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The gut microbiota has been suggested to be involved in the pathogenesis of canine atopic dermatitis (cAD). However, the gut microbiota has not been well characterized in dogs with atopic dermatitis (AD). In addition, the efficacy of fecal microbiota transplantation (FMT) in dogs with AD remains unclear. This research, therefore, aimed to characterize the gut microbiota of dogs with AD and conduct pilot evaluation of the efficacy of a single oral FMT on clinical signs and the gut microbiota of dogs with AD. For these purposes, we used 12 dogs with AD and 20 healthy dogs. The 16S rRNA analysis of the fecal microbiota revealed significant differences between 12 dogs with AD and 20 healthy dogs. Next, a single oral FMT was performed in 12 dogs with AD as a single-arm, open-label clinical trial for 56 days. A single oral FMT significantly decreased Canine Atopic Dermatitis Extent and Severity Index (CADESI)-04 scores from day 0 (median score, 16.5) to day 56 (8) and Pruritus Visual Analog Scale (PVAS) scores from days 0 (median score, 3) to day 56 (1). Furthermore, a single oral FMT changed the composition of the fecal microbiota of dogs with AD at the phylum and genus levels. The number of common amplicon sequence variants in the fecal microbiota between donor dogs and dogs with AD was positively correlated with CADESI-04 and PVAS reduction ratios 56 days after FMT. Our findings suggest that the gut microbiota plays a pivotal role in the pathogenesis of cAD, and that oral FMT could be a new therapeutic approach targeting the gut microbiota in cAD. [ABSTRACT FROM AUTHOR]

Histiocytic sarcoma (HS) is an incurable aggressive tumor, and no consensus has been made on the treatment due to its rare occurrence. Since dogs spontaneously develop the disease and several cell lines are available, they have been advocated as translational animal models. In the present study, therefore, we explored gene mutations and aberrant molecular pathways in canine HS by next generation sequencing to identify molecular targets for treatment. Whole exome sequencing and RNA-sequencing revealed gene mutations related to receptor tyrosine kinase pathways and activation of ERK1/2, PI3K-AKT, and STAT3 pathways. Analysis by quantitative PCR and immunohistochemistry revealed that fibroblast growth factor receptor 1 (FGFR1) is over-expressed. Moreover, activation of ERK and Akt signaling were confirmed in all HS cell lines, and FGFR1 inhibitors showed dose-dependent growth inhibitory effects in two of the twelve canine HS cell lines. The findings obtained in the present study indicated that ERK and Akt signaling were activated in canine HS and drugs targeting FGFR1 might be effective in part of the cases. The present study provides translational evidence that leads to establishment of novel therapeutic strategies targeting ERK and Akt signaling in HS patients. [ABSTRACT FROM AUTHOR]

Drug detection dogs play integral roles in society. However, the interplay between their behaviors and genetic characteristics underlying their performance remains uninvestigated. Herein, more than 120,000 genetic variants were evaluated in 326 German Shepherd or Labrador Retriever dogs to profile the genetic traits associated with various behavioral traits related to the successful training of drug detection dogs. Behavioral breed differences were observed in ‘friendliness to humans’ and ‘tolerance to dogs.’ A genome-wide association study within both breeds identified 11 regions potentially associated with drug detection dog characteristics as well as ‘interest in the target’ and ‘friendliness to humans,’ which are related to drug detection abilities. Among them, 63 protein-coding genes, including Atat1 and Pfn2 known to be associated with anxiety-related or exploration behavior in mice, respectively, were located surrounding the identified candidate polymorphisms. This study highlights genetic characteristics associated with behavioral traits that are important for the successful training of drug detection dogs. Thus, these findings may facilitate improved breeding and training of these dogs. [ABSTRACT FROM AUTHOR]

DNA methylation plays important functions in gene expression regulation that is involved in individual development and various diseases. DNA methylation has been well studied in human and model organisms, but only limited data exist in companion animals like dog. Using methylation-sensitive restriction enzyme-based next generation sequencing (Canine DREAM), we obtained canine DNA methylation maps of 16 somatic tissues from two dogs. In total, we evaluated 130,861 CpG sites. The majority of CpG sites were either highly methylated (> 70%, 52.5–64.6% of all CpG sites analyzed) or unmethylated (< 30%, 22.5–28.0% of all CpG sites analyzed) which are methylation patterns similar to other species. The overall methylation status of CpG sites across the 32 methylomes were remarkably similar. However, the tissue types were clearly defined by principle component analysis and hierarchical clustering analysis with DNA methylome. We found 6416 CpG sites located closely at promoter region of genes and inverse correlation between DNA methylation and gene expression of these genes. Our study provides basic dataset for DNA methylation profiles in dogs. [ABSTRACT FROM AUTHOR]

Although some viruses have been shown to encode long non-coding RNAs (lncRNAs), how they function during their infection cycles remains elusive. We previously found an unexpectedly large number of novel transcripts, including putative lncRNAs, which were expressed from the genome of the baculovirus Bombyx mori nucleopolyhedrovirus (BmNPV). To investigate the function of baculoviral antisense lncRNAs, we selected 15 BmNPV lncRNAs expressed from the baculovirus early or late promoter motif, and constructed the corresponding promoter knockout (PKO) viruses in which nucleotide substitutions were introduced at the transcription start sites of lncRNAs. We investigated the production of budded viruses (BVs) and occlusion bodies (OBs) in PKO virus-infected cultured cells and silkworm larvae. No defects in BV and OB production were observed for most of the PKO viruses, whereas KO122AS, in which an antisense lncRNA in the Bm122 locus was disrupted, produced fewer OBs than the wild-type or repair virus both in cultured cells and in silkworm larvae. Northern blot analysis revealed that loss of this antisense lncRNAs reduced the amounts of the corresponding sense mRNA. These results suggest that the lncRNA transcribed from the Bm122 locus might contribute to virus propagation by regulating viral gene expression. This is the first study to characterize the properties and functions of baculoviral lncRNAs. [ABSTRACT FROM AUTHOR]

The baculovirus ie2 gene is one of the immediate early genes, and its product is known to transactivate viral promoters. However, the roles of Bombyx mori nucleopolyhedrovirus (BmNPV) ie2 in insect larvae are poorly understood. Here we investigated the functions of BmNPV IE2 in cultured cells and in insect larvae using two mutant viruses, BmIE2D and BmIE2CS. BmIE2D lacks the IE2 C-terminal coiled-coil domain that is required for IE2 dimerization. The other mutant BmIE2CS expresses an E3 ligase activity-deficient IE2 derivative, which is degraded more slowly compared with wild-type IE2. We found that ie2 mutations had little effect on BmNPV infection in cultured cells, whereas budded virus and occlusion body production was significantly reduced in the hemolymph of B. mori larvae infected with ie2 mutants. These results indicate that both dimerization and proper degradation of BmNPV IE2 are crucial steps for efficient virus growth in B. mori larvae, but not in cultured cells. Oral infection assays also revealed that the infectivity of the occluded form of ie2 mutants was normal in B. mori larvae, which is inconsistent with the results reported from ie2 mutants of Autographa californica NPV. This suggests that loss of IE2 function causes virus-specific effects in host insects. [ABSTRACT FROM AUTHOR]