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The possibility to manufacture hematopoietic stem cells (HSCs) in the laboratory would provide an indefinite source of cells for patients requiring bone marrow transplantation. Moreover, combined with the progress in gene editing techniques, it would provide a novel platform for gene and cell replacement therapies for a range of currently incurable congenic and acquired disorders. During my PhD, I
Systemic lupus erythematosus (SLE) is a severe chronic inflammatory autoimmune connective tissue disease. Despite major efforts, SLE remains a poorly understood disease with unpredictable course, unknown etiology and complex pathogenesis. Apoptosis combined with deficiency in clearing apoptotic cells is an important etiopathogenic event in SLE, which could contribute to the increased load of poten
Background: It has been observed that mice lacking the sulfatase modifying factor (Sumf1) developed an emphysema-like phenotype. However, it is unknown if SUMF1 may play a role in Chronic Obstructive Pulmonary Disease (COPD) in humans. The aim was to investigate if the expression and genetic regulation of SUMF1 differs between smokers with and without COPD. Methods: SUMF1 mRNA was investigated in
The aggregation of the amyloid β peptide (Aβ42), which is linked to Alzheimer's disease, can be altered significantly by modulations of the peptide's intermolecular electrostatic interactions. Variations in sequence and solution conditions have been found to lead to highly variable aggregation behaviour. Here we modulate systematically the electrostatic interactions governing the aggregation kinet
Having previously demonstrated that in-patients referred to neurology at two UK hospitals were not fully examined prior to referral, we designed an audit with 80% power to detect a 10% increase in tendon hammer or ophthalmoscope use following an educational intervention. In-patients referred to neurology over a 4 month period in the UK, Jordan, Sweden and the United Arab Emirates were asked whethe
Objective. The aims of this study were to evaluate whether treatment with tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) affects the risk of developing severe extraarticular rheumatoid arthritis (ExRA) manifestations and to investigate potential predictors for developing ExRA. Methods. A dynamic community-based cohort of patients with RA was studied (n = 1977). C
The coaggregation of the amyloid-β peptide (Aβ) and α-synuclein is commonly observed in a range of neurodegenerative disorders, including Alzheimer’s and Parkinson’s diseases. The complex interplay between Aβ and α-synuclein has led to seemingly contradictory results on whether α-synuclein promotes or inhibits Aβ aggregation. Here, we show how these conflicts can be rationalized and resolved by de
Aims: Epidemiological evidence indicates a protective effect of light to moderate alcohol consumption compared to non-drinking and heavy drinking. Although several mechanisms have been suggested, the effect of alcohol on atherosclerotic changes in vessel walls is unclear. Therefore, we explored the relationship between alcohol consumption and common carotid intima media thickness, a marker of earl
Human pluripotent stem cells (PSCs) are widely used for studying embryonic development, disease modelling, drug discovery and cell therapy development. Using human PSCs as a model has significantly contributed to our understanding of embryonic development and elucidating novel pathological mechanisms as well as developing new drugs. However, there are significant genetic and epigenetic variations
The concept that tumor-initiating cells can co-opt the self-renewal program of endogenous stem cells as a means of enforcing their unlimited proliferative potential is widely accepted, yet identification of specific factors that regulate self-renewal of normal and cancer stem cells remains limited. Using a comparative transcriptomic approach, we identify ZNF521/Zfp521 as a conserved hematopoietic
Hematopoiesis is defined as the ongoing production of blood cells. As most mature blood cells are relatively short-lived and require continuous replacement, hematopoiesis is characterized by an extraordinary turnover rate with production of trillions of new blood cells every day. To cope with the enormous proliferation required to generate sufficient numbers of blood cells to maintain homeostasis,
We present an experimental method including error analysis for the measurement of the density and compressibility of cells and microbeads; these being the two central material properties in ultrasound-based acoustophoretic applications such as particle separation, trapping, and up-concentration. The density of the microparticles is determined by using a neutrally buoyant selection process that inv
Secondary nucleation of monomers on the surface of an already existing aggregate that is formed from the same kind of monomers may lead to autocatalytic amplification of a self-assembly process. Such monomer-dependent secondary nucleation occurs during the crystallization of small molecules or proteins and self-assembled materials, as well as in protein self-assembly into fibrous structures. Indic
Quantitative soil mineralogy has been identified as a key factor influencing PROFILE weathering estimates, and is often calculated with normative methods, such as the “Analysis to Mineralogy” (‘A2M’) model. In Sweden and other countries, there is a large request for accurate base cation weathering estimates in order to establish how sustainable harvest of biomass should be performed in the future.
A mechanistic understanding of Aβ aggregation and high-resolution structures of Aβ fibrils and oligomers are vital to elucidating relevant details of neurodegeneration in Alzheimer's disease, which will facilitate the rational design of diagnostic and therapeutic protocols. The most detailed and reproducible insights into structure and kinetics have been achieved using Aβ peptides produced by reco
RNA architectonics offers the possibility to design and assemble RNA into specific shapes, such as nanoscale 3D solids or nanogrids. Combining the minute size of these programmable shapes with precise positioning on a surface further enhances their potential as building blocks in nanotechnology and nanomedicine. Here we describe a bottom-up approach to direct the arrangement of nucleic acid nanost
Background: Whether age at onset influences Alzheimer's disease (AD) progression and the effectiveness of cholinesterase inhibitor (ChEI) therapy is not clear. We aimed to compare longitudinal cognitive and global outcomes in ChEI-treated patients with early-onset Alzheimer's disease (EOAD) versus late-onset Alzheimer's disease (LOAD) in clinical practice. Methods: This 3-year, prospective, observ
Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with
There has been much interest recently in the relationship between economic conditions and mortality, with some studies showing that mortality is pro-cyclical, while others find the opposite. Some suggest that the aggregation level of analysis (e.g. individual vs. regional) matters. We use both individual and aggregated data on a sample of 20-64 year-old Swedish men from 1993 to 2007. Our results s
There has been much interest recently in the relationship between economic conditions and mortality, with some studies showing that mortality is pro-cyclical, while others find the opposite. Some suggest that the aggregation level of analysis (e.g. individual vs. regional) matters. We use both individual and aggregated data on a sample of 20–64 year-old Swedish men from 1993 to 2007. Our results s
