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Institute
Dr. Christina Terpstra-Rundel und Prof. Dr. Clemens Möller berichten über die Entwicklung des interdisziplinären Masterstudiengangs „Sustainability Studies“ an der Hochschule Albstadt-Sigmaringen, der zum Wintersemester 2024/25 gestartet ist. Im Zentrum stehen der Erwerb von Zukunftskompetenzen sowie die Verknüpfung von Praxis und wissenschaftlichem Lernen durch digitale Methoden.
Aspidasept (Pep19-2.5) and its derivative Pep19-4LF (“Aspidasept II”) are anti-infective and an-ti-inflammatory synthetic polypeptides currently in development for application against a variety of moderate to severe bacterial infections. Such severe infections could lead to systemic inflam-mation, as in the case of severe sepsis and septic shock. In addition, development as application against non-systemic diseases in the case of skin and soft tissue infections (SSTI) is ongoing. In the present study, Aspidasept and Aspidasept II and their part structures were analysed with respect to their toxic behavior in different established models against a variety of relevant cells, and in electrophysiological experiments targeting the hERG channel according to ICH S7B. Furthermore, the effects in mouse models of neurobiological behavior and the local lymph node according to OECD test guideline 429 were investigated, as well as a rat model of repeated dose toxicology according to ICH M3. The data provide conclusive information about potential toxic effects, thus specifying a therapeutic window for the application of the peptides. Therefore, these data allow us to define Aspidasept concentrations for their use in clinical studies as parenteral application.
Bewusstsein für Nachhaltigkeitsthemen ist in der Breite der Gesellschaft sowie der Wirtschaft angekommen. Der Bedarf an Nachhaltigkeitskompetenzen in Unternehmen ist groß und wächst weiter, und gerade viele junge Menschen wünschen sich, in ihrem beruflichen Umfeld auch nachhaltig tätig zu sein. Bei gleichzeitigem Fachkräftemangel sind Bildungsangebote vonnöten, die passgenaue und flexible Inhalte anbieten und eine hohe Qualität gewährleisten.
Der Bedarf an Nachhaltigkeitskompetenzen in Unternehmen ist groß und wächst weiter. Bei gleichzeitigem Fachkräftemangel sind Bildungsangebote vonnöten, die passgenaue und flexible Inhalte anbieten und eine hohe Qualität gewährleisten. An der Hochschule Albstadt-Sigmaringen wird mit einem neuen Angebot auf diese Anforderungen eingegangen: Der neue Master-Studiengang „Sustainability
Studies“, studierbar in drei Semestern, bietet eine enge Verzahnung mit der Praxis und angewandten Forschung und ist gleichzeitig so flexibel wie möglich gestaltet, um den verschiedenen Hintergründen der Studierenden gerecht zu werden. Eine Besonderheit des Studiengangs ist es dabei, dass wesentliche
Studienleistungen im Rahmen von Projekten, die bevorzugt gemeinsam mit Firmen oder Organisationen durchgeführt werden, erbracht werden können. Im Folgenden werden das Konzept, die Hintergründe sowie die Möglichkeiten für potenzielle Studierende und Unternehmen genauer vorgestellt.
Das Reflexionsportfolio bietet allen Lehrenden eine Chance, ihre Lehre selbstbestimmt und individuell auf ein neues Level zu heben. Es ist ein Werkzeug, um Lehrerfahrungen systematisch zu analysieren, sich mit anderen Lehrenden auszutauschen und kontinuierlich zu lernen. Nutzen Sie es, um Ihre Lehre effektiver, lebendiger und relevanter zu gestalten und um mehr Freude und Zufriedenheit mit Ihrer eigenen Lehre zu erreichen.
