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Osteoarthritis is a common degenerative disease in dogs, often manifested as pain, joint swelling, and lameness. Despite the lack of scientific evidence for its treatment efficacy, transcutaneous electrical nerve stimulation (TENS) is used in dogs as a pain-relieving treatment. This randomised single-blinded cross-over study investigated the effect of TENS on gait parameters in fifteen dogs with osteoarthritis. Stance time, swing time, stride time, stride length, peak vertical force (%BW), vertical impulse (%BW*sec), and symmetry indices were obtained using a pressure-sensitive mat. TENS treatment of 80 Hz and 100 µs with an individually selected amplitude was conducted for 45 min once daily for a treatment period of seven or ten days. No significant differences were seen between TENS and placebo for any of the gait parameters. Hence, in this study, TENS did not affect gait parameters, compared to placebo. Further studies are needed to confirm the observations.

Abstract DNA topoisomerase IB (TopoIB) was thought for a long time to be a eukaryotic specific enzyme. A shorter version was then found in viruses and later on in several bacteria, but not in archaea. Here, we show that a eukaryotic-like TopoIB is present in the recently sequenced genomes of two archaea of the newly proposed phylum Thaumarchaeota. Phylogenetic analyses suggest that a TopoIB was present in the last common ancestor of Archaea and Eucarya. This finding indicates that the last common ancestor of Archaea and Eucarya may have harboured a DNA genome. Reviewer This article was reviewed by Eugene Koonin and Anthony Poole

Abstract The extraordinary morphologies of viruses infecting hyperthermophilic archaea clearly distinguish them from bacterial and eukaryotic viruses. Moreover, their genomes code for proteins that to a large extend have no related sequences in the extent databases. However, a small pool of genes is shared by overlapping subsets of these viruses, and the most conserved gene, exemplified by the ORF109 of the Acidianus Filamentous Virus 3, AFV3, is present on genomes of members of three viral familes, the Lipothrixviridae, Rudiviridae, and "Bicaudaviridae", as well as of the unclassified Sulfolobus Turreted Icosahedral Virus, STIV. We present here the crystal structure of the protein (Mr = 13.1 kD, 109 residues) encoded by the AFV3 ORF 109 in two different crystal forms at 1.5 and 1.3 Å resolution. The structure of AFV3-109 is a five stranded β-sheet with loops on one side and three helices on the other. It forms a dimer adopting the shape of a cradle that encompasses the best conserved regions of the sequence. No protein with a related fold could be identified except for the ortholog from STIV1, whose structure was deposited at the Protein Data Bank. We could clearly identify a well bound glycerol inside the cradle, contacting exclusively totally conserved residues. This interaction was confirmed in solution by fluorescence titration. Although the function of AFV3-109 cannot be deduced directly from its structure, structural homology with the STIV1 protein, and the size and charge distribution of the cavity suggested it could interact with nucleic acids. Fluorescence quenching titrations also showed that AFV3-109 interacts with dsDNA. Genomic sequence analysis revealed bacterial homologs of AFV3-109 as a part of a putative previously unidentified prophage sequences in some Firmicutes.

