In vivo 13C NMR spectroscopy and metabolic modeling in the brain: a practical perspective.

In vivo 13C NMR spectroscopy has the unique capability to measure metabolic fluxes noninvasively in the brain. Quantitative measurements of metabolic fluxes require analysis of the 13C labeling time courses obtained experimentally with a metabolic model. The present work reviews the ingredients necessary for a dynamic metabolic modeling study, with particular emphasis on practical issues.

Let's K-Map Play: Juego de aprendizaje de Karnagh Maps para móvil

En este informe se describe el trabajo de fin de máster, centrado en el estudio de la gamificación como herramienta de aprendizaje aplicada a dispositivos móviles. Se ha realizado una revisión de los artículos científicos que tratan sobre el tema de la gamificación como herramienta educativa,para terminar el trabajo desarrollando un prototipo de juego para el aprendizaje de mapas de Karnaugh. Se ha optado por un desarrollo multiplataforma y se han revisado los frameworks de desarrollo más populares para desarrollo móvil multiplataforma así como los motores de juegos aplicables a este caso. Tras la implementación, se ha probado el prototipo en dos sistemas operativos móviles libres: Android y Firefox OS.

Audit report on Henry County, Iowa for the year ended June 30, 2014

Audit report on Henry County, Iowa for the year ended June 30, 2014

Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype.

The Drosophila transcription factor Prospero functions as a tumor suppressor, and it has been suggested that the human counterpart of Prospero, PROX1, acts similarly in human cancers. However, we show here that PROX1 promotes dysplasia in colonic adenomas and colorectal cancer progression. PROX1 expression marks the transition from benign colon adenoma to carcinoma in situ, and its loss inhibits growth of human colorectal tumor xenografts and intestinal adenomas in Apc(min/+) mice, while its transgenic overexpression promotes colorectal tumorigenesis. Furthermore, in intestinal tumors PROX1 is a direct and dose-dependent target of the beta-catenin/TCF signaling pathway, responsible for the neoplastic transformation. Our data underscore the complexity of cancer pathogenesis and implicate PROX1 in malignant tumor progression through the regulation of cell polarity and adhesion.

Mineralocorticoid effects in the kidney: correlation between alphaENaC, GILZ, and Sgk-1 mRNA expression and urinary excretion of Na+ and K+.

Aldosterone exerts its effects through interactions with two types of binding sites, the mineralocorticoid (MR) and the glucocorticoid (GR) receptors. Although both receptors are known to be involved in the anti-natriuretic response to aldosterone, the mechanisms of signal transduction leading to modulation of electrolyte transport are not yet fully understood. This study measured the Na(+) and K(+) urinary excretion and the mRNA levels of three known aldosterone-induced transcripts, the serum and glucocorticoid-induced kinase (Sgk-1), the alpha subunit of the epithelial Na(+) channel (alphaENaC), and the glucocorticoid-induced-leucine-zipper protein (GILZ) in the whole kidney and in isolated cortical collecting tubules of adrenalectomized rats treated with low doses of aldosterone and/or dexamethasone. The resulting plasma concentrations of both steroids were close to 1 nmol/L. Aldosterone, given with or without dexamethasone, induced anti-natriuresis and kaliuresis, whereas dexamethasone alone did not. GILZ and alphaENaC transcripts were higher after treatment with either or both hormones, whereas the mRNA abundance of Sgk-1 was increased in the cortical collecting tubule by aldosterone but not by dexamethasone. We conclude the increased expression of Sgk-1 in the cortical collecting tubules is a primary event in the early antinatriuretic and kaliuretic responses to physiologic concentrations of aldosterone. Induction of alphaENaC and/or GILZ mRNAs may play a permissive role in the enhancement of the early and/or late responses; these effects may be necessary for a full response but do not by themselves promote early changes in urinary Na(+) and K(+) excretion.

K-r/K-c but not d(N)/d(S) correlates positively with body mass in birds, raising implications for inferring lineage-specific selection

Background: The ratio of the rates of non-synonymous and synonymous substitution (d(N)/d(S)) is commonly used to estimate selection in coding sequences. It is often suggested that, all else being equal, d(N)/d(S) should be lower in populations with large effective size (Ne) due to increased efficacy of purifying selection. As N-e is difficult to measure directly, life history traits such as body mass, which is typically negatively associated with population size, have commonly been used as proxies in empirical tests of this hypothesis. However, evidence of whether the expected positive correlation between body mass and d(N)/d(S) is consistently observed is conflicting. Results: Employing whole genome sequence data from 48 avian species, we assess the relationship between rates of molecular evolution and life history in birds. We find a negative correlation between dN/dS and body mass, contrary to nearly neutral expectation. This raises the question whether the correlation might be a method artefact. We therefore in turn consider non-stationary base composition, divergence time and saturation as possible explanations, but find no clear patterns. However, in striking contrast to d(N)/d(S), the ratio of radical to conservative amino acid substitutions (K-r/K-c) correlates positively with body mass. Conclusions: Our results in principle accord with the notion that non-synonymous substitutions causing radical amino acid changes are more efficiently removed by selection in large populations, consistent with nearly neutral theory. These findings have implications for the use of d(N)/d(S) and suggest that caution is warranted when drawing conclusions about lineage-specific modes of protein evolution using this metric.

Systems Genetics of Metabolism: The Use of the BXD Murine Reference Panel for Multiscalar Integration of Traits.

Metabolic homeostasis is achieved by complex molecular and cellular networks that differ significantly among individuals and are difficult to model with genetically engineered lines of mice optimized to study single gene function. Here, we systematically acquired metabolic phenotypes by using the EUMODIC EMPReSS protocols across a large panel of isogenic but diverse strains of mice (BXD type) to study the genetic control of metabolism. We generated and analyzed 140 classical phenotypes and deposited these in an open-access web service for systems genetics (www.genenetwork.org). Heritability, influence of sex, and genetic modifiers of traits were examined singly and jointly by using quantitative-trait locus (QTL) and expression QTL-mapping methods. Traits and networks were linked to loci encompassing both known variants and novel candidate genes, including alkaline phosphatase (ALPL), here linked to hypophosphatasia. The assembled and curated phenotypes provide key resources and exemplars that can be used to dissect complex metabolic traits and disorders.

Let's K-map play : Juego de aprendizaje de Karnaugh Maps para móvil

En este informe se describe el trabajo de fin de máster, centrado en el estudio de la gamificación como herramienta de aprendizaje aplicada a dispositivos móviles. Se ha realizado una revisión de los artículos científicos que tratan sobre el tema de la gamificación como herramienta educativa, para terminar el trabajo desarrollando un prototipo de juego para el aprendizaje de mapas de Karnaugh. Se ha optado por un desarrollo multiplataforma y se han revisado los frameworks de desarrollo más populares para desarrollo móvil multiplataforma, así como los motores de juegos aplicables a este caso. Tras la implementación, se ha probado el prototipo en dos sistemas operativos móviles libres: Android y Firefox OS.