Phaidra - University of Veterinary Medicine Vienna
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Platelets mirror changes in the frontal lobe antioxidant system in Alzheimer\u27s disease
No full textBlood biomarkers reflecting Alzheimer\u27s disease (AD) pathophysiology can improve diagnosis and treatment.We applied top-down proteomics to compare frontal lobe from 17 AD cases and 11 controls to blood platelets from a second independent study group of 124 AD patients, 61 with mild cognitive impairment (MCI), and 168 controls. Findings were immunologically validated.Sixty AD-associated proteoforms were identified in frontal lobe, with 26 identically represented in platelets. Validation in platelet samples confirmed elevated glutathione S-transferase omega 1 (GSTO1) levels linked to single nucleotide polymorphism (SNP) rs4925 and increased superoxide dismutase 1 (SOD1) levels in AD. Bioinformatics revealed copper chaperone for superoxide dismutase (CCS) and glutathione peroxidase 1 (GPX1) as integral partners of these antioxidant enzymes. Both were detected to be reduced in frontal lobes and platelets in AD. SOD1 and CCS are already changed in MCI.These four novel blood biomarkers, integrated with traditional AD biomarkers, may facilitate patient risk assessment and treatment, with SOD1 and CCS alterations in MCI offering early diagnostic potential.Platelets mirror several Alzheimer\u27s disease (AD)-dependent neuronal changes, valuable for blood tests. As a start, 60 AD-associated frontal lobe proteins were identified by top-down proteomics. Fifty percent of these 60 AD-affected brain proteins are represented identically in platelets. Among these, glutathione S-transferase omega 1 (GSTO1), superoxide dismutase 1 (SOD1), copper chaperone for superoxide dismutase (CCS), and glutathione peroxidase 1 (GPX1) are identically AD related in brain and platelets. SOD1 and its crucial activating partner CCS are altered in the platelets of patients with mild cognitive impairment
YAP1 is a key regulator of EWS::FLI1-dependent malignant transformation upon IGF-1-mediated reprogramming of bone mesenchymal stem cells
No full textEwing sarcoma (EwS) is an aggressive cancer of adolescents in need of effective treatment. Insulin-like growth factor (IGF)-1 is an autocrine growth factor for EwS, but only 10% of patients respond to IGF-1 receptor (IGF-1R) blockade. Although EwS is presumed to originate from mesenchymal progenitors during bone development, targeting of the EwS driver oncogene EWS::FLI1 to the mesenchymal lineage in a mouse model does not result in tumor formation but in skeletal malformations and perinatal death. We report that transient exposure to IGF-1 concentrations mimicking serum levels during puberty reprograms limb-derived mesenchymal cells of EWS::FLI1-mutant mice to stable transformation and tumorigenicity. We identify a modular mechanism of IGF-1-driven tumor promotion in the early steps of EwS pathogenesis, in which Yap1 plays a central role. Pharmacologic Yap1/Tead inhibition reverses the transformed phenotype of EWS::FLI1-expressing cells. Our data provide a rationale for combined IGF-1R and YAP/TEAD inhibition in the treatment of EwS patients
Innovative flavoring behavior in Goffin\u27s cockatoos
No full textDunking behavior can be a foraging innovation in non-human animals in which food is dipped in a medium prior to consumption.1 Five functions of this behavior have previously been suggested (soaking, cleaning, flavoring, drowning, and transporting liquid).2,3,4,5,6,7,8 Although experimental reports exist,1,5,9,10,11 most dunking observations are anecdotal,12 making it hard to infer its function. Previously, we reported innovative dunking behavior in a group of Goffin\u27s cockatoos (Cacatua goffiniana) with the apparent function of soaking dry food.13 Here, we report cockatoos dunking in soy yogurt with the likely function of flavoring their food, something thus far only observationally reported in Japanese macaques.3,14 In an experimental setup with two types of soy yogurt and water, 9 out of 18 cockatoos dragged food through yogurt, with an overall preference for blueberry-flavored yogurt over neutral yogurt, which could not be explained by color preference alone. Furthermore, the cockatoos showed an overall preference for the combination of yogurt and noodles in a separate food preference task. This combination of quantitative and qualitative results indicates that the cockatoos use yogurt to flavor their food, preferring this combination rather than the yogurt flavor alone. Considering that not all cockatoos dunk their food in yogurt, and little overlap in individuals dunking in a previous study,13 this suggests a second food preparation innovation in this species. Our results thus provide experimental evidence of innovative food flavoring behavior outside the primate lineage, which may supplement our present understanding of the emergence of rare forms of food preparation behaviors in animals
