@phdthesis{Kreisz2024,
  author    = {Kreisz, Philipp},
  title     = {Group S1 bZIP transcription factors regulate sink tissue development by controlling carbon and nitrogen resource allocation in \(Arabidopsis\) \(thaliana\)},
  doi       = {10.25972/OPUS-32192},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321925},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The evolutionary success of higher plants is largely attributed to their tremendous developmental plasticity, which allows them to cope with adverse conditions. However, because these adaptations require investments of resources, they must be tightly regulated to avoid unfavourable trade-offs. Most of the resources required are macronutrients based on carbon and nitrogen. Limitations in the availability of these nutrients have major effects on gene expression, metabolism, and overall plant morphology. These changes are largely mediated by the highly conserved master kinase SNF1-RELATED PROTEIN KINASE1 (SnRK1), which represses growth and induces catabolic processes. Downstream of SnRK1, a hub of heterodimerising group C and S1 BASIC LEUCINE ZIPPER (bZIP) transcription factors has been identified. These bZIPs act as regulators of nutrient homeostasis and are highly expressed in strong sink tissues, such as flowers or the meristems that initiate lateral growth of both shoots and roots. However, their potential involvement in controlling developmental responses through their impact on resource allocation and usage has been largely neglected so far. Therefore, the objective of this work was to elucidate the impact of particularly S1 bZIPs on gene expression, metabolism, and plant development. Due to the high homology and suspected partial redundancy of S1 bZIPs, higher order loss-of-function mutants were generated using CRISPR-Cas9. The triple mutant bzip2/11/44 showed a variety of robust morphological changes but maintained an overall growth comparable to wildtype plants. In detail however, seedlings exhibited a strong reduction in primary root length. In addition, floral transition was delayed, and siliques and seeds were smaller, indicating a reduced supply of resources to the shoot and root apices. However, lateral root density and axillary shoot branching were increased, suggesting an increased ratio of lateral to apical growth in the mutant. The full group S1 knockout bzip1/2/11/44/53 showed similar phenotypes, albeit far more pronounced and accompanied by growth retardation. Metabolomic approaches revealed that these architectural changes were accompanied by reduced sugar levels in distal sink tissues such as flowers and roots. Sugar levels were also diminished in leaf apoplasts, indicating that long distance transport of sugars by apoplastic phloem loading was impaired in the mutants. In contrast, an increased sugar supply to the proximal axillary buds and elevated starch levels in the leaves were measured. In addition, free amino acid levels were increased in bzip2/11/44 and bzip1/2/11/44/53, especially for the important transport forms asparagine and glutamine. The increased C and N availability in the proximal tissues could be the cause of the increased axillary branching in the mutants. To identify bZIP target genes that might cause the observed shifts in metabolic status, RNAseq experiments were performed. Strikingly, clade III SUGARS WILL EVENTUALLY BE EXPORTED (SWEET) 8 genes were abundant among the differentially expressed genes. As SWEETs are crucial for sugar export to the apoplast and long-distance transport through the phloem, their reduced expression is likely to be the cause of the observed changes in sugar allocation. Similarly, the reduced expression of GLUTAMINE AMIDOTRANSFERASE 1_2.1 (GAT1_2.1), which exhibits glutaminase activity, could be an explanation for the abundance of glutamine in the mutants. Additional experiments (ATAC-seq, DAP� seq, PTA, q-RT-PCR) supported the direct induction of SWEETs and GAT1_2.1 by S1 bZIPs. To confirm the involvement of these target genes in the observed S1 bZIP mutant phenotypes, loss-of-function mutants were obtained, which showed moderately increased axillary branching. At the same time, the induced overexpression of bZIP11 in axillary meristems had the opposite effect. Collectively, a model is proposed for the function of S1 bZIPs in regulating sink tissue development. For efficient long-distance sugar transport, bZIPs may be required to induce the expression of clade III SWEETs. Thus, reduced SWEET expression in the S1 bZIP mutants would lead to a decrease in apoplastic sugar loading and a reduced supply to distal sinks such as shoot or root apices. The reduction in long� distance transport could lead to sugar accumulation in the leaves, which would then increasingly be transported via symplastic routes towards proximal sinks such as axillary branches and lateral roots or sequestered as starch. The reduced GAT1_2.1 levels lead to an abundance of glutamine, a major nitrogen transport form. The combined effect on C and N allocation results in increased nutrient availability in proximal tissues, promoting the formation of lateral plant organs. Alongside emerging evidence highlighting the power of bZIPs to steer nutrient allocation in other species, a novel but evolutionary conserved role for S1 bZIPs as regulators of developmental plasticity is proposed, while the generation of valuable data sets and novel genetic resources will help to gain a deeper understanding of the molecular mechanisms involved},
  subject      = {Molekularbiologie},
  language  = {en}
}
@phdthesis{Kumar2024,
  author    = {Kumar, Manish},
  title     = {Structural and compositional effects on tree-water relation},
  doi       = {10.25972/OPUS-32624},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-326245},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Forests are essential sources of tangible and intangible benefits, but global climate change associated with recurrent extreme drought episodes severely affects forest productivity due to extensive tree die-back. On that, it appeals to an urgency for large-scale reforestation efforts to mitigate the impact of climate change worldwide; however, there is a lack of understanding of drought-effect on sapling growth and survival mechanisms. It is also challenging to anticipate how long trees can survive and when they succumb to drought. Hence, to ensure success of reforestation programs and sustainable forest productivity, it is essential to identify drought-resistant saplings. For that, profound knowledge of hydraulic characteristics is needed. To achieve this, the study was split into two phases which seek to address (1) how the hydraulic and anatomical traits influence the sapling's growth rate under drought stress. (2) how plant water potential regulation and physiological traits are linked to species' water use strategies and their drought tolerance. The dissertation is assembled of two study campaigns