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A new genetic tool to improve immune-compromised mouse models : Derivation and CRISPR/Cas9-mediated targeting of NRG embryonic stem cell lines

Development of human hematopoietic stem cells and differentiation of embryonic stem (ES) cells/induced pluripotent stem (iPS) cells to hematopoietic stem cells are poorly understood. NOD (Non-obese diabetic)-derived mouse strains, such as NSG (NOD-Scid-il2Rg) or NRG (NOD-Rag1-il2Rg), are the best available models for studying the function of fetal and adult human hematopoietic cells as well as ES/

Transcription Factor-Forced Astrocytic Differentiation Impairs Human Glioblastoma Growth In Vitro and In Vivo

Direct cellular reprogramming has recently gained attention of cancer researchers for the possibility to convert undifferentiated cancer cells into more differentiated, postmitotic cell types. While a few studies have attempted reprogramming of glioblastoma (GBM) cells toward a neuronal fate, this approach has not yet been used to induce differentiation into other lineages and in vivo data on redu

Charge Regulation during Amyloid Formation of α-Synuclein

Electrostatic interactions play crucial roles in protein function. Measuring pKa value perturbations upon complex formation or self-assembly of e.g. amyloid fibrils gives valuable information about the effect of electrostatic interactions in those processes. Site-specific pKa value determination by solution NMR spectroscopy is challenged by the high molecular weight of amyloid fibrils. Here we rep

Preheart failure comorbidities and impact on prognosis in heart failure patients : a nationwide study

Background: Data regarding the impact of preheart failure (HF) comorbidities on the prognosis of HF are scarce, especially in the younger HF patients. Objectives: To investigate pre-existing comorbidities in HF patients versus matched controls and to assess their impact on mortality. Methods: We included all first-time in-hospital and outpatient diagnoses of HF from 1995 to 2017, and comorbidities

Incidence of Ischemic Stroke in Individuals with and without Aortic Valve Stenosis : A Danish Retrospective Cohort Study

Background and Purpose - Aortic valve stenosis may lead to atrial and ventricular remodeling, predisposes to atrial fibrillation, and may also be an independent risk factor of ischemic stroke. However, information on stroke rates among persons with aortic valve stenosis are sparse. We aimed to determine the incidence rates and relative risks of ischemic stroke in individuals with diagnosed aortic

Two-Step Acoustophoresis Separation of Live Tumor Cells from Whole Blood

There is an unmet clinical need to extract living circulating tumor cells (CTCs) for functional studies and in vitro expansion to enable drug testing and predict responses to therapy in metastatic cancer. Here, we present a novel two-step acoustophoresis (A2) method for isolation of unfixed, viable cancer cells from red blood cell (RBC) lysed whole blood. The A2 method uses an initial acoustofluid

Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study

Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) often co-occur. Defining causal pathways underlying this relationship may help optimize the prevention and treatment of both diseases. Thus, we assessed the strength and magnitude of the putative causal pathways linking dysglycemia and fatty liver, using a combination of causal inference methods.Measures of glycemia, insulin dynam

Simultaneous determination of folate and methotrexate metabolites in serum by LC-MS/MS during high-dose methotrexate therapy

High-dose methotrexate (HDMTX) is a central component in the treatment of acute lymphoblastic leukemia, osteosarcoma, and some lymphomas and brain tumors. MTX is given at lethal doses and then is followed by rescue treatment with folinic acid (FA). Despite FA rescue, many patients suffer severe toxicity. The pharmacokinetics of FA rescue have not been sufficiently studied. However, optimization of

Resonant X-ray photo-oxidation of light-harvesting iron (II/III) N-heterocyclic carbene complexes

Two photoactive iron N-heterocyclic carbene complexes [FeII(btz)2(bpy)]2+ and [FeIII(btz)3]3+, where btz is 3,3’-dimethyl-1,1’-bis(p-tolyl)-4,4’-bis(1,2,3-triazol-5-ylidene) and bpy is 2,2’-bipyridine, have been investigated by Resonant Photoelectron Spectroscopy (RPES). Tuning the incident X-ray photon energy to match core-valence excitations provides a site specific probe of the electronic struc

