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This study evaluates a clinically applicable lentiviral vector for treatment of Gaucher disease type 1. Hematopoietic stem cells transduced with the vector and transplanted into a mouse model successfully halted or reversed pathology. These data were used as proof-of-concept for regulatory filing enabling the commencement of an international phase 1/2 clinical trial.
Malfunction and amyloid formation of the Islet Amyloid Polypeptide (IAPP) are factors contributing to Type 2 diabetes. Unravelling the mechanism of IAPP aggregate formation may forward our understanding of this process and its effect on pancreatic β-islet cell. Such mechanistic studies require access to sequence homogeneous and highly pure IAPP. Here we present a new facile protocol for the produc
BRAF inhibitors (BRAFi) selectively target oncogenic BRAFV600E/K and are effective in 80% of advanced cutaneous malignant melanoma cases carrying the V600 mutation. However, the development of drug resistance limits their clinical efficacy. Better characterization of the underlying molecular processes is needed to further improve treatments. We previously demonstrated that transcription of PTEN is
Image-based analysis of breast tumour growth rate may help optimize breast cancer screening and diagnosis. It may improve the identification of aggressive tumours and suggest optimal screening intervals. Virtual clinical trial (VCT) is a simulation-based method used to evaluate and optimize medical imaging systems and design clinical trials. Our work is motivated by desire to simulate multiple scr
Aim: Statins lower cholesterol and reduce the risk of cardiovascular disease. However, the exact mechanisms of statins remain unknown. We investigated whether statin therapy associates with epigenetics in Type 2 diabetes (T2D) patients. Materials & methods: DNA methylation was analyzed in blood from newly diagnosed T2D patients in All New Diabetics in Scania (ANDIS) and a replication cohort Al
Peptides and proteins have evolved to self-assemble into supramolecular entities through a set of non-covalent interactions. Such structures and materials provide the functional basis of life. Crucially, biomolecular assembly processes can be highly sensitive to and modulated by environmental conditions, including temperature, light, ionic strength and pH, providing the inspiration for the develop
(1) Background: Methyl-group donors (MGDs), including folate, choline, betaine, and methionine, may influence breast cancer (BC) risk through their role in one-carbon metabolism; (2) Methods: We studied the relationship between dietary intakes of MGDs and BC risk, adopting data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort; (3) Results: 318,686 pre-and postmen
Low-grade inflammation and arterial stiffness are key factors in the development of vascular aging. However, the interplay between arterial stiffness and inflammation for cardiovascular (CV) disease is unclear. Aortic pulse wave velocity (aPWV) and the inflammatory markers, high-sensitivity C-reactive protein (CRP) and orosomucoid, were measured in 2710 participants (median age: 72 years). These p
OBJECTIVES: To identify variables associated with longitudinal change in meniscal extrusion, which might be used as possible targets for knee osteoarthritis (KOA) prevention. METHODS: In a high-risk population of middle-aged overweight women, meniscal extrusion was assessed with magnetic resonance imaging (1.5 T, coronal proton density, in-plane resolution 0.5 mm2, Sante DICOM Editor) at baseline
Mesenchymal cells are important components of specified niches in the lung, and can mediate a wide range of processes including tissue regeneration and repair. Dysregulation of these processes can lead to improper remodeling of tissue as observed in several lung diseases. The mesenchymal cells responsible remain poorly described, partially due to the heterogenic nature of the mesenchymal compartme
α-synuclein is an intrinsically disordered protein implicated in synaptic vesicle trafficking at the synapse. Accumulation of α-synuclein in the form of amyloid deposits coincides with the loss of dopaminergic neurons in Parkinsons disease. These deposits, referred to as Lewy Bodies, have been shown to contain membrane lipids together with the α-synuclein amyloid fibrils and other proteins. It was
BACKGROUND: Prospective and detailed investigations of smoking and prostate cancer (PCa) risk and death are lacking.OBJECTIVE: To investigate prediagnosis smoking habit (status, intensity, duration, and cessation) as a risk factor, on its own and combined with body mass index (BMI), for PCa incidence and death.DESIGN, SETTING, AND PARTICIPANTS: We included 351448 men with smoking information from
Lead has traditionally been added to brass alloys to achieve high machinability, but the exact mechanisms at work are still debated. Lead-free brass alternatives could be developed if these mechanisms were better understood. Accordingly, machinability characteristics were investigated for two brass alloys with similar mechanical properties and phase composition, but with very different machining c
The seasonal timing of moult in migratory birds is an adaptation to cope with time constraints in the annual cycle. Kiat and Izhaki analysed moult patterns in Palaearctic passerines and rejected the proposition that seasonally divided moult is an endogenously controlled strategy. Instead, they advocated the view that it occurs due to a flexible and opportunistic timing of moult. In contrast, we ar
cBN-based materials are well known for their high chemical inertness and high performance. The variation of binder phase type and amount enable improvement of performance even more. Comprehensive investigation of the influence of type of niobium compound (NbC and NbN) as a binder phase for cBN-based materials were done. Samples were prepared by high pressure high temperature (HPHT) sintering under
