EAPP

Eine Vielzahl an intra- und extrazellulären Faktoren kann in eukaryotischen Zellen ein grosses Spektrum an Schäden hervorrufen. Sie besitzen verschiedene Checkpoints in unterschiedlichen Stadien des Zellzyklus die ihnen Helfen in geeigneter Weise zu Antworten um die Integrität der Zelle zu bewahren. In unserem Labor wurde ein neuer Interaktionspartner der in die Zellzyklusregulation involvierten Transkriptionsfaktorfamilie E2F entdeckt, das E2F-Associated-Phosphoprotein (EAPP). In der nachstehenden Arbeit wurde der Einfluss von EAPP auf den Zellzyklus und durch DNA Schäden ausgelöste Checkpoints untersucht. Eine Überexpression von EAPP führt zu einem G1 Zellzyklusarrest verursacht durch den Zellzyklusinhibitor p21. Eine genauere Analyse ergab eine Regulation durch EAPP auf transkriptioneller Ebene durch zwei Sp1/3 Bindungsstellen, unabhängig von p53, einem der Hauptaktivatoren von p21 speziell nach Zellschäden. Zusätzlich zeigte eine EAPP Überexpression einen anti-apoptotischen Effekt, zumindest in einigen Fällen verursacht durch p21. Auf der anderen Seite führte ein EAPP Knockdown zu einem dramatischen Anstieg an Apoptose. Mit reduziertem EAPP fanden wir einige Proteine in niedrigeren Mengen vor. Bei normal wachsenden Zellen hatte eine Verminderung der EAPP Mengen auf 50% keine großen Auswirkungen, aber unter DNA schädigenden Bedingungen stieg der Anteil an apoptotischen Zellen verglichen mit den Kontrollzellen dramatisch an. Zusammenfassend scheint EAPP, durch seine Regulation verschiedener Proteine auf transkripionellem Niveau, eine wichtige Rolle in der Entscheidung zwischen Arrest und Reparatur oder Apoptose nach Zellschäden zu spielen. Zellen mit höheren Mengen EAPP tendieren dazu Apoptose zu vermeiden, was den EAPP Anstieg in einigen transformierten Krebszelllinien erklären würde.A huge number of extra- and intracellular factors can cause a wide spectrum of different damages to eukaryotic cells. Several checkpoints in the different cell cycle stages help to respond to these defects in an appropriate manner to maintain the integrity of the cell. In our laboratory a new interaction partner of the cell cycle regulator family E2F was discovered, namely E2F-Associated-Phosphoprotein (EAPP). In the following work the impact of EAPP on the cell cycle and DNA damage checkpoints was studied. Overexpression of EAPP causes a G1 cell cycle arrest mediated by the cell cycle inhibitor p21. A detailed study of the interplay between EAPP and p21 revealed a regulation on the transcriptional level via two Sp1/3 binding sites, independent of p53 one of the main inducers of p21 upon stress stimuli. Additionally an overexpression of EAPP had an anti-apoptotic effect mediated, at least in some cases, by p21. On the other hand a knockdown of EAPP had severe consequences to the cells leading to massive apoptosis. We found several proteins being downregulated after an EAPP decrease. Growing cells with a 50% reduction of the EAPP levels showed a quite normal behavior but upon DNA damage the apoptotic fraction greatly increases. Taken together EAPP seems to play a prominent role in the decision between arrest and repair or apoptosis after cell damages. Cells with higher EAPP levels tend to avoid apoptosis which would explain the observed increase of EAPP in several transformed cancer cell lines

PUTTING 3D MODELS INTO CONTEXT – THE SCHACHERMEYR POTTERY COLLECTION AND THE DEFC APP

[EN] In order to overcome the different knowledge schemas of research on Neolithic and Chalcolithic sites of Greece and Anatolia, an open access Django-based database called DEFC App (Digitizing Early Farming Cultures Application) has been developed. The 3D models of the Schachermeyr sherd collection are one of the many resources that will be integrated into the database. The present contribution focuses on these 3D models and their metadata and on how they are contextualized within the DEFC App database and beyond. Additionally, we discuss the 3D model provenance metadata that should accompany the 3D models in order to assure their transparency.Stuhec, S.; Aspöck, E.; Masur, A.; Andorfer, P.; Zaytseva, K. (2016). PUTTING 3D MODELS INTO CONTEXT – THE SCHACHERMEYR POTTERY COLLECTION AND THE DEFC APP. En 8th International congress on archaeology, computer graphics, cultural heritage and innovation. Editorial Universitat Politècnica de València. 449-452. https://doi.org/10.4995/arqueologica8.2015.4155OCS44945

Delir auf operativen Intensivstationen : Inzidenz und Bedeutung für das Behandlungsergebnis

