Protective Effect of HLA-DRB1*11 and Predisposition of HLA-C*04 in the Development of Severe Liver Damage in Brazilian Patients with Chronic Hepatitis C Virus Infection

The objective of this study was to investigate human leucocyte antigen (HLA) genes in patients chronically infected with hepatitis C virus (HCV) and to analyse the possible role of these genes in the progression of chronic hepatitis C. One hundred and forty-five (145) Brazilian patients infected only with HCV genotype 1 were evaluated. HLA class I (A*, B*, C*) and class II (DRB1*, DQA1*, DQB1*) typing were carried out by PCR-SSO, through Luminex technology. Associations were found with protection against development of liver damage by both DRB1*11 (5.0% versus 18.2%, P = 0.0016, OR = 0.23, CI 95% = 0.090.58; Pc=0.0208) and DRB1*11-DQA1*05-DQB1*03 haplotype (4.2% versus 15.3%, P = 0.0032; OR = 0.24, CI 95% = 0.08-0.64). Liver damage was associated with HLA-C*04 in patients with <20 years of infection (38.4% versus 9.1%, P = 0.002, OR = 6.25, CI 95% = 1.9719.7; Pc=0.0238). It is concluded that HLA alleles can influence the development of liver damage in HCV type-1 chronically infected Brazilian patients.

Crystal structure of a novel myotoxic Arg49 phospholipase A(2) homolog (zhaoermiatoxin) from Zhaoermia mangshanensis snake venom: Insights into Arg49 coordination and the role of Lys122 in the polarization of the C-terminus

The venom of Zhaoermia mangshanensis, encountered solely in Mt Mang in China's Hunan Province, exhibits coagulant, phosphodiesterase, L-amino acid oxidase, kallikrein, phospholipase A(2) and myotoxic activities. The catalytically inactive PLA(2) homolog referred to as zhaoermiatoxin is highly myotoxic and displays high myonecrotic and edema activities. Zhaoermiatoxin possesses a molecular weight of 13,972 Da, consists of 121 amino-acid residues crosslinked by seven disulfide bridges and shares high sequence homology with Lys49-PLA(2)s from the distantly related Asian pitvipers. However, zhaoermiatoxin possesses an arginine residue at position 49 instead of a lysine, thereby suggesting a secondary Lys49 -> Arg substitution which results in a catalytically inactive protein. We have determined the first crystal structure of zhaoermiatoxin, an Arg49-PLA(2), from Zhaoermia mangshanensis venom at 2.05 A resolution, which represents a novel member of phospholipase A(2) family. In this structure, unlike the Lys49 PLA(2)s, the C-terminus is well ordered and an unexpected non-polarized state of the putative calcium-binding loop due to the flip of Lys122 towards the bulk solvent is observed. The orientation of the Arg-49 side chain results in a similar binding mode to that observed in the Lys49 PLA(2)s; however, the guadinidium group is tri-coordinated by carbonyl oxygen atoms of the putative calcium-binding loop, whereas the N zeta atom of lysine is tetra-coordinated as a result of the different conformation adopted by the putative calcium-binding loop. (c) 2008 Elsevier Ltd. All rights reserved.

Precision measurements of the ∧c + and D0 lifetimes

A measurement technique of charm baryons lifetimes from hadro-production data was presented. The measurement verified the lifetime analysis procedure in a sample with higher statistical precision. Other effects studied include mass reflections; effects of the presence of a second charm particle; and mismeasurement of charm decays. Monte carlo simulations were used for the detailed study of systematic effects using the charm data.

Immunization of Balb/c mice with modified auto-antigens for induction of autoimmune sialoadenitis

Sjögren's syndrome is an autoimmune disease characterized by sialoadenitis and elevated titers of autoantibodies. To assess whether it is possible to induce inflammatory changes in salivary gland tissues, a series of immunizations in Balb/c mice have been undertaken, using salivary gland extract, modified or not, added to several adjuvants. Mice's humoral immune response to salivary gland antigens was monitored by ELISA. Inflammatory cells infiltrating gland tissue were seen 3 months after immunization with salivary gland extract modified with pepsin (AgGp) and metaperiodate (AgGMp). Although pathological progression was not observed, the histopathological picture was similar to the initial phase of Sjögren's syndrome. In addition, a monoclonal antibody reactive with 3 gland polypeptides and anhydrase carbonic II was rescued among B cells from immunized mice. Thus, immunizations with modified autoantigens were able to initiate pathological damage to glandular tissue and stimulate the proliferation of auto-reactive B cells.

Meiotic pairing of B chromosomes, multiple sexual system, and Robertsonian fusion in the red brocket deer Mazama americana (Mammalia, Cervidae)

Deer species of the genus Mazama show significant inter and intraspecific chromosomal variation due to the occurrence of rearrangements and B chromosomes. Given that carriers of aneuploidies and structural rearrangements often show anomalous chromosome pairings, we here performed a synaptonemal complex analysis to study chromosome pairing behavior in a red brocket deer (Mazama americana) individual that is heterozygous for a Robertsonian translocation, is a B chromosome carrier, and has a multiple sex chromosome system (XY1Y2). The synaptonemal complex in spermatocytes showed normal chromosome pairings for all chromosomes, including the autosomal and sex trivalents. The electromicrographs showed homology among B chromosomes since they formed bivalents, but they also appeared as univalents, indicating their anomalous behavior and non-Mendelian segregation. Thus, synaptonemal complex analysis is a useful tool to evaluate the role of B chromosomes and rearrangements during meiosis on the intraspecific chromosomal variation that is observed in the majority of Mazama species. © FUNPEC-RP.

