DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein oligomers

Protein self-organization is essential for the establishment and maintenance of nuclear architecture and for the regulation of gene expression. We have shown previously that the Proline-Rich Homeodomain protein (PRH/Hex) self-assembles to form oligomeric complexes that bind to arrays of PRH binding sites with high affinity and specificity. We have also shown that many PRH target genes contain suitably spaced arrays of PRH sites that allow this protein to bind and regulate transcription. Here, we use analytical ultracentrifugation and electron microscopy to further characterize PRH oligomers. We use the same techniques to show that PRH oligomers bound to long DNA fragments self-associate to form highly ordered assemblies. Electron microscopy and linear dichroism reveal that PRH oligomers can form protein–DNA fibres and that PRH is able to compact DNA in the absence of other proteins. Finally, we show that DNA compaction is not sufficient for the repression of PRH target genes in cells. We conclude that DNA compaction is a consequence of the binding of large PRH oligomers to arrays of binding sites and that PRH is functionally and structurally related to the Lrp/AsnC family of proteins from bacteria and archaea, a group of proteins formerly thought to be without eukaryotic equivalents

Adolescent self-control predicts midlife hallucinatory experiences:40-year follow-up of a national birth cohort

Associations between self-control in adolescence and adult mental health are unclear in the general population; to our knowledge, no study has investigated self-control in relation to psychotic-like symptoms

DNA compaction by the higher-order assembly of PRH/Hex homeodomain protein oligomers

Protein self-organization is essential for the establishment and maintenance of nuclear architecture and for the regulation of gene expression. We have shown previously that the Proline-Rich Homeodomain protein (PRH/Hex) self-assembles to form oligomeric complexes that bind to arrays of PRH binding sites with high affinity and specificity. We have also shown that many PRH target genes contain suitably spaced arrays of PRH sites that allow this protein to bind and regulate transcription. Here, we use analytical ultracentrifugation and electron microscopy to further characterize PRH oligomers. We use the same techniques to show that PRH oligomers bound to long DNA fragments self-associate to form highly ordered assemblies. Electron microscopy and linear dichroism reveal that PRH oligomers can form protein–DNA fibres and that PRH is able to compact DNA in the absence of other proteins. Finally, we show that DNA compaction is not sufficient for the repression of PRH target genes in cells. We conclude that DNA compaction is a consequence of the binding of large PRH oligomers to arrays of binding sites and that PRH is functionally and structurally related to the Lrp/AsnC family of proteins from bacteria and archaea, a group of proteins formerly thought to be without eukaryotic equivalents

Different Attentional Patterns for Regret and Disappointment: An Eye-tracking Study.

The unfavorable comparison between the obtained and expected outcomes of our choices may elicit disappointment. When the comparison is made with the outcome of alternative actions, emotions like regret can serve as a learning signal. Previous work showed that both anticipated disappointment and regret influence decisions. In addition, experienced regret is associated with higher emotional responses than disappointment. Yet it is not clear whether this amplification is due to additive effects of disappointment and regret when the outcomes of alternative actions are available, or whether it reflects the learning feature of regret signals. In this perspective, we used eye-tracking to measure the visual pattern of information acquisition in a probabilistic lottery task. In the partial feedback condition, only the outcome of the chosen lottery was revealed, while in the complete feedback condition, participants could compare their outcome with that of the non-chosen lottery, giving them the opportunity to experience regret. During the decision phase, visual patterns of information acquisition were consistent with the assessment of anticipated regret, in addition to a clear assessment of lotteries' expected values. During the feedback phase, subjective ratings and eye-tracking results confirmed that participants compared their outcome with the outcome of the non-chosen lottery in the complete feedback condition, particularly after a loss, and ignored the non-realized outcome of the chosen option. Moreover, participants who made more visual saccades consistent with counterfactual comparisons during the feedback period anticipated regret more in their decisions. These results are consistent with the proposed adaptive function of regret

Orbitofrontal cortex, emotional decision-making and response to cognitive behavioural therapy for psychosis

