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Characterizing inflammatory transcription hubs in ARID1A-deficient PDAC subtypes
No full textThe SWitch/Sucrose Non-Fermentable (SWI/SNF) complex functions as a tumor suppressor in several tumor entities, including pancreatic ductal adenocarcinoma (PDAC). The AT-rich interaction domain-containing protein 1A (ARID1A) is the most frequently altered subunit of this complex. It is believed to play a crucial role in the chromatin remodeling activity of SWI/SNF by its direct DNA-binding domain and its interaction with transcriptional cofactors. We demonstrate that ARID1A deficiency displays a significant effect on tumor progression in PDAC. Mechanistically, we show that ARID1A deficiency drives the enrichment of gene signatures linked to inflammatory cytokines and inflammatory tumor promoting transcription factors (TFs), suggesting that targeting inflammatory transcription hubs might represent a promising therapeutic strategy in ARID1A-deficient PDAC. Specifically, we find that ARID1A- deficiency promotes transcriptional reprogramming processes mediated by the inflammatory tumor-promoting TFs cJUN and MAZ (Myc associated zinc finger). On this regard, in vitro CHIP-seq analysis shows that the absence of ARID1A enhances binding of H3K27ac, a histone mark of transcriptional activity, at promoter regions with higher enrichment of MAZ consensus site. MAZ binding was confirmed via chromatin immunoprecipitation (ChIP) at the promoter region of the LIF (Leukemia Inhibitory Factor) gene, a candidate ARID1A target gene. Moreover, the expression of MAZ proved to be involved in the activation of the inflammatory STAT3 signaling pathway by controlling an autocrine loop through the regulation of the LIF expression and secretion. In parallel, we also addressed the contribution of AP1 TFs in regulating the same candidate inflammatory and tumor-associated genes. In particular, the TF cJUN seems to be an ideal candidate considering the significant enrichment of the consensus site at the distal ARID1A-bound regions. cJUN binding was confirmed at the enhancer of the LIF gene and its downregulation leads to decreased LIF expression in ARID1A-deficient PDAC subtypes. Moreover, 4C-seq technology reveiled looping's formation and MAZ-cJUN-bound regions interaction upon ARID1A deficiency, suggesting that ARID1A-deficiency affects chromatin reorganization at the LIF locus. Despite its role in promoting PDAC progression, monotherapy with a LIF antibody did not significantly reduce tumor progression or improve survival in an ARID1A-deficient syngeneic PDAC model. This outcome underscores the complexity of the inflammatory network driven by ARID1A loss and suggests that LIF alone is not the sole driver of the observed tumor-promoting effects. Altogether, our findings suggest that ARID1A deficiency induces PDAC progression via fostering inflammation and indicate that the cJUN MAZ-LIF axis is a crucial player in regulating these inflammatory and tumor-promoting processes. Furthermore, these findings provide a basis for future therapeutic strategies aimed at targeting the broader network of inflammatory and tumor-promoting signals in ARID1A-deficient PDAC, emphasizing the need for combination therapies.2026-01-2
Einfluss der operativen Versorgung einer epiretinalen Gliose auf das Binokularsehen und auf die Aniseikonie
No full textEinleitung:
Patienten nach peeling-Chirurgie bei epiretinaler Gliose beklagen gelegentlich postoperativ binokluare Sehstörungen. Ziel dieser Studie war das Erfassen subjektiver Beschwerden und die Korrelation zu prä- und postoperativ objektiv messbaren Parametern bezüglich des beidäugigen Sehens aufgrund einer Aniseikonie.
Methodik:
In dieser prospektiven Kohortenstudie wurden konsekutiv Patienten mit einer einseitigen epiretinalen Gliose eingeschlossen. Es wurde präoperativ und 3 Monate postoperativ standardisiert augenärztlich und strabologisch untersucht. Alle Patienten mussten für den Einschluss mindestens einen Visus von 0,2 auf dem betroffenen Auge und auf dem Partnerauge von 0,5 erreichen. Zudem durfte keiner der Patienten eine einseitige Pseudophakie oder eine Anisometropie von mehr als 2,5 dpt. aufweisen. Bei allen Studienteilnehmern wurde in den Untersuchungen bezüglich der Testung einer Aniseikonie der New Aniseikonia Test (Awaya-Test) durchgeführt.
Ergebnisse:
Es wurden insgesamt 39 Patienten (21 w., 18 m.), mit einem Durchschnittsalter von 72 Jahren eingeschlossen. Der Visus stieg in der Ferne um 0,05 ± 0,18 und in der Nähe um 0,07 ± 0,18 an.
Im Bagolini-Test zeigten in der Ferne sowohl prä- als auch postoperativ 87,2% der Pat. ein positives Testergebnis und 12,8% eine Exklusion. In der Nah-Testung des Bagolini zeigten präoperativ 94,9% ein positives Ergebnis und 5,1% eine Exklusion; postoperativ erreichten 97,4% ein Simultansehen und 2,6% zeigten eine Exklusion. Im Titmus-Test zeigten präoperativ 97,4% ein positives Ergebnis in der Betrachtung der Fliege, postoperativ noch 89,7% ein positives Ergebnis und 10,3% ein negativen Titmus-Test.
