Cholesterol Depletion in Adipocytes Causes Caveolae Collapse Concomitant with Proteosomal Degradation of Cavin-2 in a Switch-Like Fashion

Caveolae, little caves of cell surfaces, are enriched in cholesterol, a certain level of which is required for their structural integrity. Here we show in adipocytes that cavin-2, a peripheral membrane protein and one of 3 cavin isoforms present in caveolae from non-muscle tissue, is degraded upon cholesterol depletion in a rapid fashion resulting in collapse of caveolae. We exposed 3T3-L1 adipocytes to the cholesterol depleting agent methyl-β-cyclodextrin, which results in a sudden and extensive degradation of cavin-2 by the proteasome and a concomitant movement of cavin-1 from the plasma membrane to the cytosol along with loss of caveolae. The recovery of cavin-2 at the plasma membrane is cholesterol-dependent and is required for the return of cavin-1 from the cytosol to the cell surface and caveolae restoration. Expression of shRNA directed against cavin-2 also results in a cytosolic distribution of cavin-1 and loss of caveolae. Taken together, these data demonstrate that cavin-2 functions as a cholesterol responsive component of caveolae that is required for cavin-1 localization to the plasma membrane, and caveolae structural integrity

TonEBP suppresses adipogenesis and insulin sensitivity by blocking epigenetic transition of PPAR gamma 2

TonEBP is a key transcription factor in cellular adaptation to hypertonic stress, and also in macrophage activation. Since TonEBP is involved in inflammatory diseases such as rheumatoid arthritis and atherosclerosis, we asked whether TonEBP played a role in adipogenesis and insulin resistance. Here we report that TonEBP suppresses adipogenesis and insulin signaling by inhibiting expression of the key transcription factor PPAR gamma 2. TonEBP binds to the PPAR gamma 2 promoter and blocks the epigenetic transition of the locus which is required for the activation of the promoter. When TonEBP expression is reduced, the epigenetic transition and PPAR gamma 2 expression are markedly increased leading to enhanced adipogenesis and insulin response while inflammation is reduced. Thus, TonEBP is an independent determinant of adipose insulin sensitivity and inflammation. TonEBP is an attractive therapeutic target for insulin resistance in lieu of PPAR gamma agonistsopen0

Standards for Scalable Clinical Decision Support: Need, Current and Emerging Standards, Gaps, and Proposal for Progress

Despite their potential to significantly improve health care, advanced clinical decision support (CDS) capabilities are not widely available in the clinical setting. An important reason for this limited availability of CDS capabilities is the application-specific and institution-specific nature of most current CDS implementations. Thus, a critical need for enabling CDS capabilities on a much larger scale is the development and adoption of standards that enable current and emerging CDS resources to be more effectively leveraged across multiple applications and care settings. Standards required for such effective scaling of CDS include (i) standard terminologies and information models to represent and communicate about health care data; (ii) standard approaches to representing clinical knowledge in both human-readable and machine-executable formats; and (iii) standard approaches for leveraging these knowledge resources to provide CDS capabilities across various applications and care settings. A number of standards do exist or are under development to meet these needs. However, many gaps and challenges remain, including the excessive complexity of many standards; the limited availability of easily accessible knowledge resources implemented using standard approaches; and the lack of tooling and other practical resources to enable the efficient adoption of existing standards. Thus, the future development and widespread adoption of current CDS standards will depend critically on the availability of tooling, knowledge bases, and other resources that make the adoption of CDS standards not only the right approach to take, but the cost-effective path to follow given the alternative of using a traditional, ad hoc approach to implementing CDS

Hung Out to Dry: Choice of Priority Ecoregions for Conserving Threatened Neotropical Anurans Depends on Life-History Traits

Background: In the Neotropics, nearly 35 % of amphibian species are threatened by habitat loss, habitat fragmentation, and habitat split; anuran species with different developmental modes respond to habitat disturbance in different ways. This entails broad-scale strategies for conserving biodiversity and advocates for the identification of high conservation-value regions that are significant in a global or continental context and that could underpin more detailed conservation assessments towards such areas. Methodology/Principal Findings: We identified key ecoregion sets for anuran conservation using an algorithm that favors complementarity (beta-diversity) among ecoregions. Using the WWF’s Wildfinder database, which encompasses 700 threatened anuran species in 119 Neotropical ecoregions, we separated species into those with aquatic larvae (AL) or terrestrial development (TD), as this life-history trait affects their response to habitat disturbance. The conservation target of 100 % of species representation was attained with a set of 66 ecoregions. Among these, 30 were classified as priority both for species with AL and TD, 26 were priority exclusively for species with AL, and 10 for species with TD only. Priority ecoregions for both developmental modes are concentrated in the Andes and in Mesoamerica. Ecoregions important for conserving species with AL are widely distributed across the Neotropics. When anuran life histories were ignored, species with AL were always underrepresented in priority sets

