OFICINAS AMBIENTAIS COMO ESPAÇO DE CONSTRUÇÃO DA CONSCIÊNCIA AMBIENTAL

http://dx.doi.org/10.5902/223611708647The environmental workshops act as a process of awareness and knowledge of the issue in this work will be analyzedenvironmental workshops developed in the years 2011 and 2012, with the design of Knowledge Architects withstudents from rural school Dr. Honorato de Souza Santos. The methodology used for this study was to developparticipatory research, supported by the institution, inserted in Institutional Project UFSM/Technology Socialinclusion: citizenship, environmental education and agroecology. The objective of the study is to analyze the practiceof environmental workshops as reflection-action process by students for making awareness and environmentalpreservation. The results allowed the students the awareness regarding the preservation and conservation of theenvironment and proximity and interaction between the school and the academic universe. We conclude that theworkshops fulfill the purpose of raising environmental awareness and promoting a process of awareness ofelementary students from school Dr. Honorato de Souza Santos/Cachoeira do Sul-RS.http://dx.doi.org/10.5902/223611708647As oficinas ambientais atuam como um processo de conscientização e conhecimento da problemática em questão, neste trabalho será analisado as oficinas ambientais desenvolvidas, nos anos de 2011 e 2012, junto ao Projeto Arquitetos do Saber, com estudantes da escola rural Dr. Honorato de Souza Santos. A metodologia utilizada para o desenvolvimento desse estudo foi a pesquisa participante, apoiada pela instituição, inserido no Projeto Institucional UFSM/Tecnologias de Inclusão social: cidadania, educação ambiental e agroecologia. O objetivo do estudo é analisar a prática das oficinas ambientais como processo de reflexão-ação por parte dos estudantes para a tomada da consciência e preservação ambiental. Os resultados alcançados permitiram aos alunos a tomada de consciência em relação à preservação e conservação do meio ambiente e aproximação e interação entre o universo escolar e o meio acadêmico. Conclui-se que as oficinas cumprem o propósito de despertar a percepção ambiental e promover um processo de conscientização dos alunos do ensino fundamental da escola Dr. Honorato de Souza Santos/Cachoeira do Sul-RS.

OFICINAS AMBIENTAIS COMO ESPAÇO DE CONSTRUÇÃO DA CONSCIÊNCIA AMBIENTAL

http://dx.doi.org/10.5902/223611708647The environmental workshops act as a process of awareness and knowledge of the issue in this work will be analyzedenvironmental workshops developed in the years 2011 and 2012, with the design of Knowledge Architects withstudents from rural school Dr. Honorato de Souza Santos. The methodology used for this study was to developparticipatory research, supported by the institution, inserted in Institutional Project UFSM/Technology Socialinclusion: citizenship, environmental education and agroecology. The objective of the study is to analyze the practiceof environmental workshops as reflection-action process by students for making awareness and environmentalpreservation. The results allowed the students the awareness regarding the preservation and conservation of theenvironment and proximity and interaction between the school and the academic universe. We conclude that theworkshops fulfill the purpose of raising environmental awareness and promoting a process of awareness ofelementary students from school Dr. Honorato de Souza Santos/Cachoeira do Sul-RS.http://dx.doi.org/10.5902/223611708647As oficinas ambientais atuam como um processo de conscientização e conhecimento da problemática em questão, neste trabalho será analisado as oficinas ambientais desenvolvidas, nos anos de 2011 e 2012, junto ao Projeto Arquitetos do Saber, com estudantes da escola rural Dr. Honorato de Souza Santos. A metodologia utilizada para o desenvolvimento desse estudo foi a pesquisa participante, apoiada pela instituição, inserido no Projeto Institucional UFSM/Tecnologias de Inclusão social: cidadania, educação ambiental e agroecologia. O objetivo do estudo é analisar a prática das oficinas ambientais como processo de reflexão-ação por parte dos estudantes para a tomada da consciência e preservação ambiental. Os resultados alcançados permitiram aos alunos a tomada de consciência em relação à preservação e conservação do meio ambiente e aproximação e interação entre o universo escolar e o meio acadêmico. Conclui-se que as oficinas cumprem o propósito de despertar a percepção ambiental e promover um processo de conscientização dos alunos do ensino fundamental da escola Dr. Honorato de Souza Santos/Cachoeira do Sul-RS

