Activation of Hes1 and Msx1 in transgenic mouse embryonic stem cells increases differentiation into neural crest derivatives

The neural crest (NC) comprises an ectodermal multipotent cell population that produces peripheral neurons, cartilage and smooth muscle cells, among other phenotypes. The participation of Hes1 and Msx1 when expressed in mouse embryonic stem cells (mESCs) undergoing NC differentiation is unexplored. In this work, we generated stable mESCs transfected with constructs encoding chimeric proteins in which the ligand binding domain of glucocorticoid receptor (GR), which is translocated to the nucleus by dexamethasone addition, is fused to either Hes1 (HGR) or Msx1 (MGR), as well as double-transgenic cells (HGR+MGR). These lines continued to express pluripotency markers. Upon NC differentiation, all lines exhibited significantly decreased Sox2 expression and upregulated Sox9, Snai1 and Msx1 expression, indicating NC commitment. In parallel experiments, dexamethasone was added to induce nuclear translocation of the chimeric proteins at early stages, and we found that Collagen IIa transcripts were increased in MGR cells, whereas coactivation of HGR+MGR caused a significant increase in Smooth muscle actin (alpha-Sma) transcripts. Immunostaining showed that activation in HGR+MGR cells induced higher proportions of BETA-TUBULIN III+ and alpha-SMA+ cells. These findings indicate that nuclear translocation of MSX1 might be used to produce chondrocytes at higher efficiencies, but simultaneous activation of HES1 and MSX1 increases the generation of smooth muscle and neuronal cells.Fil: Mendez Maldonado, Karla. Universidad Nacional Autónoma de México; MéxicoFil: Vega López, Guillermo Alfredo. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Biología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Caballero Chacón, Sara. Universidad Nacional Autónoma de México; MéxicoFil: Aybar, Manuel Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia; ArgentinaFil: Velasco, Ivan. Universidad Nacional Autónoma de México; Méxic

La convivencia en los centros educativos de educación básica en Iberoamérica

La presente aportación recoge la visión de 46 especialistas de quince países iberoamericanos sobre las formas de entender y promover la convivencia escolar en los centros educativos de los distintos países. Sus aportaciones son un conjunto de descripciones, experiencias y valoraciones significativas y en relación al contexto considerado. Las aportaciones no buscan tanto radiografiar la temática a nivel teórico como presentar lo más significativo de cada realidad y las propuestas que, al respecto, se realizan. La orientación es claramente organizativa, si consideramos que una parte común de todas las aportaciones tiene que ver con las políticas de convivencia escolar, programas aplicados, aspectos organizativos a nivel de institución, experiencias significativas y retos para la mejora. Se cubre así y de nuevo un propósito fundamental de la Red AGE, como es el de fomentar el intercambio de experiencias, la promoción del conocimiento sobre administración y gestión educativa y la reflexión sobre la práctica de la gestión. La finalidad última es la de mejorar el funcionamiento de los centros educativos (y, a través de ellos, de los sistemas educativos), procurando sean de calidad y un instrumento para el cambio profesional y social

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Producción de células similares a la glia de Schwann a partir de células madreneurales, para la reparación de lesiones medulares en rata

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias. Departamento de Biología Molecular. Fecha de lectura: 25-03-200

Intra-Abdominal Fat Adipocyte Hypertrophy through a Progressive Alteration of Lipolysis and Lipogenesis in Metabolic Syndrome Rats

This study evaluates the progressive participation of enzymes involved in lipolysis and lipogenesis, leading to adipocyte hypertrophy in a metabolic syndrome (MS) rat model caused by chronic consumption of 30% sucrose in drinking water. A total of 70 male Wistar rats were divided into two groups: C and MS. Each of these groups were then subdivided into five groups which were sacrificed as paired groups every month from the beginning of the treatment until 5 months. The intra-abdominal fat was dissected, and the adipocytes were extracted. Lipoprotein lipase (LPL), hormone-sensitive lipase (HSL), protein kinases A (PKA), and perilipin A expressions were determined. The LPL and HSL activities were evaluated by spectrophotometry. Histological staining was performed in adipose tissue. Significant increases were observed in blood pressure, HOMA-IR, leptin, triglycerides, insulin, intra-abdominal fat, and number of fat cells per field (p = 0.001) and in advanced glycosylation products, adipocyte area, LPL, HSL activities and/or expression (p ≤ 0.01) in the MS groups progressively from the third month onward. Lipogenesis and lipolysis were increased by LPL activity and HSL activity and/or expression. This was associated with hyperinsulinemia and release of non-esterified fatty acids causing a positive feedback loop that contributes to the development of adipocyte hypertrophy

The Morphofunctional Effect of the Transplantation of Bone Marrow Stromal Cells and Predegenerated Peripheral Nerve in Chronic Paraplegic Rat Model via Spinal Cord Transection

