A reliable measure of similarity based on dependency for short time series: an application to gene expression networks

Background: Microarray techniques have become an important tool to the investigation of genetic relationships and the assignment of different phenotypes. Since microarrays are still very expensive, most of the experiments are performed with small samples. This paper introduces a method to quantify dependency between data series composed of few sample points. The method is used to construct gene co-expression subnetworks of highly significant edges. Results: The results shown here are for an adapted subset of a Saccharomyces cerevisiae gene expression data set with low temporal resolution and poor statistics. The method reveals common transcription factors with a high confidence level and allows the construction of subnetworks with high biological relevance that reveals characteristic features of the processes driving the organism adaptations to specific environmental conditions. Conclusion: Our method allows a reliable and sophisticated analysis of microarray data even under severe constraints. The utilization of systems biology improves the biologists ability to elucidate the mechanisms underlying celular processes and to formulate new hypotheses.

Lack of Galectin-3 Disturbs Mesenteric Lymph Node Homeostasis and B Cell Niches in the Course of Schistosoma mansoni Infection

Galectin-3 is a beta-galactoside-binding protein that has been shown to regulate pathophysiological processes, including cellular activation, differentiation and apoptosis. Recently, we showed that galectin-3 acts as a potent inhibitor of B cell differentiation into plasma cells. Here, we have investigated whether galectin-3 interferes with the lymphoid organization of B cell compartments in mesenteric lymph nodes (MLNs) during chronic schistosomiasis, using WT and galectin-3(-/-) mice. Schistosoma mansoni synthesizes GalNAc beta 1-4(Fuc alpha 1-3) GlcNAc(Lac-DiNAc) structures (N-acetylgalactosamine beta 1-4 N-acetylglucosamine), which are known to interact with galectin-3 and elicit an intense humoral response. Antigens derived from the eggs and adult worms are continuously drained to MLNs and induce a polyclonal B cell activation. In the present work, we observed that chronically-infected galectin-3(-/-) mice exhibited a significant reduced amount of macrophages and B lymphocytes followed by drastic histological changes in B lymphocyte and plasma cell niches in the MLNs. The lack of galectin-3 favored an increase in the lymphoid follicle number, but made follicular cells more susceptible to apoptotic stimuli. There were an excessive quantity of apoptotic bodies, higher number of annexin V(+)/PI(-) cells, and reduced clearance of follicular apoptotic cells in the course of schistosomiasis. Here, we observed that galectin-3 was expressed in nonlymphoid follicular cells and its absence was associated with severe damage to tissue architecture. Thus, we convey new information on the role of galectin-3 in regulation of histological events associated with B lymphocyte and plasma cell niches, apoptosis, phagocytosis and cell cycle properties in the MLNs of mice challenged with S. mansoni.

HLA-G 14-bp Insertion/Deletion Polymorphism Is a Risk Factor for HTLV-1 Infection

About 95% of HTLV-1 infected patients remain asymptomatic throughout life, and the risk factors associated with the development of related diseases, such as HAM/TSP and ATL, are not fully understood. The human leukocyte antigen-G molecule (HLA-G), a nonclassical HLA class I molecule encoded by MHC, is expressed in several pathological conditions, including viral infection, and is related to immunosuppressive effects that allow the virus-infected cells to escape the antiviral defense of the host. The 14-bp insertion/deletion polymorphism of exon 8 HLA-G gene influences the stability of the transcripts and could be related to HTLV-1-infected cell protection and to the increase of proviral load. The present study analyzed by conventional PCR the 14-bp insertion/deletion polymorphism of exon 8 HLA-G gene in 150 unrelated healthy subjects, 82 HTLV-1 infected patients with symptoms (33 ATL and 49 HAM), and 56 asymptomatic HTLV-1 infected patients (HAC). In addition, the proviral load was determined by quantitative real-time PCR in all infected groups and correlated with 14-bp insertion/deletion genotypes. The heterozygote genotype frequencies were significantly higher in HAM, in the symptomatic group, and in infected patients compared to control (p < 0.05). The proviral load was higher in the symptomatic group than the HAC group (p < 0.0005). The comparison of proviral load and genotypes showed that -14-bp/-14-bp genotype had a higher proviral load than +14-bp/-14-bp and +14-bp/+14-bp genotypes. Although HLA-G 14-bp polymorphism does not appear to be associated

