La importancia de los proyectos y redes innovadoras para el avance de la enseñanza de las Ciencias: el caso de un profesor de la Red IRES

Este articulo presenta la descripción y análisis del Modelo de Investigación en la Escuela que fundamenta el Proyecto IRES (Investigación y Renovación Escolar) y el análisis en profundidad de una entrevista a un maestro en el área de ciencias que pertenece a la red de este proyecto: Red IRES. Los resultados ponen en evidencia la importancia que ha tenido para este profesor la pertenencia al proyecto y al colectivo de docentes que lo impulsan, así como la pertinencia del modelo para sustentar los cambios introducidos en el aula. Destaca también la relevancia, para su evolución profesional, del diálogo entre docentes de todos los niveles del sistema educativo, incluida la universidad. Proponemos que estas experiencias sean más reconocidas y valoradas en el ámbito de la Enseñanza de las Ciencias y en las instancias gubernamentales.This article presents the description and analysis of the Research Model in the School that bases the IRES Project (Research and School Renovation) and the in-depth analysis of an interview with a science teacher belonging to the network of this project: IRES Network. The results show how important it is for this teacher to belong to the project and to the group of teachers that promote it, as well as the relevance of the model to support the changes introduced in the classroom. It also highlights the relevance, for its professional evolution, of the dialogue between teachers at all levels of the education system, including the university. We propose that these experiences be more recognized and valued in the field of Science Teaching and in governmental instances

CXCL12 N-terminal end is sufficient to induce chemotaxis and proliferation of neural stem/progenitor cells

Neural stem/progenitor cells (NSC) respond to injury after brain injuries secreting IL-1, IL-6, TNF-alpha, IL-4 and IL-10, as well as chemokine members of the CC and CXC ligand families. CXCL12 is one of the chemokines secreted at an injury site and is known to attract NSC-derived neuroblasts, cells that express CXCL12 receptor, CXCR4. Activation of CXCR4 by CXCL12 depends on two domains located at the N-terminal of the chemokine. in the present work we aimed to investigate if the N-terminal end of CXCL12, where CXCR4 binding and activation domains are located, was sufficient to induce NSC-derived neuroblast chemotaxis. Our data show that a synthetic peptide analogous to the first 21 amino acids of the N-terminal end of CXCL12, named PepC-C (KPVSLSYRCPCRFFESHIARA), is able to promote chemotaxis of neuroblasts in vivo, and stimulate chemotaxis and proliferation of CXCR4+ cells in vitro, without affecting NSC fate. We also show that PepC-C upregulates CXCL12 expression in vivo and in vitro. We suggest the N-terminal end of CXCL12 is responsible for a positive feedback loop to maintain a gradient of CXCL12 that attracts neuroblasts from the subventricular zone into an injury site. (C) 2013 the Authors. Published by Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo, Escola Paulista Med, Dept Biochem, São Paulo, BrazilUniversidade Federal de São Paulo, Neurobiol Lab, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biochem, São Paulo, BrazilUniversidade Federal de São Paulo, Neurobiol Lab, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, São Paulo, BrazilFAPESP: 2005/04061-8FAPESP: 2012/00652-5CNPq: 573909/2008-3]Web of Scienc

SLC6A4 STin2 VNTR genetic polymorphism is associated with tobacco use disorder, but not with successful smoking cessation or smoking characteristics: a case control study.

The aim of this study was to determine if variable number of tandem repeats (VNTR) in the second intron (STin2) of the serotonin transporter (SLC6A4) gene was associated with tobacco use disorder, successful smoking cessation, or smoking characteristics. In this case-control study, patients with current tobacco use disorder, diagnosed according to DSM IV criteria (n = 185), and never-smokers, diagnosed according to CDC criteria (n = 175), were recruited and received 52 weeks of combined pharmacotherapy and cognitive therapy. Successful smoking cessation was defined as exhaled carbon monoxide < 6 ppm. SLC6A4 gene STin2 VNTR polymorphism was assessed using a Multiplex-PCR-based method. At baseline, participants were evaluated using the Fagerström Test for Nicotine Dependence (FTND) and the ASSIST scale

Genetic Polymorphisms of the TGFB1 Signal Peptide and Promoter Region: Role in Wilms Tumor Susceptibility?