Functional recovery following spinal cord injury (SCI) is limited by poor axonal and cellular regeneration as well as the failure to replace damaged myelin. Employed separately, both the transplantation of the predegenerated peripheral nerve (PPN) and the transplantation of bone marrow stromal cells (BMSCs) have been shown to promote the regrowth and remyelination of the damaged central axons in SCI models of hemisection, transection, and contusion injury. With the aim to test the effects of the combined transplantation of PPN and BMSC on regrowth, remyelination, and locomotor function in an adult rat model of spinal cord (SC) transection, 39 Fischer 344 rats underwent SC transection at T9 level. Four weeks later they were randomly assigned to traumatic spinal cord injury (TSCI) without treatment, TSCI + Fibrin Glue (FG), TSCI + FG + PPN, and TSCI + FG + PPN + BMSCs. Eight weeks after, transplantation was carried out on immunofluorescence and electron microscope studies. The results showed greater axonal regrowth and remyelination in experimental groups TSCI + FG + PPN and TSCI + FG + PPN + BMSCs analyzed with GAP-43, neuritin, and myelin basic protein. It is concluded that the combined treatment of PPN and BMSCs is a favorable strategy for axonal regrowth and remyelination in a chronic SC transection model

Excessive Consumption <i>Hibiscus sabdariffa</i> L. Increases Inflammation and Blood Pressure in Male Wistar Rats via High Antioxidant Capacity: The Preliminary Findings

Hibiscus sabdariffa L. (HSL) has high amounts of antioxidants and many beneficial effects in several pathologies. However, few studies describe the possible harmful effects of high concentrations of HSL. Here we evaluate the effect of excessive and chronic consumption of infusions with different percentages of HSL on some oxidative stress markers in serum, and the possible association with inflammation and increased systolic blood pressure (SBP), in healthy rats. A total of 32 male Wistar rats were used to form 4 groups with 8 animals each. Group 1 control (drinking tap water), group 2, 3 and 4, drinking water supplemented with 15, 30 and 60 g/L of HSL calyxes respectively. SBP was evaluated and determinations in serum of the NO3−/NO2− ratio, glutathione (GSH), total antioxidant capacity (TAC), selenium (Se), TNF-α, IL-1α/IL-1F1, IL-1β, IL-10, extracellular superoxide dismutase (EcSOD), thioredoxin reductase (TrxR) and glutathione peroxidase (GPx) activities, were evaluated. The SBP (p = 0.01), GPx activity, GSH, TAC, Se, TNF-α and EcSOD activities (p ≤ 0.001) and IL-1α/IL-1F1, IL-1β, TrxR and NO3−/NO2− (p ≤ 0.05), were increased but IL-10 (p < 0.001) was decreased in rats that consumed the 3 and 6% HSL infusions. The excessive and chronic consumption of HSL may increase the TAC that could lead to a proinflammatory state which is associated with hypertension

Fibroblast activation and abnormal extracellular matrix remodelling as common hallmarks in three cancer-prone genodermatoses

Altres ajuts: CIBERER; European Regional Development Funds; Comunidad de Madrid (AvanCell-CM S2017/BMD-3692); Fundació La Marato de TV3 (201331-30); CERCA Programme, Generalitat de Catalunya; Fundación Científica de la Asociación Española Contra el Cancer.Background: Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three cancer-prone genodermatoses whose causal genetic mutations cannot fully explain, on their own, the array of associated phenotypic manifestations. Recent evidence highlights the role of the stromal microenvironment in the pathology of these disorders. Objectives: To investigate, by means of comparative gene expression analysis, the role played by dermal fibroblasts in the pathogenesis of RDEB, KS and XPC. Methods: We conducted RNA-Seq analysis, which included a thorough examination of the differentially expressed genes, a functional enrichment analysis and a description of affected signalling circuits. Transcriptomic data were validated at the protein level in cell cultures, serum samples and skin biopsies. Results: Interdisease comparisons against control fibroblasts revealed a unifying signature of 186 differentially expressed genes and four signalling pathways in the three genodermatoses. Remarkably, some of the uncovered expression changes suggest a synthetic fibroblast phenotype characterized by the aberrant expression of extracellular matrix (ECM) proteins. Western blot and immunofluorescence in situ analyses validated the RNA-Seq data. In addition, enzyme-linked immunosorbent assay revealed increased circulating levels of periostin in patients with RDEB. Conclusions: Our results suggest that the different causal genetic defects converge into common changes in gene expression, possibly due to injury-sensitive events. These, in turn, trigger a cascade of reactions involving abnormal ECM deposition and underexpression of antioxidant enzymes. The elucidated expression signature provides new potential biomarkers and common therapeutic targets in RDEB, XPC and KS. What's already known about this topic?. Recessive dystrophic epidermolysis bullosa (RDEB), Kindler syndrome (KS) and xeroderma pigmentosum complementation group C (XPC) are three genodermatoses with high predisposition to cancer development. Although their causal genetic mutations mainly affect epithelia, the dermal microenvironment likely contributes to the physiopathology of these disorders. What does this study add?. We disclose a large overlapping transcription profile between XPC, KS and RDEB fibroblasts that points towards an activated phenotype with high matrix-synthetic capacity. This common signature seems to be independent of the primary causal deficiency, but reflects an underlying derangement of the extracellular matrix via transforming growth factor-β signalling activation and oxidative state imbalance. What is the translational message?. This study broadens the current knowledge about the pathology of these diseases and highlights new targets and biomarkers for effective therapeutic intervention. It is suggested that high levels of circulating periostin could represent a potential biomarker in RDEB