Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells.

Connexins (Cxs) are a family of proteins that form two different types of ion channels: hemichannels and gap junction channels. These channels participate in cellular communication, enabling them to share information and act as a synchronized syncytium. This cellular communication has been considered a strong tumor suppressor, but it is now recognized that some type of Cxs can be pro-tumorigenic. For example, Cx46 expression is increased in human breast cancer samples and correlates with cancer stem cell (CSC) characteristics in human glioma. Thus, we explored whether Cx46 and glioma cells, can set up CSC and epithelial-to-mesenchymal transition (EMT) properties in a breast cancer cell line. To this end, we transfected MCF-7 cells with Cx46 attached to a green fluorescent protein (Cx46GFP), and we determined how its expression orchestrates both the gene-expression and functional changes associated with CSC and EMT. We observed that Cx46GFP increased Sox2, Nanog, and OCT4 mRNA levels associated with a high capacity to form monoclonal colonies and tumorspheres. Similarly, Cx46GFP increased the mRNA levels of n-cadherin, Vimentin, Snail and Zeb1 to a higher migratory and invasive capacity. Furthermore, Cx46GFP transfected in MCF-7 cells induced the release of higher amounts of VEGF, which promoted angiogenesis in HUVEC cells. We demonstrated for the first time that Cx46 modulates CSC and EMT properties in breast cancer cells and thus could be relevant in the design of future cancer therapies.

Condiciones de seguridad en calderas de vapor de empresas afiliadas a una administradora de riesgos profesionales en Antioquia, 2009 / Safety conditions of steam boilers in companies associated with a professional risk administration company in Antioquia, 2009

Objetivo: determinar las condiciones de seguridad de las calderas en empresas afiliadas a una administradora de riesgosprofesionales en Antioquia, Colombia, caracterizando sus condiciones de operación, identificando sus riesgos asociados y valorando su nivel de seguridad. Metodología: serealizó un estudio descriptivo en veinte empresas que utilizan calderas de vapor en su proceso productivo. Se aplicóuna encuesta de condiciones de operación al jefe de mantenimientoy al calderista de cada una, se realizó una matriz de peligros con base en la guía técnica colombiana gtc-45y se aplicó un instrumento de evaluación para determinar el nivel de seguridad. Resultados: el 70% de las calderas evaluadas obtuvieron una calificación de deficiente (menos de 65 puntos) de acuerdo con la escala validada por expertos; las calderas restantes solo alcanzaron una calificación de aceptable(66 a 81 puntos). Asimismo, se observó que en el 85% de las calderas no se tiene instructivo de operación y que el60% de ellas no tienen ningún tipo de alarma. Conclusiones: las calderas presentan condiciones de seguridad deficientes, principalmente en relación con la ausencia de protocolos deoperación, la formación a los calderistas y poca vigilancia por parte de las autoridades competentes.

Objective: to determine the safety conditions of steam boilersin companies associated with a professional risk administrationcompany in Antioquia, Colombia. To this end, their operation conditions shall be characterized, the associated risksidentified, and their safety level assessed. Methodology: a descriptive cross-sectional study was carried out in twenty companies whose production processes involve boilers. A survey on the conditions for operation was applied on both the maintenance managers and the boilers’ operators in eachcompany. A hazard risk assessment matrix was made as instructedin the GTC-45 Colombian technical guide, and an assessmentinstrument was applied to determine the safety level for each boiler. Results: 70% of the assessed boilers obtaineda low score (less than 65 points) according to the scale, which has been validated by experts; the remaining boilers obtained an acceptable score (66 to 81 points). It was also found that85% of the boilers had no operating instructions, and 60% of them did not have any kind of alarm. Conclusions: the studied boilers had poor security conditions, mainly related to theabsence of operation protocols, boiler operator training, and poor supervision by competent authorities.

Una mutación en el gen PARK2 causa enfermedad de Parkinson juvenil en una extensa familia colombiana / Mutation c.255delA in the PARK2 gene as cause of juvenile Parkinson´s disease in a large Colombian family

La enfermedad de Parkinson (EP) es común y se debe a degeneración de las neuronas dopaminérgicas en la sustancia nigra y en otras áreas del cerebro. Varios genes y mutaciones han sido implicados en ella y la mayoría de estas últimas han sido identificadas en el gen PARK2. Reportamos la evaluación de este gen PARK2 y de su región flanqueante en una gran familia de origen caucano, al suroccidente de Colombia. Los padres son primos hermanos y cuatro de sus diez hijos resultaron afectados en edad juvenil. La evaluación molecular incluyó tipificación de microsatélites (STR) y la secuencia directa de los exones del gen. Nuestros hallazgos evidenciaron la presencia en condición homocigota de la mutación c.255delA, en el exón 2 de PARK2. Además, se pudo identificar un haplotipo portado por ambos padres y presente en condición homocigota en los hijos afectados. Del mismo modo se observó una alta tasa de recombinantes en la extensión de la región cromosómica analizada. La mutación c.255delA en PARK2 ya había sido reportada previamente en familias tanto de Francia como de España. Nuestros resultados reconfirman la participación del gen PARK2 en la etiología de la enfermedad de Parkinson, en particular de la forma juvenil. Además, considerando que la mutación identificada en la familia que presentamos ya había sido previamente encontrada en poblaciones europeas, es probable que haya llegado a Colombia desde allí. Alternativamente, esta mutación pudo ocurrir de manera recurrente en un ancestro más cercano de la familia estudiada; para verificar ambas posibilidades sería necesario evaluar marcadores flanqueantes de la mutación, en los cromosomas europeos y colombianos portadores de la mutación. Tales marcadores pueden ser STR (como se reporta en este estudio) o alternativamente, SNP.

Parkinson´s is a common disease (PD) caused by degeneration of dopaminergic neurons in the substantia nigra and other brain areas. Several genes and mutations have been implicated in its pathogenesis, the latter have been identified mainly in the PARK2 gene. We report the evaluation of this gene and of its flanking region in a large family from the southwestern part of Colombia. The parents are first cousins and four out of their ten children were affected at juvenile age. Molecular evaluation included typing of microsatelites (SSTRs) and direct sequencing of the exons of the gene. Our findings showed the presence, in a homozygous manner, of the mutation c.255delA, at exon 2 of PARK2. In addition, it was possible to identify a haplotype carried by both parents, and present in a homozygous manner in the affected children. A high rate of recombinants was observed in the analysed chromosomal region. Mutation c.255delA in PARK2 had been previously reported in families from both France and Spain. Our findings reconfirm the role of the PARK2 gene in the etiology of Parkinson´s disease, in particular of its juvenile form. Furthermore, taking into account that the identified mutation had been previously found in European populations, it is likely that it came into Colombia from that continent. Alternatively, this mutation might have occurred in a recurrent manner in a close ancestor of the studied family. In order to verify both possibilities it would be necessary to test flanking markers of the mutation in both European and Colombian chromosomes carrying it. Such markers could be either STRs, as reported in this study, or SNPs.