Die horizontale Aniseikonie nahm von präoperativ 3,72% ± 4,04 auf postoperativ 2,54% ± 2,72 ab. Die vertikale Aniseikonie ergab präoperativ einen Mittelwert von 5,05% ± 4,72 und postoperativ von 3,13% ± 3,29. In Bezug auf die Veränderungen der Aniseikonie prä- gegen postoperativ ergab sich somit ein Signifikanzniveau für die horizontale Messung von p=0,03 und für die vertikale Messung von p=0,01.
Schlussfolgerung:
Die Teilnehmer der Untersuchung wiesen 3 Monate nach erfolgter operativer Versorgung der epiretinalen Gliose eine erwartete Visusverbesserung auf. Das Simultansehen und die Stereopsis besserte sich ebenfalls leicht. Auffällig war der Rückgang der horizontalen und vertikalen Aniseikonie. Bei monuklarer Chirurgie sollte auch binokularen Aspekten mehr Aufmerksamkeit gewidmet werden.Introduction:
Patients undergoing peeling surgery for epiretinal membrane occasionally complain of binocular visual disturbances postoperatively. The aim of this study was to record subjective complaints and the correlation to pre- and postoperative objectively measurable parameters regarding binocular vision due to aniseikonia.
Methods:
In this prospective cohort study, consecutive patients with unilateral epiretinal membrane were included. Preoperative and 3 months postoperative standardized ophthalmologic and strabologic examinations were performed. To be included, all patients had to achieve a visual acuity of at least 0.2 in the affected eye and 0.5 in the fellow eye. In addition, none of the patients were allowed to have unilateral pseudophakia or anisometropia of more than 2.5 dpt. All study participants underwent the New Aniseikonia Test (Awaya test) to test for aniseikonia.
Results:
A total of 39 patients (21 female, 18 male) with an average age of 72 years were included. Visual acuity increased by 0.05 ± 0.18 in distance vision and 0.07 ± 0.18 in near vision.
In the Bagolini test, 87.2% of patients showed a positive test result in distance vision both pre- and postoperatively and 12.8% showed an exclusion. In the near vision Bagolini test, 94.9% constituted a positive result preoperatively and 5.1% showed an exclusion; postoperatively, 97.4% achieved simultaneous vision and 2.6% showed an exclusion. In the Titmus test, 97.4% constituted a positive result preoperatively when looking at the fly, 89.7% a positive result postoperatively and 10.3% a negative Titmus test.
Horizontal aniseikonia decreased from 3.72% ± 4.04 preoperatively to 2.54% ± 2.72 postoperatively. Vertical aniseikonia showed a mean value of 5.05% ± 4.72 preoperatively and 3.13% ± 3.29 postoperatively. With regard to the changes in aniseikonia preoperatively versus postoperatively, the significance level for the horizontal measurement was p=0.03 and for the vertical measurement p=0.01.
Conclusion:
The participants in the study showed the expected improvement in visual acuity 3 months after surgical treatment of epiretinal memrane. Simultaneous vision and stereopsis also improved slightly. The decrease in horizontal and vertical aniseikonia was striking. In monocular surgery, more attention should also be paid to binocular aspects.2025-08-1
Studies on deverbal *-tó- formations in Ancient Greek and Indo-European
No full textThis dissertation offers a comprehensive re-evaluation of the deverbal/deradical formations built with the *-tó- suffix in Proto-Indo-European (PIE) and its ancient daughter languages, with a particular focus on Ancient Greek. The study aims to provide a functional and empirically grounded description of the suffix's original function by combining comparative philology with insights from functional-typological linguistics. It challenges traditional handbook descriptions, specifically the assumption of inherent "voice neutrality", positing that the primary function of the suffix was to form resultative participles oriented toward the patient or the subject of unaccusative verbs. Seemingly "active" or agent-oriented forms are explained through the concept of the Affected Agent, where the agent undergoes a relevant change of state, while the voice neutrality observed in Greek is interpreted as a secondary innovation rather than a preserved archaism. It also offers a scenario for the emergence of modal meanings: these were not inherited traits of the PIE suffix but developed later through pragmatic inferences and semantic reanalysis.2026-01-2
Charakterisierung der spezifischen, T-Zell- vermittelten Immunitätslage gegen das Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) bei Risikogruppen (IMMUNEBRIDGE_ED)
No full textZielsetzung
Das Ziel war eine Charakterisierung der spezifischen zellulären T-Zell-vermittelten Immunitätslage der Risikogruppen für eine potenziell schwerwiegende COVID-19 Erkrankung durchzuführen.
Methoden
Diese Dissertation nutzt bevölkerungsbezogene Daten aus einer Kohortenstudie von Erwachsenen über einen Zeitraum von 5 Monaten, die im Rahmen von IMMUNEBRIDGE_ED an der Universitätsmedizin Göttingen erfasst wurden. Die Datenerhebung erfolgte durch Befragung der Studienteilnehmenden, Sichtung der digitalen Krankenakten sowie ausschließlich für die Studie angefertigte Interferon-Gama-Release-Assay-Tests (IGRA-Tests). Die IGRA-Tests wurden für eine Bestimmung der T-Zell spezifische Antwort gegen Bereiche des Spike Proteins (S1 Domäne) des Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) durchgeführt. Die aus der Anamnese und den Akten erhobenen Gruppenmerkmale der Teilnehmenden wurden mit den Ergebnissen der IGRA-Tests in statistische Zusammenhänge gesetzt, um mögliche Einflussfaktoren zu identifizieren. Neben deskriptiven Analysen wurden je nach Datenqualität bzw. Skalierung der zu untersuchenden Daten der Chi²-Test, Korrelationen nach Spearman, der Kruskall-Wallis-Test und der Mann-Whitney-U-Test durchgeführt. Um die Beziehungen zwischen Merkmalen und abhängigen Variablen darzustellen, wurden darüber hinaus binomial-logistische und multilineare Regressionen durchgeführt.
