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Item type: Item , Iron regulatory protein 1-deficient mice exhibit hypospermatogenesis(2025) Harrer, Aileen; Ghatpande, Niraj; Grimaldini, Tiziana; Fietz, Daniela; Kumar, Vishnu; Pleuger, Christiane; Fijak, Monika; Föppl, Dankward T.; Rynio, Lennart P.; Schuppe, Hans-Christian; Pilatz, Adrian; Bartkuhn, Marek; Procida-Kowalski, Tara; Guttmann-Raviv, Noga; Bhushan, Sudhanshu; Meyron-Holtz, Esther G.; Meinhardt, AndreasImbalances in testicular iron levels are linked to compromised sperm production and male infertility. Iron regulatory proteins (IRP) 1 and 2 play crucial roles in cellular iron regulation. We investigated the role of IRP1 on spermatogenesis using Irp1-deficient mice (Irp1−/−). Histological analysis of the testis of Irp1−/− mice revealed hypospermatogenesis with a significant reduction in the number of elongated spermatids and daily sperm production compared to wild-type (WT) mice. Flow cytometry of germ cells from WT and Irp1−/− mice showed reduction in spermatocytes and round and elongated spermatids in Irp1−/− mice, which was confirmed by histological and immunofluorescence quantification. Finally, stage VIII of spermatogenesis, crucial for spermatid maturation, was less frequent in Irp1−/− testicular cross-sections. Hypospermatogenesis worsened with age despite unchanged intratesticular iron levels. Mechanistically, this was due to increased oxidative stress indicated by elevated 8-Oxoguanine (8-OxoG) levels, a DNA lesion resulting from reactive oxygen species (ROS). Furthermore, bulk RNA-seq data indicated compromised DNA damage repair and cell cycle processes, including mitosis and meiosis in Irp1−/− mice, which may explain hypospermatogenesis. Our results suggest that IRP1 deletion leads to hypospermatogenesis due to impaired cell cycle progression, decreased DNA damage repair capacity, and oxidative damage. Altogether, this study uncovers a role for IRP1, independent of traditional mechanisms of iron regulation.Item type: Item , Crypt4GH-JS: securely storing sensitive data online with client-side encryption(2025) Thelen, Fabienne; Hochmuth, Jannis; Griep, Sven; Schwab, Benedikt; Goesmann, Alexander; Förster, FrankMotivation and Results: Crypt4GH-JS is a browser-ready implementation of the Crypt4GH file encryption standard written in JavaScript. While having minimal to no impact on data upload and download throughput this library enables on-the-fly encryption of arbitrary data in web applications, regardless of whether on the client or server side. As development moves more and more toward cloud-native applications, this library represents a significant step forward for flexible data security in the context of opaque cloud storage systems. Availability and implementation: Crypt4GH-JS can be installed via Node Package Manager (https://www.npmjs.com/package/crypt4gh_js) or through its public GitHub Repository (https://github.com/fathelen/crypt4ghJS), where the source code is available. Crypt4GH-JS can be tested in the browser using our demonstration website, which can be found at: https://fathelen.github.io/crypt4ghJS/.Item type: Item , Sleep Deprivation and Negotiation(2025) Halfmann, Emma; Hüffmeier, Joachim; Faber, Nadira S.; Häusser, Jan A.In a series of five studies, we examined the effects of sleep deprivation on negotiation outcomes. In three experiments (total N = 398), sleep-deprived dyads versus dyads with regular sleep participated in (Studies 1 and 2) or observed (Study 3) an integrative negotiation. In all three studies, we found no evidence that sleep deprivation reduces the quality of agreements in terms of joint economic outcomes. A Bayesian meta-analysis across studies supported this finding. These findings contradict our theoretical prediction and also laypersons’ expectations (Study 4). However, we found first evidence for compensatory effort in sleep-deprived individuals that could account for the absence of the expected effect. We conducted qualitative interviews with 22 German elected politicians (including heads of state and federal ministers; Study 5). Their responses shed light on the nature of compensatory strategies to cope with sleep deprivation in real-life negotiations.Item type: Item , A Validation Approach for Determining Fetal Blood Groups Non-Invasively by High-Sensitive Next-Generation Sequencing(2025) Wienzek-Lischka, Sandra; Soelter, Marion; Froelich, Annika; Ernst-Schlegel, Marion; Gattenloehner, Stefan; Braeuninger, Andreas; Sachs, Ulrich J.Introduction: For pregnant women