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Entry Mechanism (entry + mechanism)
Selected AbstractsCharacterization of host-range and cell entry properties of the major genotypes and subtypes of hepatitis C virus,HEPATOLOGY, Issue 2 2005Dimitri Lavillette Because of the lack of a robust cell culture system, relatively little is known about the molecular details of the cell entry mechanism for hepatitis C virus (HCV). Recently, we described infectious HCV pseudo-particles (HCVpp) that were generated by incorporating unmodified HCV E1E2 glycoproteins into the membrane of retroviral core particles. These initial studies, performed with E1E2 glycoproteins of genotype 1, noted that HCVpp closely mimic the cell entry and neutralization properties of parental HCV. Because sequence variations in E1 and E2 may account for differences in tropism, replication properties, neutralization, and response to treatment in patients infected with different genotypes, we investigated the functional properties of HCV envelope glycoproteins from different genotypes/subtypes. Our studies indicate that hepatocytes were preferential targets of infection in vitro, although HCV replication in extrahepatic sites has been reported in vivo. Receptor competition assays using antibodies against the CD81 ectodomain as well as ectopic expression of CD81 in CD81-deficient HepG2 cells indicated that CD81 is used by all the different genotypes/subtypes analyzed to enter the cells. However, by silencing RNA (siRNA) interference assays, our results show that the level of Scavenger Receptor Class-B Type-I (SR-BI) needed for efficient infection varies between genotypes and subtypes. Finally, sera from chronic HCV carriers were found to exhibit broadly reactive activities that inhibited HCVpp cell entry, but failed to neutralize all the different genotypes. In conclusion, we characterize common steps in the cell entry pathways of the major HCV genotypes that should provide clues for the development of cell entry inhibitors and vaccines. (HEPATOLOGY 2005;41:265,274.) [source] Adenoviral vectors for gene transfer and therapyTHE JOURNAL OF GENE MEDICINE, Issue S1 2004Christoph Volpers Abstract Due to the very efficient nuclear entry mechanism of adenovirus and its low pathogenicity for humans, adenovirus-based vectors have become gene delivery vehicles that are widely used for transduction of different cell types, especially for quiescent, differentiated cells, in basic research, in gene therapy applications, and in vaccine development. As an important basis for their use as gene medicine, adenoviral vectors can be produced in high titers, they can transduce cells in vivo with transgenes of more than 30 kb, and they do not integrate into the host cell genome. Recent advances in the development of adenoviral vectors have brought considerable progress on issues like target cell specificity and tropism modification, long-term expression of the transgene, as well as immunogenicity and toxicity in vivo, and have suggested that the different generations of non-replicative and replicative vectors available today will each suit best for certain applications. Copyright © 2004 John Wiley & Sons, Ltd. [source] Endogenous Markups and Fiscal PolicyTHE MANCHESTER SCHOOL, Issue 2004Luís F. Costa This paper analyses a simple imperfectly competitive general equilibrium model where the entry mechanism generates an endogenous markup. In this second-best world fiscal policy is more effective than in Walrasian or in fixed-markup monopolistic competition models, as it produces efficiency gains through entry. [source] Recent insights into the mechanisms of Chlamydia entryCELLULAR MICROBIOLOGY, Issue 12 2005Alice Dautry-Varsat Summary Chlamydia are widespread bacteria that grow in human and animal cells. They enter their host cell, establish an intracellular environment favourable for their multiplication and finally exit the host cell. A combination of host cell factors and of bacterial proteins contribute to pathogen entry. Recent advances have shed new light on the entry mechanism, following attachment. Here we review recent data concerning endocytosis, host cell signalling, proteins secreted by the bacteria, the actin cytoskeleton in entry and the involvement of small GTPases. [source] Structural Investigation of the HIV-1 Envelope Glycoprotein gp160 Cleavage Site 3: Role of Site-Specific Mutations,CHEMBIOCHEM, Issue 12 2004Lucia Falcigno Dr. Abstract Proteolytic processing of HIV gp160 to produce gp120 and gp41 is performed by PC enzymes. This process is a prerequisite for the virus infectivity, since both gp120 and gp41 participate in the virus HIV-1 entry mechanism. The structure of the gp120/gp41 junction remains to be elucidated, and the structural features required for molecular recognition between HIV-1 gp160 and proteolytic enzymes have not been clarified. Furin is the best PC candidate for the gp160 proteolytic processing known to date. In previous studies on model peptides, we have shown the relevance of an N-terminal helix for the proper recognition of