Abstract Background The concept of a genomic core, defined as the set of genes ubiquitous in all genomes of a monophyletic group, has become crucial in comparative and evolutionary genomics. However, it is still a matter of debate whether lateral gene transfers (LGT) may affect the components of genomic cores, preventing their use to retrace species evolution. We have recently reconstructed the phylogeny of Archaea by using two large concatenated datasets of core proteins involved in translation and transcription, respectively. The resulting trees were largely congruent, showing that informational gene components of the archaeal genomic core belonging to two distinct molecular systems contain a coherent signal for archaeal phylogeny. However, some incongruence remained between the two phylogenies. This may be due either to undetected LGT and/or to a lack of sufficient phylogenetic signal in the datasets. Results We present evidence strongly favoring of the latter hypothesis. In fact, we have updated our transcription and translation datasets with five new archaeal genomes for a total of 6384 and 2928 amino acid positions, respectively, and 25 taxa. This increase in taxonomic sampling led to the nearly complete convergence of the transcription-based and translation-based trees on a single phylogenetic pattern for archaeal evolution. In fact, only a single incongruence persisted between the two phylogenies. This concerned Methanopyrus kandleri, whose placement remained strongly biased in the transcription tree due to its above average evolutionary rates, and could not be counterbalanced due to the lack of availability of closely related and/or slower-evolving relatives. Conclusion To our knowledge, this is the first report of evidence that the phylogenetic signal harbored by components of the archaeal translation apparatus is confirmed by additional markers belonging to a second molecular system (i.e. transcription). This rules out the risk of circularity when inferring species evolution by small subunit ribosomal RNA and ribosomal protein sequences, since it has been suggested that concerted LGT may affect these markers. Our results strongly support the existence of a core of proteins that has evolved mainly through vertical inheritance in Archaea, and carries a bona fide phylogenetic signal that can be used to retrace the evolutionary history of this domain. The identification and analysis of additional molecular markers not affected by LGT should continue defining the emerging picture of a genuine phylogenetic core for the third domain of life.

Viruses modulate ecosystems by directly altering host metabolisms through auxiliary metabolic genes. However, viral genomes are not known to encode the core components of translation machinery, such as ribosomal proteins (RPs). Here, using reference genomes and global-scale viral metagenomic datasets, we identify 14 different RPs across viral genomes arising from cultivated viral isolates and metagenome-assembled viruses. Viruses tend to encode dynamic RPs, easily exchangeable between ribosomes, suggesting these proteins can replace cellular versions in host ribosomes. Functional assays confirm that the two most common virus-encoded RPs, bS21 and bL12, are incorporated into 70S ribosomes when expressed in Escherichia coli. Ecological distribution of virus-encoded RPs suggests some level of ecosystem adaptations as aquatic viruses and viruses of animal-associated bacteria are enriched for different subsets of RPs. Finally, RP genes are under purifying selection and thus likely retained an important function after being horizontally transferred into virus genomes.

Topoisomerase I (TOP1) relaxes both positive and negative supercoils by nicking DNA and after rotation of the broken DNA strand closes the nick. Here, the authors present the DNA free crystal structure of TOP1 from the hyperthermophilic archaeon Caldiarchaeum subterraneum in the open form and discuss the mechanism of how DNA enters the catalytic site of TOP1.

Abstract We have determined the lipid, protein and miRNA composition of skeletal muscle (SkM)-released extracellular vesicles (ELVs) from Ob/ob (OB) vs wild-type (WT) mice. The results showed that atrophic insulin-resistant OB-SkM released less ELVs than WT-SkM, highlighted by a RAB35 decrease and an increase in intramuscular cholesterol content. Proteomic analyses of OB-ELVs revealed a group of 37 proteins functionally connected, involved in lipid oxidation and with catalytic activities. OB-ELVs had modified contents for phosphatidylcholine (PC 34-4, PC 40-3 and PC 34-0), sphingomyelin (Sm d18:1/18:1) and ceramides (Cer d18:1/18:0) and were enriched in cholesterol, likely to alleviated intracellular accumulation. Surprisingly many ELV miRNAs had a nuclear addressing sequence, and targeted genes encoding proteins with nuclear activities. Interestingly, SkM-ELV miRNA did not target mitochondria. The most significant function targeted by the 7 miRNAs altered in OB-ELVs was lipid metabolism. In agreement, OB-ELVs induced lipid storage in recipient adipocytes and increased lipid up-take and fatty acid oxidation in recipient muscle cells. In addition, OB-ELVs altered insulin-sensitivity and induced atrophy in muscle cells, reproducing the phenotype of the releasing OB muscles. These data suggest for the first time, a cross-talk between muscle cells and adipocytes, through the SkM-ELV route, in favor of adipose tissue expansion.

The way interactions at the microscopic scale influence emerging flow properties in complex fluids at the macroscopic scale is one of the core problems in soft matter physics. This work provides experimental evidence together with a theoretical explanation for ‘Oobleck waves’, an instability arising from the coupling between the flow free surface and the non-monotonic rheological laws of shear-thickening suspensions.