Ergebnisse
Von den 257 in die Analyse eingeschlossenen Teilnehmenden zeigten die IGRA-Tests einen großen Anteil mit n = 80 (31,13 %) an invaliden Resultaten, bei n = 177 (68,87 %) validen Testergebnissen. Für diesen großen Anteil an invaliden Testergebnissen wurde die Zusammensetzung der Studienpopulation mit schweren Vorerkrankungen angenommen. Bei den validen IGRA-Testergebnissen wiesen acht Patienten ein negatives (3,11 %), sieben Patienten ein borderline (2,72 %) und 162 (63,04 %) ein positives IGRA-Test Ergebnis auf.
Als einflussnehmende Merkmale auf die IGRA-Testergebnisse konnten in der Studienpopulation vor allem eine bestehende Immunsuppression bezüglich der zu erwartenden Test-Validität (p = 0,001) sowie der Interferon-Gamma Sekretion (p = 0,048), die zeitlichen Abstände zu einer zuletzt durchlebten COVID-19 Erkrankung in Betracht auf die Test-Validität (p = 0,02) sowie der Interferon-Gamma Sekretion (p = 0,021) und die angewandten Impfstoffregime (p = 0,036) identifiziert werden. In der Studienkohorte zeigte sich zudem ein unerwartetes Ergebnis, dass die Gruppe der adipösen StudienpatientInnen (Body-Mass-Index ≥ 30 kg/m²) eine höhere Interferon-Gamma Sekretion aufwiesen (p = 0,049).
Zudem zeigte sich bei den invaliden IGRA-Test-Ergebnissen eine geringere Stimulierbarkeit der T-Zellen mit einem Mitogen (p < 0,001) und dem spezifischen SARS-CoV-2 S1-Domänen Protein (p < 0,001) im Vergleich mit den validen Ergebnissen.
Schlussfolgerung
Zusammenfassend ließ sich bei circa zwei Dritteln der StudienteilnehmerInnen aus den Risikogruppen eine gute T-Zell-Reaktion erfassen, was auf eine ausgeprägte zelluläre Immunkompetenz gegenüber SARS-CoV-2 bei diesem Anteil hinwies. In dieser Studie beeinflusste vor allem das Vorliegen einer Immunsuppression die Testqualität zu Ungunsten der validen IGRA-Test Ergebnisse und die Höhe der gemessenen Interferon-Gamma-Werte.Purpose
The aim of the study was to characterise the specific T-cell mediated immune response in at-risk groups of patients for a potential severe course of COVID-19.
Methods
This dissertation uses population based-data from a cohort study of adults over a five month period collected as a part of IMMUNEBRIDGE_ED at the Universitätsmedizin Göttingen. Data was collected by interviewing the study group, reviewing the digital medical records and interferon-gamma release assay tests (IGRA tests). The IGRA tests were performed to determine the T-cell specific response against areas of the spike protein of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). The collected group characteristics of the participants were statistically correlated with the results of the IGRA tests in order to identify possible influencing factors. In addition to descriptive analyses, the Chi² test, correlations according to Spearman, the Kruskall-Wallis test and the Mann-Whitney U test were carried out depending on the data quality or scaling of the data to be examined. In addition, binomial-logistic and multilinear regressions were carried out to illustrate the relationships between characteristics and dependent variables.
Results
Of the 257 participants included in the analysis, the IGRA tests showed an unusually large proportion of invalid results n = 80 (31,13 %) and n = 177 valid test results (68,87 %). The composition of the study population with severe pre-existing conditions was assumed to account for this large proportion of invalid test results. Among the valid IGRA test results, 8 (3,11 %) patients had a negative, 7 (2,72 %) patients a borderline and 162 (63,04 %) a positive IGRA test result.
The main characteristics identified as influencing the IGRA test results in the study population were an existing immunosuppressive therapy with regard to the expected test validity (p = 0,001) and interferon-gamma secretion (p = 0,048), the time intervals to a recent COVID-19 disease with regard to test validity (p = 0,02) and interferon-gamma secretion (p = 0,021) and the vaccine regimen used (p = 0,036). The study cohort also showed an unexpected result that the group of obese (body mass index ≥ 30 kg/m²) study patients had a higher interferon-gamma secretion (p = 0,049) compared to non-obese patients.
In addition, the invalid IGRA test results showed a lower responsiveness to stimulate the T-cell with a mitogen (p < 0,001) and the specific SARS-CoV-2 S1 domain protein (p < 0,001) compared to the valid results.
Conclusion
In summary, a good T-cell reaction was recorded in approximately two thirds of the study participants from the at-risk groups of patients, indicating a pronounced cellular immunocompetence against SARS-CoV-2 in this proportion. In this study, the presence of an existing immunosuppressive therapy in particular influenced the test quality to the detriment of the valid IGRA test results and the level of the measured interferon-gamma values.2025-08-2
Firms’ Real and Reporting Responses to Tax Policy: Evidence on Investment Incentives, Anti-Avoidance Measures, and Dispute Resolution
No full textThis dissertation investigates how corporate behavior is shaped by tax policy, distinguishing between real responses and reporting responses. Drawing on three empirical studies, it explores firms’ reactions to investment incentives, anti-avoidance rules, and dispute resolution mechanisms in cross-border taxation. The results provide insights into the effectiveness and (un)intended consequences of different tax instruments, contributing to the literature on the intersection of taxation and firm behavior.