The macrophage-derived neutrophil chemotactic factor, MNCF: A lectin with TNF-alpha-like activities on neutrophils

The macro phage-derived neutrophil chemotactic factor (MNCF) is an alpha-galactoside-binding lectin, known to induce dexamethasone-insensitive neutrophil recruitment. We further characterized MNCF effects on neutrophils and showed that it shares with TNF-alpha the ability to delay apoptosis and to trigger degranulation. MNCF and TNF-alpha effects show similar kinetics and involve Src kinases and MAPKinases dependent pathways. They were, however, clearly distinguished, since the soluble TNF-receptor etanercept prevented TNF but not MNCF effects, while melibiose disaccharide inhibited MNCF but not TNF effects. Absorption of MNCF on detoxi-gel did not alter its properties, precluding an LPS contamination effect. By contrast, galectin-3 required LPS to activate neutrophils. Specific antibodies allowed to further demonstrate that MNCF and galectin-3 are two distinct molecules. Finally, MNCF- and IL-8-induced neutrophil activation differed by their kinetic and sensitivity to pertussis toxin. In conclusion, MNCF is a distinct neutrophil agonist, with pro-inflammatory activities involving its carbohydrate recognition domain. (C) 2008 Elsevier Inc. All rights reserved.

Inhibition of Expression of HTLV-1 Structural Genes Mediated by Short Hairpin RNA In Vitro

Background: Human T-lymphotropic virus 1 (HTLV-1) is associated with the T-cell malignancy known as adult T-cell leukemia! lymphoma (ATLL) and with a disorder called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Currently, the treatment of these diseases is based on symptom relief. RNA interference (RNAi) technology has been described as an efficient mechanism for development of new therapeutic methods. Thus, the aim of this study was to evaluate the inhibition of HTLV-1 structural proteins using short hairpin RNAs (shRNAs) expressed by non-viral vectors. Materials and Methods: Reporter plasmids that express enhanced green fluorescent protein-Gag (EGFP-Gag) and EGFP-Env fusion proteins and vectors that express shRNAs corresponding to the HTLV-1 gag and env genes were constructed. shRNA vectors and reporter plasmids were simultaneously transfected into HEK 293 cells. Results: Fluorescence microscopy, flow cytometry and real-time PCR showed that shRNAs were effective in inhibiting the fusion proteins. Conclusion: These shRNAs are effective against the expression of structural genes and may provide an approach to the development of new therapeutic agents.

Silencing of HTLV-1 gag and env genes by small interfering RNAs in HEK 293 cells

Since the discovery of RNAi technology, several functional genomic and disease therapy studies have been conducted using this technique in the field of oncology and virology. RNAi-based antiviral therapies are being studied for the treatment of retroviruses such as HIV-1. These studies include the silencing of regulatory, infectivity and structural genes. The HTLV-1 structural genes are responsible for the synthesis of proteins involved in the entry, assembly and release of particles during viral infection. To examine the possibility of silencing HTLV-1 genes gag and env by RNA interference technology, these genes were cloned into reporter plasmids. These vectors expressed the target mRNAs fused to EGFP reporter genes. Three small interference RNAs (siRNAs) corresponding to gag and three corresponding to env were designed to analyze the effect of silencing by RNAi technology. The plasmids and siRNAs were co-transfected into HEK 293 cells. The results demonstrated that the expression of the HTLV-1 gag and env genes decreased significantly in vitro. Thus, siRNAs can be used to inhibit HTLV-1 structural genes in transformed cells, which could provide a tool for clarifying the roles of HTLV-1 structural genes, as well as a therapy for this infection. (C) 2011 Elsevier B.V. All rights reserved.

Galectin-3 regulates peritoneal B1-cell differentiation into plasma cells

Extracellular galectin-3 participates in the control of B2 lymphocyte migration and adhesion and of their differentiation into plasma cells. Here, we analyzed the role of galectin-3 in B1-cell physiology and the balance between B1a and B1b lymphocytes in the peritoneal cavity. In galectin-3(-/-) mice, the total number of B1a lymphocytes was lower, while B1b lymphocyte number was higher as compared to wild-type mice. The differentiation of B1a cells into plasma cells was associated with their abnormal adhesion and location on the mesentery. The B220 and CD43, constitutively expressed by B1 lymphocytes, were respectively up- and downregulated in galectin-3(-/-) mice. Mononuclear cells were strongly adhered to the mesenteric membranes of both CD43(-/-) and galectin-3(-/-) mice, but in contrast to CD43(-/-) mice, the accumulation of B1 cells in peritoneal membranes in galectin-3(-/-) mice was accompanied by their functional differentiation into plasma cells. We have shown that in the absence of galectin-3, B1-cell differentiation into plasma cells is favored and the dynamic equilibrium of B1-cell populations in the peritoneum is maintained through a compensatory increase in B1b lymphocytes.