carried out on saplings at the Chair of Botany II, University of W{\"u}rzburg, Germany. The first study involved three ecologically important temperate broadleaved tree species — saplings of 18-month (Acer pseudoplatanus, Betula pendula, and Sorbus aucuparia) — grown from seeds in contrasting conditions (inside a greenhouse and outside), with the latter being subjected to severe natural heat waves. In the second study, two additional temperate species (Fagus sylvatica and Tilia cordata) were added. The drying-out event was conducted using a randomised blocked design by monitoring plant water status in a climate-controlled chamber and a greenhouse. In campaign I, I present the result based on analysed data of 82 plants of temperate deciduous species and address the juvenile growth rate trade-off with xylem safety-efficiency. Our results indicate biomass production varies considerably due to the contrasted growing environment. High hydraulic efficiency is necessary for increased biomass production, while safety-efficiency traits are decoupled and species-specific. Furthermore, productivity was linked considerably to xylem safety without revealing a well-defined pattern among species. Moreover, plasticity in traits differed between stressed and non-stressed plants. For example, safety-related characteristics were more static than efficiency-related traits, which had higher intra-specific variation. Moreover, we recorded anatomical and leaf traits adjustments in response to a stress condition, but consistency among species is lacking. In campaign II, I combined different ways to estimate the degree of isohydry based on water potential regulation and connected the iso-anisohydric spectrum (i.e., hydroscape area, HSA) to hydraulic traits to elucidate actual plant performance during drought. We analysed plant water potential regulation (Ψpd and Ψmd) and stomatal conductance of 28-29 month saplings of five species. I used a linear mixed modelling approach that allowed to control individual variations to describe the water potential regulation and tested different conceptual definitions of isohydricity. The combined methods allowed us to estimate species' relative degree of isohydry. Further, we examined the traits coordination, including hydraulic safety margin, HSM; embolism resistance, P88; turgor loss, Ψtlp; stomata closure, Ps90; capacitance, C; cuticular conductance, gmin, to determine time to hydraulic failure (Thf). Thf is the cumulative effect of time to stomata closure (Tsc) and time after stomatal closure to catastrophic hydraulic failure (Tcrit). Our results show the species' HSA matches their stomatal stringency, which confirms the relationship between stomatal response and leaf water potential decline. Species that close stomata at lower water potential notably had a larger HSA. Isohydric behaviour was mostly associated with leaf hydraulic traits and poorly to xylem safety traits. Species' degree of isohydry was also unrelated to the species' time to death during drying-out experiments. This supports the notion that isohydry behaviours are linked to water use rather than drought survival strategies. Further, consistent with our assumptions, more isohydric species had larger internal water storage and lost their leaf turgor at less negative water potentials. Counter to our expectations, neither embolism resistance nor the associated hydraulic safety margins were related to metrics of isohydry. Instead, our results indicate traits associated with plant drought response to cluster along two largely independent axes of variation (i.e., stomatal stringency and xylem safety). Furthermore, on the temporal progression of plant drought responses, stomatal closure is critical in coordinating various traits to determine species' hydraulic strategies. Desiccation avoidance strategy was linked to Tsc and coordinated traits response of Ps90, Ψtlp, and HSA, whereas desiccation tolerance was related to Tcrit and traits such as lower P88 value, high HSM, and lower gmin. Notably, the shoot capacitance (C) is crucial in Thf and exhibits dichotomous behaviour linked to both Tsc and Tcrit. In conclusion, knowledge of growth rate trade-offs with xylem safety-efficiency combined with traits linked to species' hydraulic strategies along the isohydry could substantially enhance our ability to identify drought-resistant saplings to ensure the success of reforestation programs and predicting sensitivity to drought for achieving sustainable forest ecosystems.},
  subject      = {Wachstumsrate},
  language  = {en}
}
@misc{Stark2024,
  type      = {Master Thesis},
  author    = {Stark, Luise},
  title     = {Flechten erz{\"a}hlen. Eine kulturanthropologische Studie {\"u}ber allt{\"a}gliche {\"A}sthetiken},
  doi       = {10.25972/OPUS-36978},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369784},
  school      = {Universit{\"a}t W{\"u}rzburg},
  pages     = {105},
  year      = {2024},
  abstract  = {Als Systemsprenger menschlicher Ordnungen und Wissenschaftstraditionen finden sich Flechten auf der ganzen Welt und bleiben doch oft unbemerkt. Das macht den Symbionten aus Pilz und Alge in urbanen, l{\"a}ndlichen und digitalen R{\"a}umen interessant f{\"u}r eine alltagswissenschaftliche Untersuchung. Menschliche Geschichten {\"u}ber Flechten sind gef{\"u}llt mit Vermutungen, H{\"o}rensagen und Assoziationen. Denn augenscheinlich sind Flechten in Deutschland wieder auf dem Vormarsch, sitzen vermehrt in den geliebten Obstb{\"a}umen, erobern Denkm{\"a}ler oder die heimischen Terrassen. Der Pilz im Symbionten wird als Gefahr f{\"u}r Leib und Leben erz{\"a}hlt, die pflanzliche Alge hingegen als Schmuck und nat{\"u}rliches Heilmittel. Ihre Auf- und Abwertung gibt viel {\"u}ber die Ordnungen des Anthropoz{\"a}ns preis. Kommen die Flechten selbst zu Wort, verfliegen diese kurzweiligen Narrative. Unbemerkt schaffen sie es durch das Bewachsen und Einf{\"a}rben von Oberfl{\"a}chen, dass Menschen R{\"a}ume anders lesen. Flechten geben uns nicht nur ein Gef{\"u}hl von Zeit, die schon vergangen ist, sondern formen redundante Wege von Wasser, Licht und Ber{\"u}hrung nach. Anhand der Flechte als {\"a}sthetischer Erfahrung wird hier ihre enorme Wirkmacht auf menschliche Alltage herausgearbeitet.},
  subject      = {Flechten},
  language  = {de}
}
@phdthesis{Banaschewski2024,
  author    = {Banaschewski, Nora Malaika Marcia Cath{\´e}rine},
  title     = {Erleichterungslernen bei Jugendlichen mit nicht-suizidalem selbstverletzendem Verhalten},