The first study evaluates the fiscal effects of corporate tax rate cuts, accelerated depreciation, and investment tax credits during an economic downturn in Germany. Using a dynamic microsimulation model based on firm-level data, it quantifies the relief each measure provides and its impact on investment. The findings suggest that while tax rate cuts offer broad and immediate relief, they provide only limited investment incentives. In contrast, investment tax credits, particularly when structured as direct subsidies, offer more targeted incentives, including for loss-making firms. Accelerated depreciation schemes can be effective, but their benefits depend on firms’ ability to utilize loss offsets. Overall, the study highlights the importance of aligning tax instruments with policy objectives, such as short-term liquidity support versus long-term investment stimulation.
The second study examines how multinational enterprises (MNEs) respond to the introduction of the Nexus Approach in Intellectual Property (IP) Box regimes. Designed as an anti-avoidance measure under the OECD’s BEPS initiative, the Nexus Approach links preferential IP tax treatment to local R&D activity. Using affiliate- and group-level panel data in a stacked difference-in-differences design, the study shows that MNEs reduce patent shifting to IP Box jurisdictions after the Nexus Approach is introduced. Instead, they increase investment and innovation in IP Box countries. However, the results indicate that this shift largely reflects a reallocation of activity within the MNE rather than a net increase in innovation or investment. These findings underline how anti-avoidance rules can succeed in curbing the separation of value creation and profit taxation; however, they also disadvantage non-IP Box countries, as firms respond by shifting real innovation activities to IP Box jurisdictions to retain tax benefits.
The third study investigates the effect of arbitration clauses in double tax treaties on profit shifting and foreign direct investment (FDI). Using bilateral data and a stacked difference-in-differences design, the study finds that arbitration clauses reduce the risk of double taxation and thereby incentivize profit shifting, especially where tax rate differentials are large. However, they do not increase real FDI; in fact, real investment declines slightly, and shifted profits tend to be distributed rather than reinvested. These results reveal a potential trade-off. While arbitration clauses enhance legal certainty, they may also weaken the link between taxation and economic substance.2025-08-0
Effects of cover crop functional traits and termination timing on nitrous oxide emissions and soil nitrogen dynamics in a humid temperate crop rotation
No full textAgricultural soils are the largest anthropogenic source of nitrous oxide (N2O), a potent greenhouse gas and ozone-depleting substance. Emissions of N2O primarily result from microbial processes such as nitrification and denitrification, which are strongly influenced by soil nitrogen (N) availability, moisture, and carbon (C) inputs. In the context of climate change mitigation and sustainable nutrient management, reducing N2O emissions from croplands remains a major challenge.
Cover crops (CCs) are widely promoted as a key component of sustainable agriculture due to their ability to improve soil structure, reduce erosion, enhance soil organic matter, and retain nutrients. They are also expected to mitigate N2O emissions by scavenging residual N and supporting soil health. However, research findings on their effectiveness remain inconsistent. Reported outcomes vary depending on species traits, biomass production, site conditions, and management practices, particularly termination timing and residue management.
This thesis investigates how CC functional traits and termination timing influence N2O emissions, soil mineral nitrogen (SMN) dynamics, and soil organic carbon (SOC) sequestration in humid temperate agroecosystems. Through multi-site and multi-year field experiments, the work evaluates short and medium-term biogeochemical responses to different CC species across soils of varying texture. The studies combine field-based N2O flux measurements, SMN analysis, microbial profiling, and long-term SOC modeling.
The first study assessed three winter CC species: winter rye as a frost-tolerant grass, saia oat as a frost-sensitive grass, and spring vetch as a frost-sensitive legume, in comparison to a bare fallow control across four site-years. Non-legume CC species reduced SMN levels during autumn and winter and thereby lowered nitrate leaching risk. However, frost-sensitive species triggered substantial N2O emissions during freeze-thaw periods, and high-biomass CCs such as rye resulted in the highest N2O emissions following incorporation into moist soils. Despite this, rye also showed the greatest potential for C sequestration and mitigation of indirect N2O emissions by reducing nitrate leaching risk. These results highlight the trade-offs between N retention, direct and indirect N2O emissions, and long-term SOC storage, emphasizing the importance of balanced and species-informed CC strategies.
The second study focused on the effect of termination timing using oil radish as a cruciferous winter CC. Early autumn termination was compared with spring termination and a fallow control across five site-years. Although CCs reduced SMN prior to winter, early termination significantly increased winter N2O emissions in fine-textured loamy soils due to anaerobic decomposition of residues. This effect was not observed in sandy soils, where nitrate leaching was likely the dominant N loss pathway. Early termination also increased SMN availability in spring in loamy soils, which may benefit early crop growth and reduce fertilizer requirements. In contrast, late termination reduced winter N2O emissions but may shift the risk to the spring period, especially under fertilized conditions or where pre-emptive N uptake by CCs reduces SMN availability for the subsequent crop. Microbial analyses revealed increased abundance of genes involved in nitrification and denitrification under early termination during winter, although gene abundance did not correlate strongly with measured N2O fluxes.
