Spectrométrie de masse de biomolécules par photoionisation à pression atmosphérique

La photoionisation à pression atmosphérique (APPI) permet d analyser des biomolécules hydrophobes donc difficilement observables avec les sources d ions connues comme l électro-nébulisation (ESI) ou la désorption-ionisation laser assistée par matrice (MALDI). Elle permet d étudier les interactions d un faisceau de photons irradiant dans l ultraviolet grâce à un nébullisat, à pression atmosphérique, contenant un mélange de molécules. Elle génère de nombreuses fragmentations et permet d obtenir d emblée sans expérience MS/MS supplémentaire des fragments non observables avec les autres techniques de fragmentation en source. Le but de ce travail a été d étendre le champ d application de l APPI à des biomolécules plus ou moins polaires et d approfondir l élucidation des voies de fragmentations par la compréhension des mécanismes réactionnels mis en jeu. Les expériences faites à l aide de la lampe au krypton ont permis d obtenir des spectres riches de fragments divers voire même exotiques et caractéristiques d une longueur d onde fixée à 10,0eV et minoritairement à 10,6 eV. L utilisation du rayonnement synchrotron a donné l avantage d ajouter une dimension supplémentaire à ces spectres APPI-MS qui est la variation de longueur d onde (4-20 eV ou 300-60 nm). Ce nouveau paramètre apporte des informations complémentaires grâce à l étude de l évolution des réactions mises en jeu selon les longueurs d ondes choisies. L étude des mécanismes APPI a donc mené à la mise en évidence de réactions mettant en jeu des électrons ou menant à des ions fragments radicalaires provenant de réactions jamais observées auparavant avec les sources d ions connues. L utilisation combinée de la source APPI et du rayonnement synchrotron est un outil très efficace pour la caractérisation de nouvelles molécules grâce à cette grande variation de longueur d ondes possible apportant même des informations supplémentaires à celles obtenues avec la lampe au krypton à même longueur d onde.Atmospheric Pressure Photionisation (APPI) allows for the analysis of hydrophobic biomolecules which are unobservable with the common ionization techniques as electrospray ionization (ESI) or the matrix assisted laser desorption ionization (MALDI). This allows for the study of the interactions between a photon beam irradiating in the VUV thanks to a nebulisate and a mixture of molecules at atmospheric pressure. It generates numerous fragment ions, many of which are unobservable with the other in-source fragmentation techniques, and immediately provides structural information with no supplementary MS/MS experiment. The goal of this work was to spread the application of APPI to more or even less polar biomolecules and to elucidate their fragmentation pathways through a deepened understanding of reaction mechanisms involved. The experiments utilized a krypton lamp which provided rich mass spectra of various and even exotic fragment ions and characteristics of a wavelength fixed mainly at 10.0 eV and in a smaller proportion at 10.6 eV. The use of synchrotron radiation gave the advantage of adding a supplementary dimension to these APPI-MS spectra which is the wavelength variation (4-20eV or 300-60 nm). This new parameter brings complementary information coming from the reactions never seen before with the known ion sources. The combined use of APPI source and synchrotron radiation is a very effective tool for the characterization of new molecules thanks to the large possibility of wavelength variation providing supplementary information to that obtained with the krypton lamp at the same wavelength.EVRY-Bib. électronique (912289901) / SudocSudocFranceF

Ribosomes slide on lysine-encoding homopolymeric A stretches.

Protein output from synonymous codons is thought to be equivalent if appropriate tRNAs are sufficiently abundant. Here we show that mRNAs encoding iterated lysine codons, AAA or AAG, differentially impact protein synthesis: insertion of iterated AAA codons into an ORF diminishes protein expression more than insertion of synonymous AAG codons. Kinetic studies in E. coli reveal that differential protein production results from pausing on consecutive AAA-lysines followed by ribosome sliding on homopolymeric A sequence. Translation in a cell-free expression system demonstrates that diminished output from AAA-codon-containing reporters results from premature translation termination on out of frame stop codons following ribosome sliding. In eukaryotes, these premature termination events target the mRNAs for Nonsense-Mediated-Decay (NMD). The finding that ribosomes slide on homopolymeric A sequences explains bioinformatic analyses indicating that consecutive AAA codons are under-represented in gene-coding sequences. Ribosome ‘sliding’ represents an unexpected type of ribosome movement possible during translation. DOI: http://dx.doi.org/10.7554/eLife.05534.00

Phenomenology, socio-demographic factors and outcome upon discharge of manic and mixed episodes in hospitalized adolescents

