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971.
972.
Barth H Schnober EK Neumann-Haefelin C Thumann C Zeisel MB Diepolder HM Hu Z Liang TJ Blum HE Thimme R Lambotin M Baumert TF 《Journal of virology》2008,82(7):3466-3479
Class B scavenger receptors (SR-Bs) bind lipoproteins and play an important role in lipid metabolism. Most recently, SR-B type I (SR-BI) and its splicing variant SR-BII have been found to mediate bacterial adhesion and cytosolic bacterial invasion in mammalian cells. In this study, we demonstrate that SR-BI is a key host factor required for hepatitis C virus (HCV) uptake and cross-presentation by human dendritic cells (DCs). Whereas monocytes and T and B cells were characterized by very low or undetectable SR-BI expression levels, human DCs demonstrated a high level of cell surface expression of SR-BI similar to that of primary human hepatocytes. Antibodies targeting the extracellular loop of SR-BI efficiently inhibited HCV-like particle binding, uptake, and cross-presentation by human DCs. Moreover, human high-density lipoprotein specifically modulated HCV-like particle binding to DCs, indicating an interplay of HCV with the lipid transfer function of SR-BI in DCs. Finally, we demonstrate that anti-SR-BI antibodies inhibit the uptake of cell culture-derived HCV (HCVcc) in DCs. In conclusion, these findings identify a novel function of SR-BI for viral antigen uptake and recognition and may have an important impact on the design of HCV vaccines and immunotherapeutic approaches aiming at the induction of efficient antiviral immune responses. 相似文献
973.
Chitin in the peritrophic membrane of Acarus siro (Acari: Acaridae) as a target for novel acaricides
Sobotnik J Kudlikova-Krizkova I Vancova M Munzbergova Z Hubert J 《Journal of economic entomology》2008,101(3):1028-1033
The peritrophic membrane in Acarus siro L. (Acari: Acaridae) is produced by distinct cells located in the ventriculus. In this study, the chitin inside the peritrophic membrane was detected using wheat germ-lectin conjugated with colloidal gold (10 nm). The chitin fibrils of the peritrophic membrane were a target for chitin effectors, including 1) chitinase, which hydrolyzes chitin fibers inside the peritrophic membrane; 2) calcofluor, which binds to chitin and destroys the peritrophic membrane mesh structure; and 3) diflubenzuron, which inhibits chitin synthesis. In addition, soybean trypsin protease inhibitor (STI) and cocktails of chitinase/calcofluor, diflubenzuron/calcofluor and chitinase/STI were tested. These compounds were supplemented in diets and an increase of population initiated from 50 individuals was observed after 21 d of cultivation. Final A. siro densities on experimental and control diets were compared. The chitin in the peritrophic membrane was determined to be a suitable target for novel acaricidal compounds for suppressing the population growth of A. siro. The most effective compounds were calcofluor and diflubenzuron, whereas the suppressive effects of chitinase and STI were low. The failure of chitinase could be due to its degradation by endogenous proteases. The combination of chitinase and STI suppressed A. siro population growth more effectively than when they were tested in oral admission separately. The combinations of calcofluor/chitinase or calcofluor/difluorbenzuron showed no additive effects on final A. siro density. The presence of chitin in peritrophic membrane provides a target for novel acaricidal compounds, which disrupt peritrophic membrane structure. The suitability of chitin effectors and their practical application in the management of stored product mites is discussed. 相似文献
974.
A. M. O'Keeffe † S. Hubert ‡ M. Voisin B. Houeix D. Cotter § M. T. Cairns 《Journal of fish biology》2008,73(2):436-443
Expression of somatolactin (SL) mRNA was quantified during smoltification at 2 week intervals during January and February and weekly during March, April and May 2004 in a line-bred ranching stock of Atlantic salmon Salmo salar . Gene expression of SL (and a splice variant termed SL180 ) was lower in fish sampled in the later weeks of smoltification than in those at the beginning, a pattern opposite to that of gill Na+ K+ -ATPase activity. 相似文献
975.