Das Delir wird ist mit einer erhöhten Mortalität der betroffenen Patienten assoziiert. Die vorliegenden Studie „Delir auf operativen Intensivstationen: Inzidenz und Bedeutung für das Behandlungsergebnis“ zeigt anhand 88 Patienten die Auftretenshäufigkeit eines Delirs und seiner Subtypen auf den operativen Intensivstationen der Universitätsklinik Bonn und vergleicht sie mit den internationalen Literaturdaten. Weiterhin sollte das Behandlungsergebnis der Patienten, die während ihres Intensivaufenthaltes ein Delir bekamen, mit dem Ergebnis der nicht-deliranten Patienten verglichen werden. Als Parameter des Behandlungsergebnisses wurden die Aufenthaltsdauer auf der Intensivstation, die Dauer der maschinellen Beatmung, die Aufenthaltsdauer im Krankenhaus und das Überleben 180 Tage nach der Operation bzw. der Aufnahme auf eine Intensivstation angesehen. Die objektive Erkrankungsschwere und der pflegerische Aufwand der Patienten wurde mit den Scoringsystemen SAPS-II, APACHE-II, TISS-28, und SOFA erhoben. Beide Gruppen wurden hinsichtlich der Scores und einigen in der Literatur vertretenden Risikofaktoren verglichen. Das Delir wurde mittels der gut validierten und reliablen Confusion Assessment Method for Intensive Care Units (CAMICU) diagnostiziert und mit der subjektiven Meinung des Pflegepersonals verglichen. Zur Realisierung wurden von September 2007 bis einschließlich Dezember 2007 alle Patienten, die auf die Chirurgische und Anästhesiologische Intensivstation aufgenommen wurden und die Exklusionskriterien nicht erfüllten, täglich getestet. Die Ergebnisse zeigen, dass das Delir auf den operativen Intensivstationen der Universitätskliniken Bonn eine hohe Prävalenz hat und fügen sich somit schlüssig in die publizierten Auftretenswahrscheinlichkeiten anderer Arbeiten ein. Das Behandlungsergebnis ist bei deliranten Patienten schlechter: Sie haben eine höhere Mortalität, verbleiben längere Zeit auf der Intensivstation, werden länger beatmet und verbleiben längere Zeit im Krankenhaus als die nicht-deliranten Patienten. Die akute Erkrankungsschwere scheint ein wichtiger Faktor für das Auftreten eines Delirs zu sein. Diese Erkrankungsschwere konnten durch höhere SAPS-II und SOFA Scores abgebildet werden. Der APACHE-II scheint bei dem relativ kleinen Patientenkollektiv keine verlässliche Einschätzung zu geben, da die beiden Patientenkollektive bei nicht signifikanten APACHE-II-Scores einen statistisch signifikanten Unterschied im Bezug auf die Mortalitätsrate zu haben. Vorerkrankungen der Patienten zeigen in Bezug auf das Delir keinen wesentlichen Einfluss; folglich kann die aktuelle Erkrankung, die den Patienten auf die Intensivstation gebracht hat, ein wichtiger Faktor sein. Der Mehraufwand, den delirante Patienten verursachen, ist sowohl durch die akute Erkrankungsschwere, als auch durch die Komplikationen des Delirs verursacht. Die Benutzung eines Delir Testsystems ist sinnvoll, um dem Übersehen eines Delirs vorzubeugen oder es früh zu erkennen. Ein routinemäßiges Monitoring stellt eine Voraussetzung für eine erfolgreiche Therapie dar

The stiffness of elastomeric surfaces influences the mechanical properties of endothelial cells

Optimal characterization of the mechanical properties of both cells and their surrounding is an issue of major interest. Indeed, cell function and development are strongly influenced by external stimuli. Furthermore, a change in cell mechanics might, in some cases, associate with diseases or malfunctioning. In this work, atomic force microscopy (AFM) was applied to examine the mechanical properties of the silicone elastomer polydimethylsiloxane (PDMS) a common substrate in cell culture. Force spectroscopy analysis was done over different specimens of this elastomeric material containing varying ratios of resin to cross-linker in its structure (5:1, 10:1, 20:1, 30:1 and 50:1), which impacts the final material properties (e.g., stiffness, elasticity). To quantify the mechanical properties of the PDMS, factors as the modulus of Young, the maximum adhesive forces as well as both relaxation amplitudes and times upon constant height contact of the tip (dwell time different of zero) were calculated from the different segments forming the force curves. It is demonstrated that the material stiffness is increased by prior oxygen plasma treatment of the sample, required for hydrophilic switching, contrarily to what observed for its adhesiveness. Subsequent incubation of endothelial HUVEC cells on top of these plasma treated PDMS systems yields minor variation in cell mechanics in comparison to those obtained on a glass reference, on which cells show much higher spreading tendency and, by extension, a remarkable membrane hardening. Thus, surface wettability turns a factor of higher relevance than substrate stiffness inducing variations in the cell mechanics.Comment: manuscript (12 pages, 4 figures, 2 tables), supplementary information (2 pages and 3 figures), the main results of the manuscript are based on a master thesi

The Structure-Function Relationship of PAMAM Dendrimers as Robust Oil Dispersants

