Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation

Background\ud Succinate is an intermediate of the citric acid cycle as well as an extracellular circulating molecule, whose receptor, G protein-coupled receptor-91 (GPR91), was recently identified and characterized in several tissues, including heart. Because some pathological conditions such as ischemia increase succinate blood levels, we investigated the role of this metabolite during a heart ischemic event, using human and rodent models.\ud \ud \ud Results\ud We found that succinate causes cardiac hypertrophy in a GPR91 dependent manner. GPR91 activation triggers the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), the expression of calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) and the translocation of histone deacetylase 5 (HDAC5) into the cytoplasm, which are hypertrophic-signaling events. Furthermore, we found that serum levels of succinate are increased in patients with cardiac hypertrophy associated with acute and chronic ischemic diseases.\ud \ud \ud Conclusions\ud These results show for the first time that succinate plays an important role in cardiomyocyte hypertrophy through GPR91 activation, and extend our understanding of how ischemia can induce hypertrophic cardiomyopathy.CAPESFAPEMIG (Pronex)INCT- Carbon NanotubesCNPqHHM

O Programa de Cidades Históricas : por uma política integrada de preservação do patrimônio cultural urbano

O Programa de Cidades Históricas (PCH), implementado a partir de 1973, foi o primeiro programa federal que investiu recursos para a recuperação do patrimônio cultural urbano. Implementado pelo Ministério do Planejamento, buscava o desenvolvimento econômico das cidades históricas e dialogava com outros assuntos em pauta naquele momento, como o desenvolvimento urbano e regional e o turismo cultural. Tinha em sua concepção uma mudança na maneira de abordar as cidades históricas: a partir do entendimento da cidade como produtora de capital, o patrimônio cultural geraria desenvolvimento econômico pelo seu consumo para a atividade turística. De 1973 a 1979, foram investidos 17,3 milhões de dólares, realizando-se 143 obras em monumentos (85% dos investimentos); 8 cursos de qualificação de mão de obra nos três níveis (superior, intermediário e operário); 7 planos urbanísticos; 6 obras em espaços públicos (urbanos); e 10 ações de tipos diversos. Nossa análise busca entender essa política a partir do seu processo de formulação e implementação, no período de 1972 a 1979. Pretende, nesse sentido: a) avaliar as relações de poder em jogo durante a construção e a implementação do programa; b) compreender o grau de sucesso que o programa obteve na construção de um Sistema Nacional de Patrimônio Cultural, analisando sua articulação junto aos estados e outros órgãos federais; e c) avaliar o papel do programa enquanto indutor de novas práticas institucionais no campo da preservação do patrimônio cultural, especialmente com relação ao Iphan e aos estados federativos brasileiros.The Historic Cities Program (PCH: 1973-1979) was the first federal program that has invested resources to the recovery of the urban cultural heritage. Implemented by the Ministry of Planning, sought economic development of historic towns and dialogued with other items on the agenda at the time, such as urban and regional development and cultural tourism. It brought a change in the way of approach the historic towns: from the understanding of the city as a producer of capital, heritage would generate economic development through its consume by the tourism. From 1973 to 1979 it was invested 17.3 million dollars, performing 143 works on monuments (85% of investments); 8 hand-to-work training courses in three levels (top, middle and working class); 7 urban plans; 6 works in public spaces (urban); and 10 shares of various types. Our analysis seeks to understand this policy from its formulation and implementation in the period from 1972 to 1979. The aim, in this sense, is: a) to assess the power relations at play during construction and implementation of the Program; b) to understand the degree of success that the program achieved in building a national system, analyzing its relationship with states and other federal agencies; and c) to evaluate the role of Program while inducing new institutional practices in the field of preservation of cultural heritage, especially with regard to Iphan

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio