@article{HofmannBraunPozgajetal.2014, author = {Hofmann, Sebastian and Braun, Attila and Pozgaj, Rastislav and Morowski, Martina and V{\"o}gtle, Timo and Nieswandt, Bernhard}, title = {Mice lacking the SLAM family member CD84 display unaltered platelet function in hemostasis and thrombosis}, series = {PLoS One}, volume = {9}, journal = {PLoS One}, number = {12}, doi = {10.1371/journal.pone.0115306}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126477}, pages = {e115306}, year = {2014}, abstract = {Background Platelets are anuclear cell fragments derived from bone marrow megakaryocytes that safeguard vascular integrity by forming thrombi at sites of vascular injury. Although the early events of thrombus formation—platelet adhesion and aggregation—have been intensively studied, less is known about the mechanisms and receptors that stabilize platelet-platelet interactions once a thrombus has formed. One receptor that has been implicated in this process is the signaling lymphocyte activation molecule (SLAM) family member CD84, which can undergo homophilic interactions and becomes phosphorylated upon platelet aggregation. Objective The role of CD84 in platelet physiology and thrombus formation was investigated in CD84-deficient mice. Methods and Results We generated CD84-deficient mice and analyzed their platelets in vitro and in vivo. \(Cd84^{-/-}\) platelets exhibited normal activation and aggregation responses to classical platelet agonists. Furthermore, CD84 deficiency did not affect integrin-mediated clot retraction and spreading of activated platelets on fibrinogen. Notably, also the formation of stable three-dimensional thrombi on collagen-coated surfaces under flow ex vivo was unaltered in the blood of \(Cd84^{-/-}\) mice. In vivo, \(Cd84^{-/-}\) mice exhibited unaltered hemostatic function and arterial thrombus formation. Conclusion These results show that CD84 is dispensable for thrombus formation and stabilization, indicating that its deficiency may be functionally compensated by other receptors or that it may be important for platelet functions different from platelet-platelet interactions.}, language = {en} } @article{DechHolzwarthAsametal.2021, author = {Dech, Stefan and Holzwarth, Stefanie and Asam, Sarah and Andresen, Thorsten and Bachmann, Martin and Boettcher, Martin and Dietz, Andreas and Eisfelder, Christina and Frey, Corinne and Gesell, Gerhard and Gessner, Ursula and Hirner, Andreas and Hofmann, Matthias and Kirches, Grit and Klein, Doris and Klein, Igor and Kraus, Tanja and Krause, Detmar and Plank, Simon and Popp, Thomas and Reinermann, Sophie and Reiners, Philipp and Roessler, Sebastian and Ruppert, Thomas and Scherbachenko, Alexander and Vignesh, Ranjitha and Wolfmueller, Meinhard and Zwenzner, Hendrik and Kuenzer, Claudia}, title = {Potential and challenges of harmonizing 40 years of AVHRR data: the TIMELINE experience}, series = {Remote Sensing}, volume = {13}, journal = {Remote Sensing}, number = {18}, issn = {2072-4292}, doi = {10.3390/rs13183618}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246134}, year = {2021}, abstract = {Earth Observation satellite data allows for the monitoring of the surface of our planet at predefined intervals covering large areas. However, there is only one medium resolution sensor family in orbit that enables an observation time span of 40 and more years at a daily repeat interval. This is the AVHRR sensor family. If we want to investigate the long-term impacts of climate change on our environment, we can only do so based on data that remains available for several decades. If we then want to investigate processes with respect to climate change, we need very high temporal resolution enabling the generation of long-term time series and the derivation of related statistical parameters such as mean, variability, anomalies, and trends. The challenges to generating a well calibrated and harmonized 40-year-long time series based on AVHRR sensor data flown on 14 different platforms are enormous. However, only extremely thorough pre-processing and harmonization ensures that trends found in the data are real trends and not sensor-related (or other) artefacts. The generation of European-wide time series as a basis for the derivation of a multitude of parameters is therefore an extremely challenging task, the details of which are presented in this paper.