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Insulin is packaged into secretory granules that depart the Golgi and undergo a maturation process that involves changes in the protein and lipid composition of the granules. Here, we show that insulin secretory granules form physical contacts with the endoplasmic reticulum and that the lipid exchange protein oxysterol-binding protein (OSBP) is recruited to these sites in a Ca2+-dependent manner.

Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well

Cell cycle progression and lipid metabolism are well-coordinated processes required for proper cell proliferation. In liver diseases that arise from dysregulated lipid metabolism, proliferation is diminished. To study the outcome of CDK1 loss and blocked hepatocyte proliferation on lipid metabolism and the consequent impact on whole-body physiology, we performed lipidomics, metabolomics, and RNA-s

Walking is a simple form of exercise, widely promoted for its health benefits. Self-reported walking pace has been associated with a range of cardiorespiratory and cancer outcomes, and is a strong predictor of mortality. Here we perform a genome-wide association study of self-reported walking pace in 450,967 European ancestry UK Biobank participants. We identify 70 independent associated loci (P <

Thermal actions are considered in the design of bridges, as temperature variations can lead to restraint stresses and subsequent cracking. However, load descriptions are in some cases oversimplified or incompatible with modern applications, and background studies are limited. This paper therefore aims to develop a more detailed load description for the load case describing temperature differences

This experimental study adapts a usage-based perspective on L2 acquisition (Bybee 2008; Ellis 2008) and focuses on the production of French subject-verb (SV) agreement in number (singular vs. plural). Previous studies show that the acquisition of this agreement is a long and gradual process in L2 French (Bartning & Schlyter 2004; Prévost 2009; Michot 2015). This study examines the influence of

The lack of treatments during the recent Ebola and Zika outbreaks dramatically exposed the vulnerability of the global health system and the dire consequences thereof. But even where therapies against infectious diseases had been available, an additional threat has gained world-wide attention: antimicrobial resistance (AMR). A growing number of microbial organisms are becoming resistant to availab

OBJECTIVE: The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more

This paper estimates the impact of university education on medical care use and its income related inequality. We do this by exploiting an arbitrary university eligibility rule in Sweden combined with regression discontinuity design for the years 2003-2013 for students who graduated 2003-2005. We find a clear jump in university attendance due to university eligibility. This jump coincides with a p

Impaired albumin reabsorption by proximal tubular epithelial cells (PTECs) has been highlighted in diabetic nephropathy (DN), but little is known about the underlying molecular mechanisms. Here we find that ORAI1-3, are preferentially expressed in PTECs and downregulated in patients with DN. Hyperglycemia or blockade of insulin signaling reduces the expression of ORAI1-3. Inhibition of ORAI channe

The rise of ICT and the shift toward jobs with more flexibility in working hours and places of work sparked popular debates about potential for a ‘rural renaissance’. A key argument was that there are increasing possibilities to live in the countryside while being employed in large cities. This paper uses data spanning two decades to examine trends in and characteristics of employee–employer ties

Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and

Knowledge about the past, current and future distribution of the human population is fundamental for tackling many global challenges. Censuses are used to collect information about population within a specified spatial unit. The spatial units are usually arbitrarily defined and their numbers, size and shape tend to change over time. These issues make comparisons between areas and countries difficu