Phaidra - University of Veterinary Medicine Vienna
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A matter of differentiation: equine enteroids as a model for the in vivo intestinal epithelium
No full textEpithelial damage due to gastrointestinal disorders frequently causes severe disease in horses. To study the underlying pathophysiological processes, we aimed to establish equine jejunum and colon enteroids (eqJE, eqCE) mimicking the in vivo epithelium. Therefore, enteroids were cultivated in four different media for differentiation and subsequently characterized histomorphologically, on mRNA and on protein level in comparison to the native epithelium of the same donor horses to identify ideal culture conditions for an in vitro model system. With increasing enterocyte differentiation, the enteroids showed a reduced growth rate as well as a predominantly spherical morphology and less budding compared to enteroids in proliferation medium. Combined or individual withdrawal of stem cell niche pathway components resulted in lower mRNA expression levels of stem cell markers and concomitant differentiation of enterocytes, goblet cells and enteroendocrine cells. For eqCE, withdrawal of Wnt alone was sufficient for the generation of differentiated enterocytes with a close resemblance to the in vivo epithelium. Combined removal of Wnt, R-spondin and Noggin and the addition of DAPT stimulated differentiation of eqJE at a similar level as the in vivo epithelium, particularly with regard to enterocytes. In summary, we successfully defined a medium composition that promotes the formation of eqJE and eqCE consisting of multiple cell types and resembling the in vivo epithelium. Our findings emphasize the importance of adapting culture conditions to the respective species and the intestinal segment. This in vitro model will be used to investigate the pathological mechanisms underlying equine gastrointestinal disorders in future studies
Integrating One Health into Systems Science
No full textOne Health Systems Science. The three subsystems of One Health (ecosystem, human and animal health) are integrated in the Systems Science concept, where objects or adaptive agents (circles) interact with a dynamic environment, and Systems Thinking can lead it intervations (Systems Design) generating a change in One Health outcomes. Real-time genomic data retrieved from the three subsystems porvide information fo Systems Thinking and Systems Design.Unlabelled Image
Annual Report 2023 / Messerli Research Institute
No full textThe Annual Report gives an overview of academic life at the Messerli Research Institute, summarising the latest news in research and teaching of the previous year. This report is available in german and english
Genome assembly of the dyeing poison frog provides insights into the dynamics of transposable element and genome-size evolution
No full textGenome size varies greatly across the tree of life and transposable elements are an important contributor to this variation. Among vertebrates, amphibians display the greatest variation in genome size, making them ideal models to explore the causes and consequences of genome size variation. However, high-quality genome assemblies for amphibians have, until recently, been rare. Here, we generate a high-quality genome assembly for the dyeing poison frog, Dendrobates tinctorius. We compare this assembly to publicly available frog genomes and find evidence for both large-scale conserved synteny and widespread rearrangements between frog lineages. Comparing conserved orthologs annotated in these genomes revealed a strong correlation between genome size and gene size. To explore the cause of gene-size variation, we quantified the location of transposable elements relative to gene features and find that the accumulation of transposable elements in introns has played an important role in the evolution of gene size in D. tinctorius, while estimates of insertion times suggest that many insertion events are recent and species-specific. Finally, we carry out population-scale mobile-element sequencing and show that the diversity and abundance of transposable elements in poison frog genomes can complicate genotyping from repetitive element sequence anchors. Our results show that transposable elements have clearly played an important role in the evolution of large genome size in D. tinctorius. Future studies are needed to fully understand the dynamics of transposable element evolution and to optimize primer or bait design for cost-effective population-level genotyping in species with large, repetitive genomes
Sex Matters-Insights from Testing Drug Efficacy in an Animal Model of Pancreatic Cancer
