Neurosteroids and focal epileptic disorders

Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. The most studied neurosteroids—allopregnanolone and allotetrahydrodeoxycorticosterone (THDOC)—are known to modulate GABAA receptor-mediated transmission, thus playing a role in controlling neuronal network excitability. Given the role of GABAA signaling in epileptic disorders, neurosteroids have profound eects on seizure generation and play a role in the development of chronic epileptic conditions (i.e., epileptogenesis). We review here studies showing the eects induced by neurosteroids on epileptiform synchronization in in vitro brain slices, on epileptic activity in in vivo models, i.e., in animals that were made epileptic with chemoconvulsant treatment, and in epileptic patients. These studies reveal that neurosteroids can modulate ictogenesis and the occurrence of pathological network activity such as interictal spikes and high-frequency oscillations (80–500 Hz). Moreover, they can delay the onset of spontaneous seizures in animal models of mesial temporal lobe epilepsy. Overall, this evidence suggests that neurosteroids represent a new target for the treatment of focal epileptic disorders

Valorisation de l'acide D-glucarique par une synthèse rapide, simple, verte et sans solvant de polyamides linéaires et non protégés à partir d'un dérivé estérifié

« Bien que les plastiques soient essentiels (peu coûteux et durables), leur production est énorme et ne fait qu'augmenter, ce qui cause des impacts considérables sur la santé humaine et animale et sur l'environnement. Ces problèmes, provoqués par la formation (produits fossiles utilisés) des plastiques et la gestion inappropriée de leurs déchets, peuvent être atténués par le développement de polymères biosourcés, biodégradables et recyclables. L'abondance et le faible coût des sucres en font une classe de molécules de choix pour la synthèse de polymères biosourcés. La modification des groupes fonctionnels des sucres et de leur structure représente aussi un avantage. De plus, les sucres possèdent une diversité stéréochimique et dans leurs propriétés physiques et chimiques.Cette recherche a pour but de valoriser l'acide D-glucarique par la formation d'un polyamide. Cette synthèse permet aussi d'offrir une voie alternative à la pétrochimie. Éventuellement, ce procédé de polymérisation permettra de valoriser des résidus provenant de la biomasse.La recherche a permis la synthèse sans solvant de polyamides biosourcés, polyhydroxylés et linéaires (aucun polyester formé) à partir du D-glucarate de diéthyle. L'acide D-glucarique, un dérivé du glucose, permet une synthèse à haut rendement du diester. Le D-glucarate de diéthyle est un mélange de ses formes linéaires et cycliques (lactone à 5 membres). La polycondensation du 1,6-hexaméthylènediamine (HMDA) et du D-glucarate de diéthyle a conduit à la formation d'un polyamide avec des rendements entre 67-94 %. Le monomère a été synthétisé à partir d'un excès d'HMDA (10/1). Un poly(hexaméthylène D-glucaramide) de 4108 g/mol (14 unités répétitives) et ayant une température de transition vitreuse de 46 °C a été synthétisé. Les