@article{DongBoeppleThieletal.2023, author = {Dong, Meng and B{\"o}pple, Kathrin and Thiel, Julia and Winkler, Bernd and Liang, Chunguang and Schueler, Julia and Davies, Emma J. and Barry, Simon T. and Metsalu, Tauno and M{\"u}rdter, Thomas E. and Sauer, Georg and Ott, German and Schwab, Matthias and Aulitzky, Walter E.}, title = {Perfusion air culture of precision-cut tumor slices: an ex vivo system to evaluate individual drug response under controlled culture conditions}, series = {Cells}, volume = {12}, journal = {Cells}, number = {5}, issn = {2073-4409}, doi = {10.3390/cells12050807}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311030}, year = {2023}, abstract = {Precision-cut tumor slices (PCTS) maintain tissue heterogeneity concerning different cell types and preserve the tumor microenvironment (TME). Typically, PCTS are cultured statically on a filter support at an air-liquid interface, which gives rise to intra-slice gradients during culture. To overcome this problem, we developed a perfusion air culture (PAC) system that can provide a continuous and controlled oxygen medium, and drug supply. This makes it an adaptable ex vivo system for evaluating drug responses in a tissue-specific microenvironment. PCTS from mouse xenografts (MCF-7, H1437) and primary human ovarian tumors (primary OV) cultured in the PAC system maintained the morphology, proliferation, and TME for more than 7 days, and no intra-slice gradients were observed. Cultured PCTS were analyzed for DNA damage, apoptosis, and transcriptional biomarkers for the cellular stress response. For the primary OV slices, cisplatin treatment induced a diverse increase in the cleavage of caspase-3 and PD-L1 expression, indicating a heterogeneous response to drug treatment between patients. Immune cells were preserved throughout the culturing period, indicating that immune therapy can be analyzed. The novel PAC system is suitable for assessing individual drug responses and can thus be used as a preclinical model to predict in vivo therapy responses.}, language = {en} } @article{HeisigWeberEnglbergeretal.2012, author = {Heisig, Julia and Weber, David and Englberger, Eva and Winkler, Anja and Kneitz, Susanne and Sung, Wing-Kin and Wolf, Elmar and Eilers, Martin and Wei, Chia-Lin and Gessler, Manfred}, title = {Target Gene Analysis by Microarrays and Chromatin Immunoprecipitation Identifies HEY Proteins as Highly Redundant bHLH Repressors}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75341}, year = {2012}, abstract = {HEY bHLH transcription factors have been shown to regulate multiple key steps in cardiovascular development. They can be induced by activated NOTCH receptors, but other upstream stimuli mediated by TGFß and BMP receptors may elicit a similar response. While the basic and helix-loop-helix domains exhibit strong similarity, large parts of the proteins are still unique and may serve divergent functions. The striking overlap of cardiac defects in HEY2 and combined HEY1/HEYL knockout mice suggested that all three HEY genes fulfill overlapping function in target cells. We therefore sought to identify target genes for HEY proteins by microarray expression and ChIPseq analyses in HEK293 cells, cardiomyocytes, and murine hearts. HEY proteins were found to modulate expression of their target gene to a rather limited extent, but with striking functional interchangeability between HEY factors. Chromatin immunoprecipitation revealed a much greater number of potential binding sites that again largely overlap between HEY factors. Binding sites are clustered in the proximal promoter region especially of transcriptional regulators or developmental control genes. Multiple lines of evidence suggest that HEY proteins primarily act as direct transcriptional repressors, while gene activation seems to be due to secondary or indirect effects. Mutagenesis of putative DNA binding residues supports the notion of direct DNA binding. While class B E-box sequences (CACGYG) clearly represent preferred target sequences, there must be additional and more loosely defined modes of DNA binding since many of the target promoters that are efficiently bound by HEY proteins do not contain an Ebox motif. These data clearly establish the three HEY bHLH factors as highly redundant transcriptional repressors in vitro and in vivo, which explains the combinatorial action observed in different tissues with overlapping expression.}, subject = {Biologie}, language = {en} } @phdthesis{Winkler2023, author = {Winkler, Julia}, title = {The Experience of Emotional Shifts as a Narrative Process: Investigating the Relationship of Emotional Shifts and Transportation and Their Roles in Narrative Persuasion}, doi = {10.25972/OPUS-32179}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321794}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Emotional shifts are often a fundamental part of the narrative experience and engrained into the schematic structures of stories. Recent theoretical work suggests that these shifts are key for narrative influence and are interconnected with transportation, a known mechanism of narrative effects. Empirical research examining this proposition is still scarce, inconclusive, and lacking measures that assess the experience of emotional shifts throughout a narrative to explain effects. This thesis aims to contribute to this research lacuna and investigates the link between emotional shifts, transportation, and story-consistent outcomes using different methods to measure emotional shifts in the moment they occur (Manuscript \#1 and \#2), and using various narrative stimuli (audiovisual, written, auditive). Manuscript \#1 uses real-time-response (RTR) measurement to examine the relationship of valence shifts experienced during film viewing with transportation and