Nuclear Factor-Kappa B Family Member RelB Inhibits Human Immunodeficiency Virus-1 Tat-Induced Tumor Necrosis Factor-Alpha Production

Human Immunodeficiency Virus-1 (HIV-1)-associated neurocognitive disorder (HAND) is likely neuroinflammatory in origin, believed to be triggered by inflammatory and oxidative stress responses to cytokines and HIV protein gene products such as the HIV transactivator of transcription (Tat). Here we demonstrate increased messenger RNA for nuclear factor-kappa B (NF-κB) family member, transcription factor RelB, in the brain of doxycycline-induced Tat transgenic mice, and increased RelB synthesis in Tat-exposed microglial cells. Since genetic ablation of RelB in mice leads to multi-organ inflammation, we hypothesized that Tat-induced, newly synthesized RelB inhibits cytokine production by microglial cells, possibly through the formation of transcriptionally inactive RelB/RelA complexes. Indeed, tumor necrosis factor-alpha (TNFα) production in monocytes isolated from RelB deficient mice was significantly higher than in monocytes isolated from RelB expressing controls. Moreover, RelB overexpression in microglial cells inhibited Tat-induced TNFα synthesis in a manner that involved transcriptional repression of the TNFα promoter, and increased phosphorylation of RelA at serine 276, a prerequisite for increased RelB/RelA protein interactions. The Rel-homology-domain within RelB was necessary for this interaction. Overexpression of RelA itself, in turn, significantly increased TNFα promoter activity, an effect that was completely blocked by RelB overexpression. We conclude that RelB regulates TNFα cytokine synthesis by competitive interference binding with RelA, which leads to downregulation of TNFα production. Moreover, because Tat activates both RelB and TNFα in microglia, and because Tat induces inflammatory TNFα synthesis via NF-κB, we posit that RelB serves as a cryoprotective, anti-inflammatory, counter-regulatory mechanism for pathogenic NF-κB activation. These findings identify a novel regulatory pathway for controlling HIV-induced microglial activation and cytokine production that may have important therapeutic implications for the management of HAND

Surface modification of a granite building stone in central Rio de Janeiro

In order to evaluate environmental controls on the soiling formation and decay of building stones a set of mapping and physical and chemical analyses were carried out on granite from a historical church in the polluted centre of Rio de Janeiro. These techniques highlight the increasing of threatening damage on generally perceived as a durable building material, caused by granular disaggregation and contour scaling in areas close to ground level. Mapping also indicated the formation of black crusts over entire building façades, concentrated on areas sheltered from rain-wash. Analyses demonstrated the influence of marine aerosols, rock and mortar composition and mostly of the atmospheric pollutants on the decay and soiling of the granite. Much of the decay is associated specifically with the presence of halite (NaCl) and gypsum (CaS04.2H2O). The fact that black, gypsum crusts are able to develop over entire façades in a humid subtropical environment is testimony to the high levels of local pollution, especially particulate deposition. Reduced rainwash, in sheltered micro-environments of narrow, canyon-like streets, overcomes the gypsum tendency to bewashed away from buildings façades. These observations further highlight that decay processes are primarily controlled by microclimatic conditions.<br>Com o objetivo de se avaliar os controles ambientais na formação de crostas e deterioração de rochas ornamentais em fachadas de prédios históricos, uma série de mapeamentos e análises fisicas e químicas foram realizados em granitos da fachada de uma igreja histórica numa área poluída no centro da cidade do Rio de Janeiro. Estas técnicas destacam a ameaça crescente dos danos causados pela desagregação granular e esfoliação da rocha que é fortemente percebido por se tratar de um material de alta durabilidade usado na fachada do prédio em áreaslocalizadas ao nível do chão. O exercício de mapeamento possibilitou a demarcação e observação das áreas afetadas pela formação de crosta negra sobre toda a fachada do prédio, principalmente concentradas em áreas abrigadas da ação da chuva. As análises demonstraram a influência de aerosóis marinhos, composição das rochas e argamassas e dos poluentes atmosféricos na deterioração e formação de crostas no granito. Muito da deterioração é associado especificamente a presença de sais, tais como halita (NaCl) e gipsita (CaS0(4).2H2O). O fato da crosta negra de gipsita ser capaz de se desenvolver sobre toda a fachada do prédio, em um ambiente sub-tropical úmido é testemunha da eficácia dos altos níveis de poluição local, especialmente da deposição de particulados, e da reduzida lavagem pela chuva em um micro-ambiente protegido,em ruas estreitas, que funcionam como corredores de poluição, impedindo a tendência da gipsita ser lavada das fachadas dos prédios históricos. Essa observação destaca que os processos de intemperismo operante, são principalmente controlados por condições microclimáticas