MOONS : the new Multi-Object Spectrograph for the VLT

MOONS is the new Multi-Object Optical and Near-infrared Spectrograph currently under construction for the Very Large Telescope (VLT) at ESO. This remarkable instrument combines, for the first time, the collecting power of an 8-m telescope, 1000 fibres with individual roboticp ositioners, and both low- and high-resolution simultaneous spectral coverage across the 0.64–1.8 μm wavelength range. This facility will provide the astronomical community with a powerful, world-leading instrument able to serve a wide range of Galactic, extragalactic and cosmological studies. Construction is now proceeding full steam ahead and this overview article presents some of the science goals and the technical description of the MOONS instrument. More detailed information on the MOONS surveys is provided in the other dedicated articles in this Messenger issue.Publisher PD

Effects of Detergent on α-Synuclein Structure: A Native MS-Ion Mobility Study

The intrinsically disordered protein α-synuclein plays a major role in Parkinson’s disease. The protein can oligomerize resulting in the formation of various aggregated species in neuronal cells, leading to neurodegeneration. The interaction of α-synuclein with biological cell membranes plays an important role for specific functions of α-synuclein monomers, e.g., in neurotransmitter release. Using different types of detergents to mimic lipid molecules present in biological membranes, including the presence of Ca2+ ions as an important structural factor, we aimed to gain an understanding of how α-synuclein interacts with membrane models and how this affects the protein conformation and potential oligomerization. We investigated detergent binding stoichiometry, affinity and conformational changes of α-synuclein taking detergent concentration, different detergent structures and charges into account. With native nano-electrospray ionization ion mobility-mass spectrometry, we were able to detect unique conformational patterns resulting from binding of specific detergents to α-synuclein. Our data demonstrate that α-synuclein monomers can interact with detergent molecules irrespective of their charge, that protein-micelle interactions occur and that micelle properties are an important factor

Prediction of liver disease in patients whose liver function tests have been checked in primary care : model development and validation using population-based observational cohorts

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.Peer reviewedPublisher PD

Performantiemaatstaven voor ontslagmanagement. Een aanzet tot kwaliteitsmeting

peer reviewe

Ultrasound Shear Wave Elastography Helps Discriminate Low‐grade From High‐grade Bowel Wall Fibrosis in Ex Vivo Human Intestinal Specimens

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135467/1/jum201433122115.pd

Comparison of noncontrast MRI magnetization transfer and T2‐Weighted signal intensity ratios for detection of bowel wall fibrosis in a Crohn's disease animal model

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113105/1/jmri24815.pd

Excluding venous thromboembolism using point of care D-dimer tests in outpatients: a diagnostic meta-analysis

Objective To review the evidence on the diagnostic accuracy of the currently available point of care D-dimer tests for excluding venous thromboembolism

Native Ion Mobility-Mass Spectrometry Reveals the Formation of β-Barrel Shaped Amyloid-β Hexamers in a Membrane-Mimicking Environment.

The mechanisms behind the Amyloid-β (Aβ) peptide neurotoxicity in Alzheimer's disease are intensely studied and under debate. One suggested mechanism is that the peptides assemble in biological membranes to form β-barrel shaped oligomeric pores that induce cell leakage. Direct detection of such putative assemblies and their exact oligomeric states is however complicated by a high level of heterogeneity. The theory consequently remains controversial, and the actual formation of pore structures is disputed. We herein overcome the heterogeneity problem by employing a native mass spectrometry approach and demonstrate that Aβ(1-42) peptides form coclusters with membrane mimetic detergent micelles. The coclusters are gently ionized using nanoelectrospray and transferred into the mass spectrometer where the detergent molecules are stripped away using collisional activation. We show that Aβ(1-42) indeed oligomerizes over time in the micellar environment, forming hexamers with collision cross sections in agreement with a general β-barrel structure. We also show that such oligomers are maintained and even stabilized by addition of lipids. Aβ(1-40) on the other hand form significantly lower amounts of oligomers, which are also of lower oligomeric state compared to Aβ(1-42) oligomers. Our results thus support the oligomeric pore hypothesis as one important cell toxicity mechanism in Alzheimer's disease. The presented native mass spectrometry approach is a promising way to study such potentially very neurotoxic species and how they could be stabilized or destabilized by molecules of cellular or therapeutic relevance

Horizontally acquired papGII-containing pathogenicity islands underlie the emergence of invasive uropathogenic Escherichia coli lineages.

Escherichia coli is the leading cause of urinary tract infection, one of the most common bacterial infections in humans. Despite this, a genomic perspective is lacking regarding the phylogenetic distribution of isolates associated with different clinical syndromes. Here, we present a large-scale phylogenomic analysis of a spatiotemporally and clinically diverse set of 907 E. coli isolates, including 722 uropathogenic E. coli (UPEC) isolates. A genome-wide association approach identifies the (P-fimbriae-encoding) papGII locus as the key feature distinguishing invasive UPEC, defined as isolates associated with severe UTI, i.e., kidney infection (pyelonephritis) or urinary-source bacteremia, from non-invasive UPEC, defined as isolates associated with asymptomatic bacteriuria or bladder infection (cystitis). Within the E. coli population, distinct invasive UPEC lineages emerged through repeated horizontal acquisition of diverse papGII-containing pathogenicity islands. Our findings elucidate the molecular determinants of severe UTI and have implications for the early detection of this pathogen

Prognosis research strategy (PROGRESS) 1: a framework for researching clinical outcomes.

The PROGRESS series (www.progress-partnership.org) sets out a framework of four interlinked prognosis research themes and provides examples from several disease fields to show why evidence from prognosis research is crucial to inform all points in the translation of biomedical and health related research into better patient outcomes. Recommendations are made in each of the four papers to improve current research standards What is prognosis research? Prognosis research seeks to understand and improve future outcomes in people with a given disease or health condition. However, there is increasing evidence that prognosis research standards need to be improved Why is prognosis research important? More people now live with disease and conditions that impair health than at any other time in history; prognosis research provides crucial evidence for translating findings from the laboratory to humans, and from clinical research to clinical practice This first article introduces the framework of four interlinked prognosis research themes and then focuses on the first of the themes - fundamental prognosis research, studies that aim to describe and explain future outcomes in relation to current diagnostic and treatment practices, often in relation to quality of care Fundamental prognosis research provides evidence informing healthcare and public health policy, the design and interpretation of randomised trials, and the impact of diagnostic tests on future outcome. It can inform new definitions of disease, may identify unanticipated benefits or harms of interventions, and clarify where new interventions are required to improve prognosis