TIGAR inclusion pathology is specific for Lewy body diseases

BACKGROUND: We previously reported up-regulation of tigarb (the zebrafish orthologue? of human TIGAR, TP53 - Induced Glycolysis and Apoptosis Regulator) in a zebrafish pink1-/- model of Parkinson's disease (PD). Genetic inactivation of tigarb led to the rescue of dopaminergic neurons and mitochondrial function in pink-/- zebrafish. The aim of this study was to determine the relevance of TIGAR for human PD, investigate its disease specificity and identify relevant upstream and downstream mechanisms. MATERIALS AND METHODS: TIGAR Immunohistochemistry using a range of antibodies was undertaken for detailed assessment of TIGAR in formalin-fixed, paraffin-embedded tissue from post mortem brains of PD patients and other neurodegenerative disorders (n = 10 controls, 10 PD cases, 10 dementia with Lewy bodies, 5 motor neurone disease (MND), 3 multiple system atrophy (MSA) and complemented by immunohistochemistry for p53, hexokinase I (HK-I) and hexokinase II (HK-II; n = 4 control, 4 PD, and 4 dementia with Lewy bodies). RESULTS: TIGAR was detected in Lewy bodies and Lewy neurites in the substantia nigra of sporadic PD and Dementia with Lewy bodies (DLB) patients. Staining of adjacent sections confirmed the presence of TIGAR alongside alpha-synuclein in these LB and Neurites. In contrast, TIGAR-positive aggregates were not seen in cortical Lewy bodies. TIGAR protein was also absent in both TDP-43-positive inclusions in MND and glial cytoplasmic inclusions in MSA. Subsequent investigation of the TIGAR-upstream regulator p53 and the downstream targets HK-I and HK-II in PD brains suggested a possible mild increase in HK-I. CONCLUSIONS: TIGAR protein, is present in SN Lewy bodies of both sporadic PD and DLB. The absence of TIGAR protein in the pathological inclusions of MND or MSA suggests disease specificity and further raises the possibility that TIGAR may be involved in PD pathogenesis

MinION Analysis and Reference Consortium: Phase 1 data release and analysis

The advent of a miniaturized DNA sequencing device with a high-throughput contextual sequencing capability embodies the next generation of large scale sequencing tools. The MinION™ Access Programme (MAP) was initiated by Oxford Nanopore Technologies™ in April 2014, giving public access to their USB-attached miniature sequencing device. The MinION Analysis and Reference Consortium (MARC) was formed by a subset of MAP participants, with the aim of evaluating and providing standard protocols and reference data to the community. Envisaged as a multi-phased project, this study provides the global community with the Phase 1 data from MARC, where the reproducibility of the performance of the MinION was evaluated at multiple sites. Five laboratories on two continents generated data using a control strain of Escherichia coli K-12, preparing and sequencing samples according to a revised ONT protocol. Here, we provide the details of the protocol used, along with a preliminary analysis of the characteristics of typical runs including the consistency, rate, volume and quality of data produced. Further analysis of the Phase 1 data presented here, and additional experiments in Phase 2 of E. coli from MARC are already underway to identify ways to improve and enhance MinION performance

Transition rates and nuclear structure changes in mirror nuclei 47Cr and 47V

Lifetime measurements in the mirror nuclei 47Cr and 47V were performed by means of the Doppler-shift attenuation method using the multidetector array EUROBALL, in conjunction with the ancillary detectors ISIS and the Neutron Wall. The determined transition strengths in the yrast cascades are well described by full pf shell model calculations.Comment: Latex2e, 11 pages, 3 figure

Coexistence of 'alpha+ 208Pb' cluster structures and single-particle excitations in 212Po

Excited states in 212Po have been populated by alpha transfer using the 208Pb(18O,14C) reaction at 85MeV beam energy and studied with the EUROBALL IV gamma multidetector array. The level scheme has been extended up to ~ 3.2 MeV excitation energy from the triple gamma coincidence data. Spin and parity values of most of the observed states have been assigned from the gamma angular distributions and gamma -gamma angular correlations. Several gamma lines with E(gamma) < 1 MeV have been found to be shifted by the Doppler effect, allowing for the measurements of the associated lifetimes by the DSAM method. The values, found in the range [0.1-0.6] ps, lead to very enhanced E1 transitions. All the emitting states, which have non-natural parity values, are discussed in terms of alpha-208Pb structure. They are in the same excitation-energy range as the states issued from shell-model configurations.Comment: 21 pages, 19 figures, corrected typos, revised arguments in Sect. III

Are shallow-water shrimps proxies for hydrothermal-vent shrimps to assess the impact of deep-sea mining?

