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Mitochondrial respiratory chain complex I dysfunction induced by N-methyl carbamate ex vivo can be alleviated with a cell-permeable succinate prodrug

Human exposure to carbamates and organophosphates poses a serious threat to society and current pharmacological treatment is solely targeting the compounds' inhibitory effect on acetylcholinesterase. This toxicological pathway, responsible for acute symptom presentation, can be counteracted with currently available therapies such as atropine and oximes. However, there is still significant long-ter

Developing ActivABLES for community-dwelling stroke survivors using the Medical Research Council framework for complex interventions

Background: Novel technical solutions are called for to promote home-based exercise among community-dwelling stroke survivors supported by their caregivers. Lack of resources and knowledge about how to accomplish it, has been demonstrated. The objective of this study is to describe in detail the development of ActivABLES, a technical intervention to promote home-based exercise and physical activit

The social context of nearest neighbors shapes educational attainment regardless of class origin

We study the association between sociospatial neighborhood conditions throughout childhood and educational attainment in adulthood. Using unique longitudinal microdata for a medium-sized Swedish town, we geocode its population at the address level, 1939 to 1967, and link individuals to national registers, 1968 to 2015. Thus, we adopt a long-term perspective on the importance of nearby neighbors du

Unity Makes Strength : Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A2 and Cytotoxins

Toxin synergism is a complex biochemical phenomenon, where different animal venom proteins interact either directly or indirectly to potentiate toxicity to a level that is above the sum of the toxicities of the individual toxins. This provides the animals possessing venoms with synergistically enhanced toxicity with a metabolic advantage, since less venom is needed to inflict potent toxic effects

Pre-treatment allostatic load and metabolic dysregulation predict SSRI response in major depressive disorder : A preliminary report

BackgroundMajor depressive disorder (MDD) is associated with increased allostatic load (AL; a measure of physiological costs of repeated/chronic stress-responding) and metabolic dysregulation (MetD; a measure of metabolic health and precursor to many medical illnesses). Though AL and MetD are associated with poor somatic health outcomes, little is known regarding their relationship with antidepres

Impact of α-synuclein pathology on transplanted hESC-derived dopaminergic neurons in a humanized α-synuclein rat model of PD

Preclinical assessment of the therapeutic potential of dopamine (DA) neuron replacement in Parkinson's disease (PD) has primarily been performed in the 6-hydroxydopamine toxin model. While this is a good model to assess graft function, it does not reflect the pathological features or progressive nature of the disease. In this study, we establish a humanized transplantation model of PD that better

The Role of Matrix Metalloproteinases (MMP-2 and MMP-9) in Ageing and Longevity : Focus on Sicilian Long-Living Individuals (LLIs)

Extracellular matrix metalloproteinases (MMPs) are a group of proteins that activate substrates by enzymatic cleavage and, on the basis of their activities, have been demonstrated to play a role in ageing. Thus, in order to gain insight into the pathophysiology of ageing and to identify new markers of longevity, we analysed the activity levels of MMP-2 and MMP-9 in association with some relevant h

Confronting experimental data with heavy-ion models : Rivet for heavy ions

The Rivet library is an important toolkit in particle physics, and serves as a repository for analysis data and code. It allows for comparisons between data and theoretical calculations of the final state of collision events. This paper outlines several recent additions and improvements to the framework to include support for analysis of heavy ion collision simulated data. The paper also presents

Local structure and magnetism of Fe2O3 maghemite nanocrystals : The role of crystal dimension

Here we report on the impact of reducing the crystalline size on the structural and magnetic properties of γ-Fe2O3 maghemite nanoparticles. A set of polycrystalline specimens with crystallite size ranging from ~2 to ~50 nm was obtained combining microwave plasma synthesis and commercial samples. Crystallite size was derived by electron microscopy and synchrotron powder diffraction, which was used

Evolution and structure of technological systems - An innovation output network

The mechanisms responsible for the structure and evolution of technological systems are not fully understood. This study examines the network of supply and use of significant innovations across industries in Sweden, 1970-2013. The results suggest that at least 30% of innovation patterns can be statistically predicted by network stimulus from both backward and forward linkages in the Swedish econom

Five years of pharmaceutical industry funding of patient organisations in Sweden: cross-sectional study of companies, patient organisations and drugs

BackgroundMany patient organisations collaborate with drug companies, resulting in concerns about commercial agendas influencing patient advocacy. We contribute to an international body of knowledge on patient organisation-industry relations by considering payments reported in the industry’s centralised ‘collaboration database’ in Sweden. We also investigate possible commercial motives behind the

The prion fragment PrP106-127 adopts a secondary structure typical of aggregated fibrils in langmuir monolayers of brain lipid extract

Understanding protein aggregation is essential to unveil molecular mechanisms associated with neurodegenerative diseases such as Alzheimer's, Huntington's and spongiform encephalopathy, particularly to determine the role of interaction with cell membranes. In this study, we employ Langmuir monolayers as cell membrane models to mimic interaction with the peptide KTNMHKHMAGAAAAGAVVGGLG−OH, a fragmen

Performance of new and aged injectors with and without fuel additives in a light duty diesel engine

Two sets of diesel injectors are tested in combination with common fuel additives in a multi-cylinder light-duty diesel engine. One set consists of new injectors and the other is aged by over 100,000 km use in a vehicle. Four fuels are tested with these injector sets to investigate the impact of fuel additives on combustion and emission characteristics. The results show that the aged injectors con

Introducing PIONEER : a project to harness big data in prostate cancer research

Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. Launched by the Innovative Medicines Initiative 2 and part of the Big Data for Better Outcomes Programme (BD4BO), the overarching goal of PIONEER is

The effect of LRRK2 loss-of-function variants in humans

Human genetic variants predicted to cause loss-of-function of protein-coding genes (pLoF variants) provide natural in vivo models of human gene inactivation and can be valuable indicators of gene function and the potential toxicity of therapeutic inhibitors targeting these genes1,2. Gain-of-kinase-function variants in LRRK2 are known to significantly increase the risk of Parkinson’s disease3,4, su

Herwig 7.2 release note

A new release of the Monte Carlo event generator Herwig (version 7.2) is now available. This version introduces a number of improvements over the major version 7.0, notably: multi-jet merging with the dipole shower at LO and NLO QCD; spin correlations in both the dipole and angular-ordered parton showers; an improved choice of evolution variable in the angular-ordered parton shower; improvements t

Search for light long-lived neutral particles produced in pp collisions at √s=13TeV and decaying into collimated leptons or light hadrons with the ATLAS detector

Several models of physics beyond the Standard Model predict the existence of dark photons, light neutral particles decaying into collimated leptons or light hadrons. This paper presents a search for long-lived dark photons produced from the decay of a Higgs boson or a heavy scalar boson and decaying into displaced collimated Standard Model fermions. The search uses data corresponding to an integra

Gendering foreign policy : A comparative framework for analysis

This article seeks to explain the rise of pro-gender norms and feminist strategies in foreign policy, which are increasingly salient in global politics. How can this trend be theorized? In what ways is this development resisted and contested by other states and international actors? To what extent can we trace continuity and change in regard to gender and foreign policy? To address these major res