Neuropsychopharmacological profiling of scoparone in mice.

Scoparone (6,7-dimethoxycoumarin) is a simple coumarin from botanical drugs of Artemisia species used in Traditional Chinese Medicine and Génépi liquor. However, its bioavailability to the brain and potential central effects remain unexplored. We profiled the neuropharmacological effects of scoparone upon acute and subchronic intraperitoneal administration (2.5-25 mg/kg) in Swiss mice and determined its brain concentrations and its effects on the endocannabinoid system (ECS) and related lipids using LC-ESI-MS/MS. Scoparone showed no effect in the forced swimming test (FST) but, administered acutely, led to a bell-shaped anxiogenic-like behavior in the elevated plus-maze test and bell-shaped procognitive effects in the passive avoidance test when given subchronically and acutely. Scoparone rapidly but moderately accumulated in the brain (Cmax < 15 min) with an apparent first-order elimination (95% eliminated at 1 h). Acute scoparone administration (5 mg/kg) significantly increased brain arachidonic acid, prostaglandins, and N-acylethanolamines (NAEs) in the FST. Conversely, subchronic scoparone treatment (2.5 mg/kg) decreased NAEs and increased 2-arachidonoylglycerol. Scoparone differentially impacted ECS lipid remodeling in the brain independent of serine hydrolase modulation. Overall, the unexpectedly potent central effects of scoparone observed in mice could have toxicopharmacological implications for humans

Pharmacometabolic Effects of Pteryxin and Valproate on Pentylenetetrazole-Induced Seizures in Zebrafish Reveal Vagus Nerve Stimulation.

Zebrafish (Danio rerio) assays provide a versatile pharmacological platform to test compounds on a wide range of behaviors in a whole organism. A major challenge lies in the lack of knowledge about the bioavailability and pharmacodynamic effects of bioactive compounds in this model organism. Here, we employed a combined methodology of LC-ESI-MS/MS analytics and targeted metabolomics with behavioral experiments to evaluate the anticonvulsant and potentially toxic effects of the angular dihydropyranocoumarin pteryxin (PTX) in comparison to the antiepileptic drug sodium valproate (VPN) in zebrafish larvae. PTX occurs in different Apiaceae plants traditionally used in Europe to treat epilepsy but has not been investigated so far. To compare potency and efficacy, the uptake of PTX and VPN into zebrafish larvae was quantified as larvae whole-body concentrations together with amino acids and neurotransmitters as proxy pharmacodynamic readout. The convulsant agent pentylenetetrazole (PTZ) acutely reduced the levels of most metabolites, including acetylcholine and serotonin. Conversely, PTX strongly reduced neutral essential amino acids in a LAT1 (SLCA5)-independent manner, but, similarly to VPN specifically increased the levels of serotonin, acetylcholine, and choline, but also ethanolamine. PTX dose and time-dependent manner inhibited PTZ-induced seizure-like movements resulting in a ~70% efficacy after 1 h at 20 µM (the equivalent of 4.28 ± 0.28 µg/g in larvae whole-body). VPN treated for 1 h with 5 mM (the equivalent of 18.17 ± 0.40 µg/g in larvae whole-body) showed a ~80% efficacy. Unexpectedly, PTX (1-20 µM) showed significantly higher bioavailability than VPN (0.1-5 mM) in immersed zebrafish larvae, possibly because VPN in the medium dissociated partially to the readily bioavailable valproic acid. The anticonvulsive effect of PTX was confirmed by local field potential (LFP) recordings. Noteworthy, both substances specifically increased and restored whole-body acetylcholine, choline, and serotonin levels in control and PTZ-treated zebrafish larvae, indicative of vagus nerve stimulation (VNS), which is an adjunctive therapeutic strategy to treat refractory epilepsy in humans. Our study demonstrates the utility of targeted metabolomics in zebrafish assays and shows that VPN and PTX pharmacologically act on the autonomous nervous system by activating parasympathetic neurotransmitters

