University of Giessen

As organizations face an aging workforce, it is crucial to understand the role of leaders’ age in their interactions with employees. Seminal theories on aging cast age as a key factor shaping individuals’ interpersonal behaviors, for example when handling conflicts. We integrate this notion with insights from generativity research to investigate the role of leaders’ age in their active conflict management strategies through two distinct pathways. Depending on a leader’s generativity, leaders’ age may differentially shape both their perceptions of leader-member exchange (LMX) quality and their emotion regulation knowledge, thereby advancing either more constructive or more destructive approaches toward employee conflicts. Results from Study 1, a time-lagged study of 303 leaders, revealed that age is negatively related to their LMX perceptions and, thus, to leaders’ constructive approaches toward employee conflicts—but only among leaders with lower generativity. Study 2, a cross-sectional study of 84 leader-employee teams, revealed that leaders’ age is positively associated with their emotion regulation knowledge, which in turn is negatively related to their destructive conflict management—but only among leaders with higher generativity. Our findings reveal key mechanisms linking leader age to conflict management and underscore leader generativity as a crucial boundary condition in these relationships.

Mycoviruses, viruses that infect fungi, have been identified across nearly every fungal taxon. Despite their widespread presence , the ecological effects of mycoviruses remain poorly understood. They can influence the biology of their hosts in various ways, including altering growth, reproduction, and pathogenicity. Their ability to induce either fungal hyper-or hypovirulence and thus regulate general fungal fitness by increasing fungal aggressiveness or, conversely, in extreme cases, converting harmful fungi into beneficial ones, has attracted increasing attention in recent years as a potential means of protecting plants from fungal diseases and pests. Increasing difficulties in controlling fungal diseases, pests and weeds with synthetic chemical pesticides, exacerbated by the emergence of resistance or tolerance to certain active ingredients, and stricter regulatory requirements due to environmental and health concerns, have stimulated interest in alternative approaches. In parallel with the introduction of double-stranded (ds)RNA-based products for crop protection and the fundamental knowledge generated in this field in recent years, the potential use of mycoviruses to control pathogenic fungi appears to be within reach. This review highlights recent advances in the field and emphasizes the potential of mycoviruses as biological control agents (BCAs), with the emphasis on the utilization of mycovirus-induced fungal hypovirulence to control fungi that cause plant diseases and mycovirus-induced fungal hypervirulence to protect plants from fungal hosts such insect pests or weeds.

Inflammatory processes have been implicated in the pathophysiology of depression. In human studies, inflammation has been shown to act as a critical disease modifier, promoting susceptibility to depression and modulating specific endophenotypes of depression. However, there is scant documentation of how inflammatory processes are associated with neural activity in patients with depression. We therefore tested the hypothesis that the peripheral inflammation markers IL-6 and TNF-α correlate with neural resting state network functional connectivity in depression using functional magnetic resonance imaging (fMRI) and compared it with healthy controls. We used fMRI to investigate the functional connectivity (FC) of the resting state Default Mode Network (DMN) and Salience/Ventral Attention Network (SAL) and their association with the peripheral inflammation markers IL-6 and TNF-α in 25 patients with depression and compared it to 24 healthy subjects. Results of this imaging study revealed that both DMN and SAL resting state networks are differentially associated with distinct immunological pathways depending on whether a person has a depressive phenotype or is healthy. While the DMN FC correlated with the concentration of the cytokine IL-6 in healthy subjects, SAL FC’s connectivity correlated with the cytokine TNF-α's concentration. This study highlights the importance of peripheral inflammatory processes in depression and suggests a modulatory effect on neural resting state networks depending on the state of depression.

