The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner

The NKCC1 ion transporter contributes to the pathophysiology of common neurological disorders, but its function in microglia, the main inflammatory cells of the brain, has remained unclear to date. Therefore, we generated a novel transgenic mouse line in which microglial NKCC1 was deleted. We show that microglial NKCC1 shapes both baseline and reactive microglia morphology, process recruitment to the site of injury, and adaptation to changes in cellular volume in a cell-autonomous manner via regulating membrane conductance. In addition, microglial NKCC1 deficiency results in NLRP3 inflammasome priming and increased production of interleukin-1 beta (IL-1 beta), rendering microglia prone to exaggerated inflammatory responses. In line with this, central (intracortical) administration of the NKCC1 blocker, bumetanide, potentiated intracortical lipopolysaccharide (LPS)-induced cytokine levels. In contrast, systemic bumetanide application decreased inflammation in the brain. Microglial NKCC1 KO animals exposed to experimental stroke showed significantly increased brain injury, inflammation, cerebral edema, and, worse, neurological outcome. Thus, NKCC1 emerges as an important player in controlling microglial ion homeostasis and inflammatory responses through which microglia modulate brain injury. The contribution of microglia to central NKCC1 actions is likely to be relevant for common neurological disorders.Peer reviewe

Multicentre comparison of a diagnostic assay: Aquaporin-4 antibodies in neuromyelitis optica

Objective Antibodies to cell surface central nervous system proteins help to diagnose conditions which often respond to immunotherapies. The assessment of antibody assays needs to reflect their clinical utility. We report the results of a multicentre study of aquaporin (AQP) 4 antibody (AQP4-Ab) assays in neuromyelitis optica spectrum disorders (NMOSD). Methods Coded samples from patients with neuromyelitis optica (NMO) or NMOSD (101) and controls (92) were tested at 15 European diagnostic centres using 21 assays including live (n=3) or fixed cell-based assays (n=10), flow cytometry (n=4), immunohistochemistry (n=3) and ELISA (n=1). Results Results of tests on 92 controls identified 12assays as highly specific (0-1 false-positive results). 32 samples from 50 (64%) NMO sera and 34 from 51 (67%) NMOSD sera were positive on at least two of the 12 highly specific assays, leaving 35 patients with seronegative NMO/spectrum disorder (SD). On the basis of a combination of clinical phenotype and the highly specific assays, 66 AQP4-Ab seropositive samples were used to establish the sensitivities (51.5-100%) of all 21 assays. The specificities (85.8-100%) were based on 92 control samples and 35 seronegative NMO/SD patient samples. Conclusions The cell-based assays were most sensitive and specific overall, but immunohistochemistry or flow cytometry could be equally accurate in specialist centres. Since patients with AQP4-Ab negative NMO/SD require different management, the use of both appropriate control samples and defined seronegative NMOSD samples is essential to evaluate these assays in a clinically meaningful way. The process described here can be applied to the evaluation of other antibody assays in the newly evolving field of autoimmune neurology

Directional turnover towards larger-ranged plants over time and across habitats

Species turnover is ubiquitous. However, it remains unknown whether certain types of species are consistently gained or lost across different habitats. Here, we analysed the trajectories of 1827 plant species over time intervals of up to 78 years at 141 sites across mountain summits, forests, and lowland grasslands in Europe. We found, albeit with relatively small effect sizes, displacements of smaller- by larger-ranged species across habitats. Communities shifted in parallel towards more nutrient-demanding species, with species from nutrient-rich habitats having larger ranges. Because these species are typically strong competitors, declines of smaller-ranged species could reflect not only abiotic drivers of global change, but also biotic pressure from increased competition. The ubiquitous component of turnover based on species range size we found here may partially reconcile findings of no net loss in local diversity with global species loss, and link community-scale turnover to macroecological processes such as biotic homogenisation

<scp>ReSurveyEurope</scp>: A database of resurveyed vegetation plots in Europe

AbstractAimsWe introduce ReSurveyEurope — a new data source of resurveyed vegetation plots in Europe, compiled by a collaborative network of vegetation scientists. We describe the scope of this initiative, provide an overview of currently available data, governance, data contribution rules, and accessibility. In addition, we outline further steps, including potential research questions.ResultsReSurveyEurope includes resurveyed vegetation plots from all habitats. Version 1.0 of ReSurveyEurope contains 283,135 observations (i.e., individual surveys of each plot) from 79,190 plots sampled in 449 independent resurvey projects. Of these, 62,139 (78%) are permanent plots, that is, marked in situ, or located with GPS, which allow for high spatial accuracy in resurvey. The remaining 17,051 (22%) plots are from studies in which plots from the initial survey could not be exactly relocated. Four data sets, which together account for 28,470 (36%) plots, provide only presence/absence information on plant species, while the remaining 50,720 (64%) plots contain abundance information (e.g., percentage cover or cover–abundance classes such as variants of the Braun‐Blanquet scale). The oldest plots were sampled in 1911 in the Swiss Alps, while most plots were sampled between 1950 and 2020.ConclusionsReSurveyEurope is a new resource to address a wide range of research questions on fine‐scale changes in European vegetation. The initiative is devoted to an inclusive and transparent governance and data usage approach, based on slightly adapted rules of the well‐established European Vegetation Archive (EVA). ReSurveyEurope data are ready for use, and proposals for analyses of the data set can be submitted at any time to the coordinators. Still, further data contributions are highly welcome.</jats:sec