  doi       = {10.25972/OPUS-32367},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323673},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Die Erleichterung von einem k{\"o}rperlichen Schmerzreiz besitzt appetitiven Charakter (Leknes et al., 2008; 2011; Seymour et al., 2005), aktiviert belohnungsassoziierte Hirnstrukturen (Leknes et al., 2011; Leknes \& Brock, 2014; Leknes \& Tracey, 2008; Navratilova \& Porreca, 2014) und f{\"o}rdert durch ihre Konditionierbarkeit als Erleichterungslernen bezeichnete appetitive Lern- und Konditionierungsprozesse (Andreatta et al., 2010, 2012; 2013; 2017; Gerber et al., 2014; Tanimoto et al., 2004; Yarali et al., 2008). Die vorliegende Arbeit best{\"a}tigt das angewandte Versuchsparadigma als valides Modell f{\"u}r Erleichterungslernen im Menschen und zeigt erstmals, dass der appetitive Charakter von Schmerzerleichterung auch in Jugendlichen konditionierbar ist. Erfolgreiches Erleichterungslernen zeigte sich dabei in der untersuchten Stichprobe lediglich auf impliziter, nicht aber auf expliziter, kognitiver Ebene. Dies st{\"u}tzt Thesen und vorherige Forschungsbefunde einer Dualit{\"a}t assoziativen Lernens in ein implizites Lernen, welches vornehmlich subkortikale Strukturen erfordert und ein explizites Lernen, das vorrangig kortikale Strukturen wie den pr{\"a}frontalen Cortex involviert (Andreatta et al., 2010; Strack \& Deutsch, 2004; Williams et al., 2001). Die Beobachtungen einer differenten Furcht- versus Erleichterungs-Extinktion best{\"a}rken die Thesen eines diversen neuronalen Hintergrunds dieser beiden Lernformen (Diegelmann et al., 2013; Gerber et al., 2014; Yarali et al., 2009; Yarali \& Gerber, 2010). Gleichzeitig werfen die Studienergebnisse die Frage auf, ob und inwiefern im Erleichterungslernen von Jugendlichen Unterschiede zu jenem in Erwachsenen bestehen. Die Hypothese einer verst{\"a}rkten Akquisition von Erleichterungslernen bei Jugendlichen mit NSSV im Vergleich zu gesunden Jugendlichen ließ sich in der vorliegenden Studie nicht best{\"a}tigen. Somit liefern die Ergebnisse keinen direkten Hinweis darauf, dass ein verst{\"a}rktes Lernen durch Schmerzerleichterung an der {\"A}tiopathogenese von NSSV beteiligt sein k{\"o}nnte. Die vorliegende Arbeit zeigte vielmehr die Tendenz eines abgeschw{\"a}chten impliziten Erleichterungslernens bei den Jugendlichen mit NSSV. Die tendenziellen Gruppenunterschiede ließen sich nicht hinreichend durch eine differente aktuelle Stimmungslage oder durch eine unterschiedlich starke Auspr{\"a}gung aversiver emotionaler Anspannungen oder momentaner Angstaffekte erkl{\"a}ren. Innerhalb der Gruppe Jugendlicher mit NSSV zeigte sich auch kein Hinweis darauf, dass der Erfolg von Erleichterungslernen vom Schweregrad des NSSV oder von der aktuellen Einnahme von Antidepressiva abh{\"a}ngig sein k{\"o}nnte. Explorative Analysen ergaben, dass Gruppeneffekte in der vorliegenden Studie wom{\"o}glich aufgrund einer statistischen Untersch{\"a}tzung, bedingt durch einen zu geringen Stichprobenumfang, nicht das Signifikanzniveau erreichten und dass Unterschiede im Erleichterungslernen von Jugendlichen mit und ohne NSSV tats{\"a}chlich sogar noch st{\"a}rker ausgepr{\"a}gt sein k{\"o}nnten. Somit sollte die vorliegende Arbeit als Pilotstudie f{\"u}r zuk{\"u}nftige gr{\"o}ßer angelegte Studien zu Erleichterungslernen bei NSSV betrachtet werden. Zuk{\"u}nftige Studien erscheinen insbesondere sinnvoll mit Blick auf die hohe klinische sowie gesellschaftliche Relevanz von NSSV f{\"u}r welches, trotz der hohen Pr{\"a}valenzen und des deutlich erh{\"o}hten Morbidit{\"a}ts- und Mortalit{\"a}tsrisikos, zum aktuellen Zeitpunkt noch keine hinreichenden Erkl{\"a}rungsmodelle bestehen. Die Studie best{\"a}tigte das Vorliegen eines erh{\"o}hten Grades aversiver emotionaler Anspannung in Jugendlichen mit NSSV, welcher zuvor nur an Erwachsenen mit einer BPD untersucht und festgestellt worden war (Niedtfeld et al., 2010; Stiglmayr et al., 2005). Die Abnahme negativer Affekte bei den Jugendlichen mit NSSV im Studienverlauf repliziert die Ergebnisse vorheriger Studien, in denen eine Reduktion selbst-berichteter negativer Affekte durch die Beendigung eines Schmerzreizes beobachtet wurde (Bresin et al., 2010; Bresin \& Gordon, 2013). Damit best{\"a}rken die Studienergebnisse bestehende Erkl{\"a}rungsmodelle f{\"u}r NSSV, welche eine entscheidende Beteiligung der k{\"o}rperlichen Schmerzen und der Schmerzerleichterung bei der Selbstverletzung an der Affektregulation vermuten. Weiterhin wirft die vorliegende Arbeit die Frage auf, welche Rolle eine ver{\"a}nderte Wahrnehmung von Schmerz und Schmerzerleichterung in der {\"A}tiopathogenese von NSSV einnimmt und wie diese sich auf Lernprozesse auswirkt. Insgesamt erbr{\"a}chten weitere Erkenntnisse {\"u}ber den potenziellen Zusammenhang von NSSV und abweichendem Erleichterungslernen ein besseres Verst{\"a}ndnis f{\"u}r Mechanismen der Entstehung und Aufrechterhaltung von NSSV und b{\"o}ten zudem m{\"o}glicherweise Ans{\"a}tze f{\"u}r neue Therapiem{\"o}glichkeiten des St{\"o}rungsbildes.},
  subject      = {Selbstbesch{\"a}digung},
  language  = {de}
}
@phdthesis{Geissendoerfer2024,
  author    = {Geißend{\"o}rfer, Lisa},
  title     = {The Macroeconomic Dimensions of Credit: A Comprehensive Analysis of Finance, Inequality and Growth},
  doi       = {10.25972/OPUS-37003},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370037},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Besonders einflussreich f{\"u}r das moderne Verst{\"a}ndnis zur makro{\"o}konomischen Rolle von Banken und Kredit ist die monet{\"a}re Wachstumstheorie von Schumpeter. Ausgehend von dieser wird in dieser Dissertation die makro{\"o}konomische Rolle des Finanzsystems f{\"u}r die (1) Erzeugung von Wirtschaftswachstum, (2) Lenkung von {\"o}konomischen Ressourcen und (3) Verteilung von Wohlstand untersucht. In Kapitel 3 wird zun{\"a}chst empirisch gezeigt, dass 1.) ein positiver Zusammenhang zwischen dem Wachstum von Krediten und Wirtschaftswachstum besteht, auch f{\"u}r entwickelte L{\"a}nder, 2.) kein empirischer Zusammenhang von Haushaltssparen und Wirtschaftswachstum festgestellt werden kann, und 3.) auf l{\"a}nderspezifischer Ebene sowohl positive, als auch negative und insignifikante Effekte von Kredit auf Wirtschaftswachstum existieren. Damit zeigt sich eine breite empirische Evidenz f{\"u}r Schumpeters monet{\"a}re Hypothesen. Eine besonders interessante Anwendung von Schumpeters Wachstumstheorie zeigt sich in China. Die Ergebnisse der empirischen Analyse legen nahe, dass es generell einen positiven Zusammenhang zwischen Kredit- und Wirtschaftswachstum in China gibt, der aber nicht linear in Bezug auf Regionen, Zeitpunkte und Gr{\"o}ße des Finanzsystems ist. Weiterhin deuten die Ergebnisse darauf hin, dass die kreditfinanzierte Industriepolitik in China zu mehr Investitionen und BIP-Wachstum beigetragen haben k{\"o}nnte, wobei es jedoch Nichtlinearit{\"a}ten zwischen einzelnen Branchen und Unternehmenstypen gibt. Zuletzt wird in Kapitel 5 die Frage aufgeworfen, welche Rolle das Finanzsystem bei der Verteilung des Wohlstands spielt. W{\"a}hrend Kredite an Haushalte und Unternehmen, zusammen mit Indikatoren zum Arbeits- und Sparverhalten, sowie zur Altersstruktur der Bev{\"o}lkerung, die wichtigsten Determinanten von Verm{\"o}gensungleichheit sind, zeigen sich in der Beziehung von Krediten und Verm{\"o}gensungleichheit ebenfalls verschiedene Nichtlinearit{\"a}ten, u.a. im Bezug auf den Entwicklungsstand von Finanzsystemen und Wohneigentumsquoten.},