Background: The existence of bipolar disorder type I (BD-I) during adolescence is now clearly established whereas there are still some controversies on BD-II and BD-NOS diagnosis, mainly in Europe (O'Dowd in Br Med J 29, 2006). Little is known on the phenomenology and potential short-term prognosis factors of bipolar episodes in this age population. In particular, very few studies examine this issue on inpatients in the European context of free access to care. Objective: To describe the phenomenology of acute manic and mixed episodes in hospitalized adolescents and to analyse potential predictive factors associated with clinical improvement at discharge and length of hospitalization. Methods: A total of 80 subjects, aged 12–20 years, consecutively hospitalized for a manic or mixed episode. Socio-demographic and clinical data were extracted by reviewing patients' charts. We used a multivariate analysis to evaluate short-term outcome predictors. Results: The sample was characterized by severe impairment, high rates of psychotic features (N = 50, 62.5%), a long duration of stay (mean 80.4 days), and an overall good improvement (86% very much or much improved). Thirty-three (41.3 %) patients had a history of depressive episodes, 13 (16.3%) had manic or brief psychotic episodes but only 3 (3.7%) had a history of attention deficit/ hyperactivity disorders. More manic episodes than mixed episodes were identified in subjects with mental retardation (MR) and in subjects from migrant and/or low socio-economic families. Overall severity and female gender predicted better improvement in GAF scores. Poor insight and the existence of psychotic features predicted longer duration of stay. Conclusion: These results suggest that severe manic and mixed episodes in adolescents with BD-I need prolonged inpatient care to improve and that socio-cultural factors and MR should be examined more closely in youth with BD

Positive youth development in swimming: clarification and consensus of key psychosocial assets

The purpose of this study was to gain a more cohesive understanding of the assets considered necessary to develop in young swimmers to ensure both individual and sport specific development. This two stage study involved (a) a content analysis of key papers to develop a list of both psychosocial skills for performance enhancement and assets associated with positive youth development, and (b) in-depth interviews involving ten expert swim coaches, practitioners and youth sport scholars. Five higher order categories containing seventeen individual assets emerged. These results are discussed in relation to both existing models of positive youth development and implications for coaches, practitioners and parents when considering the psychosocial development of young British swimmers

Reconstructing grassland fire history using sedimentary charcoal: Considering count, size and shape

Citation: Leys, B. A., Commerford, J. L., & McLauchlan, K. K. (2017). Reconstructing grassland fire history using sedimentary charcoal: Considering count, size and shape. Plos One, 12(4), 15. doi:10.1371/journal.pone.0176445Fire is a key Earth system process, with 80% of annual fire activity taking place in grassland areas. However, past fire regimes in grassland systems have been difficult to quantify due to challenges in interpreting the charcoal signal in depositional environments. To improve reconstructions of grassland fire regimes, it is essential to assess two key traits: (1) charcoal count, and (2) charcoal shape. In this study, we quantified the number of charcoal pieces in 51 sediment samples of ponds in the Great Plains and tested its relevance as a proxy for the fire regime by examining 13 potential factors influencing charcoal count, including various fire regime components (e.g. the fire frequency, the area burned, and the fire season), vegetation cover and pollen assemblages, and climate variables. We also quantified the width to length (W: L) ratio of charcoal particles, to assess its utility as a proxy of fuel types in grassland environments by direct comparison with vegetation cover and pollen assemblages. Our first conclusion is that charcoal particles produced by grassland fires are smaller than those produced by forest fires. Thus, a mesh size of 120 mu m as used in forested environments is too large for grassland ecosystems. We recommend counting all charcoal particles over 60 mu m in grasslands and mixed grass-forest environments to increase the number of samples with useful data. Second, a W: L ratio of 0.5 or smaller appears to be an indicator for fuel types, when vegetation surrounding the site is before composed of at least 40% grassland vegetation. Third, the area burned within 1060m of the depositional environments explained both the count and the area of charcoal particles. Therefore, changes in charcoal count or charcoal area through time indicate a change in area burned. The fire regimes of grassland systems, including both human and climatic influences on fire behavior, can be characterized by long-term charcoal records

Expanding the clinical spectrum of hereditary fibrosing poikiloderma with tendon contractures, myopathy and pulmonary fibrosis due to <i>FAM111B </i>mutations

