Le niveau de compréhension de l’anglais des étudiants en médecine peut être amélioré. Résultats d’une stratégie d’évaluation systématique

Objectives To describe the level of English of a population of medical students and the improvement after the implementation of systematic assessment that all students achieve a minimal level. Population and methods For the past 5 years, all medical students in our medical school have been taking the Test of English for International Communication (TOEIC). The baseline population (students entering second year in 2004) had no specific obligation. After 2004, a score above 600 was mandatory for graduation. Teaching was oriented towards training for the TOEIC and the number of hours was more important for low-level students. Results The mean score has increased from 618 ± 146 in 2004, to 687 ± 94, 717 ± 97, 733 ± 96 and 731 ± 104 for the next four years. The proportion of students who do not achieve a score of 550 (B1 level of the European framework) has decreased from 30 to 0%. Discussion Improving the level of English of French medical students is possible, if this is made a priority. The objective, as set in engineering studies, that all medical students reach a B2 level would require national guidelines

Connecting Berezinskii-Kosterlitz-Thouless and BEC Phase Transitions by Tuning Interactions in a Trapped Gas.

We study the critical point for the emergence of coherence in a harmonically trapped two-dimensional Bose gas with tunable interactions. Over a wide range of interaction strengths we find excellent agreement with the classical-field predictions for the critical point of the Berezinskii-Kosterlitz-Thouless (BKT) superfluid transition. This allows us to quantitatively show, without any free parameters, that the interaction-driven BKT transition smoothly converges onto the purely quantum-statistical Bose-Einstein condensation transition in the limit of vanishing interactions.This work was supported by AFOSR, ARO, DARPA OLE, and EPSRC [Grant No. EP/K003615/1]. N. N. acknowledges support from Trinity College, Cambridge, R. P. S. from the Royal Society, and K. G. H. V. from DAAD.This is the author accepted manuscript. The final version is available from APS via http://dx.doi.org/10.1103/PhysRevLett.114.25530

Models of human core transcriptional regulatory circuitries

A small set of core transcription factors (TFs) dominates control of the gene expression program in embryonic stem cells and other well-studied cellular models. These core TFs collectively regulate their own gene expression, thus forming an interconnected auto-regulatory loop that can be considered the core transcriptional regulatory circuitry (CRC) for that cell type. There is limited knowledge of core TFs, and thus models of core regulatory circuitry, for most cell types. We recently discovered that genes encoding known core TFs forming CRCs are driven by super-enhancers, which provides an opportunity to systematically predict CRCs in poorly studied cell types through super-enhancer mapping. Here, we use super-enhancer maps to generate CRC models for 75 human cell and tissue types. These core circuitry models should prove valuable for further investigating cell-type–specific transcriptional regulation in healthy and diseased cells.United States. National Institutes of Health (HG002668

An integrated computational-experimental approach reveals Yersinia pestis genes essential across a narrow or a broad range of environmental conditions

Background The World Health Organization has categorized plague as a re-emerging disease and the potential for Yersinia pestis to also be used as a bioweapon makes the identification of new drug targets against this pathogen a priority. Environmental temperature is a key signal which regulates virulence of the bacterium. The bacterium normally grows outside the human host at 28 °C. Therefore, understanding the mechanisms that the bacterium used to adapt to a mammalian host at 37 °C is central to the development of vaccines or drugs for the prevention or treatment of human disease. Results Using a library of over 1 million Y. pestis CO92 random mutants and transposon-directed insertion site sequencing, we identified 530 essential genes when the bacteria were cultured at 28 °C. When the library of mutants was subsequently cultured at 37 °C we identified 19 genes that were essential at 37 °C but not at 28 °C, including genes which encode proteins that play a role in enabling functioning of the type III secretion and in DNA replication and maintenance. Using genome-scale metabolic network reconstruction we showed that growth conditions profoundly influence the physiology of the bacterium, and by combining computational and experimental approaches we were able to identify 54 genes that are essential under a broad range of conditions. Conclusions Using an integrated computational-experimental approach we identify genes which are required for growth at 37 °C and under a broad range of environments may be the best targets for the development of new interventions to prevent or treat plague in humans

Cerebrovascular and blood-brain barrier impairments in Huntington's disease: Potential implications for its pathophysiology: Vascular impairments in HD

