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961.
West Nile virus (WNV) is transmitted to vertebrate hosts primarily by infected Culex mosquitoes. Transmission of arboviruses by the bite of infected mosquitoes can potentiate infection in hosts compared to viral infection by needle inoculation. Here we examined the effect of mosquito transmission on WNV infection and systematically investigated multiple factors that differ between mosquito infection and needle inoculation of WNV. We found that mice infected with WNV through the bite of a single infected Culex tarsalis mosquito exhibited 5- to 10-fold-higher viremia and tissue titers at 24 and 48 h postinoculation and faster neuroinvasion than mice given a median mosquito-inoculated dose of WNV (10(5) PFU) by needle. Mosquito-induced enhancement was not due to differences in inoculation location, because additional intravenous inoculation of WNV did not enhance viremia or tissue titers. Inoculation of WNV into a location where uninfected mosquitoes had fed resulted in enhanced viremia and tissue titers in mice similar to those in mice infected by a single infected mosquito bite, suggesting that differences in where virus is deposited in the skin and in the virus particle itself were not responsible for the enhanced early infection in mosquito-infected mice. In addition, inoculation of mice with WNV mixed with salivary gland extract (SGE) led to higher viremia, demonstrating that mosquito saliva is the major cause of mosquito-induced enhancement. Enhanced viremia was not observed when SGE was inoculated at a distal site, suggesting that SGE enhances WNV replication by exerting a local effect. Furthermore, enhancement of WNV infection still occurred in mice with antibodies against mosquito saliva. In conclusion, saliva from C. tarsalis is responsible for enhancement of early WNV infection in vertebrate hosts. 相似文献
962.
Synergistic activation of ENaC by three membrane-bound channel-activating serine proteases (mCAP1, mCAP2, and mCAP3) and serum- and glucocorticoid-regulated kinase (Sgk1) in Xenopus Oocytes 下载免费PDF全文
Vuagniaux G Vallet V Jaeger NF Hummler E Rossier BC 《The Journal of general physiology》2002,120(2):191-201
Sodium balance is maintained by the precise regulation of the activity of the epithelial sodium channel (ENaC) in the kidney. We have recently reported an extracellular activation of ENaC-mediated sodium transport (I(Na)) by a GPI-anchored serine protease (mouse channel-activating protein, mCAP1) that was isolated from a cortical collecting duct cell line derived from mouse kidney. In the present study, we have identified two additional membrane-bound serine proteases (mCAP2 and mCAP3) that are expressed in the same cell line. We show that each of these proteases is able to increase I(Na) 6-10-fold in the Xenopus oocyte expression system. I(Na) and the number (N) of channels expressed at the cell surface (measured by binding of a FLAG monoclonal I(125)-radioiodinated antibody) were measured in the same oocyte. Using this assay, we show that mCAP1 increases I(Na) 10-fold (P < 0.001) but N remained unchanged (P = 0.9), indicating that mCAP1 regulates ENaC activity by increasing its average open probability of the whole cell (wcP(o)). The serum- and glucocorticoid-regulated kinase (Sgk1) involved in the aldosterone-dependent signaling cascade enhances I(Na) by 2.5-fold (P < 0.001) and N by 1.6-fold (P < 0.001), indicating a dual effect on N and wcP(o). Compared with Sgk1 alone, coexpression of Sgk1 with mCAP1 leads to a ninefold increase in I(Na) (P < 0.001) and 1.3-fold in N (P < 0.02). Similar results were observed for mCAP2 and mCAP3. The synergism between CAPs and Sgk1 on I(Na) was always more than additive, indicating a true potentiation. The synergistic effect of the two activation pathways allows a large dynamic range for ENaC-mediated sodium regulation crucial for a tight control of sodium homeostasis. 相似文献
963.
