Solulin reduces infarct volume and regulates gene-expression in transient middle cerebral artery occlusion in rats

<p>Abstract</p> <p>Background</p> <p>Thrombolysis after acute ischemic stroke has only proven to be beneficial in a subset of patients. The soluble recombinant analogue of human thrombomodulin, Solulin, was studied in an <it>in vivo </it>rat model of acute ischemic stroke.</p> <p>Methods</p> <p>Male SD rats were subjected to 2 hrs of transient middle cerebral artery occlusion (tMCAO). Rats treated with Solulin intravenously shortly before reperfusion were compared to rats receiving normal saline i.v. with respect to infarct volumes, neurological deficits and mortality. Gene expression of IL-6, IL-1β, TNF-α, MMP-9, CD11B and GFAP were semiquantitatively analyzed by rtPCR of the penumbra.</p> <p>Results</p> <p>24 hrs after reperfusion, rats were neurologically tested, euthanized and infarct volumes determined. Solulin significantly reduced mean total (p = 0.001), cortical (p = 0.002), and basal ganglia (p = 0.036) infarct volumes. Hippocampal infarct volumes (p = 0.191) were not significantly affected. Solulin significantly downregulated the expression of IL-1β (79%; p < 0.001), TNF-α (59%; p = 0.001), IL-6 (47%; p = 0.04), and CD11B (49%; p = 0.001) in the infarcted cortex compared to controls.</p> <p>Conclusions</p> <p>Solulin reduced mean total, cortical and basal ganglia infarct volumes and regulated a subset of cytokines and proteases after tMCAO suggesting the potency of this compound for therapeutic interventions.</p

Euclid preparation: XXVII. A UV-NIR spectral atlas of compact planetary nebulae for wavelength calibration

The Euclid mission will conduct an extragalactic survey over 15 000 deg2 of the extragalactic sky. The spectroscopic channel of the Near-Infrared Spectrometer and Photometer (NISP) has a resolution of R~450 for its blue and red grisms that collectively cover the 0.93-1.89 μm range. NISP will obtain spectroscopic redshifts for 3 107 galaxies for the experiments on galaxy clustering, baryonic acoustic oscillations, and redshift space distortion. The wavelength calibration must be accurate within 5 A to avoid systematics in the redshifts and downstream cosmological parameters. The NISP pre-flight dispersion laws for the grisms were obtained on the ground using a Fabry-Perot etalon. Launch vibrations, zero gravity conditions, and thermal stabilisation may alter these dispersion laws, requiring an in-flight recalibration. To this end, we use the emission lines in the spectra of compact planetary nebulae (PNe), which were selected from a PN database. To ensure completeness of the PN sample, we developed a novel technique to identify compact and strong line emitters in Gaia spectroscopic data using the Gaia spectra shape coefficients. We obtained VLT/X-shooter spectra from 0.3 to 2.5 μm for 19 PNe in excellent seeing conditions and a wide slit, mimicking Euclid's slitless spectroscopy mode but with a ten times higher spectral resolution. Additional observations of one northern PN were obtained in the 0.80- 1.90 μm range with the GMOS and GNIRS instruments at the Gemini North Observatory. The collected spectra were combined into an atlas of heliocentric vacuum wavelengths with a joint statistical and systematic accuracy of 0.1 A in the optical and 0.3 A in the near-infrared. The wavelength atlas and the related 1D and 2D spectra are made publicly available

High-Frequency Dynamics of Ocean pH: A Multi-Ecosystem Comparison

The effect of Ocean Acidification (OA) on marine biota is quasi-predictable at best. While perturbation studies, in the form of incubations under elevated pCO2, reveal sensitivities and responses of individual species, one missing link in the OA story results from a chronic lack of pH data specific to a given species' natural habitat. Here, we present a compilation of continuous, high-resolution time series of upper ocean pH, collected using autonomous sensors, over a variety of ecosystems ranging from polar to tropical, open-ocean to coastal, kelp forest to coral reef. These observations reveal a continuum of month-long pH variability with standard deviations from 0.004 to 0.277 and ranges spanning 0.024 to 1.430 pH units. The nature of the observed variability was also highly site-dependent, with characteristic diel, semi-diurnal, and stochastic patterns of varying amplitudes. These biome-specific pH signatures disclose current levels of exposure to both high and low dissolved CO2, often demonstrating that resident organisms are already experiencing pH regimes that are not predicted until 2100. Our data provide a first step toward crystallizing the biophysical link between environmental history of pH exposure and physiological resilience of marine organisms to fluctuations in seawater CO2. Knowledge of this spatial and temporal variation in seawater chemistry allows us to improve the design of OA experiments: we can test organisms with a priori expectations of their tolerance guardrails, based on their natural range of exposure. Such hypothesis-testing will provide a deeper understanding of the effects of OA. Both intuitively simple to understand and powerfully informative, these and similar comparative time series can help guide management efforts to identify areas of marine habitat that can serve as refugia to acidification as well as areas that are particularly vulnerable to future ocean change

