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Institute
- Theodor-Boveri-Institut für Biowissenschaften (99)
- Medizinische Klinik und Poliklinik II (45)
- Institut für Anorganische Chemie (38)
- Neurologische Klinik und Poliklinik (32)
- Institut für Organische Chemie (29)
- Klinik und Poliklinik für Anästhesiologie (ab 2004) (26)
- Institut für Psychologie (24)
- Institut für Geographie und Geologie (23)
- Institut für Klinische Epidemiologie und Biometrie (22)
- Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik) (22)
Sonstige beteiligte Institutionen
- Agricultural Center, BASF SE, 67117 Limburgerhof, Germany (1)
- Core Unit Systemmedizin (1)
- Institute of Organic Chemistry and Center for Molecular Biosciences Innsbruck, CMBI, Leopold-Franzens University Innsbruck, Austria (1)
- Interdisciplinary Center for Clinical Research (1)
- Mildred Scheel Early Career Center (1)
- Paul Scherrer Institut (1)
Zusammenfassung
Der Beitrag stellt vor, wie die Universitätsbibliothek Würzburg im Rahmen ihrer Veranstaltungen rund um das 400-jährige Jubiläum für die Studierenden im Lesesaal ein Escape Game konzipierte und veranstaltete. Nach einem kurzen Abriss, woher das Konzept des Live-Action Escape Game stammt, liegt der Fokus auf den konkreten Arbeitsschritten, die mit der Umsetzung dieses an wissenschaftlichen Bibliotheken bisher wenig vertretenen Formats verbunden waren.
Kaussner, Y. ; Kuraszkiewicz, A. M. ; Schoch, S. ; Markel, Petra ; Hoffmann, S. ; Baur-Streubel, R. ; Kenntner-Mabiala, R. ; Pauli, P.
Objectives
Virtual reality exposure therapy (VRET) is a promising treatment for patients with fear of driving. The present pilot study is the first one focusing on behavioral effects of VRET on patients with fear of driving as measured by a post-treatment driving test in real traffic.
Methods
The therapy followed a standardized manual including psychotherapeutic and medical examination, two preparative psychotherapy sessions, five virtual reality exposure sessions, a final behavioral avoidance test (BAT) in real traffic, a closing session, and two follow-up phone assessments after six and twelve weeks. VRE was conducted in a driving simulator with a fully equipped mockup. The exposure scenarios were individually tailored to the patients’ anxiety hierarchy. A total of 14 patients were treated. Parameters on the verbal, behavioral and physiological level were assessed.
Results
The treatment was helpful to overcome driving fear and avoidance. In the final BAT, all patients mastered driving tasks they had avoided before, 71% showed an adequate driving behavior as assessed by the driving instructor, and 93% could maintain their treatment success until the second follow-up phone call. Further analyses suggest that treatment reduces avoidance behavior as well as symptoms of posttraumatic stress disorder as measured by standardized questionnaires (Avoidance and Fusion Questionnaire: p < .10, PTSD Symptom Scale–Self Report: p < .05).
Conclusions
VRET in driving simulation is very promising to treat driving fear. Further research with randomized controlled trials is needed to verify efficacy. Moreover, simulators with lower configuration stages should be tested for a broad availability in psychotherapy.
RNA aptamers form compact tertiary structures and bind their ligands in specific binding sites. Fluorescence-based strategies reveal information on structure and dynamics of RNA aptamers. Here we report the incorporation of the universal emissive nucleobase analog 4-cyanoindole into the fluorogenic RNA aptamer Chili, and its application as a donor for supramolecular FRET to bound ligands DMHBI+ or DMHBO+. The photophysical properties of the new nucleobase-ligand-FRET pair revealed structural restraints for the overall RNA aptamer organization and identified nucleotide positions suitable for FRET-based readout of ligand binding. This strategy is generally suitable for binding site mapping and may also be applied for responsive aptamer devices.
Comprehensive investigation in motor neuron disease is vital not to miss a treatable differential diagnosis. Neuroborreliosis should be considered during an ALS work‐up. However, false‐positive CSF results do occur, and thus, results should be interpreted carefully in context of all clinical test results.
Rational drug design of Axl tyrosine kinase type I inhibitors as promising candidates against cancer
(2020)
The high level of Axl tyrosine kinase expression in various cancer cell lines makes it an attractive target for the development of anti-cancer drugs. In this study, we carried out several sets of in silico screening for the ATP-competitive Axl kinase inhibitors based on different molecular docking protocols. The best drug-like candidates were identified, after parental structure modifications, by their highest affinity to the target protein. We found that our newly designed compound R5, a derivative of the R428 patented analog, is the most promising inhibitor of the Axl kinase according to the three molecular docking algorithms applied in the study. The molecular docking results are in agreement with the molecular dynamics simulations using the MM-PBSA/GBSA implicit solvation models, which confirm the high affinity of R5 toward the protein receptor. Additionally, the selectivity test against other kinases also reveals a high affinity of R5 toward ABL1 and Tyro3 kinases, emphasizing its promising potential for the treatment of malignant tumors.
