Medical Research Council

Heterochronicity shapes brain network formation

Brain network formation unfolds on a nonuniform developmental timetable, with different cortical regions generating connections at different developmental phases. Generative network models (GNMs) aim to uncover the principles underpinning the organization of connectomes by creati...

Migratory dermal γδ T cells determine the balance between lung immunity and tissue damage during helminth infection

Many helminth parasites migrate through multiple host organs during infection, but how immune responses are relayed across these tissues is still poorly understood. To investigate the immune aspects of intertissue communication during infection, we established a percutaneous infe...

Genetic and pharmacologic inhibition of Keap1 dampens the pro-fibrotic program in human hepatic stellate cells

Abstract The increasing prevalence of chronic liver diseases (CLDs) is a global health concern. CLDs can cause fibrosis, and there is an urgent need for antifibrotic agents. The primary driver of fibrogenesis, transforming growth factor beta 1 (TGF-β1), activates hepatic stellate...

Sequence learning as Bayesian filtering.

Here we present a model of sequence learning and recall based on the idea that the function of memory is to maintain an up-to-date representation of the environment that can be used to guide future perception and action. The representation of the environment is considered to be a...

Antihypertensive Treatment and Risk of Metabolic Associated Fatty Liver Disease: A Drug-Target Mendelian Randomization

BACKGROUND: Metabolic dysfunction-associated fatty liver disease, conventionally known as nonalcoholic fatty liver disease (NAFLD), affects over a quarter of the global population and lacks approved pharmacological treatments. We investigated whether elevated blood pressure (BP)...

Mental health problems as mediators between childhood trauma and cardiometabolic risk behaviours in the 2004 Pelotas Birth Cohort

BACKGROUND: Childhood trauma is associated with greater engagement in health risk behaviours (HRBs) that predispose to cardiometabolic disease. However, the mechanisms underlying these associations remain poorly understood. Mental health problems are hypothesised to mediate links...

Longitudinal dynamics of gene expression and metabolomics in an aging population cohort

Multiomic profiling provides a comprehensive physiological overview at the molecular level, but understanding of its spatiotemporal dynamics remains limited in human populations. We profiled longitudinal whole-blood gene expression and metabolite levels in 335 females over 8 year...

Efficacy of Low Dose of Dihydroquercetin (DHQ) in Two Genetic Models of Neurodegeneration: Insights from FUS[1-359]-Tg and APPswe/PS1dE9 Paradigms

Dihydroquercetin (DHQ), a powerful antioxidant and regulator of cellular metabolism, was proposed for therapy of neurodegenerative disorders. Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) are serious neurodegenerative disorders with oxidative stress as an overl...

Robust inference and correlates from genetic associations with personality

Personality traits describe stable differences in how people think, feel and behave, and how they interact with and experience their social and physical environments1,2. Many questions remain unanswered about associations between DNA and personality traits, such as their robustne...

First draft genome sequence of the emerging sexually transmitted dermatophyte Trichophyton mentagrophytes genotype VII

Abstract Trichophyton mentagrophytes ITS-genotype VII (TMVII) is a globally emerging sexually transmitted dermatophyte causing severe skin infections characterised by painful, pustular lesions on the face, public area, genitalia, and trunk. To inform the prevention efforts, we pr...

Live Attenuated Influenza Vaccine (LAIV) for Children for the Prevention of Influenza Illness in Sweden: A Cost-Effectiveness Analysis

Both inactivated influenza vaccine and live attenuated influenza vaccine (LAIV) (indicated for use in children aged 2–17 years) effectively prevent influenza transmission and related outcomes. Despite high transmission among children, vaccination practices in Sweden focus primari...

Polygenic score for sleep duration in relation to the risk of Alzheimer’s disease: results from the UK biobank

Abstract INTRODUCTION Studies have suggested sleep duration may be associated with Alzheimer’s disease risk, but findings based on self-reported sleep duration are likely to be influenced by reverse causation and residual confounding bias. METHODS A polygenic score (PGS) for devi...

PLCG2 downregulation impairs synaptic function and increases Alzheimer’s disease hallmarks in neuronal cultures

We developed a high-content screening to investigate how Alzheimer’s disease (AD) genetic risk factors may affect synaptic mechanisms in rat primary neuronal cultures. Of the target genes identified, we found that Plcg2 downregulation in mouse dentate gyrus neurons consistently d...

Early Longitudinal Brain Network Changes in Huntington's Disease Before Clinical Motor Onset

Abstract Background Longitudinal studies of seed‐based functional connectivity (SBFC) in young adult Huntington's disease gene‐expanded (HDGE) individuals are rare, and none, to our knowledge, have examined adult cohorts decades from predicted clinical motor diagnosis. Objectives...

CB1 receptor-enriched functional connectivity analysis revealed target-specific modulation by cannabidiol in early psychosis

BACKGROUND: Cannabidiol (CBD) has emerged as a potential antipsychotic treatment, acting as a negative allosteric modulator of cannabinoid type-1 (CB1) receptors within the endocannabinoid system. Although previous neuroimaging studies have shown that CBD induces changes in aberr...