No full textPreclinical studies rarely test the efficacy of therapies in both sexes. The field of oncology is no exception in this regard. In a model of syngeneic, orthotopic, metastasized pancreatic ductal adenocarcinoma we evaluated the impact of sex on pathological features of this disease as well as on the efficacy and possible adverse side effects of a novel, small molecule-based therapy inhibiting KRAS:SOS1, MEK1/2 and PI3K signaling in male and female C57BL/6J mice. Male mice had less tumor infiltration of CD8-positive cells, developed bigger tumors, had more lung metastasis and a lower probability of survival compared to female mice. These more severe pathological features in male animals were accompanied by higher distress at the end of the experiment. The evaluated inhibitors BI-3406, trametinib and BKM120 showed synergistic effects in vitro. This combinatorial therapy reduced tumor weight more efficiently in male animals, although the drug concentrations were similar in the tumors of both sexes. These results underline the importance of sex-specific preclinical research and at the same time provide a solid basis for future studies with the tested compounds
Development of Highly Efficient Universal Pneumocystis Primers and Their Application in Investigating the Prevalence and Genetic Diversity of Pneumocystis in Wild Hares and Rabbits
No full textDespite its ubiquitous infectivity to mammals with strong host specificity, our current knowledge about Pneumocystis has originated from studies of merely 4% of extant mammalian species. Further studies of Pneumocystis epidemiology across a broader range of animal species require the use of assays with high sensitivity and specificity. To this end, we have developed multiple universal Pneumocystis primers targeting different genetic loci with high amplification efficiency. Application of these primers to PCR investigation of Pneumocystis in free-living hares (Lepus townsendii, n = 130) and rabbits (Oryctolagus cuniculus, n = 8) in Canada revealed a prevalence of 81% (105/130) and 25% (2/8), respectively. Genotyping analysis identified five and two variants of Pneumocystis from hares and rabbits, respectively, with significant sequence divergence between the variants from hares. Based on phylogenetic analysis using nearly full-length sequences of the mitochondrial genome, nuclear rRNA operon and dihydropteroate synthase gene for the two most common variants, Pneumocystis in hares and rabbits are more closely related to each other than either are to Pneumocystis in other mammals. Furthermore, Pneumocystis in both hares and rabbits are more closely related to Pneumocystis in primates and dogs than to Pneumocystis in rodents. The high prevalence of Pneumocystis in hares (P. sp. \u27townsendii\u27) suggests its widespread transmissibility in the natural environment, similar to P. oryctolagi in rabbits. The presence of multiple distinct Pneumocystis populations in hares contrasts with the lack of apparent intra-species heterogeneity in P. oryctolagi, implying a unique evolution history of P. sp. \u27townsendii\u27 in hares
Near chromosome-level and highly repetitive genome assembly of the snake pipefish Entelurus aequoreus (Syngnathiformes: Syngnathidae)
No full textThe snake pipefish, Entelurus aequoreus (Linnaeus, 1758), is a northern Atlantic fish inhabiting open seagrass environments that recently expanded its distribution range. Here, we present a highly contiguous, near chromosome-scale genome of E. aequoreus. The final assembly spans 1.6 Gbp in 7,391 scaffolds, with a scaffold N50 of 62.3 Mbp and L50 of 12. The 28 largest scaffolds (>21 Mbp) span 89.7% of the assembly length. A BUSCO completeness score of 94.1% and a mapping rate above 98% suggest a high assembly completeness. Repetitive elements cover 74.93% of the genome, one of the highest proportions identified in vertebrates. Our demographic modeling identified a peak in population size during the last interglacial period, suggesting the species might benefit from warmer water conditions. Our updated snake pipefish assembly is essential for future analyses of the morphological and molecular changes unique to the Syngnathidae
Traces of Canine Inflammatory Bowel Disease Reflected by Intestinal Organoids
