20 research outputs found
Modelagem computacional da rede de drenagem urbana usando alternativas LID em uma sub-bacia na cidade de Maringá, Paraná, Brasil
With urbanization development, inundations and urban floods become more frequent. In the city of Maringa, Parana, this type of event is often observed in some specific dense urban locations, resulted by intense rainfall. In this context, the objective of this paper is to perform a computational modelling in the urban drainage network, most specifically in the sub-basin defined by the intersection of avenues Guaiapo and Palmares, in the city of Maringa, Parana, considering the current situation and with the application of Low Impact Development (LID) compensatory techniques. In this regard, the computational program SewerGEMS® was used to develop the scenarios simulations. The results shown that the actual network is undersized (Scenario 01), and it is proposed the adoption of LID compensatory measures (Scenarios 02, 03 and 04). The computational modelling in the elaboration of the scenarios was effective and it may support the municipal urban management with the implementation of an adequate and efficient system of stormwater management.Com o avanço da urbanização, tornam-se frequentes os problemas de alagamentos, inundações e enchentes urbanas. Na cidade de Maringá, Paraná, constatam-se alagamentos frequentes, decorrentes de chuvas intensas, em pontos específicos densamente urbanizadas. Neste contexto, o objetivo desse trabalho é elaborar cenários de um trecho da rede de drenagem urbana, mais especificamente no ponto de cruzamento entre as avenidas Guaiapó e dos Palmares, localizado na cidade de Maringá, Paraná: com a situação atual e utilizando técnicas compensatórias de Low Impact Development (LID). Para isso, foi utilizado o programa computacional SewerGEMS® a fim de realizar as simulações dos cenários propostos. Os resultados mostraram que a rede atual no trecho considerado está subdimensionada (Cenário 1) e uma das soluções propostas é a adoção de técnicas compensatórias LID para construção dos Cenários 2, 3 e 4. Conclui-se que a modelagem computacional para a elaboração de cenários mostrou-se efetiva e pode ser uma grande aliada para fornecer subsídios para a gestão municipal urbana, auxiliando na implementação de um manejo de águas urbanas adequado e eficiente.
Chlamydia Inhibit Host Cell Apoptosis by Degradation of Proapoptotic BH3-only Proteins
Chlamydia are obligate intracellular bacteria that replicate in a vacuole inside a host cell. Chlamydial infection has been shown to protect the host cell against apoptotic stimuli. This is likely important for the ability of Chlamydia to reproduce in human cells. Here we show that resistance to apoptosis is conveyed by the destruction of the proapoptotic BH3-only proteins Bim/Bod, Puma, and Bad during infection. Apoptotic stimuli were blocked upstream of the mitochondrial activation of Bax/Bak. During infection with both species, Chlamydia trachomatis and Chlamydia pneumoniae, Bim protein gradually disappeared without noticeable changes in Bim mRNA. The disappearance was blocked by inhibitors of the proteasome. Infected cells retained sensitivity to Bim expressed by transfection, indicating functional relevance of the Bim disappearance. Fusion to Bim targeted the green fluorescent protein for destruction during infection. Analysis of truncation mutants showed that a short region of Bim containing the BH3 domain was sufficient for destruction during chlamydial infection. Like Bim, Puma and Bad proteins disappeared during infection. These results reveal a novel way by which microbes can interfere with the host cell's apoptotic machinery, and provide a molecular explanation of the cellular resistance to apoptosis during infection with Chlamydia
Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease
Chlamydiae replicate in a vacuole within epithelial cells and commonly induce cell damage and a deleterious inflammatory response of unknown molecular pathogenesis. The chlamydial protease-like activity factor (CPAF) translocates from the vacuole to the cytosol, where it cleaves several cellular proteins. CPAF is synthesized as an inactive precursor that is processed and activated during infection. Here, we show that CPAF can be activated in uninfected cells by experimentally induced oligomerization, reminiscent of the activation mode of initiator caspases. CPAF activity induces proteolysis of cellular substrates including two novel targets, cyclin B1 and PARP, and indirectly results in the processing of pro-apoptotic BH3-only proteins. CPAF activation induces striking morphological changes in the cell and, later, cell death. Biochemical and ultrastructural analysis of the cell death pathway identify the mechanism of cell death as nonapoptotic. Active CPAF in uninfected human cells thus mimics many features of chlamydial infection, implicating CPAF as a major factor of chlamydial pathogenicity, Chlamydia-associated cell damage, and inflammation
Atuação e contribuições científicas do Grupo de Pesquisa “Gestão Integrada de Águas Urbanas” da Universidade Estadual de Maringá, Paraná, Brasil