  subject      = {Kredit},
  language  = {en}
}
@article{GilSepulcreLindnerSchindleretal.2021,
  author    = {Gil-Sepulcre, Marcos and Lindner, Joachim O. and Schindler, Dorothee and Velasco, Luc{\´i}a and Moonshiram, Dooshaye and R{\"u}diger, Olaf and DeBeer, Serena and Stepanenko, Vladimir and Solano, Eduardo and W{\"u}rthner, Frank and Llobet, Antoni},
  title     = {Surface-promoted evolution of Ru-bda coordination oligomers boosts the efficiency of water oxidation molecular anodes},
  series = {Journal of the American Chemical Society},
  volume    = {143},
  journal   = {Journal of the American Chemical Society},
  number    = {30},
  doi       = {10.1021/jacs.1c04738},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-351514},
  pages     = {11651-11661},
  year      = {2021},
  abstract  = {A new Ru oligomer of formula {[Ru-\(^{II}\)(bda-\(\kappa\)-N\(^2\)O\(^2\))(4,4'-bpy)]\(_{10}\)(4,4'-bpy)}, 10 (bda is [2,2'-bipyridine]-6,6'-dicarbox-ylate and 4,4'-bpy is 4,4'-bipyridine), was synthesized and thoroughly characterized with spectroscopic, X-ray, and electrochemical techniques. This oligomer exhibits strong affinity for graphitic materials through CH-\(\pi\) interactions and thus easily anchors on multiwalled carbon nanotubes (CNT), generating the molecular hybrid material 10@CNT. The latter acts as a water oxidation catalyst and converts to a new species, 10'(H\(_2\)O)\(_2\)@CNT, during the electrochemical oxygen evolution process involving solvation and ligand reorganization facilitated by the interactions of molecular Ru catalyst and the surface. This heterogeneous system has been shown to be a powerful and robust molecular hybrid anode for electrocatalytic water oxidation into molecular oxygen, achieving current densities in the range of 200 mA/cm\(^2\) at pH 7 under an applied potential of 1.45 V vs NHE. The remarkable long-term stability of this hybrid material during turnover is rationalized based on the supramolecular interaction of the catalyst with the graphitic surface.},
  language  = {en}
}
@article{GronwaldHoosHottenrott2019,
  author    = {Gronwald, Thomas and Hoos, Olaf and Hottenrott, Kuno},
  title     = {Effects of Acute Normobaric Hypoxia on Non-linear Dynamics of Cardiac Autonomic Activity During Constant Workload Cycling Exercise},
  series = {Frontiers in Physiology},
  volume    = {10},
  journal   = {Frontiers in Physiology},
  doi       = {10.3389/fphys.2019.00999},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369199},
  year      = {2019},
  abstract  = {Aim: Measurements of Non-linear dynamics of heart rate variability (HRV) provide new possibilities to monitor cardiac autonomic activity during exercise under different environmental conditions. Using detrended fluctuation analysis (DFA) technique to assess correlation properties of heart rate (HR) dynamics, the present study examines the influence of normobaric hypoxic conditions (HC) in comparison to normoxic conditions (NC) during a constant workload exercise. Materials and Methods: Nine well trained cyclists performed a continuous workload exercise on a cycle ergometer with an intensity corresponding to the individual anaerobic threshold until voluntary exhaustion under both NC and HC (15\% O2). The individual exercise duration was normalized to 10\% sections (10-100\%). During exercise HR and RR-intervals were continuously-recorded. Besides HRV time-domain measurements (meanRR, SDNN), fractal correlation properties using short-term scaling exponent alpha1 of DFA were calculated. Additionally, blood lactate (La), oxygen saturation of the blood (SpO2), and rating of perceived exertion (RPE) were recorded in regular time intervals. Results: We observed significant changes under NC and HC for all parameters from the beginning to the end of the exercise (10\% vs. 100\%) except for SpO2 and SDNN during NC: increases for HR, La, and RPE in both conditions; decreases for SpO2 and SDNN during HC, meanRR and DFA-alpha1 during both conditions. Under HC HR (40-70\%), La (10-90\%), and RPE (50-90\%) were significantly-higher, SpO2 (10-100\%), meanRR (40-70\%), and DFA-alpha1 (20-60\%) were significantly-lower than under NC. Conclusion: Under both conditions, prolonged exercise until voluntary exhaustion provokes a lower total variability combined with a reduction in the amplitude and correlation properties of RR fluctuations which may be attributed to increased organismic demands. Additionally, HC provoked higher demands and loss of correlation properties at an earlier stage during the exercise regime, implying an accelerated alteration of cardiac autonomic regulation.},
  language  = {en}
}
@article{FahmyGarciaFarrellWitteBoumaetal.2019,
  author    = {Fahmy-Garcia, Shorouk and Farrell, Eric and Witte-Bouma, Janneke and Robbesom-van den Berge, Iris and Suarez, Melva and Mumcuoglu, Didem and Walles, Heike and Kluijtmans, Sebastiaan G. J. M. and van der Eerden, Bram C. J. and van Osch, Gerjo J. V. M. and van Leeuwen, Johannes P. T. M. and van Driel, Marjolein},
  title     = {Follistatin Effects in Migration, Vascularization, and Osteogenesis in vitro and Bone Repair in vivo},
  series = {Frontiers in Bioengineering and Biotechnology},
  volume    = {7},
  journal   = {Frontiers in Bioengineering and Biotechnology},
  doi       = {10.3389/fbioe.2019.00038},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227617},
  year      = {2019},
  abstract  = {The use of biomaterials and signaling molecules to induce bone formation is a promising approach in the field of bone tissue engineering. Follistatin (FST) is a glycoprotein able to bind irreversibly to activin A, a protein that has been reported to inhibit bone formation. We investigated the effect of FST in critical processes for bone repair, such as cell recruitment, osteogenesis and vascularization, and ultimately its use for bone tissue engineering. In vitro, FST promoted mesenchymal stem cell (MSC) and endothelial cell (EC) migration as well as essential steps in the formation and expansion of the vasculature such as EC tube-formation and sprouting. FST did not enhance osteogenic differentiation of MSCs, but increased committed osteoblast mineralization. In vivo, FST was loaded in an in situ gelling formulation made by alginate and recombinant collagen-based peptide microspheres and implanted in a rat calvarial defect model. Two FST variants (FST288 and FST315) with major differences in their affinity to cell-surface proteoglycans, which may influence their effect upon in vivo bone repair, were tested. In vitro, most of the loaded FST315 was released over 4 weeks, contrary to FST288, which was mostly retained in the biomaterial. However, none of the FST variants improved in vivo bone healing compared to control. These results demonstrate that FST enhances crucial processes needed for bone repair. Further studies need to investigate the optimal FST carrier for bone regeneration.},