Overall, the results show that the environmental performance of CCs is highly context specific, shaped by interactions among soil properties, climate, CC functional traits, and management practices. Methodologically, the thesis demonstrates the value of integrating field data, molecular analyses, and modeling to assess the environmental trade-offs of CC-based N management. Limitations include the use of non-continuous gas sampling, limited temporal resolution of microbial measurements, the absence of direct C measurements, and incomplete annual N2O budgets across all site-years in the termination study.
This work shows that CCs can contribute to climate-smart N management and C sequestration when adapted to local conditions. It calls for systems-based approaches that integrate agronomy, soil microbiology, and environmental modeling. Site-specific guidance for CC selection and termination will be essential to optimize N retention, minimize GHG emissions, and realize the multifunctional benefits of CCs in temperate cropping systems.2025-08-1
Advanced Correlation Spectroscopy and Nanofluidics in Single-Molecule Biophysics
No full textFluorescence Correlation Spectroscopy (FCS) is a powerful and widelyused technique in biophysics for studying biomolecules and their interactionsat the single-molecule level. However, traditional FCS hasnotable limitations. First, it is highly sensitive to imperfections in theoptical system, which are often unavoidable in practical applications.In this work, we extend the use and uncover new applications of advancedFCS techniques—including antibunching FCS, PhotoinducedElectron Transfer (PET) FCS, Dual-Color FCS (2fFCS), and RotationalDiffusion FCS—to investigate a range of phenomena relevant to the lifesciences. These include the photophysics of fluorescent molecules, theintramolecular dynamics of Intrinsically Disordered Proteins (IDPs),and the docking-undocking dynamics of ribosomes with translocons.Secondly, while FCS techniques provide valuable insights, they arefundamentally ensemble-averaging approaches. True single-moleculetechniques, such as the Anti-Brownian Electrokinetic (ABEL) trap andsingle-molecule burst analysis, have emerged over the past decadesbut remain limited in widespread use due to the complexity of therequired instrumentation. Recent advancements in nanofluidics, fueledby knowledge transfer from the field of microfabrication to the lifesciences, offer promising solutions. To harness this potential, we havedeveloped a nanofluidic-based fabrication process from the groundup, aiming to simplify instrumentation and make single-molecule biophysicsmore accessible. Our ultimate objectives include the trappingof single biomolecules within nanochannels and measuring electriccharges of bimolecules under physiological conditions.2025-11-0
Impact of species diversity and composition on yield, nutritive value and drought stress in lucerne-grass swards
No full textIn Deutschland umfasst Dauergrünland und grasbasierter Feldfutterbau, einschließlich Leguminosengras, ein Drittel der gesamten landwirtschaftlichen Nutzfläche. Der grasbasierte Feldfutterbau trägt nicht nur zur Futterversorgung von Wiederkäuern bei, sondern bietet auch agronomische Vorteile für die Fruchtfolge. Zu den Vorteilen gehören beispielsweise eine höhere Artenvielfalt und höhere Bodenkohlenstoffgehalte, sowie die Reduzierung von Unkraut, was wiederum den Folgekulturen zugutekommt. Die zusätzlichen Leistungen sind besonders wichtig in restriktiven Systemen wie dem ökologischen Landbau. Insbesondere dort bieten Leguminosen durch die symbiotische Fixierung von Stickstoff (N) Vorteile, da die Fruchtfolge mit N angereichert wird und der Bedarf an synthetischen N-Düngern sinkt. Für die Milchproduktion besteht ein zusätzlicher Vorteil darin, dass Leguminosen in der Ration die Futteraufnahme erhöhen und zudem Milchvieh kostengünstiger mit Rohprotein (CP) versorgen, als dies bei der üblichen Kraftfutterfütterung der Fall ist. Der Klimawandel verschärft die Herausforderungen in der Grundfutterproduktion, indem er die Häufigkeit von Trockenheit und Niederschlagsschwankungen erhöht, wodurch Ertrag und Futterwert beeinflusst werden. Um die Widerstandsfähigkeit zu erhöhen, verlagert sich der Futterbau auf trockenheitstolerantere Arten und vielfältige Artenmischungen. In dieser Hinsicht bieten Leguminosengrasmischungen im Vergleich zu reinen Grasbeständen in der Regel höhere Erträge, eine bessere Leistung unter trockenen Bedingungen und längere Erntefenster, ohne dass es schnell zu starken Veränderungen des Futterwerts kommt. Diese Vorteile ergeben sich aus den interspezifischen Interaktionen und der Nischenkomplementarität, die häufig als Nettomischungseffekt (NE) beschrieben werden. Um ressourceneffiziente Artenkombinationen in Mischungen zu ermitteln, ist die Analyse der Wassernutzungseffizienz (WUE) ein wertvolles Instrument, da sie die Leistung des gesamten Bestandes widerspiegelt. Im Gegensatz dazu können artspezifische Reaktionen anhand der Kohlenstoffisotopenverhältnisse (δ13C) bestimmt werden, die mit der Schließung der Stomata und Trockenstress in Verbindung gebracht werden.
