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Item type:Item, Methanemissionen von Milchkühen: Evaluierung von abgeleiteten Kenngrößen und deren phänotypischen und genetischen Beziehungen zu Produktionsmerkmalen und funktionalen Merkmalen bei Milchkühen(2026) Fehmer, LenaDer Klimawandel betrifft die gesamte Weltbevölkerung. Die wissenschaftlichen Forschungen hierzu sind umfassend und vielschichtig, mit dem übergeordneten Ziel, die globale Erwärmung zu begrenzen. Ein Ansatz, der insbesondere in Europa verfolgt wird, ist die Reduzierung des Ausstoßes von Klimagasen in der Landwirtschaft. Da die Landwirtschaft jedoch eine zentrale Rolle in der Nahrungsmittelproduktion einnimmt, kann sie nicht einfach „abgeschafft“ werden. Vielmehr muss sie so weiterentwickelt werden, dass eine nachhaltige Ernährung der Menschheit auch in Zukunft – und damit über viele Generationen hinweg – auf dieser Erde möglich bleibt. Ziel der vorliegenden Arbeit war es, im Bereich der Landwirtschaft den Ausstoß von Klimagasen in der Milchviehhaltung zu untersuchen und Möglichkeiten zur Reduktion dieser Emissionen aufzuzeigen. Im Fokus stand dabei insbesondere das Treibhausgas Methan (CH4), das in erheblichem Maße von Milchkühen produziert wird. Zu diesem Zweck wurden umfangreiche Messungen (n = 2.076) der Methanproduktion von Milchkühen in zehn Praxisbetrieben durchgeführt. Ergänzend wurden sowohl genetische als auch genomische Analysen vorgenommen. Die erhobenen Methanwerte wurden hinsichtlich bedeutender exogener Einflussfaktoren, die die Messungen potenziell verfälschen könnten, korrigiert und anschließend als Methanmerkmale mit phänotypischen Produktionsmerkmalen in Beziehung gesetzt. Ferner wurden Heritabilitäten für die entwickelten Methanmerkmale geschätzt sowie genomweite Assoziationsstudien (GWAS) durchgeführt, um Gene zu identifizieren, die mit der Methanproduktion in Zusammenhang stehen. Ziel war es, mögliche züchterische Einflussmöglichkeiten auf die Methanemissionen von Milchkühen zu bewerten. Die Ergebnisse dieser Arbeit zeigten unter anderem eine hohe negative phänotypische Korrelation zwischen der Methanintensität (CH4/Mkg) und der Milchmenge [kg] (r = −0,75). Zudem wurde ein Einfluss der Fütterung auf die Methanproduktion festgestellt: Je höher die Energiedichte der Ration, desto geringer fiel die Methanemission aus. Weiterhin konnte eine moderat positive Zuchtwertkorrelation zwischen Methanmerkmalen und dem Erstkalbealter ermittelt werden. Die geschätzten Heritabilitäten der hier entwickelten Methanmerkmale lagen mit h² = 0,024 auf einem sehr niedrigen Niveau und damit unterhalb der Werte anderer Studien. Methan stellt ein komplexes Merkmal dar, das von zahlreichen biologischen und umweltbedingten Faktoren beeinflusst wird. Dies deutet darauf hin, dass eine direkte züchterische Beeinflussung der Methanproduktion nur eingeschränkt möglich ist. Diese Annahme wird auch durch die Ergebnisse der genomweiten Assoziationsstudien gestützt: Es konnte kein einzelnes Gen identifiziert werden, das in direktem Zusammenhang mit der Methanproduktion steht – wie dies beispielsweise bei der Milchleistung und dem DGAT-Gen der Fall ist. Stattdessen wurden überwiegend Gene detektiert, die indirekten Einfluss auf die Methanproduktion nehmen, etwa über den Energiestoffwechsel oder die Fettsynthese. Zu diesen Genen gehören unter anderem das B3GNT3-Gen, welches im Allgemeinen Stoffwechselvorgänge beeinflusst, und das NIPSNAP3A-Gen, welches bei einer Ketoseerkrankung eine Rolle spielt, oder das ZC3H14-Gen, welches an der Protein- und Fettsäurenzusammensetzung der Milch beteiligt ist. Die Ergebnisse dieser Studie zeigten, dass Methan als Merkmal in der Rinderzucht grundsätzlich von Interesse sein kann, eine gezielte Zucht auf niedrigen Methanausstoß allein jedoch aufgrund der komplexen biologischen Zusammenhänge kaum realisierbar und auch nicht erstrebenswert erscheint. Ein in dieser Arbeit nicht vertiefter, jedoch relevanter Aspekt betrifft die genetische Beziehung zwischen dem Wirtstier Rind und seinem Pansenmikrobiom, das für den Großteil der Methanproduktion verantwortlich ist. Ein zukünftiges Ziel könnte darin bestehen, über das Mikrobiom des Pansens indirekten genetischen Einfluss auf die Methanproduktion zu nehmen und damit neue Ansätze für eine nachhaltige Zuchtstrategie zu entwickeln.Item type:Item, cGMP Signalling in Smooth Muscle Cells of the Vasculature and the Male Reproductive Tract(2025) Rager, Christine AngelikaNumerous therapeutics target the relaxation of smooth muscle. A signalling molecule that plays a decisive role in this process is cyclic guanosine monophosphate (cGMP). Most knowledge about the cGMP signalling system has been generated based on cell culture. Lately, conclusions regarding smooth muscle physiology based purely on in vitro data have been highly debated. Especially for vascular smooth muscle cells, which are characterized by high plasticity, drastic changes under cell culturing condition have been shown, by which the cGMP system, among others, seems to be strongly affected. Since the culture-induced modification of the cell genotype involves various reference genes, the comparison between in vivo and in