TGF-beta has paradoxical and context dependent effects on proliferation and anoikis in human colorectal cancer cell lines.

Transforming growth factor-beta (TGF-beta) is a pluripotent cytokine that can have both tumor suppressing and tumor promoting effects on epithelial cells. It is unclear what determines when TGF-beta and its signaling pathway act predominantly as a tumor suppressor pathway or as a tumor-promoter pathway and whether TGF-beta can have both classes of effects concurrently on a cell. We investigated the effect of TGF-beta on anoikis in colorectal cancer cell lines sensitive to TGF-beta-mediated growth inhibition to determine if the context of the cells could be one of the factors that would affect whether TGF-beta exerts tumor suppressor or oncogene activity on colon cancer cells. We observed variable effects of TGF-beta on anoikis in these cell lines, even though they all are growth-inhibited by TGF-beta. Thus, we show that TGF-beta has variable effects on anoikis in colon cancer cell lines that likely reflects the effects of concurrent gene mutations in the cancer cells and the activation state of the signaling pathways controlled by these genes

Producción y caracterización de un anticuerpo monoclonal que reconoce el fragmento 28-30 kDa de la proteína MSP-1 de Plasmodium falciparum

Merozoites of the malaria parasite Plasmodium falciparum have on their surface proteolytic processed fragments of MSP-1 (merozoite surface protein-1). These fragments have relative molecularweights of approximately 83, 42, 38, 28-30 kDa, respectively In this study we describe the characterization of a monoclonal antibody. denominated 8F4, that recognizes MSP-1 based upon the following characteristics: 1) subcellular location of the antigen, 2) relative molecular weight, 3) time of expression during the asexual life cycle of the parasite, 4) the association of the protein with the plasma membrane and 5) epitopes shared with MSP-1. In addition, it was found that 8F4 recognizes the 28-30 kDa fragment that arises as a consequence of the first proteolyiic processing of MSP-1. The study confirms that such fragment is excluded from the merozoite surface during invasion, suggesting that it makes part of a complex of polypeptides which is released from the merozoite before the invasion process takes place. This is the first report of a monoclonal antibody which specifically recognizes this polypeptide.Los merozoitos del parásito Plasmodium falciparum contienen en su superficie los fragmentos producidos por el primer procesamiento proteolítico de la proteina MSP-1 (merozoite surface protein-1). Dichos fragmentos tienen pesos moleculares relativos aproximados de 83, 42, 38 y 28-30 kDa, respectivamente. En este estudio se describe la producción y caracterización de un anticuerpo monoclonal, denominado 8F4, que reconoce la proteina MSP-1 dadas las siguientes características del antigeno: 1) localización subcelular, 2) peso molecular relativo, 3) período de expresión durante el ciclo eritrocítrico, 4) tipo de asociación con la membrana plasmática del parásito y 5) presencia de epítopes compartidos con MSP-1. Adicionalmente. se estableció que 8F4 reconoce el fragmento de 28-30 kDa, producto del primer procesamiento proteolitico de MSP-1. Los análisis realizados permiten confirmar que MSP-1, 28-30 , no permanece en la superficie del merozoito desoués de ocurrida la invasión. lo cual suoiere oue hace oarte del com.o le.io de polipéptidos que es liberado por el merozoito previamente al evento de la invasión. 8F4 es el primer anticuerpo monoclonal reportado hasta el momento que reconoce específicamente este fragmento

Vitamin D Deficiency Promotes Liver Tumor Growth in Transforming Growth Factor-β/Smad3-Deficient Mice Through Wnt and Toll-like Receptor 7 Pathway Modulation.

Disruption of the TGF-β pathway is associated with liver fibrosis and suppression of liver tumorigenesis, conditions associated with low Vitamin D (VD) levels. However, potential contributions of VD to liver tumor progression in the context of TGF-β signaling remain unexplored. Our analyses of VD deprivation (VDD) in in vivo models of liver tumor formation revealed striking three-fold increases in tumor burden in Smad3(+/-) mice, with a three-fold increase in TLR7 expression compared to controls. ChIP and transcriptional assays confirm Smad3 binding at two TLR7 promoter SBE sites. Molecular interactions between TGF-β pathway and VDD were validated clinically, where an absence of VD supplementation was associated with low TGF-β pathway member expression levels and β-catenin activation in fibrotic/cirrhotic human liver tissues. Subsequent supplementing VD led to restoration of TGF-β member expression with lower β-catenin levels. Bioinformatics analysis provides positive supportive correlation between somatic mutations for VD-related genes and the TGF-β pathway. We conclude that VDD promotes tumor growth in the context of Smad3 disruption, potentially through regulation of TLR7 expression and β-catenin activation. VD could therefore be a strong candidate for liver cancer prevention in the context of aberrant Smad3 signaling

