Structural Dynamics of the Ubiquitin Specific Protease USP30 in Complex with a Cyanopyrrolidine-Containing Covalent Inhibitor.

Inhibition of the mitochondrial deubiquitinating (DUB) enzyme USP30 is neuroprotective and presents therapeutic opportunities for the treatment of idiopathic Parkinson's disease and mitophagy-related disorders. We integrated structural and quantitative proteomics with biochemical assays to decipher the mode of action of covalent USP30 inhibition by a small-molecule containing a cyanopyrrolidine reactive group, . The inhibitor demonstrated high potency and selectivity for endogenous USP30 in neuroblastoma cells.

Public engagement to refine a whole-school intervention to promote adolescent mental health.

Background: Despite high rates of adolescent mental health problems, there are few effective school-based interventions to address this. Whole-school interventions offer a feasible and sustainable means of promoting mental health, but few have to date been evaluated. Previously we trialled the Learning Together intervention comprising local needs assessment, student and staff participation in decision-making, restorative practice, and a social and emotional skills curriculum.

Qualitative study of the feasibility and acceptability of implementation, and potential mechanisms of Learning Together for Mental Health, a whole-school intervention aiming to promote mental health and wellbeing in secondary schools.

Background: Despite high rates of adolescent mental-health problems, there are few effective whole-school interventions to address this. Whole-school interventions offer a feasible and sustainable means of promoting mental health. We previously evaluated the Learning Together (LT) intervention which was effective in preventing bullying (primary outcome), promoting mental well-being, psychological functioning, and reducing substance use (secondary outcomes).

Assessing the evidence for health benefits of low-level weight loss: a systematic review.

Individuals with excess weight are at a higher risk for various physical and mental health conditions. Interventions targeting weight loss can improve health, with modest weight loss of five to ten percent of body weight often considered clinically meaningful for enhancing health outcomes. However, the benefits of achieving low-level weight loss ( < 5% body weight) are poorly understood.

Native mass spectrometry prescreening of G protein-coupled receptor complexes for cryo-EM structure determination.

G protein-coupled receptors (GPCRs) are essential transmembrane proteins playing key roles in human health and disease. Understanding their atomic-level molecular structure and conformational states is imperative for advancing drug development. Recent breakthroughs in single-particle cryogenic electron microscopy (cryo-EM) have propelled the structural biology of GPCRs into a new era.