Background Myasthenia gravis (MG) is an autoimmune disorder affecting neuromuscular junctions, leading to fluctuating muscle weakness. While many patients respond well to standard immunosuppression, a substantial subgroup faces ongoing disease activity. Emerging treatments such as complement factor C5 inhibition (C5IT) and neonatal Fc receptor (FcRn) antagonism hold promise for these patients. However, the current landscape is hindered by a paucity of comparative data that is crucial for treatment decisions. Objective This study aims to compare the effectiveness and safety of C5IT and FcRn antagonists in a real-world setting. Methods A retrospective analysis of 153 MG patients from 8 German specialised MG centres receiving either C5IT (26 eculizumab, 80 ravulizumab) or efgartigimod (47 patients) was conducted. Propensity score matching (PSM) was employed to compare changes in MG-specific outcome parameters within the first 6 months after treatment initiation, along with safety profiles and concomitant MG therapy. Results Both treatment strategies led to rapid clinical improvements and substantial reductions in prednisolone doses. However, insufficient response was noted in 20%–49.1% of patients based on Quantitative MG and MG Activities of Daily Living (MG-ADL) scores. We did not identify any new safety concerns. After PSM, 40 patients remained in each group. In both cohorts, reductions in MG-ADL as prespecified primary study endpoint were comparable. Moreover, analyses of secondary outcome parameters demonstrated similar results for C5IT versus FcRn. Conclusion In contrast to current meta-analyses and indirect comparisons of clinical trial data, our real-world study demonstrates comparable efficacy and safety of C5IT and FcRn antagonism in MG.

Background and Aim: Anaplasmosis in small ruminants is a tick-borne infection caused mainly by the obligate intraerythrocytic bacterium Anaplasma ovis. It is usually subclinical, with persistent infection in affected animals, but acute disease can occur, particularly in young animals. The pathogen is widespread in Central Asia and neighboring regions. In Kazakhstan, the infection was first detected in 1929. However, until now, diagnosis in the country has been based on traditional microscopic examination of blood smears. There were no reliable data on the prevalence and genetic diversity of Anaplasma spp. in sheep in Kazakhstan. This study aimed to determine the occurrence of Anaplasma spp. infection in sheep in southern Kazakhstan, a high-risk region for tick-borne diseases, using PCR and to identify the species by sequencing. Materials and Methods: A cross-sectional study was conducted on apparently healthy adult ewes from 77 settlements in 34 districts of Kyzylorda, Turkistan, Zhambyl, Almaty, and Jetisu, southern Kazakhstan. A total of 2553 whole blood samples collected in midsummer 2022 and 2023 were analyzed for Anaplasma spp. using polymerase chain reaction targeting the 404 bp groEL gene fragment. The amplification products from the 441 positive samples were sequenced using the Sanger sequencing method. Phylogenetic analysis of the obtained sequences was performed using the maximum likelihood model. Results: Overall, 1017/2553 (39.8%; 95% confidence interval: 37.9%-41.7%) ewes tested were positive for Anaplasma spp. Positive animals were found in 68/77 (88%) of the settlements from which samples were taken. The percentage of Anaplasma spp.-positive ewes varied significantly from 21.3% to 50.1% in the provinces. Altitude <500 m above sea level was identified as a risk factor for Anaplasma infection. All amplification products were identified as A. ovis through sequencing. Phylogenetic analysis of the groEL gene fragment sequences revealed the presence of two A. ovis genotypes; one was 100% identical to sequences from isolates from China and the other was >99.5% identical to isolates from Africa, Cyprus, and China. Conclusion: This first molecular study revealed a widespread of A. ovis infection in adult ewes in southern Kazakhstan. Altitude <500 m was identified as a risk factor. Therefore, clinical cases associated with A. ovis are expected in this region, especially in young animals. Future studies are needed to determine the clinical and economic impact of anaplasmosis on sheep production in the country, to investigate seasonal patterns of infection, and to identify tick species or other arthropods that act as local vectors. This information is useful for developing possible control measures and evaluating their effectiveness.

The Dermatology Life Quality Index (DLQI) should be used to assess treatment success in psoriasis (PSO). However, the DLQI does not assess the importance and achievement of treatment goals. The Patient Benefit Index (PBI) is a questionnaire that takes both into account. Currently, there is insufficient knowledge about the modulating variables of the PBI and whether it can complement the assessment of the DLQI. In a longitudinal cohort study, 82 patients with PSO were assessed before and up to sixteen weeks after a new treatment episode. The PBI was compared with patients with atopic dermatitis (AD) (n = 61). The effects of gender, age, type of therapy, improvement in body surface area (BSA), anxiety/depression, DLQI and individual coping were assessed. “Getting better skin quickly” was most important in PSO. Improved BSA, anxiety/depression, DLQI, male gender and initiation of biological therapy had the most positive effects. Partial mediation was found for the reduction of anxiety/depression and improved coping. The PBI may be considered an appropriate outcome measure of treatment success in PSO, complementing the DLQI. Patients with clinically relevant anxiety/depression and inadequate coping should be offered adjuvant psychosomatic treatment.