Serum Periostin May Help to Identify Patients with Poor Collaterals in the Hyperacute Phase of Ischemic Stroke

Background: Periostin is a glycoprotein that mediates cell functions in the extracellular matrix and appears to be a promising biomarker in neurological damage, such as ischemic stroke (IS). We aimed to measure serum periostin levels in the hyperacute phase of ischemic stroke to explore its predictive power in identification of patients with poor collaterals (ASPECT &lt; 6). Methods: We prospectively enrolled 122 patients with acute ischemic stroke within the first 6 h after onset. The early ischemic changes were evaluated by calculating ASPECT score on admission using a native CT scan. An unfavorable outcome was defined as the modified Rankin Scale (mRS) &gt; 2 at 90 days follow-up. Blood samples were collected on admission immediately after CT scan and periostin serum concentrations were determined by ELISA. Results: The admission concentration of serum periostin was significantly higher in patients with unfavorable outcome than in patients with favorable outcome (615 ng/L, IQR: 443&ndash;1070 vs. 390 ng/L, 260&ndash;563, p &lt; 0.001). In a binary logistic regression model, serum periostin level was a significant predictor for ASPECT &lt; 6 status on admission, within 6 h after stroke onset (OR, 5.911; CI, 0.990&ndash;0.999; p = 0.015). Conclusion: Admission periostin levels can help to identify patients who are not suitable for neurointervention, especially if advanced neuroimaging is not available

Preparation and characterization of multiwalled carbon nanotube/In2O3 composites

We have prepared multiwalled carbon nanotube (MWCNT)/In2O3 composites using a simple impregnation method. The precursor compound indium(III) chloride (InCl3) was used to cover the surface of MWCNTs and distilled water was used as solvent. The applied mass ratio was 4:1 (In2O3/MWCNT), and during the calcination process different temperatures (300, 350 and 400 degrees C) were investigated. The produced materials were characterized by X-ray diffraction, energy-dispersive X-ray spectroscopy, Raman spectroscopy, Fourier transform infrared spectroscopy, transmission and scanning electron microscopy, and a thermogravimetric analysis was executed also. The average thickness of the produced surface layer and the average sizes of the In2O3 particles were calculated with the Scherrer formula and the ImageJ-program. The results show that the heat treatment temperature affected the characteristic morphology and the crystal structure of the as-prepared composite. These multiwalled carbon nanotube-based composites are promising candidates as gas sensors and catalyst. (c) 2013 Elsevier Ltd. All rights reserved

Chemical challenges during the synthesis of MWCNT-based inorganic nanocomposite materials

Multiwalled carbon nanotubes (MWCNTs) were successfully covered with metal oxides - such as TiO2, ZnO, Al2O3, SnO2, and In2O3 nanoparticles - with different preparation methods under solvent conditions. The applied synthesis techniques were impregnation, a hydrothermal process and a ball-milling method. As-prepared inorganic coverage layers were characterized by TEM, HRTEM, SEM, SEM-EDX, and X-ray diffraction techniques. Results revealed that the choice of synthesis technique affects the quality and the layer structure of the deposited inorganic particles on the surface of carbon nanotubes. These materials might be suitable for nanotechnology applications. (C) 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei

The effect of titania precursor on the morphology of prepared TiO2/MWCNT nanocomposite materials

Since materials science is of great importance, the application of composite materials based on carbon nanotubes (CNTs) is widely investigated. Current work is aimed at preparing nanocomposites of TiO2/MWCNT using an impregnation method combined with slow hydrolysis. Different titanium alkoxide compounds as Ti(OEt)(4), Ti(OiPr)(4), and Ti(OBu)(4), respectively, were used as precursor materials to cover the surface of CNTs in ethanolic medium. In our samples themass ratiowas 10:1 (TiO2:MWCNT). The produced composite materials were characterized by X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), Raman microscopy, transmission (TEM) and scanning electron microscopy (SEM) techniques; moreover, thermal analysis and the determination of the specific surface area (BET) were also carried out. These as-prepared TiO2/MWCNT composites were also tested as photocatalysts in degradation reaction of the model compound salicylic acid. (C) 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei