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Item Stress Affects Mast Cell Proteases in Murine Skin in a Model of Atopic Dermatitis-like Allergic Inflammation(2024) Rommel, Frank R.; Tumala, Susanne; Urban, Anna-Lena; Siebenhaar, Frank; Kruse, Johannes; Gieler, Uwe; Peters, Eva M. J.Stress exposure worsens allergic inflammatory diseases substantially. Mast cells (MCs) play a key role in peripheral immune responses to neuroendocrine stress mediators such as nerve growth factor (NGF) and substance P (SP). Mast cell proteases (MCPs) and cholinergic factors (Chrna7, SLURP1) were recently described to modulate MC stress response. We studied MCPs and Chrna7/SLURP1 and their interplay in a mouse model for noise induced stress (NiS) and atopic dermatitis-like allergic inflammation (AlD) and in cultured MC lacking Chrna7. We found that the cholinergic stress axis interacts with neuroendocrine stress mediators and stress-mediator cleaving enzymes in AlD. SP-cleaving mMCP4+ MC were upregulated in AlD and further upregulated by stress in NiS+AlD. Anti-NGF neutralizing antibody treatment blocked the stress-induced upregulation in vivo, and mMCP4+ MCs correlated with measures of AlD disease activity. Finally, high mMCP4 production in response to SP depended on Chrna7/SLURP1 in cultured MCs. In conclusion, mMCP4 and its upstream regulation by Chrna7/SLURP1 are interesting novel targets for the treatment of allergic inflammation and its aggravation by stress.Item Impaired Semen Quality in Patients with Chronic Prostatitis(2024) Rosellen, Jens; Dittmar, Florian; Hauptmann, Arne; Diemer, Thorsten; Schuppe, Hans-Christian; Schagdarsurengin, Undraga; Fritzenwanker, Moritz; Wagenlehner, Florian; Pilatz, AdrianBackground/Objectives: Chronic prostatitis/chronic pelvic pain syndrome CP/CPPS is a rather common condition and in recent years many studies have shown contradictory results regarding its impact on semen quality. This prospective cohort study set out to investigate how CP/CPPS affected the parameters of semen in a prospective cohort of patients compared with the WHO 2021 reference group. Methods: From 2013 to 2022, a total of 1071 patients with suspicion of CP/CPPS received a comprehensive andrological examination. Complete semen analysis was carried out in compliance with WHO 2010 guidelines, comparing every study population semen variable to the WHO 2021 reference group (n~3500). Results: All evaluated semen parameters had median values that fell within a normal range. Nonetheless, approximately 25% of patients had values for each semen variable that were lower than the WHO reference group’s fifth percentile. In particular, bacteriospermia was associated with a negative impact on semen volume. Conclusions: This is the largest study that compares all standard semen parameters in patients suffering from CP/CPPS to WHO 2021 reference values. It provides evidence of an impairment of conventional semen parameters.Item Bis(2,2,2 trifluoroethyl) Phosphonate as a Convenient Precursor for the Synthesis of H-Phosphonates(2024) Pohl, Jean-Marie; Stöhr, Fabian; Kramer, Tim; Becker, Jonathan; Göttlich, RichardA microwave-assisted synthesis of dialkyl and cyclic H-phosphonates via bis(2,2,2 trifluoroethyl) phosphonate (BTFEP) is described. This method enables the synthesis of various cyclic H-phosphonates and hetero-substituted dialkyl H-phosphonates by simple alcoholysis under non-inert and additive-free conditions. Short reaction times and the requirement for only stoichiometric amounts of alcohol render this method attractive for synthetic applications.Item Prediction of Initial CRP\/Albumin Ratio on In-Hospital Mortality in Isolated Traumatic Brain Injury Patients(2024) Friedrich, Michaela; Haferkorn, Kristin; Stein, Marco; Uhl, Eberhard; Bender, MichaelThe CRP/albumin ratio (CAR) is a mortality predictor in intensive care unit (ICU) patients. The aim of the current study was to investigate the ability of CAR to predict in-hospital mortality (IHM) in patients with isolated traumatic brain injury (iTBI). We performed a retrospective analysis including 200 patients with iTBI admitted to our neurosurgical intensive care unit (NICU) between September 2014 and December 2016. Serum biomarkers, demographic and radiological data, several ICU scores, and cardiopulmonary parameters were analyzed. The rate of IHM was 27.5% (55/200) and significantly associated with a higher AIS head score (p < 0.0001), a lower albumin level (p < 0.0001), and the necessity of a higher level of inspiratory oxygen fraction (p = 0.002). Furthermore, advanced age (odds ratio [OR] = 0.953, 95% confidence interval [CI] = 0.927–0.981, p = 0.001), a lower GCS score (OR = 1.347, 95% CI = 1.203–1.509, p < 0.0001), a higher level of lactate (OR = 0.506, 95% CI = 0.353–0.725, p < 0.0001), a higher CAR (OR = 0.547, 95% CI = 0.316–0.945, p = 0.031) and a higher norepinephrine application rate (OR = 0.000, 95% CI 0.000–0.090, p = 0.016) were identified as independent predictors of IHM. ROC analysis showed an association between IHM and a CAR cut-off value of >0.38 (Youden index 0.073, sensitivity: 27.9, specificity: 64.8, p = 0.044). We could identify a CAR > 0.38 as a new independent predictor for IHM in patients with iTBI.Item Current Insights into Sublethal Effects of Pesticides on Insects(2024) Bartling, Merle-Theresa; Brandt, Annely; Hollert, Henner; Vilcinskas, AndreasThe effect of pesticides on insects is often discussed in terms of acute and chronic toxicity, but an important and often overlooked aspect is the impact of sublethal doses on insect physiology and behavior. Pesticides can influence various physiological parameters of insects, including the innate immune system, development, and reproduction, through a combination of direct effects on specific exposed tissues and the modification of behaviors that contribute to health and reproductive success. Such behaviors include mobility, feeding, oviposition, navigation, and the ability to detect pheromones. Pesticides also have a profound effect on insect learning and memory. The precise effects depend on many different factors, including the insect species, age, sex, caste, physiological condition, as well as the type and concentration of the active ingredients and the exposure route. More studies are needed to assess the effects of different active ingredients (and combinations thereof) on a wider range of species to understand how sublethal doses of pesticides can contribute to insect decline. This review reflects our current knowledge about sublethal effects of pesticides on insects and advancements in the development of innovative methods to detect them.Item Does Cell-Type-Specific Silencing of Monoamine Oxidase B Interfere with the Development of Right Ventricle (RV) Hypertrophy or Right Ventricle Failure in Pulmonary Hypertension?(2024) Brosinsky, Paulin; Heger, Jacqueline; Sydykov, Akylbek; Weiss, Astrid; Klatt, Stephan; Czech, Laureen; Kraut, Simone; Schermuly, Ralph Theo; Schlüter, Klaus-Dieter; Schulz, RainerIncreased mitochondrial reactive oxygen species (ROS) formation is important for the development of right ventricular (RV) hypertrophy (RVH) and failure (RVF) during pulmonary hypertension (PH). ROS molecules are produced in different compartments within the cell, with mitochondria known to produce the strongest ROS signal. Among ROS-forming mitochondrial proteins, outer-mitochondrial-membrane-located monoamine oxidases (MAOs, type A or B) are capable of degrading neurotransmitters, thereby producing large amounts of ROS. In mice, MAO-B is the dominant isoform, which is present in almost all cell types within the heart. We analyzed the effect of an inducible cardiomyocyte-specific knockout of MAO-B (cmMAO-B KO) for the development of RVH and RVF in mice. Right ventricular hypertrophy was induced by pulmonary artery banding (PAB). RV dimensions and function were measured through echocardiography. ROS production (dihydroethidium staining), protein kinase activity (PamStation device), and systemic hemodynamics (in vivo catheterization) were assessed. A significant decrease in ROS formation was measured in cmMAO-B KO mice during PAB compared to Cre-negative littermates, which was associated with reduced activity of protein kinases involved in hypertrophic growth. In contrast to littermates in which the RV was dilated and hypertrophied following PAB, RV dimensions were unaffected in response to PAB in cmMAO-B KO mice, and no decline in RV systolic function otherwise seen in littermates during PAB was measured in cmMAO-B KO mice. In conclusion, cmMAO-B KO mice are protected against RV dilatation, hypertrophy, and dysfunction following RV pressure overload compared to littermates. These results support the hypothesis that cmMAO-B is a key player in causing RV hypertrophy and failure during PH.Item Apples and oranges: PTSD patients and healthy individuals are not comparable in their subjective and physiological responding to emotion induction and bilateral stimulation(2024) Pape, Valeska; Sammer, Gebhard; Hanewald, Bernd; Schäflein, Eva; Rauschenbach, Fritz; Stingl, MarkusObjectives: Bilateral stimulation is a core element of Eye Movement Desensitization and Reprocessing Therapy, a psychotherapeutic intervention for the treatment of Posttraumatic Stress Disorder (PTSD). Promising previous findings showed measurable physiological