Ultra-frequent HRAS p.Q61R somatic mutation in canine acanthomatous ameloblastoma reveals pathogenic similarities with human ameloblastoma

Ameloblastoma is a locally aggressive odontogenic tumour that occurs in humans and dogs. Most ameloblastomas (AM) in humans harbour mutually-exclusive driving mutations in BRAF, HRAS, KRAS, NRAS or FGFR2 that activate MAPK signalling, and in SMO that activates Hedgehog signalling. The remarkable clinical and histological similarities between canine acanthomatous ameloblastoma (CAA) and AM suggest they may harbour similar driving mutations. In this study, aimed at characterizing the mutational status of SMO, BRAF, HRAS, KRAS, NRAS and FGFR2 in CAA, we used RNA sequencing, Sanger sequencing and restriction fragment length polymorphism assays to demonstrate that 94% of CAA (n = 16) harbour a somatic HRAS p.Q61R mutation. The similarities in MAPK-activating mutational profiles between CAA and AM implicate conserved molecular mechanisms of tumorigenesis, thus, qualifying the dog as a potentially useful model of disease. Given the relevance of RAS mutations in the pathogenesis of odontogenic tumours and other types of cancer, the results of this study are of comparative, translational, and veterinary value

Serpulina pilosicoli sp. nov., the Agent of Porcine Intestinal Spirochetosis

Phenotypic and genetic traits of porcine intestinal spirochete strain P43/6/78T (= ATCC 51139T) (T = type strain), which is pathogenic and weakly beta-hemolytic, were determined in order to confirm the taxonomic position of this organism and its relationships to previously described species of intestinal spirochetes. In BHIS broth, P43/6/78T cells had a doubling time of 1 to 2 h and grew to a maximum cell density of 2 x 109 cells per ml at 37 to 42°C. They hydrolyzed hippurate, utilized D-glucose, D-fructose, sucrose, D-trehalose, D-galactose, D-mannose, maltose, N-acetyl-D-glucosamine, D-glucosamine, pyruvate, L-fucose, D-cellobiose, and D-ribose as growth substrates, and produced acetate, butyrate, ethanol, H2, and CO2 as metabolic products. They consumed substrate amounts of oxygen and had a G+C content (24.6 mol%) similar to that of Serpulina hyodysenteriae B78T (25.9 mol%). Phenotypic traits that could be used to distinguish strain P43/6/78T from S. hyodysenteriae and Serpulina innocens included its ultrastructural appearance (each strain P43/6/78T cell had 8 or 10 periplasmic flagella, with 4 or 5 flagella inserted at each end, and the cells were thinner and shorter and had more pointed ends than S. hyodysenteriae and S. innocens cells), its faster growth rate in liquid media, its hydrolysis of hippurate, its lack of β-glucosidase activity, and its metabolism of D-ribose. DNA-DNA relative reassociation experiments in which the S1 nuclease method was used revealed that P43/6/78T was related to, but was genetically distinct from, both S. hyodysenteriae B78T (level of sequence homology, 25 to 32%) and S. innocens B256T (level of sequence homology, 24 to 25%). These and previous results indicate that intestinal spirochete strain P43/6/78T represents a distinct Serpulina species. Therefore, we propose that strain P43/6/78 should be designated as the type strain of a new species, Serpulina pilosicoli

Ocorrência e identificação de espiroquetas intestinais em suínos em granjas de porte industrial de duas regiões criatórias do Estado do Rio Grande do Sul, em relação à medicação da ração Ocurrence and identification of swine intestinal spirochetes in industrial pig herds from two raising areas in the State of Rio Grande do Ssul, Brazil, in relation to feed medication

As infecções intestinais por espiroquetas em suínos, na fase que se segue ao alojamento nos prédios de recria, são predispostas por fatores como o estresse da movimentação, mistura entre animais imunes e excretores com leitões não imunes, deficiências nas condições ambientais e troca no tipo da ração usada. Para contrabalançar esses efeitos, é uma prática rotineira a inclusão de antimicrobianos à ração, em doses de promoção de crescimento ou de controle. O presente trabalho avaliou a ocorrência da infecção por Brachyspira spp. em rebanhos suínos do Estado do Rio Grande do Sul, tentando relacionar com o tipo de programa de uso de antimicrobianos adotado. Foram examinados 393 suabes retais colhidos de 38 granjas do RS (22 usando rações medicadas e 16 com ração sem medicação). A B. hyodysenteriae e B. pilosicoli foram detectadas respectivamente em 0% e 6,25% das granjas medicadas e de 31,8% e 45,5% das granjas não medicadas. Entre os suabes examinados, a B. hyodysenteriae e B. pilosicoli estavam presentes respectivamente em 0 e 0,6% dos materiais colhidos de granjas medicadas e de 3,9% e 7,3% em granjas não medicadas. O presente trabalho suporta a opinião de diversos autores que sugeriram a influência direta da inclusão de antimicrobianos à ração em doses de promoção de crescimento ou em dose de controle e a ocorrência de diarréias espiroquetais em leitões. Entretanto, pelas características multifatoriais desse tipo de patologia, seriam necessários estudos adicionais abrangendo um número maior de variáveis entre aquelas possivelmente envolvidas no desencadeamento das diarréias, antes que fosse obtida uma conclusão definitiva.<br>Intestinal spirochaetal infections in pigs following transportation to growing facilities is predisposed by stressful factors such as contact between carriers and non-immune piglets, defficient environment and diet changes. To neutralize such effects, it is a common practice to include antimicrobials to feed in promoting or control levels. The present work assessed the occurrence of Brachyspira infection in pig herds in the State of Rio Grande do Sul, Brazil, trying to relate the infection with the feed medication program. A total of 393 rectal swabs collected from 38 farms were bacteriologically examined (22 from farms using medicated feed and 16 with non-medicated feed). B. hyodysenteriae and B. pilosicoli were isolated respectively from 0% and 6,25% in medicated herds and from 31.8% and 45.5% in non-medicated farms. B. hyodysenteriae and B. pilosicoli were isolated respectively from 0% and 0.6% swabs collected in medicated farms and from 3.9% and 7.3% swabs from non-medicated farms. The present work agrees with several authors who suggest a direct influence of inclusion of antimicrobials to feed in promotion on growth levels on spirochaetal diarrhoea in pigs. However, considering the multifactorial determination of this condition, additional studies investigating the importance of other variables would be necessary to reach a definitive conclusion about the role of medication in the determination of diarrhoea caused by pathogenic spirochetes