with a history of fetal and neonatal alloimmune thrombocytopenia (FNAIT) or hemolytic disease of the fetus and newborn (HDFN), prenatal intervention in subsequent pregnancies may be necessary to prevent complications for the fetus. A non-invasive prenatal diagnostic procedure (NIPD) is recommended for fetal blood group genotyping. RT-PCR is used for fetal RHD determination as a reliable screening method with high sensitivity and specificity. For other antigens with variants involving single-base substitutions, droplet digital PCR (ddPCR) and next-generation sequencing (NGS) are recommended to reduce the risk of false-negative results. Only NGS offers the possibility of determining the cell-free fetal DNA (cffDNA) fraction in maternal plasma by sequencing additional gene fragments in parallel, but no standard exists for assay validation. Material and Methods: A custom-made primer panel was designed to target the common platelet and red cell antigens involved in fetal red cell and platelet incompatibilities, as well as additional anonymous single-nucleotide polymorphism (SNP) targets for use as an internal control. Amplicon-based NGS was carried out using semiconductor sequencing. For HPA-1a (HPA*1A, ITGB3) and K (KEL*01.01, KEL) assay validation, the limit of detection (LOD) and limit of quantification (LOQ) were estimated, as were false-positive antithetic alleles, linearity, and inter-assay variation, using cell-free DNA (cfDNA) extracted from the blood samples of healthy blood donors. An additional analysis was performed using 23 diagnostic samples from 21 pregnant women. Results: Regression analysis of dilution series using HPA-1a- and K-positive cell-free plasma samples in antigen-negative donor plasma showed that recovery is definitely feasible up to an HPA*1A and KEL*01.01 allele frequency of 1%. Base calls of false-positive antithetic alleles were detected with a maximum of 0.25% using 21 healthy blood donors. The LOD was estimated to be 0.2057% (mean + 3 SD) for HPA*1A with a LOQ of 0.6298% (mean + 10 SD). For KEL*01.01, the LOD was 0.1706% (mean + 3 SD) and the LOQ was 0.5314% (mean + 10 SD). The analysis of 15 of 21 cases with diagnostic samples from pregnant women with neonatal blood available for confirmatory testing resulted in 100% concordant results. The fetal fraction of these samples was calculated with a median of 11.03% (95% CI: 8.89, 13.20). Conclusions: NGS for non-invasive fetal blood group genotyping is an accurate and reliable method. In-house validation of the used assays can be performed using healthy donors to determine the LOD, LOQ and sensitivity. The threshold for paternally inherited fetal HPA*1A and KEL*01.01 alleles could be set at 1% (i.e., 2% fetal fraction) to obtain reliable test results. Internal controls for assessing the fetal fraction are essential to avoid false-negative test results.Item type: Item , In Vitro Inhibition of Cryptosporidium parvum Infection by the Olive Oil Component Oleocanthal(2025) Ampama, M. Nguele; Hanke, Dominik; Velásquez, Zahady D.; Wäber, Nadine B.; Hermosilla, Carlos; Taubert, Anja; Mazurek, SybilleHuman cryptosporidiosis caused by the zoonotic apicomplexan parasite Cryptosporidium parvum represents a neglected and re-emerging poverty-related disease. C. parvum possesses minimalistic metabolic capacities and highly depends on its intestinal epithelial host cell for intracellular replication. Based on previous results showing that glycolysis and glutaminolysis inhibition diminished C. parvum replication in vitro, we here investigated the impact of the olive oil component oleocanthal on C. parvum infection in HCT-8 cells under physioxia (5% O2) and hyperoxia (21% O2). Oleocanthal targets a broad spectrum of regulatory molecules, amongst which mTOR represents a master regulator of glycolysis and glutaminolysis. Using a host cell pre-treatment as well as a pre- and post-infection treatment protocol, 5 µM oleocanthal reduced C. parvum infection rates between 51% and 94%. Host cellular metabolic conversion rates linked oleocanthal-induced inhibition of C. parvum infection with an impairment in glutaminolysis, representing an important metabolic pathway in intestinal cells. The principal involvement of mTOR in C. parvum inhibition was confirmed by another mTOR-inhibitor (PP242, 0.5 µM), which also reduced C. parvum infection by 70–77%. Given that oleocanthal is not a selective mTOR inhibitor, we assume that this compound drives a multi-target-based inhibition of asexual C. parvum replication, amongst which mTOR is addressed.