Ion beam analysis of a-C:H films on alloy steel substrate

An a-C:H thin film deposited by plasma immersion ion implantation and deposition on alloy steel (16MnCr5) was analyzed using a self-consistent ion beam analysis technique.In the self-consistent analysis, the results of each individual technique are combined in a unique model, increasing confidence and reducing simulation errors.Self-consistent analysis, then, is able to improve the regular ion beam analysis since several analyses commonly used to process ion beam data still rely on handling each spectrum independently.The sample was analyzed by particle-induced x-ray emission (for trace elements), elastic backscattering spectrometry (for carbon), forward recoil spectrometry (for hydrogen) and Rutherford backscattering spectrometry (for film morphology).The self-consistent analysis provided reliable chemical information about the film, despite its heavy substrate.As a result, we could determine precisely the H/C ratio, contaminant concentration and some morphological characteristics of the film, such as roughness and discontinuities.© 2013 Elsevier B.V.All rights reserved.

Isolation, homology modeling and renal effects of a C-type natriuretic peptide from the venom of the Brazilian yellow scorpion (Tityus serrulatus)

Mammalian natriuretic peptides (NPs) have been extensively investigated for use as therapeutic agents in the treatment of cardiovascular diseases. Here, we describe the isolation, sequencing and tridimensional homology modeling of the first C-type natriuretic peptide isolated from scorpion venom. In addition, its effects on the renal function of rats and on the mRNA expression of natriuretic peptide receptors in the kidneys are delineated. Fractionation of Tityusserrulatus venom using chromatographic techniques yielded a peptide with a molecular mass of 2190.64Da, which exhibited the pattern of disulfide bridges that is characteristic of a C-type NP (TsNP, T. serrulatus Natriuretic Peptide). In the isolated perfused rat kidney assay, treatment with two concentrations of TsNP (0.03 and 0.1μg/mL) increased the perfusion pressure, glomerular filtration rate and urinary flow. After 60min of treatment at both concentrations, the percentages of sodium, potassium and chloride transport were decreased, and the urinary cGMP concentration was elevated. Natriuretic peptide receptor-A (NPR-A) mRNA expression was down regulated in the kidneys treated with both concentrations of TsNP, whereas NPR-B, NPR-C and CG-C mRNAs were up regulated at the 0.1μg/mL concentration. In conclusion, this work describes the isolation and modeling of the first natriuretic peptide isolated from scorpion venom. In addition, examinations of the renal actions of TsNP indicate that its effects may be related to the activation of NPR-B, NPR-C and GC-C. © 2013 Elsevier Ltd.

O A.B.C. de Lima Barreto (1916-1922)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Identification of b-quark jets with the CMS experiment

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Vertical transmission of hepatitis C virus: A tale of multiple outcomes

Globally, hepatitis C virus (HCV) infection affects approximately 130 million people and 3 million new infections occur annually. HCV is also recognized as an important cause of chronic liver disease in children. The absence of proofreading properties of the HCV RNA polymerase leads to a highly error prone replication process, allowing HCV to escape host immune response. The adaptive nature of HCV evolution dictates the outcome of the disease in many ways. Here, we investigated the molecular evolution of HCV in three unrelated children who acquired chronic HCV infection as a result of mother-to-child transmission, two of whom were also coinfected with HIV-1. The persistence of discrete HCV variants and their population structure were assessed using median joining network and Bayesian approaches. While patterns of viral evolution clearly differed between subjects, immune system dysfunction related to HIV coinfection or persistent HCV seronegativity stand as potential mechanisms to explain the lack of molecular evolution observed in these three cases. In contrast, treatment of HCV infection with PegIFN, which did not lead to sustained virologic responses in all 3 cases, was not associated with commensurate variations in the complexity of the variant spectrum. Finally, the differences in the degree of divergence suggest that the mode of transmission of the virus was not the main factor driving viral evolution. (C) 2013 Elsevier B. V. All rights reserved.

Impact of Quantity of Resin, C-factor, and Geometry on Resin Composite Polymerization Shrinkage Stress in Class V Restorations

Objective: This study evaluated the effect of quantity of resin composite, C-factor, and geometry in Class V restorations on shrinkage stress after bulk fill insertion of resin using two-dimensional finite element analysis.Methods: An image of a buccolingual longitudinal plane in the middle of an upper first premolar and supporting tissues was used for modeling 10 groups: cylindrical cavity, erosion, and abfraction lesions with the same C-factor (1.57), a second cylindrical cavity and abfraction lesion with the same quantity of resin (QR) as the erosion lesion, and then all repeated with a bevel on the occlusal cavosurface angle. The 10 groups were imported into Ansys 13.0 for two-dimensional finite element analysis. The mesh was built with 30,000 triangle and square elements of 0.1 mm in length for all the models. All materials were considered isotropic, homogeneous, elastic, and linear, and the resin composite shrinkage was simulated by thermal analogy. The maximum principal (MPS) and von Mises stresses (VMS) were analyzed for comparing the behavior of the groups.Results: Different values of angles for the cavosurface margin in enamel and dentin were obtained for all groups and the higher the angle, the lower the stress concentration. When the groups with the same C-factor and QR were compared, the erosion shape cavity showed the highest MPS and VMS values, and abfraction shape, the lowest. A cavosurface bevel decreased the stress values on the occlusal margin. The geometry factor overcame the effects of C-factor and QR in some situations.Conclusion: Within the limitations of the current methodology, it is possible to conclude that the combination of all variables studied influences the stress, but the geometry is the most important factor to be considered by the operator.

Common Descent of B Chromosomes in Two Species of the Fish Genus Prochilodus (Characiformes, Prochilodontidae)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

The effects of the C-terminal amidation of mastoparans on their biological actions and interactions with membrane-mimetic systems

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)