The anti-diabetic PPARy agonist Pioglitazone inhibits cell proliferation and induces metabolic reprogramming in prostate cancer

Prostate cancer (PCa) and Type 2 diabetes (T2D) often co-occur, yet their relationship remains elusive. While some studies suggest that T2D lowers PCa risk, others report conflicting data. This study investigates the effects of peroxisome proliferator-activated receptor (PPAR) agonists Bezafibrate, Tesaglitazar, and Pioglitazone on PCa tumorigenesis. Analysis of patient datasets revealed that high PPARG expression correlates with advanced PCa and poor survival. The PPAR? agonists Pioglitazone and Tesaglitazar notably reduced cell proliferation and PPAR? protein levels in primary and metastatic PCa-derived cells. Proteomic analysis identified intrinsic differences in mTORC1 and mitochondrial fatty acid oxidation (FAO) pathways between primary and metastatic PCa cells, which were further disrupted by Tesaglitazar and Pioglitazone. Moreover, metabolomics, Seahorse Assay-based metabolic profiling, and radiotracer uptake assays revealed that Pioglitazone shifted primary PCa cells\u27 metabolism towards glycolysis and increased FAO in metastatic cells, reducing mitochondrial ATP production. Furthermore, Pioglitazone suppressed cell migration in primary and metastatic PCa cells and induced the epithelial marker E-Cadherin in primary PCa cells. In vivo, Pioglitazone reduced tumor growth in a metastatic PC3 xenograft model, increased phosho AMPK? and decreased phospho mTOR levels. In addition, diabetic PCa patients treated with PPAR agonists post-radical prostatectomy implied no biochemical recurrence over five to ten years compared to non-diabetic PCa patients. Our findings suggest that Pioglitazone reduces PCa cell proliferation and induces metabolic and epithelial changes, highlighting the potential of repurposing metabolic drugs for PCa therapy

Glycans of parasitic nematodes - from glycomes to novel diagnostic tools and vaccines

Nematodes, commonly known as roundworms, are among the most prevalent and diverse multicellular organisms on Earth, belonging to the large phylum Nematoda. In addition to free-living species, many nematodes are parasitic, infecting plants, animals, and humans. Nematodes possess a wide array of genes responsible for carbohydrate metabolism and glycosylation. The glycosylation processes in parasitic nematodes often result in unique glycan modifications that are not present in their hosts. These distinct glycans can be highly immunogenic to mammalian hosts and play significant immunoregulatory roles during infection. This mini-review article summarises the glycosylation capabilities and characteristics of parasitic nematodes based on glycomic data. It also highlights recent research advances that explore the biological significance of nematode glycans and their potential for diagnostic and vaccine applications

Development and Validation of Targeted Metabolomics Methods Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for the Quantification of 235 Plasma Metabolites

Plasma contains metabolites with diverse physicochemical properties, ranging from highly polar to highly apolar, and concentrations spanning at least nine orders of magnitude. Plasma metabolome analysis is valuable for monitoring health and evaluating medical interventions but is challenging due to the metabolome\u27s diversity and complexity. This study aims to develop and validate targeted LC-MS/MS methods for quantifying 235 mammalian metabolites from 17 compound classes in porcine plasma without prior derivatization. Utilizing reversed-phase and hydrophilic interaction liquid chromatography coupled with tandem mass spectrometry, each analyte is identified and quantified using two selected reaction monitoring (SRM) transitions. Fast polarity switching and scheduled SRM enhance the metabolome coverage and throughput, enabling the analysis of one sample in about 40 min. A simple "dilute and shoot" sample preparation protocol was employed, with samples injected at two dilution levels to align metabolite concentrations within calibration curve ranges. Validation in porcine plasma included assessments of carryover, linearity, detection and quantification limits, repeatability and recovery. The method was further applied to plasma samples from various animal species, demonstrating its applicability to human and animal studies. This study establishes two robust LC-MS/MS methods for comprehensive porcine plasma metabolome quantification, advancing large-scale targeted metabolomics in biomedical research

Imaging and outcome correlates of ctDNA methylation markers in prostate cancer: a comparative, cross-sectional [??Ga]Ga-PSMA-11 PET/CT study

To validate the clinical utility of a previously identified circulating tumor DNA methylation marker (meth-ctDNA) panel for disease detection and survival outcomes, meth-ctDNA markers were compared to PSA levels and PSMA PET/CT findings in men with different stages of prostate cancer (PCa).122 PCa patients who underwent [??Ga]Ga-PSMA-11 PET/CT and plasma sampling (03/2019-08/2021) were analyzed. cfDNA was extracted, and a panel of 8 individual meth-ctDNA markers was queried. PET scans were qualitatively and quantitatively assessed. PSA and meth-ctDNA markers were compared to PET findings, and their relative prognostic value was evaluated.PSA discriminated best between negative and tumor-indicative PET scans in all (AUC 0.77) and hormone-sensitive (hsPC) patients (0.737). In castration-resistant PCa (CRPC), the meth-ctDNA marker KLF8 performed best (AUC 0.824). CHST11 differentiated best between non- and metastatic scans (AUC 0.705) overall, KLF8 best in hsPC and CRPC (AUC 0.662, 0.85). Several meth-ctDNA markers correlated low to moderate with the tumor volume in all (5/8) and CRPC patients (6/8), while PSA levels correlated moderately to strongly with the tumor volume in all groups (all p?<?0.001). CRPC overall survival was independently associated with LDAH and PSA (p?=?0.0168, p?<?0.001).The studied meth-ctDNA markers are promising for the minimally-invasive detection and prognostication of CRPC but do not allow for clinical characterization of hsPC. Prospective studies are warranted for their use in therapy response and outcome prediction in CRPC and potential incremental value for PCa monitoring in PSA-low settings

