31 research outputs found
Clinical importance and intra-host diversity of Torque teno sus virus (TTSuV) in swine
Draft Genome Sequence of Pseudomonas carnis Strain 23-145, Causing Blue Discolorations on Rabbit Carcasses
Here, we report the genome sequence of Pseudomonas carnis strain 23-145, which was recovered from a rabbit carcass with blue discolorations. The strain harbored two trpABCDF loci involved in tryptophan biosynthesis, which is characteristic of blue-pigment-producing Pseudomonas strains
First description of Arthroderma lilyanum in a rabbit with a focal alopecic area of the forelimb
Dermatophytosis is an important zoonotic disease in pet rabbits. While common clinical signs of dermatophytosis can occur, rabbits can also be asymptomatically infected. This case report describes a rabbit from Switzerland, with a focal alopecic area on one forepaw. Dermatophyte culture of a hair and skin sample taken from the lesion revealed growth of a dermatophyte, that was identified as the recently described species Arthroderma (A.) lilyanum by sequencing of the internal transcribed spacer (ITS) and β-tubulin genes. After local treatment with a disinfectant containing octenidine dihydrochloride and phenoxyethanol twice daily for two weeks, the lesion fully healed. Although it is not clear whether the dermatophyte was responsible for the lesion or if it was an incidental finding with an asymptomatic infection, the current report shows, that the host spectrum and geographical distribution of A. lilyanum are broader than previously thought
TRAF6 Phosphorylation Prevents Its Autophagic Degradation and Re-Shapes LPS-Triggered Signaling Networks
The ubiquitin E3 ligase TNF Receptor Associated Factor 6 (TRAF6) participates in a large number of different biological processes including innate immunity, differentiation and cell survival, raising the need to specify and shape the signaling output. Here, we identify a lipopolysaccharide (LPS)-dependent increase in TRAF6 association with the kinase IKKε (inhibitor of NF-κB kinase subunit ε) and IKKε-mediated TRAF6 phosphorylation at five residues. The reconstitution of TRAF6-deficient cells, with TRAF6 mutants representing phosphorylation-defective or phospho-mimetic TRAF6 variants, showed that the phospho-mimetic TRAF6 variant was largely protected from basal ubiquitin/proteasome-mediated degradation, and also from autophagy-mediated decay in autolysosomes induced by metabolic perturbation. In addition, phosphorylation of TRAF6 and its E3 ligase function differentially shape basal and LPS-triggered signaling networks, as revealed by phosphoproteome analysis. Changes in LPS-triggered phosphorylation networks of cells that had experienced autophagy are partially dependent on TRAF6 and its phosphorylation status, suggesting an involvement of this E3 ligase in the interplay between metabolic and inflammatory circuits
Crowdsourced mapping of unexplored target space of kinase inhibitors
Despite decades of intensive search for compounds that modulate the activity of particular protein targets, a large proportion of the human kinome remains as yet undrugged. Effective approaches are therefore required to map the massive space of unexplored compound-kinase interactions for novel and potent activities. Here, we carry out a crowdsourced benchmarking of predictive algorithms for kinase inhibitor potencies across multiple kinase families tested on unpublished bioactivity data. We find the top-performing predictions are based on various models, including kernel learning, gradient boosting and deep learning, and their ensemble leads to a predictive accuracy exceeding that of single-dose kinase activity assays. We design experiments based on the model predictions and identify unexpected activities even for under-studied kinases, thereby accelerating experimental mapping efforts. The open-source prediction algorithms together with the bioactivities between 95 compounds and 295 kinases provide a resource for benchmarking prediction algorithms and for extending the druggable kinome. The IDG-DREAM Challenge carried out crowdsourced benchmarking of predictive algorithms for kinase inhibitor activities on unpublished data. This study provides a resource to compare emerging algorithms and prioritize new kinase activities to accelerate drug discovery and repurposing efforts
Screening of Swiss Pig Herds for Hepatitis E Virus: A Pilot Study
