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981.
A new conditional mouse mutant reveals specific expression and functions of connexin36 in neurons and pancreatic beta-cells 总被引:1,自引:0,他引:1
982.
Skupin A Kettenmann H Winkler U Wartenberg M Sauer H Tovey SC Taylor CW Falcke M 《Biophysical journal》2008,94(6):2404-2411
Ca2+ oscillations have been considered to obey deterministic dynamics for almost two decades. We show for four cell types that Ca2+ oscillations are instead a sequence of random spikes. The standard deviation of the interspike intervals (ISIs) of individual spike trains is similar to the average ISI; it increases approximately linearly with the average ISI; and consecutive ISIs are uncorrelated. Decreasing the effective diffusion coefficient of free Ca2+ using Ca2+ buffers increases the average ISI and the standard deviation in agreement with the idea that individual spikes are caused by random wave nucleation. Array-enhanced coherence resonance leads to regular Ca2+ oscillations with small standard deviation of ISIs. 相似文献
983.
Transcutaneous anti-influenza vaccination promotes both CD4 and CD8 T cell immune responses in humans 总被引:1,自引:0,他引:1
Vogt A Mahé B Costagliola D Bonduelle O Hadam S Schaefer G Schaefer H Katlama C Sterry W Autran B Blume-Peytavi U Combadiere B 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(3):1482-1489
Induction of T cell responses has become one of the major goals in therapeutic vaccination against viral diseases and cancer. The use of the skin as target organ for vaccine has been spurred by recent implication of epithelial dendritic cells in CD8 cell cross-priming and suggests that vaccination via the transcutaneous (TC) route may be relevant in the induction of cellular immune responses. We have previously shown that TC application of nanoparticles, on human skin explants, allows targeting of epidermal dendritic cells, possibly via hair follicles. In this study, we have investigated cellular immune responses against an influenza protein-based vaccine by TC vaccination, compared with i.m. vaccination in humans. In this study on 11 healthy volunteers, we found that a newly developed protocol based on cyanoacrylate skin surface stripping induced a significant increase in IFN-gamma-producing T cells specific for influenza vaccine by ELISPOT assays. Interestingly, TC vaccination induced both effector CD4 and CD8 T cell responses, whereas i.m. injection induced strong effector CD4 in the absence of CD8 T cells, as assessed by intracellular cytokine staining and tetramer analyses. This study proposes new perspectives for the development of vaccination strategies that trigger T cell immune responses in humans. 相似文献
984.
Sakowicz-Burkiewicz M Nishanth G Helmuth U Drögemüller K Busch DH Utermöhlen O Naumann M Deckert M Schlüter D 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(8):5601-5612
Protein kinase C-theta (PKC-theta) is essential for the activation of T cells in autoimmune disorders, but not in viral infections. To study the role of PKC-theta in bacterial infections, PKC-theta(-/-) and wild-type mice were infected with Listeria monocytogenes (LM). In primary and secondary listeriosis, the numbers of LM-specific CD8 and CD4 T cells were drastically reduced in PKC-theta(-/-) mice, resulting in increased CFUs in spleen and liver of both PKC-theta(-/-) C57BL/6 and BALB/c mice. Furthermore, immunization with peptide-loaded wild-type dendritic cells induced LM-specific CD4 and CD8 T cells in wild-type but not in PKC-theta(-/-) mice. In listeriosis, transfer of wild-type T cells into PKC-theta(-/-) mice resulted in a normal control of Listeria, and, additionally, a selective expression of PKC-theta in LM-specific T cells was sufficient to drive a normal proliferation and survival of these T cells in LM-infected PKC-theta(-/-) recipients, illustrating a cell-autonomous function of PKC-theta in LM-specific T cells. Conversely, adoptively transferred PKC-theta(-/-) T cells were partially rescued from cell death and proliferated in LM-infected wild-type recipients, demonstrating that a PKC-theta deficiency of LM-specific T cells can be partially compensated for by a wild-type environment. Additionally, in vitro experiments showed that only the addition of IL-2, but not an inhibition of caspase-3, induced proliferation and prevented death of PKC-theta(-/-) T cells stimulated with LM-infected wild-type dendritic cells, further demonstrating that the impaired proliferation and survival of PKC-theta(-/-) T cells in listeriosis is not intrinsically fixed and can be experimentally improved. 相似文献
985.
Reichardt W Dürr C von Elverfeldt D Jüttner E Gerlach UV Yamada M Smith B Negrin RS Zeiser R 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(7):4770-4779
Dendritic cells (DC) play a major role in the pathogenesis of graft-vs-host disease (GvHD). Directed modification of surface molecules on DC that provide instructive signals for T cells may create a tolerogenic DC phenotype that affects GvHD severity. To investigate the impact of the mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) on in vivo migratory capacities, tolerogenic function, and B7 superfamily surface expression on DC following allogeneic hematopoietic cell transplantation (aHCT), we generated a platform for magnetic resonance imaging and bioluminescence imaging based cell trafficking studies. Luciferase transgenic DC were labeled with superparamagnetic iron oxide nanoparticles bound to a murine IgG Ab that allowed for Fc-gammaR-mediated endocytosis. Locally injected luc(+) DC could be tracked within their anatomical context by bioluminescence imaging and magnetic resonance imaging after aHCT, based on stable intracellular localization of superparamagnetic iron oxide-IgG complexes. RAPA preconditioned DC (DC-R) displayed reduced expression of MHC class II, B7-1 (CD80), and B7-2 (CD86) but not B7-H4 whose ligation of T cells has a profound inhibitory effect on their proliferation and cytokine secretion. DC-R of recipient genotype reduced GvHD severity that is compatible with their tolerogenic phenotype. CCR5, CCR7, and CD62L expression was not affected by mTOR inhibition, which allowed for DC-R in vivo trafficking to secondary lymphoid compartments where immunregulation is required. This study is the first to delineate the impact of RAPA on DC migration and tolerogenic function after aHCT. Modification of the DC phenotype by mTOR inhibition may have therapeutic potential in an attempt to reduce GvHD following aHCT. 相似文献
986.