Novel reporter systems for facile evaluation of I-SceI-mediated genome editing

Two major limitations to achieve efficient homing endonuclease-stimulated gene correction using retroviral vectors are low frequency of gene targeting and random integration of the targeting vectors. To overcome these issues, we developed a reporter system for quick and facile testing of novel strategies to promote the selection of cells that undergo targeted gene repair and to minimize the persistence of random integrations and non-homologous end-joining events. In this system, the gene target has an I-SceI site upstream of an EGFP reporter; and the repair template includes a non-functional EGFP gene, the positive selection transgene MGMTP140K tagged with mCherry, and the inducible Caspase-9 suicide gene. Using this dual fluorescent reporter system it is possible to detect properly targeted integration. Furthermore, this reporter system provides an efficient approach to enrich for gene correction events and to deplete events produced by random integration. We have also developed a second reporter system containing MGMTP140K in the integrated target locus, which allows for selection of primary cells with the integrated gene target after transplantation. This system is particularly useful for testing repair strategies in primary hematopoietic stem cells. Thus, our reporter systems should allow for more efficient gene correction with less unwanted off target effects

Cuerpo y educación : variaciones en torno a un mismo tema

El presente texto es una compilación de los trabajos realizados por el Instituto para la Investigación Educativa y el Desarrollo Pedagógico, IDEP, con un grupo de investigadores que orientaron los estudios y los procesos de cualificación en el ámbito de Subjetividad, diversidad e interculturalidad, propuesto desde el Componente de Educación y Políticas Públicas del proyecto misional del IDEP. El hilo conductor en cada uno de los textos es el lugar del cuerpo, unas veces como eje central de la propuesta investigativa, y otras como elemento relevante desde su relación con distintas dimensiones que surgen en los diferentes trabajos desarrollados por los colectivos de maestros y maestras.Presentación 1. Obertura 1.1 Cuerpo y recreación. Reconfiguración subjetiva a través del uso de las prácticas lúdico-creativas 2. Primer Movimiento 2.1. Reflexiones sobre el cuerpo. Conciencia, experiencia, vivencias 2.2. El cuerpo de la memoria. Políptico de mnemotecnias 3. Segundo Movimiento 3.1. Cuerpo y Erotismo en la Escuela. Discursos y Tensiones 3.2. El Poder de la Apariencia. Construcciones Escolares del Cuerpo 4. Tercer Movimiento 4.1. Diversidad epistémica e interculturalidad crítica. Una perspectiva para los estudios sobre diversidad en la escuela 4.2. Territorio y derechos. Cartografías Corporales en la Investigación sobre Territorio en los Contextos Escolares 5. Coda 5.1. Videojuegos y conocimiento: un estado de la cuestió

Database of spatial distribution of non indigenous species in Spanish marine waters

Research in marine Spanish waters are focused on several actions to achieve an effectively management on protected areas, with the active participation of the stakeholders and research as basic tools for decision-making. Among these actions, there is one about the knowledge and control on NIS. One of its objectives is the creation of NIS factsheets, which are going to be added to the National Marine Biodiversity Geographical System (GIS) providing complementary information about taxonomic classification, common names, taxonomic synonyms, species illustrations, identification morphological characters, habitat in the native and introduced regions, biological and ecological traits, GenBank DNA sequences, world distribution, first record and evolution in the introduced areas, likely pathways of introduction, effects in the habitats and interaction with native species, and potential management measures to apply. The database will also provide data for (1) the European online platforms, (2) the environmental assessment for the Descriptor 2 (D2-NIS) of the EU Marine Strategy Framework Directive (MSFD), as well as (3) supporting decisions made by stakeholders. It is the result of extensive collaboration among scientist, manager’s and citizen science in the Spanish North-Atlantic, South-Atlantic, Gibraltar Strait-Alboran, Levantine-Balearic and Canary Islands marine divisions, providing an updated overview of the spatial distribution of relevant extended and invasive NIS of recent and established NIS introduced by maritime transport and aquaculture pathways, as well as on cryptogenic or native species in expansion due to the climatic water warming trend