}, language = {en} } @phdthesis{Hofmann2013, author = {Hofmann, Sebastian}, title = {Studies on the function and regulation of CD84, GPVI and Orai2 in genetically modified mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-87949}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2013}, abstract = {Platelet activation and aggregation at sites of vascular injury are essential processes to limit blood loss but they also contribute to arterial thrombosis, which can lead to myocardial infarction and stroke. Stable thrombus formation requires a series of events involving platelet receptors which contribute to adhesion, activation and aggregation of platelets. Regulation of receptor expression by (metallo-)proteinases has been described for several platelet receptors, but the molecular mechanisms are ill-defined. The signaling lymphocyte activation molecule (SLAM) family member CD84 is expressed in immune cells and platelets, however its role in platelet physiology was unclear. In this thesis, CD84 deficient mice were generated and analyzed. In well established in vitro and in vivo assays testing platelet function and thrombus formation, CD84 deficient mice displayed phenotypes indistinguishable from wild-type controls. It was concluded that CD84 in platelets does not function as modulator of thrombus formation, but rather has other functions. In line with this, in the second part of this thesis, a novel regulation mechanism for platelet CD84 was discovered and elucidated. Upon platelet activation, the N-terminus of CD84 was found to be cleaved exclusively by the a disintegrin and metalloproteinase 10 (ADAM10), whereas the intracellular part was cleaved by calpain. In addition, regulation of the platelet activating collagen receptor glycoprotein VI (GPVI) was studied and it was shown that GPVI is in contrast to CD84 differentially regulated by ADAM10 and ADAM17. A novel role of CD84 under pathophysiological conditions was revealed as CD84 deficient mice were protected from ischemic stroke in the model of transient middle cerebral artery occlusion and this protection was based on the lack of CD84 in T cells. Ca2+ is an essential second messenger that facilitates activation of platelets and diverse functions in different eukaryotic cell types. Store-operated Ca2+ entry (SOCE) represents the major mechanism leading to rise in intracellular Ca2+ concentration in non-excitable cells. The Ca2+ sensor STIM1 (stromal interaction molecule 1) and the SOC channel subunit protein Orai1 are established mediators of SOCE in platelets. STIM2 is the major STIM isoform in neurons, but the role of the SOC channel subunit protein Orai2 in platelets and neurons has remained elusive. In the third part of this thesis, Orai2 deficient mice were generated and analyzed. Orai2 was dispensable for platelet function, however, Orai2 deficient mice were protected from ischemic neurodegeneration and this phenotype was attributed to defective SOCE in neurons.}, subject = {Thrombozyt}, language = {en} } @article{KollingBackhausHofmannetal.2022, author = {Kolling, Markus and Backhaus, Joy and Hofmann, Norbert and Keß, Stefan and Krastl, Gabriel and Soliman, Sebastian and K{\"o}nig, Sarah}, title = {Students' perception of three-dimensionally printed teeth in endodontic training}, series = {European Journal of Dental Education}, volume = {26}, journal = {European Journal of Dental Education}, number = {4}, doi = {10.1111/eje.12743}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318676}, pages = {653 -- 661}, year = {2022}, abstract = {Introduction In endodontic education, there is a need for thorough training prior to students embarking on clinical treatment. The aim of this study was to use three-dimensional printing technology to create a new model and to compare its suitability for training purposes with resin blocks and extracted teeth. Materials and Methods Multi-jet-modelling (MJM) produced the 3D model replicating a common difficulty in root-canal morphology. An evaluation study comprising 88 students was run in the sixth semester (summer 2018 and winter 2018/2019). A new questionnaire assessed students' perception of training models and educational environment. Welch's t-test analysed significant differences. Results The most pronounced differences between models were noted when rating material hardness, radiopacity, root-canal configuration and suitability for practising. Students estimated their learning outcome as greater with 3D-printed teeth compared to resin blocks. Three-dimensionally printed teeth received significantly lower ratings with regard to enthusiasm, the learning of fine motor skills and spatial awareness, when compared to human teeth (p ≤ .001). However, 3D-printed teeth were appreciated for additional benefits, such as their cleanliness, availability and standardisation of training opportunities with complex root-canal configurations. Conclusion Students preferred extracted human teeth to 3D-printed teeth with respect to their physical characteristics and training experience. However, educational advantages may compensate for the shortcomings. The new questionnaire proved both adequate and accurate to assess the models and educational environment in endodontic training. The new 3D-printed teeth enhanced the learning opportunities.}, language = {en} }