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Item type: Item , Establishing pangenome graph as a framework for the analysis of the impact of structural variation on gene expression(2025) Yildiz, GözdeThis thesis addresses key challenges and opportunities in structural variation (SV) detection, genotyping, and downstream analyses using pangenome variation graphs for Brassica napus. By integrating different sequencing technologies and available bioinformatics tools, it demonstrates strategies to optimize the analysis of complex plant genomes, which are typically large, repetitive, and polyploid. Popular mapping and SV calling pipelines were evaluated using both simulated and real datasets from major crops, including rapeseed, tomato, maize, and soybean, across low to medium sequencing depths. The results demonstrate the feasibility of cost-effective SV detection, identifying the most efficient aligners and callers that achieve robust performance even at low coverage (≥5×). These findings provide a practical framework for population-scale crop studies, where sequencing costs and coverages are often a limiting factor. A graph-based pangenome approach was developed by combining long-read SV discovery with pangenome reference, allowing comparison with existing references to assess and reduce reference bias. This strategy enabled the identification of SVs, the construction of graph-based pangenomes, and subsequent SV genotyping in larger populations using short-read data, eliminating the need for costly de novo assemblies. The approach is therefore scalable, accessible, and suitable for high-throughput crop genomics. Importantly, integration with gene expression data revealed that many SVs, particularly those linked to transposable elements, significantly affect gene regulation and may underlie key agronomic traits. Overall, this thesis demonstrates that SVs are not only a major source of genetic diversity but also critical drivers of gene regulatory variation in crops. By providing benchmarking guidelines, novel graph-based pipelines, and functional insights into SVs, it lays the foundation for incorporating structural variation into future genome-informed breeding and trait discovery, ultimately supporting the development of more resilient and productive crop varieties.Item type: Item , Effects of Polyamide Microplastic Particles on Aquatic Outdoor Ecosystems - A Mesocosm Study(2026) Kruckenfellner, LukasThe protection and preservation of ecosystems, their biodiversity and the inherent ecosystem services should be a central goal of current scientific efforts. Not only the increasing chemical pollution, but also the increased occurrence of plastic is putting constant stress on ecosystems and individuals. There are many regulations and standardized procedures to assess the potential risk that chemical substances can have on the environment. This is not the case for particles such as microplastic. Although the uptake and transfer of microplastic particles along the food chain has already been proven, it is difficult to obtain a comparative overview of the ecotoxicological risk due to the large number of different parent substances, sizes, shapes and chemical additives. Standing water bodies such as lakes or reservoirs are a potential sink for such particles due to the lack of hydrodynamic pressure. This can lead to strong accumulations compared to the lotic inflows. The plastic particles, some of which are colonized by biofilms, can be mistaken for food or ingested unselectively by the organisms. This leads potentially to biomagnification in natural systems.<br> Since this can only be inadequately reproduced in classical laboratory studies, an aquatic field model ecosystem study was carried out in this project to investigate the influence of polyamide particles on aquatic biocoenosis. Particles with a size range of 5-50 µm were applied to the model ecosystems in three concentrations four times over a period of ten days in order to simulate a continuous influx of particles. In addition, a particulate control was used in the experiment to compare the potential effects of pure particles with those of the polyamide microplastic. Abiotic parameters and representatives of all trophic levels were regularly sampled and evaluated over a period of more than 100 days. The primary producers were represented by the chlorophyll a content in free-floating algae and the consumers and decomposers by animal plankton and larger invertebrates. The concentrations used in the approximately 1000 L systems were 1.5 mg L⁻¹, 15 mg L⁻¹ and 150 mg L⁻¹. In addition to pure abundance counts, the biovolume of adult and larval macroinvertebrates was also recorded and emergence time was established as a new endpoint for higher-tier studies.