Spörri R Joller N Hilbi H Oxenius A 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(10):7121-7130
Neutrophils are essential players in innate immune responses to bacterial infection. Despite the striking resistance of Legionella pneumophila (Lpn) to bactericidal neutrophil function, neutrophil granulocytes are important effectors in the resolution of legionellosis. Indeed, mice depleted of neutrophils were unable to clear Lpn due to a lack of the critical cytokine IFN-gamma, which is produced by NK cells. We demonstrate that this can be ascribed to a previously unappreciated role of neutrophils as major NK cell activators. In response to Lpn infection, neutrophils activate caspase-1 and produce mature IL-18, which is indispensable for the activation of NK cells. Furthermore, we show that the IL-12p70 response in Lpn-infected neutropenic mice is also severely reduced and that the Lpn-induced IFN-gamma production by NK cells is strictly dependent on IL-12. However, since dendritic cells, and not neutrophils, are the source of Lpn-induced IL-12, its paucity is a consequence of the absence of IFN-gamma produced by NK cells rather than the absence of neutrophils per se. Therefore, neutrophil-derived IL-18, in combination with dendritic cell-produced IL-12, triggers IFN-gamma synthesis in NK cells in Lpn-infected mice. We propose a novel central role for neutrophils as essential IL-18 producers and hence NK cell "helpers" in bacterial infection. 相似文献
976.
Kaddouri H Djimdé A Dama S Kodio A Tekete M Hubert V Koné A Maiga H Yattara O Fofana B Sidibe B Sangaré CP Doumbo O Le Bras J 《International journal for parasitology》2008,38(7):791-798
In vitro susceptibility to antimalarial drugs of Malian Plasmodium falciparum isolates collected between 2004 and 2006 was studied. Susceptibility to chloroquine and to three artemisinin-based combination therapy (ACT) component drugs was assessed as a first, to our knowledge, in vitro susceptibility study in Mali. Overall 96 Malian isolates (51 from around Bamako and 45 collected from French travellers returning from Mali) were cultivated in a CO2 incubator. Fifty percent inhibitory concentrations (IC50s) were measured by either hypoxanthine incorporation or Plasmodium lactate dehydrogenase (pLDH) ELISA. Although the two sets of data were generated with different methods, the global IC50 distributions showed parallel trends. A good concordance of resistance phenotype with pfcrt 76T mutant genotype was found within the sets of clinical isolates tested. We confirm a high prevalence of P. falciparum in vitro resistance to chloroquine in Mali (60–69%). While some isolates showed IC50s close to the cut-off for resistance to monodesethylamodiaquine, no decreased susceptibility to dihydroartemisinin or lumefantrine was detected. This study provides baseline data for P. falciparum in vitro susceptibility to ACT component drugs in Mali. 相似文献
977.
Spirig T Tiaden A Kiefer P Buchrieser C Vorholt JA Hilbi H 《The Journal of biological chemistry》2008,283(26):18113-18123
The opportunistic pathogen Legionella pneumophila replicates in human lung macrophages and in free-living amoebae. To accommodate the transfer between host cells, L. pneumophila switches from a replicative to a transmissive phase. L. pneumophila harbors a gene cluster homologous to the Vibrio cholerae cqsAS quorum sensing system, encoding a putative autoinducer synthase (lqsA) and a sensor kinase (lqsS), which flank a response regulator (lqsR). LqsR is an element of the L. pneumophila virulence regulatory network, which promotes pathogen-host cell interactions and inhibits entry into the replicative growth phase. Here, we show that lqsA functionally complements a V. cholerae cqsA autoinducer synthase deletion mutant and, upon expression in L. pneumophila or Escherichia coli, produces the diffusible signaling molecule LAI-1 (Legionella autoinducer-1). LAI-1 is distinct from CAI-1 (Cholerae autoinducer-1) and was identified as 3-hydroxypentadecan-4-one using liquid chromatography coupled to high resolution tandem mass spectrometry. The activity of both LqsA and CqsA was abolished upon mutation of a conserved lysine, and covalent binding of the cofactor pyridoxal 5'-phosphate to this lysine was confirmed by mass spectrometry. Thus, LqsA and CqsA belong to a family of pyridoxal 5'-phosphate-dependent autoinducer synthases, which produce the alpha-hydroxyketone signaling molecules LAI-1 and CAI-1. 相似文献
978.
