A. Foster Jamie Bates Hailing Sun Ting Wang Bryan C. Fuchs 《Cell metabolism》2019,29(1):174-182.e5
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All living organisms must repair DNA double-stranded breaks (DSBs) in order to survive. Many bacteria rely on nonhomologous end joining (NHEJ) when only a single copy of the genome is available and maintain NHEJ pathways with a minimum of two proteins. In this issue, Bhattarai and colleagues identify additional factors that can work together to aid in survival of stationary-phase cells with chromosomal breaks. 相似文献
950.
Solid-State NMR Studies of Full-Length BamA in Lipid Bilayers Suggest Limited Overall POTRA Mobility
Tessa Sinnige Markus Weingarth Marie Renault Lindsay Baker Jan Tommassen Marc Baldus 《Journal of molecular biology》2014
The outer membrane protein BamA is the key player in β-barrel assembly in Gram-negative bacteria. Despite the availability of high-resolution crystal structures, the dynamic behavior of the transmembrane domain and the large periplasmic extension consisting of five POTRA (POlypeptide-TRansport-Associated) domains remains unclear. We demonstrate reconstitution of full-length BamA in proteoliposomes at low lipid-to-protein ratio, leading to high sensitivity and resolution in solid-state NMR (ssNMR) experiments. We detect POTRA domains in ssNMR experiments probing rigid protein segments in our preparations. These results suggest that the periplasmic region of BamA is firmly attached to the β-barrel and does not experience fast global motion around the angle between POTRA 2 and 3. We show that this behavior holds at lower protein concentrations and elevated temperatures. Chemical shift variations observed after reconstitution in lipids with different chain lengths and saturation levels are compatible with conformational plasticity of BamA's transmembrane domain. Electron microscopy of the ssNMR samples shows that BamA can cause local disruptions of the lipid bilayer in proteoliposomes. The observed interplay between protein–protein and protein–lipid interactions may be critical for BamA-mediated insertion of substrates into the outer membrane. 相似文献