Evaluierung des Bruker NIRS-Gerätes “MPA“ zur Analyse von ausgewählten Milchinhaltsstoffen

Diplomarbeit - Veterinärmedizinische Universität Wien - 2025In dieser Studie wurde die Eignung des auf NIRS-Technologie basierenden „Multipurpose Analysers MPA" der Firma Bruker zur Analyse ausgewählter Milchbestandteile (Fett-%, Eiweiß-% und Laktose-%) untersucht. Als Referenzmethode wurden die Ergebnisse des beim Landeskontrollverband Niederösterreich verwendeten Milkoscan FT+ (Firma FOSS, Dänemark) herangezogen. Die Evaluierung des Bruker-Gerätes erfolgte am Lehr- und Forschungsgut der Veterinärmedizinischen Universität Vetfarm, wobei routinemäßig im Rahmen der Milchleistungsprüfung gewonnene Milchproben verwendet wurden. Bei der statistischen Auswertung wurde die Korrelation nach Spearman ermittelt. Für Milchfett- und Milcheiweißgehalt (%) waren die ermittelten Korrelationen (0,81 bzw. 0,94) „stark“ und für Laktose-% (0,71) „mittelstark“ und jeweils signifikant. Für die weitere Auswertung wurde noch das Bland-Altman Verfahren gewählt. Bei Fett-% ist das 95% Konfidenzintervall recht groß und bei Laktose-% sind die Differenzen weit gestreut. Die Messergebnisse waren insgesamt vielversprechend und das Gerät kann sowohl in der Praxis, als auch auf den landwirtschaftlichen Höfen verwendet werdenDiploma thesis - University of Veterinary Medicine Vienna - 2025In this study, the suitability of the “Multipurpose Analyser MPA“ from Bruker, which is based on NIRS technology, for analysing selected milk components (fat %, protein % and lactose %) was investigated. The results of the Milkoscan FT+ (FOSS, Denmark) used by the Landeskontrollverband Niederösterreich were used as a reference method. The Bruker device was evaluated at Vetfarm of the University of Veterinary Medicine Vienna. The correlation according to Spearman was determined in the statistical analysis. The correlation for fat-%, protein-% and lactose-% was very high and significant in each case. The Bland-Altman method was selected for further analysis. For fat-% the 95% confidence interval was quite wide and for lactose-% the differences were widely scattered. Overall, the measurement results were promising and the device can be used in practice and on farms

Comparative pathogenesis of aerosol-induced colibacillosis reveals greater susceptibility in broiler chicks compared to layer chicks, with systemic clearance of bacteria but persistence in the bursa of Fabricius

Avian colibacillosis presents significant challenges to the poultry industry by adversely affecting bird health and productivity and raising global public health concerns. While numerous studies on colibacillosis in broiler and layer chickens have been reported, a comparative investigation on the disease progression following respiratory infection in these two chicken types under identical conditions is lacking. This study aimed to compare the clinical, pathological, and microbiological features in broilers and layers experimentally infected with ilux2-marked E. coli PA14/17480/5-ovary strain (ilux2-APEC). Sixty-four 2-week-old specific pathogen-free chicks (32 broilers, 32 layers) were divided into four groups (n = 16), with control and infected groups for each type. Birds were necropsied at 3, 7, 10, and 14 days post-infection (dpi). In infected groups, spleen-to-body weight ratios were significantly higher compared to their respective controls. Mean maximum clinical scores, macroscopic, and microscopic lesions were significantly higher in infected broilers than in infected layers. Infected broilers showed a higher incidence of ilux2-APEC re-isolation from respiratory tissues compared to infected layers. Additionally, ilux2-APEC was re-isolated from blood, femoral head, heart, liver, and spleen exclusively in infected broilers. Unexpectedly, bioluminescence imaging identified bacterial colonization in the bursa of Fabricius in both infected groups, persisting up to 14 dpi. Immunohistochemistry detected Escherichia coli in trachea, lung, air sac, heart, liver spleen, and bursa of Fabricius, with higher detection rates in infected broilers. These findings highlight the increased susceptibility of broilers to APEC infection, suggesting a need for targeted disease control measures and potential genetic selection for improved disease resistance in broilers

Differences in dogs\u27 and wolves\u27 human-directed greeting behaviour: facial expressions, body language, and the problem of human biases