The aim of the present study was to evaluate the use of a novel intraoperative cone-beam computed tomography (CBCT)-based automated registration system for frameless stereotactic brain biopsy in companion animals. An experimental cadaveric study evaluated thalamic and piriform lobe target site needle placement error in three dogs and three cats without a history of intracranial disease. Diagnostic accuracy and diagnostic yield were prospectively evaluated in twenty-four client-owned dogs and four cats with intracranial disease. Twenty-one procedures were performed post mortem (eighteen dogs and three cats), and seven biopsy procedures were performed in alive patients (six dogs and one cat). Procedural duration was evaluated in ten post mortem and four living patients. Outcome was evaluated in six dogs and one cat. In dogs, the calculated median needle placement error was 1.8 mm (range 0.71–2.84 mm) and 1.53 mm (range 1.45–1.99 mm) for piriform lobe and thalamus target sites, respectively. In cats, the calculated median needle placement error was 0.79 mm (range 0.6–1.91 mm) for the piriform lobe target site and 1.29 mm (range 0.47–2.69 mm) for the thalamic target site. The diagnostic yield was 96.4% (95% CI 0.81–0.99), the diagnostic accuracy was 94.4% (95% CI 0.72–0.99). Median total procedural duration for post mortem biopsies was 57.5 min (range 41–69 min). Median total procedural duration for intra vitam biopsies was 122.5 min (range 103–136 min). Three dogs were discharged 1 day after biopsy and one dog after 6 days. Two dogs and one cat were euthanized 24 and 48 h after biopsy. Intraoperative CBCT-based automated image registration for frameless stereotactic biopsies in companion animals is capable of providing diagnostic brain biopsy specimens independent of skull size and morphology with diagnostic yield and accuracy comparable to published values for diverse frameless and frame-based stereotaxy systems used in veterinary medicine. Duration of the procedure is not negatively affected and within the published range with other systems. Mobile intraoperative CBCT-based registration combined with neuronavigation delivers diagnostic brain biopsies in companion animals.

Microbial communities from hypersaline ponds, dominated by halophilic archaea, are considered specific of such extreme conditions. The associated viral communities have accordingly been shown to display specific features, such as similar morphologies among different sites. However, little is known about the genetic diversity of these halophilic viral communities across the Earth. Here, we studied viral communities in hypersaline ponds sampled on the coast of Senegal (8-36% of salinity) using metagenomics approach, and compared them with hypersaline viromes from Australia and Spain. The specificity of hyperhalophilic viruses could first be demonstrated at a community scale, salinity being a strong discriminating factor between communities. For the major viral group detected in all samples (Caudovirales), only a limited number of halophilic Caudovirales clades were highlighted. These clades gather viruses from different continents and display consistent genetic composition, indicating that they represent related lineages with a worldwide distribution. Non-tailed hyperhalophilic viruses display a greater rate of gene transfer and recombination, with uncharacterized genes conserved across different kind of viruses and plasmids. Thus, hypersaline viral communities around the world appear to form a genetically consistent community that are likely to harbour new genes coding for enzymes specifically adapted to these environments.

Microbial communities from hypersaline ponds, dominated by halophilic archaea, are considered specific of such extreme conditions. The associated viral communities have accordingly been shown to display specific features, such as similar morphologies among different sites. However, little is known about the genetic diversity of these halophilic viral communities across the Earth. Here, we studied viral communities in hypersaline ponds sampled on the coast of Senegal (8-36% of salinity) using metagenomics approach, and compared them with hypersaline viromes from Australia and Spain. The specificity of hyperhalophilic viruses could first be demonstrated at a community scale, salinity being a strong discriminating factor between communities. For the major viral group detected in all samples (Caudovirales), only a limited number of halophilic Caudovirales clades were highlighted. These clades gather viruses from different continents and display consistent genetic composition, indicating that they represent related lineages with a worldwide distribution. Non-tailed hyperhalophilic viruses display a greater rate of gene transfer and recombination, with uncharacterized genes conserved across different kind of viruses and plasmids. Thus, hypersaline viral communities around the world appear to form a genetically consistent community that are likely to harbour new genes coding for enzymes specifically adapted to these environments.

