Impact of seasonal and Organ-Related Fluctuations on the anthelmintic properties and chemical profile of Cladium mariscus (L.) Pohl Extracts

The use of plants and their metabolites stands as a promising option to tackle parasitic infections by gastrointestinal nematodes (GIN) in integrated control strategies. Still, the influence of environmental and phenological factors, and their interactions, in the wild on the metabolomics and biological properties of target plant species, is often disregarded. In this work, we hypothesized that variations in the anthelmintic (AH) properties and chemical composition of extracts from the salt tolerant species Cladium mariscus L. Pohl (sawgrass) may be influenced by seasonal factors and organ-parts. To test this hypothesis, acetone/water extracts were prepared from dried biomass obtained from aerial organs collected from sawgrass in consecutive seasons and tested against Haemonchus contortus and Trichostrongylus colubriformis by the larval exsheathment inhibition assay (LEIA) and egg hatching inhibition assay (EHIA). To ascertain the role of plant organ, the activity of leaves and inflorescences extracts from summer samples was compared. The role of polyphenols in the anthelmintic activity depending on GINs and fluctuations across seasons and plant organs was assessed using polyvinylpolypyrrolidone (PVPP), coupled with an in-depth chemical profiling analysis using high-performance liquid chromatography completed with electrospray ionization mass spectrometric detection (HPLC-ESI-MSn). Main differences in anthelmintic activities were observed for summer and autumn samples, for both assays. Moreover, inflorescences' extracts were significantly more active than those from leaves against both parasite species on EHIA and against H. contortus on LEIA. Application of PVPP totally inhibit the AH effects based on EHIA and only partly for LEIA. Non-treated PVPP extracts were predominantly composed of flavan-3-ols, proanthocyanidins, luteolin and glycosylated flavonoids, while two flavonoid glycosides were quantified in all PVPP-treated samples. Thus, the activity of such compounds should be further explored, although some unknown metabolites remain to be identified. This study reinforces the hypothesis of the AH potential of sawgrass and of its polyphenolic metabolites uses as nutraceutical and/or phytotherapeutic drugs.info:eu-repo/semantics/publishedVersio

Entwicklung von Phytophthora-resistentem Zuchtmaterial für den ökologischen Landbau

Die Ansprüche des ökologischen Landbaus an Kartoffelsorten unterscheiden sich zum Teil erheblich von denen des konventionellen Anbaus. Dies ist bedingt durch den alternativen Pflanzenschutz mit mechanischer Unkrautbekämpfung sowie durch eine in der Regel geringere Stickstoffversorgung der Pflanzen. Darum benötigt der ökologische Landbau spezielle Sorten, die neben den vom Verbraucher gewünschten Qualitätsmerkmalen auch eine hohe Widerstandsfähigkeit gegenüber Krankheiten und Schädlingen besitzen, durch schnelle Jugendentwicklung das Unkrautwachstum unterdrücken und eine hohe Nährstoffeffizienz aufweisen. Um neue Zuchtstämme zu schaffen, in denen die im Biolandbau gewünschten Eigenschaften kombiniert vorliegen, etablierte das seit 2012 im „Bundesprogramm Ökologischer Landbau und andere Formen nachhaltiger Landwirtschaft“ geförderte Projekt „Entwicklung von Phytophthora-resistentem Zuchtmaterial für den ökologischen Landbau“ ein Zuchtprogramm speziell für den ökologischen Kartoffelanbau. Für die Züchtung auf geringe Anfälligkeit gegenüber der Kraut- und Knollenfäule, die durch den Oomyceten Phytophthora infestans hervorgerufen wird, wurde auf resistente Kartoffelklone aus der Vorzüchtung des Julius-Kühn Institutes zurückgegriffen. Die untersuchten Zuchtstämme und Vergleichssorten wurden parallel in einem Beobachtungsanbau hinsichtlich weiterer agronomischer und qualitativer Eigenschaften wie Ertragsleistung, Wuchsform, Stärkegehalt, Speise- und Veredelungseignung und Abreifeverhalten untersucht. Weitere Resistenzen sowie gewünschte Qualitätsmerkmale wurden aus modernen Hochleistungssorten deutscher Züchtungsunternehmen und historischen Sorten der IPK Genbank während des Projektverlaufs ins Zuchtmaterial eingebracht. Neben der Evaluierung der Prüfglieder hinsichtlich der Resistenzeigenschaften wurden zur Erweiterung des Basiszuchtmaterials zahlreiche Kreuzungen durchgeführt. Hierbei wurden die Kreuzungseltern gezielt aus den im Projekt geprüften Sorten und Zuchtstämmen ausgewählt. Für die Bewertung und die Selektion der Klone wurde ein partizipativer Züchtungsansatz gewählt und dafür drei ökologisch wirtschaftende, landwirtschaftliche Betriebe ins Projekt eingebunden. Die Betriebsleiter wurden intensiv geschult und führten die Bewertung der Klone und die Selektion der Knollen in enger Zusammenarbeit mit den wissenschaftlichen Mitarbeitern der Institute durch. Ein solches Modell ist bislang in der der deutschen Kartoffelzüchtung einzigartig. Wissenschaftlich begleitet wurden die Züchtungsarbeiten durch eine phänotypische und genotypische Charakterisierung des Ausgangsmaterials und der Zuchtklone. Ziel hierbei war es, Grundlagen für eine molekulare Selektion KF-resistenter Nachkommen zu schaffen. Hierzu wurden an einem Prüfgliedsortiment Assoziationsstudien mit DArT- und SNP-Markern durchgeführt und ausgewertet. Im Projekt wurden am IPK erstmalig zwei Sortimente umfassend genetisch mittels zwei verschiedener Markersysteme zu charakterisiert. Mit den erzielten Ergebnisse konnten Duplikatgruppen innerhalb der Genbankakzessionen aufgedeckt sowie Unstimmigkeiten erkannt und bereinigt werden. Damit wurde das Genbankmanagement verbessert und nutzerorientiert gestaltet. Somit hat das Projekt eine nachhaltigere und intensivere Nutzung pflanzengenetischer Ressourcen ermöglicht. Dadurch ist es Züchtern wie auch Forschungsinstitutionen zukünftig möglich, zielgerichteter auf genetische Ressourcen der Kartoffel zuzugreifen und diese in die eigenen Zuchtprogramme und Forschungsprojekte einzubringen

