University of Tübingen

About: University of Tübingen is a education organization based out in Tübingen, Germany. It is known for research contribution in the topics: Population & Immune system. The organization has 40555 authors who have published 84108 publications receiving 3015320 citations. The organization is also known as: Eberhard Karls University & Eberhard-Karls-Universität Tübingen.

Using the jackknife-based scoring method for measuring LRP onset effects in factorial designs.

Abstract: Miller, Patterson, and Ulrich (1998) introduced a jackknife-based method for measuring the differences between two conditions in the onset latencies of the lateralized readiness potential (LRP). The present paper generalizes such jackknife-based methods to factorial experiments with any combination of within- and between subjects factors. Specifically, we introduce a subsample scoring method to assess potential main and interaction effects on LRP onsets within conventional yet slightly adjusted analyses of variance (ANOVAs) and post hoc comparison procedures.

Multimodel ensembles of wheat growth: many models are better than one

Abstract: Crop models of crop growth are increasingly used to quantify the impact of global changes due to climate or crop management. Therefore, accuracy of simulation results is a major concern. Studies with ensembles of crop models can give valuable information about model accuracy and uncertainty, but such studies are difficult to organize and have only recently begun. We report on the largest ensemble study to date, of 27 wheat models tested in four contrasting locations for their accuracy in simulating multiple crop growth and yield variables. The relative error averaged over models was 24-38% for the different end-of-season variables including grain yield (GY) and grain protein concentration (GPC). There was little relation between error of a model for GY or GPC and error for in-season variables. Thus, most models did not arrive at accurate simulations of GY and GPC by accurately simulating preceding growth dynamics. Ensemble simulations, taking either the mean (e-mean) or median (e-median) of simulated values, gave better estimates than any individual model when all variables were considered. Compared to individual models, e-median ranked first in simulating measured GY and third in GPC. The error of e-mean and e-median declined with an increasing number of ensemble members, with little decrease beyond 10 models. We conclude that multimodel ensembles can be used to create new estimators with improved accuracy and consistency in simulating growth dynamics. We argue that these results are applicable to other crop species, and hypothesize that they apply more generally to ecological system models.

Genomic analyses identify hundreds of variants associated with age at menarche and support a role for puberty timing in cancer risk

Abstract: The timing of puberty is a highly polygenic childhood trait that is epidemiologically associated with various adult diseases. Using 1000 Genomes Project-imputed genotype data in up to ∼370,000 women, we identify 389 independent signals (P < 5 × 10-8) for age at menarche, a milestone in female pubertal development. In Icelandic data, these signals explain ∼7.4% of the population variance in age at menarche, corresponding to ∼25% of the estimated heritability. We implicate ∼250 genes via coding variation or associated expression, demonstrating significant enrichment in neural tissues. Rare variants near the imprinted genes MKRN3 and DLK1 were identified, exhibiting large effects when paternally inherited. Mendelian randomization analyses suggest causal inverse associations, independent of body mass index (BMI), between puberty timing and risks for breast and endometrial cancers in women and prostate cancer in men. In aggregate, our findings highlight the complexity of the genetic regulation of puberty timing and support causal links with cancer susceptibility.

Nonalcoholic Fatty Liver Disease in Humans Is Associated with Increased Plasma Endotoxin and Plasminogen Activator Inhibitor 1 Concentrations and with Fructose Intake

Abstract: Results of animal experiments suggest that consumption of refined carbohydrates (e.g. fructose) can result in small intestinal bacterial overgrowth and increased intestinal permeability, thereby contributing to the development of nonalcoholic fatty liver disease (NAFLD). Furthermore, increased plasminogen activator inhibitor (PAI)-1 has been linked to liver damage of various etiologies (e.g. alcohol, endotoxin, nonalcoholic). The aim of the present pilot study was to compare dietary factors, endotoxin, and PAI-1 concentrations between NAFLD patients and controls. We assessed the dietary intake of 12 patients with NAFLD and 6 control subjects. Plasma endotoxin and PAI-1 concentrations as well as hepatic expression of PAI-1 and toll-like receptor (TLR) 4 mRNA were determined. Despite similar total energy, fat, protein, and carbohydrate intakes, patients with NAFLD consumed significantly more fructose than controls. Endotoxin and PAI-1 plasma concentrations as well as hepatic TLR4 and PAI-1 mRNA expression of NAFLD patients were significantly higher than in controls. The plasma PAI-1 concentration was positively correlated with the plasma endotoxin concentration (Spearman r = 0.83; P < 0.005) and hepatic TLR4 mRNA expression (Spearman r = 0.54; P < 0.05). Hepatic mRNA expression of PAI-1 was positively associated with dietary intakes of carbohydrates (Spearman r = 0.67; P < 0.01), glucose (Spearman r = 0.58; P < 0.01), fructose (Spearman r = 0.58; P < 0.01), and sucrose (Spearman r = 0.70; P < 0.01). In conclusion, our results suggest that dietary fructose intake, increased intestinal translocation of bacterial endotoxin, and PAI-1 may contribute to the development of NAFLD in humans.

Expression of the B7-Related Molecule B7-H1 by Glioma Cells: A Potential Mechanism of Immune Paralysis

Abstract: Human glioblastoma is a highly lethal tumor that is known for its immune inhibitory capabilities. B7-homologue 1 (B7-H1), a recently identified homologue of B7.1/2 (CD80/86), has been described to exert costimulatory and immune regulatory functions. We investigated the expression and the functional activity of B7-H1 in human glioma cells in vitro and in vivo. Although lacking B7.1/2 (CD80/86), all 12 glioma cell lines constitutively expressed B7-H1 mRNA and protein. Exposure to IFN-gamma strongly enhanced B7-H1 expression. Immunohistochemical analysis of malignant glioma specimens revealed strong B7-H1 expression in all 10 samples examined, whereas no B7-H1 expression could be detected on normal brain tissues. To elucidate the functional significance of glioma cell-related B7-H1 expression, we performed coculture experiments of glioma cells with alloreactive CD4+ and CD8+ T cells. Glioma-related B7-H1 was identified as a strong inhibitor of CD4+ as well as CD8+ T-cell activation as assessed by increased cytokine production (IFN-gamma, interleukin-2, and interleukin-10) and expression levels of the T-cell activation marker (CD69) in the presence of a neutralizing antibody against B7-H1 (mAb 5H1). B7-H1 expression may thus significantly influence the outcome of T-cell tumor cell interactions and represents a novel mechanism by which glioma cells evade immune recognition and destruction.