Shiqi Zhang Holger A. Lindner Sarah Kabtni Jaap van den Born Stephan Bakker Gerjan Navis Bernard Kr?mer Benito Yard Sibylle Hauske 《PloS one》2016,11(1)
Background and Aims
The proportion of serum carnosinase (CN-1) recognized by RYSK173 monoclonal antibody negatively correlates with CN-1 activity. We thus hypothesized that the epitope recognized by RYSK173 is accessible only in a catalytically incompetent conformation of the zinc dependent enzyme and we mapped its position in the CN-1 structure. Since patients with kidney failure are often deficient in zinc and other trace elements we also assessed the RYSK173 CN-1 proportion in serum of these patients and studied the influence of hemodialysis hereon in relation to Zn2+ and Cu2+ concentration during hemodialysis.Methods and Results
Epitope mapping using myc-tagged CN-1 fragments and overlapping peptides revealed that the RYSK173 epitope directly contributes to the formation of the dinuclear Zn center in the catalytic domain of homodimeric CN-1. Binding of RYSK173 to CN-1 was however not influenced by addition of Zn2+ or Cu2+ to serum. In serum of healthy controls the proportion of CN-1 recognized by RYSK173 was significantly lower compared to end-stage renal disease (ESRD) patients (1.12 ± 0.17 vs. 1.56 ± 0.40% of total CN-1; p<0.001). During hemodialysis the relative proportion of RYSK173 CN-1 decreased in parallel with increased serum Zn2+ and Cu2+ concentrations after dialysis.Conclusions
Our study clearly indicates that RYSK173 recognizes a sequence within the transition metal binding site of CN-1, thus supporting our hypothesis that metal binding to CN-1 masks the epitope. The CN-1 RYSK173 proportion appears overall increased in ESRD patients, yet it decreases during hemodialysis possibly as a consequence of a relative increase in transition metal bound enzyme. 相似文献964.
Rune Jacobsen Torben Martinussen Lene Christiansen Bernard Jeune Karen Andersen‐Ranberg James W. Vaupel Kaare Christensen 《Aging cell》2010,9(6):1004-1009
Studies of Nordic twins suggest an increased genetic influence on mortality with age. Contrary to this, the heterogeneity hypothesis predicts that the mortality of individuals carrying a ‘frail’ or ‘risky’ genotype in a population will approach that of noncarriers with age because of selection pressure. The ApoE ε4 allele is associated with an increased mortality risk, and its effect has been suggested to decrease with age. Here, we investigated the effect of ApoE ε4 allele on survival in a sample of the healthiest and long‐lived Danes. The study population comprised Danes born in 1905 and a replicate sample of the 1895 cohort. For the 1905 cohort, a total of 350 carriers and 1256 noncarriers of the ApoE ε4 allele were followed from 1998 until death or end of follow‐up. Cox regression models were used for the analysis. Of the 1606 persons with known ApoE ε4 status in 1998, 1546 had died at the end of the 10‐year follow‐up. Carriers of the ApoE ε4 allele had an increased mortality compared to noncarriers, and the influence of ApoE status on mortality increased in the age interval 92–103. For the covariates sex and independency status, the difference in relative risk of death between groups decreased with advancing age. Our findings of increasing influence of ApoE ε4 allele on mortality with age do not support previous findings of decreased influence ApoE ε4 allele on mortality with age, and alternative models such as the multifactorial threshold models should be considered for understanding the genetic effects on mortality at advanced age. 相似文献
965.