Stojące i płynące wody Poznania

Książka zawiera 139 stron, 153 barwne fotografie oraz 135 pozycji literaturyZamiarem autorów tego opracowania było zebranie i przybliżenie czytelnikowi podstawowych wiadomości o jak największej liczbie zbiorników i cieków wodnych, znajdujących się w granicach administracyjnych Poznania. Do przedstawionych danych należy przede wszystkim położenie zbiorników, przebieg cieków wodnych, ich cechy morfometryczne, ale również tam, gdzie to było możliwe – informacje o walorach przyrodniczych, turystyczno-krajobrazowych i o jakości wody. Mają one zachęcić mieszkańców Poznania do odwiedzania opisanych miejsc w ramach wycieczek, spacerów czy choćby po to, by odpocząć od zgiełku ulic miasta i trudów pracy zawodowej. Mają również rozbudzić zainteresowanie otaczającą przyrodą młodzież szkolną, będąc uzupełnieniem wiedzy zdobywanej w ramach zajęć szkolnych.Wydanie książki dofinansowano ze środków budżetowych Miasta Poznani

Argumentacja w edukacji: postulaty badań edukacyjnych w polskiej szkole argumentacji

Uwzględniając dotychczasową działalność Polskiej Szkoły Argumentacji, w szczególności jej działalność edukacyjną wyeksponowaną podczas XV konferencji ArgDiaP, sformułowaliśmy postulaty dotyczące dalszej działalności edukacyjnej Szkoły. Ich realizacja w ciągu najbliższych lat mogłaby stanowić grunt dla długoterminowych celów edukacyjnych, takich jak (1) opracowanie spójnego programu nauczania sztuki argumentowania i krytycznego myślenia w szkołach podstawowych i średnich oraz (2) zaprojektowanie ogólnopolskich standardów i ram nauczania przedmiotów powiązanych z argumentacją i krytycznym myśleniem na poziomie studiów uniwersyteckich

Relationship Between Anti-DFS70 Autoantibodies and Oxidative Stress

Background: The anti-DFS70 autoantibodies are one of the most commonly and widely described agent of unknown clinical significance, frequently detected in healthy individuals. It is not known whether the DFS70 autoantibodies are protective or pathogenic. One of the factors suspected of inducing the formation of anti-DFS70 antibodies is increased oxidative stress. We evaluated the coexistence of anti-DFS70 antibodies with selected markers of oxidative stress and investigated whether these antibodies could be considered as indirect markers of oxidative stress. Methods: The intensity of oxidative stress was measured in all samples via indices of free-radical damage to lipids and proteins such as total oxidant status (TOS), concentrations of lipid hydroperoxides (LPH), lipofuscin (LPS), and malondialdehyde (MDA). The parameters of the non-enzymatic antioxidant system, such as total antioxidant status (TAS) and uric acid concentration (UA), were also measured, as well as the activity of superoxide dismutase (SOD). Based on TOS and TAS values, the oxidative stress index (OSI) was calculated. All samples were also tested with indirect immunofluorescence assay (IFA) and 357 samples were selected for direct monospecific anti DFS70 enzyme-linked immunosorbent assay (ELISA) testing. Results: The anti-DFS70 antibodies were confirmed by ELISA test in 21.29% of samples. Compared with anti-DFS70 negative samples we observed 23% lower concentration of LPH (P =.038) and 11% lower concentration of UA (P =.005). TOS was 20% lower (P =.014). The activity of SOD was up to 5% higher (P =.037). The Pearson correlation showed weak negative correlation for LPH, UA, and TOS and a weak positive correlation for SOD activity. Conclusion: In samples positive for the anti-DFS70 antibody a decreased level of oxidative stress was observed, especially in the case of samples with a high antibody titer. Anti-DFS70 antibodies can be considered as an indirect marker of reduced oxidative stress or a marker indicating the recent intensification of antioxidant processes

Temperature Effects Explain Continental Scale Distribution of Cyanobacterial Toxins

Insight into how environmental change determines the production and distribution of cyanobacterial toxins is necessary for risk assessment. Management guidelines currently focus on hepatotoxins (microcystins). Increasing attention is given to other classes, such as neurotoxins (e.g., anatoxin-a) and cytotoxins (e.g., cylindrospermopsin) due to their potency. Most studies examine the relationship between individual toxin variants and environmental factors, such as nutrients, temperature and light. In summer 2015, we collected samples across Europe to investigate the effect of nutrient and temperature gradients on the variability of toxin production at a continental scale. Direct and indirect effects of temperature were the main drivers of the spatial distribution in the toxins produced by the cyanobacterial community, the toxin concentrations and toxin quota. Generalized linear models showed that a Toxin Diversity Index (TDI) increased with latitude, while it decreased with water stability. Increases in TDI were explained through a significant increase in toxin variants such as MC-YR, anatoxin and cylindrospermopsin, accompanied by a decreasing presence of MC-LR. While global warming continues, the direct and indirect effects of increased lake temperatures will drive changes in the distribution of cyanobacterial toxins in Europe, potentially promoting selection of a few highly toxic species or strains.Peer reviewe

