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151.
152.
Chromosome ends are known hotspots of meiotic recombination and double-strand breaks. We monitored mitotic sister chromatid exchange (SCE) in telomeres and subtelomeres and found that 17% of all SCE occurs in the terminal 0.1% of the chromosome. Telomeres and subtelomeres are significantly enriched for SCEs, exhibiting rates of SCE per basepair that are at least 1,600 and 160 times greater, respectively, than elsewhere in the genome. 相似文献
153.
In the context of viral infections, autophagy induction can be beneficial or inhibitory. Within the Paramyxoviridae family, only morbilliviruses have been investigated and are reported to induce autophagy. Here we show that morbilliviruses rapidly induce autophagy and require this induction for efficient cell-to-cell spread. Coexpression of both glycoproteins in cells expressing one of the cellular receptors was required for autophagy induction, and LC3 punctum formation, indicative of autophagy, was mainly observed in syncytia. A similar correlation between syncytium formation and autophagy induction was also observed for other paramyxovirus glycoproteins, suggesting that membrane fusion-mediated autophagy may be common among paramyxoviruses and possibly other enveloped viruses. 相似文献
154.
The immune cell adaptor adhesion and degranulation promoting adaptor protein (ADAP) and its binding to T-cell adaptor Src kinase-associated protein of 55 kDa (SKAP-55) play a key role in the modulation of T-cell adhesion. While primary binding occurs via SKAP-55 SH3 domain binding to a proline-rich region in ADAP, a second interaction occurs between the ADAP C-terminal SH3 domain (ADAP-SH3c) and a non-canonical RKXXY294XXY297 motif in SKAP-55. Increasing numbers of non-canonical SH3 domain binding motifs have been identified in a number of biological systems. The presence of tyrosine residues in the SKAP-55 RKXXY294XXY297 motif suggested that phosphorylation might influence this unusual SH3 domain interaction. Here, we show that the Src kinase p59fyn can induce the in vivo phosphorylation of the motif, and this event blocks ADAP-SH3c domain binding to the peptide motif. The importance of tyrosine phosphorylation was confirmed by plasmon resonance interaction analysis showing that phosphorylation of Tyr294 residue plays a central role in mediating dissociation, whereas phosphorylation of the second Tyr297 had no effect. Although loss of this secondary interaction did not result in the disruption of the complex, the Y294F mutation blocked T-cell receptor-induced up-regulation of lymphocyte function-associated antigen-1-mediated adhesion to intercellular adhesion molecule-1 and interleukin-2 promoter activity. Our findings identify a RKXXY294 motif in SKAP-55 that mediates unique ADAP SH3c domain binding and is needed for LFA-1-mediated adhesion and cytokine production. 相似文献
155.
Crandall H Dunn DM Ma Y Wooten RM Zachary JF Weis JH Weiss RB Weis JJ 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(11):7930-7942
The murine model of Lyme disease provides a unique opportunity to study the localized host response to similar stimulus, Borrelia burgdorferi, in the joints of mice destined to develop severe arthritis (C3H) or mild disease (C57BL/6). Pathways associated with the response to infection and the development of Lyme arthritis were identified by global gene expression patterns using oligonucleotide microarrays. A robust induction of IFN-responsive genes was observed in severely arthritic C3H mice at 1 wk of infection, which was absent from mildly arthritic C57BL/6 mice. In contrast, infected C57BL/6 mice displayed a novel expression profile characterized by genes involved in epidermal differentiation and wound repair, which were decreased in the joints of C3H mice. These expression patterns were associated with disease state rather than inherent differences between C3H and C57BL/6 mice, because C57BL/6-IL-10(-/-) mice infected with B. burgdorferi develop more severe arthritis than C57BL/6 mice and displayed an early gene expression profile similar to C3H mice. Gene expression profiles at 2 and 4 wk postinfection revealed a common response of all strains that was likely to be important for the host defense to B. burgdorferi and mediated by NF-kappaB-dependent signaling. The gene expression profiles identified in this study add to the current understanding of the host response to B. burgdorferi and identify two novel pathways that may be involved in regulating the severity of Lyme arthritis. 相似文献
156.
157.
