Src Family Kinases and p38 Mitogen-Activated Protein Kinases Regulate Pluripotent Cell Differentiation in Culture

Multiple pluripotent cell populations, which together comprise the pluripotent cell lineage, have been identified. The mechanisms that control the progression between these populations are still poorly understood. The formation of early primitive ectoderm-like (EPL) cells from mouse embryonic stem (mES) cells provides a model to understand how one such transition is regulated. EPL cells form from mES cells in response to l-proline uptake through the transporter Slc38a2. Using inhibitors of cell signaling we have shown that Src family kinases, p38 MAPK, ERK1/2 and GSK3β are required for the transition between mES and EPL cells. ERK1/2, c-Src and GSK3β are likely to be enforcing a receptive, primed state in mES cells, while Src family kinases and p38 MAPK are involved in the establishment of EPL cells. Inhibition of these pathways prevented the acquisition of most, but not all, features of EPL cells, suggesting that other pathways are required. L-proline activation of differentiation is mediated through metabolism and changes to intracellular metabolite levels, specifically reactive oxygen species. The implication of multiple signaling pathways in the process suggests a model in which the context of Src family kinase activation determines the outcomes of pluripotent cell differentiation

Clinical Study A Reappraisal of Chemotherapy-Induced Liver Injury in Colorectal Liver Metastases before the Era of Antiangiogenics

Background and Aims. Chemotherapy of colorectal liver metastases can induce hepatotoxicity in noncancerous liver. We describe these lesions and assess risk factors and impacts on postresection morbidity and mortality in naive patients to chemotherapy before the era of bevacizumab. Methods. Noncancerous liver tissue lesions were analysed according to tumour, chemotherapy, surgery, and patient characteristics. Results. Fifty patients aged 62 ± 9.3 years were included between 2003 and 2007. Thirty-three (66%) received chemotherapy, with Folfox (58%), Folfiri (21%), LV5FU2 (12%), or Xelox (9%) regimens. Hepatotoxicity consisted of 18 (36%) cases of severe sinusoidal dilatation (SD), 13 (26%) portal fibrosis, 7 (14%) perisinusoidal fibrosis (PSF), 6 (12%) nodular regenerative hyperplasia (NRH), 2 (4%) steatosis >30%, zero steatohepatitis, and 16 (32%) surgical hepatitis. PSF was more frequent after chemotherapy (21% versus 0%, = 0.04), especially LV5FU2 ( = 0.02). SD was associated with oxaliplatin (54.5% versus 23.5%, = 0.05) and low body mass index ( = 0.003). NRH was associated with oxaliplatin ( = 0.03) and extensive resection ( = 0.04). No impact on mortality and morbidity was observed, apart postoperative elevation of bilirubin levels in case of PSF ( = 0.03), longer hospitalization in case of surgical hepatitis ( = 0.03), and greater blood loss in case of portal fibrosis ( = 0.03). Conclusions. Chemotherapy of colorectal liver metastases induces sinusoidal dilatation related to oxaliplatin and perisinusoidal fibrosis related to 5FU, without any impact on postoperative mortality

Food metabolomics applied in cohorts to accelerate the discovery of nutritional biomarkers

communication orale : Claudine ManachThe Second International Congress of Translational Research in Human Nutrition is organised by the Research Centre in Human Nutrition (CRNH) of Auvergne, of which INRA is a member, in collaboration with NuGO, European Association of universities and research institutes in the field of nutrigenomics.The purpose of dietary assessment is to estimate usual and recent intake of foods, nutrients, bioactive compounds and food contaminants for exploration of associations with health outcomes and monitoring of population nutritional status. These data are still extremely difficult to obtain. Methods currently used are based on dietary questionnaires which have inherent limitations linked to self-reporting. A complementary approach to questionnaires is the use of biomarkers. However, only a few biomarkers have been properly validated, which do not cover the wide range offoods consumed. Metabolomics has emerged as a promising approach to discover nutritional biomarkers. Typically, plasma or urine samples collected before and after acute intake of a specific food are profiled using NMR or high resolution Mass Spectrometry (MS) and compared usingmultivariate statistics to pinpoint the signals reflecting the consumption of the target food. In a proof-of-concept study on citrus, we showed that urine profiling of cohort subjects stratified by consumption could be a more effective strategy for discovery of sensitive biomarkers of intake

Use of high resolution mass spectrometry for identification of specific biomarkers of coffee consumption

Présentation poster : Y. FillâtreThe Second International Congress of Translational Research in Human Nutrition is organised by the Research Centre in Human Nutrition (CRNH) of Auvergne, of which INRA is a member, in collaboration with NuGO, European Association of universities and research institutes in the field of nutrigenomicsANR Phenomenep ALIA-2010-007 Conseil Regional Auvergne-FEDER post-doc grantAs part of the ANR PhenoMeNEp project, non-targeted profiling is used to identify potential biomarkers of plant food consumption. Using 24 hour dietary recall and food frequency questionnaire data, 144 high (median 974 grams/day) and 66 low (median 305 grams/day) consumers of fruit and vegetables were selected from the French SU.VI.MAX2 cohort. Morning spot urine samples from each subjec

Jack-of-all-trades effects drive biodiversity-ecosystem multifunctionality relationships in European forests.