effects of bilateral stimulation in healthy individuals, but studies that replicated these findings in PTSD patients are sparse. Methods: 23 patients with PTSD and 30 healthy controls were confronted with affective standard scripts (pleasant, neutral, unpleasant) while bilateral tactile stimulation was applied. Monolateral and no stimulation served as control conditions. Noise-induced startle reflex response (valence measure) and galvanic skin response (arousal measure) were used for physiological responses and the valence and arousal scale of the Self-Assessment-Manikin for subjective responses. Results: Both groups showed a subjective distress reduction for unpleasant scripts and a subjective attention increase for positive scripts under bilateral stimulation. In healthy individuals, this was also for physiological measures, and a general startle-reducing effect of bilateral stimulation in the absence of affective stimuli was found. In PTSD patients, however, the effects were restricted on the subjective level, and no concomitant physiological effects were observed. Conclusions and significance: The findings indicate, that generalizing the effects of BLS in healthy individuals to PTSD patients may be problematic. The herein-reported group differences can be explained by PTSD-specific peculiarities in emotion processing and cognitive processing style.Item An Optimized Protocol for the Generation of Alveolospheres from Wild-Type Mice(2024) Zabihi, Mahsa; Khadim, Ali; Schäfer, Theresa M.; Alexopoulos, Ioannis; Bartkuhn, Marek; El Agha, Elie; Vazquez-Armendariz, Ana I.; Herold, SusanneOrganoid models have become an integral part of the research methodology in the lung field. These systems allow for the study of progenitor and stem cell self-renewal, self-organization, and differentiation. Distinct models of lung organoids mimicking various anatomical regions of mature lungs have emerged in parallel to the increased gain of knowledge regarding epithelial stem and progenitor cell populations and the corresponding mesenchymal cells that populate the in vivo niche. In the distal lung, type 2 alveolar epithelial cells (AEC2s) represent a stem cell population that is engaged in regenerative mechanisms in response to various insults. These cells self-renew and give rise to AEC1s that carry out gas exchange. Multiple experimental protocols allowing the generation of alveolar organoids, or alveolospheres, from murine lungs have been described. Among the drawbacks have been the requirement of transgenic mice allowing the isolation of AEC2s with high viability and purity, and the occasional emergence of bronchiolar and bronchioalveolar organoids. Here, we provide a refined gating strategy and an optimized protocol for the generation of alveolospheres from wild-type mice. Our approach not only overcomes the need for transgenic mice to generate such organoids, but also yields a pure culture of alveolospheres that is devoid of bronchiolar and bronchioalveolar organoids. Our protocol contributes to the standardization of this important research tool.Item Transforming food systems in the Global South: a radical approach(2024) Suarez, Andres; Ume, ChukwumaSustainability within food systems (FS) transcends approaches that only consider FS transformation via changing agricultural practices or consumption patterns. The essence lies in addressing the root causes of current unsustainable FS and their associated social and environmental ramifications. This paper aims to outline the solutions needed to revamp these challenges, by paying special attention to the state-capital nexus in the context of the FS’global core-periphery dialectics. Thereby, we embrace radical political agroecology as being essential in promoting sustainability within the FS, especially in the Global South. Agroecology is proposed as the strategy to address the food system’s complexity in terms of the social, environmental, and economic embeddedness. We conclude with potential solutions that contribute to the pathway for FS sustainability.Item Facial emotion recognition in children of parents with a mental illness(2024) Werkmann, Naomi Leona; Luczejko, Arleta Angelika; Hagelweide, Klara; Stark, Rudolf; Weigelt, Sarah; Christiansen, Hanna; Kieser, Meinhard; Otto, Kathleen; Reck, Corinna; Steinmayr, Ricarda; Wirthwein, Linda; Zietlow, Anna-Lena; Schwenck, ChristinaObjective: Facial emotion recognition (FER) is a fundamental social skill essential for adaptive social behaviors, emotional development, and overall well-being. FER impairments have been linked to various mental disorders, making it a critical transdiagnostic mechanism influencing the development and trajectory