The aim of the present study was to investigate the rs1800468 (G-800A), rs1800469 (C-509T), rs1800470 (C29T), and rs1800471 (G74C) TGFB1 genetic polymorphisms and their haplotype structures in patients with Wilms Tumor (WT) and neoplasia-free controls. The genomic DNA was extracted from 35 WT patients and 160 neoplasia-free children, and the TGFB1 polymorphisms were genotyped by polymerase chain reaction, followed by restriction fragment length polymorphism. The haplotype structures were inferred, and permutation and logistic regression tests were performed to check for differences in haplotype distribution between the control and WT individuals. Positive associations were found in the recessive model for rs1800469 T allele (OR: 8.417; 95% CI: 3.177 to 22.297; P < 0.001) and for the rs1800470 C allele (OR: 3.000; 95% CI: 1.296 to 6.944; P = 0.01). Haplotype analysis revealed a significant negative association between GCTG and WT (OR: 0.236, 95% CI: 0.105 to 0.534; P = 0.0002); by contrast, the GTTG haplotype was associated with increased risk for WT (OR: 12.0; 95% CI: 4.202 to 34.270; P < 0.001). Furthermore, rs1800469 was negatively correlated with tumor size and a trend toward a positive correlation for capsular invasion was observed in the dominant model (Tau-b: −0.43, P = 0.02 and tau-b: 0.5, P = 0.06, respectively). This is the first study with rs1800468, rs1800469, rs1800470, and rs1800471 TGFB1 polymorphisms in WT, and our results suggest that the TGFB1 promoter and signal peptide region polymorphisms may be associated with WT susceptibility and clinical presentation

Genetic Polymorphism and Expression of CXCR4 in Breast Cancer

CXCR4 genetic polymorphisms, as well as their expression level, have been associated with cancer development and prognosis. The present study aimed to investigate the influence of CXCR4 rs2228014 polymorphism on its mRNA and protein expression in breast cancer samples. It was observed that patients presented higher CXCR4 mRNA relative expression (5.7-fold) than normal mammary gland, but this expression was not correlated with patients clinicopathological features (nuclear grade, nodal status, ER status, PR status, p53 staining, Ki67 index, and HER-2 status). Moreover, CXCR4 mRNA relative expression also did not differ regarding the presence or absence of T allele (p=0.301). In the immunohistochemical assay, no difference was observed for CXCR4 cytoplasmic protein staining in relation to different genotypes (p=0.757); however, high cytoplasmic CXCR4 staining was verified in invasive breast carcinoma (p<0.01). All in all, the results from present study indicated that rs2228014 genetic variant does not alter CXCR4 mRNA or protein expression. However, this receptor was more expressed in tumor compared to normal tissue, in both RNA and protein levels, suggesting its promising applicability in the general context of mammary carcinogenesis

Eqlb mutation causes changes in gene expression of cell cycle control of precursors of cerebellar neurons

