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Myofibroblasts emerge during alveolar regeneration following influenza-virus-induced lung injury
(2025) Khadim, Ali; Kiliaris, Georgios; Vazquez-Armendariz, Ana Ivonne; Procida-Kowalski, Tara; Glaser, David; Bartkuhn, Marek; Malik, Tanya; Chu, Xuran; Moiseenko, Alena; Kuznetsova, Irina; Ahmadvand, Negah; Lingampally, Arun; Hadzic, Stefan; Alexopoulos, Ioannis; Chen, Yuexin; Günther, Andreas; Behr, Jürgen; Neumann, Jens; Schiller, Herbert B.; Li, Xiaokun; Weissmann, Norbert; Braun, Thomas; Seeger, Werner; Wygrecka, Malgorzata; Morty, Rory E.; Herold, Susanne; El Agha, Elie
Estimation of genetic parameters and derivation of economic weights for health and welfare indicators to improve breeding strategies in the Merinoland sheep population
(2025-12) Oberpenning, Jennifer
The aim of this cumulative dissertation is to advance the scientific and practical foundations for sustainable sheep breeding by integrating genetic, phenotypic, and economic perspectives, with a particular focus on health and welfare traits such as tail length. Across three complementary studies, this work investigates (chapter 2) the genetic architecture and trait interrelationships of tail length and growth traits in Merinoland sheep, (chapter 3) the heterogeneity of German sheep production systems and their implications for breeding goal prioritization, and (chapter 4) the development of an enhanced bio‑economic modelling framework to derive economic values for a broad spectrum of breeding traits, including novel welfare and disease resistance traits. Together, these studies contribute to a more holistic understanding of how welfare‑oriented breeding strategies can be implemented without compromising production efficiency or economic viability. The first study provides a detailed quantitative‑genetic analysis of tail length (TL) and its associations with key growth traits. Using single‑trait, multiple‑trait, and structural equation models (SEM), the study demonstrates that TL is highly heritable, indicating strong potential for genetic shortening of tails as an alternative to tail docking. Importantly, SEM approaches reveal that phenotypic pathways linking TL to growth performance differ from the underlying genetic correlations. While the genetic correlations between TL and weight traits are positive, suggesting antagonistic relationships from a breeding perspective, the SEM-based time-lagged phenotypic effects are negative. This implies that longer tails may impair growth due to increased susceptibility to contamination and infection. These findings highlight the importance of modelling trait interdependencies not only genetically, but also through causal phenotypic pathways that reflect environmental and health‑related risk factors. The study thus establishes a methodological and conceptual foundation for integrating welfare traits into breeding programs while accounting for their complex biological relationships. Building on this genetic perspective, the second study shifts focus to the diversity of production environments and management systems within the German sheep sector. Through hierarchical clustering of 25 sheep farms, three distinct production system types are identified, differing in herd size, production orientation, and management philosophy (e.g. organic vs. conventional). Using a contingent valuation approach, the study derives cluster‑specific economic weights for 12 breeding goal traits based on farmers’ willingness to pay for genetic improvement. While most traits show similar valuation across clusters, feed utilization exhibits significant differences, underscoring the influence of production context on economic trait relevance. Notably, all clusters assign substantial importance to the trait category “health and welfare,” including tail length, with values ranging from 24% to 29%. In some clusters, welfare traits are prioritized even above performance traits. These results emphasize that modern breeding goals must be tailored to 4 production system characteristics and increasingly reflect societal and farmer‑driven expectations regarding animal welfare and functional robustness. The third study further deepens the economic evaluation by extending the ECOWEIGHT bio‑economic model to incorporate health and welfare traits more explicitly. The enhanced model allows for the integration of disease incidence, treatment costs, and herd‑level tail‑length status, enabling the derivation of marginal and relative economic values for 15 breeding traits in Merinoland sheep. Fertility and lamb survival traits emerge as the economically most influential, collectively accounting for most of the relative economic value. In contrast, health traits, parasite resistance, tail length, and production traits contribute only marginally to overall economic value in the evaluated research herd, largely due to its exceptionally high health status. Sensitivity analyses altering the proportion of short‑tailed animals reveal only minor shifts in economic values, suggesting that welfare‑oriented breeding for shorter tails can be implemented without substantial economic trade‑offs. The study also highlights the need for broader datasets representing more diverse production environments to ensure generalizable economic evaluations. Taken together, the three studies provide a comprehensive framework for incorporating welfare traits, particularly tail length, into sheep breeding programs. The genetic analyses demonstrate the feasibility of selecting for shorter tails while revealing the importance of accounting for phenotypic pathways linked to health risks. The characterization of production systems underscores that welfare traits are increasingly valued by farmers and should be reflected in breeding goals. Finally, the bio‑economic modelling confirms that incorporating welfare traits does not compromise economic efficiency and can be supported by flexible modelling tools capable of accommodating complex trait patterns. This cumulative work therefore contributes to the development of breeding strategies that align genetic potential, economic viability, and societal expectations for improved animal welfare in modern sheep production.
