Benefits of belonging: experimental manipulation of social inclusion to enhance psychological and physiological health parameters.

OBJECTIVE: Acute changes in social belonging are important triggers for alterations in health and well-being, yet research has emphasised the negative effects of 'exclusion' at the expense of evaluating the potentially positive effects of 'inclusion'. This study examined the impact of acute belonging on physiological and psychological outcomes. DESIGN AND MAIN OUTCOME MEASURES: A healthy population (N = 138) were randomly allocated to 'included' or 'excluded' conditions. Condition-dependent differences in pre/during-task heart rate and pre/post-task self-reports of negative/positive mood, and social self-esteem, were assessed. RESULTS: Included participants showed decreased heart rate and negative mood, and increased social self-esteem. No inclusion-related change in positive mood was shown. An increase in heart rate was observed in excluded participants though no changes in negative/positive mood or social self-esteem were shown. Shifts in social self-esteem acted as a mechanism through which inclusion/exclusion impacted upon negative and positive mood alterations. Results remained significant in presence of covariates (sex, global self-esteem, rumination and social anxiety). CONCLUSION: Findings suggest that acting to enhance belonging through 'inclusion' resulted in adaptive physiological and psychological outcomes. Neutral and potentially protective responses were observed in the immediate aftermath of 'exclusion'. Self-esteem served as one route through which these effects were transmitted

Influence of pressure on the Boson peak: Stronger than elastic medium transformation

International audienc

Targeting PfCLK3 with covalent inhibitors: a novel strategy for malaria treatment

Malaria still causes over 600,000 deaths annually, with rising resistance to frontline drugs by Plasmodium falciparum increasing this number each year. New medicines with novel mechanisms of action are, therefore, urgently needed. In this work, we solved the cocrystal structure of the essential malarial kinase PfCLK3 with the reversible inhibitor TCMDC-135051 (1), enabling the design of covalent inhibitors targeting a unique cysteine residue (Cys368) poorly conserved in the human kinome. Chloroacetamide 4 shows nanomolar potency and covalent inhibition in both recombinant protein and P. falciparum assays. Efficacy in parasites persisted after a 6 h washout, indicating an extended duration of action. Additionally, 4 showed improved kinase selectivity and a high selectivity index against HepG2 cells, with a low propensity for resistance (log MIR > 8.1). To our knowledge, compound 4 is the first covalent inhibitor of a malarial kinase, offering promising potential as a lead for a single-dose malaria cure