PAMAM dendrimers have recently been investigated as efficient and biocompatible oil dispersants utilizing their encapsulation capacity; however, their high cationic charge density has been shown to be cytotoxic. It is therefore imperative to mitigate cationic charge-induced toxicity and understand the effects of such changes. Presented here is a synergistic experimental and computational approach to examine the effects of varying terminal surface charge on the capacity of dendrimers to disperse model liner, polycyclic aromatic, and hybrid hydrocarbons. Uncharged dendrimers collapse by forming intramolecular hydrogen bonds, which reduce the hosting capability. On the other hand, changing the surface charges from positive to negative greatly shifts the pKa of tertiary amines of the PAMAM dendrimer interior. As a result, the negatively charged dendrimers have a significant percentage of tertiary amines protonated, ∼30%. This unexpected change in the interior protonation state causes electrostatic interactions with the anionic terminal groups, leading to contraction and a marked decrease in hydrocarbon hosting capacity. The present work highlights the robust nature of dendrimer oil dispersion and also illuminates potentially unintended or unanticipated effects of varying dendrimer surface chemistry on their encapsulation or hosting efficacy, which is important for their environmental, industrial, and biomedical applications

HHT-Related Epistaxis and Pregnancy—A Retrospective Survey and Recommendations for Management from an Otorhinolaryngology Perspective

Appropriate management of hereditary hemorrhagic telangiectasia (HHT) is of particular importance in females, as HHT-mediated modifications of the vascular bed and circulation are known to increase the risk of complications during pregnancy and delivery. This study was undertaken to evaluate female HHT patients’ awareness of and experience with HHT during pregnancy and delivery, with a focus on epistaxis. In this retrospective study, 46 females (median age: 60 years) with confirmed HHT completed a 17-item questionnaire assessing knowledge of HHT and its pregnancy-associated complications, the severity of epistaxis during past pregnancies and deliveries, and the desire for better education and counselling regarding HHT and pregnancy. Results revealed that 85% of participants were unaware of their disease status prior to the completion of all pregnancies. Further, 91% reported no knowledge of increased pregnancy-related risk due to HHT. In regard to epistaxis, 61% of respondents reported experiencing nosebleeds during pregnancy. Finally, approximately a third of respondents suggested that receiving counseling on the risks of HHT in pregnancy could have been helpful. Findings suggest that awareness of HHT and its potential for increasing pregnancy-related risk is poor. Best practices in HHT management should be followed to minimize negative effects of the disorder

Human Stem Cell-Derived Neurons: A System to Study Human Tau Function and Dysfunction

Background: Intracellular filamentous deposits containing microtubule-associated protein tau constitute a defining characteristic of many neurodegenerative disorders. Current experimental models to study tau pathology in vitro do not usually recapitulate the tau expression pattern characteristic of adult human brain. In this study, we have investigated whether human embryonic stem cell-derived neurons could be a good model to study human tau distribution, function and dysfunction. Methodology/Principal Findings: Using RT-PCR, immunohistochemistry, western blotting and cell transfections we have investigated whether all 6 adult human brain tau isoforms are expressed in neurons derived from human embryonic and fetal stem cells and whether 4 repeat tau over-expression alone, or with the F3 tau repeat fragment, (amino acid 258–380 of the 2N4R tau isoform with the DK280 mutation) affects tau distribution. We found that the shortest 3 repeat tau isoform, similarly to human brain, is the first to be expressed during neuronal differentiation while the other 5 tau isoforms are expressed later. Over expression of tau with 4 repeats affects tau cellular distribution and the short tau F3 fragment appears to increase tau phosphorylation but this effect does not appear to be toxic for the cell. Conclusions: Our results indicate that human embryonic stem cell-derived neurons express all 6 tau isoforms and are

Gustatory Function in Acute COVID‐19 ‐ Results From Home‐Based Psychophysical Testing

Objective Gustatory function during COVID-19 is self-reported by around 50% of patients. However, only a few studies assessed gustation using psychophysical testing during acute infection. The objective of this study is to test gustatory function on threshold tests in the very first days of COVID-19. Methods Psychophysical testing consisted of validated and blinded tests for olfaction (NHANES Pocket Smell Test) and gustation (Taste Strips Test). These test kits were sent to home-quarantined patients and self-administered using a detailed instruction sheet. Results A total of 51 patients were included in this study. Testing was performed 6.5 ± 2.7 days after sampling of respiratory swabs. At this time 37% of patients stated to currently experience a gustatory impairment. The mean Taste Strips score was 10.0 ± 3.4 with 28% scoring in the range of hypogeusia. Interestingly, no significant difference in the results of gustatory testing could be observed between the group with subjectively preserved gustation and the group with self-rated taste impairment. Conclusion During the very first days of COVID-19, psychophysical gustatory testing revealed hypogeusia in 28%. This is far lower than patients' self-reports. Different from previous studies, we did not find clear evidence for an impairment of only certain taste qualities