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Solís de Mataojo, Uruguay

Tort L.F.L.,Oswaldo Cruz Institute FIOCRUZ | Volotao E.d.M.,Oswaldo Cruz Institute FIOCRUZ | de Mendonca M.C.L.,Oswaldo Cruz Institute FIOCRUZ | da Silva M.F.M.,Oswaldo Cruz Institute FIOCRUZ | And 6 more authors.
Journal of Clinical Virology

Background: Group A rotavirus (RV-A) genotype P[8]G9 has emerged as one of the leading causes of gastroenteritis in children worldwide and currently is recognized as one of the five most common genotypes detected in humans. High intragenotype diversity in G9 RV-A has been observed, and nowadays, based on the genetic variability of the VP7 gene, six different phylogenetic lineages and eleven sublineages were described. Objectives: To study the degree of genetic variation and evolution of Brazilian P[8]G9 RV-A strains. Study design: Phylogenetic analysis of 19 P[8]G9 RV-A strains isolated from 2004 to 2007 in five different Brazilian states was conducted using the NSP1, NSP3, NSP5, VP4 and VP7 genes. For the VP4 and VP7 genes, 3D protein structure predictions were generated to analyze the spatial distribution of amino acid substitutions observed in Brazilian strains. Results: Based on the phylogenetic analyses, all Brazilian strains clustered within lineage G9-III and P[8]-3 for VP7 and VP4, respectively, and were classified as genotype A1, T1 and H1 for the NSP1, NSP3 and NSP5 genes, respectively. Interestingly, all the strains isolated in Acre State (Northern Brazil) formed a closely related cluster clearly separated from the other Brazilian and prototype strains with regard to the five genes studied. Unique amino acid substitutions were observed in Acre strains in comparison with the prototype and Brazilian strains. Conclusion: Inclusion of Acre strains in the phylogenetic analysis revealed the presence of a novel genetic variant and demonstrated a diversification of P[8]G9 rotaviruses in Brazil. © 2010 Elsevier B.V. All rights reserved. Source

Santos-Nogueira E.,Autonomous University of Barcelona | Lopez-Serrano C.,Autonomous University of Barcelona | Hernandez J.,Autonomous University of Barcelona | Lago N.,Pasteur Institute of Montevideo | And 6 more authors.
Journal of Neuroscience

Lysophosphatidic acid (LPA) is an extracellular lipid mediator involved in many physiological functions that signals through six known G-protein-coupled receptors (LPA1–LPA6). A wide range of LPA effects have been identified in the CNS, including neural progenitor cell physiology, astrocyte and microglia activation, neuronal cell death, axonal retraction, and development of neuropathic pain. However, little is known about the involvement of LPA in CNS pathologies. Herein, we demonstrate for the first time that LPA signaling via LPA1 contributes to secondary damage after spinal cord injury. LPA levels increase in the contused spinal cord parenchyma during the first 14 d. To model this potential contribution of LPA in the spinal cord, we injected LPA into the normal spinal cord, revealing that LPA induces microglia/macrophage activation and demyelination. Use of a selective LPA1 antagonist or mice lacking LPA1 linked receptormediated signaling to demyelination, which was in part mediated by microglia. Finally, we demonstrate that selective blockade of LPA1 after spinal cord injury results in reduced demyelination and improvement in locomotor recovery. Overall, these results support LPA– LPA1 signaling as a novel pathway that contributes to secondary damage after spinal cord contusion in mice and suggest that LPA1 antagonism might be useful for the treatment of acute spinal cord injury. © 2015, the authors. Source

Berois N.,Pasteur Institute of Montevideo | Heard I.,Institute Pasteur Paris | Heard I.,University Pierre and Marie Curie | Fort Z.,Preventive Clinics | And 7 more authors.
Journal of Medical Virology

The aim of this work was to describe the prevalence of type-specific Human papillomavirus (HPV) infection in women attending organized cervical cancer screening program in Uruguay. Nine hundred sixty-five liquid cervical cell samples obtained after collection of cervical smears for cytology were assessed for HPV DNA using the Papillocheck system (Greiner BioOne). The overall prevalence of High-Risk (HR) HPV infections was 20.8% and increased from 16.5% in women with normal cytology to 93.3% in HSIL. Prevalence of HPV 16 and/or 18 was 6.3% and HPV 16 was the most prevalent genotype in normal cytology (3.6%). The five most prevalent genotypes were HPV 16, 31, 51, 56, and 39. The overall prevalence peaked below age 30. This study provides essential baseline information at national level on type-specific HPV prevalence in Uruguay before the introduction of HPV vaccination. It documents the current prevalence of each of the oncogenic genotypes in a population attending cervical cancer screening program, suggesting that at least 64.7% of high risk lesions are potentially preventable by available HPV vaccines, and possibly augmentable if cross-protection against non-vaccine HPV types 31, 33, and 45 is confirmed. © 2013 Wiley Periodicals, Inc. Source

Robles A.,University of the Republic of Uruguay | Medeiros A.,University of the Republic of Uruguay | Berois N.,Pasteur Institute of Montevideo | Balter H.S.,University of the Republic of Uruguay | And 3 more authors.
Nuclear Medicine and Biology

The tumor-associated structure N-acetyl-galactosamine-O-Ser/Thr (Tn antigen), which is overexpressed in various tumor cell types, notably of the breast, ovary and colon, is an interesting determinant that is useful for cancer diagnosis and follow-up. The aim of this research was to study different assay strategies in order to determine the most sensitive system for further application in epitope characterization and binding assessment. The tetrameric isolectin obtained from Vicia villosa seeds (VVLB4) shows high affinity for the tumor-associated structure. A monoclonal antibody against VVLB4, MabVV34, was generated, and the interaction between MabVV34 and VVLB4 was studied by means of binding and inhibition assays. Several synthetic peptides (10 amino acid sequences) designed from the amino acid sequence of VVLB4 and obtained from trypsin digestion were tested to determine which amino acids were involved in the interaction between MabVV34 and VVLB4. The further unraveling of this epitope was investigated by inhibition using designed synthetic peptides as well as mixtures mimicking variable density effect. Under the experimental circumstances, MabVV34 was able to inhibit the binding of VVLB4 to Tn. Two of the four peptide sequences assayed showed better inhibition properties. Finally, mixtures containing these selected sequences allowed the evaluation of binding and inhibition as a function of Tn density. We conclude that the present study facilitates the further development of a specific Tn marker and may contribute to the development of Tn-like radiolabelled peptides or Tn-specific radiolabelled fragments providing a highly selective tool for cancer diagnosis and treatment. This strategy may contribute to characterize the new generation of radiopharmaceuticals for diagnosis and therapy based on biomolecules like antibodies, fragments or peptides, whose application is directly guided by their specific molecular recognition. © 2010. Source

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