No full textInflammatory bowel disease (IBD) is a chronic inflammatory condition that affects humans and several domestic animal species, including cats and dogs. In this study, we have analyzed duodenal organoids derived from canine IBD patients using quantitative proteomics. Our objective was to investigate whether these organoids show phenotypic traits of the disease compared with control organoids obtained from healthy donors. To this aim, IBD and control organoids were subjected to quantitative proteomics analysis via liquid chromatography-mass spectrometry. The obtained data revealed notable differences between the two groups. The IBD organoids exhibited several alterations at the levels of multiple proteins that are consistent with some known IBD alterations. The observed phenotype in the IBD organoids to some degree mirrors the corresponding intestinal condition, rendering them a compelling approach for investigating the disease and advancing drug exploration. Additionally, our study revealed similarities to some human IBD biomarkers, further emphasizing the translational and comparative value of dogs for future investigations related to the causes and treatment of IBD. Relevant proteins such as CALU, FLNA, MSN and HMGA2, which are related to intestinal diseases, were all upregulated in the IBD duodenal organoids. At the same time, other proteins such as intestinal keratins and the mucosal immunity PIGR were depleted in these IBD organoids. Based on these findings, we propose that these organoids could serve as a valuable tool for evaluating the efficacy of therapeutic interventions against canine IBD
Retrospektive Evaluierung der diagnostischen Aussagekraft der CRP-Bestimmung beim Hund
No full textThe aim of this study was to find out if the c-reactive protein (CRP) allows a differentiation between the aetiologies of illnesses. Furthermore the author intended to find out if there is a connection between CRP and shifts in the leukogram as well giving an overview about the current state of research regarding the diagnostic value of CRP. Therefore all CRP values that have been measured in 2022 in dogs at the Veterinary University of Vienna have been evaluated retrospectively. The data has been divided into the four covariable-groups leukopenia, leucocytosis, neutrophilia and leftward shift and additionally into another four etiological-groups, named inflammation, trauma, neoplasia and degeneration. The CRP values of all groups have been tested on normal distribution using the Kolmogorov-Smirnov-test and have been described by matching location and distribution parameters. The connection between the CRP concentrations and the covariable values of each group has been tested using the Pearson correlation coefficient, whereas the CRP concentrations of the different etiological-groups have been compared with the Kruskal-Wallis- test. The analyses showed that the CRP concentration does not allow to differentiate between aetiologies and that elevated CRP values moderately correlate with leukopenia and poorly correlate with neutrophilia within +/-24 hours. In addition this research revealed, that CRP concentrations enable the differentiation between patients with leftward shift and leucocytosis, as well as leftward shift and neutrophilia.Diplomarbeit - Veterinärmedizinische Universität Wien - 2024Die vorliegende Arbeit befasst sich mit der Frage, ob anhand des C-reaktiven Proteins (CRP) zwischen verschiedenen Krankheitsätiologien unterschieden werden kann und ob es einen Zusammenhang zwischen dem CRP und bestimmten Veränderungen des weißen Blutbildes gibt. Zudem möchte sie einen Überblick über den aktuellen Forschungsstand bezüglich der diagnostischen Anwendbarkeit des CRP liefern. Dazu wurden retrospektiv alle erhöhten CRP-Messungen von Hunden, die im Jahr 2022 an der Veterinärmedizinischen Universität Wien durchgeführt wurden erhoben. Diese Patienten wurden anhand veränderter Parameter des weißen Blutbildes in die vier Kovariablen-Gruppen Leukopenie, Leukozytose, Neutrophilie und Linksverschiebung, sowie anhand der Vorstellungsursache in die ätiologischen Gruppen entzündlich, traumatisch, neoplastisch und degenerativ eingeteilt. Die Werte jeder Gruppe wurden mittels Kolmogorov-Smirnov-Test auf Normalverteilung überprüft und durch passende Streuungs- und Lageparameter beschrieben. Anhand des Pearson-Korrelationskoeffizienten wurde der Zusammenhang zwischen den CRP-Konzentrationen und der Kovariable einer Gruppe überprüft und die CRP-Konzentrationen der verschiedenen ätiologischen Gruppen wurden mit einem Kruskal-Wallis-Test verglichen. Die Untersuchungen ergaben, dass anhand der CRP-Konzentration kein Rückschluss auf die Ursache einer Erkrankung getroffen werden kann und eine erhöhte CRP-Konzentration mit moderater Wahrscheinlichkeit innerhalb von +/- 24 Stunden mit einer Leukopenie und mit geringgradiger Wahrscheinlichkeit mit einer Neutrophilie einhergeht. Außerdem konnte herausgefunden werden, dass anhand der CRP-Konzentration zwischen Patienten mit Linksverschiebung und Leukozytose, sowie zwischen Patienten mit Linksverschiebung und Neutrophilie unterschieden werden kann