Theory and Applications of X-ray Standing Waves in Real Crystals

Theoretical aspects of x-ray standing wave method for investigation of the real structure of crystals are considered in this review paper. Starting from the general approach of the secondary radiation yield from deformed crystals this theory is applied to different concreat cases. Various models of deformed crystals like: bicrystal model, multilayer model, crystals with extended deformation field are considered in detailes. Peculiarities of x-ray standing wave behavior in different scattering geometries (Bragg, Laue) are analysed in detailes. New possibilities to solve the phase problem with x-ray standing wave method are discussed in the review. General theoretical approaches are illustrated with a big number of experimental results.Comment: 101 pages, 43 figures, 3 table

Infinitive Wh-relatives in romance : consequences for the truncation-versus-intervention debate

Romance clitic left dislocation is widespread across all kinds of nonroot contexts, but it is forbidden in infinitive wh-relatives. This article investigates the extent and nature of this restriction and the consequences it raises for the truncation and intervention analyses of the left periphery of embedded sentences. We will show that current proposals cannot account for the whole gamut of data. In consequence, we will propose that infinitive wh-relatives display a maximally syncretic left periphery, whereas infinitive wh-interrogatives have a full-fledged left periphery, crucially involving ForceP, because they are selected by a higher predicate. This crucial difference between infinitive relatives and interrogatives will also be shown to be consistent with the existence of specialized complementizers for the former but not the latte

Affected Experiencers

Numerous languages permit an NP that is not selected by the verb to be added to a clause, with several different possible interpretations. We divide such non-selected arguments into possessor, benefactive, attitude holder, and affected experiencer categories, on the basis of syntactic and semantic differences between them. We propose a formal analysis of the affected experiencer construction. In our account, a syntactic head Aff(ect) introduces the experiencer argument, and adds a conventional implicature to the effect that any event of the type denoted by its syntactic sister is the source of the experiencer’s psychological experience. Hence, our proposal involves two tiers of meaning: the at-issue meaning of the sentence, and some not-at-issue meaning (an implicature). A syntactic head can introduce material on both tiers. Additionally, we allow two parameters of variation: (i) the height of the attachment of Aff, and (ii) how much of the semantics is at-issue and how much is an implicature. We show that these two parameters account for the attested variation across our sample of languages, as well as the significant commonalities among them. Our analysis also accounts for significant differences between affected experiencers and the other types of non-selected arguments, and we also note a generalization to the effect that purely not-at-issue non-selected arguments can only be weak or clitic pronouns

Identification of the Allosteric Regulatory Site of Insulysin

Background: Insulin degrading enzyme (IDE) is responsible for the metabolism of insulin and plays a role in clearance of the Ab peptide associated with Alzheimer's disease. Unlike most proteolytic enzymes, IDE, which consists of four structurally related domains and exists primarily as a dimer, exhibits allosteric kinetics, being activated by both small substrate peptides and polyphosphates such as ATP.Principal Findings: the crystal structure of a catalytically compromised mutant of IDE has electron density for peptide ligands bound at the active site in domain 1 and a distal site in domain 2. Mutating residues in the distal site eliminates allosteric kinetics and activation by a small peptide, as well as greatly reducing activation by ATP, demonstrating that this site plays a key role in allostery. Comparison of the peptide bound IDE structure (using a low activity E111F IDE mutant) with unliganded wild type IDE shows a change in the interface between two halves of the clamshell-like molecule, which may enhance enzyme activity by altering the equilibrium between closed and open conformations. in addition, changes in the dimer interface suggest a basis for communication between subunits.Conclusions/Significance: Our findings indicate that a region remote from the active site mediates allosteric activation of insulysin by peptides. Activation may involve a small conformational change that weakens the interface between two halves of the enzyme.United States Public Health ServicesUniv Kentucky, Dept Mol & Cellular Biochem, Lexington, KY 40536 USAUniv Kentucky, Struct Biol Ctr, Lexington, KY USAUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, Escola Paulista Med, São Paulo, BrazilUnited States Public Health Services: NS38041United States Public Health Services: DA02243United States Public Health Services: DA016176United States Public Health Services: P20 RR20171United States Public Health Services: T32 DA016176Web of Scienc

Human cell types important for Hepatitis C Virus replication in vivo and in vitro. Old assertions and current evidence