Polymetallic seafloor massive sulphide deposits are potential targets for deep-sea mining, but high concentrations of metals (including copper - Cu) may be released during exploitation activities, potentially inducing harmful impact. To determine whether shallow-water shrimp are suitable ecotoxicological proxies for deep-sea hydrothermal vent shrimp the effects of waterborne Cu exposure (3 and 10 days at 0.4 and 4 μM concentrations) in Palaemon elegans, Palaemon serratus, and Palaemon varians were compared with Mirocaris fortunata. Accumulation of Cu and a set of biomarkers were analysed. Results show different responses among congeneric species indicating that it is not appropriate to use shallow-water shrimps as ecotoxicological proxies for deep-water shrimps. During the evolutionary history of these species they were likely subject to different chemical environments which may have induced different molecular/biochemical adaptations/tolerances. Results highlight the importance of analysing effects of deep-sea mining in situ and in local species to adequately assess ecotoxicological effects under natural environmental conditions.This work was developed under the MIDAS project (Managing im-pacts of deep-sea resource exploitation), funded by the EuropeanCommission, European Union, 7th Framework Programme under thetheme“Sustainable management of Europe's deep sea and sub-seafloorresources”(Grant Agreement 603418). This work was also supported bythe Fundação para a Ciência e Tecnologia I.P. Portugal (FCT) and theDireção-Geral de Política do Mar (DGPM), Portugal through the projectMining2/2017/001–MiningImpact 2 (JPI Oceans), and FCT furtherfunded the grants CEECIND005262017 and UID/MAR/00350/2013.We acknowledge the captains and crews of the oceanographic ship“Pourquoi Pas?”, and the pilots of Victor 6000 Remotely OperatedVehicle, for their dedicated assistance during sampling of vent shrimps.We are also grateful to F. Lallier, chief scientist of the Biobaz cruise. Wewould like to warmly thank Océanopolis staffmembers, J-M Carré, SDelaporte and O Gouello, for their important contributions to shrimpmaintenance.info:eu-repo/semantics/publishedVersio

Observing Supermassive Black Holes across cosmic time: from phenomenology to physics

In the last decade, a combination of high sensitivity, high spatial resolution observations and of coordinated multi-wavelength surveys has revolutionized our view of extra-galactic black hole (BH) astrophysics. We now know that supermassive black holes reside in the nuclei of almost every galaxy, grow over cosmological times by accreting matter, interact and merge with each other, and in the process liberate enormous amounts of energy that influence dramatically the evolution of the surrounding gas and stars, providing a powerful self-regulatory mechanism for galaxy formation. The different energetic phenomena associated to growing black holes and Active Galactic Nuclei (AGN), their cosmological evolution and the observational techniques used to unveil them, are the subject of this chapter. In particular, I will focus my attention on the connection between the theory of high-energy astrophysical processes giving rise to the observed emission in AGN, the observable imprints they leave at different wavelengths, and the methods used to uncover them in a statistically robust way. I will show how such a combined effort of theorists and observers have led us to unveil most of the SMBH growth over a large fraction of the age of the Universe, but that nagging uncertainties remain, preventing us from fully understating the exact role of black holes in the complex process of galaxy and large-scale structure formation, assembly and evolution.Comment: 46 pages, 21 figures. This review article appears as a chapter in the book: "Astrophysical Black Holes", Haardt, F., Gorini, V., Moschella, U and Treves A. (Eds), 2015, Springer International Publishing AG, Cha

Gemini Observations of Galaxies in Rich Early Environments (GOGREEN) I: survey description

We describe a new Large Program in progress on the Gemini North and South telescopes: Gemini Observations of Galaxies in Rich Early Environments (GOGREEN). This is an imaging and deep spectroscopic survey of 21 galaxy systems at 1 10 in halo mass. The scientific objectives include measuring the role of environment in the evolution of low-mass galaxies, and measuring the dynamics and stellar contents of their host haloes. The targets are selected from the SpARCS, SPT, COSMOS, and SXDS surveys, to be the evolutionary counterparts of today's clusters and groups. The new red-sensitive Hamamatsu detectors on GMOS, coupled with the nod-and-shuffle sky subtraction, allow simultaneous wavelength coverage over λ ∼ 0.6–1.05 μm, and this enables a homogeneous and statistically complete redshift survey of galaxies of all types. The spectroscopic sample targets galaxies with AB magnitudes z΄ < 24.25 and [3.6] μm < 22.5, and is therefore statistically complete for stellar masses M* ≳ 1010.3 M⊙, for all galaxy types and over the entire redshift range. Deep, multiwavelength imaging has been acquired over larger fields for most systems, spanning u through K, in addition to deep IRAC imaging at 3.6 μm. The spectroscopy is ∼50 per cent complete as of semester 17A, and we anticipate a final sample of ∼500 new cluster members. Combined with existing spectroscopy on the brighter galaxies from GCLASS, SPT, and other sources, GOGREEN will be a large legacy cluster and field galaxy sample at this redshift that spectroscopically covers a wide range in stellar mass, halo mass, and clustercentric radius

Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci

Refractive error (RE) is a complex, multifactorial disorder characterized by a mismatch between the optical power of the eye and its axial length that causes object images to be focused off the retina. The two major subtypes of RE are myopia (nearsightedness) and hyperopia (farsightedness), which represent opposite ends of the distribution of the quantitative measure of spherical refraction. We performed a fixed effects meta-analysis of genome-wide association results of myopia and hyperopia from 9 studies of European-derived populations: AREDS, KORA, FES, OGP-Talana, MESA, RSI, RSII, RSIII and ERF. One genome-wide significant region was observed for myopia, corresponding to a previously identified myopia locus on 8q12 (p = 1.25610-8), which has been reported by Kiefer et al. as significantly associated with myopia age at onset and Verhoeven et al. as significantly associated to mean spherical-equivalent (MSE) refractive error. We observed two genomewide significant association