Neuron-Derived Semaphorin 3A Is an Early Inducer of Vascular Permeability in Diabetic Retinopathy via Neuropilin-1

SummaryThe deterioration of the inner blood-retinal barrier and consequent macular edema is a cardinal manifestation of diabetic retinopathy (DR) and the clinical feature most closely associated with loss of sight. We provide evidence from both human and animal studies for the critical role of the classical neuronal guidance cue, semaphorin 3A, in instigating pathological vascular permeability in diabetic retinas via its cognate receptor neuropilin-1. We reveal that semaphorin 3A is induced in early hyperglycemic phases of diabetes within the neuronal retina and precipitates initial breakdown of endothelial barrier function. We demonstrate, by a series of orthogonal approaches, that neutralization of semaphorin 3A efficiently prevents diabetes-induced retinal vascular leakage in a stage of the disease when vascular endothelial growth factor neutralization is inefficient. These observations were corroborated in TgCre-Esr1/Nrp1flox/flox conditional knockout mice. Our findings identify a therapeutic target for macular edema and provide further evidence for neurovascular crosstalk in the pathogenesis of DR

Analyse physico-chimique de l’eau de l’unité d’hémodialyse du chr de Saint- Louis (Sénégal)

L’insuffisance rénale chronique est un des problèmes majeurs de la santé publique dans le monde. Au Sénégal, une étude récente réalisée dans la population générale adulte avait retrouvé une prévalence de l’ordre de 6,1%. «L’eau pour dilution de concentrées d’hémodialyse» est produite en continue et utilisée en grande quantité chez l’hémodialysé chronique, donc il apparaît primordial de veiller à sa bonne qualité. Au Sénégal, aucune étude n’a été faite à ce jour pour évaluer l’efficacité du système de traitement de l’eau pour dilution des concentrés de dialyse dans les différents centres de dialyse du pays. L’objectif de ce travail est de contrôler l’efficacité du système de traitement de l’eau pour dilution de concentrées d’hémodialyse afin de s’assurer de son innocuité. Les prélèvements ont été effectués au niveau de trois points clés du circuit de traitement de l’eau pour hémodialyse. A l’entrée et à la sortie de l’osmoseur, à la sortie de la boucle de distribution. Les analyses ont été effectuées à l’aide d’électrodes spécifiques. Les valeurs de potentiels ont permis de tracer les courbes d’étalonnage. La détermination par régression des pentes et des ordonnées à l’origine de la relation de Nernst donne E(mV ) = B - A Log Cm avec des coefficients de corrélation variant entre 0,988 et 0,999 prouvant que 98% au moins des variations de tensions mesurées (E) sont attribuables à la concentration. L’analyse physico-chimique des teneurs en chlorures, nitrates et fluorures révèle des teneurs plus élevées à l’entrée de l’osmoseur qu’à la sortie. Ces basses valeurs découlent du rôle de l’osmoseur qui filtre une grande partie des électrolytes. Par contre, à la sortie de la boucle de distribution les teneurs en électrolytes des différents échantillons étaient plus importantes que celles à la sortie de l’osmoseur. Cette forte concentration en électrolytes atteste d’une pollution par la boucle de distribution de l’eau déjà filtrée par l’osmoseur. L’intérêt de cette étude réside dans le fait qu’elle met en lumière l’importance du contrôle de la qualité de l’eau pour l’hémodialyse et la nécessité d’un bon planning de maintenance préventive efficace de l’ensemble de la boucle de traitement d’eau au sein de chaque centre.© 2016 International Formulae Group. All rights reserved.Mots clés: Hémodialyse, eau, chlorures, fluorures, nitrates, électrodes spécifiquesEnglish Title: Physicochemical analysis of Saint–Louis regional hospital’s hemodialysis unit’s water (Senegal)English AbstractChronic kidney disease is a major public health problem worldwide. In Senegal, a recent study in the general adult population found a prevalence of about 6,1%. "Water for diluting concentrated hemodialysis" is produced and used continuously at high levels in hemodialysis chronic. It is therefore essential to ensure its quality. In Senegal, no study has been done to assess the effectiveness of water treatment system for dialysis concentrates dilution in different dialysis centers of the country. The objective of this work is to monitor the effectiveness of the water treatment system for hemodialysis concentrated dilution to ensure its safety. The samples were taken on key issues of hemodialysis water’s treatment circuit. Three levels of sampling were selected. At the entrance and at the outlet of the reverse osmosis unit at the outlet of the distribution loop. Analyses were performed using specific electrodes. Potential values allowed us to map the calibration curves. Determination by regression of slopes and intercepts of the Nernst relation gives with correlation coefficients ranging from 0.988 to 0.999 showing that at least 98% of the measured voltages fluctuations (E) are attributable to the concentration. Physicochemical analysis of the levels of chlorides, nitrates and fluorides reveals higher levels at the entrance of the reverse osmosis unit than at the outlet. These low values resulting of the role of reverse osmosis which filter much of the electrolytes. For against, at the outlet of the distribution loop the electrolyte content of the different samples were greater than those at the outlet of the reverse osmosis unit. This high electrolyte concentration attests to pollution of the water distribution loop already filtered by reverse osmosis. The interest of this study lies in the fact that it highlights the importance of monitoring the quality of water for hemodialysis and the need for good planning for effective preventive maintenance throughout the water treatment loop within each center.© 2016 International Formulae Group. All rights reserved.Keywords: Hemodialysis, water, nitrates, fluoride, chloride, specific electrode

