Programa Institucional de Bolsa de Iniciação à Docência (PIBID) e a Formação de Professores de Química – Subprojeto UnB/Sobradinho-DF

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The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer

International audienceHeparan sulfate (HS) proteoglycan chains are key components of the breast tumor microenvironment that critically influence the behavior of cancer cells. It is established that abnormal synthesis and processing of HS play a prominent role in tumorigenesis, albeit mechanisms remain mostly obscure. HS function is mainly controlled by sulfotransferases, and here we report a novel cellular and pathophysiological significance for the 3-O-sulfotransferase 3-OST3A (HS3ST3A), catalyzing the final maturation step of HS, in breast cancer. We show that 3-OST3A is epigenetically repressed in all breast cancer cell lines of a panel representative of distinct molecular subgroups, except in human epidermal growth factor receptor 2-positive (HER2+) sloan-kettering breast cancer (SKBR3) cells. Epigenetic mechanisms involved both DNA methylation and histone modifications, producing different repressive chromatin environments depending on the cell molecular signature. Gain and loss of function experiments by cDNA and siRNA transfection revealed profound effects of 3-OST3A expression on cell behavior including apoptosis, proliferation, response to trastuzumab in vitro and tumor growth in xenografted mice. 3-OST3A exerted dual activities acting as tumor-suppressor in lumA-michigan cancer foundation (MCF)-7 and triple negative-MD Anderson (MDA) metastatic breast (MB)-231 cells, or as an oncogenic factor in HER2+-SKBR3 cells. Mechanistically, fluorescence-resonance energy transfer-fluorescence-lifetime imaging microscopy experiments indicated that the effects of 3-OST3A in MCF-7 cells were mediated by altered interactions between HS and fibroblast growth factor-7 (FGF-7). Further, this interplay between HS and FGF-7 modulated downstream ERK, AKT and p38 cascades, suggesting that altering 3-O-sulfation affects FGFR2IIIb-mediated signaling. Corroborating our cellular data, a clinical study conducted in a cohort of breast cancer patients uncovered that, in HER2+ patients, high level expression of 3-OST3A in tumors was associated with reduced relapse-free survival. Our findings define 3-OST3A as a novel regulator of breast cancer pathogenicity, displaying tumor-suppressive or oncogenic activities in a cell-and tumor-dependent context, and demonstrate the clinical value of the HS-O-sulfotransferase 3-OST3A as a prognostic marker in HER2+ patients

Programa Institucional de Bolsa de Iniciação à Docência (Pibid) e a Formação de Professores de Química – Subprojeto UnB/Ceilândia-DF

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Burnout and engagement in university students: A psychometric analysis of the MBI-SS and UWES-S

No Abstract. South African Journal of Higher Education Vol. 21 (1) 2007: pp.147-16

A concentrating solar power value proposition for South Africa

CITATION: Gauche, P., Von Backstrom, T. W. & Brent, A. C. 2013. A concentrating solar power value proposition for South Africa. Journal of Energy in Southern Africa, 24(1):67–76, doi:10.17159/2413-3051/2014/v24i1a3122.The original publication is available at https://journals.assaf.org.za/index.php/jesa/indexConcentrating solar power (CSP) offers the potential for a high degree of localization and an alternative strategy to meet electricity demand for South Africa in a future of uncertain conventional resources. The integrated resource plan (IRP) makes strides to introduce renewables to the electricity generation system by 2030, but we argue that the proposed energy mix is too reliant on resources that are not only unsustainable but also at risk in the short to medium term. Coal and other conventional resources may be more limited than originally anticipated, which if true, requires action to be taken soon. CSP is currently the only sustainable and dispatchable energy technology that could domestically supply a significant portion of South Africa’s electricity needs. A balanced mix of PV, wind and CSP can provide the energy supply needed in South Africa, but steps are required soon to take advantage of the localization potential and excellent sustainable energy resources.https://journals.assaf.org.za/index.php/jesa/article/view/3122Publisher's versio