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Fluorescence microscopy studies of interactions between monomeric α-Synuclein and lipid membranes

α-Synuclein (α-Syn), is an intrinsically disordered protein present in the substantia nigra part of the brain. α-Syn is commonly known to associate with lipid membranes containing anionic lipids. Hence, the protein is hypothesized to be involved in the vesicle trafficking at the synapses, but there are yet many unanswered questions regarding the full physiological role of the protein. During the d

Photo-Induced Cross-Linking of Unmodified α-Synuclein Oligomers

Photo-induced cross-linking of unmodified proteins (PICUP) has been used in the past to study size distributions of protein assemblies. PICUP may, for example, overcome the significant experimental challenges related to the transient nature, heterogeneity, and low concentration of amyloid protein oligomers relative to monomeric and fibrillar species. In the current study, a reaction chamber was de

A randomized trial involving a multifunctional diet reveals systematic lipid remodeling and improvements in cardiometabolic risk factors in middle aged to aged adults

BACKGROUND: A multifunctional diet (MFD) combining foods and ingredients with proven functional properties, such as fatty fish and fiber-rich foods, among others, was developed and shown to markedly reduce cardiometabolic risk-associated factors.OBJECTIVE: Here, we aim at examining metabolic physiological changes associated with these improvements.METHODS: Adult overweight individuals without othe

Microvesicles in plasma reflect coronary flow reserve in patients with cardiovascular disease

High levels of microvesicles (MVs), a type of extracellular vesicles, are detected in several pathological conditions. We investigated the connection between coronary flow reserve (CFR), a prognostic clinical parameter that reflects blood flow in the heart, with levels of MVs and their cargo, from plasma of patients with cardiovascular disease. The PROFLOW study consists of 220 patients with prior

Surveillance of COVID-19 vaccine effectiveness : A real-time case-control study in southern Sweden

The extensive register infrastructure available for coronavirus disease 2019 surveillance in Scania county, Sweden, makes it possible to classify individual cases with respect to hospitalisation and disease severity, stratify on time since last dose and demographic factors, account for prior infection and extract data for population controls automatically. In the present study, we developed a case

Pre-Treatment Integrase Inhibitor Resistance and Natural Polymorphisms among HIV-1 Subtype C Infected Patients in Ethiopia

Dolutegravir-based antiretroviral therapy (ART) has been scaled up in many developing countries, including Ethiopia. However, subtype-dependent polymorphic differences might influence the occurrence of HIV-drug-resistance mutations (HIVDRMs). We analyzed the prevalence of pre-treatment integrase strand transfer inhibitor (INSTI) HIVDRMs and naturally occurring polymorphisms (NOPs) of the integrase

Human Embryonic Stem Cell-Derived Dopaminergic Grafts Alleviate L-DOPA Induced Dyskinesia

BACKGROUND: First-in-human studies to test the efficacy and safety of human embryonic stem cells (hESC)-derived dopaminergic cells in the treatment of Parkinson's disease (PD) are imminent. Pre-clinical studies using hESC-derived dopamine neuron transplants in rat models have indicated that the benefits parallel those shown with fetal tissue but have thus far failed to consider how ongoing L-DOPA

Schlafen2 is a regulator of quiescence in adult murine hematopoietic stem cells

Even though hematopoietic stem cells (HSC) are characterized by their ability to self-renew and differentiate, they primarily reside in quiescence. Despite the immense importance of this quiescent state, its maintenance and regulation is still incompletely understood. Schlafen2 (Slfn2) is a cytoplasmic protein known to be involved in cell proliferation, differentiation, quiescence, interferon resp

Regulome analysis in B-acute lymphoblastic leukemia exposes Core Binding Factor addiction as a therapeutic vulnerability

The ETV6-RUNX1 onco-fusion arises in utero, initiating a clinically silent pre-leukemic state associated with the development of pediatric B-acute lymphoblastic leukemia (B-ALL). We characterize the ETV6-RUNX1 regulome by integrating chromatin immunoprecipitation- and RNA-sequencing and show that ETV6-RUNX1 functions primarily through competition for RUNX1 binding sites and transcriptional repress

The T-type calcium channel CaV3.2 regulates insulin secretion in the pancreatic β-cell

Voltage-gated Ca2+ (CaV) channel dysfunction leads to impaired glucose-stimulated insulin secretion in pancreatic β-cells and contributes to the development of type-2 diabetes (T2D). The role of the low-voltage gated T-type CaV channels in β-cells remains obscure. Here we have measured the global expression of T-type CaV3.2 channels in human islets and found that gene expression of CACNA1H, encodi

Post-covid medical complaints following infection with SARS-CoV-2 Omicron vs Delta variants

The SARS-CoV-2 Omicron (B.1.1.529) variant has been associated with lesssevere acute disease, however, concerns remain as to whether long-termcomplaints persist to a similar extent as for earlier variants. Studying 1 323 145persons aged 18-70 years living in Norway with and without SARS-CoV-2infection in a prospective cohort study, we found that individuals infected withOmicron had a similar risk

Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery

Stem cell therapies for Parkinson’s disease (PD) have entered first-in-human clinical trials using a set of technically related methods to produce mesencephalic dopamine (mDA) neurons from human pluripotent stem cells (hPSCs). Here, we outline an approach for high-yield derivation of mDA neurons that principally differs from alternative technologies by utilizing retinoic acid (RA) signaling, inste

Striatal hand deformities in Parkinson's disease - hand surgical perspectives

BackgroundThe knowledge about striatal hand deformities (SHD) in Parkinson’s disease (PD), has recently increased but need more attention due to their early impact on dexterity. The focus of clinical studies has been on the staging of SHD severity and neurological features. However, a hand surgical perspective has not been considered.ObjectivesOur purpose was to examine SHD in patients with PD usi

Inverted CD8 T-Cell Exhaustion and Co-Stimulation Marker Balance Differentiate Aviremic HIV-2-Infected From Seronegative Individuals

HIV-2 is less pathogenic compared to HIV-1. Still, disease progression may develop in aviremic HIV-2 infection, but the driving forces and mechanisms behind such development are unclear. Here, we aimed to reveal the immunophenotypic pattern associated with CD8 T-cell pathology in HIV-2 infection, in relation to viremia and markers of disease progression. The relationships between pathological diff

Investigating the causal relationships between excess adiposity and cardiometabolic health in men and women

AIMS/HYPOTHESIS: Excess adiposity is differentially associated with increased risk of cardiometabolic disease in men and women, according to observational studies. Causal inference studies largely assume a linear relationship between BMI and cardiometabolic outcomes, which may not be the case. In this study, we investigated the shapes of the causal relationships between BMI and cardiometabolic dis

Circulating triglycerides are associated with human adipose tissue DNA methylation of genes linked to metabolic disease

Dysregulation of circulating lipids is a central element for the metabolic syndrome. However, it is not well established whether human subcutaneous adipose tissue is affected by or affect circulating lipids through epigenetic mechanisms. Hence, our aim was to investigate the association between circulating lipids and DNA methylation levels in human adipose tissue. DNA methylation and gene expressi