  language  = {en}
}
@article{GalKilenczAlbertetal.2019,
  author    = {G{\´a}l, Bernadett I. and Kilencz, T{\"u}nde and Albert, Anita and Demeter, Ildik{\´o} and Hegedűs, Kl{\´a}ra M{\´a}ria and Janka, Zolt{\´a}n and Csifcs{\´a}k, G{\´a}bor and {\´A}lmos, P{\´e}ter Z.},
  title     = {Mild Effect of Nalmefene on Alcoholic Cue-Induced Response Invigoration in Alcohol Use Disorder Without Accompanying Changes in Electrophysiological Signatures of Early Visual Processing and Executive Control},
  series = {Frontiers in Pharmacology},
  volume    = {10},
  journal   = {Frontiers in Pharmacology},
  doi       = {10.3389/fphar.2019.01087},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369182},
  year      = {2019},
  abstract  = {Nalmefene is approved for as-needed pharmacological treatment in alcohol use disorder (AUD) by the European Medicines Agency. While the cellular effects of nalmefene have been thoroughly investigated, data are very limited on how this agent influences neural signals associated with inhibitory control and the visual analysis of environmental cues. This double-blind crossover study assessed the behavioral and neural effects of acute nalmefene administration in patients diagnosed with AUD. In experiment 1, we validated our experimental paradigm (electroencephalography combined with a modified Go/NoGo task using images of alcoholic and nonalcoholic drinks as prime stimuli) in 20 healthy adults to ensure that our protocol is suitable for assessing the behavioral and neural aspects of executive control. In experiment 2, we recruited 19 patients with AUD, and in a double-blind crossover design, we investigated the effects of nalmefene versus placebo on task performance (response accuracy, the sensitivity index, and reaction times), visual responses to appetitive cues (occipital P1, N1, and P2 components), and electrophysiological markers of conflict detection and response inhibition (frontal N2 and P3 waveforms). Under placebo, patients produced faster reaction times to alcohol-primed Go stimuli, an effect that was weak despite being statistically significant. However, the effect of alcoholic cues on the speed of response initiation disappeared after receiving nalmefene. We found no placebo versus nalmefene difference regarding our patients' ability to accurately inhibit responses to NoGo stimuli or for occipital and frontal event-related potentials. Our results suggest that nalmefene might be potent in reducing the vigor to act upon alcoholic cues in AUD patients, but this effect is most probably mediated via subcortical (rather than cortical) neural circuits.},
  language  = {en}
}
@article{FrankeConzelmannGruenblattetal.2019,
  author    = {Franke, Maximilian and Conzelmann, Annette and Gr{\"u}nblatt, Edna and Werling, Anna M. and Spieles, Helen and Wewetzer, Christoph and Warnke, Andreas and Romanos, Marcel and Walitza, Susanne and Renner, Tobias J.},
  title     = {No Association of Variants of the NPY-System With Obsessive-Compulsive Disorder in Children and Adolescents},
  series = {Frontiers in Molecular Neuroscience},
  volume    = {12},
  journal   = {Frontiers in Molecular Neuroscience},
  doi       = {10.3389/fnmol.2019.00112},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229051},
  year      = {2019},
  abstract  = {Obsessive-compulsive disorder (OCD) causes severe distress and is therefore counted by the World Health Organisation (WHO) as one of the 10 most impairing illnesses. There is evidence for a strong genetic underpinning especially in early onset OCD (eoOCD). Though several genes involved in neurotransmission have been reported as candidates, there is still a need to identify new pathways. In this study, we focussed on genetic variants of the Neuropeptide Y (NPY) system. NPY is one of the most abundant neuropeptides in the human brain with emerging evidence of capacity to modulate stress response, which is of high relevance in OCD. We focussed on tag-SNPs of NPY and its receptor gene NPY1R in a family-based approach. The sample comprised 86 patients (children and adolescents) with eoOCD with both their biological parents. However, this first study on genetic variants of the NPY-system could not confirm the association between the investigated SNPs and eoOCD. Based on the small sample size results have to be interpreted as preliminary and should be replicated in larger samples. However, also in an additional GWAS analysis in a large sample, we could not observe an associations between NPY and OCD. Overall, these preliminary results point to a minor role of NPY on the stress response of OCD.},
  language  = {en}
}
@article{GeranUeckerPruessetal.2019,
  author    = {Geran, Rohat and Uecker, Florian C. and Pr{\"u}ss, Harald and Haeusler, Karl Georg and Paul, Friedemann and Ruprecht, Klemens and Harms, Lutz and Schmidt, Felix A.},
  title     = {Olfactory and Gustatory Dysfunction in Patients With Autoimmune Encephalitis},
  series = {Frontiers in Neurology},
  volume    = {10},
  journal   = {Frontiers in Neurology},
  doi       = {10.3389/fneur.2019.00480},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232921},
  year      = {2019},
  abstract  = {Objective: To test the hypothesis that olfactory (OF) and gustatory function (GF) is disturbed in patients with autoimmune encephalitides (AE). Methods: The orthonasal OF was tested in 32 patients with AE and 32 age- and sex-matched healthy controls (HC) with the standardized Threshold Discrimination Identification (TDI) score. This validated olfactory testing method yields individual scores for olfactory threshold (T), odor discrimination (D), and identification (I), along with a composite TDI score. The GF was determined by the Taste Strip Test (TST). Results: Overall, 24/32 (75\%) of patients with AE, but none of 32 HC (p < 0.001) had olfactory dysfunction in TDI testing. The results of the threshold, discrimination and identification subtests were significantly reduced in patients with AE compared to HC (all p < 0.001). Assessed by TST, 5/19 (26.3\%) of patients with AE, but none of 19 HC presented a significant limitation in GF (p < 0.001). The TDI score was correlated with the subjective estimation of the olfactory capacity on a visual analog scale (VAS; rs = 0.475, p = 0.008). Neither age, sex, modified Rankin Scale nor disease duration were associated with the composite TDI score. Conclusions: This is the first study investigating OF and GF in AE patients. According to unblinded assessment, patients with AE have a reduced olfactory and gustatory capacity compared to HC, suggesting that olfactory and gustatory dysfunction are hitherto unrecognized symptoms in AE. Further studies with larger number of AE patients would be of interest to verify our results.},
  language  = {en}
}
@article{JarickMokhtariSchelleretal.2018,