The prolyl hydroxylase enzymes are positively associated with hypoxia-inducible factor-1α and vascular endothelial growth factor in human breast cancer and alter in response to primary systemic treatment with epirubicin and tamoxifen

Introduction: The purpose of the present study was to investigate the relationship of expression of hypoxia inducible factor (HIF)-1α-modifying enzymes prolyl hydroxylase (PHD)1, PHD2 and PHD3 to response of tumours and survival in breast cancer patients enrolled in a phase II trial of neoadjuvant anthracycline and tamoxifen therapy.Methods: The expression of PHD1, PHD2 and PHD3 together with HIF-1α and the HIF-inducible genes vascular endothelial cell growth factor (VEGF) and carbonic anhydrase IX were assessed by immunohistochemistry using a tissue microarray approach in 211 patients with T2-4 N0-1 breast cancer enrolled in a randomised trial comparing single-agent epirubicin versus epirubicin and tamoxifen as the primary systemic treatment.Results: PHD1, PHD2 and PHD3 were detected in 47/179 (26.7%), 85/163 (52.2%) and 69/177 (39%) of tumours at baseline. PHD2 and PHD3 expression was moderate/strong whereas PHD1 expression was generally weak. There was a significant positive correlation between HIF-1α and PHD1 (P = 0.002) and PHD3 (P < 0.05) but not PHD2 (P = 0.41). There was a significant positive relationship between VEGF and PHD1 (P < 0.008) and PHD3 (P = 0.001) but not PHD2 (P = 0.09). PHD1, PHD2 and PHD3 expression was significantly increased after epirubicin therapy (all P < 0.000) with no significant difference in PHD changes between the treatment arms. There was no significant difference in response in tumours that expressed PHDs and PHD expression was not associated with survival.Conclusions: Although expression of the PHDs was not related to response or survival in patients receiving neoadjuvant epirubicin, our data provide the first evidence that these enzymes are upregulated on therapy in breast cancer and that the biological effects independent of HIF make them therapeutic targets. © 2011 Fox et al.; licensee BioMed Central Ltd

Variations in basement membrane mechanics are linked to epithelial morphogenesis

International audienceThe regulation of morphogenesis by the basement membrane (BM) may rely on changes in its mechanical properties. To test this, we developed an atomic force microscopy-based method to measure BM mechanical stiffness during two key processes in Drosophila ovarian follicle development. First, follicle elongation depends on epithelial cells that collectively migrate, secreting BM fibrils perpendicularly to the anteroposterior axis. Our data show that BM stiffness increases during this migration and that fibril incorporation enhances BM stiffness. In addition, stiffness heterogeneity, due to oriented fibrils, is important for egg elongation. Second, epithelial cells change their shape from cuboidal to either squamous or columnar. We prove that BM softens around the squamous cells and that this softening depends on the TGF beta pathway. We also demonstrate that interactions between BM constituents are necessary for cell flattening. Altogether, these results show that BM mechanical properties are modified during development and that, in turn, such mechanical modifications influence both cell and tissue shapes

Hypoxia-related biological markers as predictors of epirubicinbased treatment responsiveness and resistance in locally advanced breast cancer

PURPOSE: To identify hypoxia-related biomarkers indicative of response and resistance to epirubicin treatment in patients with locally advanced breast cancer. PATIENTS AND METHODS: One hundred seventy-six women with T2-4 N0-1 breast tumours were randomly assigned to receive epirubicin 120 mg/m2/1-21 (EPI ARM), epirubicin 120 mg/m2/1-21 + erythropoietin 10.000 IU sc three times weekly (EPI-EPO ARM) and epirubicin 40 mg/m2/w-q21 (EPI-W ARM). Sixteen tumour proteins involved in cell survival, hypoxia, angiogenesis and growth factor, were assessed by immunohistochemistry in pre-treatment samples. A multivariate generalized linear regression approach was applied using a penalized least-square minimization to perform variable selection and regularization. RESULTS: VEGF and GLUT-1 expression were significantly positively associated with complete response (CR) to treatment in all leave-one-out iterations. Bcl-2 expression was inversely correlated with pCR, whilst EPO expression was positively correlated with pathological complete response (pCR). Haemaglobin and HIF-1a nuclear expression were inversely correlated with pCR. HB and HIF-1a expression were associated with a higher risk of relapse and overall survival. CONCLUSION: Hypoxic biomarkers determines the epirubicin resistance in breast cancer. Assessment of such biomarkers, may be useful for predicting chemosensitivity and also anthracycline-based treatment outcome

