445 research outputs found
Integrative analysis of SF-1 transcription factor dosage impact on genome-wide binding and gene expression regulation
Steroidogenic Factor-1 (SF-1) is a nuclear receptor that has a pivotal role in the development of adrenal glands and gonads and in the control of steroid hormone production, being also implicated in the pathogenesis of adrenocortical tumors. We have analyzed the mechanisms how SF-1 controls gene expression in adrenocortical cells and showed that it regulates different categories of genes according to its dosage. Significant correlations exist between the localization of SF-1-binding sites in chromatin under different dosage conditions and dosage-dependent regulation of gene expression. Our study revealed unexpected functional interactions between SF-1 and Neuron-Restrictive Silencer Factor/RE1-Silencing Transcription Factor (NRSF/REST), which was first characterized as a repressor of neuronal gene expression in non-neuronal tissues, in the regulation of gene expression in steroidogenic cells. When overexpressed, SF-1 reshapes the repertoire of NRSF/REST—regulated genes, relieving repression of key steroidogenic genes. These data show that NRSF/REST has a novel function in regulating gene expression in steroidogenic cells and suggest that it may have a broad role in regulating tissue-specific gene expression programs
Bone sialoprotein is predictive of bone metastases in resectable non small cell lung carcinoma: A case–control study and prevalence data
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Diagnostic and prognostic role of steroidogenic factor 1 in adrenocortical carcinoma: a validation study focusing on clinical and pathologic correlates
Highly Sulfated K5 Escherichia coli Polysaccharide Derivatives Inhibit Respiratory Syncytial Virus Infectivity in Cell Lines and Human Tracheal-Bronchial Histocultures.
Respiratory syncytial virus (RSV) exploits cell surface heparan sulfate proteoglycans (HSPGs) as attachment receptors. The interaction between RSV and HSPGs thus presents an attractive target for the development of novel inhibitors of RSV infection. In this study, selective chemical modification of the Escherichia coli K5 capsular polysaccharide was used to generate a collection of sulfated K5 derivatives with a backbone structure that mimics the heparin/heparan sulfate biosynthetic precursor. The screening of a series of N-sulfated (K5-NS), O-sulfated (K5-OS), and N,O-sulfated (K5-N,OS) derivatives with different degrees of sulfation revealed the highly sulfated K5 derivatives K5-N,OS(H) and K5-OS(H) to be inhibitors of RSV. Their 50% inhibitory concentrations were between 1.07 nM and 3.81 nM in two different cell lines, and no evidence of cytotoxicity was observed. Inhibition of RSV infection was maintained in binding and attachment assays but not in preattachment assays. Moreover, antiviral activity was also evident when the K5 derivatives were added postinfection, both in cell-to-cell spread and viral yield reduction assays. Finally, both K5-N,OS(H) and K5-OS(H) prevented RSV infection in human-derived tracheal/bronchial epithelial cells cultured to form a pseudostratified, highly differentiated model of the epithelial tissue of the human respiratory tract. Together, these features put K5-N,OS(H) and K5-OS(H) forward as attractive candidates for further development as RSV inhibitors
Mammalian target of rapamycin pathway activation is associated to RET mutation status in medullary thyroid carcinoma.
Differential expression profiles of cell-to-matrix-related molecules in adrenal cortical tumors: Diagnostic and prognostic implications
The molecular mechanisms of adrenocortical carcinoma development are incompletely defined. De-regulation of cellular-to-extracellular matrix interactions and angiogenesis appear among mechanisms associated to the malignant phenotype. Our aim was to investigate, employing PCR-based array profiling, 157 molecules involved in cell-to-matrix interactions and angiogenesis in a frozen series of 6 benign and 6 malignant adrenocortical neoplasms, to identify novel pathogenetic markers. In 14 genes, a significant dysregulation was detected in adrenocortical carcinomas as compared to adenomas, most of them being downregulated. Three exceptions—hyaluronan synthase 1 (HAS-1), laminin α3 and osteopontin genes—demonstrated an increased expression in adrenocortical carcinomas of 4.46, 4.23 and 20.32-fold, respectively, and were validated by immunohistochemistry on a series of paraffin-embedded tissues, including 20 adenomas and 73 carcinomas. Osteopontin protein, absent in all adenomas, was expressed in a carcinoma subset (25/73) (p = 0.0022). Laminin α3 and HAS-1 were mostly expressed in smooth muscle and endothelial cells of the vascular network of both benign and malignant adrenocortical tumors. HAS-1 was also detected in tumor cells, with a more intense pattern in carcinomas. In this group, strong expression was significantly associated with more favorable clinicopathological features. These data demonstrate that cell-to-matrix interactions are specifically altered in adrenocortical carcinoma and identify osteopontin and HAS-1 as novel potential diagnostic and prognostic biomarkers, respectively, in adrenal cortical tumors
Resultados de la enseñanza de estrategias de lectura y escritura en la alfabetización temprana de niños con riesgo social
Introducción: La evidencia científica reciente
destaca la importancia de la alfabetización temprana
como fundamento del aprendizaje lector posterior, especialmente
en niños en riesgo social, pero no existen
las condiciones adecuadas para alcanzar su desarrollo.
El objetivo del estudio fue evaluar los resultados de una
intervención focalizada en el aprendizaje temprano de
la lectura y la escritura de niños con riesgo social (5 años
3 meses promedio). Material y Métodos: Se evaluaron
339 niños(as) (132 grupo intervención/207 grupo comparación),
al inicio y al fin del año escolar. Los profesores
del grupo de intervención participaron en un programa
de desarrollo profesional de un año que incluyó
capacitación y acompañamiento para la aplicación de
estrategias de enseñanza de la alfabetización temprana.
Resultados: Se observó un resultado positivo en el conocimiento
del alfabeto, la escritura emergente y el reconocimiento
visual de palabras, no en comprensión
oral. Discusión: Se contrastan los resultados con otros
programas de intervención en niños con riesgo social,
resaltando la importancia de la capacitación y el acompañamiento
a los educadores
RAS mutations are the predominant molecular alteration in poorly differentiated thyroid carcinomas and bear prognostic impact
DNA copy number alterations and PPARG amplification in a patient with multifocal bladder urothelial carcinoma
Clinicopathological study of a series of 92 adrenocortical carcinomas: from a proposal of simplified diagnostic algorithm to prognostic stratification.
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