Maintenance and reversibility of paroxysmal atrial fibrillation in JDP2 overexpressing mice
(2025) Euler, Gerhild; Heger, Jacqueline; Rossol, Marcel; Schulz, Rainer; Parahuleva, Mariana; Kockskämper, Jens
Heart-specific overexpression of transcriptional regulator JDP2 (jun dimerization protein 2) for 5 weeks provokes paroxysmal atrial fibrillation (AF) in mice. We now investigated whether AF and atrial remodeling will be reversible upon termination of JDP2 overexpression, and whether paroxysmal AF converts to permanent AF in the presence of maintained JDP2 overexpression. Cardiac-specific JDP2 overexpression for 5 weeks, resulting in paroxysmal AF, was either continued or repressed via a tet-off system for another 5 weeks. ECGs were recorded weekly. Thereafter, heart and lung weights, and atrial mRNA and protein expression were determined. Extending JDP2 overexpression did not aggravate the AF phenotype, still paroxysmal AF, prolongation of PQ intervals, and atrial hypertrophy were present. This phenotype was completely reversible upon cessation of JDP2 overexpression. A massive downregulation of connexin40 and calcium handling proteins, including SERCA2a, calsequestrin, and ryanodine receptor, was observed in atria after prolonged JDP2 overexpression. In conclusion, atrial remodeling and paroxysmal AF under JDP2 overexpression are not sufficient to maintain or aggravate AF in the absence of JDP2. The comparison of the two groups indicates that the downregulation of Calcium proteins and connexins is an important factor in the maintenance of the disease.
Menstrual blood loss as an initial trigger for adaptation of iron metabolism in eumenorrheic female athletes : an exploratory study
(2025) Nolte, Svenja; Maier, Celina; Klügel, Simon; Weyh, Christopher; Hacker, Sebastian; Badenhorst, Claire; Krüger, Karsten
Iron deficiency is a risk factor for impaired performance and recovery. While exercise-related iron losses are well-documented, the role of menstrual blood loss (MBL) as a physiological trigger of iron regulation remains underexplored. This study examined whether MBL in eumenorrheic female athletes induces measurable hematological and iron-related responses, accounting for sex hormone fluctuations. Ten regional-level football players underwent menstrual cycle tracking and venous blood sampling in both the early follicular and mid-luteal phases. Hematological parameters, iron markers (ferritin and hepcidin), erythropoietic markers (erythropoietin and reticulocytes), and inflammatory markers (myeloperoxidase [MPO] and C-reactive protein [CRP]) were measured. MBL was assessed using the Pictorial Blood Loss Assessment Chart (PBAC). Analyses included descriptive statistics, correlation, and linear mixed modeling. MBL was significantly associated with ferritin (β = −0.289, p = 0.001), reticulocyte counts (β = 0.004, p = 0.019), and reticulocyte production index (β = 0.004, p = 0.027). MPO and CRP showed inverse correlations with MBL, suggesting potential immunomodulatory effects. No interaction between MBL and cycle phase was found. MBL appears to stimulate compensatory erythropoiesis in female athletes, largely independent of hormonal phase. Incorporating MBL assessment into athlete monitoring may support individualized strategies to maintain iron balance and optimize performance.
Natural killer cells from endurance-trained older adults show improved functional and metabolic responses to adrenergic blockade and mTOR inhibition
(2025) Minuzzi, Luciele Guerra; Batatinha, Helena; Weyh, Christopher; Balasubramanian Lakshmi, Vidya Srokshna; Fiuza-Luces, Carmen; Gálvez, Beatriz G.; Lucia, Alejandro; Teixeira, Ana Maria; Sommer, Natascha; Rosa-Neto, José Cesar; Lira, Fabio Santos; Krüger, Karsten
Aging is associated with immune dysfunction, but long-term endurance training may confer protective effects on immune cell function. This study investigates how natural killer (NK) cell phenotypes, functional markers, and metabolism differ between endurance-trained and untrained older adults. Ex vivo expanded NK cells from endurance-trained (63.6 ± 2.1 years) and untrained (64.3 ± 3.3 years) males were exposed to adrenergic blockade (propranolol; 0–200 ng/mL) or mTOR inhibition (rapamycin; 10–100 ng/mL), both with or without PMA-induced inflammatory stimulation. Flow cytometry assessed NK subsets, activation (CD38, CD57, CD107a, NKG2D), senescence (KLRG1), and inhibitory markers (PD-1, LAG-3, TIM-3, NKG2A). Seahorse analysis measured metabolic parameters. Trained participants displayed healthier immune profiles (lower NLR, SII) and higher effector NK cells with lower cytotoxic subsets. Propranolol at 100 ng/mL blunted PMA-driven increases in CD57, CD107a, and NKG2D, while potentiating regulatory markers KLRG1, LAG-3, and PD-1 in the trained group, indicating stronger immunoregulation. With rapamycin, trained NK cells preserved NKG2D and CD107a at 10 ng/mL, maintaining cytotoxicity and degranulation. In contrast, at 100 ng/mL rapamycin plus PMA, trained NK cells shifted toward an effector phenotype with higher CD57 and CD107a, yet a blunted PMA-increased LAG-3 and TIM-3, suggesting resistance to exhaustion. PD-1 and KLRG1 remained elevated, reflecting balanced immune control. Mitochondrial analysis revealed that trained NK cells exhibited higher basal and maximal OCR, greater spare respiratory capacity, and OCR/ECAR ratio, reflecting superior metabolic fitness. These findings indicate that endurance-trained older adults have NK cells with greater functional adaptability, reduced senescence, and enhanced metabolism under inflammatory and pharmacological stress.