  author    = {Jarick, Katja J. and Mokhtari, Zeinab and Scheller, Lukas and Hartweg, Julia and Thusek, Sina and Le, Duc-Dung and Ranecky, Maria and Shaikh, Haroon and Qureischi, Musga and Heinze, Katrin G. and Beilhack, Andreas},
  title     = {Photoconversion of Alloreactive T Cells in Murine Peyer's Patches During Acute Graft-Versus-Host Disease: Tracking the Homing Route of Highly Proliferative Cells In Vivo},
  series = {Frontiers in Immunology},
  volume    = {9},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2018.01468},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323309},
  year      = {2018},
  abstract  = {The regulation of immune cell migration throughout the body is essential to warrant immunosurveillance and to maintain immune homeostasis. Marking and tracking of these cells has proven important to study mechanisms of immune cell trafficking and cell interaction in vivo. Photoconversion is a well-suited technique for intravital application because it enables contactless time- and location-specific marking of cells in the tissue without surgically manipulating the microenvironment of the cells in question. However, in dividing cells the converted fluorescent protein may decline quickly. Here, we provide a detailed description of the photoconversion technique and its applicability to tracking highly proliferating T cells from the priming site of T cell activation to peripheral target organs of effector function in a preclinical model. Dendra2+ T cells were photoconverted in the Peyer's patches during the initiation phase of acute graft-versus-host disease (GvHD) and tracked through the mesenteric lymph nodes and the peripheral blood to the small intestine with flow cytometry and intravital two-photon microscopy. Photoconverted alloreactive T cells preserved the full proliferative capacity, homing, and migration of alloreactive T cells in the intestinal lamina propria. We conclusively proved that photoconversion of highly proliferative alloreactive T cells in the Peyer's patches is an effective tool to study trafficking of alloreactive T cells under physiologic conditions and to GvHD target tissues. This technique can also be applied to the study of immune cell tracking under inflammatory and non-inflammatory conditions.},
  language  = {en}
}
@article{HammerHalderKleihetal.2018,
  author    = {Hammer, Eva M. and Halder, Sebastian and Kleih, Sonja C. and K{\"u}bler, Andrea},
  title     = {Psychological Predictors of Visual and Auditory P300 Brain-Computer Interface Performance},
  series = {Frontiers in Neuroscience},
  volume    = {12},
  journal   = {Frontiers in Neuroscience},
  doi       = {10.3389/fnins.2018.00307},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-369207},
  year      = {2018},
  abstract  = {Brain-Computer Interfaces (BCIs) provide communication channels independent from muscular control. In the current study we used two versions of the P300-BCI: one based on visual the other on auditory stimulation. Up to now, data on the impact of psychological variables on P300-BCI control are scarce. Hence, our goal was to identify new predictors with a comprehensive psychological test-battery. A total of N = 40 healthy BCI novices took part in a visual and an auditory BCI session. Psychological variables were measured with an electronic test-battery including clinical, personality, and performance tests. The personality factor "emotional stability" was negatively correlated (Spearman's rho = -0.416; p < 0.01) and an output variable of the non-verbal learning test (NVLT), which can be interpreted as ability to learn, correlated positively (Spearman's rho = 0.412; p < 0.01) with visual P300-BCI performance. In a linear regression analysis both independent variables explained 24\% of the variance. "Emotional stability" was also negatively related to auditory P300-BCI performance (Spearman's rho = -0.377; p < 0.05), but failed significance in the regression analysis. Psychological parameters seem to play a moderate role in visual P300-BCI performance. "Emotional stability" was identified as a new predictor, indicating that BCI users who characterize themselves as calm and rational showed worse BCI performance. The positive relation of the ability to learn and BCI performance corroborates the notion that also for P300 based BCIs learning may constitute an important factor. Further studies are needed to consolidate or reject the presented predictors.},
  language  = {en}
}
@article{HersterBittnerCodreaetal.2019,
  author    = {Herster, Franziska and Bittner, Zsofia and Codrea, Marius Cosmin and Archer, Nathan K. and Heister, Martin and L{\"o}ffler, Markus W. and Heumos, Simon and Wegner, Joanna and Businger, Ramona and Schindler, Michael and Stegner, David and Sch{\"a}kel, Knut and Grabbe, Stephan and Ghoreschi, Kamran and Miller, Lloyd S. and Weber, Alexander N. R.},
  title     = {Platelets Aggregate With Neutrophils and Promote Skin Pathology in Psoriasis},
  series = {Frontiers in Immunology},
  volume    = {10},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2019.01867},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320175},
  year      = {2019},
  abstract  = {Psoriasis is a frequent systemic inflammatory autoimmune disease characterized primarily by skin lesions with massive infiltration of leukocytes, but frequently also presents with cardiovascular comorbidities. Especially polymorphonuclear neutrophils (PMNs) abundantly infiltrate psoriatic skin but the cues that prompt PMNs to home to the skin are not well-defined. To identify PMN surface receptors that may explain PMN skin homing in psoriasis patients, we screened 332 surface antigens on primary human blood PMNs from healthy donors and psoriasis patients. We identified platelet surface antigens as a defining feature of psoriasis PMNs, due to a significantly increased aggregation of neutrophils and platelets in the blood of psoriasis patients. Similarly, in the imiquimod-induced experimental in vivo mouse model of psoriasis, disease induction promoted PMN-platelet aggregate formation. In psoriasis patients, disease incidence directly correlated with blood platelet counts and platelets were detected in direct contact with PMNs in psoriatic but not healthy skin. Importantly, depletion of circulating platelets in mice in vivo ameliorated disease severity significantly, indicating that both PMNs and platelets may be relevant for psoriasis pathology and disease severity.},
  language  = {en}
}
@article{GryszelSchlossarekWuerthneretal.2023,
  author    = {Gryszel, Maciej and Schlossarek, Tim and W{\"u}rthner, Frank and Natali, Mirco and Głowacki, Eric Daniel},
  title     = {Water-soluble cationic perylene diimide dyes as stable photocatalysts for H\(_2\)O\(_2\) evolution},
  series = {ChemPhotoChem},
  volume    = {7},
  journal   = {ChemPhotoChem},
  number    = {9},
  issn      = {2367-0932},
  doi       = {10.1002/cptc.202300070},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-370250},
  year      = {2023},
