The effects of electrical hippocampal kindling of seizures on amino acids and kynurenic acid concentrations in brain structures

Our study demonstrated that the development of seizures during the electrically induced kindling of seizures is associated with significant changes in the concentration of kynurenic acid (KYNA) and its precursor, tryptophan (TRP). The primary finding of our study was an increase in KYNA levels and the KYNA/TRP ratio (a theoretical index of activity of the kynurenine pathway) in the amygdala and hippocampus of kindled animals. We also found decreases in the concentration of tryptophan in the hippocampus and prefrontal cortex. Changes in the concentration of KYNA and TRP in the amygdala were accompanied by a significant decrease in γ-Aminobutryic Acid (GABA) levels and an increase in the glutamate/GABA ratio. Moreover, we found a significant negative correlation between the local concentrations of KYNA and glutamate in the amygdala of kindled rats. However, there were no changes in the local concentrations of the following amino acids: glutamate, aspartate, glutamine, glycine, taurine and alanine. In conclusion, these new results suggest a modulatory influence of KYNA on the process of epileptogenesis, characterized by a negative relationship between the KYNA and glutamate systems in the amygdala

Extrapolating from model organisms in pharmacology

In this chapter we explore the process of extrapolating causal claims from model organisms to humans in pharmacology. We describe and compare four strategies of extrapolation: enumerative induction, comparative process tracing, phylogenetic reasoning, and robustness reasoning. We argue that evidence of mechanisms plays a crucial role in several strategies for extrapolation and in the underlying logic of extrapolation: the more directly a strategy establishes mechanistic similarities between a model and humans, the more reliable the extrapolation. We present case studies from the research on atherosclerosis and the development of statins, that illustrate these strategies and the role of mechanistic evidence in extrapolation

Balancing the immune response in the brain: IL-10 and its regulation

Background: The inflammatory response is critical to fight insults, such as pathogen invasion or tissue damage, but if not resolved often becomes detrimental to the host. A growing body of evidence places non-resolved inflammation at the core of various pathologies, from cancer to neurodegenerative diseases. It is therefore not surprising that the immune system has evolved several regulatory mechanisms to achieve maximum protection in the absence of pathology. Main body: The production of the anti-inflammatory cytokine interleukin (IL)-10 is one of the most important mechanisms evolved by many immune cells to counteract damage driven by excessive inflammation. Innate immune cells of the central nervous system, notably microglia, are no exception and produce IL-10 downstream of pattern recognition receptors activation. However, whereas the molecular mechanisms regulating IL-10 expression by innate and acquired immune cells of the periphery have been extensively addressed, our knowledge on the modulation of IL-10 expression by central nervous cells is much scattered. This review addresses the current understanding on the molecular mechanisms regulating IL-10 expression by innate immune cells of the brain and the implications of IL-10 modulation in neurodegenerative disorders. Conclusion: The regulation of IL-10 production by central nervous cells remains a challenging field. Answering the many remaining outstanding questions will contribute to the design of targeted approaches aiming at controlling deleterious inflammation in the brain.We acknowledge the Portuguese Foundation for Science and Technology (FCT) for providing a PhD grant to DLS (SFRH/BD/88081/2012) and a post-doctoral fellowship to SR (SFRH/BPD/72710/2010). DS, AGC and SR were funded by FEDER through the Competitiveness Factors Operational Programme (COMPETE) and National Funds through FCT under the scope of the project POCI-01-0145-FEDER007038; and by the project NORTE-01-0145-FEDER-000013, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). The MS lab was financed by Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT in the framework of the project “Institute for Research and Innovation in Health Sciences ” (POCI-01-0145-FEDER-007274). MS is a FCT Associate Investigator. The funding body had no role in the design of the study and collection, analysis, and interpretation of the data and in writing the manuscript

Group of Notified Bodies for the Construction Products Directive CPD and the participation of Building Research Institute in its work

Budowanie wspólnego europejskiego rynku wyrobów budowlanych nie jest procesem zakończonym. Ponad dwadzieścia lat funkcjonowania dyrektywy budowlanej (CPD) nie przyniosło spodziewanych efektów. Czy jej zastąpienie przez rozporządzenie 305/11 (CPD) poprawi sytuację? To pokaże czas. Tak jak pokazał, że niektóre z narzędzi wprowadzonych dyrektywą wytrzymały próbę czasu, w tym zharmonizowane specyfikacje techniczne i instytucja Jednostek Notyfikowanych. W artykule znalazły się informacje o platformie ich współpracy - Grupie Jednostek Notyfikowanych do dyrektywy CPD, jej strukturze, zadaniach i efektach ponad dziesięcioletniej pracy oraz roli ITB w tym procesie.The formation of the common European market of construction products has not been finished yet. The system based on the Construction Products Directive, which has been functioning for over twenty years, has not been fruitful enough. The question whether replacing the CPD by regulation 305/11 will improve the situation will be verified in the nearest future. What we know at the moment is that some of the tools introduced by the CPD have been verified positively, including harmonized standards and notified bodies. The article contains information about the platform of their cooperation - Group of Notified Bodies to CPD, as well as its structure, tasks, and results of its members' efforts and the role the ITB has played in the process

Anthropogenic changes of the “Old Copper Basin” area landscape (North-Sudetic Synclinorium) in the light of LiDAR-based geomorphometric analysis and archival data

