Phaidra - University of Veterinary Medicine Vienna
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Genomic dissection of Escherichia marmotae provides insights into diversity and pathogenic potential
No full textAnthropogenic activities enhance the interconnection of human, animal, and environmental habitats and drive the evolution and inter-niche transmission of bacteria. Clear identification of emerging bacteria and pathogen control is therefore a public health priority. In 2015, the novel Escherichia species Escherichia marmotae was assigned, but due to the lack of appropriate detection and typing technologies, the One Health impact of this species is still being unraveled. E. marmotae represents a missing link in the impact of Escherichia spp. Here, we report 25 E. marmotae identified by next-generation sequencing that were previously phenotypically characterized as Escherichia coli during national zoonosis monitoring of food-producing animals. Applying fastANI to 153?738 published Escherichia spp. genome assemblies, we identified further 124 E. marmotae, originally classified as E. coli. Phylogenomics of all 149 isolates reveals an undefined population structure that is independent of the ecological niche. We highlight the phenotypic, genomic, and plasmid diversity of E. marmotae and provide evidence for gene flow across the species. The latter is illustrated by the acquisition of antibiotic resistance plasmids and pathogenicity islands, such as the type III secretion system. Thus, our comprehensive genomic overview of an emerging potential opportunistic pathogen underlines the importance of improved detection and characterization
NUP98 oncofusions in myeloid malignancies: An update on molecular mechanisms and therapeutic opportunities
No full textAcute myeloid leukemia (AML) is an aggressive hematological malignancy with a heterogeneous molecular landscape. In the pediatric context, the NUP98 gene is a frequent target of chromosomal rearrangements that are linked to poor prognosis and unfavorable treatment outcomes in different AML subtypes. The translocations fuse NUP98 to a diverse array of partner genes, resulting in fusion proteins with novel functions. NUP98 fusion oncoproteins induce aberrant biomolecular condensation, abnormal gene expression programs, and re-wired protein interactions which ultimately cause alterations in the cell cycle and changes in cellular structures, all of which contribute to leukemia development. The extent of these effects is steered by the functional domains of the fusion partners and the influence of concomitant somatic mutations. In this review, we discuss the complex characteristics of NUP98 fusion proteins and potential novel therapeutic approaches for NUP98 fusion-driven AML
Evaluation of a Temperature/Humidity Data Logger for the Usage in Cattle Barns
No full textClimate change is a worldwide problem that is manifested in livestock farming with a decrease in animal health and welfare and economic losses due to heat stress. Therefore, a precise and continuous recording of the barn climate is essential to be able to implement actions at a certain threshold. The aim of this study was to evaluate a logger for temperature and humidity (Kestrel Drop D2) marketed for on-farm use in comparison to various other temperature/humidity data loggers under field conditions. Four different sensors were used and placed in different settings in cattle barns to correlate temperature and humidity measurements. Data were recorded for over a year in total. The data were very highly correlated. Furthermore, the area under the curve for the evaluated logger in comparison to the other ones was 0.99 to 1.0, using a temperature-humidity index cut-off of 72, often set to define heat stress. In conclusion, the evaluated logger performed equally well as the other used devices. For on-farm use, it is suitable
Survey in ruminants from Rwanda revealed high diversity and prevalence of extended-spectrum cephalosporin-resistant Enterobacterales
No full textAntimicrobial resistance (AMR) in Enterobacterales constitutes a significant threat to the health of both humans and animals and a socioeconomic problem. Enterobacterales, mainly Escherichia coli, carrying β-lactamases has become one of the main indicators to estimate the burden of AMR in animals within "One Health" approach.To assess the presence of extended-spectrum cephalosporin-resistant Enterobacterales associated with ruminants (cattle, sheep, goats) habituated in all five provinces of Rwanda and to perform in depth characterization of isolates.We screened 454 rectal swabs from 203 cows, 170 goats, and 81 sheep and selective isolation of extended-spectrum cephalosporin-resistant Enterobacterales was conducted. Isolates were identified as a members of the order Enterobacterales by MALDI-TOF MS and further characterized by susceptibility testing and by whole-genome sequencing.Out of the 454 samples, 64 extended-spectrum cephalosporin-resistant Enterobacterales were isolated from 58 animals. Isolates belonged to seven bacterial species and were identified as Escherichia coli (n = 54), Enterobacter bugandensis (n = 4), Enterobacter mori (n = 2), Klebsiella pneumoniae (n = 2), Enterobacter dykesii (n = 1), and Citrobacter freundii (n = 1). All isolates displayed an Extended-spectrum β-lactamases (ESBL) phenotype, with exception of Citrobacter freundii isolate displayed both an ESBL and AmpC phenotype. In addition, all Enterobacter isolates were identified as stably de-repressed AmpC-producers. ESBLs genes, blaCTX-M-15 was predominant. Resistance to tetracycline and tet(A) was most frequently observed among non-β-lactam resistance. Forty-eight isolates displayed multidrug-resistance phenotypes. A shiga toxin-producing E. coli and an enterotoxigenic E. coli isolate were observed. Genome comparisons revealed thirty-five E. coli sequence types (ST) (ST10, ST307 being predominate).Considering the high proximity between ruminants and humans in Rwanda, the dissemination of antimicrobial drug resistance highlights the public health threats and requires the joint and multisectoral action of human and veterinary medicine, at human-animal-environment interfaces. Therefore, it is important to establish national and global "One Health" surveillance programs of AMR to tackle the antibiotic-resistant crisis in human and veterinary medicine
