ExxonMobil in Europe’s Shale Gas Fields: Quitting Early or Fighting It Out?

This article focuses on the oil and gas supermajor, ExxonMobil, and its business in the unconventional gas field in Europe. The purpose was to investigate whether and how ExxonMobil runs its natural gas operations differently among European countries and possible reasons for divergent strategies. After a brief introduction of the firm, ExxonMobil’s approach in Europe in general will be discussed. Two countries are in focus: Poland and Germany. The key finding is that the firm indeed has shown different approaches and strategies. In Poland, ExxonMobil faced a supportive, positive environment but quit quickly when its small investment resulted only in disappointing results. The firm, however, was a newcomer which had not much to lose. In contrast, its German unconventional gas operations are connected to broad conventional activities and are being defended by an extensive effort to win back public support

ExxonMobil in Europe’s Shale Gas Fields: Quitting Early or Fighting It Out?

This article focuses on the oil and gas supermajor, ExxonMobil, and its business in the unconventional gas field in Europe. The purpose was to investigate whether and how ExxonMobil runs its natural gas operations differently among European countries and possible reasons for divergent strategies. After a brief introduction of the firm, ExxonMobil’s approach in Europe in general will be discussed. Two countries are in focus: Poland and Germany. The key finding is that the firm indeed has shown different approaches and strategies. In Poland, ExxonMobil faced a supportive, positive environment but quit quickly when its small investment resulted only in disappointing results. The firm, however, was a newcomer which had not much to lose. In contrast, its German unconventional gas operations are connected to broad conventional activities and are being defended by an extensive effort to win back public support.Keywords: energy, energy policy, ExxonMobil, fracking, Germany, hydraulic fracturing, Poland, public acceptance, regulatory politics, shale gas, unconventional gas, US

Immortalized pathological human myoblasts: towards a universal tool for the study of neuromuscular disorders

<p>Abstract</p> <p>Background</p> <p>Investigations into both the pathophysiology and therapeutic targets in muscle dystrophies have been hampered by the limited proliferative capacity of human myoblasts. Isolation of reliable and stable immortalized cell lines from patient biopsies is a powerful tool for investigating pathological mechanisms, including those associated with muscle aging, and for developing innovative gene-based, cell-based or pharmacological biotherapies.</p> <p>Methods</p> <p>Using transduction with both telomerase-expressing and cyclin-dependent kinase 4-expressing vectors, we were able to generate a battery of immortalized human muscle stem-cell lines from patients with various neuromuscular disorders.</p> <p>Results</p> <p>The immortalized human cell lines from patients with Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, congenital muscular dystrophy, and limb-girdle muscular dystrophy type 2B had greatly increased proliferative capacity, and maintained their potential to differentiate both <it>in vitro </it>and <it>in vivo </it>after transplantation into regenerating muscle of immunodeficient mice.</p> <p>Conclusions</p> <p>Dystrophic cellular models are required as a supplement to animal models to assess cellular mechanisms, such as signaling defects, or to perform high-throughput screening for therapeutic molecules. These investigations have been conducted for many years on cells derived from animals, and would greatly benefit from having human cell models with prolonged proliferative capacity. Furthermore, the possibility to assess <it>in vivo </it>the regenerative capacity of these cells extends their potential use. The innovative cellular tools derived from several different neuromuscular diseases as described in this report will allow investigation of the pathophysiology of these disorders and assessment of new therapeutic strategies.</p

Data Flow Framework: A persona-based repository to modeling recommender systems

International audienceThe present project comes to propose a framework of data acquisition and structured repository in order to be able to apply machine learning techniques to content recommendation. For this, it is intended to use as a basis the modeling and prediction of future scenarios created from the AvaSUS (Virtual Learning Environment of Single Health System in Brazil) data, coverage of primary care in Brazil data, quality indicators from primary care, health facilities and health professional data, as well as data from diseases with mandatory notification. The AvaSUS data are obtained directly from the its database, whereas the others are part of a data lake built for research. The construction of a repository is due to the need of conformation of the structures, to this was chosen to work with the Experience API (or xApi) which defines an ontology structuring users and resources from one action

