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The complement receptor C3AR constitutes a novel therapeutic target in NPM1-mutated AML

Mutated Nucleophosmin 1 (NPM1) is the most common genetic alteration in acute myeloid leukemia (AML), found in approximately 30% of cases. Although mutations in this gene are considered favorable according to current risk stratification guidelines, a large fraction of patients will suffer from relapse, demonstrating the urgent need for new treatment options. Therefore, we aimed to identify cell su

Missed Evaporation from Atmospherically Relevant Inorganic Mixtures Confounds Experimental Aerosol Studies

Sea salt aerosol particles are highly abundant in the atmosphere and play important roles in the global radiative balance. After influence from continental air, they are typically composed of Na+, Cl-, NH4+, and SO42- and organics. Analogous particle systems are often studied in laboratory settings by atomizing and drying particles from a solution. Here, we present evidence that such laboratory st

Reduced volume of diabetic pancreatic islets in rodents detected by synchrotron X-ray phase-contrast microtomography and deep learning network

The pancreatic islet is a highly structured micro-organ that produces insulin in response to rising blood glucose. Here we develop a label-free and automatic imaging approach to visualize the islets in situ in diabetic rodents by the synchrotron radiation X-ray phase-contrast microtomography (SRμCT) at the ID17 station of the European Synchrotron Radiation Facility. The large-size images (3.2 mm ×

Molecular dynamics simulations of nanometric cutting of single crystal copper sheets using a diamond tool

Nanometric cutting of a single crystal copper workpiece of different crystallographic orientations by a stiff cylindrical cubic diamond tool has been investigated by MD simulations using the freeware LAMMPS. The chip evolves during the cutting process and forms depending on crystal orientation, cutting velocity and tool geometry. It was found that no significant difference in the cutting force mag

Direct role of FLT3 in regulation of early lymphoid progenitors

Given that FLT3 expression is highly restricted on lymphoid progenitors, it is possible that the established role of FLT3 in the regulation of B and T lymphopoiesis reflects its high expression and role in regulation of lymphoid-primed multipotent progenitors (LMPPs) or common lymphoid progenitors (CLPs). We generated a Flt3 conditional knock-out (Flt3fl/fl) mouse model to address the direct role

What Do Demographics Have To Do With It? An Oaxaca-Blinder Decomposition of Changes over Time in Inequalities in Alcohol, Narcotics and Tobacco-Related Ill Health in Sweden

The purpose of this study was to document historical trends and socioeconomic inequalities in ill health outcomes related to alcohol consumption, narcotics use and tobacco smoking over the seventeen years prior to the implementation of the Swedish government’s first strategy for alcohol, narcotics, doping and tobacco (ANDT) in 2011. We also sought to explain the changes over time in terms of chang

Past forest composition, structures and processes – How paleoecology can contribute to forest conservation

The importance of long-term historical information derived from paleoecological studies has long been recognized as a fundamental aspect of effective conservation. However, there remains some uncertainty regarding the extent to which paleoecology can inform on specific issues of high conservation priority, at the scale for which conservation policy decisions often take place. Here we review to wha

ADAMTS-7 is associated with a high-risk plaque phenotype in human atherosclerosis

Several large-scale genome-wide association studies have identified single-nucleotide polymorphisms in the genomic region of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats (ADAMTS)-7 and associations to coronary artery disease. Experimental studies have provided evidence for a functional role of ADAMTS-7 in both injury-induced vascular neointima formation and development of

Fasting levels of growth hormone are associated with carotid intima media thickness but are not affected by fluvastatin treatment

Background: Growth hormone (GH) has been linked to cardiovascular disease but the exact mechanism of this association is still unclear. We here test if the fasting levels of GH are cross-sectionally associated with carotid intima media thickness (IMT) and whether treatment with fluvastatin affects the fasting level of GH. Methods: We examined the association between GH and IMT in 4425 individuals

Epidemiology of valvular heart disease in a Swedish nationwide hospital-based register study

Objective: Transitions in the spectrum of valvular heart diseases (VHDs) in developed countries over the 20th century have been reported from clinical case series, but large, contemporary population-based studies are lacking.Methods: We used nationwide registers to identify all patients with a first diagnosis of VHD at Swedish hospitals between 2003 and 2010. Age-stratified and sex-stratified inci

Interleukin 4 induces apoptosis of acute myeloid leukemia cells in a Stat6 dependent manner

Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth and survival in a cytokine screen using fluorescently labeled AML cells. RNA-sequencing of the AML cells revealed an IL4-induced upregulation of Stat6 target genes and enrichment of apopt

Circulating cadmium concentration and risk of aortic aneurysms : A nested case-control study within the Malmö Diet and Cancer cohort

Background and aims Diet and smoking expose the general population to cadmium (Cd), which is a toxic metal that accumulates in the arterial wall. In experimental studies, Cd causes reductions in proliferation of smooth muscle cells and cellular synthesis of procollagen. The aim of this study was to examine whether blood Cd levels, a valid measure of Cd exposure, are associated with increased risk

Coffee, tea and melanoma risk : findings from the European Prospective Investigation into Cancer and Nutrition

In vitro and animal studies suggest that bioactive constituents of coffee and tea may have anticarcinogenic effects against cutaneous melanoma; however, epidemiological evidence is limited to date. We examined the relationships between coffee (total, caffeinated or decaffeinated) and tea consumption and risk of melanoma in the European Prospective Investigation into Cancer and Nutrition (EPIC). EP

The reconstruction of past forest dynamics over the last 13,500 years in SW Sweden

Evidence for unbroken continuity of tree taxa over the last c. 13,500 years is presented from a biodiversity ‘hotspot’ nature reserve in south-west Sweden.Forest composition, continuity, fire and disturbance events are reconstructed using palaeoecological methods. A lake record reveals that Pinus sylvestris,Betula spp., Salix spp., Populus tremula and Hippophae rhamnoides were the initial trees sc

Construction of Adaptive Multistep Methods for Problems with Discontinuities, Invariants, and Constraints

The wide variety of physical phenomena, such as motion of objects, reaction among chemical substances, electricity flow in a circuit can be described by equations with quantities that vary along time.The rate at which a quantity is changing with respect to its independent variable (time), is represented by its derivative. Thus, these phenomena are modeled by equations with differential variables tAdaptive multistep methods have been widely used to solve initial value problems. These ordinary differential equations (ODEs) may arise from semi-discretization of time-dependent partial differential equations(PDEs) or may combine with some algebraic equations to represent a differential algebraic equations (DAEs).In this thesis we study the initialization of multistep methods and parametrize som

Preserved function of afferent parvalbumin-positive perisomatic inhibitory synapses of dentate granule cells in rapidly kindled mice

Parvalbumin- (PV-) containing basket cells constitute perisomatic GABAergic inhibitory interneurons innervating principal cells at perisomatic area, a strategic location that allows them to efficiently control the output and synchronize oscillatory activity at gamma frequency (30–90 Hz) oscillations. This oscillatory activity can convert into higher frequency epileptiform activity, and therefore c

The calcium channel subunit gamma-4 is regulated by MafA and necessary for pancreatic beta-cell specification

Voltage-gated Ca2+ (CaV) channels trigger glucose-induced insulin secretion in pancreatic beta-cell and their dysfunction increases diabetes risk. These heteromeric complexes include the main subunit alpha1, and the accessory ones, including subunit gamma that remains unexplored. Here, we demonstrate that CaV gamma subunit 4 (CaVγ4) is downregulated in islets from human donors with diabetes, diabe