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991.
Vidalain PO Laine D Zaffran Y Azocar O Servet-Delprat C Wild TF Rabourdin-Combe C Valentin H 《Journal of virology》2002,76(13):6415-6424
In the thymus, epithelial cells comprise a heterogeneous population required for the generation of functional T lymphocytes, suggesting that thymic epithelium disruption by viruses may compromise T-cell lymphopoiesis in this organ. In a previous report, we demonstrated that in vitro, measles virus induced differentiation of cortical thymic epithelial cells as characterized by (i) cell growth arrest, (ii) morphological and phenotypic changes, and (iii) apoptotis as a final step of this process. In the present report, we have analyzed the mechanisms involved. First, measles virus-induced differentiation of thymic epithelial cells is shown to be strictly dependent on beta interferon (IFN-beta) secretion. In addition, transfection with double-stranded RNA, a common intermediate of replication for a broad spectrum of viruses, is reported to similarly mediate thymic epithelial cell differentiation through IFN-beta induction. Finally, we demonstrated that recombinant IFN-alpha, IFN-beta, or IFN-gamma was sufficient to induce differentiation and apoptosis of uninfected thymic epithelial cells. These observations suggested that interferon secretion by either infected cells or activated leukocytes, such as plasmacytoid dendritic cells or lymphocytes, may induce thymic epithelium disruption in a pathological context. Thus, we have identified a new mechanism that may contribute to thymic atrophy and altered T-cell lymphopoiesis associated with many infections. 相似文献
992.
The nuclear lamina, along with associated nuclear membrane proteins, is a nexus for regulating signaling in the nucleus. Numerous human diseases arise from mutations in lamina proteins, and experimental models for these disorders have revealed aberrant regulation of various signaling pathways. Previously, we reported that the inner nuclear membrane protein Lem2, which is expressed at high levels in muscle, promotes the differentiation of cultured myoblasts by attenuating ERK signaling. Here, we have analyzed mice harboring a disrupted allele for the Lem2 gene (Lemd2). No gross phenotypic defects were seen in heterozygotes, although muscle regeneration induced by cardiotoxin was delayed. By contrast, homozygous Lemd2 knockout mice died by E11.5. Although many normal morphogenetic hallmarks were observed in E10.5 knockout embryos, most tissues were substantially reduced in size. This was accompanied by activation of multiple MAP kinases (ERK1/2, JNK, p38) and AKT. Knockdown of Lem2 expression in C2C12 myoblasts also led to activation of MAP kinases and AKT. These findings indicate that Lemd2 plays an essential role in mouse embryonic development and that it is involved in regulating several signaling pathways. Since increased MAP kinase and AKT/mTORC signaling is found in other animal models for diseases linked to nuclear lamina proteins, LEMD2 should be considered to be another candidate gene for human disease. 相似文献
993.
Neutrophil CD64 expression and serum IL-8: sensitive early markers of severity and outcome in sepsis
Livaditi O Kotanidou A Psarra A Dimopoulou I Sotiropoulou C Augustatou K Papasteriades C Armaganidis A Roussos C Orfanos SE Douzinas EE 《Cytokine》2006,36(5-6):283-290
The aim of the present study was to investigate which biomarker/s reliably assess severity and mortality early in the sepsis process. In 47 critically-ill patients within the 24h of septic onset, Interleukins (IL)-8, -1beta, -6, -10, and -12p70, tumor necrosis factor-alpha (TNF-alpha), procalcitonin (PCT) and C-reactive protein (CRP) were measured in serum. Additionally, CD64 expression was measured in neutrophils. In early sepsis, neutrophil CD64 expression and IL-8 levels are the only biomarkers that increased with sepsis severity, differentiating disease stages: sepsis, severe sepsis and septic shock (p<0.001). The biomarkers that best evaluate the severity of sepsis (via APACHE II) were CD64, IL-8 and IL-6 (p<0.01), and the severity of organ failure (via SOFA) were CD64 and IL-8 (p<0.01). CD64 expression and IL-8 levels were associated with mortality within 28-days (OR=1.3, p=0.01 for CD64 and OR=1.26, p=0.024 for IL-8 by logistic regression analysis) and ROC curve analysis showed high sensitivity and specificity for predicting sepsis stages and the 28 day mortality. We conclude that there is an early increase of neutrophil CD64 expression and IL-8 levels during sepsis. Based on this single measurement it is possible to reliably assess the stage, detect the severity and predict the 28-day mortality of sepsis. 相似文献
994.
Sedelnikova OA Horikawa I Zimonjic DB Popescu NC Bonner WM Barrett JC 《Nature cell biology》2004,6(2):168-170
Humans and animals undergo ageing, and although their primary cells undergo cellular senescence in culture, the relationship between these two processes is unclear. Here we show that gamma-H2AX foci (gamma-foci), which reveal DNA double-strand breaks (DSBs), accumulate in senescing human cell cultures and in ageing mice. They colocalize with DSB repair factors, but not significantly with telomeres. These cryptogenic gamma-foci remain after repair of radiation-induced gamma-foci, suggesting that they may represent DNA lesions with unrepairable DSBs. Thus, we conclude that accumulation of unrepairable DSBs may have a causal role in mammalian ageing. 相似文献
995.
