SECA EXTREMA DE 2012 NO SEMIÁRIDO BAIANO E SEUS IMPACTOS: INFORMAÇÕES CLIMÁTICAS DIFUNDIDAS PELA MÍDIA

Este trabalho visa analisar a forma como a mídia impressa no estado da Bahia transmite informações climáticas na época da seca. Para tanto, edições de dois jornais diários, referentes ao ano de 2012, foram analisadas. Considerou-se as matérias veiculadas sobre o tema, e os aspectos conceituais relacionados à transmissão da notícia foram avaliados. Os resultados sugerem que as mídias analisadas disseminaram as informações climáticas de maneira sensacionalista, além de apresentar erros conceituais. Concluiu-se que a mídia analisada, que poderia ser o veículo por meio do qual a população pudesse desconstruir a concepção de um ambiente hostil normalmente vinculado ao semiárido, propaga informações que corroboram para manter uma visão pejorativa da região

Uso de drogas e o aumento das infecções sexualmente transmissíveis: uma revisão sistemática: Drug use and the increase in sexually transmitted infections: a systematic review

Populações de usuários de drogas têm sido associadas a epidemias de infecções ou Infecções Sexualmente Transmissíveis, especialmente a infecção pelo HIV (que está associada a drogas injetáveis, uso de equipamentos contaminados para drogas injetáveis e sexo inseguro). A droga mais associada às DSTs é a cocaína fumável de base livre (crack), devido ao aumento dos comportamentos sexuais de risco. Diante disso, o presente estudo teve como objetivo compreender o impacto do uso de drogas no aumento das infecções sexualmente transmissíveis. Para isso, adotou-se como metodologia a revisão sistemática de literatura, realizando buscas nas bases de dados Scielo, Pubmed e BVS/Medline a partir do uso de descritores DeCS/MeSH e aplicação de critérios de inclusão e exclusão. A partir da análise e interpretação dos dados, concluiu-se que que pessoas que fazem uso abusivo de drogas lícitas ou ilícitas, sejam elas mulheres, homens, adolescentes, jovens, adultos, idosos, em situação de rua ou não, tendem a desenvolver comportamentos vulneráveis que pode resultar em IST. Somado a isso, enquanto comportamento de risco, tem-se a preferência por não usar preservativo, seja em relações sexuais com pessoas monogâmicas como com dois ou mais parceiros. Nesses casos, tanto o uso exacerbado de drogas como a falta de informação sobre comportamento sexual demonstram-se insuficientes

Killing Two Angry Birds with One Stone: Autophagy Activation by Inhibiting Calpains in Neurodegenerative Diseases and Beyond

Proteolytic machineries execute vital cellular functions and their disturbances are implicated in diverse medical conditions, including neurodegenerative diseases. Interestingly, calpains, a class of Ca2+-dependent regulatory proteases, can modulate the degradational system of autophagy by cleaving proteins involved in this pathway. Moreover, both machineries are common players in many molecular pathomechanisms and have been targeted individually or together, as a therapeutic strategy in experimental setups. In this review, we briefly introduce calpains and autophagy, with their roles in health and disease, and focus on their direct pathologically relevant interplay in neurodegeneration and beyond. The modulation of calpain activity may comprise a promising treatment approach to attenuate the deregulation of these two essential mechanisms

Neurodegenerative phosphoprotein signaling landscape in models of SCA3

Spinocerebellar ataxia type 3 (SCA3) is a rare neurodegenerative disorder resulting from an aberrant expansion of a polyglutamine stretch in the ataxin-3 protein and subsequent neuronal death. The underlying intracellular signaling pathways are currently unknown. We applied the Reverse-phase Protein MicroArray (RPMA) technology to assess the levels of 50 signaling proteins (in phosphorylated and total forms) using three in vitro and in vivo models expressing expanded ataxin-3: (i) human embryonic kidney (HEK293T) cells stably transfected with human ataxin-3 constructs, (ii) mouse embryonic fibroblasts (MEF) from SCA3 transgenic mice, and (iii) whole brains from SCA3 transgenic mice. All three models demonstrated a high degree of similarity sharing a subset of phosphorylated proteins involved in the PI3K/AKT/GSK3/mTOR pathway. Expanded ataxin-3 strongly interfered (by stimulation or suppression) with normal ataxin-3 signaling consistent with the pathogenic role of the polyglutamine expansion. In comparison with normal ataxin-3, expanded ataxin-3 caused a pro-survival stimulation of the ERK pathway along with reduced pro-apoptotic and transcriptional responses

Calpains as novel players in the molecular pathogenesis of spinocerebellar ataxia type 17

Spinocerebellar ataxia type 17 (SCA17) is a neurodegenerative disease caused by a polyglutamine-encoding trinucleotide repeat expansion in the gene of transcription factor TATA box-binding protein (TBP). While its underlying pathomechanism is elusive, polyglutamine-expanded TBP fragments of unknown origin mediate the mutant protein’s toxicity. Calcium-dependent calpain proteases are protagonists in neurodegenerative disorders. Here, we demonstrate that calpains cleave TBP, and emerging C-terminal fragments mislocalize to the cytoplasm. SCA17 cell and rat models exhibited calpain overactivation, leading to excessive fragmentation and depletion of neuronal proteins in vivo. Transcriptome analysis of SCA17 cells revealed synaptogenesis and calcium signaling perturbations, indicating the potential cause of elevated calpain activity. Pharmacological or genetic calpain inhibition reduced TBP cleavage and aggregation, consequently improving cell viability. Our work underlines the general significance of calpains and their activating pathways in neurodegenerative disorders and presents these proteases as novel players in the molecular pathogenesis of SCA17. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04274-6

KPNB1 modulates the Machado-Joseph disease protein ataxin-3 through activation of the mitochondrial protease CLPP

Machado–Joseph disease (MJD) is characterized by a pathological expansion of the polyglutamine (polyQ) tract within the ataxin-3 protein. Despite its primarily cytoplasmic localization, polyQ-expanded ataxin-3 accumulates in the nucleus and forms intranuclear aggregates in the affected neurons. Due to these histopathological hallmarks, the nucleocytoplasmic transport machinery has garnered attention as an important disease relevant mechanism. Here, we report on MJD cell model-based analysis of the nuclear transport receptor karyopherin subunit beta-1 (KPNB1) and its implications in the molecular pathogenesis of MJD. Although directly interacting with both wild-type and polyQ-expanded ataxin-3, modulating KPNB1 did not alter the intracellular localization of ataxin-3. Instead, overexpression of KPNB1 reduced ataxin-3 protein levels and the aggregate load, thereby improving cell viability. On the other hand, its knockdown and inhibition resulted in the accumulation of soluble and insoluble ataxin-3. Interestingly, the reduction of ataxin-3 was apparently based on protein fragmentation independent of the classical MJD-associated proteolytic pathways. Label-free quantitative proteomics and knockdown experiments identified mitochondrial protease CLPP as a potential mediator of the ataxin-3-degrading effect induced by KPNB1. We confirmed reduction of KPNB1 protein levels in MJD by analyzing two MJD transgenic mouse models and induced pluripotent stem cells (iPSCs) derived from MJD patients. Our results reveal a yet undescribed regulatory function of KPNB1 in controlling the turnover of ataxin-3, thereby highlighting a new potential target of therapeutic value for MJD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00018-022-04372-5