<br> The analysis of the samples revealed effects on the abundance of seed shrimps (Ostracoda). All polyamide treatments showed significant reductions compared to the control, with the effects at the highest concentration being the most long-term. No effects were observed in the particle control. A significantly earlier Emergence mean Time was observed in the emerged individuals of a subfamily of non-biting midges (Orthocladiinae). With a duration of 114 days this study is one of few to include long exposure, a particulate treated control and an environmentally realistic concentration of polyamide particles and gives important information for the risk assessment of microplastic under near-natural conditions.Item type: Item , The Effect of Application Mode and Aging on the Micro-tensile Bond Strength of Universal Adhesives to Enamel of Primary Teeth(2026) Hamdy, Dina Hassan SalaheldeenThe increased demand for simple and efficient adhesive systems made current multimode universal adhesives of great interest in pediatric dentistry. These are mainly characterized by a reduction in the number of application steps, hence limiting the duration of treatment during restorative procedures, together with achieving good dentin adhesion. However, application protocols for universal adhesives have not been defined precisely for primary enamel. Furthermore, the effect of aging was ignored, which lead to reporting higher bond strength values than the real ones due to overlooking the effect of factors, such as thermal stresses and normal daily functions on the bond strength. Thus, the aim of this study was to evaluate the effect of selective acid etching, different etching times, and active rubbing of universal adhesives on the microtensile bond strength to the enamel of primary teeth and to determine the stability of selective acid etching after 6 months aging in an aqueous solution. Sound human primary molars were sectioned mesiodistally. Tooth halves (n=113) were randomized into 3 groups based on the adhesive used: SU: Scotchbond Universal (3M); CU: Clearfil Universal Bond Quick (Kuraray Noritake); iBU: iBond Universal (Heraeus Kulzer). Aprismatic enamel was removed, then groups were subdivided according to application mode into 4 subgroups (SG): SGA: self-etch mode, SGB: 30s-selective etching, SGC: 15s-selective etching, SGD: active rubbing of the adhesive. Adhesives and composite were added (Filtek Z250, 3M). Samples were incubated in distilled water at +37°C for 24h, while separate samples for SGA& SGC were aged for 6 months. Specimens were dissected into rods (0.7 mm × 0.7 mm; IsoMet Highspeed Pro, Buehler), then tested for microtensile bond strength (µTBS; TC-550, Syndicad). Failure patterns were evaluated under light microscope (AZ100M, Nikon). Data were analysed with linear mixed effects model (restricted maximum likelihood, REML) and Sidak post-hoc-tests using SPSS 26.0 (Statistical Packages for Social Sciences, IBM Statistics, Armonk, NY, USA) with significance level set at α < 0.05. Our results showed that selective-etching increased µ-TBS of universal adhesives to primary enamel (p < 0.001) without significance between enamel etching for 15 s and 30 s (p > 0.05). Six-month aging significantly reduced the µ-TBS of SU in SGC (p = 0.014) compared to µ-TBS after 24h incubation. So, it was concluded that, selective etching with phosphoric acid remains the gold standard for bonding universal adhesives to primary enamel. Etching time showed no significant effect on µ-TBS. Aging may affect the µ-TBS of SU applied on 15 s phosphoric acid etched primary enamel.Item type: Item , Der Wunsch nach sozialer Distanz zu Menschen mit Psoriasis als Ausdruck von Stigmatisierung bei Psoriasis-Patient:innen und Hautgesunden(2025) Munz, Johanna Lydia MariaPsoriasis ist eine chronisch-entzündliche Hauterkrankung, die häufig mit einer hohen psychosozialen Belastung einhergeht. Ein Grund dafür kann das Erleben von Stigmatisierung sein, zu der sowohl Fremdstigmatisierung durch die Gesellschaft als auch Selbststigmatisierung durch die Betroffenen selbst gehört. Personen mit Psoriasis erleben mehr Stigmatisierung als Personen ohne Hauterkrankungen. Bislang war jedoch unklar, inwiefern sich Psoriasis-Patient:innen und hautgesunde Personen in ihren stigmatisierenden Einstellungen gegenüber anderen Personen mit Psoriasis unterscheiden. Daher war es das Ziel dieser Studie, den Wunsch nach sozialer Distanz zu Personen mit unterschiedlich schwer ausgeprägten Psoriasis-Läsionen im Gesicht zwischen diesen beiden Gruppen zu vergleichen und darüber hinaus Alters- und Geschlechtsunterschiede sowie weitere potenzielle Prädiktoren für stigmatisierende Einstellungen gegenüber Psoriasis zu