Caractérisation de la fonction des complexes histone déacétylases Rpd3S et Set3C

La chromatine est essentielle au maintien de l’intégrité du génome, mais, ironiquement, constitue l’obstacle principal à la transcription des gènes. Plusieurs mécanismes ont été développés par la cellule pour pallier ce problème, dont l’acétylation des histones composant les nucléosomes. Cette acétylation, catalysée par des histones acétyl transférases (HATs), permet de réduire la force de l’interaction entre les nucléosomes et l’ADN, ce qui permet à la machinerie transcriptionnelle de faire son travail. Toutefois, on ne peut laisser la chromatine dans cet état permissif sans conséquence néfaste. Les histone déacétylases (HDACs) catalysent le clivage du groupement acétyle pour permettre à la chromatine de retrouver une conformation compacte. Cette thèse se penche sur la caractérisation de la fonction et du mécanisme de recrutement des complexes HDACs Rpd3S et Set3C. Le complexe Rpd3S est recruté aux régions transcrites par une interaction avec le domaine C-terminal hyperphosphorylé de Rpb1, une sous-unité de l’ARN polymérase II. Toutefois, le facteur d’élongation DSIF joue un rôle dans la régulation de cette association en limitant le recrutement de Rpd3S aux régions transcrites. L’activité HDAC de Rpd3S, quant à elle, dépend de la méthylation du résidu H3K36 par l’histone méthyltransférase Set2. La fonction du complexe Set3C n’est pas clairement définie. Ce complexe est recruté à la plupart de ses cibles par l’interaction entre le domaine PHD de Set3 et le résidu H3K4 di- ou triméthylé. Un mécanisme indépendant de cette méthylation, possiblement le même que pour Rpd3S, régit toutefois l’association de Set3C aux régions codantes des gènes les plus transcrits. La majorité de ces résultats ont été obtenus par la technique d’immunoprécipitation de la chromatine couplée aux biopuces (ChIP-chip). Le protocole technique et le design expérimental de ce type d’expérience fera aussi l’objet d’une discussion approfondie.Chromatin is essential for the maintenance of genomic integrity but, ironically, is also the main barrier to gene transcription. Many mechanisms, such as histone acetylation, have evolved to overcome this problem. Histone acetylation, catalyzed by histone acetyltransferases (HATs), weakens the internucleosomal and nucleosome-DNA interactions, thus permitting the transcriptional machinery access to its template. However, this permissive chromatin state also allows for opportunistic DNA binding events. Histone deacetylases (HDACs) help restore a compact chromatin structure by catalyzing the removal of acetyl moieties from histones. This thesis focuses on the characterization of the function and of the recruitment mechanism of HDAC complexes Rpd3S and Set3C. The Rpd3S complex is recruited to actively transcribed coding regions through interactions with the hyperphosphorylated C-terminal domain of Rpb1, a subunit of RNA polymerase II, with the DSIF elongation factor playing a role in limiting this recruitment. However, the HDAC activity of Rpd3S depends on H3K36 methylation, which is catalyzed by the Set2 histone methyltransferase. The Set3C complex’ function is still not clearly defined. It is recruited to most of its targets through the interaction between the Set3 PHD domain and di- or trimethylated H3K4. However, Set3C recruitment to genes displaying high RNA polymerase II occupancy is independent of H3K4 methylation. The mechanism by which Set3C is recruited to this gene subset is under investigation. These results have mostly been obtained through chromatin immunoprecipitation coupled to tiling microarrays (ChIP-chip). The protocol and experimental design challenges inherent to this technique will also be discussed in depth

Gene expression comparison by microarray analysis between two Triticum aestivum cultivars that differ in freezing tolerance

Cold tolerance in plants is a complex trait that occurs in many plants during growth at low temperature, a process known as cold acclimation. This process is a multigenic system and there is broad variation in the range of freezing tolerance that can be achieved by different wheat cultivars. To identify genes that are regulated by cold treatment and to characterize their expression profiles a microarray was constructed with PCR amplified cDNA inserts from 1187 wheat Expressed Sequence Tags (ESTs) that represent 948 genes. Two Triticum aestivum L. cultivars, Norstar and Glenlea that differ in their capacity to develop freezing tolerance were used to compare the changes in gene expression during cold acclimation. Microarray analysis is a powerful and rapid approach to gene discovery and for studying global gene expression. In species in which large scale mutant screening and transgenic studies are not currently practical, genotype comparison is an especially good approach to identify candidate genes for important agronomic traits. The analysis reveals that the transcript levels of over 300 genes were altered by cold treatment. Among these, 65 genes were differently regulated in the freezing-tolerant and the less-freezing-tolerant cultivars on at least one time point. These genes encode for protein kinases, putative transcription factors, Ca 2+ binding proteins, Golgi localized protein, inorganic pyrophosphatase, cell wall associated hydrolase, 2-oxoglutarate/malate translocator, and aspartate-tRNA ligase