  abstract  = {Photocatalytic generation of hydrogen peroxide, H\(_2\)O\(_2\), has gained increasing attention in recent years, with applications ranging from solar energy conversion to biophysical research. While semiconducting solid-state materials are normally regarded as the workhorse for photogeneration of H\(_2\)O\(_2\), an intriguing alternative for on-demand H\(_2\)O\(_2\) is the use of photocatalytic organic dyes. Herein we report the use of water-soluble dyes based on perylene diimide molecules which behave as true molecular catalysts for the light-induced conversion of dissolved oxygen to hydrogen peroxide. In particular, we address how to obtain visible-light photocatalysts which are stable with respect to aggregation and photochemical degradation. We report on the factors affecting efficiency and stability, including variable electron donors, oxygen partial pressure, pH, and molecular catalyst structure. The result is a perylene diimide derivative with unprecedented peroxide evolution performance using a broad range of organic donor molecules and operating in a wide pH range.},
  language  = {en}
}
@article{KasaragodSchindelin2018,
  author    = {Kasaragod, Vikram B. and Schindelin, Hermann},
  title     = {Structure-Function Relationships of Glycine and GABAA Receptors and Their Interplay With the Scaffolding Protein Gephyrin},
  series = {Frontiers in Molecular Neuroscience},
  volume    = {11},
  journal   = {Frontiers in Molecular Neuroscience},
  doi       = {10.3389/fnmol.2018.00317},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325607},
  year      = {2018},
  abstract  = {Glycine and γ-aminobutyric acid (GABA) are the major determinants of inhibition in the central nervous system (CNS). These neurotransmitters target glycine and GABAA receptors, respectively, which both belong to the Cys-loop superfamily of pentameric ligand-gated ion channels (pLGICs). Interactions of the neurotransmitters with the cognate receptors result in receptor opening and a subsequent influx of chloride ions, which, in turn, leads to hyperpolarization of the membrane potential, thus counteracting excitatory stimuli. The majority of glycine receptors and a significant fraction of GABAA receptors (GABAARs) are recruited and anchored to the post-synaptic membrane by the central scaffolding protein gephyrin. This ∼93 kDa moonlighting protein is structurally organized into an N-terminal G-domain (GephG) connected to a C-terminal E-domain (GephE) via a long unstructured linker. Both inhibitory neurotransmitter receptors interact via a short peptide motif located in the large cytoplasmic loop located in between transmembrane helices 3 and 4 (TM3-TM4) of the receptors with a universal receptor-binding epitope residing in GephE. Gephyrin engages in nearly identical interactions with the receptors at the N-terminal end of the peptide motif, and receptor-specific interaction toward the C-terminal region of the peptide. In addition to its receptor-anchoring function, gephyrin also interacts with a rather large collection of macromolecules including different cytoskeletal elements, thus acting as central scaffold at inhibitory post-synaptic specializations. Dysfunctions in receptor-mediated or gephyrin-mediated neurotransmission have been identified in various severe neurodevelopmental disorders. Although biochemical, cellular and electrophysiological studies have helped to understand the physiological and pharmacological roles of the receptors, recent high resolution structures of the receptors have strengthened our understanding of the receptors and their gating mechanisms. Besides that, multiple crystal structures of GephE in complex with receptor-derived peptides have shed light into receptor clustering by gephyrin at inhibitory post-synapses. This review will highlight recent biochemical and structural insights into gephyrin and the GlyRs as well as GABAA receptors, which provide a deeper understanding of the molecular machinery mediating inhibitory neurotransmission.},
  language  = {en}
}
@article{SchneiderWiewelhoveRaederetal.2019,
  author    = {Schneider, Christoph and Wiewelhove, Thimo and Raeder, Christian and Flatt, Andrew A. and Hoos, Olaf and Hottenrott, Laura and Schumbera, Oliver and Kellmann, Michael and Meyer, Tim and Pfeiffer, Mark and Ferrauti, Alexander},
  title     = {Heart Rate Variability Monitoring During Strength and High-Intensity Interval Training Overload Microcycles},
  series = {Frontiers in Physiology},
  volume    = {10},
  journal   = {Frontiers in Physiology},
  doi       = {10.3389/fphys.2019.00582},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231515},
  year      = {2019},
  abstract  = {Objective: In two independent study arms, we determine the effects of strength training (ST) and high-intensity interval training (HIIT) overload on cardiac autonomic modulation by measuring heart rate (HR) and vagal heart rate variability (HRV). Methods: In the study, 37 well-trained athletes (ST: 7 female, 12 male; HIIT: 9 female, 9 male) were subjected to orthostatic tests (HR and HRV recordings) each day during a 4-day baseline period, a 6-day overload microcycle, and a 4-day recovery period. Discipline-specific performance was assessed before and 1 and 4 days after training. Results: Following ST overload, supine HR, and vagal HRV (Ln RMSSD) were clearly increased and decreased (small effects), respectively, and the standing recordings remained unchanged. In contrast, HIIT overload resulted in decreased HR and increased Ln RMSSD in the standing position (small effects), whereas supine recordings remained unaltered. During the recovery period, these responses were reversed (ST: small effects, HIIT: trivial to small effects). The correlations between changes in HR, vagal HRV measures, and performance were weak or inconsistent. At the group and individual levels, moderate to strong negative correlations were found between HR and Ln RMSSD when analyzing changes between testing days (ST: supine and standing position, HIIT: standing position) and individual time series, respectively. Use of rolling 2-4-day averages enabled more precise estimation of mean changes with smaller confidence intervals compared to single-day values of HR or Ln RMSSD. However, the use of averaged values displayed unclear effects for evaluating associations between HR, vagal HRV measures, and performance changes, and have the potential to be detrimental for classification of individual short-term responses. Conclusion: Measures of HR and Ln RMSSD during an orthostatic test could reveal different autonomic responses following ST or HIIT which may not be discovered by supine or standing measures alone. However, these autonomic changes were not consistently related to short-term changes in performance and the use of rolling averages may alter these relationships differently on group and individual level.},
  language  = {en}
}
@article{KervarrecSamimiGuyetantetal.2019,
