B cell and/or autoantibody deficiency do not prevent neuropsychiatric disease in murine systemic lupus erythematosus

Background: Neuropsychiatric lupus (NPSLE) can be one of the earliest clinical manifestations in human lupus. However, its mechanisms are not fully understood. In lupus, a compromised blood-brain barrier may allow for the passage of circulating autoantibodies into the brain, where they can induce neuropsychiatric abnormalities including depression-like behavior and cognitive abnormalities. The purpose of this study was to determine the role of B cells and/or autoantibodies in the pathogenesis of murine NPSLE. Methods: We evaluated neuropsychiatric manifestations, brain pathology, and cytokine expression in constitutively (JhD/MRL/lpr) and conditionally (hCD20-DTA/MRL/lpr, inducible by tamoxifen) B cell-depleted mice as compared to MRL/lpr lupus mice. Results: We found that autoantibody levels were negligible (JhD/MRL/lpr) or significantly reduced (hCD20-DTA/MRL/lpr) in the serum and cerebrospinal fluid, respectively. Nevertheless, both JhD/MRL/lpr and hCD20-DTA/MRL/lpr mice showed profound depression-like behavior, which was no different from MRL/lpr mice. Cognitive deficits were also observed in both JhD/MRL/lpr and hCD20-DTA/MRL/lpr mice, similar to those exhibited by MRL/lpr mice. Furthermore, although some differences were dependent on the timing of depletion, central features of NPSLE in the MRL/lpr strain including increased blood-brain barrier permeability, brain cell apoptosis, and upregulated cytokine expression persisted in B cell-deficient and B cell-depleted mice. Conclusions: Our study surprisingly found that B cells and/or autoantibodies are not required for key features of neuropsychiatric disease in murine NPSLE

Colorectal carcinomas with microsatellite instability display a different pattern of target gene mutations according to large bowel site of origin

<p>Abstract</p> <p>Background</p> <p>Only a few studies have addressed the molecular pathways specifically involved in carcinogenesis of the distal colon and rectum. We aimed to identify potential differences among genetic alterations in distal colon and rectal carcinomas as compared to cancers arising elsewhere in the large bowel.</p> <p>Methods</p> <p>Constitutional and tumor DNA from a test series of 37 patients with rectal and 25 patients with sigmoid carcinomas, previously analyzed for microsatellite instability (MSI), was studied for <it>BAX</it>, <it>IGF2R</it>, <it>TGFBR2</it>, <it>MSH3</it>, and <it>MSH6 </it>microsatellite sequence alterations, <it>BRAF </it>and <it>KRAS </it>mutations, and <it>MLH1 </it>promoter methylation. The findings were then compared with those of an independent validation series consisting of 36 MSI-H carcinomas with origin from each of the large bowel regions. Immunohistochemical and germline mutation analyses of the mismatch repair system were performed when appropriate.</p> <p>Results</p> <p>In the test series, <it>IGFR2 </it>and <it>BAX </it>mutations were present in one and two out of the six distal MSI-H carcinomas, respectively, and no mutations were detected in <it>TGFBR2</it>, <it>MSH3</it>, and <it>MSH6</it>. We confirmed these findings in the validation series, with <it>TGFBR2 </it>and <it>MSH3 </it>microsatellite mutations occurring less frequently in MSI-H rectal and sigmoid carcinomas than in MSI-H colon carcinomas elsewhere (<it>P </it>= 0.00005 and <it>P </it>= 0.0000005, respectively, when considering all MSI-carcinomas of both series). No <it>MLH1 </it>promoter methylation was observed in the MSI-H rectal and sigmoid carcinomas of both series, as compared to 53% found in MSI-H carcinomas from other locations (<it>P </it>= 0.004). <it>KRAS </it>and <it>BRAF </it>mutational frequencies were 19% and 43% in proximal carcinomas and 25% and 17% in rectal/sigmoid carcinomas, respectively.</p> <p>Conclusion</p> <p>The mechanism and the pattern of genetic changes driving MSI-H carcinogenesis in distal colon and rectum appears to differ from that occurring elsewhere in the colon and further investigation is warranted both in patients with sporadic or hereditary disease.</p