In dieser Arbeit werden die agronomischen Auswirkungen verschiedener Kombinationen der potenziell trockenheitstoleranteren Gräser Knaulgras (Dactylis glomerata L.) und Rohrschwingel (Festuca arundinacea Schreb.) mit Luzerne (Medicago sativa L.), deren Reinsaaten und einer Standardmischung aus Luzerne, Lieschgras (Phleum pratense L.) und Wiesenschwingel (Festuca pratensis Huds.) an vier Standorten über zwei Hauptanbaujahre untersucht. Das Ziel dieser Studie besteht darin, die Auswirkungen des Mischanbaus auf den Ertrag, den Futterwert und den Trockenstress zu bewerten. Darüber hinaus sollen der Mischungseffekt und die Rolle der verschiedenen Graspartner bei der Beeinflussung dieser Parameter ermittelt werden.
In Kapitel 1 wurden die Ertragsleistung und der NE von Luzernegrasmischungen untersucht. Die Trockenmasseerträge (DM) unterschieden sich nicht signifikant zwischen den Mischungen und Luzerne Reinsaat, unabhängig von den Umweltbedingungen. Auch die Mischungszusammensetzung hatte nur einen geringen Einfluss auf den Ertrag. Dagegen wirkten sich die Niederschlagsmengen deutlich auf die DM-Erträge aus. Das Auftreten eines positiven NE in den Mischungen deutet auf vorteilhafte interspezifische Interaktionen hin. Die Integration von trockenheitstoleranten Gräsern in luzernebasierte Mischungen scheint vielversprechend zu sein, um den Feldfutterbau zu diversifizieren, ohne die agronomische Leistung zu mindern.
In Kapitel 2 wurde der Futterwert der verschiedenen Mischungen und Reinsaaten untersucht, um ihr Potenzial als Futterquelle im Kontext des Klimawandels zu bewerten. Dabei zeigten sich signifikante Interaktionen zwischen Mischung, Standort und Jahr. Insgesamt wiesen die Mischungen bei den analysierten Parametern einen ausgewogeneren Futterwert auf als die Reinsaaten. Der beobachtete NE in den Mischungen führte zu höheren Werten bei den Neutral- und Säure-Detergenzien-Fasern, sowie beim Verhältnis CP zu wasserlöslichen Kohlenhydraten, als erwartet. Umgekehrt lagen die Werte für wasserlösliche Kohlenhydrate und umsetzbare Energie bei den Mischungen unter den erwarteten Werten. Die beobachteten Effekte traten meist unabhängig von der Mischungszusammensetzung oder der Artenanzahl auf. Informationen zum NE können hilfreich sein, um den Futterwert von Luzernegrasmischungen zu optimieren.
In Kapitel 3 wurden die WUE und der Trockenstress in der Dreiartenmischung im Vergleich zu Reinsaaten analysiert. Wie erwartet, zeigten die Grasreinsaaten an allen Standorten eine signifikant niedrigere WUE als die Luzernegrasmischung und die Luzerne Reinsaat. Die δ13C-Werte aus den vergleichsweisen trockenen Bedingungen in 2020 lassen erkennen, dass die Grasreinsaaten einen stärkeren Trockenstress aufwiesen als die Luzernegrasmischung oder die Luzerne Reinsaat. Hinsichtlich der artspezifischen Trockenstressreaktion zeigte die Luzerne keinen Unterschied zwischen den Anbausystemen Reinsaat und Mischung. Im Gegensatz dazu profitierten die Gräser vom Mischanbau und es wurde bei den Gräsern aus der Mischung ein geringeren Trockenstress (negativere δ13C-Werte) gemessen als aus den Reinsaaten. Diese Ergebnisse unterstreichen den Vorteil des Mischanbaus von Arten zur Reduzierung von Trockenstress bei Gräsern.
Innerhalb eines 18-jährigen Vergleichszeitraums zählten die Versuchsjahre 2020 und 2021 an zwei Standorten zu den trockensten bzw. feuchtesten, was den DM-Ertrag erheblich beeinflusste. Dies unterstreicht die Relevanz der Ergebnisse dieser Studie im Zusammenhang mit klimatischen Extremen. Trotz der unterschiedlichen Umweltbedingungen erzielten alle Mischungen mit trockenheitstoleranten Gräsern, die Standardmischung sowie Luzerne Reinsaat vergleichbare DM-Erträge, was ihre Eignung unter wechselnden Klimabedingungen bestätigt. Die zeitliche Stabilität des Futterwerts (gemessen anhand des Variationskoeffizienten) war bei den Luzernegrasmischungen und der Luzerne Reinsaat ähnlich und ist vermutlich auf den dominierenden Einfluss der Luzerne in Bezug auf den Artenanteil zurückzuführen. Daraus ergibt sich, dass der Mischanbau in dieser Hinsicht keinen zusätzlichen Vorteil brachte. Dennoch führte der Mischanbau von Luzerne mit Knaulgras und Rohrschwingel zu einem NE, sowohl in Bezug auf den Ertrag als auch auf den Futterwert. Diese Effekte lassen sich auf positive interspezifische Interaktionen und eine verbesserte N-Verfügbarkeit zurückführen. Der NE bestärkt insbesondere in N-limitierten Systemen wie dem ökologischen Landbau den Nutzen des Anbaus von Mischungen. Darüber hinaus eignen sich Mischungen mit einem ausgewogenen Nährstoffprofil gut für die Umtriebsweide oder als ein Hauptfuttermittel. Der Luzerneanteil in den Mischungen entsprach oft den Leguminosenanteilen aus anderen Studien, die dort mit optimaler Verdaulichkeit und Milchleistung in Verbindung gebracht wurden.
