178 research outputs found
Different levels of variability in subtypes 1b and 4a of hepatitis C viruses
No full textWe performed genetic and phenic analyses to evaluate nucleotide and amino-acid sequences of the amino-terminus of the E1 protein of HCV genotype 1b (extracted from databank) and 4a (characterised in this study). The non-synonymous (ka) mutation analysis demonstrated that the genome of genotype 1b was not saturated by variations, with a rate of transition/transversion (s/v) of 1.5, which is similar to the expected ratio (i.e., 2.0). The s/v ratio in genotype 4a isolates was lower (0.98), indicating saturation due long-term variability. Moreover, the genotype 1b sequences showed a higher number of ka mutations (s+v) (mean of 2.8 per sequence) than genotype 4a (mean of 1.5). The introduction of ka mutations resulted in a higher degree of amino acid variability in genotype 4a. In the genome of genotype 1b, each nucleotide mutation introduced new amino acids, with a Granthan distance of 3.35-42.5, whereas for genotype 4a the distances ranged from 48.8 to 102.1. The phenic analysis also indicated different and complex patterns of amino-acid substitution. Finally, diverse isoelectric points and hydrophobicity were predicted for the two genotypes, with a higher acidity for genotype 4a E1 proteins
Strutture di informazione geospaziale e processi di conoscenza per l'identificazione della connettività ecosistemica potenziale
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Lack of WHV integration nearby N-myc2 and in the downstream b3n and win loci in a considerable fraction of liver tumors with activated N-myc2 from naturally infected wild woodchucks
No full textIn liver tumors induced by chronic WHV infection in the WHV/woodchuck model of HBV infection, activation of genes of the myc family by WHV insertion has been well documented. Several studies have shown that N-myc2 is by far the most frequently involved, and in most cases, its transcriptional activation is due to WHV insertion nearby the gene. N-myc2 has been shown to be also activated by WHV insertion in two downstream loci, b3n and win. Although the extent of insertion in these latter loci in woodchuck tumors has not been investigated, their discovery has led to the notion that therein WHV insertion accounts for N-myc2 activation in the remaining tumors expressing the proto-oncogene in absence of any detectable alteration nearby the gene, a notion remained unproved and not further investigated yet. In the majority of cases, the above observations were derived from tumors developed in colony born laboratory bred woodchucks experimentally infected with standardized viral inocula, mostly of the same lineage. In the present work, we investigated a survey of liver tumors naturally developed in wild woodchucks with naturally acquired chronic WHV infection. Tumors had histological features of well to moderately differentiated HCCs. In most animals, multiple tumor nodules were observed; in the great majority of cases, they were shown to be independent tumors because their WHV integration patterns were not clonally related. 53 independent tumors were investigated for N-myc activation and WHV integration nearby N-myc genes and in the b3n and win loci. Comparison of our results with data from previous studies revealed that, in tumors from naturally infected wild woodchucks, the frequency of WHV integration nearby N-myc2 has a tendency to be lower and, in addition, N-myc2 activation is due to WHV integration nearby the gene significantly less frequently than in tumors from experimentally infected colony born animals (12/28, 43% vs. 15/20, 75%, P = 0.0397). These findings are likely related to the less uniform conditions as to infecting virus and host genetic background in naturally infected wild woodchucks with respect to experimentally infected colony born woodchucks and suggest that viral and/or host factors may influence the site of viral insertion finally detected in overt tumors. In addition, more than one third (11/28, 39%) tumors with activated N-myc2 transcription did not show rearrangement either nearby the gene, or in b3n or in win. These findings challenge the notion that integration in the downstream b3n and win loci is responsible for N-myc2 activation in tumors lacking insertion nearby N-myc2 and suggest that in a considerable fraction of liver tumors, at least from wild woodchucks, N-myc2 activation might be due either to WHV integration in further regions of the N-myc2 chromosomal domain or to other mechanisms related or unrelated to viral insertion
Molecular epidemiology of hepatitis C virus genotype 4 isolates in Egypt and analysis of the variability of envelope proteins E1 and E2 in patients with chronic hepatitis