vitro is often found to be difficult. The aim of this work was therefore to find a reference gene that allows the direct comparison of aortic smooth muscle cells in the intact vessels versus culture at the gene expression level, and ideally enable the characterization of sex-dependent differences. Subsequently, the reference gene U2 was then used to compare the expression of the natriuretic peptide receptors (GC-A, GC-B, NPRC) and the receptor for nitric oxide (sGC) in intact tissue versus cell culture and four receptors which are known to significantly regulate the intracellular cGMP level were investigated. The comparison showed a drastic change in the expression profile of the aortic cells in culture. With the exception of Gc-a, which maintained a stable expression level, the expression of all receptors increased dramatically in cell culture. It can be suggested that this difference probably leads to a disturbance of cellular cGMP homeostasis due to a shift in the ratio of the receptors to each other. Since antibodies, especially for the natriuretic peptide receptors, still do not allow satisfactory detection, the gene expression data were confirmed at the functional level using cGMP ELISA. No significant differences between the two sexes could be detected besides a higher fluctuation range of the data points in females. This could suggest a cycle-related regulation of the cGMP system. The second part of this thesis focused on smooth muscle cells in the male reproductive tract. Contrary to the vascular chapter of this work, only intact tissue was used for the investigations. In the testis, smooth muscle cells surround the germinal epithelium of the seminiferous tubules in which the sperm are produced. Here the smooth muscle cells play an important role in transporting the seminal fluid and the spermatozoa it contains through the tubular lumen towards the epididymis. To ensure this directed transport, the superficial muscle layer of the testicular tubules contracts. A hypothesis based on preliminary results of this work suggests that the intensity of contraction is precisely coordinated with the spermatogenesis in a timely manner. The aim of the second chapter of this thesis was therefore to establish a method to detect spontaneous contractions and their alteration by relaxing and contracting substances and to evaluate these with regard to different stages of spermatogenesis. Using a previously tested method for live recording, seminiferous tubules of the rat were recorded before and after spermiation. For the evaluation, an analysis tool was adapted, that had previously been used in parasitology and involves the imaging tool FIJI. Using this tool, tissue contractions could be differentiated in terms of their general intensity, amplitude and frequency. It was shown that the seminiferous tubules before and after spermiation differ drastically with regard to their spontaneous contraction behaviour. Further experiments also showed that these contractions could be attenuated to the same extent by treatment with nitric oxide and, interestingly, also by noradrenaline. The extent to which treatment with relaxing (nitric oxide) and contracting (noradrenaline) stimulants influences the different parameters of the contractions (intensity, amplitude, frequency) requires further investigation in order to develop the FIJI-based analysis method for pharmacological/diagnostic purposes in the future.Item type:Item, Multifactorial patterns of low performance development in german elite athletes(2025) Wiedenbrüg, Kati; Roffler, Andrea; Reichert, Lukas; Mutz, Michael; Zentgraf, Karen; Krüger, KarstenIntroduction: Low performance development (LPD) has been related to several training-related, biological or psychosocial factors. However, there is still hardly any comprehensive research on its multifactorial nature. Tis study explored whether factors previously associated with LPD manifest as cross-disciplinary pattern combinations across such athletes. Methods: Cluster analyses were computed based on performance-related (speed and strength of the lower body), biological (ratio TNFα:IL10; fT3, leptin, insulin) and psychosocial (perceived social support; mental well-being) data from 62 of 296 elite athletes whose performance development was below the samples’ average range. Group comparisons were calculated for demographic, anthropometric, nutritional and sleep-related variables, as well as for additional psychosocial (critical life events; perceived stress) and biological (single infammatory markers) variables. Results: Six patterns were identifed, which could be described via domain-specifc characteristics (lower body dynamics and social support), via an interdisciplinary combination of factors (social support, mental well-being and/or lower body dynamics) or by no characteristic pattern at group level. Conclusion: In general, this study extends research on LPD and illustrates the limited validity of generalisations while emphasising the additional value of individualisation for athletes who drop behind their peers. Moreover, the identifed Patterns point to the limitations of taking a cross-disciplinary approach at group levelItem