Abstract Background Reports of osteoblastic tumours are limited to a few case reports in veterinary medicine. Osteoblastoma-like osteosarcoma has been accepted by the World Health Organization as an intermediate form between an osteosarcoma and osteoblastoma. This type of tumour indicates an osteosarcoma, that may resemble osteoblastoma clinically, histologically, and radiologically and have the capability for metastasis. Osteoblastoma-like osteosarcoma has not been described in veterinary medicine so far. Case presentation An eight-year old cat was presented due to progressive ataxia and paraparesis of the pelvic limbs. Imaging confirmed a well-defined, extradural mass originating from the spinous process of the second thoracic vertebra (T2) leading to severe compression of the spinal cord. Decompressive cytoreduction was achieved by removal of the mass after dorsal laminectomy of T1. After recovering from an acute worsening 3.5 weeks after surgery, the cat had an improved neurological status and the dorsal compression was resolved at follow-up 8 months later. A focal contrast enhancing lesion was still evident at the base of T2 spinous process and lung metastasis was additionally suspected. Based on histopathological, radiographic, and clinical features, an “osteoblastoma-like osteosarcoma” was suspected. Conclusions To the best of our knowledge, this is the first description of this tumour in veterinary medicine. In addition, this case report highlights the difficulty in the diagnosis and definition of osseous neoplasia in cats and provides a literature review.

Objective: To objectively assess the cervical paraspinal musculature of French bulldogs (FBs) using computed tomography (CT) scan-based measurements, outline differences in other breeds published in the literature, and investigate the potential influence of its cervical paraspinal musculature on predisposed sites for intervertebral disk disease.Animals: Thirty FBs that underwent CT scans of the cervical spine from the skull to C7/T1 were enrolled. Fifteen dogs were patients suffering from intervertebral disk herniation (IVDH group), and 15 dogs underwent CT scans due to brachycephalic obstructive airway syndrome (BOAS group).Methods: At the level of each cervical intervertebral disk from C2/C3 to C7/T1, measurements were performed and statistically analyzed. On the sagittal CT scan reconstruction, the height ratio of the dorsal to ventral paraspinal musculature and the angle of the disk axis to vertebral body length were assessed. On the transverse plane, the area ratio of the dorsal and ventral paraspinal musculature and the ratio of force moments were determined at each intervertebral disk level. Finally, ratios were compared to the values of Labrador retrievers and dachshunds published by Hartmann et al. (1).Results: Comparing the two FB groups, one significant difference was detected in the mean height ratio of the dorsal to ventral paraspinal musculature at the level of C5/C6 (P = 0.0092) and C6/C7 (P = 0.0076), with IVDH FBs having the more prominent dorsal paraspinal musculature. At the level of C3/C4, a significantly less prominent dorsal paraspinal musculature in FBs than in dachshunds (P = 0.0058) and a significantly steeper disk to vertebral body angulation were observed (P = 0.0005).Conclusion: Although some incidental differences were found, most parameters did not significantly differ between the BOAS and IVDH FBs. Significant conformational differences in the cervical paraspinal musculature and disk to vertebral body length angulation were found between FBs and two other breeds (chondrodystrophic and non-chondrodystrophic). This study's findings suggest that the paraspinal musculature is an additional biomechanical influencing factor on the preferential sites of IVDH in the cervical spine and that other major factors exist in IVDH development, especially in FBs.

