A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamics

Glutamate excitotoxicity leads to fragmented mitochondria in neurodegenerative diseases, mediated by nitric oxide and S-nitrosylation of dynamin-related protein 1, a mitochondrial outer membrane fission protein. Optic atrophy gene 1 (OPA1) is an inner membrane protein important for mitochondrial fusion. Autosomal dominant optic atrophy (ADOA), caused by mutations in OPA1, is a neurodegenerative disease affecting mainly retinal ganglion cells (RGCs). Here, we showed that OPA1 deficiency in an ADOA model influences N-methyl-D-aspartate (NMDA) receptor expression, which is involved in glutamate excitotoxicity and oxidative stress. Opa1enu/+ mice show a slow progressive loss of RGCs, activation of astroglia and microglia, and pronounced mitochondrial fission in optic nerve heads as found by electron tomography. Expression of NMDA receptors (NR1, 2A, and 2B) in the retina of Opa1enu/+ mice was significantly increased as determined by western blot and immunohistochemistry. Superoxide dismutase 2 (SOD2) expression was significantly decreased, the apoptotic pathway was activated as Bax was increased, and phosphorylated Bad and BcL-xL were decreased. Our results conclusively demonstrate that not only glutamate excitotoxicity and/or oxidative stress alters mitochondrial fission/fusion, but that an imbalance in mitochondrial fission/fusion in turn leads to NMDA receptor upregulation and oxidative stress. Therefore, we propose a new vicious cycle involved in neurodegeneration that includes glutamate excitotoxicity, oxidative stress, and mitochondrial dynamics

A systematic review of outcome and outcome-measure reporting in randomised trials evaluating surgical interventions for anterior-compartment vaginal prolapse: a call to action to develop a core outcome set

INTRODUCTION: We assessed outcome and outcome-measure reporting in randomised controlled trials evaluating surgical interventions for anterior-compartment vaginal prolapse and explored the relationships between outcome reporting quality with journal impact factor, year of publication, and methodological quality. METHODS: We searched the bibliographical databases from inception to October 2017. Two researchers independently selected studies and assessed study characteristics, methodological quality (Jadad criteria; range 1-5), and outcome reporting quality Management of Otitis Media with Effusion in Cleft Palate (MOMENT) criteria; range 1-6], and extracted relevant data. We used a multivariate linear regression to assess associations between outcome reporting quality and other variables. RESULTS: Eighty publications reporting data from 10,924 participants were included. Seventeen different surgical interventions were evaluated. One hundred different outcomes and 112 outcome measures were reported. Outcomes were inconsistently reported across trials; for example, 43 trials reported anatomical treatment success rates (12 outcome measures), 25 trials reported quality of life (15 outcome measures) and eight trials reported postoperative pain (seven outcome measures). Multivariate linear regression demonstrated a relationship between outcome reporting quality with methodological quality (β = 0.412; P = 0.018). No relationship was demonstrated between outcome reporting quality with impact factor (β = 0.078; P = 0.306), year of publication (β = 0.149; P = 0.295), study size (β = 0.008; P = 0.961) and commercial funding (β = -0.013; P = 0.918). CONCLUSIONS: Anterior-compartment vaginal prolapse trials report many different outcomes and outcome measures and often neglect to report important safety outcomes. Developing, disseminating and implementing a core outcome set will help address these issues

BioTIME 2.0: Expanding and Improving a Database of Biodiversity Time Series

Motivation Here, we make available a second version of the BioTIME database, which compiles records of abundance estimates for species in sample events of ecological assemblages through time. The updated version expands version 1.0 of the database by doubling the number of studies and includes substantial additional curation to the taxonomic accuracy of the records, as well as the metadata. Moreover, we now provide an R package (BioTIMEr) to facilitate use of the database. Main Types of Variables Included The database is composed of one main data table containing the abundance records and 11 metadata tables. The data are organised in a hierarchy of scales where 11,989,233 records are nested in 1,603,067 sample events, from 553,253 sampling locations, which are nested in 708 studies. A study is defined as a sampling methodology applied to an assemblage for a minimum of 2 years. Spatial Location and Grain Sampling locations in BioTIME are distributed across the planet, including marine, terrestrial and freshwater realms. Spatial grain size and extent vary across studies depending on sampling methodology. We recommend gridding of sampling locations into areas of consistent size. Time Period and Grain The earliest time series in BioTIME start in 1874, and the most recent records are from 2023. Temporal grain and duration vary across studies. We recommend doing sample-level rarefaction to ensure consistent sampling effort through time before calculating any diversity metric. Major Taxa and Level of Measurement The database includes any eukaryotic taxa, with a combined total of 56,400 taxa. Software Format csv and. SQL

