β-synuclein potentiates synaptic vesicle dopamine uptake and rescues dopaminergic neurons from MPTP-induced death in the absence of other synucleins.

Synucleins, a family of three proteins highly expressed in neurons, are predominantly known for the direct involvement of α-synuclein in the aetiology and pathogenesis of Parkinson's and certain other neurodegenerative diseases, but their precise physiological functions are still not fully understood. Previous studies have demonstrated the importance of α-synuclein as a modulator of various mechanisms implicated in chemical neurotransmission, but information concerning the involvement of other synuclein family members, β-synuclein and γ-synuclein, in molecular processes within presynaptic terminals is limited. Here we demonstrated that the vesicular monoamine transporter 2 (VMAT2)-dependent dopamine uptake by synaptic vesicles isolated from the striatum of mice lacking β-synuclein is significantly reduced. Reciprocally, reintroduction, either in vivo or in vitro, of β-synuclein but not α- or γ-synuclein improves uptake by triple α/β/γ-synuclein deficient striatal vesicles. We also showed that the resistance of dopaminergic neurons of the substantia nigra pars compacta (SNpc) to subchronic administration of the Parkinson's disease-inducing prodrug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) depends on the presence of β-synuclein but only when one or both other synucleins are absent. Furthermore, proteomic analysis of synuclein-deficient synaptic vesicles vs those containing only β-synuclein revealed differences in their protein compositions. We suggest that the observed potentiation of dopamine uptake by β-synuclein might be caused by different protein architecture of the synaptic vesicles. It is also feasible that such structural changes improve synaptic vesicle sequestration of 1-methyl-4-phenylpyridinium (MPP+), a toxic metabolite of MPTP, which would explain why dopaminergic neurons expressing β-synuclein and lacking α-synuclein and/or γ-synuclein are resistant to this neurotoxin

Microstructure and biomechanical characteristics of bone substitutes for trauma and orthopaedic surgery

Abstract. BACKGROUND: Many (artificial) bone substitute materials are currently available for use in orthopaedic trauma surgery. Objective data on their biological and biomechanical characteristics, which determine their clinical application, is mostly lacking. The aim of this study was to investigate structural and in vitro mechanical properties of nine bone substitute cements registered for use in orthopaedic trauma surgery in the Netherlands. METHODS: Seven calcium phosphate cements (BoneSource®, Calcibon®, ChronOS®, Eurobone®, HydroSet™, Norian SRS®, and Ostim®), one calcium sulphate cement (MIIG® X3), and one bioactive glass cement (Cortoss®) were tested. Structural characteristics were measured by micro-CT scanning. Compression strength and stiffness were determined following unconfined compression tests. RESULTS: Each bone substitute had unique characteristics. Mean total porosity ranged from 53% (Ostim®) to 0.5% (Norian SRS®). Mean pore size exceeded 100 μm only in Eurobone® and Cortoss® (162.2 ± 107.1 μm and 148.4 ± 70.6 μm, respectively). However, 230 μm pores were found in Calcibon®, Norian SRS®, HydroSet™, and MIIG® X3. Connectivity density ranged from 27/cm3 for HydroSet™ to 0.03/cm3 for Calcibon®. The ultimate compression strength was highest in Cortoss® (47.32 MPa) and lowest in Ostim® (0.24 MPa). Young's Modulus was highest in Calcibon® (790 MPa) and lowest in Ostim® (6 MPa). CONCLUSIONS: The bone substitutes tested display a wide range in structural properties and compression strength, indicating that they will be suitable for different clinical indications. The data outlined here will help surgeons to select the most suitable products currently available for specific clinical indications

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 1: The LBNF and DUNE Projects

This document presents the Conceptual Design Report (CDR) put forward by an international neutrino community to pursue the Deep Underground Neutrino Experiment at the Long-Baseline Neutrino Facility (LBNF/DUNE), a groundbreaking science experiment for long-baseline neutrino oscillation studies and for neutrino astrophysics and nucleon decay searches. The DUNE far detector will be a very large modular liquid argon time-projection chamber (LArTPC) located deep underground, coupled to the LBNF multi-megawatt wide-band neutrino beam. DUNE will also have a high-resolution and high-precision near detector

The Single-Phase ProtoDUNE Technical Design Report

ProtoDUNE-SP is the single-phase DUNE Far Detector prototype that is under construction and will be operated at the CERN Neutrino Platform (NP) starting in 2018. ProtoDUNE-SP, a crucial part of the DUNE effort towards the construction of the first DUNE 10-kt fiducial mass far detector module (17 kt total LAr mass), is a significant experiment in its own right. With a total liquid argon (LAr) mass of 0.77 kt, it represents the largest monolithic single-phase LArTPC detector to be built to date. It's technical design is given in this report

The Single-Phase ProtoDUNE Technical Design Report

ProtoDUNE-SP is the single-phase DUNE Far Detector prototype that is under construction and will be operated at the CERN Neutrino Platform (NP) starting in 2018. ProtoDUNE-SP, a crucial part of the DUNE effort towards the construction of the first DUNE 10-kt fiducial mass far detector module (17 kt total LAr mass), is a significant experiment in its own right. With a total liquid argon (LAr) mass of 0.77 kt, it represents the largest monolithic single-phase LArTPC detector to be built to date. It's technical design is given in this report

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report, Volume 4 The DUNE Detectors at LBNF

A description of the proposed detector(s) for DUNE at LBN