Composition of the essential oil from Salvia verticillata L. collected in Eastern Austria
No full textSalvia verticillata (Lamiaceae) is a small herb from the dry grassland in Southern Europe and Western Asia. Inflorescences had about 0.2 % essential oil, leaves 0.1 % and stems less than 0.01%. The essential oils were composed mainly of sesquiterpene hydrocarbons. On average, in all three plant parts the following compounds were identified in decreasing order: germacrene D > (E)-beta-caryophyllene > bicyclogermacrene > alpha-humulene > spathulenol > beta-bourbonene. In inflorescences, germacrene D, (E)-beta-caryophyllene and bicyclogermacrene occurred in nearly equal amounts, while in leaves germacrene D accounted often for more than 50% of the essential oil
On the origin of the P-element invasion in Drosophila simulans
No full textThe horizontal transfer (HT) of the P-element is one of the best documented cases of the HT of a transposable element. The P-element invaded natural D. melanogaster populations between 1950 and 1980 following its HT from Drosophila willistoni, a species endemic to South and Central America. Subsequently, it spread in D. simulans populations between 2006 and 2014, following a HT from D. melanogaster. The geographic region where the spread into D. simulans occurred is unclear, as both involved species are cosmopolitan. The P-element differs between these two species by a single base substitution at site 2040, where D. melanogaster carries a \u27G\u27 and D. simulans carries an \u27A\u27. It has been hypothesized that this base substitution was a necessary adaptation that enabled the spread of the P-element in D. simulans, potentially explaining the 30-50-year lag between the invasions of D. melanogaster and D. simulans. To test this hypothesis, we monitored the invasion dynamics of P-elements with both alleles in experimental populations of D. melanogaster and D. simulans. Our results indicate that the allele at site 2040 has a minimal impact on the invasion dynamics of the P-element and, therefore, was not necessary for the invasion of D. simulans. However, we found that the host species significantly influenced the invasion dynamics, with higher P-element copy numbers accumulating in D. melanogaster than in D. simulans. Finally, based on SNPs segregating in natural D. melanogaster populations, we suggest that the horizontal transfer of the P-element from D. melanogaster to D. simulans likely occurred around Tasmania
Cooperative Hedgehog/GLI and JAK/STAT signaling drives immunosuppressive tryptophan/kynurenine metabolism via synergistic induction of IDO1 in skin cancer
No full textPharmacological targeting of Hedgehog (HH)/GLI has proven effective for certain blood, brain and skin cancers including basal cell carcinoma (BCC). However, limited response rates and the development of drug resistance call for improved anti-HH therapies that take synergistic crosstalk mechanisms and immune evasion strategies into account. In previous work, we demonstrated that cooperation of HH/GLI and Interleukin 6 (IL6)/STAT3 signaling drives BCC growth. Whether synergistic HH-IL6 signaling promotes BCC via the activation of immune evasion mechanisms remained unclear.HH-IL6 regulated immunosuppressive genes such as indoleamine 2,3-dioxygenase 1 (IDO1) were identified by gene expression profiling. IDO1 expression was evaluated in human BCC and melanoma models by qPCR and Western blot analyses. The cis-regulatory region of IDO1 was interrogated for HH-IL6-regulated GLI and STAT transcription factor binding and epigenetic modifications by targeted chromatin-immunoprecipitation and bisulfite pyrosequencing. Functional analyses of the immunosuppressive effects of IDO1 involved HPLC-MS measurements of its metabolites and the assessment of T cell proliferation via flow cytometry. Bioinformatic analyses of GLI-STAT cooperation were conducted on published bulk and single-cell RNA-seq data of human BCC and melanoma patients.We identified IDO1 as a target gene of cooperative GLI-STAT activity in BCC and melanoma. GLI1 and STAT3 transcription factors synergistically enhanced IDO1 expression by jointly binding to the cis-regulatory region of IDO1 and by increasing active chromatin marks at the histone level. In human melanoma cells, inhibition of GLI1 expression prevented the induction of IDO1 expression in response to IL6/STAT3 and IFN?/STAT1 signaling. Pharmacological targeting of HH/GLI signaling reduced IDO1 expression, resulting in decreased production of the immunosuppressive metabolite kynurenine. Further, inhibition of GLI1 enhanced the efficacy of the selective IDO1 inhibitor epacadostat and rescued T cell proliferation by attenuating IDO1/kynurenine-mediated immunosuppression. Elevated expression of IDO1 correlated with active HH/GLI and JAK/STAT signaling in skin cancer patients supporting the clinical relevance of the mechanistic data presented.These results identify the immunosuppressive IDO1-kynurenine pathway as a novel pro-tumorigenic target of oncogenic GLI and STAT1/STAT3 cooperation. Our data suggest simultaneous pharmacological targeting of these signaling axes as rational combination therapy in melanoma and non-melanoma skin cancers