of mental disorders. FER has also been found to play a role in the transgenerational transmission of mental disorders, with the majority of research suggesting FER impairments in children of parents with a mental illness (COPMI). Previous research primarily concentrated on COPMI of parents with internalizing disorders, which does not cover the full spectrum of outpatient mental health service populations. Furthermore, research focuses on varying components of FER by using different assessment paradigms, making it challenging to compare study results. To address these gaps, we comprehensively investigated FER abilities in COPMI using multiple tasks varying in task characteristics. Methods: We included 189 children, 77 COPMI and 112 children of parents without a diagnosed mental illness (COPWMI), aged 6 to 16 years. We assessed FER using three tasks with varying task demands: an emotional Go/NoGo task, a morphing task, and a task presenting short video sequences depicting different emotions. We fitted separate two-level hierarchical Bayesian models (to account for sibling pairs in our sample) for reaction times and accuracy rates for each task. Good model fit was assured by comparing models using varying priors. Results: Contrary to our expectations, our results revealed no general FER deficit in COPMI compared to COPWMI. The Bayesian models fitted for accuracy in the morphing task and Go/NoGo task yielded small yet significant effects. However, Bayes factors fitted for the models suggested that these effects could be due to random variations or noise in the data. Conclusions: Our study does not support FER impairments as a general feature of COPMI. Instead, individual factors, such as the type of parental disorder and the timing of its onset, may play a crucial role in influencing FER development. Future research should consider these factors, taking into account the diverse landscape of parental mental disorders.Item Human dendritic cell interactions with the zoonotic parasite Cryptosporidium parvum result in activation and maturation(2024) Ross, Ralf; Hasheminasab, Seyed Sajjad; Conejeros, Iván; Gärtner, Ulrich; Kamena, Faustin; Krueger, Andreas; Taubert, Anja; Hermosilla, CarlosCryptosporidiosis in humans is caused by infection of the zoonotic apicomplexan parasite Cryptosporidium parvum. In 2006, it was included by the World Health Organization (WHO) in the group of the most neglected poverty-related diseases. It is characterized by enteritis accompanied by profuse catarrhalic diarrhea with high morbidity and mortality, especially in children of developing countries under the age of 5 years and in HIV patients. The vulnerability of HIV patients indicates that a robust adaptive immune response is required to successfully fight this parasite. Little is known, however, about the adaptive immune response against C. parvum. To have an insight into the early events of the adaptive immune response, we generated primary human dendritic cells (DCs) from monocytes of healthy blood donors and exposed them to C. parvum oocysts and sporozoites in vitro. DCs are equipped with numerous receptors that detect microbial molecules and alarm signals. If stimulation is strong enough, an essential maturation process turns DCs into unique activators of naïve T cells, a prerequisite of any adaptive immune response. Parasite exposure highly induced the production of the pro-inflammatory cytokines/chemokines interleukin (IL)-6 and IL-8 in DCs. Moreover, antigen-presenting molecules (HLA-DR and CD1a), maturation markers, and costimulatory molecules required for T-cell stimulation (CD83, CD40, and CD86) and adhesion molecules (CD11b and CD58) were all upregulated. In addition, parasite-exposed human DCs showed enhanced cell adherence, increased mobility, and a boosted but time-limited phagocytosis of C. parvum oocysts and sporozoites, representing other prerequisites for antigen presentation. Unlike several other microbial stimuli, C. parvum exposure rather led to increased oxidative consumption rates (OCRs) than extracellular acidification rates (ECARs) in DCs, indicating that different metabolic pathways were used to provide energy for DC activation. Taken together, C. parvum-exposed human DCs showed all hallmarks of successful maturation, enabling them to mount an effective adaptive immune response.Item Pneumococcal hydrogen peroxide regulates host cell kinase activity(2024) Bazant, Jasmin; Weiss, Astrid; Baldauf, Julia; Schermuly, Ralph Theo; Hain, Torsten; Lucas, Rudolf; Mraheil, Mobarak AbuIntroduction: Protein kinases are indispensable reversible molecular switches that adapt and control protein functions during cellular processes requiring