Determann RM Wolthuis EK Choi G Bresser P Bernard A Lutter R Schultz MJ 《American journal of physiology. Lung cellular and molecular physiology》2008,294(2):L344-L350
Clara cell protein levels are elevated in plasma of individuals with mild or subclinical lung injury. We studied the influence of two mechanical ventilation strategies on local and systemic levels of Clara cell protein (CC16) and compared them with levels of soluble receptor for advanced glycation end products (sRAGE) and surfactant proteins (SP)-A and -D in patients undergoing elective surgery. Saved samples from a previously reported investigation were used for the study. Forty patients planned for elective surgery were randomized to mechanical ventilation with either a conventional tidal volume (V(T)) of 12 ml/kg without positive end-expiratory pressure (PEEP) or low V(T) of 6 ml/kg and 10 cmH(2)O PEEP. Plasma and bronchoalveolar lavage fluid (BALF) was collected directly after intubation and after 5 h of mechanical ventilation. While systemic levels of SP-A and SP-D remained unchanged, systemic levels of CC16 and sRAGE increased significantly in both groups after 5 h (P < 0.001 for both). BALF levels of SP-A, SP-D, CC16, and sRAGE remained unaffected. No differences were found between the two mechanical ventilation strategies regarding any of the measured biological markers. In conclusion, systemic levels of CC16 and sRAGE rise after 5 h in patients receiving mechanical ventilation for elective surgery. Mechanical ventilation with lower tidal volumes and PEEP did not have a different effect on levels of biomarkers of lung epithelial injury compared with conventional mechanical ventilation. 相似文献
966.
Murilo S. Dias Thierry Oberdorff Bernard Hugueny Fabien Leprieur Céline Jézéquel Jean‐François Cornu Sébastien Brosse Gael Grenouillet Pablo A. Tedesco 《Ecology letters》2014,17(9):1130-1140
The relative importance of contemporary and historical processes is central for understanding biodiversity patterns. While several studies show that past conditions can partly explain the current biodiversity patterns, the role of history remains elusive. We reconstructed palaeo‐drainage basins under lower sea level conditions (Last Glacial Maximum) to test whether the historical connectivity between basins left an imprint on the global patterns of freshwater fish biodiversity. After controlling for contemporary and past environmental conditions, we found that palaeo‐connected basins displayed greater species richness but lower levels of endemism and beta diversity than did palaeo‐disconnected basins. Palaeo‐connected basins exhibited shallower distance decay of compositional similarity, suggesting that palaeo‐river connections favoured the exchange of fish species. Finally, we found that a longer period of palaeo‐connection resulted in lower levels of beta diversity. These findings reveal the first unambiguous results of the role played by history in explaining the global contemporary patterns of biodiversity. 相似文献
967.
Eric Vivès Claude Granier Paul Prevot Bernard Lebleu 《International journal of peptide research and therapeutics》1997,4(4-6):429-436
Summary Tat, a 86-amino acid protein involved in the replication of Human Immunodeficiency Virus type 1 (HIV-1), is able to translocate
efficiently through the plasma membrane and to reach the nucleus to transactivate the viral genome. The region 37–72 of the
Tat protein, centered on a cluster of basic amino acids, has been assigned to this translocation activity. Recent data in
our group have attributed this membrane translocating activity to a peptide extending from residues 48 to 60, which contains
a cluster of eight basic amino acids within a linear sequence of nine residues. Internalization of this peptide into cells
occurred within minutes at concentrations as low as 100 nM. In order to define more precisely the involvement of these basic
amino acids in peptide translocation, several analogues carrying deletions or substitutions of one, or several, of the basic
residues were synthesized and tested for their cellular uptake and nuclear translocation. A direct correlation between the
overall charge of the peptide and its cell internalization was found. In addition, the covalent linkage of this short basic
peptide allows the efficient translocation of a non-membrane permeant peptide. 相似文献
968.
Russian honey bee (Hymenoptera: Apidae) colonies: Acarapis woodi (Acari: Tarsonemidae) infestations and overwintering survival 总被引:1,自引:0,他引:1
De Guzman LI Rinderer TE Bigalk M Tubbs H Bernard SJ 《Journal of economic entomology》2005,98(6):1796-1801
Honey bee, Apis mellifera L. (Hymenoptera: Apidae), colonies infested by parasitic mites are more prone to suffer from a variety of stresses, including cold temperature. We evaluated the overwintering ability of candidate breeder lines of Russian honey bees, most of which are resistant to both Varroa destructor Anderson & Trueman and Acarapis woodi (Rennie), during 1999-2001. Our results indicate that Russian honey bee colonies (headed by original and supersedure queens) can successfully overwinter in the north, even during adverse weather conditions, owing to their frugal use of food stores and their resistance to tracheal mite infestations. In contrast, colonies of Italian honey bees consumed more food, had more mites, and lost more adult bees than Russian honey bees, even during unusually mild winter conditions. 相似文献
969.