The method of corpus analysis in the study of logos and ethos

Celem artykułu jest prezentacja procesu badawczego wykorzystującego lingwistyczne metody korpusowe do wzbogacania fi lozofi cznych teorii logosu (tj. struktur inferencyjnych) i etosu (tj. struktur komunikacyjnych powiązanych z charakterem czy wiarygodnością mówcy). Te dwa typy zjawisk komunikacyjnych przyciągały uwagę fi lozofów od czasów starożytnych, kiedy to Arystoteles, jako jeden z pierwszych, zaproponował sposób rozumienia tych pojęć w swojej Retoryce. Współcześnie problem eksplozji danych, związany z rozwojem nowoczesnych technologii i Internetu, postawił przed fi lozofi ą nowe wyzwanie: możliwość zautomatyzowania procesu przetwarzania dużych zasobów danych i wydobywania informacji dotyczących tego, jakie opinie i argumenty ludzie formułują, oraz tego, kto jest uznawany za wiarygodnego mówcę, wymaga dobrego zrozumienia tego, w jaki sposób ludzie faktycznie konstruują struktury logosu i etosu – nawet jeżeli są to niepoprawne konstrukcje. Stąd też w naszych badaniach stosujemy następującą metodologię: (1) wychodzimy od teorii fi lozofi cznych, (2) następnie wybieramy dziedzinę dyskursu, dla której chcemy zidentyfi kować typowe językowe zachowania związane z logosem i etosem, (3) dane te analizujemy przy użyciu wybranych teorii, (4) na podstawie statystyk i wglądu w naturę danego dyskursu formułujemy nowe twierdzenia dotyczące interesujących nas zjawisk, (5) aby w końcu móc zastosować wyniki tych badań do wspierania automatycznego wydobywania struktur logosu i etosu z dużych zasobów danych języka naturalnego.The aim of this paper is to discuss research process which employs linguistic methods of corpus analysis in order to better understand dialogue strategies people use. Theories developed in such a way are then suitable to be used for argument mining, i.e. for automated identifi cation and extraction of these strategies from large resources of texts in natural language. The paper considers two types of communication phenomena related to Aristotelian notions of logos (i.e. inferential premise-conclusion structures) and ethos (i.e.communication structures related to the character of the speaker). The goal of the paper is accomplished in four steps. The task of identifying the main problem (Sect. 1) allows us to give an outline of the corpus study method for automated argument mining (Sect. 2). Next, the explication of this method paves the way for discussing two examples of applying the corpus method to analyse logos and ethos, namely controversy and consensus (Sect. 3) and ethotic structures in a dialogue (Sect. 4)

Enzymatic profile, adhesive and invasive properties of Candida albicans under the influence of selected plant essential oils

The influence of essential oils (EOs) used at sublethal level, on the presence and intensity of Candida albicans virulence factors was evaluated. Minimal inhibitory concentrations (MICs) of Lemon balm, Citronella, Geranium and Clove oils were established as 0.097% (v/v). Using the agar plates with substrates for proteases, phospholipases and hemolysins it was shown that C. albicans ATCC 10231 and C. albicans ATCC 90028 strains differed in the type and amount of enzymes produced. No significant difference in their total amount could be detected after pretreatment for 24 h with EOs at ½ MIC. However, the short-term (1 h) acting oils at MIC caused a statistically significant reduction in this activity. In the API ZYM test it was demonstrated that both strains exhibited activity of the same 9 out of 19 enzyme types and that EOs caused a significant decrease in the release of some of them. In the presence of subMIC of EOs, or when the fungus had previously been exposed to the MIC of oil, germ tubes formation was significantly and irreversibly reduced. Such C. albicans spotted on the Spider agar containing EOs at subMICs were unable to penetrate the agar. A significant decrease in the C. albicans adhesion to the fibroblast monolayer with respect to controls was also demonstrated when yeasts had been exposed to EOs at MIC (1 h) in liquid medium. Thus, it has been shown that tested oils, used even at subMIC, exhibit significant activity reducing the presence/quantity of important C. albicans virulence factors