rapid responses to internal and external events. Bacterial infections can affect kinase-mediated phosphorylation events, with consequences for both innate and adaptive immunity, through regulation of antigen presentation, pathogen recognition, cell invasiveness and phagocytosis. Streptococcus pneumoniae (Spn), a human respiratory tract pathogen and a major cause of community-acquired pneumoniae, affects phosphorylation-based signalling of several kinases, but the pneumococcal mediator(s) involved in this process remain elusive. In this study, we investigated the influence of pneumococcal H2O2 on the protein kinase activity of the human lung epithelial H441 cell line, a generally accepted model of alveolar epithelial cells. Methods: We performed kinome analysis using PamGene microarray chips and protein analysis in Western blotting in H441 lung cells infected with Spn wild type (SpnWT) or with SpnΔlctOΔspxB -a deletion mutant strongly attenuated in H2O2 production- to assess the impact of pneumococcal hydrogen peroxide (H2O2) on global protein kinase activity profiles. Results: Our kinome analysis provides direct evidence that kinase activity profiles in infected H441 cells significantly vary according to the levels of pneumococcal H2O2. A large number of kinases in H441 cells infected with SpnWT are significantly downregulated, whereas this no longer occurs in cells infected with the mutant SpnΔlctOΔspxB strain, which lacks H2O2. In particular, we describe for the first time H2O2-mediated downregulation of Protein kinase B (Akt1) and activation of lymphocyte-specific tyrosine protein kinase (Lck) via H2O2-mediated phosphorylation.Item Individual differences in face salience and rapid face saccades(2024) Broda, Maximilian Davide; Borovska, Petra; de Haas, BenjaminHumans saccade to faces in their periphery faster than to other types of objects. Previous research has highlighted the potential importance of the upper face region in this phenomenon, but it remains unclear whether this is driven by the eye region. Similarly, it remains unclear whether such rapid saccades are exclusive to faces or generalize to other semantically salient stimuli. Furthermore, it is unknown whether individuals differ in their face-specific saccadic reaction times and, if so, whether such differences could be linked to differences in face fixations during free viewing. To explore these open questions, we invited 77 participants to perform a saccadic choice task in which we contrasted faces as well as other salient objects, particularly isolated face features and text, with cars. Additionally, participants freely viewed 700 images of complex natural scenes in a separate session, which allowed us to determine the individual proportion of first fixations falling on faces. For the saccadic choice task, we found advantages for all categories of interest over cars. However, this effect was most pronounced for images of full faces. Full faces also elicited faster saccades compared with eyes, showing that isolated eye regions are not sufficient to elicit face-like responses. Additionally, we found consistent individual differences in saccadic reaction times toward faces that weakly correlated with face salience during free viewing. Our results suggest a link between semantic salience and rapid detection, but underscore the unique status of faces. Further research is needed to resolve the mechanisms underlying rapid face saccades.Item Tracking effects of extreme drought on coniferous forests from space using dynamic habitat indices(2024) Safaei, Mojdeh; Kleinebecker, Till; Weis, Manuel; Große-Stoltenberg, AndréTerrestrial ecosystems such as coniferous forests in Central Europe are experiencing changes in health status following extreme droughts compounding with severe heat waves. The increasing temporal resolution and spatial coverage of earth observation data offer new opportunities to assess these dynamics. Dense time-series of optical satellite data allow for computing Dynamic Habitat Indices (DHIs), which have been predominantly used in biodiversity studies. However, DHIs cover three aspects of vegetation changes that could be affected by drought: annual productivity, minimum cover, and seasonality. Here, we evaluate the health status of coniferous forests in the federal state of Hesse in Germany over the period 2017–2020 including the severe drought year of 2018 using DHIs based on the Normalized Difference Vegetation Index (NDVI) for drought assessment. To identify the most important variables affecting coniferous forest die-off, a series of environmental variables together with the three DHIs components were used in a logistic regression (LR) model. Each DHI component changed significantly across non-damaged and damaged sites in all years (p-value 0.05). When comparing 2017 to 2019, DHI-based annual productivity decreased and seasonality increased. Most importantly, none of the DHI components had reached pre-drought conditions, which likely indicates a change in ecosystem functioning. We also identified spatially explicit areas highly affected by drought. The LR model revealed that in addition to common environmental parameters related to temperature, precipitation, and elevation, DHI components were the most important factors explaining the health status. Our analysis demonstrates the potential of DHIs to capture the effect of drought events on Central European coniferous forest ecosystems. Since the spaceborne data are available at the global level, this approach can be applied to track the dynamics of ecosystem conditions in other regions, at larger spatial scales, and for other Land Use/Land Cover types.Item The significance of glutaredoxins for diabetes mellitus and its complications(2024) Zhou, Mengmeng; Hanschmann, Eva-Maria; Römer, Axel; Linn, Thomas; Petry, Sebastian FriedrichDiabetes mellitus is a non-communicable metabolic disease hallmarked by chronic hyperglycemia caused by beta-cell failure. Diabetic complications affect the vasculature and result in macro- and microangiopathies, which account for a significantly increased morbidity and mortality. The rising incidence and prevalence of diabetes is a major global health burden. There are no feasible strategies for beta-cell preservation available in daily clinical practice. Therefore, patients rely on antidiabetic drugs or the application of exogenous insulin. Glutaredoxins (Grxs) are ubiquitously expressed and highly conserved members of the thioredoxin family of proteins. They have specific functions in redox-mediated signal transduction, iron homeostasis and biosynthesis of iron-sulfur (FeS) proteins, and the regulation of cell proliferation, survival, and function. The involvement of Grxs in chronic diseases has been a topic of research for several decades, suggesting them as therapeutic targets. Little is known about their role in diabetes and its complications. Therefore, this review summarizes the available literature on the significance of Grxs in diabetes and its complications. In conclusion, Grxs are differentially expressed in the endocrine pancreas and in tissues affected by diabetic complications, such as the heart, the kidneys, the eye, and the vasculature. They are involved in several pathways essential for insulin signaling, metabolic inflammation, glucose and fatty acid uptake and processing, cell survival, and iron and mitochondrial metabolism. Most studies describe significant changes in glutaredoxin expression and/or activity in response to the diabetic metabolism. In general, mitigated levels of Grxs are associated with oxidative distress, cell damage, and even cell death. The induced overexpression is considered a potential part of the cellular stress-response, counteracting oxidative distress and exerting beneficial impact on cell function such as insulin secretion, cytokine expression, and enzyme activity.Item Effect of replacing soybean meal with Hermetia illucens meal on cecal microbiota, liver transcriptome, and plasma metabolome of broilers(2024) Beller, Simone; Grundmann, Sarah M.; Pies, Klara; Most, Erika; Schuchardt, Sven; Seel, Waldemar; Simon, Marie-Christine; Eder, Klaus; Ringseis, RobertDespite the existence of a number of studies investigating the effect of insect meal on the growth performance of broilers, knowledge about the metabolic effects of insect meal in broilers is still scarce. Thus, the present study investigated the effect of partial replacement of soybean meal with Hermetia illucens (HI) larvae meal on the liver transcriptome, the plasma metabolome, and the cecal microbiota in broilers. For the study, 72 male one-day-old Cobb 500 broilers were divided into three groups and fed 3 different diets with either 0% (HI0), 7.5% (HI7.5), or 15% (HI15) defatted HI meal for 35 d. Each group consisted of 6 cages (replicates) with 4 broilers/cage. While body weight (BW) gain, feed intake, and feed:gain ratio did not differ between groups, breast muscle weight, carcass yield, and apparent ileal digestibility (AID) of 5 amino acids were higher in group HI15 than in group HI0 (P < 0.05). Indicators of α-diversity (Chao1 and Observed) in the cecal digesta were higher in groups HI15 and HI7.5 than in group HI0 (P < 0.05). The abundance of 5 families and 18 genera, all of which belonged to the Firmicutes phylum, in the cecal digesta differed among groups (P < 