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71.
72.
Both NK cells and CTLs kill virus-infected and tumor cells. However, the ways by which these killer cells recognize the infected or the tumorigenic cells are different, in fact almost opposite. CTLs are activated through the interaction of the TCR with MHC class I proteins. In contrast, NK cells are inhibited by MHC class I molecules. The inhibitory NK receptors recognize mainly MHC class I proteins and in this regard practically all of the HLA-C proteins are recognized by inhibitory NK cell receptors, while only certain HLA-A and HLA-B proteins interact with these receptors. Sophisticated viruses developed mechanisms to avoid the attack of both NK cells and CTLs through, for example, down regulation of HLA-A and HLA-B molecules to avoid CTL recognition, leaving HLA-C proteins on the cell surface to inhibit NK cell response. Here we provide the first example of a virus that through specific down regulation of HLA-C, harness the NK cells for its own benefit. We initially demonstrated that none of the tested HSV-2 derived microRNAs affect NK cell activity. Then we show that surprisingly upon HSV-2 infection, HLA-C proteins are specifically down regulated, rendering the infected cells susceptible to NK cell attack. We identified a motif in the tail of HLA-C that is responsible for the HSV-2-meduiated HLA-C down regulation and we show that the HLA-C down regulation is mediated by the viral protein ICP47. Finally we show that HLA-C proteins are down regulated from the surface of HSV-2 infected dendritic cells (DCs) and that this leads to the killing of DC by NK cells. Thus, we propose that HSV-2 had developed this unique and surprising NK cell-mediated killing strategy of infected DC to prevent the activation of the adaptive immunity. 相似文献
73.
Thomas Jans Erika Graf Christian Jacob Ulrike Zwanzger Silke Groß-Lesch Swantje Matthies Evgeniy Perlov Klaus Hennighausen Melanie Jung Michael Rösler Monika Schulte-Altedorneburg Alexander von Gontard Susann Hänig Esther Sobanski Barbara Alm Luise Poustka Lucia Bliznak Michael Colla Laura Gentschow Roland Burghardt Harriet Salbach-Andrae Katja Becker Martin Holtmann Christine Freitag Andreas Warnke Alexandra Philipsen 《Attention deficit and hyperactivity disorders》2013,5(1):29-40
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Norbert Pfeiffer Julia Lamparter Adrian Gericke Franz H. Grus Esther M. Hoffmann Jochen Wahl 《Cell and tissue research》2013,353(2):245-251
Intraocular pressure (IOP)-lowering therapy has been shown to arrest or retard the progression of optic neuropathy typical for glaucoma and can, thus, be described as neuroprotective. At present, six classes of medical therapy are employed, namely parasympathomimetics, alpha/beta-sympathomimetics, β-blockers, carbonic anhydrase inhibitors, α2-adrenergic receptor agonists and prostaglandin analogues. For several of these substances, some experimental evidence exists of a possible neuroprotective mechanism, beyond their IOP-lowering activity. β-Blockers are involved in the up-regulation of brain-derived neurotrophic factor (BDNF) and can decrease glutamate-mediated NMDA receptor activation. Not only systemic but also topical carbonic anhydrase inhibitors are able to increase retinal blood flow. α2-Adrenergic receptor agonists can up-regulate the formation of BDNF and anti-apoptotic factors. Prostaglandin analogues increase blood flow to the eye, possibly including the retina. To date, evidence for a neuroprotective effect independent of IOP regulation in human glaucoma is scarce and has only been shown to be likely for the α2-adrenergic receptor agonist, brimonidine. 相似文献
76.