Sistema de Avalia????o de Desempenho Individual do Inmetro (Siadi)

O Inmetro desenvolveu e implementou modelo de avalia????o de desempenho individual, instrumento de gest??o capaz de promover nova cultura baseada no m??rito, exig??ncia, motiva????o e reconhecimento. Adota remunera????o vari??vel vinculada ao desempenho, com crit??rios objetivos e regras claras, elaborados a partir de amplo debate com os servidores; a avalia????o ?? realizada por comit??s com maioria dos membros externos ?? institui????o, rompendo com a pr??tica limitada da avalia????o exclusivamente pelas chefias. O ciclo ?? anual e o processo consta basicamente da pactua????o de um plano de trabalho do servidor com sua chefia ao in??cio do ciclo, vinculado ao conjunto de objetivos institucionais. A an??lise, ao final do ciclo, do relat??rio de atividades do servidor e do parecer de sua chefia ?? conduzida pelo Comit?? de Avalia????o. A participa????o dos servidores nos dois primeiros ciclos foi irrestrita, com excelente receptividade, independente dos resultados

Sistema Nacional de Gest??o do Conhecimento em Seguran??a P??blica

Visando subsidiar o processo de gest??o do Sistema ??nico de Seguran??a P??blica, a Secretaria Nacional de Seguran??a P??blica (Senasp) investe esfor??os, desde 2003, na cria????o de sistemas nacionais de coleta de dados, na moderniza????o da infraestrutura de TI e na qualifica????o dos profissionais para a produ????o desses dados e o desenvolvimento de insumos, a fim de auxiliar na distribui????o de recursos do Fundo Nacional de Seguran??a P??blica. Todas essas iniciativas comp??em o Sistema Nacional de Gest??o do Conhecimento em Seguran??a P??blica. Em parceria com profissionais e pesquisadores da ??rea e gestores de outros ??rg??os p??blicos, foi estruturada uma nova forma de fazer seguran??a p??blica. As a????es come??aram a ser baseadas em diagn??sticos; a distribui????o de recursos passou a obedecer um sistema de incentivos calcado em indicadores estat??sticos, fundamentais na constru????o do conhecimento necess??rio para aprimorar a efici??ncia, a efic??cia e a efetividade das pol??ticas de seguran??a. Paralelamente, procurou-se difundir a cultura da transpar??ncia e divulga????o de estat??sticas criminais

Sisbio: Sistema de Autoriza????o e Informa????o em Biodiversidade

O Sisbio ?? um sistema informatizado de autoriza????o e de informa????o que objetiva melhorar o atendimento a pesquisadores cujos estudos envolvem coleta de material biol??gico ou s??o desenvolvidos em unidades de conserva????o da natureza ou ainda, em cavernas. Por meio do preenchimento e envio de formul??rios pela internet, pesquisadores solicitam ao Instituto Chico Mendes de Conserva????o da Biodiversidade (ICMBio) autoriza????es para as atividades supracitadas. Pelo sistema, os pesquisadores tamb??m apresentam seus relat??rios de atividades, cujas informa????es compor??o um banco de dados georreferenciado. Anteriormente, essas autoriza????es eram emitidas em papel a partir da an??lise do projeto de pesquisa impresso enviado por correio. Os relat??rios das atividades autorizadas eram arquivados em processos, tornando as informa????es neles contidas pouco dispon??veis para a consulta. O Sisbio mudou esse quadro, promovendo celeridade e transpar??ncia na an??lise, bem como a otimiza????o da gest??o e uso da informa????o

Revis??o dos Procedimentos de P??s-Registro de Medicamentos

O Grupo de Trabalho (GT) de revis??o do regulamento t??cnico para p??s-registro de -medicamentos da Anvisa vem trabalhando na desburocratiza????o e celeridade dos procedimentos regulat??rios referentes ?? atualiza????o de dados do medicamento ap??s a obten????o de seu registro. Esses s??o itens de fundamental import??ncia para o est??mulo da produ????o e da qualidade dos medicamentos comercializados no pa??s. Foi feita uma classifica????o das modifica????es p??s-registro de medicamentos conforme o risco sanit??rio, a complexidade de an??lise e testes farmacot??cnicos. A abordagem permitiu efici??ncia da an??lise t??cnica e, uma vez que esses procedimentos tornaram-se mais c??leres, houve maior previsibilidade nas a????es de p??s-registro com a ado????o dos novos fluxos e prazos de an??lise

