Heterogeneity for IGF-II production maintained by public goods dynamics in neuroendocrine pancreatic cancer

The extensive intratumor heterogeneity revealed by sequencing cancer genomes is an essential determinant of tumor progression, diagnosis, and treatment. What maintains heterogeneity remains an open question because competition within a tumor leads to a strong selection for the fittest subclone. Cancer cells also cooperate by sharing molecules with paracrine effects, such as growth factors, and heterogeneity can be maintained if subclones depend on each other for survival. Without strict interdependence between subclones, however, nonproducer cells can free-ride on the growth factors produced by neighboring producer cells, a collective action problem known in game theory as the “tragedy of the commons,” which has been observed in microbial cell populations. Here, we report that similar dynamics occur in cancer cell populations. Neuroendocrine pancreatic cancer (insulinoma) cells that do not produce insulin-like growth factor II (IGF-II) grow slowly in pure cultures but have a proliferation advantage in mixed cultures, where they can use the IGF-II provided by producer cells. We show that, as predicted by evolutionary game theory, producer cells do not go extinct because IGF-II acts as a nonlinear public good, creating negative frequency-dependent selection that leads to a stable coexistence of the two cell types. Intratumor cell heterogeneity can therefore be maintained even without strict interdependence between cell subclones. Reducing the amount of growth factors available within a tumor may lead to a reduction in growth followed by a new equilibrium, which may explain relapse in therapies that target growth factors

Die Mastleistung und Schlachtkörperqualität unterschiedlicher genetischer Schweineherkünfte in konventioneller und ökologischer Haltung

A study was conducted to examine growth and carcass composition of genetically different pigs under conventional and organic conditions. The pig genotypes were Bundeshybridzuchtprogramm (BHZP), Schwäbisch Hällisches Schwein (SH), Angler Sattelschwein (AS), Piétrain x SH (PIxSH), Piétrain x AS (PIxAS), Piétrain x Deutsches Edelschwein (PIxDE) and Duroc x Deutsche Landrasse (DUxDL). A total number of 650 pigs were kept at two test stations. This paper presents results of the test station Neu-Ulrichstein where the genotypes BHZP, SH and PIxSH were tested. Growth and carcass chracteristics of 80 pigs per environment (conventional housing and feeding vs. organic housing and feeding) were analysed using a linear model including the fixed effects of sex, genotype, environment and the interaction of geno-type and environment. Genotype was found to have a significant influence on growth and carcass quality, whereas the BHZP-pigs had a higher daily gain, meat percentage and meat to fat ratio. The influence of the environment was significant for daily gain only, with pigs under conventional conditions gaining 110 g more than pigs under organic conditions. No statistically significant interactions between genotype and environment could be found for this part of the study. With exception of the feed con-version ratio under conventional conditions, the BHZP-pigs showed the best perform-ance and carcass quality in both environments when compared to the PIxSH- and SH- genotypes

Sugar-to-base correlation in nucleic acids with a 5D APSY-HCNCH or two 3D APSY-HCN experiments

A five-dimensional (5D) APSY (automated projection spectroscopy) HCNCH experiment is presented, which allows unambiguous correlation of sugar to base nuclei in nucleic acids. The pulse sequence uses multiple quantum (MQ) evolution which enables long constant-time evolution periods in all dimensions, an improvement that can also benefit non-APSY applications. Applied with an RNA with 23 nucleotides the 5D APSY-HCNCH experiment produced a complete and highly precise 5D chemical shift list within 1.5h. Alternatively, and for molecules where the out-and-stay 5D experiment sensitivity is not sufficient, a set of out-and-back 3D APSY-HCN experiments is proposed: an intra-base (3D APSY-b-HCN) experiment in an MQ or in a TROSY version, and an MQ sugar-to-base (3D APSY-s-HCN) experiment. The two 3D peak lists require subsequent matching via the N1/9 chemical shift values to one 5D peak list. Optimization of the 3D APSY experiments for maximal precision in the N1/9 dimension allowed matching of all 15N chemical shift values contained in both 3D peak lists. The precise 5D chemical shift correlation lists resulting from the 5D experiment or a pair of 3D experiments also provide a valuable basis for subsequent connection to chemical shifts derived with other experiment

Specific wheat fractions influence hepatic fat metabolism in diet-induced obese mice

Low whole grain consumption is a risk factor for the development of non-communicable diseases such as type 2 diabetes. Dietary fiber and phytochemicals are bioactive grain compounds, which could be involved in mediating these beneficial effects. These compounds are not equally distributed in the wheat grain, but are enriched in the bran and aleurone fractions. As little is known on physiological effects of different wheat fractions, the aim of this study was to investigate this aspect in an obesity model. For twelve weeks, C57BL/6J mice were fed high-fat diets (HFD), supplemented with one of four wheat fractions: whole grain flour, refined white flour, bran, or aleurone. The different diets did not affect body weight, however bran and aleurone decreased liver triglyceride content, and increased hepatic n-3 polyunsaturated fatty acid (PUFA) concentrations. Furthermore, lipidomics analysis revealed increased PUFA concentration in the lipid classes of phosphatidylcholine (PC), PC-ether, and phosphatidylinositol in the plasma of mice fed whole grain, bran, and aleurone supplemented diets, compared to refined white flour. Furthermore, bran, aleurone, and whole grain supplemented diets increased microbial alpha-diversity, but only bran and aleurone increased the cecal concentrations of short-chain fatty acids. The effects on hepatic lipid metabolism might thus at least partially be mediated by microbiota-dependent mechanisms