Gradient in cytoplasmic pressure in germline cells controls overlying epithelial cell morphogenesis

International audienceIt is unknown how growth in one tissue impacts morphogenesis in a neighboring tissue. To address this, we used the Drosophila ovarian follicle, in which a cluster of 15 nurse cells and a posteriorly located oocyte are surrounded by a layer of epithelial cells. It is known that as the nurse cells grow, the overlying epithelial cells flatten in a wave that begins in the anterior. Here, we demonstrate that an anterior to posterior gradient of decreasing cytoplasmic pressure is present across the nurse cells and that this gradient acts through TGFβ to control both the triggering and the progression of the wave of epithelial cell flattening. Our data indicate that intrinsic nurse cell growth is important to control proper nurse cell pressure. Finally, we reveal that nurse cell pressure and subsequent TGFβ activity in the stretched cells combine to increase follicle elongation in the anterior, which is crucial for allowing nurse cell growth and pressure control. More generally, our results reveal that during development, inner cytoplasmic pressure in individual cells has an important role in shaping their neighbors

Nuclear localization of TRK-A in liver cells

The liver represents a site of expression of neurotrophins and their receptors. We have characterized the expression and intracellular localization of the nerve growth factor (NGF) receptor, Trk-A, in liver cells in vivo and in vitro. In both normal and fibrotic liver tissue, Trk-A immunostaining was present in different cell types, including parenchymal cells and cells of the inflammatory infiltrate. In hepatocytes and activated stellate cells (HSC), Trk-A showed a predominant nuclear localization, both in the presence and absence of injury. In cultured HSC, Trk-A was found to be functional, because exposure of the cells to recombinant NGF resulted in stimulation of cell migration and activation of intracellular signaling pathways, including Ras-ERK and PI3K/Akt. Remarkably, in cultured HSC, Trk-A staining was found constitutively in the nucleus. In these cells, Trk-A could be stained only by antibodies directed against the intracellular domain but not by those recognizing the extracellular portion of Trk-A suggesting that the intracellular portion of the receptor is the major determinant of nuclear Trk-A staining. In contrast to HSC, freshly isolated hepatocytes did not show any nuclear localization of the intracellular portion of Trk-A. In pheocromocytoma cells, nuclear staining for Trk-A was not present in conditions of serum deprivation, but could be induced by exposure to NGF or to a mixture of soluble mediators. We conclude that nuclear localization of the intracellular domain of Trk-A is observed constitutively in liver cells such as HSC, while in other cell types it could be induced in response to soluble factors

Hypoxia-inducible factor-1\u3b1 expression predicts a poor response to primary chemoendocrine therapy and disease-free survival in primary human breast cancer

PURPOSE: To investigate the relationship of hypoxia-inducible factor-1alpha (HIF-1alpha) tumor expression in predicting the response to epirubicin and disease-free survival (DFS) in patients with breast cancer enrolled in a single institution trial of primary anthracycline and tamoxifen therapy. EXPERIMENTAL DESIGN: The expression of HIF-1alpha was assessed by immunohistochemistry in 187 patients with T(2-4) N(0-1) breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin + tamoxifen as primary systemic treatment. All patients postoperatively received four cycles of the four weekly i.v. CMF regimen (cyclophosphamide, methotrexate, and 5-fluorouracil). Patients with estrogen receptor (ER)-positive primary tumors also underwent 5 years of treatment with adjuvant tamoxifen. Carbonic anhydrase IX (CAIX) was also scored as a marker of HIF activity. RESULTS: Overall response to therapy progressively decreased with increasing tumor HIF-1alpha (P < 0.05), and HIF-1alpha was an independent predictor of response (P < 0.048). HIF-1alpha expression was also associated with a significantly shorter DFS (P < 0.02) in all patients and in ER-positive but not in ER-negative patients. Furthermore, CAIX positivity conferred a significantly shorter DFS (P = 0.02) compared with CAIX-negative tumors in patients with HIF-1alpha-negative tumors. CONCLUSIONS: HIF-1alpha expression in patients with breast cancer is a marker of poor therapy response and outcome, especially in ER-positive patients. The combination of two hypoxia markers has greater utility than assessing just one, and patients with hypoxia markers in their tumors may be suitable for administration of drugs that reduce HIF-1alpha expression and increase oxygen delivery to the tumor bed before starting neoadjuvant therapie