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic The past and the near future

BackgroundThis study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases.Materials and methodsA survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019.ResultsQuestionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples.ConclusionsThe COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe

Analysis of the expression of nine secreted matrix metalloproteinases and their endogenous inhibitors in the brain of mice subjected to ischaemic stroke.

Matrix metalloproteinases (MMPs) are a family of more than twenty secreted and cell-surface endopeptidases. Among them, MMP2, MMP3 and MMP9 are involved in blood-brain barrier injury and neuronal death after cerebral ischaemia. On the other hand, very little is known about the expression of the other secreted MMPs. Herein, we compared the global changes in MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12 and MMP13, and their endogenous inhibitors TIMP1 and TIMP2, both at the mRNA and protein levels, during the hyperacute (6 h), acute (24 h) and subacute (72 h) stages following transient focal cerebral ischaemia and treatment with recombinant tissue plasminogen activator (rtPA). We observed a significant increase in MMP1, MMP2, MMP9, MMP10, MMP13 and TIMP1 levels during the acute stage of reperfusion, which was further amplified during the subacute stage for MMP1, MMP2, MMP10 and TIMP1. In general, no change of MMP3, MMP7, MMP8, MMP12 and TIMP2 was observed. However, rtPA treatment induced a rapid increase in MMP1/TIMP2, MMP2/TIMP2, MMP8/TIMP2 and MMP9/TIMP2 ratios during the hyperacute stage of reperfusion compared to saline treatment, which may have potential implications in the early disruption of the blood-brain barrier after rtPA treatment

Distribution of sterol and fatty alcohol biomarkers in particulate matter from the frontal structure of the Alboran Sea (S.W Mediterranean Sea)

Sterol and fatty alcohol biomarkers were analyzed in suspended and sinking particles from the water column (20-300 m) of the Almeria-Oran frontal zone to characterize the biogenic sources and biogeochemical processes. Diatom- and haptophyte-related sterols were predominant at all sites and vertical distributions of sterol, and fatty alcohol biomarkers in sinking particles were markedly different from suspended particles. In contrast to the relatively fresh sinking particles with elevated concentrations of phyto- and zooplanktonic sterols, suspended particles were extensively degraded with increasing depth and exhibited a more terrestrial and zooplanktonic signature with depth. Sterol and alcohol biomarkers distributions and delta(13)C values from the jet core and the associated gyre of Atlantic waters showed a decoupling between the sinking particles of 100- and 300-m depth, demonstrating the influence of lateral advection in the frontal zone. In contrast, vertical transport of the particulate organic matter in Mediterranean waters was interpreted from the similar isotopic and molecular composition at both depths. The high abundance of phytosterols and phytol below the euphotic zone at 100 m signified that downwelling of biomass occurred on the downstream side of the gyre. The high concentrations of phytosterols and POC, in combination with the high phytosterols/phytol ratio, indicated the accumulation of detrital plant material in the oligotrophic Mediterranean waters near the frontal zone. A higher contribution of phytol in the sinking particles collected during the night at the surface of the jet and at the upstream side of the gyre provided evidence of diel vertical zooplankton migration and important grazing by herbivorous zooplankton. Carbon isotope ratios of sterols confirmed that the 24-ethylcholest-5-en-3beta-ol, commonly associated with terrestrial sources, was a substantial constituent of the phytoplankton in this area. However, the more delta(13)C depleted values obtained for this compound in suspended particles suggested that there was some terrestrial contribution that only becomes evident after degradation of the more labile marine organic matter. (C) 2003 Elsevier Science B.V. All rights reserved