Hepatitis C Virus (HCV) is a single stranded RNA virus which produces negative strand RNA as a replicative intermediate. We analyzed 75 RT-PCR studies that tested for negative strand HCV RNA in liver and other human tissues. 85% of the studies that investigated extrahepatic replication of HCV found one or more samples positive for replicative RNA. Studies using in situ hybridization, immunofluorescence, immunohistochemistry, and quasispecies analysis also demonstrated the presence of replicating HCV in various extrahepatic human tissues, and provide evidence that HCV replicates in macrophages, B cells, T cells, and other extrahepatic tissues. We also analyzed both short term and long term in vitro systems used to culture HCV. These systems vary in their purposes and methods, but long term culturing of HCV in B cells, T cells, and other cell types has been used to analyze replication. It is therefore now possible to study HIV-HCV co-infections and HCV replication in vitro

Residential mobility of middle-class and popular sectors: the city of Buenos Aires as an arrival destination

El artículo reflexiona acerca de los patrones de movilidad residencial de individuos y hogares de sectores populares y medios que residen en dos zonas de la Ciudad de Buenos Aires configuradas en torno a patrones disimiles de segregación. La movilidad residencial es un lente privilegiado para evidenciar de qué modo la experiencia de la clase es producida y reproducida en los modos de habitar. Mediante un abordaje cualitativo y biográfico hemos analizado las especificidades que presentan las movilidades residenciales de los diferentes sectores sociales. Se identifican patrones en tres dimensiones de la movilidad residencial: su espacialidad, los arreglos residenciales que los hogares despliegan y las motivaciones que guían sus desplazamientos. Los hallazgos presentados dan cuenta de los efectos que produce la posición en la estructura social sobre la movilidad residencial, así como su interacción con la propia estructuración del espacio.The article reconstructs residential mobility patterns of individuals and households from popular and middle-class sectors residing in two areas of the city of Buenos Aires, configured around dissimilar segregation patterns. Residential mobility is a powerful lens to show how the social class experience is produced and reproduced in modes of dwelling. Through a qualitative and biographical approach, we analyzed the specificities presented by residential mobilities of different social sectors. We identified patterns in the three dimensions of residential mobility: spatiality, the residential arrangements that households employ, and the motivations that guide their movements. The findings show the effects that the position in the social structure has on residential mobility, as well as its interaction with the spatial structure itself.publishedVersionFil: Cosacov, Andrea. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina.Fil: Cosacov, Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones Biológicas; Argentina.Fil: Di Virgilio, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Gino Germani; Argentina.Fil: Najman, Mercedes. Universidad de Buenos Aires. Facultad de Ciencias Sociales; Argentina.Fil: Di Virgilio, María Mercedes. Universidad de Buenos Aires. Facultad de Ciencias Sociales; Argentina.Fil: Najman, Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigación Gino Germani; Argentina

Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner

Enveloped viruses need to fuse with a host cell membrane in order to deliver their genome into the host cell. While some viruses fuse with the plasma membrane, many viruses are endocytosed prior to fusion. Specific cues in the endosomal microenvironment induce conformational changes in the viral fusion proteins leading to viral and host membrane fusion. In the present study we investigated the entry of coronaviruses (CoVs). Using siRNA gene silencing, we found that proteins known to be important for late endosomal maturation and endosome-lysosome fusion profoundly promote infection of cells with mouse hepatitis coronavirus (MHV). Using recombinant MHVs expressing reporter genes as well as a novel, replication-independent fusion assay we confirmed the importance of clathrin-mediated endocytosis and demonstrated that trafficking of MHV to lysosomes is required for fusion and productive entry to occur. Nevertheless, MHV was shown to be less sensitive to perturbation of endosomal pH than vesicular stomatitis virus and influenza A virus, which fuse in early and late endosomes, respectively. Our results indicate that entry of MHV depends on proteolytic processing of its fusion protein S by lysosomal proteases. Fusion of MHV was severely inhibited by a pan-lysosomal protease inhibitor, while trafficking of MHV to lysosomes and processing by lysosomal proteases was no longer required when a furin cleavage site was introduced in the S protein immediately upstream of the fusion peptide. Also entry of feline CoV was shown to depend on trafficking to lysosomes and processing by lysosomal proteases. In contrast, MERS-CoV, which contains a minimal furin cleavage site just upstream of the fusion peptide, was negatively affected by inhibition of furin, but not of lysosomal proteases. We conclude that a proteolytic cleavage site in the CoV S protein directly upstream of the fusion peptide is an essential determinant of the intracellular site of fusion