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Alzheimer's Disease (AD) is characterized by cerebral accumulation of β-amyloid peptides (Aβ), which are proteolytically derived from β-amyloid precursor protein (βAPP). βAPP metabolism is highly regulated via various signal transduction systems, e.g., several serine/threonine kinases and phosphatases. Several growth factors known to act via receptor tyrosine kinases also have been demonstrated to
Background Potassium disturbances per se increase the risk of ventricular fibrillation (VF). Whether potassium disturbances in the acute phase of ST-segment-elevation myocardial infarction (STEMI) are associated with VF before primary percutaneous coronary intervention (PPCI) is uncertain. Methods and Results All consecutive STEMI patients were identified in the Eastern Danish Heart Registry from
Activating FLT3 and RAS mutations commonly occur in leukemia with KMT2A-gene rearrangements (KMT2A-r). However, how these mutations cooperate with the KMT2A-r to remodel the epigenetic landscape is unknown. Using a retroviral acute myeloid leukemia (AML) mouse model driven by KMT2A::MLLT3, we show that FLT3ITD, FLT3N676K, and NRASG12D remodeled the chromatin accessibility landscape and associated
Triosephosphate isomerase (TIM) is a proficient catalyst of the reversible isomerization of dihydroxyacetone phosphate (DHAP) to d-glyceraldehyde phosphate (GAP), via general base catalysis by E165. Historically, this enzyme has been an extremely important model system for understanding the fundamentals of biological catalysis. TIM is activated through an energetically demanding conformational cha
BACKGROUND: Balloon angioplasty with drug-coated balloons (DCBs) is frequently used during percutaneous coronary intervention for in-stent restenosis. Despite its frequent use, there is a lack of long-term data on the efficacy of DCB angioplasty. We conducted an investigation on the long-term efficacy outcome of in-stent restenosis, comparing DCBs, drug-eluting stents, and plain old balloon angiop
BACKGROUND: Children often require pain management following surgery to avoid suffering. Effective pain management has consequences for healing time and quality of life. Ibuprofen, a frequently used non-steroidal anti-inflammatory drug (NSAID) administered to children, is used to treat pain and inflammation in the postoperative period.OBJECTIVES: 1) To assess the efficacy and safety of ibuprofen (
The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood IL
CONTEXT: The I148M (rs738409-G) variant in PNPLA3 increases liver fat content but may be protective against cardiovascular disease. Insulin resistance (IR) amplifies the effect of PNPLA3-I148M on liver fat. OBJECTIVE: To study whether PNPLA3-I148M confers an antihyperlipidemic effect in insulin-resistant patients. DESIGN: Cross-sectional study comparing the impact of PNPLA3-I148M on plasma lipids
Objective: Smooth muscle cells contribute significantly to lipid-laden foam cells in atherosclerotic plaques. However, the underlying mechanisms transforming smooth muscle cells into foam cells are poorly understood. The purpose of this study was to gain insight into the molecular mechanisms regulating smooth muscle foam cell formation. Approach and results: Using human coronary artery smooth musc
Background: The growth factor progranulin has been implicated in numerous biological processes such as wound healing, inflammation and progressive tumorigenesis. Both progranulin and its receptor sortilin are known to be highly expressed in subgroups of breast cancer and have been associated with various clinical properties including tamoxifen resistance. Recent data further suggest that progranul
Cell-free DNA (cfDNA) is the major structural component of neutrophil extracellular traps (NETs), an innate immune response to infection. Antimicrobial proteins and peptides bound to cfDNA play a critical role in the bactericidal property of NETs. Recent studies have shown that NETs have procoagulant activity, wherein cfDNA triggers thrombin generation through activation of the intrinsic pathway o
CONTEXT: Oral once-daily dual-release hydrocortisone (DR-HC) replacement therapy has demonstrated an improved metabolic profile compared to conventional 3-times-daily (TID-HC) therapy among patients with primary adrenal insufficiency. This effect might be related to a more physiological cortisol profile, but also to a modified pattern of cortisol metabolism. OBJECTIVE: This work aimed to study cor
Groundwater contamination is a threat to drinking water resources and ecosystems. Remediation by injection of chemical reagents into the aquifer may be preferred to excavation to reduce cost and environmental footprint. Yet, successful remediation requires complete contact between contamination and reagents. Subsurface heterogeneities are often responsible for diffusion into low-permeable zones, w
An important element of antibody-guided vaccine design is the use of neutralizing or opsonic monoclonal antibodies to define protective epitopes in their native three-dimensional conformation. Here, we demonstrate a multimodal mass spectrometry-based strategy for in-depth characterization of antigen–antibody complexes to enable the identification of protective epitopes using the cytolytic exotoxin
This paper reframes our understanding of the discourse on work-life balance (WLB) from a global perspective, where life on the four income levels (from bottom of the wealth to top of the wealth) is equally considered. Based on a systematic literature review, our initial insights are that WLB of workers in the highest economic sectors has received significant attention from scholars and practitione
Background: A growing literature suggests associations between occupational pesticide exposure and respiratory health. In this study, we aimed to examine the association of exposure to insecticides, fungicides, and herbicides, individually and as a mixture, with respiratory health outcomes and rhinitis in avocado farmworkers from Michoacán, Mexico. Material and methods: We conducted a cross-sectio
PURPOSE: Autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) define pre-clinical autoimmune thyroid disease (AITD) which can progress to either clinical hypo- or hyperthyroidism. We determined the age at seroconversion in children genetically at risk for type 1 diabetes.METHODS: TPOAb and TgAb seropositivity were determined in 5066 healthy children with HLA DR3 or DR4 containing
BACKGROUND: By causing inflammation and tissue damage, neutrophil extracellular traps (NETs) constitute an underlying mechanism of aspiration-induced lung injury, a major factor of the low utilization of donor lungs in lung transplantation (LTx).METHOD: To determine whether NET removal during ex vivo lung perfusion (EVLP) can restore lung function and morphology in aspiration-damaged lungs, gastri
Cardiovascular disease (CVD) remains, despite intense research, the most common cause of death world-wide. The main underlying cause of CVD is atherosclerosis, which is characterised by chronic inflammation. CVD and atherosclerosis have a complex aetiology, which necessitates research into multiple areas in order to gain insight into the pathogenesis and find novel markers that could aid in identi