Research Group Integrated Urban Water Manegement (GIAU) was founded in 2014, due to the need to study and to suggest solutions to weaknesses reported in the municipality of Maringá, in Paraná State, regarding this subject. The integrated urban water management comprehend ah holistic view to potable water supply and sanitary sewage systems, water drainage management in urban areas, besides urban solid waste management. In this context, the aim of this paper is to present the research group and its main contributions up to this point. The applied method consisted in present the history from creation, formation and recent actions of the whole group and in realize a systematic review of the published papers. The main results showed that although recent, the group has worked in a proactive way in its community by means of promotion of lectures and events, besides the production of 52 publications in national and international journals, national and international events, books and book chapters. The group has also board members highly qualified, concentrating in the training of human resources. It can be concluded that the research group is consolidating, with high performance expectations.O Grupo de Pesquisa em Gestão Integrada de Águas Urbanas (GIAU) foi criado em 2014, face à necessidade de estudar e propor soluções para as deficiências constatadas no município de Maringá, no estado do Paraná, com relação a este tema. A gestão integrada das águas urbanas compreende uma visão holística para os sistemas de abastecimento de água potável e de esgotamento sanitário, manejo de águas pluviais urbanas e seu sistema de drenagem urbana, além da gestão dos resíduos sólidos urbanos. Neste contexto, o objetivo deste artigo é apresentar o grupo de pesquisa e suas principais contribuições. O método utilizado foi apresentar o histórico da criação, a formação e atuação do grupo de pesquisa e realizar uma revisão sistemática de seus artigos publicados. Os principais resultados encontrados mostraram que o grupo de pesquisa, embora bastante novo, tem atuado de maneira pró-ativa em sua comunidade por meio da ministração de palestras e promoção de eventos, além de produzir 52 publicações distribuídas em periódicos nacionais e internacionais, eventos nacionais e internacionais, livro e capítulos de livros. O grupo possui ainda um quadro de membros altamente qualificado, que se concentra na formação de recursos humanos. Conclui-se que o grupo de pesquisa, embora novo, tem se consolidado e que suas expectativas de atuação são boas, sendo que a próxima meta é a instituição de parcerias internacionais
Targeting of a Chlamydial Protease Impedes Intracellular Bacterial Growth
Chlamydiae are obligate intracellular bacteria that propagate in a cytosolic vacuole. Recent work has shown that growth of Chlamydia induces the fragmentation of the Golgi apparatus (GA) into ministacks, which facilitates the acquisition of host lipids into the growing inclusion. GA fragmentation results from infection-associated cleavage of the integral GA protein, golgin-84. Golgin-84-cleavage, GA fragmentation and growth of Chlamydia trachomatis can be blocked by the peptide inhibitor WEHD-fmk. Here we identify the bacterial protease chlamydial protease-like activity factor (CPAF) as the factor mediating cleavage of golgin-84 and as the target of WEHD-fmk-inhibition. WEHD-fmk blocked cleavage of golgin-84 as well as cleavage of known CPAF targets during infection with C. trachomatis and C. pneumoniae. The same effect was seen when active CPAF was expressed in non-infected cells and in a cell-free system. Ectopic expression of active CPAF in non-infected cells was sufficient for GA fragmentation. GA fragmentation required the small GTPases Rab6 and Rab11 downstream of CPAF-activity. These results define CPAF as the first protein that is essential for replication of Chlamydia. We suggest that this role makes CPAF a potential anti-infective therapeutic target
Protection against CD95-Induced Apoptosis by Chlamydial Infection at a Mitochondrial Step
Chlamydiae are obligate intracellular bacteria that infect human epithelial and myeloid cells. Previous work has established that chlamydiae are able to protect a cell against apoptosis induced by certain experimentally applied stimuli. Here we provide an analysis of this protective activity against the signal transduction during CD95-induced apoptosis. In HeLa cells overexpressing CD95, infection with Chlamydia trachomatis inhibited the appearance of apoptotic morphology, effector caspase activity, the activation of caspase-9 and -3, and the release of cytochrome c from mitochondria. However, caspase-8-processing and activity (measured as cleavage of Bid) were unaffected by the chlamydial infection. Similarly, infection with the species C. pneumoniae did not prevent the activation of caspase-8 but inhibited the appearance of effector caspase activity upon signaling through CD95. Furthermore, infection with C. trachomatis was able to inhibit CD95-induced apoptosis in Jurkat lymphoid cells, where a mitochondrial contribution is required, but not in SKW6.4 lymphoid cells, where caspase-8 directly activates caspase-3. Taken together, these data show that chlamydial infection can protect cells against CD95-induced apoptosis but only where a mitochondrial signaling step is necessary for apoptotic signal transduction
Roscovitine-induced Apoptosis in Neutrophils and Neutrophil Progenitors Is Regulated by the Bcl-2-Family Members Bim, Puma, Noxa and Mcl-1
<div><p>Neutrophil granulocyte (neutrophil) apoptosis plays a key role in determining inflammation in infectious and non-infectious settings. Recent work has shown that inhibitors of cyclin-dependent kinases (cdk) such as roscovitine can potently induce neutrophil apoptosis and reduce inflammation. Using a conditional Hoxb8-expression system we tested the participation of Bcl-2-family proteins to roscovitine-induced apoptosis in mouse neutrophils and in neutrophil progenitor cells. Bcl-2 strongly protected against roscovitine-induced apoptosis in neutrophils. The isolated loss of either Bim or noxa provided significant, partial protection while protection through combined loss of Bim and noxa or Bim and Puma was only slightly greater than this individual loss. The only substantial change in protein levels observed was the loss of Mcl-1, which was not transcriptional and was inhibited by proteasome blockade. In progenitor cells there was no protection by the loss of Bim alone but substantial protection by the loss of both Bim and Puma; surprisingly, strongest protection was seen by the isolated loss of noxa. The pattern of protein expression and Mcl-1-regulation in progenitor cells was very similar to the one observed in differentiated neutrophils. In addition, roscovitine strongly inhibited proliferation in progenitor cells, associated with an accumulation of cells in G2/M-phase.</p> </div