Ilary Allodi Laura Casals-Díaz Eva Santos-Nogueira Francisco Gonzalez-Perez Xavier Navarro Esther Udina 《Molecular neurobiology》2013,47(2):770-781
In this study, we screened in vitro the different capabilities of trophic factors with promising effect for enhancing selective regeneration and thus promoting specific reinnervation of target organs after peripheral nerve regeneration. We found that FGF-2 (18 kDa) was the trophic factor that exerted the most selective effect in promoting neurite outgrowth of spinal motoneurons both in terms of elongation and arborization. The mechanism underlying this effect on neuritogenesis seems related to FGF-2 enhancing the interaction between FGFR-1 and PSA-NCAM. The interaction of these two receptors is important during the early stages of neuritogenesis and pathfinding, while integrin alpha7B subunit seems to play a role during neurite stabilization. 相似文献
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Eric Allan Wolfgang W. Weisser Markus Fischer Ernst-Detlef Schulze Alexandra Weigelt Christiane Roscher Jussi Baade Romain L. Barnard Holger Beßler Nina Buchmann Anne Ebeling Nico Eisenhauer Christof Engels Alexander J. F. Fergus Gerd Gleixner Marlén Gubsch Stefan Halle Alexandra M. Klein Ilona Kertscher Annely Kuu Markus Lange Xavier Le Roux Sebastian T. Meyer Varvara D. Migunova Alexandru Milcu Pascal A. Niklaus Yvonne Oelmann Esther Pašalić Jana S. Petermann Franck Poly Tanja Rottstock Alexander C. W. Sabais Christoph Scherber Michael Scherer-Lorenzen Stefan Scheu Sibylle Steinbeiss Guido Schwichtenberg Vicky Temperton Teja Tscharntke Winfried Voigt Wolfgang Wilcke Christian Wirth Bernhard Schmid 《Oecologia》2013,173(1):223-237
In order to predict which ecosystem functions are most at risk from biodiversity loss, meta-analyses have generalised results from biodiversity experiments over different sites and ecosystem types. In contrast, comparing the strength of biodiversity effects across a large number of ecosystem processes measured in a single experiment permits more direct comparisons. Here, we present an analysis of 418 separate measures of 38 ecosystem processes. Overall, 45 % of processes were significantly affected by plant species richness, suggesting that, while diversity affects a large number of processes not all respond to biodiversity. We therefore compared the strength of plant diversity effects between different categories of ecosystem processes, grouping processes according to the year of measurement, their biogeochemical cycle, trophic level and compartment (above- or belowground) and according to whether they were measures of biodiversity or other ecosystem processes, biotic or abiotic and static or dynamic. Overall, and for several individual processes, we found that biodiversity effects became stronger over time. Measures of the carbon cycle were also affected more strongly by plant species richness than were the measures associated with the nitrogen cycle. Further, we found greater plant species richness effects on measures of biodiversity than on other processes. The differential effects of plant diversity on the various types of ecosystem processes indicate that future research and political effort should shift from a general debate about whether biodiversity loss impairs ecosystem functions to focussing on the specific functions of interest and ways to preserve them individually or in combination. 相似文献
79.
Samantha A. Spangler Sabine K. Schmitz Josta T. Kevenaar Esther de Graaff Heidi de Wit Jeroen Demmers Ruud F. Toonen Casper C. Hoogenraad 《The Journal of cell biology》2013,201(6):915-928
The presynaptic active zone mediates synaptic vesicle exocytosis, and modulation of its molecular composition is important for many types of synaptic plasticity. Here, we identify synaptic scaffold protein liprin-α2 as a key organizer in this process. We show that liprin-α2 levels were regulated by synaptic activity and the ubiquitin–proteasome system. Furthermore, liprin-α2 organized presynaptic ultrastructure and controlled synaptic output by regulating synaptic vesicle pool size. The presence of liprin-α2 at presynaptic sites did not depend on other active zone scaffolding proteins but was critical for recruitment of several components of the release machinery, including RIM1 and CASK. Fluorescence recovery after photobleaching showed that depletion of liprin-α2 resulted in reduced turnover of RIM1 and CASK at presynaptic terminals, suggesting that liprin-α2 promotes dynamic scaffolding for molecular complexes that facilitate synaptic vesicle release. Therefore, liprin-α2 plays an important role in maintaining active zone dynamics to modulate synaptic efficacy in response to changes in network activity. 相似文献
80.
Capsule Mediterranean Great Tits showed a marked increase in levels of circulating carotenoids during moult and autumn.Aims To study seasonal variation in plasma carotenoid content during a whole annual cycle for Great Tits Parus major inhabiting a Mediterranean woodland.Methods We used a sample of 71 adult male Great Tits captured in NE Spain during a whole year. Data were organized into four seasons (winter, breeding, moult and autumn). We sampled blood to extract plasma. Carotenoid plasma concentrations were analysed by High-performance liquid chromatography (HPLC).Results Lutein and zeaxanthin content varied seasonally, with a marked increase in levels during moult and autumn. Within the moulting period, levels increased gradually as the season progressed. This pattern differed significantly from that previously described in northern European populations, where high values appear mainly in the breeding season. Carotenoid concentrations (lutein: 1.2?±?0.25, zeaxanthin: 0.07?±?0.03?µg mL?1) were also lower than in northern Europe.Conclusion Mediterranean Great Tits show a very different pattern of circulating carotenoids and lower levels than northern European populations. The increasing pattern of carotenoid availability found within the moulting period raises the need to control for the effect of sampling date when analysing data on carotenoid concentrations at different times of year. 相似文献