Front Aging Neurosci

We studied the influence of emotions on autobiographical memory (AbM) in patients with Alzheimer's disease (AD), characteristically triggering atrophy in the hippocampus and the amygdala, two crucial structures sustaining memory and emotional processing. Our first aim was to analyze the influence of emotion on AbM in AD patients, on both the proportion and the specificity of emotional memories. Additionally, we sought to determine the relationship of emotional AbM to amygdalar-hippocampal volumes. Eighteen prodromal to mild AD patients and 18 age-matched healthy controls were included. We obtained 30 autobiographical memories per participant using the modified Crovitz test (MCT). Analyses were performed on global scores, rates and specificity scores of the emotional vs. neutral categories of memories. Amygdalar-hippocampal volumes were extracted from 3D T1-weighted MRI scans and tested for correlations with behavioral data. Overall, AD patients displayed a deficit in emotional AbMs as they elicited less emotional memories than the controls, however, the specificity of those memories was preserved. The deficit likely implied retrieval or storage as it was extended in time and without reminiscence bump effect. Global scores and rates of emotional memories, but not the specificity scores, were correlated to right amygdalar and hippocampal volumes, indicating that atrophy in these structures has a central role in the deficit observed. Conversely, emotional memories were more specific than neutral memories in both groups, reflecting an enhancement effect of emotion that could be supported by other brain regions that are spared during the early stages of the disease

Expression of Prostate-Specific Membrane Antigen (PSMA) on Biopsies Is an Independent Risk Stratifier of Prostate Cancer Patients at Time of Initial Diagnosis

Background: Stratifying prostate cancer (PCa) patients into risk groups at time of initial diagnosis enabling a risk-adapted disease management is still a major clinical challenge. Existing studies evaluating the prognostic potential of PSMA (prostate-specific membrane antigen) for PCa were performed on radical prostatectomy specimens (RPE), i.e., decision making for disease management was already completed at time of sample analysis. Aim of our study was to assess the prognostic value of PSMA expression for PCa patients on biopsies at time of initial diagnosis.Methods: PSMA expression was assessed by immunohistochemistry on 294 prostate biopsies with corresponding RPE, 621 primary tumor foci from 242 RPE, 43 locally advanced or recurrent tumors, 34 lymph node metastases, 78 distant metastases and 52 benign prostatic samples. PSMA expression was correlated with clinico-pathologic features. Primary endpoint was recurrence free survival. Other clinicopathologic features included WHO/ISUP grade groups, PSA serum level, TNM-stage, and R-status. Chi-square test, ANOVA-analyses, Cox-regression, and log-rank tests were performed for statistical analyses.Results: High PSMA expression on both biopsy and RPE significantly associates with a higher risk of disease recurrence following curative surgery. The 5-year-recurrence free survival rates were 88.2, 74.2, 67.7 and 26.8% for patients exhibiting no, low, medium, or high PSMA expression on biopsy, respectively. High PSMA expression on biopsy was significant in multivariate analysis predicting a 4-fold increased risk of disease recurrence independently from established prognostic markers. PSMA significantly increases during PCa progression.Conclusion: PSMA is an independent prognostic marker on biopsies at time of initial diagnosis and can predict disease recurrence following curative therapy for PCa. Our study proposes the application of the routinely used IHC marker PSMA for outcome prediction and decision making in risk-adapted PCa management on biopsies at time of initial diagnosis

Posttranscriptional Regulation of the Human LDL Receptor by the U2-Spliceosome

Background: The low-density lipoprotein receptor (LDLR) in the liver is the major determinant of LDL-cholesterol levels in human plasma. The discovery of genes that regulate the activity of LDLR helps to identify pathomechanisms of hypercholesterolemia and novel therapeutic targets against atherosclerotic cardiovascular disease.Methods: We performed a genome-wide RNA interference screen for genes limiting the uptake of fluorescent LDL into Huh-7 hepatocarcinoma cells. Top hit genes were validated by in vitro experiments as well as analyses of datasets on gene expression and variants in human populations.Results: The knockdown of 54 genes significantly inhibited LDL uptake. Fifteen of them encode for components or interactors of the U2-spliceosome. Knocking down any one of 11 out of 15 genes resulted in the selective retention of intron 3 of LDLR. The translated LDLR fragment lacks 88% of the full length LDLR and is detectable neither in non-transfected cells nor in human plasma. The hepatic expression of the intron 3 retention transcript is increased in non-alcoholic fatty liver disease as well as after bariatric surgery. Its expression in blood cells correlates with LDL-cholesterol and age. Single nucleotide polymorphisms and three rare variants of one spliceosome gene, RBM25, are associated with LDL-cholesterol in the population and familial hypercholesterolemia, respectively. Compared to overexpression of wild type RBM25, overexpression of the three rare RBM25 mutants in Huh-7 cells led to lower LDL uptake.Conclusions: We identified a novel mechanism of post-transcriptional regulation of LDLR activity in humans and associations of genetic variants of RBM25 with LDL-cholesterol levels.</p

A Missense Mutation in PPP1R15B Causes a Syndrome Including Diabetes, Short Stature, and Microcephaly.

