A heterozygous variant in the human cardiac miR-133 gene, MIR133A2, alters miRNA duplex processing and strand abundance

BACKGROUND MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Sequential cleavage of miRNA precursors results in a ~22 nucleotide duplex of which one strand, the mature miRNA, is typically loaded into the RNA-induced silencing complex (RISC) while the passenger strand is degraded. Very little is known about how genetic variation might affect miRNA biogenesis and function. RESULTS We re-sequenced the MIR1-1, MIR1-2, MIR133A1, MIR133A2, and MIR133B genes, that encode the cardiac-enriched miRNAs, miR-1 and miR-133, in 120 individuals with familial atrial fibrillation and identified 10 variants, including a novel 79T > C MIR133A2 substitution. This variant lies within the duplex at the 3' end of the mature strand, miR-133a-3p, and is predicted to prevent base-pairing and weaken thermostability at this site, favoring incorporation of the passenger strand, miR-133a-5p, into RISC. Genomic DNA fragments containing miR-133a-2 precursor sequences with 79T and 79C alleles were transfected into HeLa cells. On Northern blotting the 79T allele showed strong expression of miR-133a-3p with weak expression of miR-133a-5p. In contrast, the 79C allele had no effect on miR-133a-3p but there was a significant increase (mean 3.6-fold) in miR-133a-5p levels. Deep sequencing of small RNA libraries prepared from normal human and murine atria confirmed that nearly all the mature miR-133a was comprised of miR-133a-3p and that levels of miR-133a-5p were very low. A number of isomiRs with variations at 5' and 3' ends were identified for both miR-133a-3p and miR-133a-5p, with 2 predominant miR-133a-3p isomiRs and one predominant miR-133a-5p isomiR. Bioinformatics analyses indicate that the major miR-133a-3p and 5p isomiRs have numerous predicted target mRNAs, only a few of which are in common. CONCLUSIONS Multiple miR-133a isomiRs with potential different mRNA target profiles are present in the atrium in humans and mice. We identified a human 79T > C MIR133A2 variant that alters miRNA processing and results in accumulation of the miR-133a-5p strand that is usually degraded

Hacia nuevos dispositivos de investigación y educación en Francia: el ejemplo de la Universidad de Toulouse

La comprensió de l'estat actual de la investigació en arts, lletres, filosofia o llengües es basa en:- un fet: els investigadors, els seus col·lectius i les institucions de recerca, ja siguin públiques o privades, sempre estan finançades per la societat en què estan immerses.- una hipòtesi: aquest finançament comporta una contrapartida, ja que els resultats de la recerca han de ser útils per a la societat i utilitzables per ella.- una constatació: a les esmentades disciplines, les relacions de producció que regeixen les institucions de recerca, determinen les forces productives (professors i investigadors) i conformen les produccions (els programes de recerca i els discursos científics), no semblen satisfer les exigències de aquesta contrapartida.The understanding of the current state of research in arts, humanities, philosophy or languages is based on:- a fact: researchers, their groups and research institutions, whether public or private, are always financed by the society in which they are immersed.- a hypothesis: this financing entails a counterpart, since the results of the research must be useful for society and usable by it.- a finding: in the aforementioned disciplines, the production relations that govern the research institutions, determine the productive forces (professors and researchers) and make up the productions (research programs and scientific discourses), do not seem to satisfy the demands of that counterpart.La comprensión del estado actual de la investigación en artes, letras, filosofía o lenguas se basa en: - un hecho: los investigadores, sus colectivos y las instituciones de investigación, ya sean públicas o privadas, siempre están financiadas por la sociedad en la que están inmersas.- una hipótesis: esa financiación conlleva una contrapartida, pues los resultados de la investigación deben ser útiles para la sociedad y utilizables por ella.- una constatación: en las mencionadas disciplinas, las relaciones de producción que rigen las instituciones de investigación, determinan las fuerzas productivas (profesores e investigadores) y conforman las producciones (los programas de investigación y los discursos científicos), no parecen satisfacer las exigencias de esa contrapartida

Depressive rumination and experiential avoidance: A task based exploration

© 2014 John Wiley & Sons, Ltd. Depressive rumination has been conceptualized as being closely connected with experiential avoidance. Evidence supporting this hypothesis derives primarily from studies using self-report measures. The present study explores this idea using a task-based assessment of avoidance. College students (N=100) rated their emotional responses to 60 computer-presented images (positive, negative and neutral). Response times for the image-rating task were surreptitiously recorded, along with Ruminative Response Scale and Beck Depression Inventory II scores. Rumination was correlated with faster response times for negative, but not positive or neutral images. These findings are interpreted as lending support to the experiential avoidance conceptualization of rumination; however, consideration is also given to a potentially synergistic interpretation implicating heightened threat monitoring

Academic integrity and oral examination: an Arabian Gulf perspective

Academic dishonesty is a major challenge facing educational institutions worldwide. Within the context of undergraduate education in the Arabian Gulf, oral assessment can help validate the originality of student work, whilst simultaneously facilitating assessment in a mode highly resonant with the region\u27s own educational traditions and collectivist cultural norms. The present study aims to examine student perceptions of a group-based oral examination. This was introduced as an alternative to written examinations, and as an adjunctive assessment of a course essay. Three undergraduate sections (N = 75) of an introductory psychology course at Zayed University in the United Arab Emirates sat the oral examination. Participants were later surveyed about their experience immediately after the exam (prior to knowing their grade). The dominant themes to emerge from the analysis were relief, satisfaction with the process and ecological relevance. Another theme was a perception of fairness and promotion of academic integrity. The group oral exam appears to provide a well-tolerated, culturally resonant means of assessment, which also promotes academic integrity within the present Arabian Gulf context. © 2013 Taylor & Francis

