2,022 research outputs found

    Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes

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    Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.Comment: Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.000035

    Anxiety and self-esteem as mediators of the relation between family communication and indecisiveness in adolescence

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    Abstract In this study, we explored the unique and common contributions of anxiety, self-esteem, and family communication on indecisiveness among adolescents. Three hundred and fifty pupils from 13 to 16 years of age completed selfreport measures on indecisiveness, quality of family communication, trait anxiety, and self-esteem. The findings in this study showed that students\u2019 indecisiveness is predicted by family communication mediated by anxiety and self-esteem. These results have important implications for practice as it stresses the importance of anxiety and self-esteem. Nevertheless, the counselors could also focus on enhancing relationship-building skills by introducing the adolescents\u2019 career formation as an adolescent\u2013parent joint project.L\u2019anxie\ub4te\ub4 et l\u2019estime de soi comme me\ub4diateurs de la relation entre communication au sein de la famille et indecision chronique a` l\u2019adolescence. Dans cette e\ub4tude, nous avons explore\ub4 les contributions uniques et communes de l\u2019anxiete\ub4, de l\u2019estime de soi et de la communication au sein de la famille sur l\u2019indecision chronique aupres d\u2019adolescents. Trois cent cinquante e\ub4le`ves a\u2c6ge\ub4s de 13 a` 16 ans ont rempli des mesures d\u2019auto-e\ub4valuation de l\u2019inde\ub4cision chronique, de la qualite\ub4 de la communication familiale, de l\u2019anxie\ub4te\ub4-trait et de l\u2019estime de soi. Les re\ub4sultats de cette e\ub4tude ont montre\ub4 que l\u2019inde\ub4cision des e\ub4tudiants est explique\ub4e par la communication au sein de la famille et que ce lien est me\ub4diatise\ub4 par l\u2019anxie\ub4te\ub4 et l\u2019estime de soi. Ces re\ub4sultats ont des implications importantes pour la pratique car ils soulignent l\u2019importance de l\u2019anxie\ub4te\ub4 et l\u2019estime de soi. Ne\ub4anmoins, les conseillers pourraient e\ub4galement se concentrer sur l\u2019ame\ub4lioration des compe\ub4tences de construction relationnelle en introduisant la formation professionnelle des adolescents comme un projet conjoint adolescent-parent.Resumen. Ansiedad y Autoestima como Mediadores de la Relacio\ub4n entre Comunicacio\ub4n Familiar e Indecisio\ub4n en la Adolescencia. En este estudio, exploramos las contribuciones u\ub4nicas y comunes de la ansiedad, la autoestima y la comunicacio\ub4n de familia en la indecisio\ub4n de los adolescentes. Tres y cientos cincuenta alumnos entre los 13 y 16 an\u2dcos completaron auto-evaluaciones sobre la indecisio\ub4n, la calidad de comunicacio\ub4n familiar, los rasgos de ansiedad y la autoestima. Los resultados en este estudio muestran que la indecisio\ub4n en los estudiantes es prevista por la comunicacio\ub4n familiar mediada por la ansiedad y la autoestima. Estos resultados tiene importantes implicaciones para la practica ya que destacan la importancia de la ansiedad y la autoestima. Sin embargo, los consejeros podr\u131\ub4an tambie\ub4n focalizarse en el aumento de sus habilidades para construir relaciones mediante la introduccio\ub4n de la formacio\ub4n profesional para adolescentes como un proyecto conjunto del adolescente-padre.Angst und Selbstwertgefu\ua8 hl als Mediatoren der Beziehung zwischen Kommunikation in der Familie und Unentschlossenheit in der Adoleszenz. In dieser Studie untersuchten wir die spezifischen und gemeinsamen Beitra\ua8ge von Angst, Selbstwertgefu\ua8hl und Kommunikation in der Familie auf Unentschlossenheit unter Jugendlichen. Dreihundertfu\ua8nfzig Schu\ua8ler, zwischen 13 bis 16 Jahre alt, fu\ua8llten Skalen zur Unentschlossenheit, Qualita\ua8t der Kommunikation in der Familie, A\ua8 ngstlichkeit und Selbstwertgefu\ua8hl aus. Die Ergebnisse dieser Studie zeigten, dass Unentschlossenheit der Schu\ua8ler von Kommunikation in der Familie vorhergesagt wird, vermittelt durch Angst und Selbstwertgefu\ua8 hl. Diese Ergebnisse haben wichtige Implikationen fu\ua8r die Praxis, da sie die Bedeutung von Angst und Selbstwertgefu\ua8hl hervorheben. Dennoch ko\ua8nnten sich die Beratungspersonen durch die Einfu\ua8hrung der beruflichen Bildung der Jugendlichen als ein gemeinsames Projekt von Jugendliche-Elternteil auch auf die Verbesserung der Fa\ua8higkeiten zum Aufbau von Beziehungen konzentrieren

    The pseudogap: friend or foe of high Tc?

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    Although nineteen years have passed since the discovery of high temperature superconductivity, there is still no consensus on its physical origin. This is in large part because of a lack of understanding of the state of matter out of which the superconductivity arises. In optimally and underdoped materials, this state exhibits a pseudogap at temperatures large compared to the superconducting transition temperature. Although discovered only three years after the pioneering work of Bednorz and Muller, the physical origin of this pseudogap behavior and whether it constitutes a distinct phase of matter is still shrouded in mystery. In the summer of 2004, a band of physicists gathered for five weeks at the Aspen Center for Physics to discuss the pseudogap. In this perspective, we would like to summarize some of the results presented there and discuss its importance in the context of strongly correlated electron systems.Comment: expanded version, 20 pages, 11 figures, to be published, Advances in Physic

    Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

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    Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

    Incorporating medical interventions into carrier probability estimation for genetic counseling

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    BACKGROUND: Mendelian models for predicting who may carry an inherited deleterious mutation of known disease genes based on family history are used in a variety of clinical and research activities. People presenting for genetic counseling are increasingly reporting risk-reducing medical interventions in their family histories because, recently, a slew of prophylactic interventions have become available for certain diseases. For example, oophorectomy reduces risk of breast and ovarian cancers, and is now increasingly being offered to women with family histories of breast and ovarian cancer. Mendelian models should account for medical interventions because interventions modify mutation penetrances and thus affect the carrier probability estimate. METHODS: We extend Mendelian models to account for medical interventions by accounting for post-intervention disease history through an extra factor that can be estimated from published studies of the effects of interventions. We apply our methods to incorporate oophorectomy into the BRCAPRO model, which predicts a woman's risk of carrying mutations in BRCA1 and BRCA2 based on her family history of breast and ovarian cancer. This new BRCAPRO is available for clinical use. RESULTS: We show that accounting for interventions undergone by family members can seriously affect the mutation carrier probability estimate, especially if the family member has lived many years post-intervention. We show that interventions have more impact on the carrier probability as the benefits of intervention differ more between carriers and non-carriers. CONCLUSION: These findings imply that carrier probability estimates that do not account for medical interventions may be seriously misleading and could affect a clinician's recommendation about offering genetic testing. The BayesMendel software, which allows one to implement any Mendelian carrier probability model, has been extended to allow medical interventions, so future Mendelian models can easily account for interventions
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