Insgesamt kann Luzerne sowohl als Reinsaat als auch in Mischungen angebaut werden. Der Mischanbau bietet zusätzliche Vorteile, wie geringeren Trockenstress bei Gräsern und einen ausgewogeneren Futterwert. Besonders in N-limitierten Systemen, wie dem ökologischen Landbau, sind Luzernegrasmischungen aufgrund ihres ökologischen und ernährungsphysiologischen Nutzens besonders wertvoll. Es bedarf jedoch weiterer Forschung, um die Auswirkungen der N-Verfügbarkeit auf die Artenzusammensetzung, insbesondere des Knaulgrases, sowie die Beziehung zwischen Trockenstress (δ13C) und N-Dynamik in Luzernegrasmischungen zu untersuchen.In Germany, permanent and temporary grassland, including legume-grass swards, account for one third of the total agricultural area. Temporary grassland on arable land not only contributes to the feed supply of ruminants, but also provides agronomic benefits in crop rotation. These benefits include enhanced biodiversity, increased soil organic matter and reduced amount of weed, thus improving the conditions for subsequent crops. These additional benefits are particularly important in restrictive systems such as organic farming. Here, legumes offer further advantage of symbiotic nitrogen (N) fixation, which enriches the crop rotation with N and reduces the need for synthetic N fertilisers. Regarding dairy production, an additional benefit is that legumes can increase feed intake and provide a cost-effective source of crude protein (CP) compared to conventional concentrate feeding. However, climate change is intensifying the challenges in herbage production by increasing drought frequency and precipitation variability, which reduces yield and nutritive value. To increase resilience, herbage systems are shifting towards more drought-tolerant species and diverse species mixtures. In this regard, legume-grass mixtures typically offer higher yields, improved performance under drought conditions, and a longer harvest period without rapid loss of nutritive value compared to grass pure stands. These benefits result from interspecific interactions and niche complementarity, commonly referred to as the net mixture effect (NE). To identify resource-efficient combinations of mixed swards, the analysis of the water use efficiency (WUE) is a valuable tool, which reflects the performance of the entire sward. In contrast, species-specific responses can be determined by using carbon isotope ratios (δ13C), which are associated with stomatal closure and drought stress.
This study investigates the agronomic effects of different combinations of the potentially drought-tolerant grasses cocksfoot (Dactylis glomerata L.) and tall fescue (Festuca arundinacea Schreb.) with lucerne (Medicago sativa L.), their pure stands and a standard mixture of lucerne, timothy (Phleum pratense L.) and meadow fescue (Festuca pratensis Huds.) at four sites over two main production years. The objective of this study is to evaluate the impact of mixed cultivation on yield, nutritive value and drought stress. Additionally, it intends to determine the mixture effect and the role of different grass partners in influencing these parameters.
The yield performance and NE of lucerne-grass mixtures were examined in Chapter 1. Regardless of environmental conditions, dry matter (DM) yields did not differ significantly between the mixed swards and lucerne pure stand. The composition of the mixtures also had only a minor influence on yield. In contrast, precipitation significantly affected DM yields. The occurrence of a positive NE in the mixed swards indicates beneficial interspecific interactions. Integrating drought-tolerant grasses into lucerne-based swards appears to be a promising strategy to diversify temporary grasslands production without compromising the agronomic performance.
Chapter 2 examined the nutritive value of the different species mixtures and pure stands to assess their potential as a feed source in the context of climate change. Significant interactions were observed between sward type, site and year. Overall, the mixed swards exhibited a more balanced nutritive value than the pure stands across the analysed parameters. The observed NE in the mixed swards resulted in higher values for neutral and acid detergent fibres, as well as for the ratio of CP to water-soluble carbohydrates, than expected. Conversely, the values for water-soluble carbohydrates and metabolisable energy in mixed swards were lower than expected. The observed effects were mainly independent of the sward type or species number. Information on the NE may prove helpful to optimise the nutritive value of lucerne-grass mixtures.
Chapter 3 analysed the WUE and drought stress of the three-species sward compared to the pure stands. As expected, the grass pure stands displayed significantly lower WUE than the three-species sward and lucerne pure stand at all sites. As indicated by δ13C values under the comparably drier conditions of 2020, grass pure stands showed stronger drought stress compared to the lucerne-grass sward or lucerne pure stand. Regarding the species-specific drought stress responses, lucerne showed no difference between the pure stand and the mixture. In contrast, the grasses benefited from mixed cultivation, showing lower drought stress (more negative δ13C values) in the mixed sward than in the pure stands. These results highlight the benefits of mixed cultivation to mitigate drought stress in grasses.
Within an 18-year reference period the experimental years 2020 and 2021 ranked among the driest and wettest at two sites, significantly influencing DM yield. This further underlines the relevance of results of this study in the context of climatic extremes. Despite the varying environmental conditions, all swards containing drought-tolerant grasses, the standard sward and the lucerne pure stand achieved comparable DM yields, confirming their suitability under changing climatic conditions. The temporal stability of the nutritive value (measured by the coefficient of variation) was similar between the lucerne-grass swards and lucerne pure stand, likely due to the dominant influence of lucerne in terms of species proportion. Consequently, in this regard mixed cultivation did not offer any additional benefits. However, combining lucerne with tall fescue and cocksfoot resulted in NE in terms of both yield and nutritive value. These effects can be attributed to positive interspecific interactions and improved N availability. The NE supports the benefits of growing mixtures, particularly in N-restricted systems such as organic farming. Furthermore, mixed swards with a balanced nutritive profile are well suited for rotational grazing or as a main forage source. The proportion of lucerne in the mixed swards often corresponded to the legume proportions in other studies, which were associated with optimal digestibility and milk yield.
