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Age-related pathological impairments in directly reprogrammed dopaminergic neurons derived from patients with idiopathic Parkinson's disease

We have developed an efficient approach to generate functional induced dopaminergic (DA) neurons from adult human dermal fibroblasts. When performing DA neuronal conversion of patient fibroblasts with idiopathic Parkinson's disease (PD), we could specifically detect disease-relevant pathology in these cells. We show that the patient-derived neurons maintain age-related properties of the donor and

A Complementary Multitechnique Approach to Assess the Bias in Molecular Weight Determination of Lignin by Derivatization-Free Gel Permeation Chromatography

The growing interest in lignin valorization in the past decades calls for analytical techniques for lignin characterization, ranging from wet chemistry techniques to highly sophisticated chromatographic and spectroscopic methods. One of the key parameters to consider is the molecular weight profile of lignin, which is routinely determined by size-exclusion chromatography; however, this is by no me

In-Flight Tuning of Au-Sn Nanoparticle Properties

Multimetallic nanoparticles possess a variety of beneficial properties with potential relevance for various applications. These metallic nanoparticles can consist of randomly ordered alloys, which retain the properties of the constituting elements, or ordered intermetallics, which possess extended properties. Depending on the desired application, specific alloys or intermetallic compounds are requ

Ganglioside Micelles Affect Amyloid β Aggregation by Coassembly

Amyloid β peptide (Aβ) is the crucial protein component of extracellular plaques in Alzheimer’s disease. The plaques also contain gangliosides lipids, which are abundant in membranes of neuronal cells and in cell-derived vesicles and exosomes. When present at concentrations above its critical micelle concentration (cmc), gangliosides can occur as mixed micelles. Here, we study the coassembly of th

Plasma levels of PRO-C3, a type III collagen synthesis marker, are associated with arterial stiffness and increased risk of cardiovascular death

Background and aims: The N-terminal propeptide of type III collagen (PRO-C3) assay measures a pro-peptide released during type III collagen synthesis, an important feature of arterial stiffening and atherogenesis. There is a clinical need for improved non-invasive, cheap and easily accessible methods for evaluating individuals at risk of cardiovascular disease (CVD). In this study, we investigate

The association of copeptin with metabolic risk markers is modified by region of origin

Iraqi born immigrants in Sweden have higher prevalence of metabolic diseases compared to native Swedes. Copeptin, a marker for vasopressin, is associated with increased risk of metabolic disease. In this cross-sectional population study based on the MEDIM cohort we investigated differences in copeptin levels between Iraqi and Swedish born individuals and if the association between copeptin and car

The C-terminal domain of the antiamyloid chaperone DNAJB6 binds to amyloid-β peptide fibrils and inhibits secondary nucleation

The DNAJB6 chaperone inhibits fibril formation of aggregation-prone client peptides through interaction with aggregated and oligomeric forms of the amyloid peptides. Here, we studied the role of its C-terminal domain (CTD) using constructs comprising either the entire CTD or the first two or all four of the CTD β-strands grafted onto a scaffold protein. Each construct was expressed as WT and as a

“You don't put it down to arthritis” : A qualitative study of the first symptoms recalled by individuals with knee osteoarthritis

Objective: As part of the first phase of the OARSI Early-stage Symptomatic Knee Osteoarthritis (EsSKOA) initiative, we explored the first symptoms and experiences recalled by individuals with knee osteoarthritis (OA). Design: This qualitative study, informed by qualitative description, was a secondary analysis of focus groups (n ​= ​17 groups) and one-on-one interviews (n ​= ​3) conducted in 91 in

Characterisation of fire smoke emissions from fire retardant wood

Fire retardants are extensively used to reduce the flammability (combustibility) of wood–based construction materials in an effort to improve fire safety of buildings. However, little is known of the composition and potential risks to human health of smoke emissions produced from combustion of fire retardant treated wood. To help understand the risk to human health, fire smoke emissions produced f

Structural characterisation of α-synuclein-membrane interactions and the resulting aggregation using small angle scattering

The presence of amyloid fibrils is a hallmark of several neurodegenerative diseases. Some amyloidogenic proteins, such as α-synuclein and amyloid β, interact with lipids, and this interaction can strongly favour the formation of amyloid fibrils. In particular the primary nucleation step, i.e. the de novo formation of amyloid fibrils, has been shown to be accelerated by lipids. However, the exact m

Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006)

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

The tumour suppressor miR-34c targets MET in prostate cancer cells.

Background:The microRNA, miR-34c, is a well-established regulator of tumour suppression. It is downregulated in most forms of cancers and inhibits malignant growth by repressing genes involved in processes such as proliferation, anti-apoptosis, stemness, and migration. We have previously reported downregulation and tumour suppressive properties for miR-34c in prostate cancer (PCa).Methods:In this

Non-hemodynamic predictors of arterial stiffness after 17 years of follow-up: the Malmö Diet and Cancer study.

Arterial stiffness plays a fundamental role in the development of hypertension and is a risk factor for both cardiovascular disease and mortality. The stiffening that occurs with increasing age has, in numerous cross-sectional studies, been shown to be associated with several cardiovascular risk factors. This observational study aims to characterize the predictive and cross-sectional markers focus

miQ - a novel microRNA based diagnostic and prognostic tool for prostate cancer.

Today, the majority of prostate tumours are detected at early stages with uncertain prognosis. Therefore, we set out to identify early predictive markers of prostate cancer with aggressive progression characteristics. We measured the expression of microRNAs (miRNA) using qRT-PCR in FFPE prostatic tissue samples from a Swedish cohort of 49 patients with prostate cancer and 25 without cancer and fou

Reproducible porous silicon protein microarrays -chip manufacturing and application to clinical biomarkers

Full 3" wafer scale fabrication of porous silicon chips (pore chip protein arrays -PCPA) is reported. The PCPA is developed for the analysis of protein molecules based on the fluorescence and MALDI-TOF MS detection. The surface porosification process allows the creation of chips with different surface geometries to control the physical properties of the matrix in a highly reproducible way.

Identification of regulators of hematopoietic stem and progenitor cells in vivo in humans using population genetics

Introduction: Understanding how hematopoietic stem- and progenitor cells (HSPCs) are regulated is of central importance for the development of new therapies for blood disorders and for regenerative medicine. Traditionally, however, HSPC regulation has been studied in model systems, and little is known about the situation in vivo in humans. Methods: To learn how HSPCs are regulated under native con

Soluble CD40 levels in plasma are associated with cardiovascular disease and in carotid plaques with a vulnerable phenotype

Background and Purpose CD40 and CD40 ligand (CD40L) are costimulatory molecules of the tumor necrosis factor receptor superfamily and well known for their involvement in inflammatory diseases: atherosclerotic mouse models with disrupted CD40 signalling develop lesions of reduced size with a more stable plaque profile. This study investigated the potential of plasma and intraplaque levels of CD40 a

Low diagnostic yield of ST elevation myocardial infarction amplitude criteria in chest pain patients at the emergency department

To evaluate the diagnostic yield of the ECG criteria for ST-elevation myocardial infarction in a large cohort of emergency department chest pain patients, and to determine whether extended ECG criteria or reciprocal ST depression can improve accuracy. Design: Observational, register-based diagnostic study on the accuracy of ECG criteria for ST-elevation myocardial infarction. Between Jan 2010 and