@article{SchulteSoldaSpaenigetal.2022, author = {Schulte, Clemens and Sold{\`a}, Alice and Sp{\"a}nig, Sebastian and Adams, Nathan and Bekić, Ivana and Streicher, Werner and Heider, Dominik and Strasser, Ralf and Maric, Hans Michael}, title = {Multivalent binding kinetics resolved by fluorescence proximity sensing}, series = {Communications Biology}, volume = {5}, journal = {Communications Biology}, doi = {10.1038/s42003-022-03997-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301157}, year = {2022}, abstract = {Multivalent protein interactors are an attractive modality for probing protein function and exploring novel pharmaceutical strategies. The throughput and precision of state-of-the-art methodologies and workflows for the effective development of multivalent binders is currently limited by surface immobilization, fluorescent labelling and sample consumption. Using the gephyrin protein, the master regulator of the inhibitory synapse, as benchmark, we exemplify the application of Fluorescence proximity sensing (FPS) for the systematic kinetic and thermodynamic optimization of multivalent peptide architectures. High throughput synthesis of +100 peptides with varying combinatorial dimeric, tetrameric, and octameric architectures combined with direct FPS measurements resolved on-rates, off-rates, and dissociation constants with high accuracy and low sample consumption compared to three complementary technologies. The dataset and its machine learning-based analysis deciphered the relationship of specific architectural features and binding kinetics and thereby identified binders with unprecedented protein inhibition capacity; thus, highlighting the value of FPS for the rational engineering of multivalent inhibitors.}, language = {en} } @article{FlemmingHankirKusanetal.2021, author = {Flemming, Sven and Hankir, Mohammed K. and Kusan, Simon and Krone, Manuel and Anger, Friedrich and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Safety of elective abdominal and vascular surgery during the COVID-19 pandemic: a retrospective single-center study}, series = {European Journal of Medical Research}, volume = {26}, journal = {European Journal of Medical Research}, doi = {10.1186/s40001-021-00583-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264975}, year = {2021}, abstract = {Background Patients with coronavirus disease 2019 (COVID-19) who undergo surgery have impaired postoperative outcomes and increased mortality. Consequently, elective and semi-urgent operations on the increasing number of patients severely affected by COVID-19 have been indefinitely postponed.in many countries with unclear implications on disease progression and overall survival. The purpose of this study was to evaluate whether the establishment of a standardized screening program for acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sufficient to ensure high-quality medical and surgical treatment of COVID-19 and non-COVID-19 patients while minimizing in-hospital SARS-CoV-2 transmission. Methods The screening program comprised polymerase chain reaction (PCR) testing of nasopharyngeal swabs and a standardized questionnaire about potential symptoms for SARS-CoV-2 infection. All elective and emergency patients admitted to the surgical department of a tertiary-care hospital center in Lower Franconia, Germany, between March and May 2020 were included and their characteristics were recorded. Results Out of the study population (n = 657), 509 patients (77.5\%) had at least one risk factor for a potentially severe course of COVID-19 and 164 patients (25\%) were active smokers. The average 7-day incidence in Lower Franconia was 24.0/100,000 during the observation period. Preoperative PCR testing revealed four asymptomatic positive patients out of the 657 tested patients. No postoperative SARS-CoV-2 infection or transmission could be detected. Conclusion The implementation of a standardized preoperative screening program to both COVID-19 and non-COVID-19 patients can ensure high-quality surgical care while minimizing infection risk for healthcare workers and potential in-hospital transmission.}, language = {en} } @article{DirimanovHoegger2019, author = {Dirimanov, Stoyan and H{\"o}gger, Petra}, title = {Screening of inhibitory effects of polyphenols on Akt-phosphorylation in endothelial cells and determination of structure-activity features}, series = {Biomolecules}, volume = {9}, journal = {Biomolecules}, number = {6}, issn = {2218-273X}, doi = {10.3390/biom9060219}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197333}, pages = {219}, year = {2019}, abstract = {Polyphenols exert beneficial effects in type 2 diabetes mellitus (T2DM). However, their mechanism of action remains largely unknown. Endothelial Akt-kinase plays a key role in the pathogenesis of cardiovascular complications in T2DM and therefore the modulation of its activity is of interest. This work aimed to characterize effects of structurally different polyphenols on Akt-phosphorylation (pAkt) in endothelial cells (Ea.hy926) and to describe structure-activity features. A comprehensive screening via ELISA quantified the effects of 44 polyphenols (10 µM) on pAkt Ser473. The most pronounced inhibitors were luteolin (44 ± 18\%), quercetin (36 ± 8\%), urolithin A (35 ± 12\%), apigenin, fisetin, and resveratrol; (p < 0.01). The results were confirmed by Western blotting and complemented with corresponding experiments in HUVEC cells. A strong positive and statistically significant correlation between the mean inhibitory effects of the tested polyphenols on both Akt-residues Ser473 and Thr308 (r = 0.9478, p = 0.0003) was determined by immunoblotting. Interestingly, the structural characteristics favoring pAkt inhibition partially differed from structural features enhancing the compounds' antioxidant activity. The present study is the first to quantitatively compare the influence of polyphenols from nine different structural subclasses on pAkt in endothelial cells. These effects might be advantageous in certain T2DM-complications involving over-activation of the Akt-pathway. The suggested molecular mode of action of polyphenols involving Akt-inhibition contributes to understanding their effects on the cellular level.}, language = {en} } @article{LindenmaierDittmarHauseretal.1985, author = {Lindenmaier, W. and Dittmar, K. E. and Hauser, H. and Necker, A. and Sebald, Walter}, title = {Isolation of a functional human interleukin 2 gene from a cosmid library by recombination in vivo}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62662}, year = {1985}, abstract = {A method has been developed that allows the isolation of genomic clones from a cosmid library by homologaus recombination in vivo. This method was used to isolate a human genomic interleukin 2 (IL2) gene. The genomic cosmid library was packaged in vivo into A. phage particles. A recombination-proficient host strain carrying IL2 cDNA sequences in a non-homologaus plasmid vector was infected by the packaged cosmid library. After in vivo packaging and reinfection, recombinants carrying the antibiotic resistance genes of both vectors were selected. From a recombinant cosmid clone the chromosomal IL2 genewas restored. After DNA mediated gene transfer into mouse Ltk- cells human IL2 was expressed constitutively.}, subject = {Biochemie}, language = {en} }