0.05). Concentrations of butyric acid, valeric acid, and isobutyric acid in the cecal digesta were lower in group HI15 than in the other 2 groups (P < 0.05), whereas those of total and other short-chain fatty acids were not different between groups. Liver transcriptomics revealed a total of 70 and 61 differentially expressed transcripts between groups HI15 vs. HI0 and between groups HI7.5 vs. HI0, respectively, (P < 0.05). Targeted metabolomics identified 138 metabolites, most of which were triglyceride species, being different between the 3 groups (FDR < 0.05). According to this study, dietary inclusion of HI larvae meal has no detrimental impact but increases breast muscle weight and carcass weight in broilers suggesting that HI larvae meal can be recommended as a sustainable alternative protein source for broilers.Item Can a gradual weaning and separation process reduce weaning distress in dam-reared dairy calves? A comparison with the 2-step method(2024) Vogt, Anina; Barth, Kerstin; Waiblinger, Susanne; König von Borstel, UtaThe weaning and separation phase remains one of the biggest challenges for cow-calf contact systems, but a gradual process that better mimics the naturally occurring reduction in milk intake has not yet been scientifically investigated. Therefore, the aim of our study was to compare behavioral and physiological indicators of distress in 3-mo-old dam-reared dairy calves (with previous full-time cow-calf contact) weaned and separated either via gradual reduction of contact time with the dam (GR; 1 wk of half-day contact, 1 wk of morning contact, and 1 wk of fence-line contact before complete separation, n = 18) or via 2-step weaning using a nose flap (NF, 2 wk of access to the dam with a nose flap, 1 wk of fence-line contact before complete separation, n = 18). Behavior was recorded 1 wk before (or for lying 3 wk before) weaning start and during the 3 wk weaning and separation period with direct observations on 4 d/wk or via accelerometers (locomotor play, lying behavior). Blood and fecal samples were taken twice per week from weaning start until 3 wk after weaning start. Calves were weighed weekly. Statistical analysis was conducted using (generalized) linear mixed models. Over the whole weaning and separation phase, NF calves showed a stronger decrease in the number of lying bouts, amount of locomotor play, and ADG, as well as a higher increase in TMR feeding time compared with GR calves, whereas GR calves vocalized more often and showed more searching behavior than NF calves. Also, the neutrophil:lymphocyte ratio of NF calves was elevated on d 3 after insertion of the nose flaps compared with baseline, but showed no change for GR calves on any sampling day. Overall, results point toward a favorable effect of a gradual weaning strategy on reduction of weaning and separation distress in dam-reared dairy calves, but the method requires further improvement from the protocol used in our study.Item Analysis of genetic variants for different horn phenotypes and their inheritance in Icelandic sheep(2024) Simon, Rebecca; Elísabetardóttir, Karólína; Lühken, GesineIcelandic sheep are characterized by a great diversity in horn phenotypes. Within their breed, they show a variability in terms of this trait to an extent rarely observed elsewhere. Previously, several genetic variants were published as markers for horn status (in terms of absence or presence of horns, including scurs) and horn traits (e.g., oval horns, horn length and polyceraty). The aim of this study was to genotype, for the first time, five of these genetic variants in Icelandic sheep with different horn phenotypes, as well as to analyze their inheritance. Phenotypic and pedigree data, as well as DNA samples from two Icelandic sheep farms, were used. Genetic variants were genotyped by published PCR-based methods in all samples (n=94) or in subsets. As in other sheep breeds with variable horn status, the inheritance of the presence or absence of horns was shown to be complex in Icelandic sheep, especially when sheep carry anything other than regularly formed horns. The 1.78 kb sized RXFP2 insertion on ovine chromosome 10 previously described to be associated with polledness in several sheep breeds was also found to be present in Icelandic sheep and showed some association but not a perfect segregation with the individuals' horn statuses. Missing associations were especially seen in sheep with scurs and oval horns. Regarding horn shape, there was no agreement with the studied variants described in Chinese breeds having comparable horn traits. However, matching tendencies were seen for the horn size variant that was found in the same study. All sheep