Crystal plasticity finite element simulations of pure bending of aluminium alloy AA7108

The crystal plasticity finite element method (CP-FEM) is used to investigate the influence of microstructure on the bending behaviour of the heat treatable aluminium alloy AA7108. The study comprises two materials obtained from the AA7108 aluminium alloy by different thermo-mechanical treatments. The first one is an as-cast and homogenized material consisting of large grains with random texture, while the second one is a rolled and recrystallized material having refined grains with weak deformation texture. The behaviour of the two materials in plane-strain bending is investigated numerically and compared qualitatively to existing experimental data. The crystallographic texture and grain morphology of the materials are explicitly represented in the finite element models. The numerical results display a strong effect of the grain morphology on the bending behaviour, the surface waviness and the development of shear bands. These results are consistent with the experimental observations. The simulations further indicate that crystallographic texture affects the bending behaviour of the rolled and recrystallized material.acceptedVersion(c) 2015. This is the authors’ accepted and refereed manuscript to an article published by Springer-Verlag Franc

Evolution of the Svalbard annual snow layer during the melting phase

Understanding and monitoring the evolution of annual snow is an important aspect of cryosphere research. Changes in physical proprieties such as hardness, presence of melt layers, or the shape and size of crystals can completely modify the robustness, propriety and quality of the snow. Evaluating these changes can inform the study and prediction of avalanches. The annual snow layer is also a sink for several compounds and elements. In the polar environment, many compounds can be accumulated during winter depositions, especially during the polar night. During the spring, the combination of solar radiation and the melting of annual snow can release these compounds and elements into the atmosphere and groundwater. An in-depth investigation of the evolution of the first meter of the annual snow layer was conducted in the glacier of Austre Brøggerbreen, Svalbard, between the 27th of March and the 31st of May, in concomitance with the start of the melting phase. The present monitoring study mainly aimed to evaluate changes in the thermal profile and water content during the formation of a new ice layer as well as the re-allocation of the total dissolved salts in the different snow layers.Understanding and monitoring the evolution of annual snow is an important aspect of cryosphere research. Changes in physical proprieties such as hardness, presence of melt layers, or the shape and size of crystals can completely modify the robustness, propriety and quality of the snow. Evaluating these changes can inform the study and prediction of avalanches. The annual snow layer is also a sink for several compounds and elements. In the polar environment, many compounds can be accumulated during winter depositions, especially during the polar night. During the spring, the combination of solar radiation and the melting of annual snow can release these compounds and elements into the atmosphere and groundwater. An in-depth investigation of the evolution of the first meter of the annual snow layer was conducted in the glacier of Austre Broggerbreen, Svalbard, between the 27th of March and the 31st of May, in concomitance with the start of the melting phase. The present monitoring study mainly aimed to evaluate changes in the thermal profile and water content during the formation of a new ice layer as well as the re-allocation of the total dissolved salts in the different snow layer

Matters of the heart in bioenergetics: mitochondrial fusion into continuous reticulum is not needed for maximal respiratory activity

International audienceMitochondria are dynamic structures for which fusion and fission are well characterized for rapidly dividing cells in culture. Based on these data, it has recently been proposed that high respiratory activity is the result of fusion and formation of mitochondrial reticulum, while fission results in fragmented mitochondria with low respiratory activity. In this work we test the validity of this new hypothesis by analyzing our own experimental data obtained in studies of isolated heart mitochondria, permeabilized cells of cardiac phenotype with different mitochondrial arrangement and dynamics. Additionally, we reviewed published data including electron tomographic investigation of mitochondrial membrane-associated structures in heart cells. Oxygraphic studies show that maximal ADP-dependent respiration rates are equally high both in isolated heart mitochondria and in permeabilized cardiomyocytes. On the contrary, these rates are three times lower in NB HL-1 cells with fused mitochondrial reticulum. Confocal and electron tomographic studies show that there is no mitochondrial reticulum in cardiac cells, known to contain 5,000-10,000 individual, single mitochondria, which are regularly arranged at the level of sarcomeres and are at Z-lines separated from each other by membrane structures, including the T-tubular system in close connection to the sarcoplasmic reticulum. The new structural data in the literature show a principal role for the elaborated T-tubular system in organization of cell metabolism by supplying calcium, oxygen and substrates from the extracellular medium into local domains of the cardiac cells for calcium cycling within Calcium Release Units, associated with respiration and its regulation in Intracellular Energetic Units