Single origin of sex chromosomes and multiple origins of B chromosomes in fish genus Characidium

Chromosome painting with DNA probes obtained from supernumerary (B) and sex chromosomes in three species of fish genus Characidium (C. gomesi, C. pterostictum and C. oiticicai) showed a close resemblance in repetitive DNA content between B and sex chromosomes in C. gomesi and C. pterostictum. This suggests an intraspecific origin for B chromosomes in these two species, probably deriving from sex chromosomes. In C. oiticicai, however, a DNA probe obtained from its B chromosome hybridized with the B but not with the A chromosomes, suggesting that the B chromosome in this species could have arisen interspecifically, although this hypothesis needs further investigation. A molecular phylogenetic analysis performed on nine Characidium species, with two mtDNA genes, showed that the presence of heteromorphic sex chromosomes in these species is a derived condition, and that their origin could have been unique, a conclusion also supported by interspecific chromosome painting with a CgW probe derived from the W chromosome in C. gomesi. Summing up, our results indicate that whereas heteromorphic sex chromosomes in the genus Characidium appear to have had a common and unique origin, B chromosomes may have had independent origins in different species. Our results also show that molecular phylogenetic analysis is an excellent complement for cytogenetic studies by unveiling the direction of evolutionary chromosome changes.This research was funded by grants from the State of Sao Paulo Research Foundation (FAPESP) to EAS (2013/02143-3), grants from National Council for Research and Development (CNPq) to FF (480449/2012-0), and by Coordenacao de Aperfeicoamento de Pessoal de Nıvel Superior (CAPES)

Expressed sequence tags from Atta laevigata and identification of candidate genes for the control of pest leaf-cutting ants

<p>Abstract</p> <p>Background</p> <p>Leafcutters are the highest evolved within Neotropical ants in the tribe Attini and model systems for studying caste formation, labor division and symbiosis with microorganisms. Some species of leafcutters are agricultural pests controlled by chemicals which affect other animals and accumulate in the environment. Aiming to provide genetic basis for the study of leafcutters and for the development of more specific and environmentally friendly methods for the control of pest leafcutters, we generated expressed sequence tag data from <it>Atta laevigata</it>, one of the pest ants with broad geographic distribution in South America.</p> <p>Results</p> <p>The analysis of the expressed sequence tags allowed us to characterize 2,006 unique sequences in <it>Atta laevigata</it>. Sixteen of these genes had a high number of transcripts and are likely positively selected for high level of gene expression, being responsible for three basic biological functions: energy conservation through redox reactions in mitochondria; cytoskeleton and muscle structuring; regulation of gene expression and metabolism. Based on leafcutters lifestyle and reports of genes involved in key processes of other social insects, we identified 146 sequences potential targets for controlling pest leafcutters. The targets are responsible for antixenobiosis, development and longevity, immunity, resistance to pathogens, pheromone function, cell signaling, behavior, polysaccharide metabolism and arginine kynase activity.</p> <p>Conclusion</p> <p>The generation and analysis of expressed sequence tags from <it>Atta laevigata </it>have provided important genetic basis for future studies on the biology of leaf-cutting ants and may contribute to the development of a more specific and environmentally friendly method for the control of agricultural pest leafcutters.</p

Profile of Central and Effector Memory T Cells in the Progression of Chronic Human Chagas Disease

Chagas disease is a parasitic infection caused by protozoan Trypanosoma cruzi that affects approximately 11 million people in Latin America. The involvement of the host's immune response on the development of severe forms of Chagas disease has not been fully elucidated. Studies on the immune response against T. cruzi infection show that the immunoregulatory mechanisms are necessary to prevent the deleterious effect of excessive immune response stimulation and consequently the fatal outcome of the disease. A recall response against parasite antigens observed in in vitro peripheral blood cell culture clearly demonstrates that memory response is generated during infection. Memory T cells are heterogeneous and differ in both the ability to migrate and exert their effector function. This heterogeneity is reflected in the definition of central (TCM) and effector memory (TEM) T cells. Our results suggest that a balance between regulatory and effectors T cells may be important for the progression and development of the disease. Furthermore, the high percentage of central memory CD4+ T cells in indeterminate patients after stimulation suggests that these cells may modulate host's inflammatory response by controlling cell migration to tissues and their effector role during chronic phase of the disease