Selectivity profiling of BCRP versus P-gp inhibition: from automated collection of polypharmacology data to multi-label learning

Additional file 1. The list of descriptor names, instructions on how to run the python script, the distribution plots for the important descriptors, the heat map of activities for the dense dataset, the structure of the over-represented scaffolds in the sparse dataset, a 2D representation of a PCA run on Morgan fingerprints (ECFP-like) for both dense and sparse datasets, and the structures of the 9 misclassified compounds

Improved antenna phase center models for GLONASS

Thanks to the increasing number of active GLONASS satellites and the increasing number of multi-GNSS tracking stations in the network of the International GNSS Service (IGS), the quality of the GLONASS orbits has become significantly better over the last few years. By the end of 2008, the orbit RMS error had reached a level of 3-4cm. Nevertheless, the strategy to process GLONASS observations still has deficiencies: one simplification, as applied within the IGS today, is the use of phase center models for receiver antennas for the GLONASS observations, which were derived from GPS measurements only, by ignoring the different frequency range. Geo++ GmbH calibrates GNSS receiver antennas using a robot in the field. This procedure yields now separate corrections for the receiver antenna phase centers for each navigation satellite system, provided its constellation is sufficiently populated. With a limited set of GLONASS calibrations, it is possible to assess the impact of GNSS-specific receiver antenna corrections that are ignored within the IGS so far. The antenna phase center model for the GLONASS satellites was derived in early 2006, when the multi-GNSS tracking network of the IGS was much sparser than it is today. Furthermore, many satellites of the constellation at that time have in the meantime been replaced by the latest generation of GLONASS-M satellites. For that reason, this paper also provides an update and extension of the presently used correction tables for the GLONASS satellite antenna phase centers for the current constellation of GLONASS satellites. The updated GLONASS antenna phase center model helps to improve the orbit qualit

Laser Therapy and Dementia: A Database Analysis and Future Aspects on LED-Based Systems

Mainly because of the movement in the age pyramid, one can assume that the incidence of Alzheimer’s disease or dementia in general will increase in the coming decades. This paper employs a database analysis to examine the profile of publication activity related to this topic. Two databases were searched: PubMed and Cochrane Library. About 600 papers related to the research area “dementia and laser” and about 450 papers related to the search terms “Alzheimer and laser” were found in these two most commonly used databases. Ten plus one papers are described in detail and are discussed in the context of the laser research performed at the Medical University of Graz. First results concerning the measurement of the transmission factor (TF) through the human skull of a new LED- (light emitting diode-) based system are presented (TF = 0.0434 ± 0.0104 (SD)). The measurements show that this LED system (using the QIT (quantum optical induced transparency) effect) might be used in the treatment of dementia

A bioluminescent mouse model of pancreatic β-cell carcinogenesis

The Rip1Tag2 transgenic mouse model of pancreatic β-cell carcinogenesis has been instrumental in identifying several hallmarks of cancer, including tumor cell evasion from apoptosis, tumor angiogenesis and tumor invasion. Moreover, Rip1Tag2 mice have been helpful in the development and testing of innovative cancer therapies and tumor imaging protocols. However, based on tumor localization in the mouse, primary tumor growth and metastatic dissemination cannot be easily monitored in a longitudinal axis by non-invasive and low-technology approaches. Here, we report the generation of a new transgenic mouse line as a versatile tool to study β-cell carcinogenesis. Transgenic expression of a bicistronic messenger RNA encoding simian virus large T antigen and firefly luciferase in pancreatic β-cells recapitulates insulinoma development in a reproducible multistage process. In the mouse line called RipTag-IRES-Luciferase line (RTL) 1, the β-cell-specific expression of luciferase allows the non-invasive monitoring of primary tumor growth over time in vivo and the detection and quantification of disseminated tumor cells and micrometastases in distant organs ex vivo. When crossed to mouse lines in which the expression of cancer ‘modifier' genes has been manipulated, tumor initiation and tumor progression are similarly affected as previously reported for Rip1Tag2 mice, indicating a robust tumor progression pathway shared between the two different transgenic mouse lines. Together, the data indicate that the RTL1 mouse line will be of great value to study anti-tumoral therapeutic approaches as well as to define the functional roles of cancer- and metastasis-related genes when crossed to appropriate transgenic or gene-targeted mouse line

How do medical students value health on the EQ-5D? Evaluation of hypothetical health states compared to the general population

<p>Abstract</p> <p>Background</p> <p>Medical students gain a particular perspective on health problems during their medical education. This article describes how medical students value 10 hypothetical health states using the EQ-5D compared to the general population.</p> <p>Methods</p> <p>Based on a sample of 161 medical students (male: 41%) we compared valuations of 10 hypothetical EQ-5D health states collected in face to face interviews with the valuations of the general population. Self-reported health on the EQ-5D was also collected.</p> <p>Results</p> <p>Every third health state was valuated higher by the medical students compared to data of the general population. The differences were independent of the severity of the hypothetical health state. Concerning the self-reported health, the majority of the students (66%) reported no problems in the five EQ-5D domains (EQ-5D VAS M = 87.3 ± 9.6 SD). However, when compared to an age-matched sample the medical students show significantly more problems in the area of pain/discomfort and anxiety/depression.</p> <p>Conclusion</p> <p>Medical students have a tendency to value health states higher than the general public. Medical professionals should be continuously aware that their assessment of the patients health state can differ from the valuations of the general population.</p