64 research outputs found

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

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    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

    JDP2 overexpression provokes cardiac dysfunction in mice

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    The transcriptional regulator JDP2 (Jun dimerization protein 2) has been identified as a prognostic marker for patients to develop heart failure after myocardial infarction. We now performed in vivo studies on JDP2-overexpressing mice, to clarify the impact of JDP2 on heart failure progression. Therefore, during birth up to the age of 4 weeks cardiac-specific JDP2 overexpression was prevented by doxycycline feeding in transgenic mice. Then, JDP2 overexpression was started. Already after 1 week, cardiac function, determined by echocardiography, decreased which was also resembled on the cardiomyocyte level. After 5 weeks blood pressure declined, ejection fraction and cardiac output was reduced and left ventricular dilatation developed. Heart weight/body weight, and mRNA expression of ANP, inflammatory marker genes, collagen and fibronectin increased. Collagen 1 protein expression increased, and fibrosis developed. As an additional sign of elevated extracellular matrix remodeling, matrix metalloproteinase 2 activity increased in JDP2 mice. Thus, JDP2 overexpression is deleterious to heart function in vivo. It can be concluded that JDP2 overexpression provokes cardiac dysfunction in adult mice that is accompanied by hypertrophy and fibrosis. Thus, induction of JDP2 is a maladaptive response contributing to heart failure development

    Extrapolating from model organisms in pharmacology

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    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

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    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

    Goldmines of the Wielisławka Hill (Kaczawa Upland)

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    Autorzy przedstawiają opis górnictwa złota w rejonie masywu ryolitowego Wielisławki na Pogórzu Kaczawskim, na podstawie wyników kwerendy kartograficznej i bibliograficznej, analiz numerycznych modeli terenu LiDAR, a także prac terenowych. Niniejszy materiał wzbogacają m.in. dwie unikalne mapy, które należą do najcenniejszych dzieł kartografii górniczej na terenie Polski. Powstały one około 1556 r. jako materiał pomocniczy dla rozpatrzenia konfliktu, do jakiego doszło pomiędzy właścicielami ziemskimi a górnikami z kopalni złota na Wielisławce.This paper presents the history of the gold mining activity within the Wielisławka Hill in the Kaczawskie Foothills. The results are based on a cartographic study of bibliographical research, LIDAR DTM analysis and field work. The article contains e.g. two unique maps from the collection of the State Archive in Prague which belong to the most relevant works of the cartography of mining in Poland. They have been drawn in or around 1556 as a supplementary material for the settlement of a dispute between land owners and miners from the Wielisławka gold mine. The article demonstrates that the gold mining in the Wielisławka massif had taken place on a much larger scale than hitherto expected. The mining operation has left relics in the form of sink hole fields, heaps, adits and underground galleries entering the massif of the hill by the Kaczawa river. The Wielisławka massif is nowadays a valuable destination for geotourism

    Copper mining in the Kondratów area (Kaczawskie Foothills, SW Poland)

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    W artykule przedstawiono dzieje dawnego górnictwa w okolicach Kondratowa na Pogórzu Kaczawskim, rozwiniętego w oparciu o miedzionośne utwory dolnego cechsztynu. Eksploatację podejmowano wielokrotnie przez kilka stuleci, głównie w XVI i XVIII w. Prowadziły ją zarówno gwarectwa jak i właściciele wsi. W pracy wskazano również na występowanie pogórniczych reliktów. Autorzy przeprowadzili kwerendę biblioteczną, kartograficzną oraz prace terenowe. Dodatkowo wykonano analizy NMT LiDAR, które potwierdziły występowanie pola pingów i hałd.Field studies carried out by the authors have revealed the existence of relics of historic mining in the Kondratów area in the Kaczawskie Foothills (Sudetes), consistent with information retrieved from old mining maps. LIDAR DTM analysis has confirmed the presence of heaps and sinkholes in the study area. Their approximate age could be determined in the course of further more detailed research. Mining operation in the Kondratów area has been initiated a number of times in the past throughout the centuries. Mining works have been carried out by mining companies and land owners. The operations have reached their largest scale in the 18th century. The lack of water supply on-site to power the ore processing facilities must certainly have been a major drawback; the ore had to be transported to Leszczyna for processing. In the late 19th ct. and in the 1930s the deposits have been subject to more thorough exploration. Nevertheless, a mine has not been established. Mining plants have been built in Wilków (1940s) and Nowy Kościół (1950s-1960s) instead due to richer and more accessible deposits

    Application of geomorphometric methods in mining-related ground deformation analysis – an example of the “Nowy Kościół” Copper Mine (“The Old Copper Basin”, North-Sudetic Synclinorium)