polyamides sont solubles principalement dans le diméthylsulfoxyde (DMSO), sont majoritairement cristallins et partiellement décomposés. La nouvelle méthode de polymérisation est simple, rapide et écologique en plus de ne pas nécessiter la protection des groupes alcools et de pouvoir donner des degrés de polymérisation plus élevés ou comparables à la littérature.L'utilisation d'un solvant permettrait d'augmenter les réactions intermoléculaires, ce qui favoriserait l'obtention d'une plus haute masse moléculaire pour le polyamide. Un solvant permettrait aussi de diminuer la température réactionnelle et de réduire la décomposition. -- Mot(s) clé(s) en français : biomasse, sucre, acide D-glucarique non protégé, valorisation, HMDA, polymérisation sans solvant, synthèse verte, polyamide biosourcé, polymère linéaire. » « Although plastics are essential (inexpensive and durable), their production is huge and constantly increases, causing considerable impacts on human and animal health and on the environment. These problems, caused by the formation (fossil products used) of plastics and the inappropriate management of their waste, can be mitigated by the development of bio-based, biodegradable and recyclable polymers. The abundance and low cost of sugars make them a class of molecule of choice for the synthesis of bio-based polymers. The modification of the functional groups of sugars and their structure is also an advantage. In addition, sugars possess a diversity in stereochemistry and in their physical and chemical properties.The aim of this research is to valorize the D-glucaric acid by the formation of a polyamide. This synthesis also offers an alternative route to petrochemicals. Eventually, this polymerization process will allow the valorization of biomass residues.Research has allowed the neat synthesis of bio-based, polyhydroxylated and linear (no polyesters formed) polyamides from diethyl D-glucarate. D-glucaric acid, a derivative of glucose, enables high yield synthesis of the diester. Diethyl D-glucarate is a mixture of its linear and cyclic forms (5 membered ring lactone). The polycondensation of 1,6-hexamethylenediamine (HMDA) and diethyl D-glucarate led to the formation of a polyamide in yields between 67-94%. The monomer was synthesized from an excess of HMDA (10/1). Poly(hexamethylene D-glucaramide) of 4108 g/mol (14 repeating units) and having a glass transition temperature of 46°C was synthesized. The polyamides are soluble mainly in dimethyl sulfoxide (DMSO), are predominantly crystalline, and partially decomposed. The new polymerization method is simple, fast and environmentally friendly in addition to not requiring the protection of alcohol groups and can give higher or comparable degrees of polymerization to literature.The use of a solvent would increase the intermolecular reactions, which would promote a higher molecular weight for the polyamide. A solvent would also decrease the reaction temperature and reduce decomposition. -- Mot(s) clé(s) en anglais : biomass, sugar, unprotected D-glucaric acid, valorization, HMDA, neat polymerization, green synthesis, bio-based polyamide, linear polymer.

