Mycobacterium tuberculosis expressing phospholipase C subverts PGE2 synthesis and induces necrosis in alveolar macrophages

Abstract\ud \ud Background\ud Phospholipases C (PLCs) are virulence factors found in several bacteria. In Mycobacterium tuberculosis (Mtb) they exhibit cytotoxic effects on macrophages, but the mechanisms involved in PLC-induced cell death are not fully understood. It has been reported that induction of cell necrosis by virulent Mtb is coordinated by subversion of PGE2, an essential factor in cell membrane protection.\ud \ud \ud Results\ud Using two Mtb clinical isolates carrying genetic variations in PLC genes, we show that the isolate 97-1505, which bears plcA and plcB genes, is more resistant to alveolar macrophage microbicidal activity than the isolate 97-1200, which has all PLC genes deleted. The isolate 97-1505 also induced higher rates of alveolar macrophage necrosis, and likewise inhibited COX-2 expression and PGE2 production. To address the direct effect of mycobacterial PLC on cell necrosis and PGE2 inhibition, both isolates were treated with PLC inhibitors prior to macrophage infection. Interestingly, inhibition of PLCs affected the ability of the isolate 97-1505 to induce necrosis, leading to cell death rates similar to those induced by the isolate 97-1200. Finally, PGE2 production by Mtb 97-1505-infected macrophages was restored to levels similar to those produced by 97-1200-infected cells.\ud \ud \ud Conclusions\ud \ud Mycobacterium tuberculosis bearing PLCs genes induces alveolar macrophage necrosis, which is associated to subversion of PGE2 production.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP, grant No. 2009/07169-5), and PAA was an FAPESP fellowship recipient (Grant No. 2011/01845-9)

Choral singing therapy following stroke or Parkinsons disease: An exploration of participants experiences

© 2015 Informa UK Ltd. Purpose: People with stroke or Parkinsons disease (PD) live with reduced mood, social participation and quality of life (QOL). Communication difficulties affect 90% of people with PD (dysarthria) and over 33% of people with stroke (aphasia). These consequences are disabling in many ways. However, as singing is typically still possible, its therapeutic use is of increasing interest. This article explores the experiences of and factors influencing participation in choral singing therapy (CST) by people with stroke or PD and their significant others. Method: Participants (eight people with stroke, six with PD) were recruited from a community music therapy choir running CST. Significant others (seven for stroke, two for PD) were also recruited. Supported communication methods were used as needed to undertake semi-structured interviews (total N = 23). Results: Thematic analysis indicated participants had many unmet needs associated with their condition, which motivated them to explore self-management options. CST participation was described as an enjoyable social activity, and participation was perceived as improving mood, language, breathing and voice. Conclusions: Choral singing was perceived by people with stroke and PD to help them self-manage some of the consequences of their condition, including social isolation, low mood and communication difficulties.Implications for RehabilitationChoral singing therapy (CST) is sought out by people with stroke and PD to help self-manage symptoms of their condition.Participation is perceived as an enjoyable activity which improves mood, voice and language symptoms.CST may enable access to specialist music therapy and speech language therapy protocols within community frameworks

TGF-β-Mediated Sustained ERK1/2 Activity Promotes the Inhibition of Intracellular Growth of Mycobacterium avium in Epithelioid Cells Surrogates

Transforming growth factor beta (TGF-β) has been implicated in the pathogenesis of several diseases including infection with intracellular pathogens such as the Mycobacterium avium complex. Infection of macrophages with M. avium induces TGF-β production and neutralization of this cytokine has been associated with decreased intracellular bacterial growth. We have previously demonstrated that epithelioid cell surrogates (ECs) derived from primary murine peritoneal macrophages through a process of differentiation induced by IL-4 overlap several features of epithelioid cells found in granulomas. In contrast to undifferentiated macrophages, ECs produce larger amounts of TGF-β and inhibit the intracellular growth of M. avium. Here we asked whether the levels of TGF-β produced by ECs are sufficient to induce a self-sustaining autocrine TGF-β signaling controlling mycobacterial replication in infected-cells. We showed that while exogenous addition of increased concentration of TGF-β to infected-macrophages counteracted M. avium replication, pharmacological blockage of TGF-β receptor kinase activity with SB-431542 augmented bacterial load in infected-ECs. Moreover, the levels of TGF-β produced by ECs correlated with high and sustained levels of ERK1/2 activity. Inhibition of ERK1/2 activity with U0126 increased M. avium replication in infected-cells, suggesting that modulation of intracellular bacterial growth is dependent on the activation of ERK1/2. Interestingly, blockage of TGF-β receptor kinase activity with SB-431542 in infected-ECs inhibited ERK1/2 activity, enhanced intracellular M. avium burden and these effects were followed by a severe decrease in TGF-β production. In summary, our findings indicate that the amplitude of TGF-β signaling coordinates the strength and duration of ERK1/2 activity that is determinant for the control of intracellular mycobacterial growth

Mycobacterium tuberculosis expressing phospholipase C subverts PGE2 synthesis and induces necrosis in alveolar macrophages

