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Chiral Selectivity of Secondary Nucleation in Amyloid Fibril Propagation

Chirality is a fundamental feature of asymmetric molecules and of critical importance for intermolecular interactions. The growth of amyloid fibrils displays a strong enantioselectivity, which is manifested as elongation through the addition of monomers of the same, but not opposite, chirality as the parent aggregate. Here we ask whether also secondary nucleation on the surface of amyloid fibrils,

Type 2 diabetes burden among migrants in Europe : unravelling the causal pathways

European populations are ethnically and culturally diverse due to international migration. Evidence indicates large ethnic inequalities in the prevalence of type 2 diabetes. This review discusses the burden of type 2 diabetes and its related complications, and the potential explanatory mechanisms among migrants in Europe. The current available data suggest that the rate of type 2 diabetes is highe

Rapid and facile purification of apolipoprotein A-I from human plasma using thermoresponsive nanoparticles

Nanoparticles can be used to purify proteins from plasma. We report here the purification of apolipoprotein A-I (apoA-I) with high specificity from human plasma using copolymeric nanoparticles. We present an optimized protocol using 50:50 NiPAM:BAM copolymer nanoparticles with thermo-responsive properties as an affinity resin. Repeated pelleting and washing of nanoparticle-captured apoA-I is achie

Standardization of disaster risk management - Challenges and opportunities

This chapter discusses the question of whether increasing the level of standardization in a disaster risk management system will increase its effectiveness. Based on the results from several studies conducted in the context of the Swedish disaster risk management system, the authors argue that there are both positive and negative effects of increased standardization. More precisely, studies based

Calmodulin complexes with brain and muscle creatine kinase peptides

Calmodulin (CaM) is a ubiquitous Ca2+ sensing protein that binds to and modulates numerous target proteins and enzymes during cellular signaling processes. A large number of CaM-target complexes have been identified and structurally characterized, revealing a wide diversity of CaM-binding modes. A newly identified target is creatine kinase (CK), a central enzyme in cellular energy homeostasis. Thi

Elucidating causal effects of type 2 diabetes on ischemic heart disease from observational data on middle-aged Swedish women : a triangular analytical approach

The association between type 2 diabetes (T2D) and ischemic heart disease (IHD) is well established but the potential causal association needs further studying. In an attempt to elucidate the causal effect of T2D on IHD, we used three different analytical approaches in two different datasets. A well-defined cohort of 6047 women aged 50–59 years were included at baseline (1995 to 2000) and followed

Investigation on residual stress evolution in nickel-based alloy affected by multiple cutting operations

Machining-induced residual stresses in a part can significantly influence its performance and service time. It is common that the final surface of the part is produced after multiple cuts in the machining process. In multiple cuts, the previous cuts could often generate accumulated strain/stress and temperature on the part surface. These accumulated strain/stress and temperature will be brought to

Organizational and social work environment factors, occupational balance and no or negligible stress symptoms among Swedish principals - a cross-sectional study

BACKGROUND: Few studies have assessed the mental health of principals, or studied associations with both organizational and social work environment factors and occupational balance. The purpose of the present study was therefore to investigate associations between supporting and demanding organizational and social work environment factors, occupational balance and stress symptoms in principals.MET

The use of methadone in pediatric cancer pain - a retrospective study from a governmental cancer center in India

Background: The management of cancer-related pain relies on access to opioids. When regular opioids are not tolerated, or are insufficient, methadone is an affordable and effective analgesic. Aim: The aim of the project was to describe the pattern of use and clinical experience of methadone in pediatric cancer pain at a governmental cancer hospital in Hyderabad, one of the four Indian cancer cente

COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19) : a structured summary of a study protocol for a randomised controlled trial

Objectives: The main goal of the COVIDENZA trial is to evaluate if inhibition of testosterone signalling by enzalutamide can improve the outcome of patients hospitalised for COVID-19. The hypothesis is based on the observation that the majority of patients in need of intensive care are male, and the connection between androgen receptor signalling and expression of TMPRSS2, an enzyme important for

Airspace Dimension Assessment (AiDA) by inhaled nanoparticles: benchmarking with hyperpolarised 129Xe diffusion-weighted lung MRI

Enlargements of distal airspaces can indicate pathological changes in the lung, but accessible and precise techniques able to measure these regions are lacking. Airspace Dimension Assessment with inhaled nanoparticles (AiDA) is a new method developed for in vivo measurement of distal airspace dimensions. The aim of this study was to benchmark the AiDA method against quantitative measurements of di

Predictors of mortality in patients with different apolipoprotein E genotypes—a 20-year follow-up of Alzheimer’s disease.