Singaravelu K Nelson C Bakowski D de Brito OM Ng SW Di Capite J Powell T Scorrano L Parekh AB 《The Journal of biological chemistry》2011,286(14):12189-12201
Store-operated Ca2+ channels in the plasma membrane (PM) are activated by the depletion of Ca2+ from the endoplasmic reticulum (ER) and constitute a widespread and highly conserved Ca2+ influx pathway. After store emptying, the ER Ca2+ sensor STIM1 forms multimers, which then migrate to ER-PM junctions where they activate the Ca2+ release-activated Ca2+ channel Orai1. Movement of an intracellular protein to such specialized sites where it gates an ion channel is without precedence, but the fundamental question of how STIM1 migrates remains unresolved. Here, we show that trafficking of STIM1 to ER-PM junctions and subsequent Ca2+ release-activated Ca2+ channel activity is impaired following mitochondrial depolarization. We identify the dynamin-related mitochondrial protein mitofusin 2, mutations of which causes the inherited neurodegenerative disease Charcot-Marie-Tooth IIa in humans, as an important component of this mechanism. Our results reveal a molecular mechanism whereby a mitochondrial fusion protein regulates protein trafficking across the endoplasmic reticulum and reveals a homeostatic mechanism whereby mitochondrial depolarization can inhibit store-operated Ca2+ entry, thereby reducing cellular Ca2+ overload. 相似文献
996.
Expression of nonstructural rotavirus protein NSP4 mimics Ca2+ homeostasis changes induced by rotavirus infection in cultured cells 下载免费PDF全文
Díaz Y Chemello ME Peña F Aristimuño OC Zambrano JL Rojas H Bartoli F Salazar L Chwetzoff S Sapin C Trugnan G Michelangeli F Ruiz MC 《Journal of virology》2008,82(22):11331-11343
Rotavirus infection modifies Ca2+ homeostasis, provoking an increase in Ca2+ permeation, the cytoplasmic Ca2+ concentration ([Ca2+]cyto), and total Ca2+ pools and a decrease in Ca2+ response to agonists. A glycosylated viral protein(s), NSP4 and/or VP7, may be responsible for these effects. HT29 or Cos-7 cells were infected by the SA11 clone 28 strain, in which VP7 is not glycosylated, or transiently transfected with plasmids coding for NSP4-enhanced green fluorescent protein (EGFP) or NSP4. The permeability of the plasma membrane to Ca2+ and the amount of Ca2+ sequestered in the endoplasmic reticulum released by carbachol or ATP were measured in fura-2-loaded cells at the single-cell level under a fluorescence microscope or in cell suspensions in a fluorimeter. Total cell Ca2+ pools were evaluated as 45Ca2+ uptake. Infection with SA11 clone 28 induced an increase in Ca2+ permeability and 45Ca2+ uptake similar to that found with the normally glycosylated SA11 strain. These effects were inhibited by tunicamycin, indicating that inhibition of glycosylation of a viral protein other than VP7 affects the changes of Ca2+ homeostasis induced by infection. Expression of NSP4-EGFP or NSP4 in transfected cells induced the same changes observed with rotavirus infection, whereas the expression of EGFP or EGFP-VP4 showed the behavior of uninfected and untransfected cells. Increased 45Ca2+ uptake was also observed in cells expressing NSP4-EGFP or NSP4, as evidenced in rotavirus infection. These results indicate that glycosylated NSP4 is primarily responsible for altering the Ca2+ homeostasis of infected cells through an initial increase of cell membrane permeability to Ca2+. 相似文献
997.
Sara Guariento Anna Karawajczyk James A. Bull Gessica Marchini Martyna Bielska Xenia Iwanowa Olga Bruno Paola Fossa Fabrizio Giordanetto 《Bioorganic & medicinal chemistry letters》2017,27(1):24-29
Phosphodiesterase 4 (PDE4) inhibitors have attractive therapeutic potential in respiratory, inflammatory, metabolic and CNS disorders. The present work details the design, chemical exploration and biological profile of a novel PDE4 inhibitor chemotype. A diazepinone ring was identified as an under-represented heterocyclic system fulfilling a set of PDE4 structure-based design hypotheses. Rapid exploration of the structure activity relationships for the series was enabled by robust and scalable two/three-steps parallel chemistry protocols. The resulting compounds demonstrated PDE4 inhibitory activity in cell free and cell-based assays comparable to the Zardaverine control used, suggesting potential avenues for their further development. 相似文献
998.
Evaluation of the effectiveness of a chamomile (Matricaria chamomilla) and linseed (Linum usitatissimum) saliva substitute in the relief of xerostomia in elders 下载免费PDF全文
999.
Olga E. Belevich Yury A. Yurchenko Viktor V. Glupov Vadim Yu. Kryukov 《Applied Entomology and Zoology》2017,52(3):439-445
The influence of the fungus Metarhizium robertsii Bischoff, Rehner and Humber on the mortality of four water bug species, Cymatia coleoptrata (Fabricius), Sigara assimilis (Fieber), Ilyocoris cimicoides cimicoides (Linnaeus), and Notonecta reuteri Hungerford, and bloodsucking mosquito Anopheles messeae Falleroni, was investigated under various concentrations of conidia and different treatment types. We found that the mortality of adults of the water bug species was similar or higher than that of A. messeae, with C. coleoptrata and S. assimilis being more susceptible to M. robertsii than N. reuteri, I. c. cimicoides, and the mosquito A. messeae. Treatment with dry conidia at concentrations of 5 × 104 and 5 × 105 conidia/ml caused higher mortality of the water bug species than did treatment at the same concentrations with conidia in an aqueous suspension. In contrast, higher concentrations (5 × 106 conidia/ml) led to higher mortality after treatment with the aqueous suspension, relative to treatment with dry conidia. Our studies showed that water bugs exhibited the classical development of a mycosis with hemocoel colonization, mummification, and conidia formation on cadavers directly on the surface of the water. Possible changes in invertebrate communities in aquatic ecosystems after treatment with Metarhizium are discussed. 相似文献
1000.
Kevin A. Jernigan Olga S. Belichenko Valeria B. Kolosova Darlene J. Orr 《Journal of ethnobiology and ethnomedicine》2017,13(1):61