Cell-autonomous IL6ST activation suppresses prostate cancer development via STAT3/ARF/p53-driven senescence and confers an immune-active tumor microenvironment
No full textProstate cancer ranks as the second most frequently diagnosed cancer in men worldwide. Recent research highlights the crucial roles IL6ST-mediated signaling pathways play in the development and progression of various cancers, particularly through hyperactivated STAT3 signaling. However, the molecular programs mediated by IL6ST/STAT3 in prostate cancer are poorly understood.To investigate the role of IL6ST signaling, we constitutively activated IL6ST signaling in the prostate epithelium of a Pten-deficient prostate cancer mouse model in vivo and examined IL6ST expression in large cohorts of prostate cancer patients. We complemented these data with in-depth transcriptomic and multiplex histopathological analyses.Genetic cell-autonomous activation of the IL6ST receptor in prostate epithelial cells triggers active STAT3 signaling and significantly reduces tumor growth in vivo. Mechanistically, genetic activation of IL6ST signaling mediates senescence via the STAT3/ARF/p53 axis and recruitment of cytotoxic T-cells, ultimately impeding tumor progression. In prostate cancer patients, high IL6ST mRNA expression levels correlate with better recurrence-free survival, increased senescence signals and a transition from an immune-cold to an immune-hot tumor.Our findings demonstrate a context-dependent role of IL6ST/STAT3 in carcinogenesis and a tumor-suppressive function in prostate cancer development by inducing senescence and immune cell attraction. We challenge the prevailing concept of blocking IL6ST/STAT3 signaling as a functional prostate cancer treatment and instead propose cell-autonomous IL6ST activation as a novel therapeutic strategy
How smart was T. rex? Testing claims of exceptional cognition in dinosaurs and the application of neuron count estimates in palaeontological research
No full textRecent years have seen increasing scientific interest in whether neuron counts can act as correlates of diverse biological phenomena. Lately, Herculano-Houzel (2023) argued that fossil endocasts and comparative neurological data from extant sauropsids allow to reconstruct telencephalic neuron counts in Mesozoic dinosaurs and pterosaurs, which might act as proxies for behaviors and life history traits in these animals. According to this analysis, large theropods such as Tyrannosaurus rex were long-lived, exceptionally intelligent animals equipped with "macaque- or baboon-like cognition", whereas sauropods and most ornithischian dinosaurs would have displayed significantly smaller brains and an ectothermic physiology. Besides challenging established views on Mesozoic dinosaur biology, these claims raise questions on whether neuron count estimates could benefit research on fossil animals in general. Here, we address these findings by revisiting Herculano-Houzel\u27s (2023) work, identifying several crucial shortcomings regarding analysis and interpretation. We present revised estimates of encephalization and telencephalic neuron counts in dinosaurs, which we derive from phylogenetically informed modeling and an amended dataset of endocranial measurements. For large-bodied theropods in particular, we recover significantly lower neuron counts than previously proposed. Furthermore, we review the suitability of neurological variables such as neuron numbers and relative brain size to predict cognitive complexity, metabolic rate and life history traits in dinosaurs, coming to the conclusion that they are flawed proxies for these biological phenomena. Instead of relying on such neurological estimates when reconstructing Mesozoic dinosaur biology, we argue that integrative studies are needed to approach this complex subject
Comparative genomics of the Natural Killer Complex in carnivores
No full textThe mammalian Natural Killer Complex (NKC) harbors genes and gene families encoding a variety of C-type lectin-like proteins expressed on various immune cells. The NKC is a complex genomic region well-characterized in mice, humans and domestic animals. The major limitations of automatic annotation of the NKC in non-model animals include short-read based sequencing, methods of assembling highly homologous and repetitive sequences, orthologues missing from reference databases and weak expression. In this situation, manual annotations of complex genomic regions are necessary.This study presents a manual annotation of the genomic structure of the NKC region in a high-quality reference genome of the domestic cat and compares it with other felid species and with representatives of other carnivore families. Reference genomes of Carnivora, irrespective of sequencing and assembly methods, were screened by BLAST to retrieve information on their killer cell lectin-like receptor (KLR) gene content. Phylogenetic analysis of in silico translated proteins of expanded subfamilies was carried out.The overall genomic structure of the NKC in Carnivora is rather conservative in terms of its C-type lectin receptor gene content. A novel KLRH-like gene subfamily (KLRL) was identified in all Carnivora and a novel KLRJ-like gene was annotated in the Mustelidae. In all six families studied, one subfamily (KLRC) expanded and experienced pseudogenization. The KLRH gene subfamily expanded in all carnivore families except the Canidae. The KLRL gene subfamily expanded in carnivore families except the Felidae and Canidae, and in the Canidae it eroded to fragments.Knowledge of the genomic structure and gene content of the NKC region is a prerequisite for accurate annotations of newly sequenced genomes, especially of endangered wildlife species. Identification of expressed genes, pseudogenes and gene fragments in the context of expanded gene families would allow the assessment of functionally important variability in particular species