ObjectiveAlthough the underlying cause of Huntington's disease (HD) is well established, the actual pathophysiological processes involved remain to be fully elucidated. In other proteinopathies such as Alzheimer's and Parkinson's diseases, there is evidence for impairments of the cerebral vasculature as well as the blood–brain barrier (BBB), which have been suggested to contribute to their pathophysiology. We investigated whether similar changes are also present in HD.MethodsWe used 3‐ and 7‐Tesla magnetic resonance imaging as well as postmortem tissue analyses to assess blood vessel impairments in HD patients. Our findings were further investigated in the R6/2 mouse model using in situ cerebral perfusion, histological analysis, Western blotting, as well as transmission and scanning electron microscopy.ResultsWe found mutant huntingtin protein (mHtt) aggregates to be present in all major components of the neurovascular unit of both R6/2 mice and HD patients. This was accompanied by an increase in blood vessel density, a reduction in blood vessel diameter, as well as BBB leakage in the striatum of R6/2 mice, which correlated with a reduced expression of tight junction‐associated proteins and increased numbers of transcytotic vesicles, which occasionally contained mHtt aggregates. We confirmed the existence of similar vascular and BBB changes in HD patients.InterpretationTaken together, our results provide evidence for alterations in the cerebral vasculature in HD leading to BBB leakage, both in the R6/2 mouse model and in HD patients, a phenomenon that may, in turn, have important pathophysiological implications. Ann Neurol 2015;78:160–17

Stress from Nucleotide Depletion Activates the Transcriptional Regulator HEXIM1 to Suppress Melanoma

Studying cancer metabolism gives insight into tumorigenic survival mechanisms and susceptibilities. In melanoma, we identify HEXIM1, a transcription elongation regulator, as a melanoma tumor suppressor that responds to nucleotide stress. HEXIM1 expression is low in melanoma. Its overexpression in a zebrafish melanoma model suppresses cancer formation, while its inactivation accelerates tumor onset in vivo. Knockdown of HEXIM1 rescues zebrafish neural crest defects and human melanoma proliferation defects that arise from nucleotide depletion. Under nucleotide stress, HEXIM1 is induced to form an inhibitory complex with P-TEFb, the kinase that initiates transcription elongation, to inhibit elongation at tumorigenic genes. The resulting alteration in gene expression also causes anti-tumorigenic RNAs to bind to and be stabilized by HEXIM1. HEXIM1 plays an important role in inhibiting cancer cell-specific gene transcription while also facilitating anti-cancer gene expression. Our study reveals an important role for HEXIM1 in coupling nucleotide metabolism with transcriptional regulation in melanoma

Green Infrastructure in the Space of Flows: An Urban Metabolism

Recent research demonstrates that urban metabolism studies hold ample scope for informing more sustainable urban planning and design. The assessment of the resource flows that are required to sustain the growth and maintenance of cities can allow gaining a clear picture of how cities operate to comply with environmental performance standards and to ensure that both human and ecosystem health are preserved. Green infrastructure (GI) plays a key role in enhancing both cities’ environmental performance and health. For example, GI interventions mitigate the Urban Heat Island effect (improved thermal comfort), reduce particulate matter concentration (healthier air quality), and sequestrate and store atmospheric carbon (climate change mitigation). Research on ecosystem services and the application of the concept in urban planning provides a growing evidence base that an understanding of provisioning and regulating services can facilitate more environmentally informed GI planning and design. The contribution of GI in enhancing human health and psychological wellbeing is also evidenced in recent studies valuing both material and immaterial benefits provided by urban ecosystems, including cultural ecosystem services. Therefore, the use of ecosystem service frameworks can help reveal and quantify the role of GI in fostering both urban environmental quality and the wellbeing of human populations. However, there remains little discussion of how health and wellbeing aspects can be integrated with environmental performance objectives. In this chapter, urban metabolism thinking is proposed as a way forward, providing analytical tools to inform environmentally-optimized strategies across the urban scales. Opportunities to foster integrated urban metabolism approaches that can inform more holistic GI planning are discussed. Finally, future research avenues to incorporate the multiple dimensions of human health and wellbeing into urban metabolism thinking are highlighted

Population stratification may bias analysis of PGC-1α as a modifier of age at Huntington disease motor onset

Huntington’s disease (HD) is an inherited neurodegenerative disorder characterized by motor, cognitive and behavioral disturbances, caused by the expansion of a CAG trinucleotide repeat in the HD gene. The CAG allele size is the major determinant of age at onset (AO) of motor symptoms, although the remaining variance in AO is highly heritable. The rs7665116 SNP in PPARGC1A, encoding the mitochondrial regulator PGC-1α, has been reported to be a significant modifier of AO in three European HD cohorts, perhaps due to affected cases from Italy. We attempted to replicate these findings in a large collection of (1,727) HD patient DNA samples of European origin. In the entire cohort, rs7665116 showed a significant effect in the dominant model (p value = 0.008) and the additive model (p value = 0.009). However, when examined by origin, cases of Southern European origin had an increased rs7665116 minor allele frequency (MAF), consistent with this being an ancestry-tagging SNP. The Southern European cases, despite similar mean CAG allele size, had a significantly older mean AO (p < 0.001), suggesting population-dependent phenotype stratification. When the generalized estimating equations models were adjusted for ancestry, the effect of the rs7665116 genotype on AO decreased dramatically. Our results do not support rs7665116 as a modifier of AO of motor symptoms, as we found evidence for a dramatic effect of phenotypic (AO) and genotypic (MAF) stratification among European cohorts that was not considered in previously reported association studies. A significantly older AO in Southern Europe may reflect population differences in genetic or environmental factors that warrant further investigation