Machine learning uncovers the most robust self-report predictors of relationship quality across 43 longitudinal couples studies

Given the powerful implications of relationship quality for health and well-being, a central mission of relationship science is explaining why some romantic relationships thrive more than others. This large-scale project used machine learning (i.e., Random Forests) to 1) quantify the extent to which relationship quality is predictable and 2) identify which constructs reliably predict relationship quality. Across 43 dyadic longitudinal datasets from 29 laboratories, the top relationship-specific predictors of relationship quality were perceived-partner commitment, appreciation, sexual satisfaction, perceived-partner satisfaction, and conflict. The top individual-difference predictors were life satisfaction, negative affect, depression, attachment avoidance, and attachment anxiety. Overall, relationship-specific variables predicted up to 45% of variance at baseline, and up to 18% of variance at the end of each study. Individual differences also performed well (21% and 12%, respectively). Actor-reported variables (i.e., own relationship-specific and individual-difference variables) predicted two to four times more variance than partner-reported variables (i.e., the partner’s ratings on those variables). Importantly, individual differences and partner reports had no predictive effects beyond actor-reported relationship-specific variables alone. These findings imply that the sum of all individual differences and partner experiences exert their influence on relationship quality via a person’s own relationship-specific experiences, and effects due to moderation by individual differences and moderation by partner-reports may be quite small. Finally, relationship-quality change (i.e., increases or decreases in relationship quality over the course of a study) was largely unpredictable from any combination of self-report variables. This collective effort should guide future models of relationships

Nucleosome Structures Built from Highly Divergent Histones: Parasites and Giant DNA Viruses

In eukaryotes, genomic DNA is bound with histone proteins and packaged into chromatin. The nucleosome, a fundamental unit of chromatin, regulates the accessibility of DNA to enzymes involved in gene regulation. During the past few years, structural analyses of chromatin architectures have been limited to evolutionarily related organisms. The amino acid sequences of histone proteins are highly conserved from humans to yeasts, but are divergent in the deeply branching protozoan groups, including human parasites that are directly related to human health. Certain large DNA viruses, as well as archaeal organisms, contain distant homologs of eukaryotic histone proteins. The divergent sequences give rise to unique and distinct nucleosome architectures, although the fundamental principles of histone folding and DNA contact are highly conserved. In this article, we review the structures and biophysical properties of nucleosomes containing histones from the human parasites Giardia lamblia and Leishmania major, and histone-like proteins from the Marseilleviridae amoeba virus family. The presented data confirm the sharing of the overall DNA compaction system among evolutionally distant species and clarify the deviations from the species-specific nature of the nucleosome

Analyse génétique de la transduction du signal chez Leishmania par l'établissement et application d'un nouveau système de knock-out conditionnel

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Leishmania dual specificity tyrosine regulated kinase 1 (DYRK1) is required for sustaining Leishmania stationary phase phenotype

This work was supported by the International Division of the Institute Pasteur (ACIP A13-2013 project), the Action “KRIPIS I” (MIS 450598) co-financed by European Union and the National Ministry of Education and Religion Affairs under the Operational Strategic Reference Framework (NSRF 2007-2013) and the General Secretariat of Research and Technology (GSRT) and FAPESB/CAPES grant # PET0042/2013 from the Brazilian State and Federal governments respectively.Although the multiplicative and growth‐arrested states play key roles in Leishmania development, the regulators of these transitions are largely unknown. In an attempt to gain a better understanding of these processes, we characterised one member of a family of protein kinases with dual specificity, LinDYRK1, which acts as a stasis regulator in other organisms. LinDYRK1 over‐expressing parasites displayed a decrease in proliferation and in cell cycle re‐entry of arrested cells. Parasites lacking LinDYRK1 displayed distinct fitness phenotypes in logarithmic and stationary growth phases. In logarithmic growth‐phase, LinDYRK1‐/‐ parasites proliferated better than control lines, supporting a role of this kinase in stasis, while in stationary growth‐phase, LinDYRK1‐/‐ parasites had important defects as they rounded up, accumulated vacuoles and lipid bodies and displayed subtle but consistent differences in lipid composition. Moreover, they expressed less metacyclic‐enriched transcripts, displayed increased sensitivity to complement lysis and a significant reduction in survival within peritoneal macrophages. The distinct LinDYRK1‐/‐ growth phase phenotypes were mirrored by the distinct LinDYRK1 localisations in logarithmic (mainly in flagellar pocket area and endosomes) and late stationary phase (mitochondrion). Overall, this work provides first evidence for the role of a DYRK family member in sustaining promastigote stationary phase phenotype and infectivity.PostprintPeer reviewe

It's the motive that counts:Perceived sacrifice motives and gratitude in romantic relationships