A brain microbiome in salmonids at homeostasis
No full textEctotherms have peculiar relationships with microorganisms. For instance, bacteria are recovered from the blood and internal organs of healthy teleosts. However, the presence of microbial communities in the healthy teleost brain has not been proposed. Here, we report a living bacterial community in the brain of healthy salmonids with bacterial loads comparable to those of the spleen and 1000-fold lower than in the gut. Brain bacterial communities share >50% of their diversity with gut and blood bacterial communities. Using culturomics, we obtained 54 bacterial isolates from the brains of healthy trout. Comparative genomics suggests that brain bacteria may have adaptations for niche colonization and polyamine biosynthesis. In a natural system, Chinook salmon brain microbiomes shift from juveniles to reproductively mature adults. Our study redefines the physiological relationships between the brain and bacteria in teleosts. This symbiosis may endow salmonids with a direct mechanism to sense and respond to environmental microbes
Exploring pet rat care: A comprehensive survey of husbandry, health, behavior, and the associations between caretaker attitudes, attachment, and husbandry practices
No full textPet rats are still understudied in terms of animal welfare and human-animal interaction research. An extensive online survey targeting German-speaking rat caretakers was conducted (n = 978). One of the study\u27s goals was to investigate husbandry practices, health indicators, rat behaviors that suggest either good or compromised welfare, as well as elements of the human-animal relationship, including interactions between humans and animals, caretaker attitudes, and attachment. The second aim was to explore the associations between caretaker attitudes and attachment, and caretaker behavior, encompassing routine health checks, interactions between humans and animals, as well as the activities and enrichment provided to rats. In some instances, welfare issues were identified: insufficient space (evident in 10.6% of rats), provision of unhealthy snacks (14.6%). The vast majority of rats enjoyed a variety of enrichment objects, e.g., huts/houses (98.4%), nesting material (92.7%), hammocks (91.7%), and tunnels/tubes (83.7%). The average amount of space and time provided for roaming in case of no permanent roaming possibility (13.9 m(2) and 2.5 h per day) was positive in terms of welfare. About 79.0% of rats did not suffer from a disease diagnosed by a veterinarian. Repetitive behaviors, which may represent stereotypies, were uncommon (plucking out own fur and cage bar chewing occurred "never" in 99.1% and 81.5%). Indicators of good welfare (e.g., self-grooming, rearing, eye-boggling) were observed several times/day in 89.6%, 46.7%, and 11.6% respectively. Caretakers who formed strong bonds with their rats tended to express positive general attitudes (such as finding rats \u27\u27lovable\u27\u27 and \u27\u27fun\u27\u27), while showing little agreement with statements reflecting negative attitudes (like considering rats \u27\u27dirty\u27\u27). About 84.4% reported stroking their rat, 94.9% reported talking to it, and 70.9% mentioned hand-feeding their rat several times per day. Caretaker attitudes and attachment and human-animal interactions and caretaker behaviors correlated weakly but consistently (P < 0.01): respondents who felt more comfortable during positive interactions, stroked, hand-fed their rats, offered rat-friendly enrichment and performed health checks more often. In contrast, higher agreement to rats being \u27\u27dirty\u27\u27 related to less frequent health checks and less frequent positive human-animal interactions. The identified relationships between caretaker attitudes and behaviors can help design interventions to promote caretaker behavior that is beneficial for rat welfare
A Tempered Rationalism for a Tempered Yuck Factor—Using Disgust in Bioethics
No full textWhen it comes to invasive manipulation of animals on the biological level, reactions of disgust are common and often influential on people\u27s moral judgments. As a case in point, the Belgian Blue, a breed of hyper-enhanced cattle which will serve as a case study for the present article, has historically been met with revulsion. Traditionally, in bio- and animal ethics, this \u27yuck factor,\u27 has been denied any productive role in proper moral justification, since rationalism is still a dominant paradigm in those disciplines. This is not surprising since rationalism offers the fulfilment of certain expectations we have of morality, like universality, intersubjective communicability, and objectivity. Increasingly, however, the preconceptions of rationalism have been brought into question, both through empirical as well as philosophical insights. In this paper, we will explore a way in which researchers who are, accordingly, critical of rationalism, and who wish to take seriously the role disgust plays in the formation of moral judgments when it comes to biological manipulation of animals, can do so without abandoning those virtues of rationalism which make it such an appealing position. We will do so by offering what we call a \u27tempered\u27 kind of rationalism, that is, one which conceives of rationality in the terms of Mary Midgley, not as distinct from, but as a possible function of, well-ordered emotion