alters the lipid droplet proteome and modulates droplet dynamics.

Excess lipid droplet (LD) accumulation is associated with several pathological states, including Alzheimer's disease (AD). However, the mechanism(s) by which changes in LD composition and dynamics contribute to pathophysiology of these disorders remains unclear. Apolipoprotein E (ApoE) is a droplet associated protein with a common risk variant (E4) that confers the largest increase in genetic risk for late-onset AD.

Hepatic Inactivation of Carnitine Palmitoyltransferase 1a Lowers Apolipoprotein B Containing Lipoproteins in Mice.

Unlabelled: Genome- and epigenome-wide association studies have associated variants and methylation status of carnitine palmitoyltransferase 1a (CPT1a) to reductions in very low-density lipoprotein (VLDL) cholesterol and triglyceride levels. We report significant associations between the presence of SNPs and reductions in plasma cholesterol, as well as positive associations between hepatic Cpt1a expression and plasma cholesterol levels across inbred mouse strains. Mechanistic studies show that both wild type and human apolipoprotein B100 (apoB)-transgenic mice with liver-specific deletion of (LKO) display lower circulating apoB levels consistent with reduced LDL-cholesterol (LDL-C) and LDL particle number.

Influencing basic behavioral mechanisms of action while targeting daily walking in sedentary adults at risk for cardiovascular disease: randomised factorial design protocol.

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, though it may be prevented by increasing physical activity (PA). When behaviour change techniques (BCTs) are bundled together, they increase PA, though which individual BCTs increase PA (and the behavioural mechanism of action (MoA) responsible for said increase) have not been studied. The aim of this study is to conduct a randomised factorial experiment to determine which of four BCTs significantly engage the proposed MoA-self-efficacy for PA-in adults at risk for CVD.

Private, public, and bottled drinking water: Shared contaminant-mixture exposures and effects challenge.

Background: Humans are primary drivers of environmental-contaminant exposures worldwide, including in drinking-water (DW). In the United States, point-of-use DW (POU-DW) is supplied via private tapwater (TW), public-supply TW, and bottled water (BW). Differences in management, monitoring, and messaging and lack of directly-intercomparable exposure data influence the actual and perceived quality and safety of different DW supplies and directly impact consumer decision-making.

Catalytic inhibition of KAT6/KAT7 enhances the efficacy and overcomes primary and acquired resistance to Menin inhibitors in MLL leukaemia.

Understanding the molecular pathogenesis of MLL fusion oncoprotein (MLL-FP) leukaemia has spawned epigenetic therapies that have improved clinical outcomes in this often-incurable disease. Using genetic and pharmacological approaches, we define the individual and combined contribution of KAT6A, KAT6B and KAT7, in MLL-FP leukaemia. Whilst inhibition of KAT6A/B is efficacious in some pre-clinical models, simultaneous targeting of KAT7, with the novel inhibitor PF-9363, increases the therapeutic efficacy.