Grey matter volume (GMV) in the orbitofrontal cortex (OFC) may relate to better response to cognitive behavioural therapy for psychosis (CBTp) because of the region's role in emotional decision-making and cognitive flexibility. This study aimed to determine the relation between pre-therapy OFC GMV or asymmetry and CBTp responsiveness and emotional decision-making as measured by the Iowa Gambling Task (IGT). Thirty patients received CBTp + standard care (CBTp+SC; 25 completers) for 6-8 months. All patients (before receiving CBTp) and 25 healthy participants underwent structural magnetic resonance imaging and performed the IGT. Patients' symptoms were assessed before and after therapy. Pre-therapy OFC GMV, measured using a region-of-interest approach, and IGT performance, measured as overall learning, attention to reward, memory for past outcomes and choice consistency, were comparable between patient and healthy groups. In the CBTp+SC group, greater OFC GMV was correlated with positive symptom improvement, specifically hallucinations and persecution. Greater rightward OFC asymmetry correlated with improvement in several negative and general psychopathology symptoms. Greater left OFC GMV was associated with lower IGT attention to reward. The findings suggest that greater OFC volume and rightward asymmetry, which maintain the OFC's function in emotional decision-making and cognitive flexibility, are beneficial for CBTp responsiveness

Promoting Client Participation and Constructing Decisions in Mental Health Rehabilitation Meetings

The chapter analyzes practices by which support workers promote client participation in mental health rehabilitation meetings at the Clubhouse. While promoting client participation, the support workers also need to ascertain that at least some decisions get constructed during the meetings. This combination of goals—promoting participation and constructing decisions—leads to a series of dilemmatic practices, the dynamics of which the chapter focuses on analyzing. The support workers may treat clients’ turns retrospectively as proposals, even if the status of these turns as such is ambiguous. In the face of a lack of recipient uptake, the support workers may remind the clients about their epistemic access to the content of the proposal or pursue their agreement or commitment to the idea. These practices involve the support workers carrying primary responsibility over the unfolding of interaction, which is argued to compromise the jointness of the decision-making outcome.The chapter analyzes practices by which support workers promote client participation in mental health rehabilitation meetings at the Clubhouse. While promoting client participation, the support workers also need to ascertain that at least some decisions get constructed during the meetings. This combination of goals—promoting participation and constructing decisions—leads to a series of dilemmatic practices, the dynamics of which the chapter focuses on analyzing. The support workers may treat clients’ turns retrospectively as proposals, even if the status of these turns as such is ambiguous. In the face of a lack of recipient uptake, the support workers may remind the clients about their epistemic access to the content of the proposal or pursue their agreement or commitment to the idea. These practices involve the support workers carrying primary responsibility over the unfolding of interaction, which is argued to compromise the jointness of the decision-making outcome.Peer reviewe

The Tripartite Type III Secreton of Shigella flexneri Inserts Ipab and Ipac into Host Membranes

Bacterial type III secretion systems serve to translocate proteins into eukaryotic cells, requiring a secreton and a translocator for proteins to pass the bacterial and host membranes. We used the contact hemolytic activity of Shigella flexneri to investigate its putative translocator. Hemolysis was caused by formation of a 25-Å pore within the red blood cell (RBC) membrane. Of the five proteins secreted by Shigella upon activation of its type III secretion system, only the hydrophobic IpaB and IpaC were tightly associated with RBC membranes isolated after hemolysis. Ipa protein secretion and hemolysis were kinetically coupled processes. However, Ipa protein secretion in the immediate vicinity of RBCs was not sufficient to cause hemolysis in the absence of centrifugation. Centrifugation reduced the distance between bacterial and RBC membranes beyond a critical threshold. Electron microscopy analysis indicated that secretons were constitutively assembled at 37°C before any host contact. They were composed of three parts: (a) an external needle, (b) a neck domain, and (c) a large proximal bulb. Secreton morphology did not change upon activation of secretion. In mutants of some genes encoding the secretion machinery the organelle was absent, whereas ipaB and ipaC mutants displayed normal secretons

Fluid Intelligence and Psychosocial Outcome: From Logical Problem Solving to Social Adaptation

