Semantic text mining in early drug discovery for type 2 diabetes.

Background: Surveying the scientific literature is an important part of early drug discovery; and with the ever-increasing amount of biomedical publications it is imperative to focus on the most interesting articles. Here we present a project that highlights new understanding (e.g.

The EndoC-βH1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates.

Objective: To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates.

Methods: EndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice.

Effects of insulin therapy on weight gain and fat distribution in the HF/HS-STZ rat model of type 2 diabetes.

Background/objectives: Insulin therapy is required for many patients with the obesity-related disorder type 2 diabetes, but is also associated with weight gain. The specific location of adipose tissue location matters to cardiovascular disease (CVD) risk. We investigated effects of exogenous insulin on fat distribution in the high-fat/high-sucrose fed rat treated with streptozotocin (HF/HS-STZ) rat model of type 2 diabetes.

Identification of a conserved cis-acting region driving expression of mouse Eomesodermin to the primitive streak, node, and definitive endoderm.

The cis-acting elements that regulate Eomes transcription during embryonic development are largely unknown. Here we identify a conserved cis-acting region (EoIV) located ~20kb upstream of the Eomes coding region that faithfully drives reporter expression to sites of Eomes expression during gastrulation. Transgenic EoIV-hsp68-GFP expression was evident in the epiblast of early-streak stage mouse embryos at the site where the primitive streak is initiated.

Three-dimensional immunohistochemical characterization of lineage commitment by localization of T and FOXA2 in porcine peri-implantation embryos.

Gene expression during gastrulation in porcine embryos has been sparsely studied, but there are indications that species-specific patterns exist. Here, we investigated the three-dimensional (3D) expression of the T-box transcription factor Brachyury (T) and the forkhead box transcription factor FOXA2 by immunocytochemistry in porcine peri-gastrulation embryos. The first T(+) cells were detected in posterior epiblast of ovoid blastocysts.

Three-dimensional localisation of NANOG, OCT4, and E-CADHERIN in porcine pre- and peri-implantation embryos.

The expression patterns of NANOG and OCT4 have previously been reported to differ markedly between mammalian species indicating distinct species-specific roles during development. We investigate the three-dimensional expression pattern of NANOG and OCT4 in porcine pre- and peri-implantation embryos. The expression of NANOG differed remarkably from that reported in other species.

OCT4 expression in outgrowth colonies derived from porcine inner cell masses and epiblasts.

The present study was conducted to test different methods for porcine inner cell mass (ICM) and epiblast isolation and to evaluate the morphology and expression of pluripotency genes in ICM- and epiblast-derived outgrowth colonies (OCs) and passages thereof with particular attention on the relationship between OCT4 expression and embryonic stem cell (ESC)-like morphology. A total of 104 zona pellucida-enclosed and 101 hatched blastocysts were subjected to four different methods of ICM and epiblast isolation, respectively: Manual isolation, immunosurgery, immunosurgery with manual cleaning, or whole blastocyst culture. OCs were established on mouse embryonic fibroblast (MEF) cells and categorized according to morphology and OCT4 staining.

From zygote to implantation: morphological and molecular dynamics during embryo development in the pig.

The increasing focus on the pig as a biomedical model calls for studies which investigate morphological and molecular mechanisms during initial embryonic development in this species. In the pig, the paternal genome is actively demethylated in the zygote, whereas the maternal genome remains methylated. The major genome activation occurs at the four-cell stage, when prominent ribosome-synthesizing nucleoli develop in the blastomeres, allowing for trophectoderm and inner cell mass (ICM) differentiation.

The Dps-like protein Fri of Listeria monocytogenes promotes stress tolerance and intracellular multiplication in macrophage-like cells.

Members of the ferritin-like Dps protein family are found in a number of bacterial species, where they demonstrate the potential to bind iron, and have been implicated in tolerance to oxidative stress. In this study of the food-borne pathogen Listeria monocytogenes, the fri gene encoding a Dps homologue was deleted, and, compared to wild-type cells, it was found that the resulting mutant was less resistant to hydrogen peroxide, and demonstrated reduced survival following long-term (7-11 days) incubation in laboratory media. In view of this, it is shown that fri gene expression is controlled by the hydrogen peroxide regulator PerR, as well as the general stress sigma factor sigmaB.

Establishment of a quantitative ELISA capable of determining peptide - MHC class I interaction.

Many different assays for measuring peptide-MHC interactions have been suggested over the years. Yet, there is no generally accepted standard method available. We have recently generated preoxidized recombinant MHC class I molecules (MHC-I) which can be purified to homogeneity under denaturing conditions (i.