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Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by non-functional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to restore the resorptive function of IMO osteoclasts by lentiviral mediated gene transfer of the TCIRG1 cDNA. CD34(+) cel
The formation of amyloid fibrils by the intrinsically disordered protein alpha-synuclein is a hallmark of Parkinson disease. To characterize the microscopic steps in the mechanism of aggregation of this protein we have used in vitro aggregation assays in the presence of preformed seed fibrils to determine the molecular rate constant of fibril elongation under a range of different conditions. We sh
Global land-use change has drastic consequences for biodiversity leading to losses of ecological functioning, ecosystem services and human well-being. While species dependent on undisturbed natural habitat are most affected by conversion to agriculture, even populations of disturbance-tolerant species can be endangered in landscapes dominated by high-input mono-cultural cropping systems. This has
Objective-Obesity increases the risk of cardiovascular disease and premature death. However, not all obese subjects develop the metabolic abnormalities associated with obesity. The aim of this study was to clarify the mechanisms that induce dyslipidemia in obese subjects. Methods and Results-Stable isotope tracers were used to elucidate the pathophysiology of the dyslipidemia in hypertriglyceridem
Particle size distributions and hygroscopic growth were studied in a town in Sweden with extensive emissions from wood combustion. The average deposited fraction of particle number, surface area and volume dose in the human respiratory tract was estimated using the data set, as well as the typical deposition pattern of the two dominant particle source types: wood combustion and traffic exhaust. As
Regional climate modeling is a dynamical downscaling technique applied to the results of global climate models (GCMs) in order to acquire more information on climate simulations and climate change projections. GCMs and regional climate models (RCMs) have undergone considerable development over the past few decades, and both have increased in resolution. The higher-resolution edge of RCMs compared
In a north European context, identifying invasive species is far from trivial because the vegetation has been influenced by human activities for thousands of years. New species have immigrated continuously since the end of the last glaciation, both spontaneously and through direct or indirect help by man. Still, newly immigrated species may be problematic in a nature conservation context and may h
Background Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods In a collaborative met
The etiology of leukemias cannot entirely be explained by known risk factors, including ionizing radiation, benzene exposure, and infection with human T cell leukemia virus. A number of studies suggested that diet influences the risk of adult leukemias. However, results have been largely inconsistent. We examined the potential association between dietary factors and risk of leukemias among partici
This study investigated whether perinatal factors influenced the risk of a double diagnosis of type 1 diabetes and celiac disease.
The dynamic HIV-1 epidemic has resulted in the emergence of several different subtypes and recombinant forms that may differ in biological properties. A recombinant form of CRF02_AG and sub-subtype A3 (A3/02) was recently described based on env sequencing and associated with faster disease progression rates compared with its parental strains. Here, we performed near full-length sequencing of the A
Anthocyanidins are bioactive flavonoids with potential health-promoting effects. These may vary among single anthocyanidins considering differences in their bioavailability and some of the mechanisms involved. The aim of the present study was to estimate the dietary intake of anthocyanidins, their food sources and the lifestyle factors (sex, age, BMI, smoking status, educational level and physisic
We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100mg QD or imatinib 400mg QD and report outcome as an intention-to-treat analysis with 36months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR3.0 was reached at 3months
Pollination improves the yield of most crop species and contributes to one-third of global crop production, but comprehensive benefits including crop quality are still unknown. Hence, pollination is underestimated by international policies, which is particularly alarming in times of agricultural intensification and diminishing pollination services. In this study, exclusion experiments with strawbe
The present day global climate change is fueled by our use of fossil fuels and land use change. The already observed warming and other distinct changes in the climate system stem from these human influences and are ongoing. Due to climate system inertia, a part of the climate system's response to this historical forcing remains to manifest itself, which it will do over time. At the same time, soci
The ability of particles to activate and form cloud droplets influences the functioning of the Earth's hydrological cycle. This work links the particle water uptake at subsaturation to the critical supersaturation ratio needed for particles to become cloud condensation nuclei (CCN). Five models using the particle hygroscopic growth at subsaturation for predicting the critical supersaturation neede
Climate warming will increase the drought exposure of many forests world-wide. It is not well understood how trees adapt their hydraulic architecture to a long-term decrease in water availability. We examined 23 traits characterizing the hydraulic architecture and growth rate of branches and the dependent foliage of mature European beech (Fagus sylvatica) trees along a precipitation gradient (855-
There are inconsistent and limited data available to assess the relationship between fat intake and risk of epithelial ovarian cancer (EOC). We examined the consumption of total fat, fat sources and fat subtypes in relation to risk of EOC and its major histologic subtypes in the European Prospective Investigation into Cancer and Nutrition which includes incident invasive (n=1095) and borderline (n
