1,869 research outputs found

    Insulin trafficking in a glucose responsive engineered human liver cell line is regulated by the interaction of ATP-sensitive potassium channels and voltage- gated calcium channels

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    Type I diabetes is caused by the autoimmune destruction of pancreatic beta (â) cells [1]. Current treatment requires multiple daily injections of insulin to control blood glucose levels. Tight glucose control lowers, but does not eliminate, the onset of diabetic complications, which greatly reduce the quality and longevity of life for patients. Transplantation of pancreatic tissue as a treatment is restricted by the scarcity of donors and the requirement for lifelong immunosuppression to preserve the graft, which carries adverse side-effects. This is of particular concern as Type 1 diabetes predominantly affects children. Lack of glucose control could be overcome by genetically engineering "an artificial â-cell" that is capable of synthesising, storing and secreting insulin in response to metabolic signals. The donor cell type must be readily accessible and capable of being engineered to synthesise, process, store and secrete insulin under physiological conditions

    Rare germline variants in DNA repair genes and the angiogenesis pathway predispose prostate cancer patients to develop metastatic disease

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    Background Prostate cancer (PrCa) demonstrates a heterogeneous clinical presentation ranging from largely indolent to lethal. We sought to identify a signature of rare inherited variants that distinguishes between these two extreme phenotypes. Methods We sequenced germline whole exomes from 139 aggressive (metastatic, age of diagnosis < 60) and 141 non-aggressive (low clinical grade, age of diagnosis ≥60) PrCa cases. We conducted rare variant association analyses at gene and gene set levels using SKAT and Bayesian risk index techniques. GO term enrichment analysis was performed for genes with the highest differential burden of rare disruptive variants. Results Protein truncating variants (PTVs) in specific DNA repair genes were significantly overrepresented among patients with the aggressive phenotype, with BRCA2, ATM and NBN the most frequently mutated genes. Differential burden of rare variants was identified between metastatic and non-aggressive cases for several genes implicated in angiogenesis, conferring both deleterious and protective effects. Conclusions Inherited PTVs in several DNA repair genes distinguish aggressive from non-aggressive PrCa cases. Furthermore, inherited variants in genes with roles in angiogenesis may be potential predictors for risk of metastases. If validated in a larger dataset, these findings have potential for future clinical application

    Calidad de vida en asistentes a un programa de actividad física en Bogotá, Colombia

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    The rise of chronic noncommunicable diseases in older adults is a global public health challenge, so actions to prevent or mitigate them are necessary to improve population health but quality of life. The objective focused on and rated the quality of life in users who regularly attend the Recreovía program. Non-experimental study with descriptive cross-sectional design, conducted in 280 adult women with an average age of 56.71 ± to 10.79 years, inhabitants of the city of Bogotá, who attend the Recreovía program 3 times a week. Quality of life was evaluated with WHOQOL-BREF. A statistically significant relationship was found between quality of life and socioeconomic stratum (p=0,002), between quality of life and physical health (p&lt;0,001) and quality of life and hypertension (p=0,003). The perception of quality of life was weighted as good as referred to by the participants; as there is a relationship between intermediate and structural determinants, it encourages decision-making that actions in the population must transcend beyond collective programs but affect the living and health conditions of the population.El aumento de Enfermedades crónicas no transmisibles en los adultos mayores es un reto en salud pública a nivel mundial, por lo que las acciones que se hagan para prevenir o mitigar estas son necesarias para mejorar la salud de la población sino la calidad de vida. El objetivo se centró en evaluar la calidad de vida en las usuarias que asisten de manera regular al programa de Recreovía. Estudio no experimental con diseño descriptivo de corte transversal, realizado en 280 mujeres adultas con una edad promedio de 56.71 ± 10.79 años, habitantes de la ciudad de Bogotá, que asisten 3 veces por semana al programa de Recreovía. Se evalúo la calidad de vida con el WHOQOL-BREF. Se encontró relación estadísticamente significativa entre la calidad de vida y el estrato socioeconómico (p=0.002), entre la calidad de vida y la salud física (p&lt;0.001) y la calidad de vida e Hipertensión (p=0.003). La percepción de calidad de vida fue ponderada como buena de acuerdo con lo referido por las participantes; al existir relación entre determinantes intermedios y estructurales, alienta a tomadores de decisión que las acciones en la población deben trascender más allá de programas colectivos, sino que afecten las condiciones de vida y salud de la población

    Conventional and molecular cytogenetics of human non-medullary thyroid carcinoma: characterization of eight cell line models and review of the literature on clinical samples

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    <p>Abstract</p> <p>Background</p> <p>Cell lines are often poorly characterized from a genetic point of view, reducing their usefulness as tumor models. Our purpose was to assess the genetic background of eight commonly used human thyroid carcinoma models and to compare the findings with those reported for primary tumors of the gland.</p> <p>Methods</p> <p>We used chromosome banding analysis and comparative genomic hybridization to profile eight non-medullary thyroid carcinoma cell lines of papillary (TPC-1, FB2, K1 and B-CPAP), follicular (XTC-1) or anaplastic origin (8505C, C643 and HTH74). To assess the representativeness of the findings, we additionally performed a thorough review of cytogenetic (n = 125) and DNA copy number information (n = 270) available in the literature on clinical samples of thyroid carcinoma.</p> <p>Results</p> <p>The detailed characterization of chromosomal markers specific for each cell line revealed two cases of mistaken identities: FB2 was shown to derive from TPC-1 cells, whereas K1 cells have their origin in cell line GLAG-66. All cellular models displayed genomic aberrations of varying complexity, and recurrent gains at 5p, 5q, 8q, and 20q (6/7 cell lines) and losses at 8p, 13q, 18q, and Xp (4/7 cell lines) were seen. Importantly, the genomic profiles were compatible with those of the respective primary tumors, as seen in the meta-analysis of the existing literature data.</p> <p>Conclusion</p> <p>We provide the genomic background of seven independent thyroid carcinoma models representative of the clinical tumors of the corresponding histotypes, and highlight regions of recurrent aberrations that may guide future studies aimed at identifying target genes. Our findings further support the importance of routinely performing cytogenetic studies on cell lines, to detect cross-contamination mishaps such as those identified here.</p

    Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-

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    We report a measurement of time-integrated CP-violation asymmetries in the resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production flavor of the charm meson is determined by the charge of the accompanying pion. We apply a Dalitz-amplitude analysis for the description of the dynamic decay structure and use two complementary approaches, namely a full Dalitz-plot fit employing the isobar model for the contributing resonances and a model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57 (stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry, consistent with the standard model prediction.Comment: 15 page
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