  author    = {Kervarrec, Thibault and Samimi, Mahtab and Guy{\´e}tant, Serge and Sarma, Bhavishya and Ch{\´e}ret, J{\´e}r{\´e}my and Blanchard, Emmanuelle and Berthon, Patricia and Schrama, David and Houben, Roland and Touz{\´e}, Antoine},
  title     = {Histogenesis of Merkel Cell Carcinoma: A Comprehensive Review},
  series = {Frontiers in Oncology},
  volume    = {9},
  journal   = {Frontiers in Oncology},
  doi       = {10.3389/fonc.2019.00451},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325733},
  year      = {2019},
  abstract  = {Merkel cell carcinoma (MCC) is a primary neuroendocrine carcinoma of the skin. This neoplasia features aggressive behavior, resulting in a 5-year overall survival rate of 40\%. In 2008, Feng et al. identified Merkel cell polyomavirus (MCPyV) integration into the host genome as the main event leading to MCC oncogenesis. However, despite identification of this crucial viral oncogenic trigger, the nature of the cell in which MCC oncogenesis occurs is actually unknown. In fact, several hypotheses have been proposed. Despite the large similarity in phenotype features between MCC tumor cells and physiological Merkel cells (MCs), a specialized subpopulation of the epidermis acting as mechanoreceptor of the skin, several points argue against the hypothesis that MCC derives directly from MCs. Alternatively, MCPyV integration could occur in another cell type and induce acquisition of an MC-like phenotype. Accordingly, an epithelial as well as a fibroblastic or B-cell origin of MCC has been proposed mainly based on phenotype similarities shared by MCC and these potential ancestries. The aim of this present review is to provide a comprehensive review of the current knowledge of the histogenesis of MCC.},
  language  = {en}
}
@article{NagyvanGeffenStegneretal.2019,
  author    = {Nagy, Magdolna and van Geffen, Johanna P. and Stegner, David and Adams, David J. and Braun, Attila and de Witt, Susanne M. and Elvers, Margitta and Geer, Mitchell J. and Kuijpers, Marijke J. E. and Kunzelmann, Karl and Mori, Jun and Oury, C{\´e}cile and Pircher, Joachim and Pleines, Irina and Poole, Alastair W. and Senis, Yotis A. and Verdoold, Remco and Weber, Christian and Nieswandt, Bernhard and Heemskerk, Johan W. M. and Baaten, Constance C. F. M. J.},
  title     = {Comparative Analysis of Microfluidics Thrombus Formation in Multiple Genetically Modified Mice: Link to Thrombosis and Hemostasis},
  series = {Frontiers in Cardiovascular Medicine},
  volume    = {6},
  journal   = {Frontiers in Cardiovascular Medicine},
  doi       = {10.3389/fcvm.2019.00099},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232194},
  year      = {2019},
  abstract  = {Genetically modified mice are indispensable for establishing the roles of platelets in arterial thrombosis and hemostasis. Microfluidics assays using anticoagulated whole blood are commonly used as integrative proxy tests for platelet function in mice. In the present study, we quantified the changes in collagen-dependent thrombus formation for 38 different strains of (genetically) modified mice, all measured with the same microfluidics chamber. The mice included were deficient in platelet receptors, protein kinases or phosphatases, small GTPases or other signaling or scaffold proteins. By standardized re-analysis of high-resolution microscopic images, detailed information was obtained on altered platelet adhesion, aggregation and/or activation. For a subset of 11 mouse strains, these platelet functions were further evaluated in rhodocytin- and laminin-dependent thrombus formation, thus allowing a comparison of glycoprotein VI (GPVI), C-type lectin-like receptor 2 (CLEC2) and integrin α6β1 pathways. High homogeneity was found between wild-type mice datasets concerning adhesion and aggregation parameters. Quantitative comparison for the 38 modified mouse strains resulted in a matrix visualizing the impact of the respective (genetic) deficiency on thrombus formation with detailed insight into the type and extent of altered thrombus signatures. Network analysis revealed strong clusters of genes involved in GPVI signaling and Ca2+ homeostasis. The majority of mice demonstrating an antithrombotic phenotype in vivo displayed with a larger or smaller reduction in multi-parameter analysis of collagen-dependent thrombus formation in vitro. Remarkably, in only approximately half of the mouse strains that displayed reduced arterial thrombosis in vivo, this was accompanied by impaired hemostasis. This was also reflected by comparing in vitro thrombus formation (by microfluidics) with alterations in in vivo bleeding time. In conclusion, the presently developed multi-parameter analysis of thrombus formation using microfluidics can be used to: (i) determine the severity of platelet abnormalities; (ii) distinguish between altered platelet adhesion, aggregation and activation; and (iii) elucidate both collagen and non-collagen dependent alterations of thrombus formation. This approach may thereby aid in the better understanding and better assessment of genetic variation that affect in vivo arterial thrombosis and hemostasis.},
  language  = {en}
}
@article{VuralDopplerMeinl2018,
  author    = {Vural, Atay and Doppler, Kathrin and Meinl, Edgar},
  title     = {Autoantibodies Against the Node of Ranvier in Seropositive Chronic Inflammatory Demyelinating Polyneuropathy: Diagnostic, Pathogenic, and Therapeutic Relevance},
  series = {Frontiers in Immunology},
  volume    = {9},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2018.01029},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233279},
  year      = {2018},
  abstract  = {Discovery of disease-associated autoantibodies has transformed the clinical management of a variety of neurological disorders. Detection of autoantibodies aids diagnosis and allows patient stratification resulting in treatment optimization. In the last years, a set of autoantibodies against proteins located at the node of Ranvier has been identified in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). These antibodies target neurofascin, contactin1, or contactin-associated protein 1, and we propose to name CIDP patients with these antibodies collectively as seropositive. They have unique clinical characteristics that differ from seronegative CIDP. Moreover, there is compelling evidence that autoantibodies are relevant for the pathogenesis. In this article, we review the current knowledge on the characteristics of autoantibodies against the node of Ranvier proteins and their clinical relevance in CIDP. We start with a description of the structure of the node of Ranvier followed by a summary of assays used to identify seropositive patients; and then, we describe clinical features and characteristics linked to seropositivity. We review knowledge on the role of these autoantibodies for the pathogenesis with relevance for the emerging concept of nodopathy/paranodopathy and summarize the treatment implications.},
  language  = {en}
}