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    Podczas kartograficznych badań terenowych prowadzonych od października 2015 r. w okolicach miejscowości Nowy Kościół, na Pogórzu Kaczawskim w Sudetach Zachodnich, rozpoznano i zinwentaryzowano wiele form wskazujących na przekształcenia powierzchni terenu związane z działalnością górniczą. Kilkanaście zapadlisk, rowów i obniżeń na terenie dawnych Zakładów Górniczych (ZG) „Nowy Kościół” zaobserwowano również podczas analiz numerycznych modeli terenu oraz zdjęć satelitarnych. Określono zasięg tych form, opisano ich parametry przestrzenne i oszacowano maksymalne obniżenie powierzchni terenu w ich obrębie. Obniżenia powierzchni terenu na tym obszarze nie były jak dotąd tak szczegółowo opisane. Głównym celem przeprowadzonych badań było określenie przydatności metod geomorfometrycznych, opartych na analizie wysokorozdzielczych numerycznych modeli terenu (NMT) LiDAR, do jakościowego i ilościowego opisu deformacji powierzchni spowodowanych podziemną działalnością górniczą.During mapping work carried out since October 2015 in the Nowy Kościół area in the Kaczawskie Foothills, Western Sudetes, a number of morphological forms were identified and catalogued. They indicate surface transformation due to ceased mining activity. Several depressions and grabens were recognized during the digital terrain model and satellite images analysis. The range of deformation has been determined, and their spatial parameters and the maximal depression of the ground level within the mining area have been estimated and described. Such ground level depressions have not been examined in detail before. The main aim of the studies was to determine the usefulness of geomorphometric methods based on LiDAR digital elevation models (DEM) for the purposes of high quality description of surface deformation caused by underground mining operations

    Loading rate effect on lateral force measurements on nanostructured Ti and TiN thin films

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    International audienceTribological properties of titanium and titanium nitride nanostructured thin films as well as of silicon substrate have been studied. We report onthe effect of lateral tip displacement direction and normal force loading mode on lateral force measurements. On hard coatings such as titaniumnitride thin films, we show that the tip's scratch direction has almost no effect on lateral force measurements. A completely different behaviour hasbeen observed on titanium films. In this last case, the measured lateral force is very dependent on the scratch direction.Concerning the effect of normal force loading mode, we will show how the loading rate, rather than the sliding speed, is a very importantparameter in the case of a ramping normal load. For this purpose we have performed two sets of six scratches, for each sample. Scratch length wasfixed to 10 μm in all cases.In the first set, the scratch length and duration were kept constant. In the second one, the scratch duration was tuned in order to achieve aconstant value of the normal loading rate dFzdt. In this last case, the experimental data leads to a unique curve. This means that during nanoscratchmeasurements, normal tip displacement is controlled by the normal force loading rate. Consequently, lateral displacement speed dxdtmust be tunedin order to obtain the required value of dFzdt. This behaviour seems to be universal and not related to material hardness and Young modulus.© 2005 Elsevier B.V. All rights reserved

    Propriétés tribologiques de films minces nanostructurés

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    International audienceTribological properties of nanostructured thin films. In order todetermine the tribological properties of nanostructured thin layers of titanium andtitanium nitride with thicknesses of 300 nm, we have studied the influence of Berkovichtip’s lateral displacement orientation and normal loading rate on friction properties.For the hardest films (titanium nitride), we have showed that tip direction scratch doesnot have any effect on tribological properties. A completely different behavior isobserved for titanium. For this last case, the measured lateral force is smaller whenthe scratch test is carried out following forward tip direction. Concerning dynamicseffect on scratch measurements, we have established scaling laws for normaldisplacement versus normal force. We have showed that the relevant parameter forscratch measurements is the loading rate , deduced from these scaling laws. Thus,during scratch tests, the lateral displacement speed must be adapted to the maximumvalue of the applied normal load.Afin de déterminer les propriétés tribologiques de couches mincesnanostructurées de nitrure de titane et de titane de 300 nm d’épaisseur, nous avonsétudié l’influence du sens de déplacement latéral d’une pointe Berkovich et du tauxde chargement normal sur le comportement en frottement. Pour les films les plus durs(nitrure de titane), nous avons montré que le sens de déplacement latéral de la pointen’a aucun effet sur les propriétés tribologiques. Un comportement complètementdifférent est observé pour les films les moins durs (titane). Dans ce dernier cas, laforce latérale mesurée est plus faible lorsque le scratch test est effectué vers l’avantde la pointe. En ce qui concerne l’effet de la dynamique sur les mesures de scratch,nous avons établi des lois d’échelle pour le déplacement normal en fonction de la forcenormale. Nous avons montré que le paramètre pertinent pour les mesures est le tauxde chargement , déduit des lois d’échelle. Ainsi, durant les essais de rayures, lavitesse de déplacement latéral doit être adaptée à la valeur maximale de l’effort normalappliqué
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