Protection of Stem Cell-Derived Lymphocytes in a Primate AIDS Gene Therapy Model after In Vivo Selection

Background: There is currently no effective AIDS vaccine, emphasizing the importance of developing alternative therapies. Recently, a patient was successfully transplanted with allogeneic, naturally resistant CCR5-negative (CCR5 delta 32) cells, setting the stage for transplantation of naturally resistant, or genetically modified stem cells as a viable therapy for AIDS. Hematopoietic stem cell (HSC) gene therapy using vectors that express various anti-HIV transgenes has also been attempted in clinical trials, but inefficient gene transfer in these studies has severely limited the potential of this approach. Here we evaluated HSC gene transfer of an anti-HIV vector in the pigtailed macaque (Macaca nemestrina) model, which closely models human transplantation. Methods and Findings: We used lentiviral vectors that inhibited both HIV-1 and simian immunodeficiency virus (SIV)/HIV-1 (SHIV) chimera virus infection, and also expressed a P140K mutant methylguanine methyltransferase (MGMT) transgene to select gene-modified cells by adding chemotherapy drugs. Following transplantation and MGMT-mediated selection we demonstrated transgene expression in over 7% of stem-cell derived lymphocytes. The high marking levels allowed us to demonstrate protection from SHIV in lymphocytes derived from gene-modified macaque long-term repopulating cells that expressed an HIV-1 fusion inhibitor. We observed a statistically significant 4-fold increase of gene-modified cells after challenge of lymphocytes from one macaque that received stem cells transduced with an anti-HIV vector (p<0.02, Student's t-test), but not in lymphocytes from a macaque that received a control vector. We also established a competitive repopulation assay in a second macaque for preclinical testing of promising anti-HIV vectors. The vectors we used were HIV-based and thus efficiently transduce human cells, and the transgenes we used target HIV-1 genes that are also in SHIV, so our findings can be rapidly translated to the clinic. Conclusions: Here we demonstrate the ability to select protected HSC-derived lymphocytes in vivo in a clinically relevant nonhuman primate model of HIV/SHIV infection. This approach can now be evaluated in human clinical trials in AIDS lymphoma patients. In this patient setting, chemotherapy would not only kill malignant cells, but would also increase the number of MGMTP140K-expressing HIV-resistant cells. This approach should allow for high levels of HIV-protected cells in AIDS patients to evaluate AIDS gene therapy

Salud de los trabajadores

Actividad f&iacute;sica y su relaci&oacute;n con los factores de riesgo cardiovascular de carteros chilenosAn&aacute;lisis de resultados: riesgos psicosociales en el trabajo Suceso-Istas 21 en Cesfam Quell&oacute;nAusentismo laboral por enfermedades oftalmol&oacute;gicas, Chile 2009Brote de diarreas por norovirus, posterremoto-tsunami, Constituci&oacute;n, Regi&oacute;n del MauleCalidad de vida en profesionales de la salud p&uacute;blica chilenaCaracterizaci&oacute;n del reposo laboral en personal del SSMN durante el primer semestre de 2010Concentraci&oacute;n de nicotina en pelo en trabajadores no fumadores expuestos a humo de tabaco ambientalCondiciones de trabajo y bienestar/malestar docente en profesores de ense&ntilde;anza media de SantiagoDisfunci&oacute;n auditiva inducida por exposici&oacute;n a xilenoErgonom&iacute;a aplicada al estudio del s&iacute;ndrome de dolor lumbar en el trabajoEstimaci&oacute;n de la frecuencia de factores de riesgo cardiovascular en trabajadores de una empresa mineraExposici&oacute;n a plaguicidas inhibidores de la acetilcolinesterasa en Colombia, 2006-2009Factores de riesgo y da&ntilde;os de salud en conductores de una empresa peruana de transporte terrestre, 2009Las consecuencias de la cultura en salud y seguridad ocupacional en una empresa mineraPercepci&oacute;n de cambios en la pr&aacute;ctica m&eacute;dica y estrategias de afrontamientoPercepci&oacute;n de la calidad de vida en la Universidad del Biob&iacute;oPesos m&aacute;ximos aceptables para tareas de levantamiento manual de carga en poblaci&oacute;n laboral femeninaRiesgo coronario en trabajadores mineros seg&uacute;n la funci&oacute;n de Framingham adaptada para la poblaci&oacute;n chilenaTrastornos emocionales y riesgo cardiovascular en trabajadores de la salu