While fluid intelligence has proved to be central to executive functioning, logical reasoning and other frontal functions, the role of this ability in psychosocial adaptation has not been well characterized.Lower fluid intelligence scores were associated with physical violence, both in the role of victim and victimizer. Drug intake, especially cannabis, cocaine and inhalants and lower self-esteem were also associated with lower fluid intelligence. Finally, scores on the perceived mental health assessment were better when fluid intelligence scores were higher.Our results show evidence of a strong association between psychosocial adaptation and fluid intelligence, suggesting that the latter is not only central to executive functioning but also forms part of a more general capacity for adaptation to social contexts

Nanoparticules d’oxysulfures de lanthanides et de métaux de transition : de la synthèse colloïdale à la structure, la surface et aux propriétés optiques et magnétiques

The first part of this thesis is dedicated to lanthanide oxysulfides Ln2O2S. In the bibliographic introduction, the history and properties of the bulk compounds are presented. The reaction conditions of the syntheses of Ln2O2S nanoparticles are then detailed. Gd2O2S nanoparticles are obtained via a synthesis in organic medium using Gd(acac)3, S8 and Na(oleate). Unsupported Ce2O2S nanoparticles are obtained for the first time by keeping the nanoparticles under inert atmosphere from the synthesis to the storage. The solid solution between Gd and Ce enables the formation of (Gd,Ce)2O2S nanoparticles. Their surface and their optical and magnetic properties are studied. For the first time, a formation mechanism with nucleation and growth steps is proposed. The alkaline source which is crucial for the crystallization is still debated; the mechanistic study unveiled a new role of formation of oleate aliphatic bilayers. A second part deals with the transition metal oxysulfides. After a quick introduction on the bulk phases, the scarce nanoscaled compounds are presented. The synthesis of Ln2O2S nanoparticles used in the first part is transposed to p- and d- block transition metals. Because of the differences in the coordination modes of the metals, the transposition is challenging but promising results were obtained with several metals. A last chapter is dedicated to the synthesis of nickel sulfides and oxysulfides at ambient temperature using a reactive complex of nickel and S8.Les oxysulfures de lanthanides Ln2O2S constituent la première partie de ce travail de thèse. Dans l’introduction bibliographique, l’histoire et les propriétés des composés massifs sont rappelées. Les conditions de synthèse des nanoparticules Ln2O2S y sont aussi comparées. On synthétise ensuite des nanoparticules de Gd2O2S par synthèse en milieu organique à l’aide de Gd(acac)3, S8 et Na(oléate). Des nanoparticules de Ce2O2S sont obtenues pour la première fois en gardant les nanoparticules sous atmosphère inerte, de la synthèse au stockage. Des nanoparticules de compositions intermédiaires (Gd,Ce)2O2S sont aussi synthétisées. Leur surface est finement étudiée tout comme leurs propriétés optiques et magnétiques. Pour la première fois, un mécanisme de formation des nanoparticules Ln2O2S avec étapes de nucléation et de croissance est proposé. La source alcaline indispensable à la cristallisation est sujette à débat ; l’étude mécanistique nous permet de proposer un nouveau rôle, celui de former des bicouches aliphatiques avec les oléates. Une seconde partie est dédiée aux oxysulfures de métaux de transition. Après un rappel sur les phases massives existantes, les rares phases nanométriques sont présentées. La synthèse de nanoparticules de Ln2O2S utilisée dans la première partie est transposée aux métaux de la première série de transition. Des difficultés sont rencontrées en raison des modes de coordination différents de ces métaux mais certains composés offrent des pistes intéressantes. La synthèse de sulfures et d’oxysulfures de nickel par une synthèse à température ambiante utilisant un complexe réactif de nickel et S8 fait l’objet d’un dernier chapitre

Metal Oxysulfides: From Bulk Compounds to Nanomaterials

International audienceThis review summarizes the syntheses and applications of metal oxysulfides. Bulk compounds of rare earth and transition metals are discussed in the section Introduction. After a presentation of their main properties and applications, their structures are presented and their syntheses are discussed. The section Bulk Materials and Their Main Applications is dedicated to the growing field of nanoscaled metal oxysulfides. Synthesis and applications of lanthanide-based nanoparticles are more mature and are discussed first. Then, works on transition-metal based nanoparticles are presented and discussed. Altogether, this review highlights the opportunities offered by metal oxysulfides for application in a range of technological fields, in relation with the most advanced synthetic routes and characterization techniques