IDENTIFICATION AND CORRELATION OF A NOVEL SIADENOVIRUS IN A FLOCK OF BUDGERIGARS (MELOPSITTACUS UNDULATES) INFECTED WITH SALMONELLA TYPHIMURIUM IN THE UNITED STATES.

A flock of budgerigars (Melopsittacus undulates) was purchased from a licensed breeder and quarantined at a zoologic facility within the United States in 2016. Following 82 deaths within the flock, the remaining 66 birds were depopulated because of ongoing clinical salmonellosis despite treatment. Gross necropsy was performed on all 66 birds. Histopathologic examination was performed on 10 birds identified with gross lesions and 10 birds without. Pathologic findings were most often observed in the liver, kidney, and spleen. Lesions noted in the livers and spleens were consistent with published reports of salmonellosis in psittacine species. Multisystemic changes associated with septicemia were not noted, most likely because of antibiotic intervention before euthanasia. Of the 20 budgerigars evaluated by histopathology, six had large basophilic intranuclear inclusion bodies within tubular epithelia in a portion of the kidneys. Electronic microscopy, next-generation sequencing, Sanger sequencing, and phylogenetic analyses were used to identify and categorize the identified virus as a novel siadenovirus strain BuAdV-1 USA-IA43444-2016. The strain was 99% similar to budgerigar adenovirus 1 (BuAdV-1), previously reported in Japan, and to a psittacine adenovirus 5 recently identified in a U.S. cockatiel. Salmonella typhimurium carriers were identified via polymerase chain reaction (PCR) and bacterial culture and compared with viral carriers identified via PCR. Inclusion bodies and Salmonella detection were significant in birds with gross lesions versus those without; however, there was no correlation between budgerigars positive with siadenovirus by PCR and concurrent Salmonella infection. Identifying subclinical siadenovirus strain BuAdV-1 USA-IA43444-2016 infection in this flock significantly differs from a previous report of clinical illness in five budgerigars resulting in death caused by BuAdV-1 in Japan. S. typhimurium remains a significant pathogen in budgerigars, and zoonotic concerns prompted depopulation to mitigate the public health risks of this flock.

Computational analyses of curcuminoid analogs against kinase domain of HER2.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) has an important role in cancer aggressiveness and poor prognosis. HER2 has been used as a drug target for cancers. In particular, to effectively treat HER2-positive cancer, small molecule inhibitors were developed to target HER2 kinase. Knowing that curcumin has been used as food to inhibit cancer activity, this study evaluated the efficacy of natural curcumins and curcumin analogs as HER2 inhibitors using in vitro and in silico studies. The curcumin analogs considered in this study composed of 4 groups classified by their core structure, ß-diketone, monoketone, pyrazole, and isoxazole. RESULTS: In the present study, both computational and experimental studies were performed. The specificity of curcumin analogs selected from the docked results was examined against human breast cancer cell lines. The screened curcumin compounds were then subjected to molecular dynamics simulation study. By modifying curcumin analogs, we found that protein-ligand affinity increases. The benzene ring with a hydroxyl group could enhance affinity by forming hydrophobic interactions and the hydrogen bond with the hydrophobic pocket. Hydroxyl, carbonyl or methoxy group also formed hydrogen bonds with residues in the adenine pocket and sugar pocket of HER2-TK. These modifications could suggest the new drug design for potentially effective HER2-TK inhibitors. Two outstanding compounds, bisdemethylcurcumin (AS-KTC006) and 3,5-bis((E)-3,4-dimethoxystyryl)isoxazole (AS-KTC021 ),were well oriented in the binding pocket almost in the simulation time, 30 ns. This evidence confirmed the results of cell-based assays and the docking studies. They possessed more distinguished interactions than known HER2-TK inhibitors, considering them as a promising drug in the near future. CONCLUSIONS: The series of curcumin compounds were screened using a computational molecular docking and followed by human breast cancer cell lines assay. Both AS-KTC006 and AS-KTC021 could inhibit breast cancer cell lines though inhibiting of HER2-TK. The intermolecular interactions were confirmed by molecular dynamics simulation studies. This information would explore more understanding of curcuminoid structures and HER2-TK.