Overall, lucerne can be cultivated either as a pure stand or in mixtures. Mixed cultivation offers additional benefits, such as reduced drought stress for grasses and a more balanced nutritive value. In N-restricted systems like organic farming, lucerne-grass swards are particularly valuable due to their ecological and nutritional benefits. However, further research is needed to investigate the effects of N availability on species composition, particularly with regard to cocksfoot, as well as the relationship between drought stress (δ13C) and N dynamics in lucerne-based mixtures.2025-09-1
Mikroskopische Untersuchungen zur Struktur des Primitivknotens bei der Ente und dem Huhn
No full textThe Hensen’s node plays a central role during gastrulation, as it exhibits asymmetric development shortly after its formation and thereby establishes orientation along the transverse axis as part of the body plan. Acting as an organizer, it serves as a passageway for cells undergoing epithelial-to-mesenchymal transition (EMT) and expresses genes that regulate this process. From stage HH 3+ onward, microcavities can be detected in the primitive node of the chick, appearing as light-blue, matrix-filled spaces usually located near disrupted regions of the basal membrane. These cavities vary in size and shape, are heterogeneously filled with globular, filamentous, and amorphous components, and contain fibronectin.
The aim of this study was to determine whether the occurrence of microcavities represents a general phenomenon in avian embryos and to explore their potential function. For this purpose, duck and chicken embryos were explanted, fixed, and prepared for semithin sectioning. Microscopic imaging and systematic documentation were then performed. In all three duck embryos examined, microcavities of various shapes and dimensions were observed, with cavity number increasing with developmental stage and with a predominant localization within or beneath the right node shoulder. While most cavities were embedded in the cell-dense region of the node, a few were found in the looser mesoderm near the hypoblast. In ducks, the cavities appeared small, spindle-shaped, and numerous. Duck embryos at stages HH 5+ and HH 6 displayed a remarkably deep primitive groove, more pronounced than previously described in the literature, and distinct from the subtler groove of the chick. Additionally, the enlarged right node shoulder at stage HH 6 in ducks was particularly striking, protruding dorsally to form a marked epiblast bend. Adjacent to this, a conspicuous epiblast protrusion was observed, seemingly releasing numerous cells.
In chicken embryos, no cavities were detected at stage HH 3, but they appeared from stages HH 4–4+, varying widely in size and shape and presenting larger and more vesicular compared to those in ducks. Possible homologous structures may include the notochordal and neurenteric canals, which, unlike the cavities, are lined by differentiated epithelial cells. The Brachet’s cleft of gastrulating Xenopus, characterized by a loose fibronectin-rich matrix, may also represent a homologous structure.
Potential functions of these microcavities include the maintenance of asymmetry, stimulation of cell migration, contribution to notochord formation, or regulation of morphogen activity via fibronectin content. Alternatively, they may simply represent remnants of basal membrane disruption caused by EMT.2025-11-0
Investigation of potential determinants of food addiction in patients with morbid obesity
No full textIntroduction: Food addiction (FA) is a promising construct
regarding the multifactorial aetiology of obesity and the
search for therapeutic approaches. However, there is an
ongoing debate regarding the overlap/differentiation with
eating disorders and the classification as a substance- or
behaviour-related addiction. Energy-dense foods, especially
those combining carbohydrates and fat, are associated with
addictive eating and suspected of playing a role in the
genesis of FA. This study aims to further understand the
clinical significance of FA and to identify possible therapeutic
targets. A special focus is set on potentially addictive
foods (combination of carbohydrates and fat). Methods:
Based on the Yale Food Addiction Scale 2.0, a cohort of
112 German adults with morbid obesity was divided into
two sub-samples (patients with and without FA), which were
examined for differences in the variables listed below.
Results: The prevalence of FA was 25%. Patients meeting
criteria for FA showed higher degrees of hunger, emotional,
binge, and night eating than patients without FA. In addition,
hunger and disinhibition were found to be significant
predictors of FA. FA was not associated with sex, age, body mass index (BMI), cognitive restraint, rigid and flexible
control, prevalence of substance use, age of onset of obesity,
stress level, level of social support, reduction of BMI during a
weight loss programme, or programme withdrawal rate.
There was no significant difference in the consumption of
foods rich in both carbohydrates and fat, nor of fat or
carbohydrates alone. Conclusion: FA can be considered as a
sub-phenotype of obesity, occurring in approximately 25%
of obesity cases. Dysfunctional emotional coping mechanisms
associated with low distress tolerance showed to be
significantly related to FA and should be targeted therapeutically.
Behavioural interventions should include a biopsycho-
social model. Binge eating episodes were found to
be characteristic for FA and the already stated overlap
between FA and binge eating behaviour can be confirmed.
The results do not support a decisive difference due to a
substance-related component of FA. Despite this, the existence
of FA as a distinct entity cannot be excluded, as not all
patients with FA exhibit binges.2025-12-1