BACKGROUND: Hereditary Fibrosing Poikiloderma (HFP) with tendon contractures, myopathy and pulmonary fibrosis (POIKTMP [MIM 615704]) is a very recently described entity of syndromic inherited poikiloderma. Previously by using whole exome sequencing in five families, we identified the causative gene, FAM111B (NM_198947.3), the function of which is still unknown. Our objective in this study was to better define the specific features of POIKTMP through a larger series of patients. METHODS: Clinical and molecular data of two families and eight independent sporadic cases, including six new cases, were collected. RESULTS: Key features consist of: (i) early-onset poikiloderma, hypotrichosis and hypohidrosis; (ii) multiple contractures, in particular triceps surae muscle contractures; (iii) diffuse progressive muscular weakness; (iv) pulmonary fibrosis in adulthood and (v) other features including exocrine pancreatic insufficiency, liver impairment and growth retardation. Muscle magnetic resonance imaging was informative and showed muscle atrophy and fatty infiltration. Histological examination of skeletal muscle revealed extensive fibroadipose tissue infiltration. Microscopy of the skin showed a scleroderma-like aspect with fibrosis and alterations of the elastic network. FAM111B gene analysis identified five different missense variants (two recurrent mutations were found respectively in three and four independent families). All the mutations were predicted to localize in the trypsin-like cysteine/serine peptidase domain of the protein. We suggest gain-of-function or dominant-negative mutations resulting in FAM111B enzymatic activity changes. CONCLUSIONS: HFP with tendon contractures, myopathy and pulmonary fibrosis, is a multisystemic disorder due to autosomal dominant FAM111B mutations. Future functional studies will help in understanding the specific pathological process of this fibrosing disorder

Recognition of aminoacyl-tRNA: a common molecular mechanism revealed by cryo-EM

The accuracy of ribosomal translation is achieved by an initial selection and a proofreading step, mediated by EF-Tu, which forms a ternary complex with aminoacyl(aa)-tRNA. To study the binding modes of different aa-tRNAs, we compared cryo-EM maps of the kirromycin-stalled ribosome bound with ternary complexes containing Phe-tRNAPhe, Trp-tRNATrp, or Leu-tRNALeuI. The three maps suggest a common binding manner of cognate aa-tRNAs in their specific binding with both the ribosome and EF-Tu. All three aa-tRNAs have the same ‘loaded spring' conformation with a kink and twist between the D-stem and anticodon stem. The three complexes are similarly integrated in an interaction network, extending from the anticodon loop through h44 and protein S12 to the EF-Tu-binding CCA end of aa-tRNA, proposed to signal cognate codon–anticodon interaction to the GTPase centre and tune the accuracy of aa-tRNA selection

Les troubles bipolaires de l'adolescent (spécificités et devenir)

Pendant longtemps, on a pensé que la psychose maniaco-dépressive ne pouvait éclore qu'à l'âge adulte. Il y a une vingtaine d'années pourtant, il a été mis en évidence qu'environ un tiers des adultes maniaco-dépressifs avaient un début étonnamment précoce de leur trouble, pour la plupart à l'adolescence, pour certains dans l'enfance. Depuis lors, l'intérêt des chercheurs cliniciens pour ce que nous appelons aujourd'hui les troubles bipolaires (TB) pédiatriques n'a cessé de croître. Aujourd'hui, la notion de bipolarité chez l'enfant prépubère reste controversée tandis qu'il est admis qu'un trouble bipolaire peut débuter à l'adolescence. Les TB débutant à l'adolescence présentent néanmoins des spécificités qui les distinguent des TB classiques de l'adulte. Particularités cliniques surtout, éclairées par les aspects psychodynamiques propres à l'adolescence, mais aussi thérapeutiques. Pour certains, les TB de l'adolescent pourraient même constituer un sous-type particulier de TB sous-tendu par des bases génétiques différentes. Pour le moment, les données dans ce domaine sont plus que préliminaires. Nous ne savons également que très peu de choses sur l'évolution à l'âge adulte des ces adolescents, sujets en construction, dont l'existence est bouleversée, plus ou moins brutalement, par l'éclosion de la maladie. Préciser nos connaissances en termes de stabilité diagnostique, de profil évolutif et de facteurs pronostics de TB de l'adolescent permettrait non seulement de mieux comprendre les mécanismes étiopathogéniques enjeu dans ces troubles mais aussi d'en améliorer la prise en charge.ROUEN-BU Médecine-Pharmacie (765402102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Qui sont les preneuses de risque ? L’intention d’adopter des conduites à risque chez les étudiantes postsecondaires québécoises

