The loosely and firmly adsorbed amount of bovine serum albumin (BSA) on dental titanium and dental gold was investigated by bicinchoninic acid assay (BCA assay). This method does not require special properties of the sample like a high reflectivity or conductivity and turns the BCA assay into a valuable tool to investigate a widespread spectrum of different substrate materials, e.g., natural enamel. The experiments in this work showed that it is possible to distinguish between loosely and firmly bound protein with the BCA assay. On the here investigated dental titanium and dental gold samples the amount of adsorbed BSA was dominated by the loosely bound part. On dental gold the total amount of adsorbed BSA was significantly higher than on titanium. The amount of loosely bound BSA was high near the isoelectric points of dental titanium and dental gold while the amount of firmly adsorbed BSA on dental titanium followed the electrostatics. At high pH values (pH 9.0) conformational changes of the BSA molecules played a key role in the adsorption process.

The survival of adult-born dentate gyrus granule cells critically depends on their synaptic integration into the existing neuronal network. Excitatory inputs are thought to increase the survival rate of adult born neurons. Therefore, whether enhancing the stability of newly formed excitatory synapses by overexpressing the synaptic cell adhesion molecule SynCAM 1 improves the survival of adult-born neurons was tested. Here it is shown that overexpression of SynCAM 1 improves survival of adult-born neurons, but has no effect on the proliferation rate of precursor cells. As expected, overexpression of SynCAM 1 increased the synapse density in adult-born granule neurons. While adult-born granule neurons have very few functional synapses 15 days after birth, it was found that at this age adult-born neurons in SynCAM 1 overexpressing mice exhibited around three times more excitatory synapses, which were stronger than synapses of adult-born neurons of control littermates. In summary, the data indicated that additional SynCAM 1 accelerated synapse maturation, which improved the stability of newly formed synapses and in turn increased the likelihood of survival of adult-born neurons.

Formation and stability of synapses are required for proper brain function. While it is well established that synaptic adhesion molecules are important regulators of synapse formation, their specific role during different phases of synapse development remains unclear. To investigate the function of the synaptic cell adhesion molecule SynCAM 1 in the formation, stability, and maintenance of spines we used 2-photon in vivo imaging to follow individual spines over a long period of time. In SynCAM 1 knockout mice the survival rate of existing spines was reduced and fewer filopodia-like structures were converted into stable spines. SynCAM 1flag overexpression resulted in more stable spines and fewer filopodia-like structures. When SynCAM 1flag overexpression is turned on the spine density rapidly increases within a few days. Interestingly, the spine density stayed at an elevated level when SynCAM 1flag overexpression was turned off. Our data indicate that the SynCAM 1 induced altered spine density is not caused by the formation of newly emerging protrusions, instead SynCAM 1 stabilizes nascent synaptic contacts which promotes their maturation. Concomitant with the synaptic stabilization, SynCAM 1 generally prolongs the lifetime of spines. In summary, we demonstrate that SynCAM 1 is a key regulator of spine stability.

Post-translational modifications, like phosphorylation, ubiquitylation, and sumoylation, have been shown to impact on synaptic neurotransmission by modifying pre- and postsynaptic proteins and therefore alter protein stability, localization, or protein-protein interactions. Previous studies showed that post-translational modifications are essential during the induction of synaptic plasticity, defined by a major reorganization of synaptic proteins. We demonstrated before that neddylation, a post-translational modification that covalently binds Nedd8 to lysine-residues, strongly affects neuronal maturation and spine stability. We now analysed the consequences of inhibiting neddylation on excitatory synaptic transmission and plasticity, which will help to narrow down possible targets, to make educated guesses, and test specific candidates. Here, we show that acute inhibition of neddylation impacts on synaptic neurotransmission before morphological changes occur. Our data indicate that pre- and postsynaptic proteins are neddylated since the inhibition of neddylation impacts on presynaptic release probability and postsynaptic receptor stabilization. In addition, blocking neddylation during the induction of long-term potentiation and long-term inhibition abolished both forms of synaptic plasticity. Therefore, this study shows the importance of identifying synaptic targets of the neddylation pathway to understand the regulation of synaptic transmission and plasticity.

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ZusammenfassungDie Gesundheit der Menschen steht vor einer Reihe neuer Herausforderungen, die maßgeblich durch den fortschreitenden Klimawandel, den demografischen Wandel und die Globalisierung angetrieben werden. Der One-Health-Ansatz basiert auf dem Verständnis, dass die Gesundheit von Menschen, Tieren und Umwelt eng verknüpft ist. Bei der Umsetzung von One Health in die Praxis ergibt sich die Notwendigkeit, in der Forschung diverse und heterogene Datenströme und -typen aus den verschiedenen Sektoren zu kombinieren und zu analysieren. Verfahren der künstlichen Intelligenz (KI) bieten dabei neue Möglichkeiten zur sektorübergreifenden Beurteilung von heutigen und zukünftigen Gesundheitsgefahren.Dieser Beitrag gibt einen Überblick über verschiedene Anwendungsbereiche von KI-Verfahren im Zusammenhang mit One Health und zeigt Herausforderungen auf. Am Beispiel der Ausbreitung antimikrobieller Resistenzen (AMR), die eine zunehmende globale Gefahr im One-Health-Kontext darstellt, werden bestehende und zukünftige KI-basierte Lösungsansätze zur Eindämmung und Prävention beschrieben. Diese reichen von neuartiger Arzneientwicklung und personalisierter Therapie über gezieltes Monitoring der Antibiotikanutzung in Tierhaltung und Landwirtschaft bis hin zu einer umfassenden Umwelt-Surveillance für zukünftige AMR-Risikobewertungen.

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