No full textWe analyzed hepatitis C virus (HCV) genotype 4 isolates circulating in the Alexandria District (Egypt) in terms of genetic divergence and the presence of different subtypes. Hypervariable region 1 (HVR1) and the NH2 region of the E2 protein were characterized, and the heterogeneity of subtype 4a isolates was evaluated by analyzing epitope frequencies, immunoproteasome prediction, and possible glycosylation patterns. The heterogeneity of the nucleotide sequences was greater than that found in previous studies, which reported only subtype 4a. Subtype 4a was most common (78% of cases), yet four new subtypes were found, with subtype 4m representing 11% of the cases and the other three subtypes representing another 11%. Substantial heterogeneity was also found when the intrasubtype 4a sequences were analyzed. Differences in the probability of glycosylation and in the positions of the different sites were also observed. The analysis of the predicted cytotoxic T-lymphocyte epitopes showed differences in both the potential proteosome cleavage and the prediction score. The Egyptian isolates in our study also showed high variability in terms of the HVR1 neutralization epitope. Five of these isolates showed amino acid substitutions never previously observed (a total of six positions). Four of these residues (in four different isolates) were in positions involved in anchoring to the E2 glycoprotein core and in maintaining the HVR1 conformation. The results of this study indicate that HCV genotype 4 in Egypt is extremely variable, not only in terms of sequence, but also in terms of functional and immunological determinants. These data should be taken into account in planning the development of vaccine trials in Egypt
Hepatitis B, C and Delta virus infections in Albanian patients with chronic liver disease: evaluation of possible changes during the last 10 years
No full textImmunization of woodchucks with adjuvanted sHDAg (p24): immune response and outcome following challenge
No full textThe immunogenicity and the protection induced by an hepatitis delta virus (HDV) vaccine consisting of the small nucleoprotein (HDAg) (p24) and adjuvanted with MF59 or Freund's adjuvant (FA) were evaluated in woodchucks chronically infected with woodchuck hepatitis virus (WHV) and challenged with hepatitis delta virus. Humoral and T-cell-mediated responses to HDAg were measured. Anti-HD antibodies appeared earlier in the FA/p24 animals. After challenge, all MF59/p24 vaccinated animals showed a response to HDAg-derived peptides, compared to two of the five FA/p24 animals and one of the control animals. Serum HDV-RNA peak values and persistence were considerably reduced in immunized animals, in comparison to controls. Furthermore, HDV-RNA was absent in autopsy liver tissues of 50% of the MF59/p24 animals, whereas high levels were present in all of the FA/p24 animals and controls. Histological liver analysis performed before and after challenge revealed the presence of acute hepatitis-like lesions only in the controls. Overall, the results suggest that the MF59/p24 vaccine better controls the infection in terms of viral replication and survival. © 2003 Elsevier Ltd. All rights reserved
Load-Carrying Capacity Improvement and Seismic Upgrading of a 1914 Riveted Steel Bridge
No full textThis paper describes the analyses carried out to evaluate and improve the load-bearing capacity of an old riveted steel bridge located in the Province of Perugia, in the central part of Italy. The bridge was designed and constructed between 1914 and 1918 to carry pedestrian and light vehicle loads,
well below the current transportation requirements. It is composed of two steel spans with three continuous truss
beams and of three masonry arches with an overall length of 116 m. The metallic part of the bridge rests on two
unreinforced concrete abutments and on a pier, also made of unreinforced concrete, built inside the Tiber riverbed.
A detailed study of the assemblage of the riveted steel elements put in evidence instability problems that had caused a partial buckling in a lower chord close to the inner support.
Furthermore, the actual support system, composed of fixed bearings on the central pier and longitudinal sliding bearings on the abutments, concentrates the longitudinal seismic forces on the central pier which is unable to carry relevant horizontal loads. In this paper, the works carried out to increase the admissible traffic load and those to improve the
behaviour of the bridge under seismic actions are briefly described
Exposure to foodborne and orofecal microbes versus airborne viruses in relation to atopy and allergic asthma: epidemiological study
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