Dogs and wolves communicate effectively with humans, yet differences in their human-directed facial expressions and the role of relationship strength in shaping these behaviours remain poorly understood. This study explored the facial expressions of human-socialized wolves and dogs when greeting a bonded or familiar human through a fence. We hypothesised that differences would arise due to the domestication process, shaped further by the strength of their relationship. Additionally considering the bidirectionality integral to greeting interactions, we explored whether humans show different facial displays toward dogs versus wolves, expecting stronger differences in less bonded human partners due to unconscious biases. There was little overall difference between wolves’ and dogs’ facial expressions. However, wolves mainly displayed attentive, forward-directed ears, whereas dogs exhibited more ear positions associated with ambivalence or submission, such as rotated and downward-pushed ears. Dogs spent more time in proximity, gazing and tail wagging towards the human than wolves while both species showed more displacement behaviours (paw lift, whining, yawn) with bonded than familiar human partners. Interestingly, humans displayed more frequent, intense, and positive facial expressions toward dogs than wolves, suggesting implicit biases in human attitudes that were only partially influenced by familiarity. These results highlight the complexity of (studying) human-animal interactions. To what extent dogs’ submissive yet human-seeking behaviour is indeed species-specific, or rather results from biased human treatment during their life, and which specific mechanisms drove the likely bidirectional influence remains to be explored

Co-evolving infectivity and expression patterns drive the diversification of endogenous retroviruses

Transposable elements are major contributors to the evolution of their hosts, but the mechanisms driving their own diversification remain poorly understood. Here, we reveal key principles governing the evolution of insect endogenous retroviruses (ERVs), a class of infectious LTR-retrotransposons that encode an Envelope protein. Through comparative analyses and experimental studies of transposon replication cycles in Drosophila, we demonstrate how two crucial ERV traits-infectivity and spatiotemporal expression-co-evolve. We find that ERVs have adapted their cis-regulatory sequences to function across all ovarian cell types. Strikingly, infectious ERV lineages display distinct expression patterns in somatic cells, from where they infect the germline, whereas derived retroelement lineages that have lost infectivity are expressed exclusively in the germline. Co-evolutionary changes in the piRNA pathway, which integrates transposon promoter and sequence information into differentially expressed piRNA clusters, highlight the functional significance of the diverse ERV expression niches. By investigating a unique ERV lineage, rover, we reconstruct the molecular events that transformed an infectious ERV into a retroelement. Overall, our study uncovers fundamental mechanisms that drive the co-evolution of ERVs and their hosts, with important implications for understanding the functional diversification of LTR sequences.Online Version of Record before inclusion in an issu

Cyclin C promotes development and progression of B-cell acute lymphoblastic leukemia by counteracting p53-mediated stress responses

Despite major therapeutic advances in the treatment of acute lymphoblastic leukemia (ALL), resistances and long-term toxicities still pose significant challenges. Cyclins and their associated cyclin-dependent kinases are one focus of cancer research when looking for targeted therapies. We discovered cyclin C to be a key factor for B-cell ALL (B-ALL) development and maintenance. While cyclin C is not essential for normal hematopoiesis, Ccnc?/? BCR::ABL1+ B-ALL cells fail to elicit leukemia in mice. RNA sequencing experiments revealed a p53 pathway deregulation in Ccnc?/? BCR::ABL1+ cells resulting in the inability of the leukemic cells to adequately respond to stress. A genome-wide CRISPR/Cas9 loss-of-function screen supplemented with additional knock-outs unveiled a dependency of human B-lymphoid cell lines on CCNC. High cyclin C levels in B-cell precursor (BCP) ALL patients were associated with poor event-free survival and increased risk of early disease recurrence after remission. Our findings highlight cyclin C as a potential therapeutic target for B-ALL, particularly to enhance cancer cell sensitivity to stress and chemotherapy

Testosterone dynamics of migratory birds during stopover

Birds migrating in the spring must balance energy with hormonal preparations in anticipation of the forthcoming breeding season. We investigated the relationships between testosterone, body condition, sociality, territoriality and fueling rates in Western Subalpine Warbler (Curruca iberiae) males during a trans-Saharan stopover. Baseline testosterone was highly variable in correspondence with the transitional nature of spring stopover. Some individuals reached breeding testosterone levels while others had undetectable levels. Testosterone varied with body condition suggesting an endocrine-energy link during migration. Simulated territory intrusions induced an increase of testosterone up to physiological maxima- a similar pattern to breeding contexts. Testosterone was negatively associated with territorial male density, suggesting a \u27dear enemy\u27 effect related to the daily variation in social stability. In repeatedly-sampled individuals, stopover duration and fueling rate were not correlated with baseline testosterone. However, as testosterone decreased, body condition increased. This suggests that stopover territoriality may reduce the reported negative effects of chronically high testosterone. Our data supports the hypothesis that hormonal preparation for breeding may already occur during stopover, and that this is largely linked to body condition. In this system, the endocrine-energy relationship is likely maintained by stopover territoriality. We conclude that male-male social contexts are modulated in similar ways during spring migration as during the breeding life history stage