Abstract Background Phospholipases C (PLCs) are virulence factors found in several bacteria. In Mycobacterium tuberculosis (Mtb) they exhibit cytotoxic effects on macrophages, but the mechanisms involved in PLC-induced cell death are not fully understood. It has been reported that induction of cell necrosis by virulent Mtb is coordinated by subversion of PGE2, an essential factor in cell membrane protection. Results Using two Mtb clinical isolates carrying genetic variations in PLC genes, we show that the isolate 97-1505, which bears plcA and plcB genes, is more resistant to alveolar macrophage microbicidal activity than the isolate 97-1200, which has all PLC genes deleted. The isolate 97-1505 also induced higher rates of alveolar macrophage necrosis, and likewise inhibited COX-2 expression and PGE2 production. To address the direct effect of mycobacterial PLC on cell necrosis and PGE2 inhibition, both isolates were treated with PLC inhibitors prior to macrophage infection. Interestingly, inhibition of PLCs affected the ability of the isolate 97-1505 to induce necrosis, leading to cell death rates similar to those induced by the isolate 97-1200. Finally, PGE2 production by Mtb 97-1505-infected macrophages was restored to levels similar to those produced by 97-1200-infected cells. Conclusions Mycobacterium tuberculosis bearing PLCs genes induces alveolar macrophage necrosis, which is associated to subversion of PGE2 production

Mycobacterium tuberculosis complex differentiation using gyrB-restriction fragment length polymorphism analysis

Mycobacterium tuberculosis complex (MTBC) members are causative agents of human and animal tuberculosis. Differentiation of MTBC members is required for appropriate treatment of individual patients and for epidemiological purposes. Strains from six MTBC species - M. tuberculosis, M. bovis subsp. bovis, M. bovis BCG, M. africanum, M. pinnipedii, and "M. canetti" - were studied using gyrB-restriction fragment length polymorphism (gyrB-RFLP) analysis. A table was elaborated, based on observed restriction patterns and published gyrB sequences. To evaluate applicability of gyrB-RFLP at Instituto Adolfo Lutz, São Paulo, Mycobacterial Reference Laboratory, 311 MTBC clinical isolates, previously identified using traditional methods as M. tuberculosis (306), M. bovis (3), and M. bovis BCG (2), were analyzed by gyrB-RFLP. All isolates were correctly identified by the molecular method, but no distinction between M. bovis and M. bovis BCG was obtained. Differentiation of M. tuberculosis and M. bovis is of utmost importance, because they require different treatment schedules. In conclusion, gyrB-RFLP is accurate and easy-to-perform, with potential to reduce time needed for conventional differentiation methods. However, application for epidemiological studies remains limited, because it cannot differentiate M. tuberculosis from M. africanum subtype II, and "M. canetti", M. africanum subtype I from M. pinnipedii, and. M. bovis from M. bovis BCG

O cargo público de livre provimento na organização da administração pública federal brasileira: uma introdução ao estudo da organização da direção pública na perspectiva de estudos organizacionais Public position filled by appointment in the Brazilian federal administration: an introduction to the study of public management organization from the organizational studies perspective

A organização da administração pública federal brasileira é raramente abordada na pesquisa no campo de estudos organizacionais (EOs). Privilegia-se a tomada de decisão, seguindo-se a tradição de pesquisa operacional de cunho funcionalista. Contudo, direção é mais complexa e inclui decisão. A direção na administração pública federal brasileira se dá exclusivamente por meio de cargos de livre provimento. Tal realidade permite entender a direção como ação eminentemente política, cristalizada na organização da administração pública. Este artigo possui caráter metodológico e demonstra que o cargo público de livre provimento possui centralidade na organização da administração pública federal brasileira. Identifica, ainda, práticas de operação e interações no exercício da direção pública.<br>The organization of the Brazilian federal public administration is seldom addressed by organizational studies (OS) research. The decision-making process is privileged, according to the tradition of functionalist operational research. However, managing is more complex than decision-making, which is included by it. Management level in Brazilian federal public administration is completely filled by appointment. This reality makes us understand management as an utterly political action, crystallized in the public administration organization. This article has a methodological perspective and demonstrates that public positions filled by appointment are central to the Brazilian federal public administration,. It also identifies practices and interactions of public management

Comportamento comunicativo de indivíduos com diagnóstico de esquizofrenia

Objetivo descrever o comportamento comunicativo de indivíduos com diagnóstico de esquizofrenia em processo de reabilitação psicossocial. Métodos estudo descritivo-exploratório, com amostra por conveniência de recorte transversal. Participaram 50 indivíduos com diagnóstico de esquizofrenia, de ambos os sexos, com faixa etária entre 19 e 75 anos, usuários de um Núcleo de Saúde Mental de uma cidade do interior do estado de São Paulo, Brasil. Foi realizado levantamento nos prontuários para obter dados pessoais e o subtipo da esquizofrenia. Para avaliar o comportamento comunicativo utilizou-se a Bateria Montreal de Avaliação da Comunicação (Bateria MAC), constituída por 14 tarefas que avaliam os aspectos discursivo, pragmático inferencial, léxico-semântico e prosódico da linguagem. Resultados os indivíduos, em sua maioria, eram do sexo masculino, com baixa escolaridade, praticantes do catolicismo e com esquizofrenia do subtipo paranoide. A avaliação pela Bateria MAC apontou alterações em todas as tarefas avaliadas e a maioria dos participantes respondeu que é consciente da dificuldade comunicativa. As maiores alterações ocorreram nas tarefas de evocação lexical com critério semântico, atos de fala indiretos, discurso conversacional e discurso narrativo, e, as menores alterações, ocorreram nos componentes prosódicos no nível de compreensão, destacando-se que, o nível da produção nos aspectos linguísticos e emocionais da prosódia, também apresentou alteração considerável. Conclusão todas as tarefas avaliadas apresentaram alterações. Os aspectos mais prejudicados foram o discurso e a pragmática, que não devem ser relacionados somente aos aspectos linguísticos, mas também às características de alteração do pensamento e da cognição, ao embotamento afetivo e questões sociais desse transtorno