L’impact du suicide d’un patient chez des professionnels en santé mentale : Différences entre les femmes et les hommes

Cet article rapporte les résultats d’une recherche réalisée auprès de 141 professionnels en santé mentale pratiquant au Québec et ayant vécu le suicide d’un patient. Les professionnels ont réagi à cet événement différemment en fonction de leur sexe. Les femmes y ont répondu par un niveau de stress élevé au cours du premier mois, alors que les hommes ont dévoilé un niveau de stress faible. Le niveau élevé de stress relevé chez les femmes était accompagné de répercussions initialement plus intenses sur leur pratique professionnelle : tendance accrue à hospitaliser des patients suicidaires ou précautions accrues dans leur traitement, évaluation d’un plus grand nombre de patients comme présentant un risque de suicide, sentiment accru d’impuissance lors de l’évaluation ou du traitement de patients suicidaires, consultation plus fréquente de collègues et de superviseurs, attention accrue aux aspects légaux dans la pratique. L’article tente de mieux comprendre les différences entre les réactions des professionnels observées selon leur sexe, à la lumière des théories de la socialisation et du développement professionnel.This article presents the results of a study of 141 mental health professionals who have experienced a patient’s suicide. Results indicate that mental health professionals reacted to such suicides in different ways according to gender. Women generally responded with elevated stress levels in the first month, while men experienced stress levels that were subclinical on average. The high stress response found in women was also initially accompanied by more profound impacts on their professional practice : increased hospitalizations of suicidal patients or greater precautions in their treatment, increased evaluation of patients as being at risk for suicide, increased helplessness while assessing or treating suicidal patients, more frequent consultation of colleagues and supervisors and more attention to legal issues. Gender differences found in this study are discussed in the light of socialization and professional development theories

The Essential Role of Open Data and Software for the Future of Ultrasound-Based Neuronavigation

With the recent developments in machine learning and modern graphics processing units (GPUs), there is a marked shift in the way intra-operative ultrasound (iUS) images can be processed and presented during surgery. Real-time processing of images to highlight important anatomical structures combined with in-situ display, has the potential to greatly facilitate the acquisition and interpretation of iUS images when guiding an operation. In order to take full advantage of the recent advances in machine learning, large amounts of high-quality annotated training data are necessary to develop and validate the algorithms. To ensure efficient collection of a sufficient number of patient images and external validity of the models, training data should be collected at several centers by different neurosurgeons, and stored in a standard format directly compatible with the most commonly used machine learning toolkits and libraries. In this paper, we argue that such effort to collect and organize large-scale multi-center datasets should be based on common open source software and databases. We first describe the development of existing open-source ultrasound based neuronavigation systems and how these systems have contributed to enhanced neurosurgical guidance over the last 15 years. We review the impact of the large number of projects worldwide that have benefited from the publicly available datasets “Brain Images of Tumors for Evaluation” (BITE) and “Retrospective evaluation of Cerebral Tumors” (RESECT) that include MR and US data from brain tumor cases. We also describe the need for continuous data collection and how this effort can be organized through the use of a well-adapted and user-friendly open-source software platform that integrates both continually improved guidance and automated data collection functionalities.publishedVersio

Nouveaux copolymères de furo-et sélénophéno(3,4-c)pyrrole-4,6-dione pour l'électronique organique

Depuis maintenant quelques années, les polymères conjugués ont suscité l’intérêt de la communauté scientifique en vertu de leurs propriétés semi-conductrices intéressantes. Récemment, les copolymères de thiéno[3,4-c]pyrrole-4,6-dione (TPD) ont démontré des propriétés optiques et électroniques surprenantes. Ainsi, une partie de cette recherche traite de l’amélioration de ces copolymères par la substitution de l’atome de soufre du TPD par un atome d’oxygène ou de sélénium. Ce mémoire est divisé en cinq chapitres. Le premier offre une introduction générale du champ de recherche présentant les enjeux et mettant en contexte les objectifs principaux du projet. Les deuxième et troisième chapitres présentent quant à eux la synthèse des comonomères et copolymères modifiés relativement au TPD tandis que la caractérisation des copolymères est abordée au chapitre quatre. Finalement, un retour sur les travaux ainsi que les perspectives de ce projet se retrouvent au chapitre cinq