explorieren. Dazu bewerteten 144 Psoriasis-Patient:innen und 144 hautgesunden Personen in der quasi-experimentellen Querschnitts-Studie online jeweils drei Bilder, die verschiedene Gesichter ohne, mit milden oder mit schweren Psoriasis-Läsionen im Gesicht zeigten. Der primäre Zielparameter war der Wunsch nach sozialer Distanz zu den abgebildeten Personen. Sekundäre Zielparameter waren die wahrgenommene Attraktivität der abgebildeten Personen und die Zustimmung zu Psoriasis-bezogenen Falschaussagen. Über alle Bilder hinweg zeigten Psoriasis-Patient:innen einen geringeren Wunsch nach sozialer Distanz als die hautgesunden Kontrollen. Der Wunsch nach sozialer Distanz stieg mit der Sichtbarkeit der abgebildeten Psoriasis-Läsionen über beide Gruppen hinweg an. Darüber hinaus hatten männliche und 41- bis 65-jährige hautgesunde Personen einen stärkeren Wunsch nach sozialer Distanz als weibliche bzw. 18- bis 40-jährige hautgesunde Personen. In beiden Gruppen bewerteten Männer und 41- bis 65-jährige Personen die abgebildeten Personen als weniger attraktiv, während Männer und 18- bis 40-jährige Personen den Psoriasis-bezogenen Falschaussagen stärker zustimmten als die entsprechenden Vergleichsgruppen. Ein stärkerer Wunsch nach sozialer Distanz ging mit einer stärkeren Zustimmung zu Psoriasis-bezogenen Falschaussagen einher, die bei Hautgesunden im Allgemeinen stärker ausgeprägt war als bei Psoriasis-Patient:innen. Diese Studie zeigt, dass die Stigmatisierung von Personen mit Psoriasis sowohl bei Hautgesunden als auch bei Psoriasis-Patient:innen weit verbreitet ist, wenn auch nicht stark ausgeprägt. Die Ergebnisse der Studie unterstreichen die Notwendigkeit einer verstärkten Sensibilisierungs- und Aufklärungsarbeit zu Psoriasis, insbesondere in der Allgemeinbevölkerung, aber auch bei Psoriasis-Patient:innen. Durch effektive Maßnahmen gegen Fremdstigmatisierung und Selbststigmatisierung lassen sich die mentale Gesundheit und die Lebensqualität von Personen, die von Psoriasis betroffen sind, erheblich verbessern.Item type: Item , Evaluating the in vitro effects of selective and potent non-selective fibroblast growth factor receptor inhibition in human BL2 cells as potential therapeutic targets for multiple sclerosis(2025) von Au, Laureen JulianaB lymphocytes play a key role in the pathogenesis of multiple sclerosis (MS). While B-cell-depleting therapies have demonstrated clinical efficacy, emerging therapeutic strategies focus on functional modulation of B cells to preserve overall immune homeostasis. In addition to B cells, molecular signaling pathways such as the B cell receptor pathway, targeted by Bruton’s tyrosine kinase inhibitor and fibroblast growth factor (FGF/FGFR) signaling, important for neurodegeneration and immune regulation in the central nervous system, have gained attention. Experimental autoimmune encephalomyelitis models showed that conditional deletion of FGFR1/2 in oligodendrocytes resulted in a milder disease course, reduced inflammation, and decreased myelin and axon degeneration. In demyelinating lesions, the number of immune cells was significantly reduced, indicating that FGF/FGFR signaling might play an important role in immune cell modulation. This study investigated the effects of pharmacological FGFR inhibition on BL2 cells. Selective FGFR inhibitors (AZD4547, infigratinib) and the multikinase inhibitor dovitinib were investigated for their effects on BL2 cell proliferation, cytotoxicity, receptor expression (FGFR1/2), intracellular signaling (pERK, pAkt), and cytokine production using WST-1 and LDH assays, immunofluorescence, western blot, and RT-PCR. Under in vitro conditions, FGFR inhibition did not affect BL2 cell proliferation or exerted cytotoxic effects. Dovitinib significantly reduced the surface expression of FGFR1, pERK activation, and the secretion of the pro inflammatory cytokines IL6 and IL12, both important in the pathophysiology of MS. In contrast, selective FGFR inhibitors had only minor effects. FGFR2 mRNA levels were reduced across all treatment groups, and protein levels remained unchanged, suggesting posttranscriptional regulation or the activation of compensatory feedback mechanisms. An increase in pAkt activity, particularly following infigratinib treatment, further indicates the activation of alternative signaling pathways in response to FGFR blockade. The enhanced efficacy of dovitinib might be due to its broader kinase inhibition profile, targeting not only FGFR but also additional tyrosine kinases. In summary, this study shows that the multikinase FGFR inhibitor dovitinib can modulate pro-inflammatory B cell activity without compromising cell viability, offering a promising strategy as a targeted immunomodulatory approach for MS therapy.