In situ assembly of an injectable cardiac stimulator

Without intervention, cardiac arrhythmias pose a risk of fatality. However, timely intervention can be challenging in environments where transporting a large, heavy defibrillator is impractical, or emergency surgery to implant cardiac stimulation devices is not feasible. Here, we introduce an injectable cardiac stimulator, a syringe loaded with a nanoparticle solution comprising a conductive polym

Tribology and airborne particle emissions from grey cast iron and WC reinforced laser cladded brake discs

Laser cladding (LC) is a promising technique to overlay a protective coating on grey cast iron (GCI) brake discs to enhance the wear and corrosion resistance. This study utilized a pin-on-disc tribometer in an aerosol chamber to investigate the tribology and airborne particle emissions from tungsten carbides (WC) reinforced coating overlayed onto GCI substrate through laser cladding. Uncoated GCI

Accelerometer-based physical activity is associated with the gut microbiota in 8416 individuals in SCAPIS

Background: Previous population-based studies investigating the relationship between physical activity and the gut microbiota have relied on self-reported activity, prone to reporting bias. Here, we investigated the associations of accelerometer-based sedentary (SED), moderate-intensity (MPA), and vigorous-intensity (VPA) physical activity with the gut microbiota using cross-sectional data from th

COVID-19 vaccine uptake in Skåne county, Sweden, in relation to individual-level and area-level sociodemographic factors: a register-based cross-sectional analysis

Objectives Better understanding of societal factors associated with COVID-19 vaccination can have important implications for public health policy to increase uptake.Methods This study investigated sociodemographic determinants of COVID-19 vaccine uptake with ≥2 doses vs 0 doses, and ≥3 doses vs 2 doses, among adults (≥18 years) in a general population from Sweden followed from 27 December 2020 (n=

The association between water intake and future cardiometabolic disease outcomes in the Malmö Diet and Cancer cardiovascular cohort

The aim of this study was to explore the longitudinal association between reported baseline water intake and incidence of coronary artery disease (CAD) and type 2 diabetes in the Malmö Diet and Cancer Cohort (n = 25,369). Using cox proportional hazards models, we separately modelled the effect of plain and total (all water, including from food) water on CAD and type 2 diabetes risk, whilst adjusti

Assessment of sediment sampling techniques for ESS environmental monitoring programme

Radionuclides released and discharged into the environment from nuclear and other radiation-related facilities, such as the European Spallation Source (ESS), may accumulate in aquatic bottom sediments. Sediments should therefore, as recommended by the IAEA, be monitored regularly. This report describes the setting up of a methodology for zero-point assessments of the radiation levels in sediments

GPR162 is a beta cell CART receptor

Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells and neuronal elements. We have previously established insulinotropic actions of CART in human and rodent islets. The receptor for CART in the pancreatic beta cells is unidentified. We used RNA sequencing of Cartpt knockdown (KD) INS-1 832/13 cells and identified GPR162 as the most Cartpt-regulated receptor.

Microbially Produced Imidazole Propionate Is Associated With Heart Failure and Mortality

Background: Over the past years, it has become clear that the microbial ecosystem in the gut has a profound capacity to interact with the host through the production of a wide range of bioactive metabolites. The microbially produced metabolite imidazole propionate (ImP) is clinically and mechanistically linked with insulin resistance and type 2 diabetes, but it is unclear how ImP is associated wit

Tipping point in α-synuclein-membrane interactions from stable protein-covered vesicles to amyloid aggregation

α-synuclein is a neuronal protein implicated in neurotransmitter release. Its function is thought to critically depend on the dynamic equilibrium between its free and its membrane-bound state. α-synuclein amyloid formation, implicated in Parkinson's disease, is also modulated by lipid membranes. The interplay between these processes remains elusive yet relates to the outstanding question of what d

Predicting troponin biomarker elevation from electrocardiograms using a deep neural network

Background Elevated troponin levels are a sensitive biomarker for cardiac injury. The quick and reliable prediction of troponin elevation for patients with chest pain from readily available ECGs may pose a valuable time-saving diagnostic tool during decision-making concerning this patient population. Methods and results The data used included 15 856 ECGs from patients presenting to the emergency r