Minimum fuel round trip from a L2L_2 Earth-Moon Halo orbit to Asteroid 2006 RH120_{120}

International audienceThe goal of this paper is to design a spacecraft round trip transfer from a parking orbit to Asteroid 2006\;RH$_{120}$, during its capture time by Earth's gravity, while maximizing the final mass or equivalently minimizing the delta-v. The parking orbit is chosen as a Halo orbit around the Earth-Moon $L_2$ libration point. The round-trip transfer is composed of three portions: a rendezvous transfer departing from the parking orbit to reach 2006\;RH$_{120}$, a lock-in portion with the spacecraft following the asteroid orbit, and finally a return transfer to $L_2$. An indirect method based on the maximum principle is used for our numerical calculations. To partially address the issue of local minima, we restrict the control strategy to reflect an actuation corresponding to up to three constant thrust arcs during each portion of the transfer. The model considered here is the circular restricted four-body problem (CR4BP) with the Sun considered as a perturbation of the Earth-Moon circular restricted three body problem. A shooting method is applied to solve numerically this problem, and the rendezvous point to and departure point from \RH\ are optimized using a time discretization of the trajectory of \RH

Le théâtre quantique : ordre et désordre dans l’Espagne postmoderne

Cet article expose les premières pistes d’une réflexion sur la dramaturgie espagnole récente à partir de la notion de « quantique ». L’hypothèse de départ est la suivante : la physique quantique aurait joué un rôle fondamental dans le « désordre » de la postmodernité et aurait servi de terreau fertile à l’élaboration des grandes théories (philosophiques, historiques, sociologiques, esthétiques et dramaturgiques) du siècle dernier et du XXIe siècle. La physique quantique, en remettant en cause les principes de la physique classique, l’électromagnétisme de James Clerk Maxwell et la mécanique newtonienne principalement, oppose le discontinu au continu, le hasard à la causalité, l’interdépendance des atomes à la séparabilité et à l’objectivité. Dans le domaine des arts, l’association des oeuvres à l’esthétique quantique semble un phénomène surtout espagnol. Non seulement l’adjectif « quantique » réapparaît comme épithète pour désigner des formes artistiques diverses, mais le quantique, comme esthétique et comme éthique, devient le fer de lance d’une association internationale créée à Grenade en 1994 et connue sous le nom de Salon des Indépendants. Un des cofondateurs, Gregorio Morales, journaliste et écrivain, a publié en 1998 un essai intitulé Le cadavre de Balzac : une vision quantique de la littérature et de l’art, qui synthétise les débats qui ont eu lieu à Valence, au cours des différentes rencontres entre les membres fondateurs. Y sont réunis des articles théoriques qui étudient les différentes applications du quantique au cinéma, à la poésie, au roman, à partir d’exemples tirés des oeuvres d’Henry James, d’Antonio Enrique et de Rubén Darío. Les auteurs de cet article analysent les formes dramaturgiques contemporaines à partir de certains concepts propres à la physique quantique et particulièrement adaptés à l’étude de l’évolution du théâtre (sans pour autant, bien sûr, qu’ils soient exclusifs à l’étude du genre dramatique) : le vide quantique rempli d’énergie potentielle, la modification de l’objet observé par l’observateur, la mise en scène de l’espace-temps quantique. Le corpus de pièces quantiques sera principalement composé d’oeuvres tirées de la collection « Nouvelles scènes hispaniques », élément clef du chaînage toulousain autour du théâtre espagnol contemporain.This paper explores the first step of a research about Spanish contemporary theatre from the concept of quantum theory. The starting point of view is the following: quantum theory in physics shoud have played a very important place in postmodernity and should have influenced most of the major theories of the last century. In the field of Arts, the mark of quantum aesthetics seems to be Spanish, as expressed in the creation of a quantum society in Grenade in 1994, led by Gregorio Morales, author of a book named The Balzac's corpse: a quantum vision of literature and art. The authors of this article studies several contemporary plays using three concepts of quantum physics that are particularly helpful to analyse the evolution of theater: the quantum hole full of energy, the modification of the object seen by the observer, the staging of the quantum space and time. The choice of plays is from the collection of Spanish theater "Nouvelles scènes hispaniques", published by the University of Toulouse

Spectral asymptotics of the Dirichlet Laplacian in a conical layer

The spectrum of the Dirichlet Laplacian on conical layers is analysed through two aspects: the infiniteness of the discrete eigenvalues and their expansions in the small aperture limit. On the one hand, we prove that, for any aperture, the eigenvalues accumulate below the thresh-old of the essential spectrum: For a small distance from the essential spectrum, the number of eigenvalues farther from the threshold than this distance behaves like the logarithm of the distance. On the other hand, in the small aperture regime, we provide a two-term asymptotics of the first eigenvalues thanks to a priori localization estimates for the associated eigenfunctions. We prove that these eigenfunctions are localized in the conical cap at a scale of order the cubic root of the aperture angle and that they get into the other part of the layer at a scale involving the logarithm of the aperture angle