Glutamatergic dysfunction leads to a hyper-dopaminergic phenotype through deficits in short-term habituation: a mechanism for aberrant salience

Psychosis in disorders like schizophrenia is commonly associated with aberrant salience and elevated striatal dopamine. However, the underlying cause(s) of this hyper-dopaminergic state remain elusive. Various lines of evidence point to glutamatergic dysfunction and impairments in synaptic plasticity in the etiology of schizophrenia, including deficits associated with the GluA1 AMPAR subunit. GluA1 knockout (Gria1−/−) mice provide a model of impaired synaptic plasticity in schizophrenia and exhibit a selective deficit in a form of short-term memory which underlies short-term habituation. As such, these mice are unable to reduce attention to recently presented stimuli. In this study we used fast-scan cyclic voltammetry to measure phasic dopamine responses in the nucleus accumbens of Gria1−/− mice to determine whether this behavioral phenotype might be a key driver of a hyper-dopaminergic state. There was no effect of GluA1 deletion on electrically-evoked dopamine responses in anaesthetized mice, demonstrating normal endogenous release properties of dopamine neurons in Gria1−/− mice. Furthermore, dopamine signals were initially similar in Gria1−/− mice compared to controls in response to both sucrose rewards and neutral light stimuli. They were also equally sensitive to changes in the magnitude of delivered rewards. In contrast, however, these stimulus-evoked dopamine signals failed to habituate with repeated presentations in Gria1−/− mice, resulting in a task-relevant, hyper-dopaminergic phenotype. Thus, here we show that GluA1 dysfunction, resulting in impaired short-term habituation, is a key driver of enhanced striatal dopamine responses, which may be an important contributor to aberrant salience and psychosis in psychiatric disorders like schizophrenia

Discrimination and calibration of a prediction model for mortality is decreased in secondary transferred patients: a validation in the TraumaRegister DGU

INTRODUCTION The Revised Injury Severity Classification II (RISC II) score represents a data-derived score that aims to predict mortality in severely injured patients. The aim of this study was to assess the discrimination and calibration of RISC II in secondary transferred polytrauma patients. METHODS This study was performed on the multicentre database of the TraumaRegister DGU. Inclusion criteria included Injury Severity Score (ISS)≥9 points and complete demographic data. Exclusion criteria included patients with 'do not resuscitate' orders or late transfers (>24 hours after initial trauma). Patients were stratified based on way of admission into patients transferred to a European trauma centre after initial treatment in another hospital (group Tr) and primary admitted patients who were not transferred out (group P). The RISC II score was calculated within each group at admission after secondary transfer (group Tr) and at primary admission (group P) and compared with the observed mortality rate. The calibration and discrimination of prediction were analysed. RESULTS Group P included 116 112 (91%) patients and group Tr included 11 604 (9%) patients. The study population was predominantly male (n=86 280, 70.1%), had a mean age of 53.2 years and a mean ISS of 20.7 points. Patients in group Tr were marginally older (54 years vs 52 years) and a had slightly higher ISS (21.5 points vs 20.1 points). Median time from accident site to hospital admission was 60 min in group P and 241 min (4 hours) in group Tr. Observed and predicted mortality based on RISC II were nearly identical in group P (10.9% and 11.0%, respectively) but predicted mortality was worse (13.4%) than observed mortality (11.1%) in group Tr. CONCLUSION The way of admission alters the calibration of prediction models for mortality in polytrauma patients. Mortality prediction in secondary transferred polytrauma patients should be calculated separately from primary admitted polytrauma patients