Bar-On D Winter U Nachliel E Gutman M Fasshauer D Lang T Ashery U 《FEBS letters》2008,582(23-24):3563-3568
Mild sonication of eukaryotic cells produces native plasma membrane sheets that retain their docked organelles, cytoskeleton structures and cytoplasmic complexes. While the delicate organization of membranous protein complexes remains undisturbed, their inner plasmalemmel leaflet can be rapidly exposed to bathing solutions, enabling specific biochemical manipulations. Here, we apply this system to track membrane-biochemistry kinetics. We monitor soluble NSF-attachment protein receptor (SNARE) complex assembly and disassembly on the plasma membrane at high time resolution. The results suggest two-phase kinetics for the assembly process and dependence of the disassembly kinetics on both N-ethyl maleimide-sensitive factor (NSF) and soluble NSF-attachment protein (alpha-SNAP) concentrations. 相似文献
987.
Sebastian Wetterich Ulrike Herzschuh Hanno Meyer Lyudmila Pestryakova Birgit Plessen C. M. Larry Lopez Lutz Schirrmeister 《Hydrobiologia》2008,614(1):171-195
Taxonomical and geochemical investigations on freshwater ostracods from 15 waters in Central and Northeast (NE) Yakutia have
been undertaken in order to estimate their potential usefulness in palaeoenvironmental reconstructions based on regional fossil
records. Higher variability in environmental factors such as pH, electrical conductivity, and ionic content was observed in
thermokarst-affected lakes in Central Yakutia than in NE Yakutia lakes. Species diversity of freshwater ostracods reached
up to eight taxa per lake, mostly dominated by Candona weltneri Hartwig 1899, in Central Yakutia, whereas in NE Yakutian waters the diversity was lower and Candona muelleri jakutica Pietrzeniuk 1977 or Fabaeformiscandona inaequivalvis (Sars 1898) had highest frequencies. Coupled analyses of stable isotopes (δ18O, δ13C) and element ratios (Sr/Ca, Mg/Ca) were performed on both host waters and ostracod calcite, aiming to estimate the modern
relationships. Correlations between host waters and ostracod calcite of single species were found for δ18O, δ13C and Sr/Ca and Mg/Ca ratios. The relationships between δ18O, Mg/Ca and Sr/Ca ratios and electrical conductivity (salinity) as an expression of solute concentrations in the waters mainly
controlled by evaporation are more complicated but evident, and may be useful in future interpretation of geochemical data
from fossil Siberian ostracods.
Handling editor: K. Martens 相似文献
988.
Hirakawa H Takumi-Kobayashi A Theisen U Hirata T Nishino K Yamaguchi A 《Journal of bacteriology》2008,190(18):6276-6279
The acrS regulatory gene is located upstream of the acrEF multidrug efflux system genes. However, the roles of AcrS in regulation of drug efflux pumps have not been clearly understood. Here we show that AcrS represses other multidrug efflux genes, acrAB, which encode a major efflux system in Escherichia coli. 相似文献
989.
SoxAX cytochromes, a new type of heme copper protein involved in bacterial energy generation from sulfur compounds 总被引:1,自引:0,他引:1
Kappler U Bernhardt PV Kilmartin J Riley MJ Teschner J McKenzie KJ Hanson GR 《The Journal of biological chemistry》2008,283(32):22206-22214
SoxAX cytochromes are essential for the function of the only confirmed pathway for bacterial thiosulfate oxidation, the so-called "Sox pathway," in which they catalyze the initial formation of a S-S bond between thiosulfate and the SoxYZ carrier protein. Our work using the Starkeya novella diheme SoxAX protein reveals for the first time that in addition to two active site heme groups, SoxAX contains a mononuclear Cu(II) center with a distorted tetragonal geometry and three to four nitrogen ligands, one of which is a histidine. The Cu(II) center enhanced SoxAX activity in a newly developed, glutathione-based assay system that mimics the natural reaction of SoxAX with SoxYZ. EPR spectroscopy confirmed that the SoxAX Cu(II) center is reduced by glutathione. At pH 7 a K(m) (app) of 0.19+/-0.028 mm and a k(cat) (app) of 5.7+/-0.25s(-1) were determined for glutathione. We propose that SoxAX cytochromes are a new type of heme-copper proteins, with SoxAX-mediated S-S bond formation involving both the copper and heme centers. 相似文献
990.
Adriane Menßen Götz Edinger Joachim R Grün Ulrike Haase Ria Baumgrass Andreas Grützkau Andreas Radbruch Gerd-R Burmester Thomas Häupl 《BMC genomics》2009,10(1):1-13