Alleviating isolation stress in chickens: The benefits of home pen playback and mirrors
No full textThis study investigated whether the provision of (1) a mirror or (2) video and sound playback of conspecifics in the home pen (i.e., playback) could alleviate stress in socially isolated adult domestic chickens. Thirty adult chickens participated in the study, undergoing three-minute sessions of social isolation over three consecutive days in an arena containing a tray of food treats. Each chicken was exposed to three conditions, one per day, in a semi-randomised order: (1) mirror, (2) playback, and (3) control. Video recordings of the tests were coded for stress-related behaviours, including stress behaviour (i.e., pooled stress vocalisations and escape behaviour), vigilance, feeding, and exploration. Additionally, thermal imaging was used to measure the surface temperatures of the eye and comb. Social isolation elicited mild stress responses, as evidenced by reduced surface eye and comb temperatures along with the exhibition of stress and vigilance behaviours. Both playback and mirror conditions appeared to reduce stress behaviours compared to the control, although the effect of the mirror was not statistically significant. It is possible that the playbacks simulated the presence of a group of calm conspecifics. Vigilance behaviour, however, remained unaffected across conditions. These findings suggest that playback, and to a lesser extent mirrors, may alleviate certain stress-related behaviours in socially isolated adult chickens. As individual variation was high, future research should explore the role of individual differences in stress responses, as well as the long-term effects of repeated exposure to mirrors and playback, along with other environmental variables
Vetmed : das Magazin der Veterinärmedizinischen Universität Wien und der Gesellschaft der Freunde der Veterinärmedizinischen Universität Wien 3/2025
No full textDas Universitätsmagazin berichtet über die vielfältigen Aktivitäten der Universität in Forschung, Studium und Universitätskliniken, informiert über Tiergesundheit, Tierhaltung und Tierschutz sowie Lebensmittelsicherheit und beschäftigt sich mit Fragen der Mensch-Tier-Beziehung.Schwerpunkt: SDG 15 - Leben an Lan
Editorial: Listeria monocytogenes: do we know enough about this pathogen?
No full textNo abstract available
Comparison of pre- and intraoperative findings in 35 cats and 60 dogs presenting with gastrointestinal signs
No full textIntroduction This retrospective study compared preoperative imaging and intraoperative findings in 35 cats and 60 dogs undergoing laparotomy. Objectives The objective of this study was to evaluate the agreement between preoperative imaging and intraoperative findings in cats and dogs presenting with gastrointestinal signs. Methods The medical archive of the teaching hospital was searched from 2021 to 2022 for dogs that presented with gastrointestinal signs. Only animals with preoperative imaging and laparotomy reports within 48 h were included and reviewed. The main imaging and surgical findings were extracted and classified as either \u27agreement\u27 or \u27no agreement\u27. Patients with incomplete or vague information were excluded. Additionally, the modality used for preoperative diagnosis (plain radiography, barium study, ultrasonography, computed tomography [CT], endoscopy) and the outcome (discharged, dead) were recorded. Agreement was assessed using Cohen\u27s kappa statistic. The sensitivity and pretest probabilities of preoperative imaging were calculated using the surgical report as the reference standard. Results Agreement between the main imaging and surgical findings was achieved in 84 of 95 cases (88%). No agreement was noted in 11 patients (12%), of which 9 cases were false negative, and two cases were wrongly interpreted. Modalities used for preoperative imaging were ultrasonography (52%), plain radiography (42%), barium study (3%), CT (2%), and endoscopy (1%). Cohen\u27s kappa was 0 (p = not available) for sonography and 1 (p < 0.001) when using plain radiography. Sensitivity across all modalities, sonography, and plain radiography was 90.3, 81.6, and 100%, respectively, and corresponding pretest probabilities were 97.9, 100, and 95%. Eighty-two animals were discharged, and 13 patients either died or were euthanized. Conclusion The clinical relevance of this work is providing evidence-based data on errors (no agreement) in preoperative imaging for patients with gastrointestinal disease. Radiography had significantly higher agreement with surgical findings compared to ultrasonography in dogs and cats presenting with gastrointestinal symptoms