type:Item, Postoperative ileus after emergency surgery for acute bowel obstruction : a case-control study of predictors and impact on recovery(2025) Amati, Anca-Laura; Kümmel, Niklas; Negruta, Nicoleta; Reichert, Martin; Schwandner, Thilo; Noll, Julia; Braun, Jaqueline; Grau, Veronika; Petzoldt, Sebastian; Hecker, AndreasPurpose: Acute bowel obstruction (ABO) is a common indication for emergency abdominal surgery, often performed on a severely dilated intestine with compromised barrier function. The recovery of bowel motility in this acute setting differs from elective surgery and remains insufficiently investigated. Yet, its understanding is crucial for improving perioperative care in surgical emergencies. This study aimed to identify risk factors for postoperative ileus (POI) after emergency surgery for ABO and to explore its impact on postoperative outcomes. Methods: We retrospectively analyzed 466 patients who underwent emergency surgery for ABO between 2014 and 2020, of whom 156 developed POI. POI was defined as the absence of postoperative bowel movement requiring intravenous prokinetic therapy following an insufficient response to initial conservative measures, including oral laxatives. Perioperative predictors for POI were identified by univariate and multivariate logistic regression. The association between POI and adverse postoperative outcomes was examined using correlation analysis. Results: Multivariate analysis revealed male sex (p = 0.0009), chronic steroid therapy (p = 0.0064), high postoperative SOFA score (p = 0.0037), and elevated CRP levels on postoperative day two (p = 0.048) as independent predictors for POI. Patients with POI had significantly higher rates of postoperative respiratory (p < 0.0001) and surgical complications (p = 0.0014). Conclusion: Our findings suggest sex-dependent differences and an involvement of inflammatory processes in bowel function recovery following emergency surgery for ABO. POI in this setting is associated with increased risk of postoperative respiratory complications and surgical morbidity. These results highlight the need for targeted preventive strategies and form a solid foundation for future prospective studies aimed at optimizing perioperative care and reducing POI-related morbidity in surgical emergencies.Item type:Item, The underestimated burden of postoperative pulmonary complications in emergency laparotomy: a propensity score-matched analysis(2025) Amati, Anca-Laura; Negruta, Nicoleta; Ebert, Romina; Kümmel, Niklas; Fritzenwanker, Moritz; Wolff, Matthias; Petzoldt, Sebastian; Reichert, Martin; Hecker, AndreasIntroduction: Emergency laparotomy (EL) remains one of the highest-risk procedures in general surgery, characterized by substantial postoperative morbidity and mortality. Despite major advances in perioperative medicine, current enhanced-recovery and infection-prevention protocols are largely derived from elective surgical cohorts and are seldom validated in emergency settings. This lack of EL-specific data represents a critical gap in establishing evidence-based perioperative guidelines for this uniquely vulnerable patient population. Among postoperative complications, pulmonary complications (PPCs) are the most frequent and consequential, affecting 20–40% of patients and significantly impairing recovery and survival. This study aimed to identify preoperative predictors of PPCs and their impact on postoperative mortality, highlighting potentially actionable targets within the constraints of emergency surgical care. Methods: A total of 928 EL patients were analyzed. To control for non-modifiable demographics and comorbidities, propensity score matching generated two cohorts of 328 patients each—those with and without PPCs. Univariate and multivariate logistic regression identified independent preoperative predictors of PPCs, and survival analyses assessed their association with postoperative mortality. Results: Mortality was significantly higher in patients with PPCs (42.1%) than in those without (11.9%). Independent preoperative predictors of PPCs included ASA score (p = 0.0004), hemoglobin level (p = 0.0340), C-reactive protein-to-albumin ratio (CAR) (p = 0.0001), and colonization with multidrug-resistant organisms (MDROs) on preoperative screening (p = 0.0420). Each of these factors also predicted reduced postoperative survival. Notably, 67.3% of MDROs were not covered by initial empiric antibiotic regimens, and 28.6% of Gram-negative MDROs detected preoperatively were later isolated from the airways of patients who developed PPCs. PPC patients colonized with MDROs had a 47% higher 90-day mortality risk compared with non-colonized counterparts (HR 1.46, 95% CI 0.99–2.15). Conclusion: PPCs are the most frequent and deadly complications following EL, and their occurrence substantially worsens survival. Among identified predictors, Gram-negative MDRO colonization represents the most clinically actionable target. Tailoring empiric antibiotic therapy for high-risk, colonized EL patients could represent a pivotal step toward evidence-based, condition-specific perioperative guidelines aimed at reducing pulmonary complication–related mortality.