Global Assimilation of EOS-Aura Data as a Means of Mapping Ozone Distribution in the Lower Stratosphere and Troposphere

Ozone in the lower stratosphere and the troposphere plays an important role in forcing the climate. However, the global ozone distribution in this region is not well known because of the sparse distribution of in-situ data and the poor sensitivity of satellite based observations to the lowermost of the atmosphere. The Ozone Monitoring Instrument (OMI) and Microwave Limb Sounder (MLS) instruments on EOS-Aura provide information on the total ozone column and the stratospheric ozone profile. This data has been assimilated into NASA s Global Earth Observing System, Version 5 (GEOS-5) data assimilation system (DAS). We will discuss the results of assimilating three years of OMI and MLS data into GEOS-5. This data was assimilated alongside meteorological observations from both conventional sources and satellite instruments. Previous studies have shown that combining observations from these instruments through the Trajectory Tropospheric Ozone Residual methodology (TTOR) or using data assimilation can yield useful, yet low biased, estimates of the tropospheric ozone budget. We show that the assimilated ozone fields in this updated version of GEOS-5 exhibit an excellent agreement with ozone sonde and High Resolution Dynamics Limb Sounder (HIRDLS) data in the lower stratosphere in terms of spatial and temporal variability as well as integrated ozone abundances. Good representation of small-scale vertical features follows from combining the MLS data with the assimilated meteorological fields. We then demonstrate how this information can be used to calculate the Stratosphere - Troposphere Exchange of ozone and its contribution to the tropospheric ozone column in GEOS-5. Evaluations of tropospheric ozone distributions from the assimilation will be made by comparisons with sonde and other in-situ observations

Validation of Aura Microwave Limb Sounder O-3 and CO observations in the upper troposphere and lower stratosphere

International audienceGlobal satellite observations of ozone and carbon monoxide from the Microwave Limb Sounder (MLS) on the EOS Aura spacecraft are discussed with emphasis on those observations in the 215–100 hPa region (the upper troposphere and lower stratosphere). The precision, resolution and accuracy of the data produced by the MLS “version 2.2” processing algorithms are discussed and quantified. O3 accuracy is estimated at ~40 ppbv +5% (~20 ppbv +20% at 215 hPa) while the CO accuracy is estimated at ~30 ppbv +30% for pressures of 147 hPa and less. Comparisons with expectations and other observations show good agreements for the O3 product, generally consistent with the systematic errors quoted above. In the case of CO, a persistent factor of ~2 high bias is seen at 215 hPa. However, the morphology is shown to be realistic, consistent with raw MLS radiance data, and useful for scientific study. The MLS CO data at higher altitudes are shown to be consistent with other observations

Spatial transcriptomics identifies spatially dysregulated expression of <i>GRM3</i> and <i>USP47</i> in amyotrophic lateral sclerosis

Research Funding Medical Research Council. Grant Number: MR/L016400/1 Biogen Academy of Medical Sciences. Grant Number: 210JMG 3102 R45620 MND Scotland Engineering and Physical Sciences Research CouncilPeer reviewedPublisher PD

Tumour necrosis factor induces increased production of extracellular amyloid-β- and α-synuclein-containing aggregates by human Alzheimer's disease neurons

In addition to increased aberrant protein aggregation, inflammation has been proposed as a key element in the pathogenesis and progression of Alzheimer’s disease. How inflammation interacts with other disease pathways and how protein aggregation increases during disease are not clear. We used single-molecule imaging approaches and membrane permeabilization assays to determine the effect of chronic exposure to tumour necrosis factor, a master proinflammatory cytokine, on protein aggregation in human-induced pluripotent stem cell-derived neurons harbouring monogenic Alzheimer’s disease mutations. We report that exposure of Alzheimer’s disease neurons, but not control neurons, to tumour necrosis factor induces substantial production of extracellular protein aggregates. Aggregates from Alzheimer’s disease neurons are composed of amyloid-β and α-synuclein and induce significant permeabilization of lipid membranes in an assay of pathogenicity. These findings provide support for a causal relationship between two crucial processes in Alzheimer’s disease pathogenesis and suggest that targeting inflammation, particularly tumour necrosis factor, may have beneficial downstream effects on ameliorating aberrant protein aggregation and accumulation

A linear CO chemistry parameterization in a chemistry-transport model: evaluation and application to data assimilation

This paper presents an evaluation of a new linear parameterization valid for the troposphere and the stratosphere, based on a first order approximation of the carbon monoxide (CO) continuity equation. This linear scheme (hereinafter noted LINCO) has been implemented in the 3-D Chemical Transport Model (CTM) MOCAGE (MOdèle de Chimie Atmospherique Grande Echelle). First, a one and a half years of LINCO simulation has been compared to output obtained from a detailed chemical scheme output. The mean differences between both schemes are about ±25 ppbv (part per billion by volume) or 15% in the troposphere and ±10 ppbv or 100% in the stratosphere. Second, LINCO has been compared to diverse observations from satellite instruments covering the troposphere (Measurements Of Pollution In The Troposphere: MOPITT) and the stratosphere (Microwave Limb Sounder: MLS) and also from aircraft (Measurements of ozone and water vapour by Airbus in-service aircraft: MOZAIC programme) mostly flying in the upper troposphere and lower stratosphere (UTLS). In the troposphere, the LINCO seasonal variations as well as the vertical and horizontal distributions are quite close to MOPITT CO observations. However, a bias of ~&amp;minus;40 ppbv is observed at 700 Pa between LINCO and MOPITT. In the stratosphere, MLS and LINCO present similar large-scale patterns, except over the poles where the CO concentration is underestimated by the model. In the UTLS, LINCO presents small biases less than 2% compared to independent MOZAIC profiles. Third, we assimilated MOPITT CO using a variational 3D-FGAT (First Guess at Appropriate Time) method in conjunction with MOCAGE for a long run of one and a half years. The data assimilation greatly improves the vertical CO distribution in the troposphere from 700 to 350 hPa compared to independent MOZAIC profiles. At 146 hPa, the assimilated CO distribution is also improved compared to MLS observations by reducing the bias up to a factor of 2 in the tropics. This study confirms that the linear scheme is able to simulate reasonably well the CO distribution in the troposphere and in the lower stratosphere. Therefore, the low computing cost of the linear scheme opens new perspectives to make free runs and CO data assimilation runs at high resolution and over periods of several years