STR-818: THE EFFECT OF RELAXATION ON THE SLIP RESISTANCE OF METALLIZED FAYING SURFACES IN SLIP-CRITICAL CONNECTIONS

Metallizing has emerged as an effective protective coating for steel bridge members, providing a physical barrier and a galvanic protection. Recent research has shown that metallized faying surfaces used in high strength bolted connections provide higher slip resistance than specified values for uncoated blast-cleaned faying surfaces in North American design standards. As a particularity, relaxation of the clamping force is observed in the slip-critical connections with metallized faying surfaces. In this study, tests were designed to evaluate the effect of relaxation on the slip resistance of metallized faying surfaces in high strength bolted connections. Some design parameters included in this study are the coating thickness, the amount of bolt preload, the type of bolt and the presence of burrs. Test results showed that the relaxation of the clamping force does not adversely affect the slip resistance of connections with metallized faying surfaces

Lowbush blueberry fruit yield and growth response to inorganic and organic N-fertilization when competing with two common weed species

Inorganic N fertilizers are commonly used in commercial blueberry fields; however, this form of N can favor increased weed species’ growth, which can ultimately reduce the benefits of fertilization. We hypothesized that chipped ramial wood (CRW) compost is an effective alternative organic fertilizer for blueberry plants when weeds are present, as ericaceous shrub species are generally more efficient in utilizing organic N than herbaceous weed species. In this study, we measured the growth, fruit yield, and foliar N response of lowbush blueberry (Vaccinium angustifolium Aiton) to an application of 45 kg N ha-1 in the form of organic (CRW) or inorganic N (ammonium sulfate) in two areas of a commercial field colonized by either poverty oat grass (Danthonia spicata (L.) Beauv.) or sweet fern (Comptonia peregrina (L.) Coult.). We also assessed the impact of the fertilization treatments on litter decomposition rates. Contrary to our hypothesis, we found no significant increase in blueberry fruit yield or growth using CRW. By contrast, inorganic N-fertilization increased fruit yield by 70%. The effect was higher in the area colonized by D. spicata (+83%) than by C. peregrina (+45%). Blueberry fruit yield was on average twice higher in the area of the field having D. spicata than C. peregrina, suggesting a stronger competition with the latter. However, the increase in D. spicata density from 0–1 to >25 plants m-2 reduced fruit production by three-fold and strongly impacted vegetative growth in both fertilized and unfertilized plots. The impact of increased C. peregrina density was comparatively much lower, especially on vegetative growth, which was much higher in the area having C. peregrina. These patterns are likely due to a lower competition for N uptake with C. peregrina as this species can derive N from the atmosphere. Interestingly, the higher fruit yield in the area colonized by D. spicata occurred even in plots where the weeds were nearly absent (density of 0–1 plant m-2), revealing the influence of unidentified variables on blueberry fruit yield. We hypothesized that this difference resulted from over-optimal foliar N concentrations in the area colonized by C. peregrina as suggested by the significantly higher foliar N concentrations and by the negative correlation between foliar N concentrations and fruit yields in this area. The possibility of an influence of C. peregrina on flowering and pollination success, as well as of unidentified local site conditions is discussed. The tested N-fertilization treatments did not affect foliar N concentrations or litter decomposition rates. Overall, our results show that ammonium sulfate is very effective at increasing fruit yields but that both fruit yields and the efficiency of the N-fertilization treatment are decreased by increased D. spicata density, especially above 25 plants m-2. Although CRW did not significantly enhance fruit yields in the short term, this fertilizer may have a long-term beneficial effect

Development of a methodology for predicting landslide hazards at a regional scale

Landslide risk analysis is a common geotechnical evaluation and it aims to protect life and infrastructure. In the case of sensitive clay zones, landslides can affect large areas and are difficult to predict. Here we propose a methodology to determine the landslide hazard across a large territory, and we apply our approach to the Saint-Jean-Vianney area, Quebec, Canada. The initial step consists of creating a 3D model of the surficial deposits of the target area. After creating a chart of the material electrical resistivity adapted for eastern Canada, we applied electric induction to interpret the regional soil. We transposed parameter values obtained from the laboratory to a larger scale, that is to a regional slope using the results of a back analysis undertaken earlier, on a smaller slide within the same area. The regional 3D model of deposits is then used to develop a zonation map of slopes that are at risk and their respective constraint areas with the study region. This approach allowed us to target specific areas where a more precise stability analysis would be required. Our methodology offers an effective tool for stability analysis in territories characterized by the presence of sensitive clays

Can ‘Hebb’ Be Distracted? Testing the Susceptibility of Sequence Learning to Auditory Distraction

Sequence learning plays a key role in many daily activities such as language and skills acquisition. The present study sought to assess the nature of the Hebb repetition effect—the enhanced serial recall for a repeated sequence of items compared to random sequences—by examining the vulnerability of this classical sequence-learning phenomenon to auditory distraction. Sound can cause unwanted distraction by either interfering specifically with the processes involved in the focal task (interference-by-process), or by diverting attention away from a focal task (attentional capture). Participants were asked to perform visual serial recall, in which one to-be-remembered sequence was repeated every four trials, while ignoring irrelevant sound. Whereas both changing-state (Experiment 1) and deviant sounds (Experiment 2) disrupted recall performance compared to steady-state sounds, performance for the repeated sequence increased across repetitions at the same rate regardless of the sound condition. Such findings suggest that Hebbian sequence learning is impervious to environmental interference, which provides further evidence that the Hebb repetition effect is an analogue of word-form learning