TAO Conceptual Design Report: A Precision Measurement of the Reactor Antineutrino Spectrum with Sub-percent Energy Resolution

The Taishan Antineutrino Observatory (TAO, also known as JUNO-TAO) is a satellite experiment of the Jiangmen Underground Neutrino Observatory (JUNO). A ton-level liquid scintillator detector will be placed at about 30 m from a core of the Taishan Nuclear Power Plant. The reactor antineutrino spectrum will be measured with sub-percent energy resolution, to provide a reference spectrum for future reactor neutrino experiments, and to provide a benchmark measurement to test nuclear databases. A spherical acrylic vessel containing 2.8 ton gadolinium-doped liquid scintillator will be viewed by 10 m^2 Silicon Photomultipliers (SiPMs) of >50% photon detection efficiency with almost full coverage. The photoelectron yield is about 4500 per MeV, an order higher than any existing large-scale liquid scintillator detectors. The detector operates at -50 degree C to lower the dark noise of SiPMs to an acceptable level. The detector will measure about 2000 reactor antineutrinos per day, and is designed to be well shielded from cosmogenic backgrounds and ambient radioactivities to have about 10% background-to-signal ratio. The experiment is expected to start operation in 2022

HyMeX: A 10-Year Multidisciplinary Program on the Mediterranean Water Cycle

Drobinski, P. ... et. al.-- 20 pages, 10 figures, 1 table, supplement material http://journals.ametsoc.org/doi/suppl/10.1175/BAMS-D-12-00244.1HyMeX strives to improve our understanding of the Mediterranean water cycle, its variability from the weather-scale events to the seasonal and interannual scales, and its characteristics over one decade (2010–20), with a special focus on hydrometeorological extremes and the associated social and economic vulnerability of the Mediterranean territoriesHyMeX was developed by an international group of scientists and is currently funded by a large number of agencies. It has been the beneficiary of financial contributions from CNRS; Météo-France; CNES; IRSTEA; INRA; ANR; Collectivité Territoriale de Corse; KIT; CNR; Université de Toulouse; Grenoble Universités; EUMETSAT; EUMETNET; AEMet; Université Blaise Pascal, Clermont Ferrand; Université de la Méditerranée (Aix-Marseille II); Université Montpellier 2; CETEMPS; Italian Civil Protection Department; Université Paris- Sud 11; IGN; EPFL; NASA; New Mexico Tech; IFSTTAR; Mercator Ocean; NOAA; ENEA; TU Delft; CEA; ONERA; IMEDEA; SOCIB; ETH; MeteoCat; Consorzio LAMMA; IRD; National Observatory of Athens; Ministerio de Ciencia e Innovación; CIMA; BRGM; Wageningen University and Research Center; Department of Geophysics, University of Zagreb; Institute of Oceanography and Fisheries, Split, Croatia; INGV; OGS; Maroc Météo; DHMZ; ARPA Piemonte; ARPA-SIMC Emilia-Romagna; ARPA Calabria; ARPA Friuli Venezia Giulia; ARPA Liguria; ISPRA; University of Connecticut; Università degli Studi dell'Aquila; Università di Bologna; Università degli Studi di Torino; Università degli Studi della Basilicata; Università La Sapienza di Roma; Università degli Studi di Padova; Università del Salento; Universitat de Barcelona; Universitat de les Illes Balears; Universidad de Castilla-La Mancha; Universidad Complutense de Madrid; MeteoSwiss; and DLR. It also received support from the European Community's Seventh Framework Programme (e.g., PERSEUS, CLIM-RUN)Peer reviewe

Convergent genetic and expression data implicate immunity in Alzheimer's disease

Background Late–onset Alzheimer's disease (AD) is heritable with 20 genes showing genome wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease we extended these genetic data in a pathway analysis. Methods The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (p = 3.27×10-12 after multiple testing correction for pathways), regulation of endocytosis (p = 1.31×10-11), cholesterol transport (p = 2.96 × 10-9) and proteasome-ubiquitin activity (p = 1.34×10-6). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected p 0.002 – 0.05). Conclusions The immune response, regulation of endocytosis, cholesterol transport and protein ubiquitination represent prime targets for AD therapeutics

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Potential of Core-Collapse Supernova Neutrino Detection at JUNO

JUNO is an underground neutrino observatory under construction in Jiangmen, China. It uses 20kton liquid scintillator as target, which enables it to detect supernova burst neutrinos of a large statistics for the next galactic core-collapse supernova (CCSN) and also pre-supernova neutrinos from the nearby CCSN progenitors. All flavors of supernova burst neutrinos can be detected by JUNO via several interaction channels, including inverse beta decay, elastic scattering on electron and proton, interactions on C12 nuclei, etc. This retains the possibility for JUNO to reconstruct the energy spectra of supernova burst neutrinos of all flavors. The real time monitoring systems based on FPGA and DAQ are under development in JUNO, which allow prompt alert and trigger-less data acquisition of CCSN events. The alert performances of both monitoring systems have been thoroughly studied using simulations. Moreover, once a CCSN is tagged, the system can give fast characterizations, such as directionality and light curve

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery