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Background Bothgenetic and lifestyle factors contribute to the risk of type 2 diabetes, but the extent to which there is a synergistic effect of the 2 factors is unclear. The aim of this study was to examine the joint associations of genetic risk and diet quality with incident type 2 diabetes. Methods and findings We analyzed data from 35,759 men and women in the United States participating in the
Activation of macroautophagy/autophagy, a key mechanism involved in the degradation and removal of aggregated proteins, can successfully reverse Huntington disease phenotypes in various model systems. How neuronal autophagy impairments need to be considered in Huntington disease progression to achieve a therapeutic effect is currently not known. In this study, we used a mouse model of HTT (hunting
Naturally occurring human genetic variants that are predicted to inactivate protein-coding genes provide an in vivo model of human gene inactivation that complements knockout studies in cells and model organisms. Here we report three key findings regarding the assessment of candidate drug targets using human loss-of-function variants. First, even essential genes, in which loss-of-function variants
The acceleration of DNA sequencing in samples from patients and population studies has resulted in extensive catalogues of human genetic variation, but the interpretation of rare genetic variants remains problematic. A notable example of this challenge is the existence of disruptive variants in dosage-sensitive disease genes, even in apparently healthy individuals. Here, by manual curation of puta
Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors,
Human genetic variants predicted to cause loss-of-function of protein-coding genes (pLoF variants) provide natural in vivo models of human gene inactivation and can be valuable indicators of gene function and the potential toxicity of therapeutic inhibitors targeting these genes1,2. Gain-of-kinase-function variants in LRRK2 are known to significantly increase the risk of Parkinson’s disease3,4, su
The etiology of most neurological disorders is poorly understood and current treatments are largely ineffective. New ideas and concepts are therefore vitally important for future research in this area. This review explores the concept that dysregulation of transposable elements (TEs) contributes to the appearance and pathology of neurodevelopmental and neurodegenerative disorders. Despite TEs maki
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD usin
We propose to combine population-based register data, with a nested clinical cohort to correct misclassification and unmeasured confounding through probabilistic quantification of bias. We illustrate this approach by estimating the association between knee osteoarthritis and mortality. We used the Swedish Population Register to include all persons resident in the Skåne region in 2008 and assessed
OBJECTIVE: To determine whether exposure to cardiovascular medications and statins is associated with increased risk of giant cell arteritis (GCA). DESIGN: The population-based case-control study comprised a cohort of patients with biopsy-confirmed GCA linked to the Swedish Prescribed Drug Register to identify all exposure to drugs prior to diagnosis of GCA. Ten controls per GCA case, matched for
The synthesis and crystal structure of rhodamine 590 acid phthalate (RhAP) have been reported. This novel solid-state rhodamine derivative not only has a longer fluorescence lifetime compared to rhodamine solid-state matrixes where emission is quenched but also possesses strong nonlinear optical characteristics. The static and dynamic first- and second-order hyperpolarizabilities were calculated u
Metal halide perovskites have shown a great performance in a broad range of optoelectronic devices. The variety of preparation methods makes perovskites especially attractive, yet preparation of complex nanostructures based on these materials remains challenging. Here we present a template assisted method allowing to achieve any pre-designed arrangement of methylammonium lead triiodide (MAPbI3) po
How people wake up and regain alertness in the hours after sleep is related to how they are sleeping, eating, and exercising. Here, in a prospective longitudinal study of 833 twins and genetically unrelated adults, we demonstrate that how effectively an individual awakens in the hours following sleep is not associated with their genetics, but instead, four independent factors: sleep quantity/quali
The Baltic Sea is one of the fastest-warming marginal seas globally, and its temperature rise has adversely affected its physical and biochemical characteristics. In this study, forty years (1982–2021) of sea surface temperature (SST) data from the advanced very high resolution radiometer (AVHRR) were used to investigate spatial and temporal SST variability of the Baltic Sea. To this end, annual
Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric post
We investigate hot carrier (HC) cooling in two-dimensional (2D) perovskite single crystals by applying two complementary ultrafast spectroscopy techniques - transient absorption (TA) and time-resolved two-photon photoemission (TR-2PPE) spectroscopies. TR-2PPE directly maps the hot electron distribution and its dynamics in the conduction band to the detected photoelectron distribution. While TR-2PP
The specific viscoelastic mechanical properties of Achilles tendons are highly dependent on the structural characteristics of collagen at and between all hierarchical levels. Research has been conducted on the deformation mechanisms of positional tendons and single fibrils, but knowledge about the coupling between the whole tendon and nanoscale deformation mechanisms of more commonly injured energ
Ambient Pressure X-ray Photoelectron Spectroscopy combined with an electrochemical setup is used to study, in situ, the electrochemical oxide growth on an industrial Ni-Cr-Mo alloy. The native oxide film was characterized in vacuum and in water vapor at 17 mbar, and was found to be 11.4 Å thick and rich in Cr3+. In 0.1 M NaCl electrolyte, anodic growth of the oxide film at potentials up to 700 mV
The surface reactivity during CO oxidation over Pd(1 1 1) and Pd75%Ag25%(1 1 1) single crystals has been investigated using near ambient pressure X-ray photoelectron spectroscopy (NAP-XPS) under excess oxygen conditions (p ≈ 2 mbar, O2:CO=10). The (√6×√6) Pd5O4 surface oxide is present on Pd(1 1 1) when the surface is highly active under the applied conditions. The CO2 formation profile follows a
OBJECTIVE: This longitudinal study examines a possible causal effect between type 2 diabetes and ischemic heart disease (IHD) by using measurements on four occasions from the Swedish Statistics on Income and Living Conditions (SILC) together with nationwide healthcare registers.METHODS: This was a longitudinal study based on a random sample of men and women (n = 2014) from the Swedish population w