Parasites account for huge economic losses by infecting agriculturally important plants and animals. Furthermore, morbidity and death caused by parasites affect a large part of the world population, especially in economically weak regions. Anthelmintic drugs to tackle this challenge remain scarce and their efficiency becomes increasingly endangered by the advent of drug resistance development. In the present study, we assessed the anthelmintic potential of bis-3-chloropiperidines, a family of compounds which have already demonstrated antiproliferative activity against various cell lines. We synthesized and tested the activity of 21 bis-3-chloropiperidine derivatives against two strains of the free-living nematode Caenorhabditis elegans (N2 and DC19) and the parasitic flatworm Schistosoma mansoni. Overall, bifunctional chloropiperidines featuring an aromatic linker performed best against the tested indicator organisms and could be considered for future optimization efforts. Ultimately, out of the 21 analyzed bis-3-chloropiperidines, four derivatives (2, 5, 9 and 11) reduced vitality parameters against S. mansoni and five the motility of C. elegans (2, 4, 5, 13, 21) while exhibiting no or low cytotoxicity.

Background Sheep's tail docking is a widespread practice, which is banned or critically discussed in some countries to improve animal welfare. Objective The aim was to determine the influence of breeding for short‐tailedness (ST) or long‐tailedness (LT) in sheep on the development of reproduction parameters and lamb performance. Method One hundred forty‐nine ewes were mated with four rams according to tail length. Pregnancy and pregnancy loss rates were calculated. During pregnancy, the progesterone levels (P4) of the ewes were measured. The weight and length of the 254 lambs were recorded up to 14 weeks of life. Litter size, placenta weight, sex, stillbirths, vitality, morbidity and mortality of the lambs were also documented. Results No significant differences were found for P4 and placental weight for the two mating groups (ST and LT). Although the pregnancy rate for ST was slightly lower (75.71%) than for LT (87.34%), there was only a low significant difference (p = 0.07). The sex distribution was 61 (48.80%) male and 64 (51.20%) female lambs in the ST group and 67 (51.94%) male and 62 (48.06%) female lambs in the LT group. The twinning rate was not significantly different (ST 75.20%; LT 75.97%), and no significant difference was found in the average body length and vitality of the lambs. However, LT lambs showed better weight gains that were marginally significant (p = 0.09). Conclusion This study found no evidence that reproductive parameters or lamb performance were affected by selective breeding based on tail length.

Importance Preventive efforts in pregnancy-related alloimmunization have considerably decreased the prevalence of hemolytic disease of the fetus and newborn (HDFN). International studies are therefore essential to obtain a deeper understanding of the postnatal management and outcomes of HDFN. Taken together with numerous treatment options, large practice variations among centers may exist. Objectives To assess variations in postnatal management and outcomes of HDFN among international centers and to identify opportunities to improve care. Design, Setting, and Participants In this international, retrospective, cohort study, 31 expert centers from 22 countries retrieved data on neonates with HDFN managed between January 1, 2006, and July 1, 2021. Statistical analysis was performed from July 19, 2023, to October 28, 2024. Main Outcomes and Measures Main outcomes included the frequency of exchange transfusions, administration of intravenous immunoglobulin, administration of erythropoiesis-stimulating agents, and red blood cell transfusions, as well as the association of gestational age at birth with exchange transfusion frequency and risk factors for adverse neonatal outcomes. Results The study included 1855 neonates (median gestational age at birth, 36.4 weeks [IQR, 35.0-37.3 weeks]; 1034 boys [55.7%]), of whom 1017 (54.8%) received any form of antenatal treatment. Most neonates (1447 [78.0%]) had anti-D antibodies. Exchange transfusions were performed in 436 neonates (23.5%), with proportions in exchange transfusion frequency varying from 0% to 78% among centers. Intravenous immunoglobulin was administered to 429 of 1743 neonates (24.6%), with proportions varying from 0% to 100% among centers. A higher gestational age at birth was associated with a reduction in exchange transfusion frequency in neonates with intrauterine transfusion, decreasing from approximately 38.2% (13 of 34) at 34 weeks to 16.8% (18 of 107) after 37 weeks and 0 days. A weekly increase in gestational age at birth was associated with a 43.3% decrease (95% CI, 36.1%-49.7%) in the likelihood of adverse neonatal outcomes, and neonates who received an exchange transfusion were 1.55 (95% CI, 1.10-2.18) times more likely to experience unfavorable outcomes. Conclusions and Relevance In this cohort study of neonates with HDFN managed at 31 centers in 22 countries, significant practice variations in the postnatal management of HDFN were identified, highlighting the lack of, and need for, consensus. The study suggests that there is a potential beneficial clinical association of waiting for delivery until after 37 weeks and 0 days with frequency of exchange transfusions among neonates with HDFN. The framework to implement international guidelines is provided.