Background: Canine intervertebral disc disease (IVDD) represents a significant clinical problem in veterinary medicine, with similarities to the human pathology. Host-derived damage-associated molecular patterns like fibronectin fragments (FnF) that develop during tissue dysfunction may be of specific relevance to IVD pathologies by inducing an inflammatory response in resident cells.Aim: This project aimed to determine the presence and pathobiological role of FnF during IVD herniation in dogs, with a focus on inflammation.Methods: Herniated nucleus pulposus (NP) material from five dogs as well as non-herniated adjacent NP material from three dogs was collected during spinal surgery required due to acute IVD herniation. The presence of different types of FnF were determined by Western blot analysis. NP cells isolated from six herniated canine IVDs were then exposed to 30 kDa FnF. NP cell inflammation and catabolism was examined by investigating the expression of IL-1β, IL-6, IL-8, and COX-2, as well as MMP-1 and MMP-3 by qPCR (all targets) and ELISA (IL-6, PGE2).Results: Amongst multiple sized FnF (30, 35, 45, and >170kDa), N-terminal fragments at a size of ~30 kDa were most consistently expressed in all five herniated IVDs. Importantly, these fragments were exclusively present in herniated, but not in non-herniated IVDs. Exposure of canine NP cells to 500 nM 30 kDa FnF caused a significant upregulation of IL-6 (62.5 ± 79.9, p = 0.032) and IL-8 (53.0 ± 75.7, p = 0.031) on the gene level, whereas IL-6 protein analysis was inconclusive. Donor-donor variation was observed in response to FnF treatment, whereby this phenomenon was most evident for COX-2, with three donors demonstrating a significant downregulation (0.67 ± 0.03, p = 0.003) and three donors showing upregulation (6.9 ± 5.5, p = 0.21). Co-treatment with Sparstolonin B, a TRL-2/TRL-4 antagonist, showed no statistical difference to FnF treatment alone in all tested target genes.Conclusion: Given the presence of the 30 kDa FnF in canine herniated IVDs and the proinflammatory effect of 30 kDa FnF on NP cells, we concluded that the accumulation of FnF may be involved in the pathogenesis of canine IVDD. These results correspond to the findings in humans with IVDD.

Viruses can encode genes that regulate the host's translational machinery to their advantage. Here, the authors show that viruses encode ribosomal proteins that can be incorporated into the host’s ribosome and may affect translation.

Objective: To assess and objectively quantify, with CT-scan exams, differences in cervical paraspinal musculature and vertebrae angulation that might influence the different predisposed sites for intervertebral disk disease observed in chondrodystrophic and non-chondrodystrophic breeds.Sample: Retrospective evaluation and analysis of cervical spine CT-scans performed on 30 dogs presented for clinical reasons unrelated to a cervical disk problem. 15 chondrodystrophic (Dachshunds) and 15 non-chondrodystrophic dogs (Labrador Retrievers) were included.Procedures: Height measurements of dorsal and ventral paraspinal musculature were performed on sagittal CT-scan reconstructions to generate dorsal-to-ventral height ratios. Additionally, disk angulation to the floor of the vertebral canal was determined for each cervical disk. On transverse plane images the areas of the dorsal and the ventral paraspinal musculature were measured and ratios calculated. Furthermore, estimations of moments exerted on the disk were evaluated through calculation of a dorsal-to-ventral ratio of moments applied at the level of each disk.Results: Dachshunds showed a relatively more prominent dorsal paraspinal musculature than Labrador Retrievers with statistically significant higher dorsal-to-ventral height ratios at C3/C4, C4/C5, C7/T1 (p = 0.034*, p = 0,004**, p = 0.004**) and a dorsal-to-ventral area ratio at C3/C4 (p < 0.001**). Regarding the disk angle to the spinal canal floor along the cervical spine, Labrador Retrievers had a less steep conformation compared to Dachshunds with a significant difference at C2/C3 (p < 0.001**). Relation of moments calculations revealed statistically significant differences at C2/C3 (p = 0.021*).Conclusion and Clinical Relevance: Significant differences have been found in the cervical spine of chondrodystrophic and non-chondrodystrophic dogs, regarding paraspinal musculature height and area ratios along with ratio of moments and vertebrae angulation. These differences may affect the anatomical and biomechanical dorsal-to-ventral paraspinal muscle relationship and potentially influence the load on intervertebral disks, especially in the upper cervical spine. Our findings could play a role in understanding the development of intervertebral disk disease.