the gp160 processing site by furin. Here we analyze the effect of point mutations in peptides lacking a regular N-terminal helix. To this end, we present the structure,activity characterization of three peptide analogues of the HIV gp160 processing site that all present mutations in proline at positions P3 and/or P2,, while sharing the same N-terminal sequence, containing helix-breaking D -amino acids. Conformational analysis of the peptides was carried out in solution by NMR techniques, and furin's efficiency in cleaving them was measured. Structural findings are presented and discussed in relation to the different exhibited activity. [source] Mobile Construction Supply Chain Management Using PDA and Bar CodesCOMPUTER-AIDED CIVIL AND INFRASTRUCTURE ENGINEERING, Issue 4 2005H. Ping Tserng However, extending the construction project control system to job sites is not considered efficient because using notebooks in a harsh environment like a construction site is not particularly a conventional practice. Meanwhile, paper-based documents of the site processes are ineffective and cannot get the quick response from the office and project control center. Integrating promising information technologies such as personal digital assistants (PDA), bar code scanning, and data entry mechanisms, can be extremely useful in improving the effectiveness and convenience of information flow in construction supply chain control systems. Bar code scanning is appropriate for several construction applications, providing cost savings through increased speed and accuracy of data entry. This article demonstrates the effectiveness of a bar-code-enabled PDA application, called the mobile construction supply chain management (M-ConSCM) System, that responds efficiently and enhances the information flow between offices and sites in a construction supply chain environment. The advantage of the M-ConSCM system lies not only in improving the efficiency of work for on-site engineers, but also providing the Kanban-like visual control system for project participants to control the whole project. Moreover, this article presents a generic system architecture and its implementation. [source] Calcium influx mechanisms underlying calcium oscillations in rat hepatocytes,HEPATOLOGY, Issue 4 2008Bertina F. Jones The process of capacitative or store-operated Ca2+ entry has been extensively investigated, and recently two major molecular players in this process have been described. Stromal interacting molecule (STIM) 1 acts as a sensor for the level of Ca2+ stored in the endoplasmic reticulum, and Orai proteins constitute pore-forming subunits of the store-operated channels. Store-operated Ca2+ entry is readily demonstrated with protocols that provide extensive Ca2+ store depletion; however, the role of store-operated entry with modest and more physiological cell stimuli is less certain. Recent studies have addressed this question in cell lines; however, the role of store-operated entry during physiological activation of primary cells has not been extensively investigated, and there is little or no information on the roles of STIM and Orai proteins in primary cells. Also, the nature of the Ca2+ influx mechanism with hormone activation of hepatocytes is controversial. Hepatocytes respond to physiological levels of glycogenolytic hormones with well-characterized intracellular Ca2+ oscillations. In the current study, we have used both pharmacological tools and RNA interference (RNAi)-based techniques to investigate the role of store-operated channels in the maintenance of hormone-induced Ca2+ oscillations in rat hepatocytes. Pharmacological inhibitors of store-operated channels blocked thapsigargin-induced Ca2+ entry but only partially reduced the frequency of Ca2+ oscillations. Similarly, RNAi knockdown of STIM1 or Orai1 substantially reduced thapsigargin-induced calcium entry, and more modestly diminished the frequency of vasopressin-induced oscillations. Conclusion: Our findings establish that store-operated Ca2+ entry plays a role in the maintenance of agonist-induced oscillations in primary rat hepatocytes but indicate that other agonist-induced entry mechanisms must be involved to a significant extent. (HEPATOLOGY 2008.) [source] Cytoplasmic calcium oscillations and store-operated calcium influxTHE JOURNAL OF PHYSIOLOGY, Issue 13 2008James W. Putney Intracellular calcium oscillations have fascinated scientists for decades. They provide an important cellular signal which, unlike most signalling mechanisms, is digitally encoded. While it is generally agreed that oscillations most frequently arise from cyclical release and re-uptake of intracellularly stored calcium, it is becoming increasingly clear that influx of calcium across the plasma membrane also plays a critical role in their maintenance and even in delivering their signal to the correct cellular locus. In this review we will discuss the role played by Ca2+ entry mechanisms in Ca2+ oscillations, and approaches to understanding the molecular nature of this Ca2+ entry pathway. [source] | ||||||||||