O gerenciamento contratual aplicado no ??mbito das contrata????es do Poder Judici??rio de Alagoas

O estudo de caso trata de mudan??as na estrutura de gest??o dos contratos administrativos do Tribunal de Justi??a de Alagoas. Com a finalidade de minimizar o desperd??cio de recursos p??blicos e conferir mais transpar??ncia ?? fiscaliza????o de contratos, o ??rg??o decidiu inserir uma unidade de gest??o contratual entre a figura do fiscal do contrato e o ordenador de despesa. O caso ilustra uma melhoria na forma de gest??o de contratos administrativos e pode ser utilizado em cursos de gest??o de contratos, licita????o e temas afins para an??lise de experi??ncia bem-sucedida de mudan??a organizacional focada na gest??o contratual

Melhoria de gest??o com foco no trin??mio: pessoas, processos e tecnologia de informa????o

O trabalho iniciou-se em junho de 2005, na GMEFH1, cuja metodologia se pautava na revis??o dos processos de trabalho, levantados a partir de reuni??es semanais com um grupo representativo, na defini????o de pap??is e responsabilidades dos colaboradores da ??rea, no desenvolvimento de um sistema de informa????o que possibilitasse a consolida????o dos procedimentos e uniformiza????o de condutas e, por fim, no treinamento de uma pr??tica gestora, com estabelecimento de metas, registro e revis??o de procedimentos, bem como o monitoramento de prazos e resultados. O cen??rio anterior apresentava grande descontrole do fluxo do processo de trabalho, aus??ncia de padr??o nos procedimentos, n??mero desconhecido das peti????es sem an??lise (passivo), infraestrutura impr??pria, subjetividade na an??lise t??cnica, inexist??ncia de planejamento estrat??gico, entre outros. Ap??s a realiza????o do trabalho, foram observados os seguintes resultados: acr??scimo significativo da produtividade, apesar da redu????o do quadro-geral de pessoas (de 38 para 30) e do n??mero de t??cnicos (de 34 para 23) desempenhando a atividade-fim (an??lise 100 t??cnica para concess??o de registro de medicamentos); tratamento do passivo com redu????o de 89% das peti????es que iriam para a an??lise; grande diminui????o do tempo de resposta ao setor regulado; e padroniza????o nos procedimentos de an??lise t??cnica, trazendo uniformidade na conduta t??cnica, tema recorrentemente requisitado pelo setor regulado

Programa Bolsa Fam??lia: financiando fam??lias para o desenvolvimento

O estudo de caso trata da implementa????o do Bolsa Fam??lia, um programa de transfer??ncia de renda para fam??lias pobres, condicionada ao atendimento de exig??ncias espec??ficas por parte dos benefici??rios (comumente conhecida como ???transfer??ncia condicionada de renda???). Ap??s a descri????o dos antecedentes, apontando experi??ncias em n??vel local que inspiraram a pol??tica nacional, o autor apresenta as fases de implementa????o do programa, identificando dificuldades, cr??ticas recebidas e solu????es encontradas pelo governo federal. Em seguida, documenta impactos na redu????o da pobreza e da desigualdade social, e analisa a expans??o do espa??o p??blico originada da experi??ncia do Bolsa Fam??lia. O caso ilustra situa????o que suscita reflex??o e an??lise dos alunos com rela????o ao desenho e desenvolvimento de programa complexo de pol??tica social, podendo se desdobrar em novas pesquisas sobre o Bolsa Fam??lia, seus fatores cr??ticos e de sucesso

Reforma da administra????o p??blica e cultura pol??tica no Brasil: uma vis??o geral

Texto bastante did??tico que compreende uma revis??o da evolu????o da administra????o p??blica brasileira, dos anos 30 aos 90, incluindo tra??os da heran??a colonial. Enfoca a deteriora????o da administra????o p??blica federal e discute diretrizes para a reforma do Estado no Brasil, apontando problemas e resist??ncias pol??ticas a serem enfrentadas