Causal interrogation of neuronal networks and behavior through virally transduced ivermectin receptors

© 2016 Obenhaus, Rozov, Bertocchi, Tang, Kirsch, Betz and Sprengel.The causal interrogation of neuronal networks involved in specific behaviors requires the spatially and temporally controlled modulation of neuronal activity. For long-term manipulation of neuronal activity, chemogenetic tools provide a reasonable alternative to short-term optogenetic approaches. Here we show that virus mediated gene transfer of the ivermectin (IVM) activated glycine receptor mutant GlyRα1AG can be used for the selective and reversible silencing of specific neuronal networks in mice. In the striatum, dorsal hippocampus, and olfactory bulb, GlyRα1AG promoted IVM dependent effects in representative behavioral assays. Moreover, GlyRα1AG mediated silencing had a strong and reversible impact on neuronal ensemble activity and c-Fos activation in the olfactory bulb. Together our results demonstrate that long-term, reversible and re- inducible neuronal silencing via GlyRα1AG is a promising tool for the interrogation of network mechanisms underlying the control of behavior and memory formation

Block of NMDA receptor channels by endogenous neurosteroids: implications for the agonist induced conformational states of the channel vestibule

N-methyl-D-aspartate receptors (NMDARs) mediate synaptic plasticity, and their dysfunction is implicated in multiple brain disorders. NMDARs can be allosterically modulated by numerous compounds, including endogenous neurosteroid pregnanolone sulfate. Here, we identify the molecular basis of the use-dependent and voltage-independent inhibitory effect of neurosteroids on NMDAR responses. The site of action is located at the extracellular vestibule of the receptor's ion channel pore and is accessible after receptor activation. Mutations in the extracellular vestibule in the SYTANLAAF motif disrupt the inhibitory effect of negatively charged steroids. In contrast, positively charged steroids inhibit mutated NMDAR responses in a voltage-dependent manner. These results, in combination with molecular modeling, characterize structure details of the open configuration of the NMDAR channel. Our results provide a unique opportunity for the development of new therapeutic neurosteroid-based ligands to treat diseases associated with dysfunction of the glutamate system

Georg Schmorl prize of the German spine society (DWG) 2022: current treatment for inpatients with osteoporotic thoracolumbar fractures-results of the EOFTT study

AIM Osteoporotic thoracolumbar fractures are of increasing importance. To identify the optimal treatment strategy this multicentre prospective cohort study was performed. PURPOSE Patients suffering from osteoporotic thoracolumbar fractures were included. Excluded were tumour diseases, infections and limb fractures. Age, sex, trauma mechanism, OF classification, OF-score, treatment strategy, pain condition and mobilization were analysed. METHODS A total of 518 patients' aged 75 ± 10 (41-97) years were included in 17 centre. A total of 174 patients were treated conservatively, and 344 were treated surgically, of whom 310 (90%) received minimally invasive treatment. An increase in the OF classification was associated with an increase in both the likelihood of surgery and the surgical invasiveness. RESULTS Five (3%) complications occurred during conservative treatment, and 46 (13%) occurred in the surgically treated patients. 4 surgical site infections and 2 mechanical failures requested revision surgery. At discharge pain improved significantly from a visual analogue scale score of 7.7 (surgical) and 6.0 (conservative) to a score of 4 in both groups (p < 0.001). Over the course of treatment, mobility improved significantly (p = 0.001), with a significantly stronger (p = 0.007) improvement in the surgically treated patients. CONCLUSION Fracture severity according to the OF classification is significantly correlated with higher surgery rates and higher invasiveness of surgery. The most commonly used surgical strategy was minimally invasive short-segmental hybrid stabilization followed by kyphoplasty/vertebroplasty. Despite the worse clinical conditions of the surgically treated patients both conservative and surgical treatment led to an improved pain situation and mobility during the inpatient stay to nearly the same level for both treatments