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Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity

Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, incl

Novel insights into peptide amidation and amidating activity in the human circulation

C-terminal α-amidation is the final and essential step in the biosynthesis of several peptide hormones. Peptidylglycine α-amidating monooxygenase (PAM) is the only known enzyme to catalyse this reaction. PAM amidating activity (AMA) is known to be present in human circulation, but its physiological role and significance as a clinical biomarker remains unclear. We developed a PAM-specific amidation

Improvement of structural efficiency in metals by the control of topological arrangements in ultrafine and coarse grains

Improvement of structural efficiency in various materials is critically important for sustainable society development and the efficient use of natural resources. Recently, a lot of attention in science and engineering has been attracted to heterogeneous-structure materials because of high structural efficiency. However, strategies for the efficient design of heterogenous structures are still in th

Outcome after acute ischemic stroke is linked to sex-specific lesion patterns

Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of H

In situ measurements of oxidation–reduction potential and hydrogen peroxide concentration as tools for revealing LPMO inactivation during enzymatic saccharification of cellulose

Background: Biochemical conversion of lignocellulosic biomass to simple sugars at commercial scale is hampered by the high cost of saccharifying enzymes. Lytic polysaccharide monooxygenases (LPMOs) may hold the key to overcome economic barriers. Recent studies have shown that controlled activation of LPMOs by a continuous H2O2 supply can boost saccharification yields, while overdosing H2O2 may lea

Lung Mast Cells Have a High Constitutive Expression of Carboxypeptidase A3 mRNA That Is Independent from Granule-Stored CPA3

The mast cell granule metalloprotease CPA3 is proposed to have important tissue homeostatic functions. However, the basal CPA3 mRNA and protein expression among mast cell populations has remained poorly investigated. Using a novel histology-based methodology that yields quantitative data on mRNA and protein expression at a single-cell level, the present study maps CPA3 mRNA and protein throughout

Inflammatory depression—mechanisms and non-pharmacological interventions

Treatment of depression is hampered by the failure to identify distinct symptom profiles with distinct pathophysiologies that differentially respond to distinct treatments. We posit that inflammatory depression is a meaningful depression subtype associated with specific symptoms and biological abnormalities. We review several upstream, potentially causative, mechanisms driving low-grade inflammati

Circulating pro-neurotensin levels predict bodyweight gain and metabolic alterations in children

Background and aims: Neurotensin (NT) is an intestinal peptide released after fat ingestion, which regulates appetite and facilitates lipid absorption. Elevated plasma levels of its stable precursor pro-neurotensin (pro-NT) are associated with type 2 diabetes, obesity and cardiovascular mortality in adult populations; no data on pro-NT and metabolic disease are available in children. Aim of the st

Cookstoves, Candles, and Phthalates – Real Time Physicochemical Characterization and Human Exposure to Indoor Aerosols

Exposure to air pollution is associated with adverse health effects in humans, with special concern for exposure to fine particulate matter (PM2.5). The physicochemical properties of aerosols impact the health effects. Considering that we spend approximately 90% of our time indoors, it is important to gain increased understanding of indoor aerosol concentrations and properties. The overall aim of

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Formalized triage has been implemented in all Danish emergency departments. The validation behind formalized triage has focused on investigating predictive validity, i.e. correspondence between triage category and different outcome measures. Reliability is primarily investigated in terms of inter-rater reliability on written patient cases, and several studies have methodological limitations questi

Risk Factors for Syncope Associated With Multigenerational Relatives With a History of Syncope

Importance: Reflex syncope is the major cause of transient loss of consciousness, which affects one-third of the population, but effective treatment for individuals with severe syncope is lacking. Better understanding of reflex syncope predisposition may offer new therapeutic solutions.Objectives: To determine the familial risk of syncope in first-, second-, and third-degree relatives of affected

The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude

Gaining a mechanistic understanding of the expansion and maturation program of natural killer (NK) cells will provide opportunities for harnessing their inflammation-inducing and oncolytic capacity for therapeutic purposes. Here, we demonstrated that ID2, a transcriptional regulatory protein constitutively expressed in NK cells, supports NK cell effector maturation by controlling the amplitude and

Anisotropic dynamics of magnetic colloidal cubes studied by X-ray photon correlation spectroscopy

Herein we present our results on the investigation of the influence of external magnetic fields on the anisotropic collective dynamics of core/shell colloidal cubes having a hematite core and silica shell. Owing to the hematite cores, these micrometer-sized particles possess permanent dipole moments, which are at an angle with respect to the long diagonal of the cubes. As a result, they self-assem

Immune response and gut microbiota of mice on a diet mimicking eating habits of elderly with risk of malnutrition development

The number of elderlies is increasing but prevalence of malnutrition has been reported. The aim of the study was to determine the significance of short-term nutritional deficiencies in mice. Immune status was assessed through flow cytometry of leucocytes in Peyer’s patches (PP) and mesenteric lymph nodes (MLN), and intestinal microbiota was evaluated by terminal restriction fragment length polymor

A plasma lipid signature predicts incident coronary artery disease

Background: Dyslipidemia is a hallmark of cardiovascular disease but is characterized by crude measurements of triglycerides, HDL- and LDL cholesterol. Lipidomics enables more detailed measurements of plasma lipids, which may help improve risk stratification and understand the pathophysiology of cardiovascular disease. Methods: Lipidomics was used to measure 184 lipids in plasma samples from the M

Effect of mindfulness on physical activity in primary healthcare patients : a randomised controlled trial pilot study

Increased physical activity can have health benefits among inactive individuals. In Sweden, the healthcare system uses physical activity on prescription (PAP) to motivate patients to increase their physical activity level. Mindfulness may further heighten the internal motivation to engage in physical activity. However, previous research has not demonstrated clear evidence of such an association.AI

Experiences matter: A longitudinal study of individual-level sources of declining social trust in the United States

The US has experienced a substantial decline in social trust in recent decades. Surprisingly few studies analyze whether individual-level explanations can account for this decrease. We use three-wave panel data from the General Social Survey (2006–2014) to study the effects of four possible individual-level sources of changes in social trust: job loss, social ties, income, and confidence in politi

Fluorescence signal enhancement in antibody microarrays using lightguiding nanowires

Fluorescence-based detection assays play an essential role in the life sciences and medicine. To offer better detection sensitivity and lower limits of detection (LOD), there is a growing need for novel platforms with an improved readout capacity. In this context, substrates containing semiconductor nanowires may offer significant advantages, due to their proven light-emission enhancing, waveguidi