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- Tarek, Mohamed, et al.
(författare)
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Epidemiology, Genetic Characterization, and Pathogenesis of Avian Influenza H5N8 Viruses Circulating in Northern and Southern Parts of Egypt, 2017-2019
- 2021
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Ingår i: Animals. - : MDPI. - 2076-2615. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Simple Summary During 2020-2021, highly pathogenic avian influenza (HPAI) viruses of subtype H5N8 were spreading rapidly, and two genetically distinct lineages were detected in Europe, the Middle East, and Southeast Asia. HPAI H5N8 viruses have been circulating in Egyptian poultry flocks since 2016. In this study, 74 commercial chicken farms tested positive for HPAI H5N8 virus. Genetic characterization of the hemagglutinin (HA) and the neuraminidase (NA) of Egyptian HPAI H5N8 viruses showed a relationship with those recently isolated in Europe. Highly pathogenic avian influenza (HPAI) viruses of subtype H5N8 continue to circulate, causing huge economic losses and serious impact on poultry production worldwide. Recently, HPAIV H5N8 has been spreading rapidly, and a large number of HPAI H5N8 outbreaks have been reported in Eurasia 2020-2021. In this study, we conducted an epidemiological survey of HPAI H5N8 virus at different geographical locations in Egypt from 2017 to 2019. This was followed by genetic and pathogenic studies. Our findings highlight the wide spread of HPAI H5N8 viruses in Egypt, including in 22 governorates. The genetic analyses of the hemagglutinin (HA) and neuraminidase (NA) gene segments emphasized a phylogenetic relatedness between the Egyptian HPAI H5N8 viruses and viruses of clade 2.3.4.4b recently isolated in Europe. These findings suggest that a potential back transmission of Egyptian HPAI H5N8 virus has occurred from domestic poultry in Egypt to migratory wild birds, followed by further spread to different countries. This highlights the importance of continuous epidemiological and genetic studies of AIVs at the domestic-wild bird interface.
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| 2. |
- van Kuilenburg, André B P, et al.
(författare)
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ß-ureidopropionase deficiency : phenotype, genotype and protein structural consequences in 16 patients
- 2012
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Ingår i: Biochimica et Biophysica Acta. - : Elsevier BV. - 0006-3002 .- 1878-2434. ; 1822:7, s. 1096-108
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Tidskriftsartikel (refereegranskat)abstract
- ß-ureidopropionase is the third enzyme of the pyrimidine degradation pathway and catalyzes the conversion of N-carbamyl-ß-alanine and N-carbamyl-ß-aminoisobutyric acid to ß-alanine and ß-aminoisobutyric acid, ammonia and CO(2). To date, only five genetically confirmed patients with a complete ß-ureidopropionase deficiency have been reported. Here, we report on the clinical, biochemical and molecular findings of 11 newly identified ß-ureidopropionase deficient patients as well as the analysis of the mutations in a three-dimensional framework. Patients presented mainly with neurological abnormalities (intellectual disabilities, seizures, abnormal tonus regulation, microcephaly, and malformations on neuro-imaging) and markedly elevated levels of N-carbamyl-ß-alanine and N-carbamyl-ß-aminoisobutyric acid in urine and plasma. Analysis of UPB1, encoding ß-ureidopropionase, showed 6 novel missense mutations and one novel splice-site mutation. Heterologous expression of the 6 mutant enzymes in Escherichia coli showed that all mutations yielded mutant ß-ureidopropionase proteins with significantly decreased activity. Analysis of a homology model of human ß-ureidopropionase generated using the crystal structure of the enzyme from Drosophila melanogaster indicated that the point mutations p.G235R, p.R236W and p.S264R lead to amino acid exchanges in the active site and therefore affect substrate binding and catalysis. The mutations L13S, R326Q and T359M resulted most likely in folding defects and oligomer assembly impairment. Two mutations were identified in several unrelated ß-ureidopropionase patients, indicating that ß-ureidopropionase deficiency may be more common than anticipated.
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