Irrigation is often celebrated as a means of intensifying agricultural production and improving food and nutrition security. In the context of semi-subsistence smallholder agriculture irrigation can have a positive impact on dietary diversity through various pathways. However, studies on the linkages between irrigation and rural household nutrition show mixed results. This study argues that irrigation is not a simple agricultural input factor but is embedded in socio-technical conditions. It compares two different irrigation arrangements to understand how irrigation can contribute to transforming local food systems through different pathways. The impact of irrigation on dietary diversity and the potential impact pathways (agricultural income, production diversity and women’s empowerment) are analyzed using a propensity score matching (PSM) approach. The analysis is repeated for subsets of farmer-led and public irrigation to explore how different irrigation arrangements lead to different outcomes. The results show that both farmer-led and public irrigation have a positive impact on agricultural income and dietary diversity. The positive effect on dietary diversity was stronger in farmer-led irrigation while the income effect was stronger in public irrigation arrangement. However, the positive impact on dietary diversity appears to be dampened by a reduction in production diversity, particularly in the case of public irrigation. This study highlights that irrigation development may lead to a more diverse diet, strengthen the income pathway but weaken the production diversity pathway with the extent of this effect depending on the irrigation arrangement. Therefore, policy makers should be aware of this trade-off and seek to support irrigation that allows increased production for urban markets without compromising the dietary intake of rural households.

Interfacing metal frameworks with carbon-based materials is attractive for the bottom-up construction of nanocomposite functional materials. The stepwise layering of difunctionalized diamantanes and gold metal from physical and chemical vapor...

The mutational landscape of TP53, a tumor suppressor mutated in about half of all cancers, includes over 2,000 known missense mutations. To fully leverage TP53 mutation status for personalized medicine, a thorough understanding of the functional diversity of these mutations is essential. We conducted a deep mutational scan using saturation genome editing with CRISPR-mediated homology-directed repair to engineer 9,225 TP53 variants in cancer cells. This high-resolution approach, covering 94.5% of all cancer-associated TP53 missense mutations, precisely mapped the impact of individual mutations on tumor cell fitness, surpassing previous deep mutational scan studies in distinguishing benign from pathogenic variants. Our results revealed even subtle loss-of-function phenotypes and identified promising mutants for pharmacological reactivation. Moreover, we uncovered the roles of splicing alterations and nonsense-mediated messenger RNA decay in mutation-driven TP53 dysfunction. These findings underscore the power of saturation genome editing in advancing clinical TP53 variant interpretation for genetic counseling and personalized cancer therapy.

Infection of cells with high-risk strains of the human papillomavirus (HPV) causes cancer in various types of epithelial tissue. HPV infections are responsible for ~4.5% of all cancers worldwide. Tumorigenesis is based on the inactivation of key cellular control mechanisms by the viral proteins E6 and E7. The HPV E6 protein interacts with the cellular E3 ligase E6AP, and this complex binds to the p53 DNA-binding domain, which results in degradation of p53. Inhibition of this interaction has the potential to reactivate p53, thus preventing oncogenic transformation. Here we describe the characterization of a designed ankyrin repeat protein that binds to the same site as the HPV E6 protein, thereby displacing the E3 ligase and stabilizing p53. Interaction with the designed ankyrin repeat protein does not affect p53 DNA binding or the crucial MDM2 negative feedback loop but reactivates a p53-dependent transcriptional program in HeLa (HPV18-positive) and SiHa (HPV16-positive) cells, suggesting a potential therapeutic use.