Relative efficacy of cognitive-behavioral therapy administered by videoconference for posttraumatic stress disorder : a six-month follow-up

Until recently, only one study was published on cognitive-behavioral therapy (CBT) of posttraumatic stress disorder (PTSD) in individual therapy via videoconference (Germain, Marchand, Bouchard, Drouin, & Guay, 2009); however, it only assessed the posttreatment effect. This study presents the follow-up of Germain et al.’s (2009) study. The main goal was to compare the effectiveness after six months of CBT for PTSD either face-to-face (n = 24) or by videoconference (n = 12). Each participant received CBT for 16 to 25 weeks and completed various questionnaires before and after treatment and at a six-month follow-up. The two treatments had equivalent levels of symptom reduction (Modified PTSD Symptom Scale: η2 .05) and proportion of patients with a clinically significant change in symptoms (42% for face-to-face vs. 38% for videoconferencing, p > .05). Thus, CBT for PTSD via videoconference seems to be a viable alternative when adequate face-to-face treatments are less available

Could we use parent report as a valid proxy of child report on anxiety, depression, and distress? : a systematic investigation of father–mother–child triads in children successfully treated for leukemia

Background Systematic assessment of emotional distress is recommended in after care. Yet, it is unclear if parent report may be used as a proxy of child report. The aim of this study was to assess agreements and differences and explore possible moderators of disagreement between child and parent ratings. Methods Sixty‐two young survivors treated for acute lymphoblastic leukemia (9–18 years) and both parents responded to the Beck Youth Inventory (anxiety and depression) and the distress rating scale on the child's status. Parents completed the Brief Symptom Inventory‐18 on their own psychological status. Systematic analyses of agreement and differences were performed. Results Mother–child and father–child agreements were fair on anxiety, depression, and distress (median intraclass correlation coefficient = 0.37). Differences between parents and children were medium sized (median d = 0.55) with parents giving higher scores than their children on anxiety, depression, and distress. Mothers reported distress more frequently than fathers (39 vs. 17%) when children reported none. The child being female and lower parental income were associated with lower agreement in fathers when rating child distress. Higher levels of parental psychological symptoms were consistently associated with lower agreement. Conclusions Parent–child differences when rating adolescent survivors’ difficulties may be more important than previously thought. Parent report probably cannot be considered as a valid proxy of older child report on such internalized domains as anxiety, depression, or distress in the after‐care clinic. Parents’ report is also likely to be influenced by their own mood, a factor that should be corrected for when using their report

Screening for distress in pediatric cancer survivors : a systematic comparison of one-step and two-step strategies to minimize detection errors

Background:Childhood cancer survivors should be routinelyscreened for psychological distress. However, existing screeningtools promoted by cancer care institutions, such as the DistressThermometer (DT) generate high rates of errors. The aim of thisstudy is to help refining strategies of screening psychologicaldistress in this population by exploring two-step methods com-bining the DT on step #1 with one question on step #2.Procedure:Data from 255 survivors of childhood acutelymphoblastic leukemia aged 13–40years were analyzed (38%13–18 years, 62% 19þyears, 53% females). We used the DTon step #1 and the individual emotion items from thePediatric Quality of Life Questionnaire (PedsQL) on step #2, todetect distress, depression and anxiety as measured by stand-ard instruments. We compared sensitivity, specificity, negativeand positive predictive values, Youden index, and clinical util-ity indices, in newly developed two-step strategies.Results:The best two-step strategies to screen anxious-depressive distress were DT 2 on step #1, with the item ofSadness on step #2, and DT 2 combined with the item ofConcerns. Two-step strategies outperformed the DT alone onthe correct identification of distressed survivors. However,two-step strategies did not outperform the DT used alone onthe correct detection of no distressed survivors. Results weresimilar when predicting depression or anxiety alone.Conclusion:Completing the DT with one single question onemotions from the PedsQL may minimize the number of par-ticipants falsely identified as distressed, which could be par-ticularly pertinent in resource-limited clinics

A fabrication process for emerging nanoelectronic devices based on oxide tunnel junctions

Abstract : We present a versatile nanodamascene process for the realization of low-power nanoelectronic devices with different oxide junctions. With this process we have fabricated metal/insulator/metal junctions, metallic single electron transistors, silicon tunnel field effect transistors, and planar resistive memories. These devices do exploit one or two nanometric-scale tunnel oxide junctions based on TiO2, SiO2, HfO2, Al2O3, or a combination of those. Because the nanodamascene technology involves processing temperatures lower than 300°C, this technology is fully compatible with CMOS back-end-of-line and is used for monolithic 3D integration