post-exposure self-reported emotional flow. Manuscript \#2 reports a pilot study and two experiments in which a self-probed emotional retrospection task is used to measure the number and intensity of emotional shifts during reading. I investigate the effect of reviews on transportation, the link between transportation and emotional shifts, and their respective associations with story-consistent attitudes, social sharing intentions, and donation behavior. In Manuscript \#3, narrative structures are manipulated. Two experiments examine the effects of audio stories with shifting (positive-negative-positive) vs. positive-only emotional trajectories on the experience of happiness- and sadness-shifts, transportation, and post-exposure emotional flow. Transportation was positively linked to valence shifts (M\#1), and the number and intensity of emotional shifts (M\#2), and emotional flow (M\#1, M\#3). In M\#3, transportation was predicted by shifts in happiness, but not sadness. Emotional flow was linked to shifts in happiness, sadness, and RTR valence (M\#1, M\#3). Emotional shifts and transportation were associated with social sharing intentions, but only transportation was linked to some story-consistent attitudes (affective attitudes in particular).}, subject = {Gef{\"u}hl}, language = {en} } @article{JendretzkiHennigerSchiffmannetal.2022, author = {Jendretzki, Julia and Henniger, Dorothea and Schiffmann, Lisa and Wolz, Constanze and Kollikowski, Anne and Meining, Alexander and Einsele, Hermann and Winkler, Marcela and L{\"o}ffler, Claudia}, title = {Every fifth patient suffered a high nutritional risk — Results of a prospective patient survey in an oncological outpatient center}, series = {Frontiers in Nutrition}, volume = {9}, journal = {Frontiers in Nutrition}, issn = {2296-861X}, doi = {10.3389/fnut.2022.1033265}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311284}, year = {2022}, abstract = {Introduction Malnutrition in cancer patients often remains undetected and underestimated in clinical practice despite studies revealing prevalences from 20 to 70\%. Therefore, this study aimed to identify patient groups exposed to an increased nutritional risk in a university oncological outpatient center. Methods Between May 2017 and January 2018 we screened oncological patients there using the malnutrition universal screening tool (MUST). Qualitative data were collected by a questionnaire to learn about patients' individual information needs and changes in patients' diets and stressful personal nutrition restrictions. Results We included 311 patients with various cancers. 20.3\% (n = 63) were found to be at high risk of malnutrition, 16.4\% (n = 51) at moderate risk despite a mean body mass index (BMI) of 26.5 ± 4.7 kg/m2. The average age was 62.7 (± 11.8) with equal gender distribution (52\% women, n = 162). In 94.8\% (n = 295) unintended weight loss led to MUST scoring. Patients with gastrointestinal tumors (25\%, n = 78) and patients >65 years (22\%, n = 68) were at higher risk. Furthermore, there was a significant association between surgery or chemotherapy within six months before survey and a MUST score ≥2 (OR = 3.6). Taste changes, dysphagia, and appetite loss were also particular risk factors (OR = 2.3-3.2). Young, female and normal-weight patients showed most interest in nutrition in cancer. However, only 38\% (n = 118) had a nutritional counseling. Conclusion This study confirms that using the MUST score is a valid screening procedure to identify outpatients at risk of developing malnutrition. Here one in five was at high risk, but only 1\% would have been detected by BMI alone. Therefore, an ongoing screening procedure with meaningful parameters should be urgently implemented into the clinical routine of cancer outpatients as recommended in international guidelines.}, language = {en} } @article{LudwigReymusWinkleretal.2023, author = {Ludwig, Julia and Reymus, Marcel and Winkler, Alexander and Soliman, Sebastian and Krug, Ralf and Krastl, Gabriel}, title = {Root maturation of an immature dens invaginatus despite unsuccessful revitalization procedure: a case report and recommendations for educational purposes}, series = {Dentistry Journal}, volume = {11}, journal = {Dentistry Journal}, number = {2}, issn = {2304-6767}, doi = {10.3390/dj11020047}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304108}, year = {2023}, abstract = {Background: The clinical management of teeth with complex dens invaginatus (DI) malformations and apical periodontitis may be challenging due to the lack of routine. The aim of this case report is to describe the endodontic treatment of an immature tooth with DI and to discuss strategies for preclinical training for teeth with such malformations. Case report: A 9-year-old male presented with an immature maxillary incisor with DI (Oehlers Type II) and apical periodontitis which was diagnosed by cone beam computed tomography (CBCT). Revitalization was initially attempted but then abandoned after failure to generate a stable blood clot. Nevertheless, considerable increase in both root length and thickness could be detected after medication with calcium hydroxide followed by root canal filling with MTA as an apical plug. Conclusions: The endodontic management of teeth with DI requires thorough treatment planning. In immature teeth, under certain conditions, root maturation may occur even with conventional apexification procedures. From an educational perspective, different strategies including CBCT and 3D-printed transparent tooth models for visualization of the complex internal morphology and redesigned 3D-printed replica with various degrees of difficulty for endodontic training, can be used to overcome the challenges associated with endodontic treatment of such teeth.}, language = {en} }