There is considerable evidence that biodiversity promotes multiple ecosystem functions (multifunctionality), thus ensuring the delivery of ecosystem services important for human well-being. However, the mechanisms underlying this relationship are poorly understood, especially in natural ecosystems. We develop a novel approach to partition biodiversity effects on multifunctionality into three mechanisms and apply this to European forest data. We show that throughout Europe, tree diversity is positively related with multifunctionality when moderate levels of functioning are required, but negatively when very high function levels are desired. For two well-known mechanisms, 'complementarity' and 'selection', we detect only minor effects on multifunctionality. Instead a third, so far overlooked mechanism, the 'jack-of-all-trades' effect, caused by the averaging of individual species effects on function, drives observed patterns. Simulations demonstrate that jack-of-all-trades effects occur whenever species effects on different functions are not perfectly correlated, meaning they may contribute to diversity-multifunctionality relationships in many of the world's ecosystems.The research leading to these results received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 265171.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/ncomms1110

Biotic homogenization can decrease landscape-scale forest multifunctionality.

Many experiments have shown that local biodiversity loss impairs the ability of ecosystems to maintain multiple ecosystem functions at high levels (multifunctionality). In contrast, the role of biodiversity in driving ecosystem multifunctionality at landscape scales remains unresolved. We used a comprehensive pan-European dataset, including 16 ecosystem functions measured in 209 forest plots across six European countries, and performed simulations to investigate how local plot-scale richness of tree species (α-diversity) and their turnover between plots (β-diversity) are related to landscape-scale multifunctionality. After accounting for variation in environmental conditions, we found that relationships between α-diversity and landscape-scale multifunctionality varied from positive to negative depending on the multifunctionality metric used. In contrast, when significant, relationships between β-diversity and landscape-scale multifunctionality were always positive, because a high spatial turnover in species composition was closely related to a high spatial turnover in functions that were supported at high levels. Our findings have major implications for forest management and indicate that biotic homogenization can have previously unrecognized and negative consequences for large-scale ecosystem multifunctionality.We thank the Hainich National Park administration as well as Felix Berthold and Carsten Beinhoff for support of this study and Gerald Kaendler and the Johann Heinrich von Thünen-Institut for providing access to the German National Forest Inventory data. The research leading to these results received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement 265171.This is the final version of the article. It first appeared from the National Academy of Sciences via https://doi.org//10.1073/pnas.151790311

The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI): instrument and pre-launch testing

This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI), to be launched onboard of ESA's Herschel Space Observatory, by 2008. It includes the first results from the instrument level tests. The instrument is designed to be electronically tuneable over a wide and continuous frequency range in the Far Infrared, with velocity resolutions better than 0.1 km/s with a high sensitivity. This will enable detailed investigations of a wide variety of astronomical sources, ranging from solar system objects, star formation regions to nuclei of galaxies. The instrument comprises 5 frequency bands covering 480-1150 GHz with SIS mixers and a sixth dual frequency band, for the 1410-1910 GHz range, with Hot Electron Bolometer Mixers (HEB). The Local Oscillator (LO) subsystem consists of a dedicated Ka-band synthesizer followed by 7 times 2 chains of frequency multipliers, 2 chains for each frequency band. A pair of Auto-Correlators and a pair of Acousto-Optic spectrometers process the two IF signals from the dual-polarization front-ends to provide instantaneous frequency coverage of 4 GHz, with a set of resolutions (140 kHz to 1 MHz), better than < 0.1 km/s. After a successful qualification program, the flight instrument was delivered and entered the testing phase at satellite level. We will also report on the pre-flight test and calibration results together with the expected in-flight performance

The Evolution of Primate Short-Term Memory.

Short-term memory is implicated in a range of cognitive abilities and is critical for understanding primate cognitive evolution. To investigate the effects of phylogeny, ecology and sociality on short-term memory, we tested the largest and most diverse primate sample to date (421 non-human primates across 41 species) in an experimental delayed-response task. Our results confirm previous findings that longer delays decrease memory performance across species and taxa. Our analyses demonstrate a considerable contribution of phylogeny over ecological and social factors on the distribution of short-term memory performance in primates; closely related species had more similar short-term memory abilities. Overall, individuals in the branch of Hominoidea performed better compared to Cercopithecoidea, who in turn performed above Platyrrhini and Strepsirrhini. Interdependencies between phylogeny and socioecology of a given species presented an obstacle to disentangling the effects of each of these factors on the evolution of short-term memory capacity. However, this study offers an important step forward in understanding the interspecies and individual variation in short-term memory ability by providing the first phylogenetic reconstruction of this trait’s evolutionary history. The dataset constitutes a unique resource for studying the evolution of primate cognition and the role of short-term memory in other cognitive abilities.info:eu-repo/semantics/publishedVersio

EuReCa ONE—27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe

AbstractIntroductionThe aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.MethodsThis was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.ResultsData on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.ConclusionThe results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe.EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events