Mosaic Origins of a Complex Chimeric Mitochondrial Gene in Silene vulgaris

Chimeric genes are significant sources of evolutionary innovation that are normally created when portions of two or more protein coding regions fuse to form a new open reading frame. In plant mitochondria astonishingly high numbers of different novel chimeric genes have been reported, where they are generated through processes of rearrangement and recombination. Nonetheless, because most studies do not find or report nucleotide variation within the same chimeric gene, evolution after the origination of these chimeric genes remains unstudied. Here we identify two alleles of a complex chimera in Silene vulgaris that are divergent in nucleotide sequence, genomic position relative to other mitochondrial genes, and expression patterns. Structural patterns suggest a history partially influenced by gene conversion between the chimeric gene and functional copies of subunit 1 of the mitochondrial ATP synthase gene (atp1). We identified small repeat structures within the chimeras that are likely recombination sites allowing generation of the chimera. These results establish the potential for chimeric gene divergence in different plant mitochondrial lineages within the same species. This result contrasts with the absence of diversity within mitochondrial chimeras found in crop species

Influência da dependência energética de dosímetros termoluminescentes na medida da dose na entrada da pele em procedimentos radiográficos Influence of thermoluminescent dosimeters energy dependence on the measurement of entrance skin dose in radiographic procedures

OBJETIVO: O objetivo do presente trabalho foi avaliar a influência da dependência energética de materiais termoluminescentes na determinação da dose na entrada da pele de pacientes submetidos a exames radiográficos (radiologia geral, mamografia e radiologia odontológica). MATERIAIS E MÉTODOS: Três diferentes materiais termoluminescentes foram utilizados: LiF:Mg,Ti, LiF:Mg,Cu,P e CaSO4:Dy. Estes materiais foram expostos a fontes padronizadas de radiação X e gama, e a feixes clínicos de raios X. RESULTADOS: As curvas de calibração e de dependência energética foram obtidas. Todos os materiais apresentaram resposta linear em função do kerma no ar. Com relação à dependência energética, as amostras de CaSO4:Dy e LiF:Mg,Ti mostraram maior variação da resposta termoluminescente em função da energia efetiva do feixe de radiação. CONCLUSÃO: Os materiais testados mostraram desempenho adequado para a detecção da radiação X em feixes padronizados e clínicos. Embora as amostras de CaSO4:Dy e LiF:Mg,Ti apresentem dependência energética significativa no intervalo de energia considerado, este materiais podem ser utilizados para medição da dose de entrada na pele se fatores de correção apropriados forem utilizados.<br>OBJECTIVE: This study was aimed at evaluating the influence of the energy dependence of thermoluminescent materials on the determination of entrance skin dose in patients submitted to conventional radiographic studies (general radiology, mammography and dental radiology). MATERIALS AND METHODS: Three different thermoluminescent materials were utilized: LiF:Mg,Ti, LiF:Mg,Cu,P and CaSO4:Dy. These materials were exposed to standardized sources of X and gamma radiation and clinical X-ray beams. RESULTS: Calibration and energy dependence curves were obtained. All the materials showed a linear response as a function of the air kerma. As far as energy dependence is concerned, the CaSO4:Dy and LiF:Mg,Ti samples showed the greatest variation on thermoluminescent responses as a function of the effective radiation beam. CONCLUSION: The tested materials showed an appropriate performance for detecting X radiation on standard and clinical X-ray beams. Although CaSO4:Dy and LiF:Mg,Ti samples present a significant energy dependence in the considered energy range, these materials can be utilized for measuring entrance skin doses, provided appropriate correction factors are applied