Risks, benefits, and knowledge gaps of non-native tree species in Europe

Changing ecosystem conditions and diverse socio-economical events have contributed to an ingrained presence of non-native tree species (NNTs) in the natural and cultural European landscapes. Recent research endeavors have focused on different aspects of NNTs such as legislation, benefits, and risks for forestry, emphasizing that large knowledge gaps remain. As an attempt to fulfill part of these gaps, within the PEN-CAFoRR COST Action (CA19128) network, we established an open-access questionnaire that allows both academic experts and practitioners to provide information regarding NNTs from 20 European countries. Then, we integrated the data originating from the questionnaire, related to the country-based assessment of both peer-reviewed and grey literature, with information from available datasets (EUFORGEN and EU-Forest), which gave the main structure to the study and led to a mixed approach review. Finally, our study provided important insights into the current state of knowledge regarding NNTs. In particular, we highlighted NNTs that have shown to be less commonly addressed in research, raising caution about those characterized by an invasive behavior and used for specific purposes (e.g., wood production, soil recultivation, afforestation, and reforestation). NNTs were especially explored in the context of resilient and adaptive forest management. Moreover, we emphasized the assisted and natural northward migration of NNTs as another underscored pressing issue, which needs to be addressed by joint efforts, especially in the context of the hybridization potential. This study represents an additional effort toward the knowledge enhancement of the NNTs situation in Europe, aiming for a continuously active common source deriving from interprofessional collaboration.info:eu-repo/semantics/publishedVersio

Highest drought sensitivity and lowest resistance to growth suppression are found in the range core of the tree Fagus sylvatica L. not the equatorial range edge

Biogeographical and ecological theory suggests that species distributions should be driven to higher altitudes and latitudes as global temperatures rise. Such changes occur as growth improves at the poleward edge of a species distribution and declines at the range edge in the opposite or equatorial direction, mirrored by changes in the establishment of new individuals. A substantial body of evidence demonstrates that such processes are underway for a wide variety of species. Case studies from populations at the equatorial range edge of a variety of woody species have led us to understand that widespread growth decline and distributional shifts are underway. However, in apparent contrast, other studies report high productivity and reproduction in some range edge populations. We sought to assess temporal trends in the growth of the widespread European beech tree (Fagus sylvatica) across its latitudinal range. We explored the stability of populations to major drought events and the implications for predicted widespread growth decline at its equatorial range edge. In contrast to expectations, we found greatest sensitivity and low resistance to drought in the core of the species range, while dry range edge populations showed particularly high resistance to drought and little evidence of drought-linked growth decline. We hypothesise that this high range-edge resistance to drought is driven primarily by local environmental factors that allow relict populations to persist despite regionally unfavourable climate. The persistence of such populations demonstrates that range edge decline is not ubiquitous and is likely to be driven by declining population density at the landscape scale rather than sudden and widespread range retraction

Value of ultrasonography as a marker of early response to abatacept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results from the APPRAISE study

Objectives: To study the responsiveness of a combined power Doppler and greyscale ultrasound (PDUS) score for assessing synovitis in biologic-naïve patients with rheumatoid arthritis (RA) starting abatacept plus methotrexate (MTX). Methods: In this open-label, multicentre, single-arm study, patients with RA (MTX inadequate responders) received intravenous abatacept (∼10 mg/kg) plus MTX for 24 weeks. A composite PDUS synovitis score, developed by the Outcome Measures in Rheumatology–European League Against Rheumatism (OMERACT–EULAR)-Ultrasound Task Force, was used to evaluate individual joints. The maximal score of each joint was added into a Global OMERACT–EULAR Synovitis Score (GLOESS) for bilateral metacarpophalangeal joints (MCPs) 2–5 (primary objective). The value of GLOESS containing other joint sets was explored, along with clinical efficacy. Results: Eighty-nine patients completed the 24-week treatment period. The earliest PDUS sign of improvement in synovitis was at week 1 (mean change in GLOESS (MCPs 2–5): −0.7 (95% CIs −1.2 to −0.1)), with continuous improvement to week 24. Early improvement was observed in the component scores (power Doppler signal at week 1, synovial hyperplasia at week 2, joint effusion at week 4). Comparable changes were observed for 22 paired joints and minimal joint subsets. Mean Disease Activity Score 28 (C reactive protein) was significantly reduced from weeks 1 to 24, reaching clinical meaningful improvement (change ≥1.2) at week 8. Conclusions: In this first international prospective study, the composite PDUS score is responsive to abatacept. GLOESS demonstrated the rapid onset of action of abatacept, regardless of the number of joints examined. Ultrasound is an objective tool to monitor patients with RA under treatment. Trial registration number: NCT00767325