with four or more horns carried the already published 4 bp deletion in HOXD1, as previously described for three other sheep breeds. Interestingly, for the first time, the deletion was also detected in phenotypically polled animals originating from multi-horned families. According to the results from animals genotyped simultaneously for the RXFP2 and the HOXD1 variants, polledness in sheep with a genetic disposition for polyceraty seems not to be controlled by the RXFP2 insertion. However, this and all other findings in Icelandic sheep need to be confirmed by analyzing a higher number of well-phenotyped animals.Item Preoperative routine measurement of NT-proBNP predicts postoperative morbidity after non-cardiac surgery with intermediate or high surgical risk: an observational study(2024) Schmidt, Götz; Frieling, Nora; Schneck, Emmanuel; Habicher, Marit; Koch, Christian; Rubarth, Kerstin; Balzer, Felix; Aßmus, Birgit; Sander, MichaelBackground: Chronic heart failure (HF) is a common clinical condition associated with adverse outcomes in elderly patients undergoing non-cardiac surgery. This study aimed to estimate a clinically applicable NT-proBNP cut-off that predicts postoperative 30-day morbidity in a non-cardiac surgical cohort. Methods: One hundred ninety-nine consecutive patients older than 65 years undergoing elective non-cardiac surgery with intermediate or high surgical risk were analysed. Preoperative NT-proBNP was measured, and clinical events were assessed up to postoperative day 30. The primary endpoint was the composite morbidity endpoint (CME) consisting of rehospitalisation, acute decompensated heart failure (ADHF), acute kidney injury (AKI), and infection at postoperative day 30. Secondary endpoints included perioperative fluid balance and incidence, duration, and severity of perioperative hypotension. Results: NT-proBNP of 443 pg/ml had the highest accuracy in predicting the composite endpoint; a clinical cut-off of 450 pg/ml was implemented to compare clinical endpoints. Although 35.2% of patients had NT-proBNP above the threshold, only 10.6% had a known history of HF. The primary endpoint was the composite morbidity endpoint (CME) consisting of rehospitalisation, acute decompensated heart failure (ADHF), acute kidney injury (AKI), and infection. Event rates were significantly increased in patients with NT-proBNP > 450 pg/ml (70.7% vs. 32.4%, p < 0.001), which was due to the incidence of cardiac rehospitalisation (4.4% vs. 0%, p = 0.018), ADHF (20.1% vs. 4.0%, p < 0.001), AKI (39.8% vs. 8.3%, p < 0.001), and infection (46.3% vs. 24.4%, p < 0.01). Perioperative fluid balance and perioperative hypotension were comparable between groups. Preoperative NT-proBNP > 450 pg/ml was an independent predictor of the CME in a multivariable Cox regression model (hazard ratio 2.92 [1.72–4.94]). Conclusions: Patients with NT-proBNP > 450 pg/ml exhibited profoundly increased postoperative morbidity. Further studies should focus on interdisciplinary approaches to improve outcomes through integrated interventions in the perioperative period.Item mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema(2024) Lipskaia, Larissa; Breau, Marielle; Cayrou, Christelle; Churikov, Dmitri; Braud, Laura; Jacquet, Juliette; Born, Emmanuelle; Fouillade, Charles; Curras-Alonso, Sandra; Bauwens, Serge; Jourquin, Frederic; Fiore, Frederic; Castellano, Rémy; Josselin, Emmanuelle; Sánchez-Ferrer, Carlota; Giovinazzo, Giovanna; Lachaud, Christophe; Gilson, Eric; Flores, Ignacio; Londono-Vallejo, Arturo; Adnot, Serge; Géli, VincentLung diseases develop when telomeres shorten beyond a critical point. We constructed a mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTertCI), is expressed from the p21Cdkn1a locus. Expression of either TERT or TERTCI reduces global p21 levels in the lungs of aged mice, highlighting TERT non-canonical function. However, only TERT reduces accumulation of very short telomeres, oxidative damage, endothelial cell (ECs) senescence and senile emphysema in aged mice. Single-cell analysis of the lung reveals that p21 (and hence TERT) is expressed mainly in the capillary ECs. We report that a fraction of capillary ECs marked by CD34 and endowed with proliferative capacity declines drastically with age, and this is counteracted by TERT but not TERTCI. Consistently, only TERT counteracts decline of capillary density. Natural aging effects are confirmed using the experimental model of emphysema induced by VEGFR2 inhibition and chronic hypoxia. We conclude that catalytically active TERT prevents exhaustion of the putative CD34 + EC progenitors with age, thus protecting against capillary vessel loss and pulmonary emphysema.