Banquet S Delannoy E Agouni A Dessy C Lacomme S Hubert F Richard V Muller B Leblais V 《Cellular signalling》2011,23(7):1136-1143
Activation of the β2-adrenoceptor (β2-AR) elicits an endothelial nitric oxide synthase (eNOS)-dependent relaxation in mouse pulmonary artery, which, contrary to the muscarinic receptor-dependent relaxation, is preserved in hypoxic pulmonary arterial hypertension. We therefore characterized the signaling pathways underlying the β2-AR-mediated eNOS activation, with special focus on Gi/o proteins, protein kinases and caveolae. Functional studies (for evaluation of vasorelaxant response), Western blotting (for assessment of eNOS and caveolin-1 phosphorylation) and transmission electron microscopy (for visualization of caveolae) were conducted in pulmonary arteries from wild-type or caveolin-1 knockout mice. In wild-type isolated arteries, relaxation to the selective β2-AR agonist procaterol was reduced by inhibitors of Gi/o proteins (pertussis toxin, PTX), phosphatidylinositol 3-kinase (PI3K; wortmannin or LY 294002), Akt (Akt inhibitor X) and Src-kinase (PP2) and by cholesterol depletion (using methyl-β-cyclodextrin). Procaterol induced eNOS phosphorylation at Ser1177, which was prevented by PTX, PP2 or Akt inhibitor. Procaterol also promoted caveolin-1 phosphorylation at Tyr14, which was decreased by PTX or PP2. Caveolin-1 gene deletion resulted in endothelial caveolae disruption in mouse pulmonary artery and in potentiation of procaterol-induced relaxation. Unlike procaterol, acetylcholine-induced relaxation was unaffected by PTX, methyl-β-cyclodextrin or caveolin-1 gene deletion. To conclude, the mouse pulmonary endothelial β2-AR is coupled to a Gi/o-Src kinase-PI3K/Akt pathway to promote eNOS phosphorylation at Ser1177 leading to a NO-dependent vasorelaxation. Caveolin-1 exerts a negative control on this response that is abrogated by its phosphorylation at Tyr14, through a Gi/o-Src kinase pathway. Since pulmonary β2-AR- and muscarinic receptor-mediated relaxations differentiate in their respective signaling pathways leading to eNOS activation and sensitivities during hypoxia-induced pulmonary arterial hypertension, mechanisms underlying eNOS activation might be key determinants of pulmonary endothelial dysfunction. 相似文献
970.
Bernard Calvez 《Journal of insect physiology》1981,27(4):233-239
The progress of developmental programme in the epidermal cells of last instar larvae of Bombyx mori was determined by ecdysteroid injections in normal and in JH-treated larvae. To clarify the importance of food intake in the control of development, starved animals were also used.The instar begins with a period during which the larval programme is expressed: this occurs in the presence of 20-hydroxyecdysone. Epidermal cells can thereafter secrete pupal cuticle after ecdysteroid injection although the larval programme is normally still present. During the last period only pupal characters can be expressed either in normal or in 20-hydroxyecdysone-injected larvae.These different developmental phases are not correlated with obligatory and facultative feeding periods.Transition from the first to the second phases is correlated with the absence of JH effects on pupal genes. JH applications during the second period, however, prevent the expression of pupal characters after 20-hydroxyecdysone injection. Thus, during this period, the pupal programme is not stabilized. Cellular reprogramming itself occurs at the onset of the last developmental period and is probably under the control of ecdysteroids. 相似文献