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The molecular mechanisms regulating key fate decisions of hematopoietic stem cells (HSCs) remain incompletely understood. Here, we targeted global shRNA libraries to primary human hematopoietic stem and progenitor cells (HSPCs) to screen for modifiers of self-renewal and differentiation, and identified metastasis-associated 1 (MTA1) as a negative regulator of human HSPC propagation in vitro. Knock
BACKGROUND Exome sequencing in hundreds of thousands of persons may enable the identification of rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for the discovery of new therapeutic targets. METHODS We performed a multistage exome sequencing and genetic association analysis to identify genes in which rare protein-coding
This is the final report of a three-year project called Building Egressibility in an Ageing Society, sponsored by the Swedish research council for sustainable development (FORMAS). While accessibility is an established and widely used concept in building design, the evacuation of people with functional limitations is still at a stage in which several research gaps exist. In this context, this work
The mechanisms leading to the occurrence of extreme weather and climate events are varied and complex. They generally encompass a combination of dynamic and thermodynamic processes, as well as drivers external to the climate system, such as anthropogenic greenhouse gas emissions and land use change. Here we present the ExtremeX multi-model intercomparison experiment, which was designed to investig
The genetic background of Growth Hormone (GH) secretion is not well understood. Mutations giving rise to a stop codon have a high likelihood of affecting protein function.
Uncultivated field margins are one of the most frequent non-crop habitat types in contemporary, highintensity agricultural landscapes and may therefore be important for the persistence of many farmland species. Managing field margins in a way that preserves, and preferably enhances, their value for biodiversity is therefore important. In the present study, we evaluate how the flora of uncultivated
It has been proposed that vascular progenitor cells play an important role in vascular repair, but their possible clinical importance in cardiovascular disease has not been fully characterized. Vascular endothelial growth factor A, placental growth factor and stem cell factor (SCF) are three growth factors that are important in recruiting vascular progenitor cells. In this study, we investigated t
The inflammatory mediator procalcitonin (PCT) has previously been associated with prognosis in myocardial infarction, cancer and sepsis patients. The importance of PCT in the general population is currently unknown. Our aim was to assess the relationship between plasma PCT and the risk of all-cause and cause-specific mortality in apparently healthy individuals with no previous history of cardiovas
Resolving challenges related to the sustainability of natural capital and ecosystem services is an urgent issue. No roadmap on reaching sustainability exists; and the kind of sustainable land use required in a world that acknowledges both multiple environmental boundaries and local human well-being presents a quandary. In this commentary, we argue that a new globally consistent and expandable syst
Accumulated carbon uptake, apparent quantum yield (AQY) and light-saturated net CO2 assimilation (A(sat)) were used to assess the responses of photosynthesis to environmental conditions during spring for three consecutive years. Whole-tree chambers were used to expose 40-year-old field-grown Norway spruce trees in northern Sweden to an elevated atmospheric CO2 concentration, [CO2], of 700 mu mol C
Many studies have found close relationships between accessibility and various socio-economic indicators. Yet, since accessibility tends to have differentiated effects, both socially and spatially, there is a need for a model which allows for a disaggregated analysis of accessibility. The model should be possible to use in areas where road network data is incomplete. In this paper such an accessibi
The observational relationship between obesity and periodontitis is widely known, yet causal evidence is lacking. Our objective was to investigate causal associations between periodontitis and body mass index (BMI).
Recent Genome-Wide Association Studies (GWAS) have pinpointed different single nucleotide polymorphisms consistently associated with blood pressure (BP) and hypertension prevalence. However, little data exist regarding single nucleotide polymorphisms predicting BP variation over time and hypertension incidence. The aim of this study was to confirm the association of a genetic risk score (GRS), bas
OBJECTIVE: Cystatin C is a novel marker of cardiovascular disease (CVD), however the underlying mechanisms remain unclear. Here, we prospectively investigated whether plasma levels of cystatin C predict new-onset metabolic syndrome (MetS) as well as long-term progression and incidence of the different components of the MetS. METHODS: Cystatin C was measured in 1502 individuals included in the Malm
The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and typ
OBJECTIVE/BACKGROUND: There is limited information regarding outcome in patients not available for revascularisation. Our aim was to identify factors related to ulcer healing in diabetic patients with severe peripheral arterial disease who were not available for revascularisation. METHODS: Diabetic patients with a foot ulcer, consecutively presenting at a multidisciplinary foot centre with systoli
Rupture of atherosclerotic plaques is the major cause of acute coronary events (CEs). Plaque destabilization is the consequence of an imbalance between inflammatory-driven degradation of fibrous tissue and smooth muscle cell-dependent tissue repair. Proinflammatory factors have been documented extensively as biomarkers of cardiovascular risk but factors that contribute to stabilization of atherosc
BACKGROUND: CYP2J2 is responsible for the production of 5,6 8,9 11,12 and 14,15-epoxyeicosatrienoic acids, vasodilator and anti-inflammatory substances. It is abundantly expressed in human heart and also present in kidney and vasculature. Carriers of a common polymorphism, the CYP2J2-50G>T, rs890293, have reduced expression of CYP2J2 mRNA level in the heart putatively through the interference with
1. The rising levels of atmospheric carbon dioxide concentration ([CO2]) and temperature have the potential to substantially affect the terrestrial water and energy balance by altering the stomatal conductance and transpiration of trees. 2. Many models assume decreases in stomatal conductance and plant water use under rising [CO2], which has been used as a plausible explanation for the positive g