Aspidasept (Pep19-2.5) and its derivative Pep19-4LF (“Aspidasept II”) are anti-infective and anti-inflammatory synthetic polypeptides currently in development for application against a variety of moderate to severe bacterial infections that could lead to systemic inflammation, as in the case of severe sepsis and septic shock, as well as application to non-systemic diseases in the case of skin and soft tissue infections (SSTI). In the present study, Aspidasept and Aspidasept II and their part structures were analysed with respect to their toxic behavior in different established models against a variety of relevant cells, and in electrophysiological experiments targeting the hERG channel according to ICH S7B. Furthermore, the effects in mouse models of neurobiological behavior and the local lymph node according to OECD test guideline 429 were investigated, as well as a rat model of repeated dose toxicology according to ICH M3. The data provide conclusive information about potential toxic effects, thus specifying a therapeutic window for the application of the peptides. Therefore, these data allow us to define Aspidasept concentrations for their use in clinical studies as parenteral application.
Several neonicotinoids have recently been shown to activate the nicotinic acetylcholine receptor (nAChR) on human neurons. Moreover, imidacloprid (IMI) and other members of this pesticide family form a set of diverse metabolites within crops. Among these, desnitro-imidacloprid (DN-IMI) is of special toxicological interest, as there is evidence (i) for human dietary exposure to this metabolite, (ii) and that DN-IMI is a strong trigger of mammalian nicotinic responses. We set out here to quantify responses of human nAChRs to DN-IMI and an alternative metabolite, IMI-olefin. To evaluate toxicological hazards, these data were then compared to those of IMI and nicotine. Ca 2+ -imaging experiments on human neurons showed that DN-IMI exhibits an agonistic effect on nAChRs at sub-micromolar concentrations (equipotent with nicotine) while IMI-olefin activated the receptors less potently (in a similar range as IMI). Direct experimental data on the interaction with defined receptor subtypes were obtained by heterologous expression of various human nAChR subtypes in Xenopus
laevis oocytes and measurement of the transmembrane currents evoked by exposure to putative ligands. DN-IMI acted on the physiologically important human nAChR subtypes α7, α3β4, and α4β2 (high-sensitivity variant) with similar potency as nicotine. IMI and IMI-olefin were confirmed as nAChR agonists, although with 2–3 orders of magnitude lower potency. Molecular docking studies, using receptor models for the α7 and α4β2 nAChR subtypes supported an activity of DN-IMI
similar to that of nicotine. In summary, these data suggest that DN-IMI functionally affects human neurons similar to the well-established neurotoxicant nicotine by triggering α7 and several non-α7 nAChRs.
Functional alterations by a subgroup of neonicotinoid pesticides in human dopaminergic neurons
(2021)
Neonicotinoid pesticides, originally developed to target the insect nervous system, have been reported to interact with human receptors and to activate rodent neurons. Therefore, we evaluated in how far these compounds may trigger signaling in human neurons, and thus, affect the human adult or developing nervous system. We used SH-SY5Y neuroblastoma cells as established model of nicotinic acetylcholine receptor (nAChR) signaling. In parallel, we profiled dopaminergic neurons, generated from LUHMES neuronal precursor cells, as novel system to study nAChR activation in human post-mitotic neurons. Changes of the free intracellular Ca 2+ concentration ([Ca 2+ ] i ) were used as readout, and key findings were confirmed by patch clamp
recordings. Nicotine triggered typical neuronal signaling responses that were blocked by antagonists, such as tubocurarine and
mecamylamine. Pharmacological approaches suggested a functional expression of α7 and non-α7 nAChRs on LUHMES cells.
In this novel test system, the neonicotinoids acetamiprid, imidacloprid, clothianidin and thiacloprid, but not thiamethoxam
and dinotefuran, triggered [Ca 2+ ] i signaling at 10–100 μM. Strong synergy of the active neonicotinoids (at low micromolar concentrations) with the α7 nAChR-positive allosteric modulator PNU-120596 was observed in LUHMES and SH-SY5Y cells, and specific antagonists fully inhibited such signaling. To provide a third line of evidence for neonicotinoid signaling via nAChR, we studied cross-desensitization: pretreatment of LUHMES and SH-SY5Y cells with active neonicotinoids (at 1–10 μM) blunted the signaling response of nicotine. The pesticides (at 3–30 μM) also blunted the response to the non-α7 agonist ABT 594 in LUHMES cells. These data show that human neuronal cells are functionally affected by low micromolar concentrations of several neonicotinoids. An effect of such signals on nervous system development is a toxicological concern.