Rapid responses of vegetation to hydrological changes in Taylor Slough, Everglades National Park, Florida, USA 总被引:2,自引:2,他引:0
Thomas V. Armentano Jay P. Sah Michael S. Ross David T. Jones Hillary C. Cooley Craig S. Smith 《Hydrobiologia》2006,569(1):293-309
We analyzed the dynamics of freshwater marsh vegetation of Taylor Slough in eastern Everglades National Park for the 1979
to 2003 period, focusing on cover of individual plant species and on cover and composition of marsh communities in areas potentially
influenced by a canal pump station (“S332”) and its successor station (“S332D”). Vegetation change analysis incorporated the
hydrologic record at these sites for three intervals: pre-S332 (1961–1980), S332 (1980–1999), post-S332 (1999–2002). During
S332 and post-S332 intervals, water level in Taylor Slough was affected by operations of S332 and S332D. To relate vegetation
change to plot-level hydrological conditions in Taylor Slough, we developed a weighted averaging regression and calibration
model (WA) using data from the marl prairies of Everglades National Park and Big Cypress National Preserve. We examined vegetation
pattern along five transects. Transects 1–3 were established in 1979 south of the water delivery structures, and were influenced
by their operations. Transects 4 and 5 were established in 1997, the latter west of these structures and possibly under their
influence. Transect 4 was established in the northern drainage basin of Taylor Slough, beyond the likely zones of influence
of S332 and S332D. The composition of all three southern transects changed similarly after 1979. Where muhly grass (Muhlenbergia capillaris var. filipes) was once dominant, sawgrass (Cladium jamaicense), replaced it, while where sawgrass initially predominated, hydric species such as spikerush (Eleocharis cellulosa Torr.) overtook it. Most of the changes in species dominance in Transects 1–3 occurred after 1992, were mostly in place by
1995–1996, and continued through 1999, indicating how rapidly vegetation in seasonal Everglades marshes can respond to hydrological
modifications. During the post-S332 period, these long-term trends began reversing. In the two northern transects, total cover
and dominance of both muhly grass and sawgrass increased from 1997 to 2003. Thus, during the 1990’s, vegetation composition
south of S332 became more like that of long hydroperiod marshes, but afterward it partially returned to its 1979 condition,
i.e., a community characteristic of less prolonged flooding. In contrast, the vegetation change along the two northern transects
since 1997 showed little relationship to hydrologic status. 相似文献
158.
Opdenakker G Dillen C Fiten P Martens E Van Aelst I Van den Steen PE Nelissen I Starckx S Descamps FJ Hu J Piccard H Van Damme J Wormald MR Rudd PM Dwek RA 《Biochimica et biophysica acta》2006,1760(4):610-615
The role of extracellular proteolysis in innate and adaptive immunity and the interplay between cytokines, chemokines and proteinases are gradually becoming recognized as critical factors in autoimmune processes. Many of the involved proteinases, including those of the plasminogen activator and matrix metalloproteinase cascades, and also several cytokines and chemokines, are glycoproteins. The stability, interactions with inhibitors or receptors, and activities of these molecules are fine-controlled by glycosylation. We studied gelatinase B or matrix metalloproteinase-9 (MMP-9) as a glycosylated enzyme involved in autoimmunity. In the joints of rheumatoid arthritis patients, CXC chemokines, such as interleukin-8/CXCL8, recruit and activate neutrophils to secrete prestored neutrophil collagenase/MMP-8 and gelatinase B/MMP-9. Gelatinase B potentiates interleukin-8 at least tenfold and thus enhances neutrophil and lymphocyte influxes to the joints. When cartilage collagen type II is cleaved at a unique site by one of several collagenases (MMP-1, MMP-8 or MMP-13), it becomes a substrate of gelatinase B. Human gelatinase B cleaves the resulting two large collagen fragments into at least 33 peptides of which two have been shown to be immunodominant, i.e., to elicit activation and proliferation of autoimmune T cells. One of these two remnant epitopes contains a glycan which is important for its immunoreactivity. In addition to the role of gelatinase B as a regulator in adaptive immune processes, we have also demonstrated that it destroys interferon-beta, a typical innate immunity effector molecule and therapeutic cytokine in multiple sclerosis. Furthermore, glycosylated interferon-beta, expressed in Chinese hamster ovary cells, was more resistant to this proteolysis than recombinant interferon-beta from bacteria. These data not only prove that glycosylation of proteins is mechanistically important in the pathogenesis of autoimmune diseases, but also show that targeting of glycosylated proteinases or the use of glycosylated cytokines seems also critical for the treatment of autoimmune diseases. 相似文献
159.
Bardor M Cabrera G Rudd PM Dwek RA Cremata JA Lerouge P 《Current opinion in structural biology》2006,16(5):576-583
Plants are attractive hosts for the production of recombinant proteins. However, their inability to process authentic human N-glycan structures imposes a major limitation on their use as expression systems for therapeutic products. Several strategies have emerged to engineer plant N-glycans into human-compatible molecules. In this context, fast and reliable analytical strategies for the identification of plant N-glycan profiles have been developed to define the N-glycosylation pathways of crops, to monitor the production of plant-made pharmaceuticals and to assess in planta remodelling strategies. 相似文献
160.
Dai-Shi Su John J. Lim Elizabeth Tinney Bang-Lin Wan Mary Beth Young Kenneth D. Anderson Deanne Rudd Vandna Munshi Carolyn Bahnck Peter J. Felock Meiqing Lu Ming-Tain Lai Sinoeun Touch Gregory Moyer Daniel J. DiStefano Jessica A. Flynn Yuexia Liang Rosa Sanchez Sridhar Prasad Youwei Yan Neville J. Anthony 《Bioorganic & medicinal chemistry letters》2009,19(17):5119-5123