Várias doenças humanas atualmente conhecidas têm causas genéticas. Uma maneira de se entender as alterações moleculares que levam a essas doenças é através da análise da disfunção de um gene, que pode ser feito usando modelos animais que recapitulem tais patologias. O camundongo desempenha muito bem essa função, devido à alta porcentagem de homologia entre os genomas murino e humano. Mutações espontâneas ou quimicamente induzidas são ferramentas úteis para elucidar como um gene mutado dá origem ao fenótipo da doença. Apesar do atual banco de dados de camundongos mutantes, que é composto na sua maioria por animais nocautes, ser uma fonte valiosa de modelos animais, apenas uma pequena proporção do total de genes mamíferos é representada. Esse vazio está sendo, em parte, completado pelo estabelecimento de novos programas de mutagênese utilizando-se potentes agentes mutagênicos como N-ethyl-N-nitrosourea (ENU). Através de um projeto de mutagênese por ENU, foram isolados mutantes recessivos apresentando vários fenótipos, sendo um deles um mutante apresentando problemas de equilíbrio com características de falta de coordenação motora, denominado equilibrio (eqlb). O fenótipo apresentado por esse mutante nos levou à hipótese de que a mutação gerada poderia estar afetando o desenvolvimento do cerebelo, região do sistema nervoso que controla a execução dos movimentos e o equilíbrio. A avaliação do comportamento de camundongos adultos selvagem e mutantes em teste de desempenho em barra rotatória mostrou que o tempo de permanência dos mutantes eqlb estava significantemente diminuído em relação aos camundongos controle BALB/c. Análises histológicas de cerebelo de camundongos mutantes revelaram formação anormal das camadas celulares, com desorganização da camada de células de Purkinje, o principal tipo de neurônio do cerebelo. As análises histológicas também revelaram uma camada granular externa (CGE) mais espessa nos camundongos mutantes, quando comparados com cerebelos de camundongos selvagem de mesma idade. Ensaio de incorporação de [3H]-timidina mostrou que o espessamento dessa camada pode ser atribuído ao alto índice de proliferação observado nos cerebelos dos camundongos mutantes. Esse aumento no índice de proliferação de precursores de neurônios granulares não foi observado em outros órgãos e outras regiões do SNC, bem com também não foi observado células tronco neurais e mesenquimais derivadas da medula óssea. O mapeamento genético da mutação, usando-se marcadores microssatélites polimórficos, localizou a mutação no cromossomo 17, em uma sub-região delimitada pelo marcador D17Mit267 (3,31Mb) e o limite centromérico. Essa região possui sintenia conservada com a região telomérica do cromossomo 6 humano, a qual apresenta loci relacionados ao aparecimento de ataxias recessivas. Dois genes candidatos foram sequenciados: ENSMUSG00000044697 foi sequenciado completamente e a mutação não foi encontrada, e ENSMUSG00000046201 (Rbm16) e o sequenciamento não foi completo. Análise de expressão gênica diferencial revelou alteração na expressão de genes relacionados a doenças neurológicas e crescimento celular e proliferação nos camundongos mutantes de 6 dias pós natal, e alterações na expressão de genes relacionadas a tumor cerebral e meduloblastoma em camundongos mutantes de 15 dias de desenvolvimento pós natal.TEDEBV UNIFESP: Teses e dissertaçõe

eqlb mutation mapped to mouse chromossome 17 causes abnormal cerebellar development and ataxia

BV UNIFESP: Teses e dissertaçõe

Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical management in cancer patients, assisting in diagnostic, staging, evaluation of therapeutic response, detection of recurrence and metastasis, and development of new treatment modalities. In this context, this review aims to discuss the main tumor markers in breast carcinogenesis. The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented. Furthermore, this review shows the new molecular targets in breast cancer: CXCR4, caveolin, miRNA, and FOXP3, as promising candidates for future development of effective and targeted therapies, also with lower toxicity

CC Chemokine Receptor 5: The Interface of Host Immunity and Cancer

Solid tumors are embedded in a stromal microenvironment consisting of immune cells, such as macrophages and lymphocytes, as well as nonimmune cells, such as endothelial cells and fibroblasts. Chemokines are a type of small secreted chemotactic cytokine and together with their receptors play key roles in the immune defense. Critically, they regulate cancer cellular migration and also contribute to their proliferation and survival. The CCR5 chemokine receptor is involved in leucocytes chemotaxis to sites of inflammation and plays an important role in the macrophages, T cells, and monocytes recruitment. Additionally, CCR5 may have an indirect effect on cancer progression by controlling the antitumor immune response, since it has been demonstrated that its expression could promote tumor growth and contribute to tumor metastasis, in different types of malignant tumors. Furthermore, it was demonstrated that a CCR5 antagonist may inhibit tumor growth, consisting of a possible therapeutic target. In this context, the present review focuses on the establishment of CCR5 within the interface of host immunity, tumor microenvironment, and its potential as a targeting to immunotherapy