Lymphoid aggregates in the CNS of progressive multiple sclerosis patients lack regulatory T cells
(2020)
Bell, Luisa ; Lenhart, Alexander ; Rosenwald, Andreas ; Monoranu, Camelia M. ; Berberich-Siebelt, Friederike
In gray matter pathology of multiple sclerosis, neurodegeneration associates with a high degree of meningeal inflammatory activity. Importantly, ectopic lymphoid follicles (eLFs) were identified at the inflamed meninges of patients with progressive multiple sclerosis. Besides T lymphocytes, they comprise B cells and might elicit germinal center (GC)-like reactions. GC reactions are controlled by FOXP3+ T-follicular regulatory cells (TFR), but it is unknown if they participate in autoantibody production in eLFs. Receiving human post-mortem material, gathered from autopsies of progressive multiple sclerosis patients, indeed, distinct inflammatory infiltrates enriched with B cells could be detected in perivascular areas and deep sulci. CD35+ cells, parafollicular CD138+ plasma cells, and abundant expression of the homing receptor for GCs, CXCR5, on lymphocytes defined some of them as eLFs. However, they resembled GCs only in varying extent, as T cells did not express PD-1, only few cells were positive for the key transcriptional regulator BCL-6 and ongoing proliferation, whereas a substantial number of T cells expressed high NFATc1 like GC-follicular T cells. Then again, predominant cytoplasmic NFATc1 and an enrichment with CD3+CD27+ memory and CD4+CD69+ tissue-resident cells implied a chronic state, very much in line with PD-1 and BCL-6 downregulation. Intriguingly, FOXP3+ cells were almost absent in the whole brain sections and CD3+FOXP3+ TFRs were never found in the lymphoid aggregates. This also points to less controlled humoral immune responses in those lymphoid aggregates possibly enabling the occurrence of CNS-specific autoantibodies in multiple sclerosis patients.
Solid tumors are complex organ-like structures that consist not only of tumor cells but also of vasculature, extracellular matrix (ECM), stromal, and immune cells. Often, this tumor microenvironment (TME) comprises the larger part of the overall tumor mass. Like the other components of the TME, the ECM in solid tumors differs significantly from that in normal organs. Intratumoral signaling, transport mechanisms, metabolisms, oxygenation, and immunogenicity are strongly affected if not controlled by the ECM. Exerting this regulatory control, the ECM does not only influence malignancy and growth of the tumor but also its response toward therapy. Understanding the particularities of the ECM in solid tumor is necessary to develop approaches to interfere with its negative effect. In this review, we will also highlight the current understanding of the physical, cellular, and molecular mechanisms by which the pathological tumor ECM affects the efficiency of radio-, chemo-, and immunotherapy. Finally, we will discuss the various strategies to target and modify the tumor ECM and how they could be utilized to improve response to therapy.
Baur, Florentin ; Nietzer, Sarah L. ; Kunz, Meik ; Saal, Fabian ; Jeromin, Julian ; Matschos, Stephanie ; Linnebacher, Michael ; Walles, Heike ; Dandekar, Thomas ; Dandekar, Gudrun
To improve and focus preclinical testing, we combine tumor models based on a decellularized tissue matrix with bioinformatics to stratify tumors according to stage-specific mutations that are linked to central cancer pathways. We generated tissue models with BRAF-mutant colorectal cancer (CRC) cells (HROC24 and HROC87) and compared treatment responses to two-dimensional (2D) cultures and xenografts. As the BRAF inhibitor vemurafenib is—in contrast to melanoma—not effective in CRC, we combined it with the EGFR inhibitor gefitinib. In general, our 3D models showed higher chemoresistance and in contrast to 2D a more active HGFR after gefitinib and combination-therapy. In xenograft models murine HGF could not activate the human HGFR, stressing the importance of the human microenvironment. In order to stratify patient groups for targeted treatment options in CRC, an in silico topology with different stages including mutations and changes in common signaling pathways was developed. We applied the established topology for in silico simulations to predict new therapeutic options for BRAF-mutated CRC patients in advanced stages. Our in silico tool connects genome information with a deeper understanding of tumor engines in clinically relevant signaling networks which goes beyond the consideration of single drivers to improve CRC patient stratification.
Rubus boreofrisicus Drenckhahn & H. E.Weber ist eine bisher unbeschriebene Rubus-Art der Untergattung Rubus, Serie Discolores. Die Endblättchen der 5-zähligen, handförmigen Schösslingsblätter sind breit eiförmig bis annähernd rund, unterseits grau-weißlich, oberseits dunkelgrün und schwach behaart. Die Schösslinge sind braunrot, kantig bis schwach gefurcht, etwas behaart mit geraden bis schwach gekrümmten, 5−8 mm langen, braunroten Stacheln mit heller Spitzenhälfte. Die Blütenstiele besitzen Stieldrüsen. Rubus boreofrisicus kommt häufig im Waldgürtel und in der angrenzenden Dünenheide der nordfriesischen Insel Amrum vor und ist auch 50 km südlich von Amrum in St. Peter-Ording im Westen der Halbinsel Eiderstedt vertreten.
Für das Vorkommen einer Ranunculus auricomus-Sippe im Oberen Inntal bei Innnsbuck, Nordtirol, Österreich, existieren belegte Nachweise seit 135 Jahren. Diese Sippe sammelte L. Sarnthein am 08.06.1884, J. Murr 1887 bei Flaurling. Von beiden Aufsammlungen befinden sich Belege im Tiroler Landesmuseum (Herbarium Ferdinandeum Innsbruck; IBF). Trotz Trockenlegung der Sumpfwiesen und Eutrophierung des Biotops kommt die Art noch aktuell in einem kleinen Nasswiesenrest vor. Sie wird hier als R. sarntheinianus Dunkel beschrieben, abgebildet und ihre Taxonomie wird diskutiert. Der mutmaßlich letzte Wuchsort ist vom Aussterben bedroht. Eine graphische Darstellung soll bei Artbestimmung und Auffinden neuer Wuchsorte behilflich sein.