Background: To identify apolipoprotein E (APOE)-specific factors that may predict life expectancy after a diagnosis of Alzheimer’s disease (AD). Method: The Swedish Alzheimer Treatment Study (SATS) is a prospective, observational, clinical-practice-based, multicentre study that includes 999 participants diagnosed with mild-to-moderate AD at the start of cholinesterase inhibitor (ChEI) therapy (tim

Toward the equilibrium and kinetics of amyloid peptide self-assembly

Several devastating human diseases are linked to peptide self-assembly, but our understanding their onset and progression is not settled. This is a sign of the complexity of the aggregation process, which is prevented, catalyzed, or retarded by numerous factors in body fluids and cells, varying in time and space. Biophysical studies of pure peptide solutions contribute insights into the underlying

Less hip range of motion is associated with a greater alpha angle in people with longstanding hip and groin pain

Purpose: A higher alpha angle has been proposed to correlate with lower hip range of motion, but the association in people with longstanding hip and groin pain is currently unclear. The aims were to: (1) assess the association between range of motion and alpha angle in patients with longstanding hip and groin pain; (2) examine if a cut-off value in range of motion variables could identify patients

Commonly used estimates of the genetic contribution to disease are subject to the same fallacies as bad luck estimates

The scientific debate following the initial formulation of the “bad luck” hypothesis in cancer development highlighted how measures based on analysis of variance are inappropriately used for risk communication. The notion of “explained” variance is not only used to quantify randomness, but also to quantify genetic and environmental contribution to disease in heritability coefficients. In this pape

Cerebro-spinal fluid biomarker levels : phosphorylated tau (T) and total tau (N) as markers for rate of progression in Alzheimer's disease

BACKGROUND: We investigated the potential associations between cerebro-spinal fluid (CSF) levels of phosphorylated tau (P-tau) and total tau (T-tau) with short-term response to cholinesterase inhibitor (ChEI) treatment, longitudinal outcome and progression rates in Alzheimer's disease (AD). METHODS: This prospective, observational study included 129 participants clinically diagnosed with mild-to-m

Second primary cancers in melanoma patients critically shorten survival

Background: Survival in malignant cutaneous melanoma has improved but increasing survival will result in an increased likelihood of the occurrence of second primary cancers (SPCs). SPCs may adversely interfere with survival. We quantified survival in patients with different types of SPCs, in comparison to known poor prognostic indicators of metastatic disease. Methods: Data for melanoma and any SP

Enhancing Hematopoiesis from Murine Embryonic Stem Cells through MLL1-Induced Activation of a Rac/Rho/Integrin Signaling Axis

The Mixed Lineage Leukemia (MLL1, KMT2A) gene is critical for development and maintenance of hematopoietic stem cells (HSCs), however, whether this protein is limiting for HSC development is unknown due to lack of physiologic model systems. Here, we develop an MLL1-inducible embryonic stem cell (ESC) system and show that induction of wild-type MLL1 during ESC differentiation selectively increases

The catalytic nature of protein aggregation

The formation of amyloid fibrils from soluble peptide is a hallmark of many neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Characterization of the microscopic reaction processes that underlie these phenomena have yielded insights into the progression of such diseases and may inform rational approaches for the design of drugs to halt them. Experimental evidence suggests th

Epilepsy in immigrants and Swedish-born : A cohort study of all adults 18 years of age and older in Sweden

Purpose: We aimed to study the association between country of birth and incident epilepsy in several immigrant groups using Swedish-born individuals as referents. Method: The study population included all adults aged 18 years and older in Sweden, living and deceased, 6,690,598 in the first-generation and 6,683,125 in the second-generation sub-study. Epilepsy was defined as having at least one regi