Gratitude is robustly linked to many positive outcomes for individuals and relationships (e.g., greater life and relationship satisfaction). However, little is known about how romantic partners come to feel grateful for each other's pro-relational acts, such as when a partner makes a sacrifice. The present research examines how perceptions of partner sacrifice motives evoke gratitude. We distinguish between partner, relationship, and self-focused motives, and how they are guided by approach or avoidance orientations. We expected that perceiving a partner to sacrifice for partner-focused approach motives (i.e., to promote the partner's well-being) should evoke gratitude, as this type of motive may signal a genuine departure from self-interest. Moreover, we expected these motives to provoke greater perceptions of partner responsiveness, which should partially explain why they elicit gratitude. In contrast, perceiving a partner to sacrifice for relationship-focused motives (e.g., to promote the well-being of the relationship), or self-focused motives (e.g., to feel good about oneself), should not evoke gratitude-irrespective of an approach or avoidance orientation-as these motives may, to some extent, be perceived as tainted by self-interest. Two studies of romantic couples (N = 413), using diary methods (Studies 1 and 2) and having couples converse about a major sacrifice in the laboratory (Study 2), consistently showed that perceived partner-focused approach motives promote gratitude and that this association is partly mediated by perceived partner responsiveness. In contrast, relationship and self-focused motives (approach and avoidance oriented) were not associated with gratitude. Implications regarding perceiving and displaying sacrifice motives are discussed

To “See” Is to Feel Grateful? A Quasi-Signal Detection Analysis of Romantic Partners’ Sacrifices

Although gratitude plays a central role in the quality of relationships, little is known about how gratitude emerges, such as in response to partners’ sacrifices. Do people need to accurately see these acts to feel grateful? In two daily experience studies of romantic couples (total N = 426), we used a quasi-signal detection paradigm to examine the prevalence and consequences of (in)accurately “seeing” and missing partners’ sacrifices. Findings consistently showed that sacrifices are equally likely to be missed as they are to be accurately detected, and about half of the time people “see” a sacrifice when the partner declares none. Importantly, “seeing” partners’ sacrifices—accurately or inaccurately—is crucial for boosting gratitude. In contrast, missed sacrifices fail to elicit gratitude, and the lack of appreciation negatively colors the partner’s satisfaction with the relationship when having sacrificed. Thus, these findings illustrate the power that perception holds in romantic couples’ daily lives

Probing druggability and biological function of essential proteins in Leishmania combining facilitated null mutant and plasmid shuffle analyses

International audienceLeishmania parasites cause important human morbidity and mortality. Essential Leishmania genes escape genetic assessment by loss-of-function analyses due to lethal null mutant phenotypes, even though these genes and their products are biologically most significant and represent validated drug targets. Here we overcome this limitation using a facilitated null mutant approach applied for the functional genetic analysis of the MAP kinase LmaMPK4. This system relies on the episomal expression of the target gene from vector pXNG that expresses the Herpes simplex virus thymi-dine kinase gene thus rendering transgenic parasites susceptible for negative selection using the antiviral drug ganciclovir. Using this system we establish the genetic proof of LmaMPK4 as essential kinase in pro-mastigotes. LmaMPK4 structure/function analysis by plasmid shuffle allowed us to identify regulatory kinase sequence elements relevant for chemothera-peutic intervention. A partial null mutant, expressing an MPK4 derivative with altered ATP-binding properties , showed defects in metacyclogenesis, establishing a first link of MPK4 function to parasite differentiation. The approaches presented here are broadly applicable to any essential gene in Leishmania thus overcoming major bottlenecks for their functional genetic analysis and their exploitation for structure-informed drug development

Implication of different domains of the Leishmania major metacaspase in cell death and autophagy

International audienceMetacaspases (MCAs) are cysteine peptidases expressed in plants, fungi and protozoa, with a caspase-like histidine-cysteine catalytic dyad, but differing from caspases, for example, in their substrate specificity. The role of MCAs is subject to debate: roles in cell cycle control, in cell death or even in cell survival have been suggested. In this study, using a Leishmania major MCA-deficient strain, we showed that L. major MCA (LmjMCA) not only had a role similar to caspases in cell death but also in autophagy and this through different domains. Upon cell death induction by miltefosine or H2O2, LmjMCA is processed, releasing the catalytic domain, which activated substrates via its catalytic dyad His/Cys and a proline-rich C-terminal domain. The C-terminal domain interacted with proteins, notably proteins involved in stress regulation, such as the MAP kinase LmaMPK7 or programmed cell death like the calpain-like cysteine peptidase. We also showed a new role of LmjMCA in autophagy, acting on or upstream of ATG8, involving Lmjmca gene overexpression and interaction of the C-terminal domain of LmjMCA with itself and other proteins. These results allowed us to propose two models, showing the role of LmjMCA in the cell death and also in the autophagy pathway, implicating different protein domains