O ile parametry złożowe, historia oraz techniki eksploatacji cechsztyńskich złóż rud miedzi w synklinorium północnosudeckim były przedmiotem licznych opracowań, zagadnieniu przekształceń rzeźby terenu na obszarze tzw. Starego Zagłębia Miedziowego nie poświęcono jak dotąd szczególnej uwagi. Niniejsza praca ma na celu uzupełnienie tej luki. W artykule opisano morfologię i przeprowadzono szczegółowe analizy geomorfometryczne form pogórniczych związanych bezpośrednio z eksploatacją rud miedzi i składowaniem odpadów poeksploatacyjnych na obszarze Zagłębia. W analizie i opisie form powierzchni wykorzystano dane archiwalne, ale przede wszystkim nowe metody i możliwości związane z przetwarzaniem wysokorozdzielczych numerycznych modeli terenu (NMT LiDAR – ang. Light Detection and Ranging), które są uznawane obecnie za najwierniejsze i najdokładniejsze odwzorowanie powierzchni ziemi dostępne w formie numerycznej. Na obszarze badań wyróżniono i opisano następujące antropogeniczne formy rzeźby: wielkoskalowe deformacje powierzchni terenu (niecki osiadań i zapadliska), małoskalowe deformacje powierzchni terenu (pingi), kamieniołomy oraz formy związane ze składowaniem produktów ubocznych wydobycia i przeróbki rud miedzi – zbiorniki odpadów poflotacyjnych i hałdy. Wieloaspektowe podejście badawcze pozwoliło m.in. na zobrazowanie rozkładu przestrzennego form, oszacowanie parametrów wolumetrycznych, a także wytypowanie perspektyw rekultywacji i ochrony niektórych obiektów.While the history, techniques of exploitation and deposit parameters of the copper ores in the North-Sudetic Synclinorium have been the subject of numerous investigations, the transformations of the terrain in the so-called “Old Copper Basin” (Lower Silesia, SW Poland) have not been analysed in detail before. This paper is intended to complement this gap. The authors present the results of the detailed geomorphometric analysis of the post-mining forms related directly to the copper mining. The LiDAR-based, high-resolution Digital Terrain Models (DTMs), which have been used in the analysis and description of the landforms, are currently considered as the most accurate and precise 3D-spatial data available in the numerical form. The following anthropogenic forms are distinguished in the study area: large- and small-scale ground deformations (depressions and small sinkholes), abandoned quarries, and forms associated with the exploitation and storage of the flotation wastes – post-flotation tailings and dumps. Our investigations have allowed visualization of the spatial distribution of the forms, estimation of their total volume as well as perspectives of their reclamation and protection

Analysis of the accumulation of radiation damage in selected crystals

International audienceDamage accumulation in SiC and MgAl2O4 was interpreted in the framework of the multi step damage accumulation (MSDA) model. The concept is based on the assumption that damage build-ups occur in several stages, each step being triggered by the destabilization of the current structural organization of the material. The analysis of the damaging process may thus be regarded as an identification of the current structure at each subsequent step of the damage build-up and of the forces leading to the destabilization of current structure. The analysis of mechanical properties provides a useful tool for this purpose by allowing the recognition of the mechanisms of phase transformations and helping to clarify the detailed structures of irradiated materials. (C) 2008 Elsevier B.V. All rights reserved

Déformation inélastique induite par nanoindentation cyclique de verres métalliques à base de Zirconium

International audienceInelastic deformation induced by cyclic nanoindentation in Zr-basedbulk metallic glasses. Monotonic and cyclic nanoindentation tests were carried out onZr50Cu40Al10 bulk metallic glass (BMG) at loading rates ranging from 250 to 2500 μN/s andat ambient temperature. We found that cyclic loadings induced a mechanical softeningwhich appears to be dependent on the number of cycles and the loading rates. The effectof loading rates was compared with the same nanoindentation tests on specimens of Zrbasedmetallic glass coated with CrN and TiN films. The inelastic deformation on Zr-basedmetallic glass was studied by analysing the remnant indent morphology using atomic forcemicroscopy. A free-volume mechanism was proposed for interpreting these observationsquantitatively.Des essais de nanoindentation instrumenté pour des chargements monotoneset cycliques sur deux verres métalliques massifs (VMM) à base Zirconium ont été réalisésà température ambiante et avec une vitesse de chargement qui varie de 250 à 2500 μN/s.Nous avons trouvé que les chargements cycliques induisent un adoucissement qui sembleêtre dépendant du nombre de cycles et du taux de chargement. L’effet de la vitesse de chargementa été comparé avec des essais effectués sur des échantillons du verre métallique àbase Zirconium revêtus par des films de TiN et de CrN. La déformation inélastique dans leverre métallique à base Zirconium a été étudiée en analysant par microscopie à force atomiqueles empreintes résultantes des essais de nanoindentation. Le mécanisme de volumelibre est proposé pour l’interprétation quantitative de ces observations

Nanohardness and brittleness of irradiated spinel ceramics

International audienceThe influence of the size of crystalline regions on mechanical properties of irradiated oxides has been studied using magnesium aluminate spinel MgAl2O4. The samples characterized by different dimensions of crystalline domains, from sintered ceramics with grains of few micrometers in size up to single crystals, were used in the experiments. The samples were irradiated at room temperature with 320 keV Ar2+ ions up to fluences reaching 5 × 1016 cm−2. Nanomechanical properties were measured by using a nanoindentation technique and the resistance to crack formation by measurement of the total crack lengths made by Vickers indenter. The results revealed: correlation of nanohardness with accumulated damage, radiation-induced hardness increase in grain-boundary region and significant improvement of material resistance to crack formation