135 research outputs found
Evidence of viral adaptation to HLA class I-restricted immune pressure in chronic hepatitis C virus infection
No full textCellular immune responses are an important correlate of hepatitis C virus (HCV) infection outcome. These responses are governed by the host's human leukocyte antigen (HLA) type, and HLA-restricted viral escape mutants are a critical aspect of this host-virus interaction. We examined the driving forces of HCV evolution by characterizing the in vivo selective pressure(s) exerted on single amino acid residues within nonstructural protein 3 (NS3) by the HLA types present in two host populations. Associations between polymorphisms within NS3 and HLA class I alleles were assessed in 118 individuals from Western Australia and Switzerland with chronic hepatitis C infection, of whom 82 (69%) were coinfected with human immunodeficiency virus. The levels and locations of amino acid polymorphisms exhibited within NS3 were remarkably similar between the two cohorts and revealed regions under functional constraint and selective pressures. We identified specific HCV mutations within and flanking published epitopes with the correct HLA restriction and predicted escaped amino acid. Additional HLA-restricted mutations were identified that mark putative epitopes targeted by cell-mediated immune responses. This analysis of host-virus interaction reveals evidence of HCV adaptation to HLA class I-restricted immune pressure and identifies in vivo targets of cellular immune responses at the population level
Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity
No full textCellular immune responses during acute Hepatitis C virus (HCV) and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s) within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%). The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design
EU-Projekt : europäische Autofahrer und Verkehrssicherheit ; Befragungsergebnisse im Zeitvergleich
No full textDer Autor berichtet über den Stand und erste Auswertungen zum EU-Projekt "Soziale Einstellungen zum Straßenverkehrsrisiko in Europa" ("SARTRE 2"). Hierbei handelt es sich um eine Wiederholungsbefragung von Autofahrern in fast allen Ländern der EU und einigen weiteren Ländern.The author reports on the status of and the initial evaluations from the EU project "Social Attitudes on Road Traffic Risks in Europe" ("SARTRE 2"). This project consists of the repeat polling of car drivers in practically all the countries in the EU as well as in a number of other countries
Beneficial effect of thrombusaspiration in patients with STEMI - Results from the FITT-STEMI multicenter trial
No full textBeneficial effect of thrombusaspiration in patients with STEMI - Results from the FITT-STEMI multicenter trial
No full textFull-length characterization of hepatitis C virus subtype 3a reveals novel hypervariable regions under positive selection during acute infection.
No full textHepatitis C virus subtype 3a is a highly prevalent and globally distributed strain that is often associated with infection via injection drug use. This subtype exhibits particular phenotypic characteristics. In spite of this, detailed genetic analysis of this subtype has rarely been performed. We performed full-length viral sequence analysis in 18 patients with chronic HCV subtype 3a infection and assessed genomic viral variability in comparison to other HCV subtypes. Two novel regions of intragenotypic hypervariability within the envelope protein E2, of HCV genotype 3a, were identified. We named these regions HVR495 and HVR575. They consisted of flanking conserved hydrophobic amino acids and central variable residues. A 5-amino-acid insertion found only in genotype 3a and a putative glycosylation site is contained within HVR575. Evolutionary analysis of E2 showed that positively selected sites within genotype 3a infection were largely restricted to HVR1, HVR495, and HVR575. Further analysis of clonal viral populations within single hosts showed that viral variation within HVR495 and HVR575 were subject to intrahost positive selecting forces. Longitudinal analysis of four patients with acute HCV subtype 3a infection sampled at multiple time points showed that positively selected mutations within HVR495 and HVR575 arose early during primary infection. HVR495 and HVR575 were not present in HCV subtypes 1a, 1b, 2a, or 6a. Some variability that was not subject to positive selection was present in subtype 4a HVR575. Further defining the functional significance of these regions may have important implications for genotype 3a E2 virus-receptor interactions and for vaccine studies that aim to induce cross-reactive anti-E2 antibodies
The maintenance of adult but dependent offspring
No full textMini Dissertation (LLM)--University of Pretoria, 2019.Parenthood automatically gives rise to the obligation of a parent to support his or her child. This common-law duty arises upon the birth of a child and it is furthermore provided for in the Maintenance Act.
The Maintenance Act addresses the maintenance of both minor and major offspring. The problem, however, arises when a study of the practical execution of this right is conducted. This dissertation specifically focuses on the practicality in respect of major/adult dependent ‘children’.
This dissertation examines the laws that enact the common-law duty and the right to support. A study of how the courts have interpreted the law and directed the enforcement of this right for major/adult dependent children/offspring reveals the impracticality of the prescribed enforcement methods and a failure to understand this group’s particular needs.
This study explores alternative approaches to implementing the right of adult dependent offspring to maintenance and offers solutions to the limitations that are revealed.NONEPrivate LawLLM Child LawUnrestricte
Hemorheological Changes in Patients with Cerebral Ischemia: Differences in Comparison with Other Vascular Disorders
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THE RHEOSCOPE: A MICRORHEOLOGIC TECHNIQUE FOR DIRECT OBSER- VATION OP IN VITRO FLOW BEHAVIOR OP RED BLOOD CELLS (RBC)
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