Using ion-selective microprobes, interactive signalling between barley and Blumeria graminis or Bipolaris sorokiniana has been investigated. The question was raised whether a biotrophically growing fungus manipulates the electrical driving forces (membrane potential, transmembrane pH), required for H+ cotransport of energy-rich compounds. Electrodes were positioned in the substomatal cavity of open stomata or on the leaf surface, and pH was measured continuously up to several days during fungal development. We demonstrate that surface and apoplastic fluids are electrically coupled and respond in a similar manner to stimuli. Apoplastic pH, monitored from the moment of inoculation with conidia, reveals several phases: 2-4h after inoculation of the barley leaf with either fungus, the host displays rapid transient responses after its first contact with the fungal cell wall; apoplastic pH and pCa increases, cytoplasmic pH and pCa decreases. About 1 day after inoculation, the apoplastic pH increases by up to 2 pH units, which is thought to reflect a resistance response against the intruder. Whereas barley leaf cells possess a membrane potential of -152+/-5 mV, hyphae of B. graminis yield -251+/-8 mV, indicative of a substantial driving force advantage for the fungus. Although the resting membrane potential of barley remains constant during the first days after inoculation, leaves infected with B. sorokiniana get confronted with an energy problem, indicated by a retarded repolarization following a "light-off" stimulus. Five days after inoculation, apoplastic pH has increased to 5.97+/-0.47 (n=11) and does no longer respond to "light-off" when measured within lesions. In contrast, it stays at near normal values outside the lesions and responds to "light-off". It is concluded that biotrophically growing fungi do not manipulate the cotransport driving forces since (i) any change in apoplastic pH would be experienced by both partners; (ii) the resting membrane potential is not changed. It is suggested that measured pH changes reflect defence responses of the host against the fungus rather than fungal action to increase compatibility. 相似文献
979.
Central and peripheral cardiovascular, ventilatory, and motor effects of trout urotensin-II in the trout 总被引:2,自引:0,他引:2
Urotensin-II (U-II) was originally considered to be exclusively the product of the caudal neurosecretory system (CNSS) of teleost fish, but it has now been demonstrated that U-II is widely expressed in peripheral tissues and nervous structures of species from lampreys to mammals. However, very little is known regarding the physiological effects of this peptide in its species of origin. In the present review, we summarize the most significant results relating to the cardiovascular, ventilatory, and motor effects of centrally and peripherally administered synthetic trout U-II in our experimental animal model, the unanesthetized trout Oncorhynchus mykiss. In addition, we compare the actions of U-II with those of other neurohormonal peptides, particularly with the actions of urotensin-I, a 41-amino acid residue peptide paralogous to corticotropin-releasing hormone that is co-localized with U-II within neurons of the CNSS. 相似文献
980.
Bourgault S Vaudry D Botia B Couvineau A Laburthe M Vaudry H Fournier A 《Peptides》2008,29(6):919-932
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 38- or 27-amino acid neuropeptide with promising therapeutic applications for the treatment of several pathophysiological states related to neurodegenerative diseases. However, its use for therapeutic applications is actually limited by its restricted bioavailability and rapid degradation. Therefore, metabolically stable PACAP analogs represent promising tools to further investigate the physiological roles of PACAP and ascertain its usefulness in some clinical conditions. In this study, derivatives of PACAP27 and PACAP38 have been rationally designed to develop PAC1 receptor agonists resistant to peptidase action. Results showed that N-terminal modifications confer resistance to dipeptidyl peptidase IV, a major proteolytic process involved in PACAP degradation. Moreover, in vitro incubation of both PACAP isoforms in human plasma revealed that PACAP38 is rapidly metabolized, with a half-life of less than 5 min, while PACAP27 was stable in these experimental conditions. Hence, following the elucidation of its plasmatic metabolites, PACAP38 was modified at its putative endopeptidase and carboxypeptidase sites of cleavage. All peptide analogs were tested for their ability to bind the PAC1 receptor, as well as for their potency to induce calcium mobilization and inhibit PC12 cell proliferation through the PAC1 receptor. This approach revealed two leading compounds, i.e. acetyl-[Ala15, Ala20]PACAP38-propylamide and acetyl-PACAP27-propylamide, which exhibited improved metabolic stability and potent biological activity. This study describes innovative data related to PACAP metabolism in human plasma and depicts the development of a metabolically stable PACAP38 analog, acetyl-[Ala15, Ala20]PACAP38-propylamide, which behaves as a super-agonist towards the PAC1 receptor. 相似文献