Central nervous system hypomyelination disrupts axonal conduction and behaviour in larval zebrafish

Myelination is essential for central nervous system (CNS) formation, health and function. As a model organism, larval zebrafish have been extensively employed to investigate the molecular and cellular basis of CNS myelination, due to their genetic tractability and suitability for non-invasive live cell imaging. However, it has not been assessed to what extent CNS myelination affects neural circuit function in zebrafish larvae, prohibiting the integration of molecular and cellular analyses of myelination with concomitant network maturation. To test whether larval zebrafish might serve as a suitable platform with which to study the effects of CNS myelination and its dysregulation on circuit function, we generated zebrafish myelin regulatory factor (myrf) mutants with CNS-specific hypomyelination and investigated how this affected their axonal conduction properties and behaviour. We found that myrf mutant larvae exhibited increased latency to perform startle responses following defined acoustic stimuli. Furthermore, we found that hypomyelinated animals often selected an impaired response to acoustic stimuli, exhibiting a bias towards reorientation behaviour instead of the stimulus-appropriate startle response. To begin to study how myelination affected the underlying circuitry, we established electrophysiological protocols to assess various conduction properties along single axons. We found that the hypomyelinated myrf mutants exhibited reduced action potential conduction velocity and an impaired ability to sustain high frequency action potential firing. This study indicates that larval zebrafish can be used to bridge molecular and cellular investigation of CNS myelination with multiscale assessment of neural circuit function.SIGNIFICANCE STATEMENTMyelination of central nervous system axons is essential for their health and function, and it now clear that myelination is a dynamic life-long process subject to modulation by neuronal activity. However, it remains unclear precisely how changes to myelination affects animal behaviour and underlying action potential conduction along axons in intact neural circuits. In recent years, zebrafish have been employed to study cellular and molecular mechanisms of myelination, due to their relatively simple, optically transparent, experimentally tractable vertebrate nervous system. Here we find that changes to myelination alter the behaviour of young zebrafish and action potential conduction along individual axons, providing a platform to integrate molecular, cellular and circuit level analyses of myelination using this model

Accelerated development with increased bone mass and skeletal response to loading suggest receptor activity modifying protein-3 as a bone anabolic target

Knockout technologies provide insights into physiological roles of genes. Studies initiated into endocrinology of heteromeric G protein-coupled receptors included deletion of receptor activity modifying protein-3, an accessory protein that alters ligand selectivity of calcitonin and calcitonin-like receptors. Initially, deletion of Ramp3-/- appeared phenotypically silent, but it has emerged that mice have a high bone mass phenotype, and more subtle alterations to angiogenesis, amylin homeostasis, and a small proportion of the effects of adrenomedullin on cardiovascular and lymphatic systems. Here we explore in detail, effects of Ramp3-/- deletion on skeletal growth/development, bone mass and response of bone to mechanical loading mimicking exercise. Mouse pups lacking RAMP3 are healthy and viable, having accelerated development of the skeleton as assessed by degree of mineralisation of specific bones, and by microCT measurements. Specifically, we observed that neonates and young mice have increased bone volume and mineralisation in hindlimbs and vertebrae and increased thickness of bone trabeculae. These changes are associated with increased osteoblast numbers and bone apposition rate in Ramp3-/- mice, and increased cell proliferation in epiphyseal growth plates. Effects persist for some weeks after birth, but differences in gross bone mass between RAMP3 and WT mice lose significance in older animals although architectural differences persist. Responses of bones of 17-week old mice to mechanical loading that mimics effects of vigorous exercise is increased significantly in Ramp3-/- mice by 30% compared with WT control mice. Studies on cultured osteoblasts from Ramp3-/- mice indicate interactions between mRNA expression of RAMPs1 and 3, but not RAMP2 and 3. Our preliminary data shows that Ramp3-/- osteoblasts had increased expression β-catenin, a component of the canonical Wnt signalling pathway known to regulate skeletal homeostasis and mechanosensitivity. Given interactions of RAMPs with both calcitonin and calcitonin-like receptors to alter ligand selectivity, and with other GPCRs to change trafficking or ligand bias, it is not clear whether the bone phenotype of Ramp3-/- mice is due to alterations in signalling mediated by one or more GPCRS. However, as antagonists of RAMP-interacting receptors are growing in availability, there appears the likelihood that manipulation of the RAMP3 signalling system could provide anabolic effects therapeutically