Adipose tissue eQTL meta-analysis highlights the contribution of allelic heterogeneity to gene expression regulation and cardiometabolic traits.

Complete characterization of the genetic effects on gene expression is needed to elucidate tissue biology and the etiology of complex traits. In the present study, we analyzed 2,344 subcutaneous adipose tissue samples and identified 34,774 conditionally distinct expression quantitative trait locus (eQTL) signals at 18,476 genes. Over half of eQTL genes exhibited at least two eQTL signals.

Functional dissection of metabolic trait-associated gene regulation in steady state and stimulated human skeletal muscle cells.

Type 2 diabetes (T2D) is a common metabolic disorder characterized by dysregulation of glucose metabolism. Genome-wide association studies have defined hundreds of signals associated with T2D and related metabolic traits, predominantly in noncoding regions. While pancreatic islets have been a focal point given their central role in insulin production and glucose homeostasis, other metabolic tissues, including liver, adipose, and skeletal muscle, also contribute to T2D pathogenesis and risk.

Strain Effects on the Adsorption of Water on Cerium Dioxide Surfaces and Nanoparticles: A Modeling Outlook.

Nanocrystalline ceria exhibits significant redox activity and oxygen storage capacity. Any factor affecting its morphology can tune such activities. Strain is a promising method for controlling particle morphology, whether as core@shell structures, supported nanoparticles, or nanograins in nanocrystalline ceria.

Protocol for Cancloz: multicentre randomised, placebo-controlled, double-blind, parallel-group adaptive trial of cannabidiol for clozapine-resistant schizophrenia.

Background: Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia (TRS), only 40% of people with TRS respond, and there is limited evidence for augmentation agents. Cannabidiol (CBD) reduces positive symptoms in individuals with schizophrenia, but no trials have specifically examined its efficacy in those with clozapine-resistant schizophrenia.

Aims: To examine the clinical efficacy of CBD augmentation in people with clozapine-resistant schizophrenia.

Impact of Biological Sex on Emotional Perception Among Adults With Schizophrenia Spectrum Disorders: Protocol for a Systematic Review.

Background: It is well established that individuals with schizophrenia experience deficits in emotional perception that can impact long-term social and occupational functioning. Understanding the factors that impact these impairments is important for targeting interventions to improve recovery. In the general population, compared with males, females tend to show greater perception of emotions.

CNTools: A computational toolbox for cellular neighborhood analysis from multiplexed images.

Recent studies show that cellular neighborhoods play an important role in evolving biological events such as cancer and diabetes. Therefore, it is critical to accurately and efficiently identify cellular neighborhoods from spatially-resolved single-cell transcriptomic data or single-cell resolution tissue imaging data. In this work, we develop CNTools, a computational toolbox for end-to-end cellular neighborhood analysis on annotated cell images, comprising both the identification and analysis steps.

Markers of positive affect and brain state synchrony discriminate melancholic from non-melancholic depression using naturalistic stimuli.

Melancholia has been proposed as a qualitatively distinct depressive subtype associated with a characteristic symptom profile (psychomotor retardation, profound anhedonia) and a better response to biological therapies. Existing work has suggested that individuals with melancholia are blunted in their display of positive emotions and differ in their neural response to emotionally evocative stimuli. Here, we unify these brain and behavioural findings amongst a carefully phenotyped group of seventy depressed participants, drawn from an established Australian database (the Australian Genetics of Depression Study) and further enriched for melancholia (high ratings of psychomotor retardation and anhedonia).

Human Vascularized Macrophage-Islet Organoids to Model Immune-Mediated Pancreatic β cell Pyroptosis upon Viral Infection.

There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single cell RNA-seq analysis of human islets exposed to SARS-CoV-2 or Coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and β cell pyroptosis.

A Single Model for the Thermodynamics and Kinetics of Metal Exsolution from Perovskite Oxides.

Exsolution has emerged as an outstanding route for producing oxide-supported metal nanoparticles. For O-perovskite oxides, various late transition-metal cations can be substituted into the lattice under oxidizing conditions and exsolved as metal nanoparticles after reduction. A consistent and comprehensive description of the point-defect thermodynamics and kinetics of this phenomenon is lacking, however.

Life is better but not without challenges: experiences following discharge from community-based residential mental health rehabilitation-a qualitative content analysis.

Purpose: Community-based residential mental health rehabilitation units for people experiencing severe and persistent mental illness are increasingly available in Australia. Research completed 20 years ago suggested that people leaving these services often experienced impoverished social lives and other challenges in the community. It is unclear whether contemporary consumers experience similar difficulties.

Untangling the genetics of beta cell dysfunction and death in type 1 diabetes.

Background: Type 1 diabetes (T1D) is a complex multi-system disease which arises from both environmental and genetic factors, resulting in the destruction of insulin-producing pancreatic beta cells. Over the past two decades, human genetic studies have provided new insight into the etiology of T1D, including an appreciation for the role of beta cells in their own demise.

Scope Of Review: Here, we outline models supported by human genetic data for the role of beta cell dysfunction and death in T1D.

Attitudes toward psychedelics and psychedelic-assisted therapy among potential mental health service users and the general population in Australia.

Objective: Despite rapid advances in psychedelic sciences and the increasing number of countries legalizing psychedelics for the treatment of mental illnesses, the attitudes, knowledge and readiness of both mental health consumers and the general population remain largely unknown.

Methods: A cross-sectional survey was conducted among Australians, targeting individuals with mental illness as potential mental health service users. A sub-sample of individuals free of mental illness was also surveyed to assess attitudes in the general population.

Composition-dependent morphologies of CeO nanoparticles in the presence of Co-adsorbed HO and CO: a density functional theory study.

Catalytic activity is affected by surface morphology, and specific surfaces display greater activity than others. A key challenge is to define synthetic strategies to enhance the expression of more active surfaces and to maintain their stability during the lifespan of the catalyst. In this work, we outline an approach, based on density functional theory, to predict surface composition and particle morphology as a function of environmental conditions, and we apply this to CeO nanoparticles in the presence of co-adsorbed HO and CO as an industrially relevant test case.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer's disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole genome sequencing of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program.

Defining the passage of wisdom: A taxonomy of supervision for RANZCP trainees and Fellows.

Objective: Trainees and Fellows of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) work in complex interpersonal and organisational environments. Engagement in supervision can be a helpful way for trainees and Fellows to achieve interpersonal, professional, and organisational success. Supervision comes in many forms depending on the stage and state of one's career.

Identifying pathways to metal-organic framework collapse during solvent activation with molecular simulations.

Metal-organic framework (MOF) materials are a vast family of nanoporous solids with potential applications ranging from drug delivery to environmental remediation. Application of MOFs in these scenarios is hindered, however, by difficulties in MOF 'activation' after initial synthesis - removal of the synthesis solvent from the pores to make the pore space accessible - often leading to framework collapse if improperly performed. While experimental studies have correlated collapse to specific solvent properties and conditions, the mechanism of activation-collapse is currently unknown.

Genetic risk converges on regulatory networks mediating early type 2 diabetes.

Type 2 diabetes mellitus (T2D), a major cause of worldwide morbidity and mortality, is characterized by dysfunction of insulin-producing pancreatic islet β cells. T2D genome-wide association studies (GWAS) have identified hundreds of signals in non-coding and β cell regulatory genomic regions, but deciphering their biological mechanisms remains challenging. Here, to identify early disease-driving events, we performed traditional and multiplexed pancreatic tissue imaging, sorted-islet cell transcriptomics and islet functional analysis of early-stage T2D and control donors.