Hepatitis E virus (HEV) is an important cause of acute hepatitis in humans worldwide. In industrialised countries, most infections are caused by the zoonotic genotype 3. The main reservoir was found in pigs, with fattening pigs as the main shedders. The aim of this study was to establish a screening tool to detect HEV in pig farms. HEV-positive samples were sequenced using Sanger sequencing. First, different sample materials, including floor swabs, slurry, dust swabs and faeces were tested for HEV. Floor swabs turned out to give the best results and, in the form of sock swabs, were used for the screening of Swiss pig herds. A total of 138 pig farms were tested, with a focus on fattening pigs. Overall, 81 farms (58.8%) were HEV positive. Most sequences belonged to subtype 3h, in which they formed a specific cluster (Swiss cluster). In addition, subtype 3l and two unassigned sequences were detected. As a conclusion, sock swabs were found to be a helpful tool to screen pig herds for HEV and establish a sequence collection that may enable molecular epidemiology and support outbreak investigation and prevention
Screening of Swiss Pig Herds for Hepatitis E Virus: a pilot study
Hepatitis E virus (HEV) is an important cause of acute hepatitis in humans worldwide. In industrialised countries, most infections are caused by the zoonotic genotype 3. The main reservoir was found in pigs, with fattening pigs as the main shedders. The aim of this study was to establish a screening tool to detect HEV in pig farms. HEV-positive samples were sequenced using Sanger sequencing. First, different sample materials, including floor swabs, slurry, dust swabs and faeces were tested for HEV. Floor swabs turned out to give the best results and, in the form of sock swabs, were used for the screening of Swiss pig herds. A total of 138 pig farms were tested, with a focus on fattening pigs. Overall, 81 farms (58.8%) were HEV positive. Most sequences belonged to subtype 3h, in which they formed a specific cluster (Swiss cluster). In addition, subtype 3 l and two unassigned sequences were detected. As a conclusion, sock swabs were found to be a helpful tool to screen pig herds for HEV and establish a sequence collection that may enable molecular epidemiology and support outbreak investigation and prevention
First Report of TTSuV1 in Domestic Swiss Pigs
Serum prevalence of Torque teno sus viruses (TTSuV1 and k2; family Anelloviridae) is known to be high in the porcine population worldwide but pathogenesis and associated pathomorphological lesions remain to be elucidated. In this study, quantitative real-time PCR for detection of TTSuV1 was performed in 101 porcine samples of brain tissue, with animals showing inflammatory lesions or no histological changes. Additionally, a pathomorphological and immunohistochemical characterization of possible lesions was carried out. Selected cases were screened by TTSuV1 in situ hybridization. Furthermore, TTSuV1 quantitative real-time PCR in splenic and pulmonary tissue and in situ hybridization (ISH) in spleen, lungs, mesenteric lymph node, heart, kidney, and liver were performed in 22 animals. TTSuV1 was detected by PCR not only in spleen and lung but also in brain tissue (71.3%); however, in general, spleen and lung tissue displayed lower Ct values than the brain. Positive TTSuV1 results were frequently associated with the morphological diagnosis of non-suppurative encephalitis. Single TTSuV1-positive lymphocytes were detected by ISH in the brain but also in lungs, spleen, mesenteric lymph node and in two cases of non-suppurative myocarditis. A pathogenetic role of a TTSuV1 infection as a co-factor for non-suppurative encephalitides cannot be ruled out
First Report of TTSuV1 in Domestic Swiss Pigs
Serum prevalence of Torque teno sus viruses (TTSuV1 and k2; family Anelloviridae) is known to be high in the porcine population worldwide but pathogenesis and associated pathomorphological lesions remain to be elucidated. In this study, quantitative real-time PCR for detection of TTSuV1 was performed in 101 porcine samples of brain tissue, with animals showing inflammatory lesions or no histological changes. Additionally, a pathomorphological and immunohistochemical characterization of possible lesions was carried out. Selected cases were screened by TTSuV1 in situ hybridization. Furthermore, TTSuV1 quantitative real-time PCR in splenic and pulmonary tissue and in situ hybridization (ISH) in spleen, lungs, mesenteric lymph node, heart, kidney, and liver were performed in 22 animals. TTSuV1 was detected by PCR not only in spleen and lung but also in brain tissue (71.3%); however, in general, spleen and lung tissue displayed lower Ct values than the brain. Positive TTSuV1 results were frequently associated with the morphological diagnosis of non-suppurative encephalitis. Single TTSuV1-positive lymphocytes were detected by ISH in the brain but also in lungs, spleen, mesenteric lymph node and in two cases of non-suppurative myocarditis. A pathogenetic role of a TTSuV1 infection as a co-factor for non-suppurative encephalitides cannot be ruled out