Dysregulated endoplasmic reticulum stress and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) are associated with pancreatic β-cell failure and diabetes. Here, we report the first homozygous mutation in the PPP1R15B gene (also known as constitutive repressor of eIF2α phosphorylation [CReP]) encoding the regulatory subunit of an eIF2α-specific phosphatase in two siblings affected by a novel syndrome of diabetes of youth with short stature, intellectual disability, and microcephaly. The R658C mutation in PPP1R15B affects a conserved amino acid within the domain important for protein phosphatase 1 (PP1) binding. The R658C mutation decreases PP1 binding and eIF2α dephosphorylation and results in β-cell apoptosis. Our findings support the concept that dysregulated eIF2α phosphorylation, whether decreased by mutation of the kinase (EIF2AK3) in Wolcott-Rallison syndrome or increased by mutation of the phosphatase (PPP1R15B), is deleterious to β-cells and other secretory tissues, resulting in diabetes associated with multisystem abnormalities.This work was supported by the European Union 7th Framework Programme (project BetaBat), the Actions de Recherche Concertées de la Communauté Française, and Fonds National de la Recherche Scientifique (FNRS), Belgium, and by grants from the Agence Nationale pour la Recherche (ANR-09-GENO-021), the European Foundation for the Study of Diabetes/JDRF/Novo Nordisk, the Assistance Publique-Hôpitaux de Paris Programme Hospitalier de Recherche Clinique (DIAGENE), the GIS Maladies Rares, and the Wellcome Trust (084812/Z/08/Z). A.T.H. is a Wellcome Trust and National Institute for Health Research senior investigator, and D.R. is a Wellcome Trust Principal Research Fellow. B.A. was supported by an European Molecular Biology Organization Short-Term Fellowship and an FNRS-FRIA fellowship. M.I.-E. is a scientific collaborator of the FNRS. M.D. was supported by a doctoral fellowship from the Ministère de l’Education Nationale, de l’Enseignement Supérieur et de la Recherche, France.This is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/db15-047

Robust physical methods that enrich genomic regions identical by descent for linkage studies: confirmation of a locus for osteogenesis imperfecta

<p>Abstract</p> <p>Background</p> <p>The monogenic disease osteogenesis imperfecta (OI) is due to single mutations in either of the collagen genes ColA1 or ColA2, but within the same family a given mutation is accompanied by a wide range of disease severity. Although this phenotypic variability implies the existence of modifier gene variants, genome wide scanning of DNA from OI patients has not been reported. Promising genome wide marker-independent physical methods for identifying disease-related loci have lacked robustness for widespread applicability. Therefore we sought to improve these methods and demonstrate their performance to identify known and novel loci relevant to OI.</p> <p>Results</p> <p>We have improved methods for enriching regions of identity-by-descent (IBD) shared between related, afflicted individuals. The extent of enrichment exceeds 10- to 50-fold for some loci. The efficiency of the new process is shown by confirmation of the identification of the Col1A2 locus in osteogenesis imperfecta patients from Amish families. Moreover the analysis revealed additional candidate linkage loci that may harbour modifier genes for OI; a locus on chromosome 1q includes COX-2, a gene implicated in osteogenesis.</p> <p>Conclusion</p> <p>Technology for physical enrichment of IBD loci is now robust and applicable for finding genes for monogenic diseases and genes for complex diseases. The data support the further investigation of genetic loci other than collagen gene loci to identify genes affecting the clinical expression of osteogenesis imperfecta. The discrimination of IBD mapping will be enhanced when the IBD enrichment procedure is coupled with deep resequencing.</p

Does Culture Shape Our Understanding of Others’ Thoughts and Emotions? An Investigation Across 12 Countries

Q2Q2Measures of social cognition have now become central in neuropsychology, being essential for early and differential diagnoses, follow-up, and rehabilitation in a wide range of conditions. With the scientific world becoming increasingly interconnected, international neuropsychological and medical collaborations are burgeoning to tackle the global challenges that are mental health conditions. These initiatives commonly merge data across a diversity of populations and countries, while ignoring their specificity. Objective: In this context, we aimed to estimate the influence of participants’ nationality on social cognition evaluation. This issue is of particular importance as most cognitive tasks are developed in highly specific contexts, not representative of that encountered by the world’s population. Method: Through a large international study across 18 sites, neuropsychologists assessed core aspects of social cognition in 587 participants from 12 countries using traditional and widely used tasks. Results: Age, gender, and education were found to impact measures of mentalizing and emotion recognition. After controlling for these factors, differences between countries accounted for more than 20% of the variance on both measures. Importantly, it was possible to isolate participants’ nationality from potential translation issues, which classically constitute a major limitation. Conclusions: Overall, these findings highlight the need for important methodological shifts to better represent social cognition in both fundamental research and clinical practice, especially within emerging international networks and consortia.https://orcid.org/0000-0001-9422-3579https://orcid.org/0000-0001-6529-7077Revista Internacional - IndexadaA2N