Intra-Organ Variation in Age-Related Mutation Accumulation in the Mouse

Using a transgenic mouse model harboring chromosomally integrated lacZ mutational target genes, we previously demonstrated that mutations accumulate with age much more rapidly in the small intestine than in the brain. Here it is shown that in the small intestine point mutations preferentially accumulate in epithelial cells of the mucosa scraped off the underlying serosa. The mucosal cells are the differentiated villus cells that have undergone multiple cell divisions. A smaller age-related increase, also involving genome rearrangements, was observed in the serosa, which consists mainly of the remaining crypts and non-dividing smooth muscle cells. In the brain we observed an accumulation of only point mutations in no other areas than hypothalamus and hippocampus. To directly test for cell division as the determining factor in the generation of point mutations we compared mutation induction between mitotically active and quiescent embryonic fibroblasts from the same lacZ mice, treated with either UV (a point mutagen) or hydrogen peroxide (a clastogen). The results indicate that while point mutations are highly replication-dependent, genome rearrangements are as easily induced in non-dividing cells as in mitotically active ones. This strongly suggests that the point mutations found to have accumulated in the mucosal part of the small intestine are the consequence of replication errors. The same is likely true for point mutations accumulating in hippocampus and hypothalamus of the brain since neurogenesis in these two areas continues throughout life. The observed intra-organ variation in mutation susceptibility as well as the variation in replication dependency of different types of mutations indicates the need to not only extend observations made on whole organs to their sub-structures but also take the type of mutations and mitotic activity of the cells into consideration. This should help elucidating the impact of genome instability and its consequences on aging and disease

Administration of M. leprae Hsp65 Interferes with the Murine Lupus Progression

The heat shock protein [Hsp] family guides several steps during protein synthesis, are abundant in prokaryotic and eukaryotic cells, and are highly conserved during evolution. The Hsp60 family is involved in assembly and transport of proteins, and is expressed at very high levels during autoimmunity or autoinflammatory phenomena. Here, the pathophysiological role of the wild type [WT] and the point mutated K409A recombinant Hsp65 of M. leprae in an animal model of Systemic Lupus Erythematosus [SLE] was evaluated in vivo using the genetically homogeneous [NZBxNZW]F1 mice. Anti-DNA and anti-Hsp65 antibodies responsiveness was individually measured during the animal's life span, and the mean survival time [MST] was determined. The treatment with WT abbreviates the MST in 46%, when compared to non-treated mice [p<0.001]. An increase in the IgG2a/IgG1 anti-DNA antibodies ratio was also observed in animals injected with the WT Hsp65. Incubation of BALB/c macrophages with F1 serum from WT treated mice resulted in acute cell necrosis; treatment of these cells with serum from K409A treated mice did not cause any toxic effect. Moreover, the involvement of WT correlates with age and is dose-dependent. Our data suggest that Hsp65 may be a central molecule intervening in the progression of the SLE, and that the point mutated K409A recombinant immunogenic molecule, that counteracts the deleterious effect of WT, may act mitigating and delaying the development of SLE in treated mice. This study gives new insights into the general biological role of Hsp and the significant impact of environmental factors during the pathogenesis of this autoimmune process

Simulating the midlatitude atmospheric circulation: what might we gain from high-resolution modeling of air-sea interactions?

Purpose of Review. To provide a snapshot of the current research on the oceanic forcing of the atmospheric circulation in midlatitudes and a concise update on previous review papers. Recent findings. Atmospheric models used for seasonal and longer timescales predictions are starting to resolve motions so far only studied in conjunction with weather forecasts. These phenomena have horizontal scales of ~ 10–100 km which coincide with energetic scales in the ocean circulation. Evidence has been presented that, as a result of this matching of scale, oceanic forcing of the atmosphere was enhanced in models with 10–100 km grid size, especially at upper tropospheric levels. The robustness of these results and their underlying mechanisms are however unclear. Summary. Despite indications that higher resolution atmospheric models respond more strongly to sea surface temperature anomalies, their responses are still generally weaker than those estimated empirically from observations. Coarse atmospheric models (grid size greater than 100 km) will miss important signals arising from future changes in ocean circulation unless new parameterizations are developed

Desatando a trama das redes assistenciais sobre drogas: uma revisão narrativa da literatura

Acalorados debates sobre determinados modelos de tratamento para usuários de drogas ocorrem no âmbito da academia, das políticas públicas, além da mídia. A rede assistencial sobre drogas é apresentada neste contexto como um importante mecanismo, mas sua construção torna-se um desafio. Assim, realizou-se uma análise crítica da literatura acadêmica acerca das redes assistenciais sobre drogas, na forma de uma revisão narrativa, visando levantar seus desafios e possibilidades de consolidação. Os resultados encontrados foram: a) uma escassez de estudos específicos sobre a rede assistencial sobre drogas; b) cobertura insuficiente e desintegrada frente à demanda de tratamento; c) necessidade de se repensar o papel dos Centros de Atenção Psicossocial para Álcool e outras Drogas, visando seu fortalecimento, expansão, melhoria estrutural e readequação de práticas; d) ausência de análises críticas sobre o processo de construção dos modelos assistenciais sobre drogas nos serviços públicos; e, e) responsabilidade do Estado em fornecer melhores alternativas ao panorama encontrado, avançando no fortalecimento das ações intersetoriais, articulação do cuidado e no aprimoramento das condições de trabalho

Biodiversity of Arbuscular Mycorrhizal Fungi in South America: A Review

Identification of species is crucial in understanding how diversity changes affect ecosystemic processes. Particularly, soil microbial are key factors of ecosystemic functioning .Among soil microbes, arbuscular mycorrhizal fungi (AMF, phylum Glomeromycota) are worldwide distributed and form symbiotic associations with almost 80% of the vascular plants of the earth, except for one species, Geosiphon pyriformis, which associates with the cyanobacteria Nostoc. AMF comprise around 300 morphologically defined or 350–1000 molecularly defined taxa. Since AMF associate with aboveground community, their occurrence and composition can influence ecosystemic processes either through affecting plant community composition and thus its processes rates, or soil microbial communities, which are directly involved in nutrient cycling. Soil microorganisms are considered a potentially suitable target for studying regional and local effects on diversity. The symbiosis with AMF not only increases nutrient uptake by the plant of mainly phosphorus (P) and nitrogen (N) in exchange for plant-assimilated carbon (C), but also improves the tolerance of plants to various biotic and abiotic stresses such as pathogens, salinity, and drought