Cet article présente les résultats d’une étude exploratoire qui visait à étudier la propension à la prise de risque d’un échantillon d’étudiantes québécoises de niveau postsecondaire âgées entre 18 et 30 ans et à comparer cette propension en fonction de variables sociodémographiques (âge, statut civil, milieu de vie, niveau de scolarité). L’échantillon était composé de 233 étudiantes recrutées dans une université québécoise et dans un établissement de niveau collégial (X = 22,14 ans, ET = 2,89). Les participantes, recrutées à l’aide d’affiches publicitaires, devaient répondre à une version électronique de l’échelle DOSPERT révisée pour adultes (Domain-Specific Risk-Taking scale for adults) en version française (Blais et Weber, 2006) qui mesure l’intention d’adopter un comportement à risque et à laquelle huit questions ont été ajoutées concernant la probabilité de prise de risque en matière de sexualité, de consommation de substances psychoactives et de conduite automobile. Les résultats indiquent que 24,9 % des étudiantes sondées estiment probable qu’elles puissent avoir un rapport sexuel avec une personne rencontrée quelques heures auparavant. De plus, 15,1 % des étudiantes estiment probable qu’elles adoptent des comportements sexualisés (se dévêtir, attitude aguichante) dans un bar ou une fête et cette propension augmente considérablement s’il y a consommation de substances psychoactives (25,4 %). La consommation volontaire d’ecstasy est d’ailleurs estimée comme probable ou très probable pour 16,3 % de l’échantillon. De façon plus générale, les résultats à l’échelle DOSPERT indiquent que la propension à la prise de risque dans les domaines sociaux, des activités récréatives et de la santé et la sécurité est en moyenne plus élevée que la propension à la prise de risque dans les domaines de l’éthique ou des finances chez les étudiantes. De plus, la tendance à la prise de risque dans certains domaines varie en fonction de l’état civil, de la parentalité, du milieu de vie, du niveau de scolarité et de la propension à la prise de risque en soi.This paper presents the results of a study aiming to explore the propensity for risk-taking among post-secondary female students aged between 18 to 30 years. The propensity result is then compared to socio-demographic variables (age, civil status, life environment, education level). The sample consisted of 233 females students enrolled at a university or college X = 22,14 years, ET = 2,89 in the province of Quebec. Participants were recruited using billboards. They had to respond to a French electronic version of the DOSPERT revised scale for adults (Domain-Specific-Risk-Taking scale for adults ; Blais et Weber, 2006) assessing risk taking in five domains: health/safety, ethical, financial, social, and recreational. In addition to the questions of the DOSPERT revised scale for adults, eight supplementary questions were asked to the participants regarding the likelihood of risk-taking in terms of their sexuality, their substance use and their driving. These results revealed that a quarter of the sample of students (24.9 %) expected to voluntarily have a sexual encounter with someone they met a few hours earlier. Moreover, 15.1 % of the students would probably adopt sexual behaviors in a bar or party (such as getting undressed or adopting a teasing attitude) and the possibility increases to 25.4 % when the combination of substance use is added. Finally, 16.3 % of the participants indicated that they would voluntarily consume ecstasy. In general, results from the DSPERT scales indicated a higher propensity for risk-taking in regards to the health/safety, social and recreational domains rather than the ethical and financial domains among these students. Furthermore, risk taking propensity in specific domains varies according to civil status, parenthood, life environment, education level and risk taking per se.Este artículo presenta los resultados de un estudio exploratorio que tiene como objetivo estudiar la propensión a la toma de riesgos en una muestra de estudiantes quebequenses de nivel pos-secundario entre 18 y 30 años y comparar esta propensión en función de variables sociodemográficas (edad, estado civil, medio de vida, nivel de escolaridad). La muestra estaba compuesta por 233 estudiantes de una universidad quebequense y un establecimiento de nivel colegial (X = 22,14 ans, ET = 2,89). Las participantes, reclutadas por medio de afiches publicitarios, debían responder a una versión electrónica de la escala DOSPERT revisada para adultos (Domain-Specific Risk-Taking scale for adults) en versión francesa (Blais y Weber, 2006) que mide la intención de adoptar un comportamiento de riesgo y a la que se le agregaron ocho preguntas concernientes a la posibilidad de tomar riesgos en materia de sexualidad, de consumo de sustancias psicoactivas y de conducción de automóviles. Los resultados indican que el 24,9 % de las estudiantes encuestadas estiman probable tener una relación sexual con una persona conocida pocas horas antes. Además, el 15,1 % de las estudiantes estiman probable adoptar comportamientos sexualizados (desvestirse, actitud provocadora) en un bar o en una fiesta y que esta propensión aumenta considerablemente si hay consumo de sustancias psicoactivas (25,4 %). El consumo voluntario de éxtasis, por otra parte, es considerado probable por el 16,3 % de la muestra. De manera más general, los resultados de la escala DOSPERT indican que la propensión a la toma de riesgos en las esferas sociales, de las actividades recreativas y de la salud y seguridad es más elevada en promedio entre las estudiantes que la propensión a la toma de riesgos en los campos de la ética o de las finanzas. Además, la tendencia a la toma de riesgos en ciertos campos varía en función del estado civil, de la parentalidad, del medio de vida, del nivel de escolaridad y de la propensión a la toma de riesgos en sí misma