103 results on '"Harders F"'
Search Results
2. Host genotype affects endotoxin release in excreta of broilers at slaughter age
- Author
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Marcato, F., primary, Rebel, J. M. J., additional, Kar, S. K., additional, Wouters, I. M., additional, Schokker, D., additional, Bossers, A., additional, Harders, F., additional, van Riel, J. W., additional, Wolthuis-Fillerup, M., additional, and de Jong, I. C., additional
- Published
- 2023
- Full Text
- View/download PDF
3. Host genotype affects endotoxin release in excreta of broilers at slaughter age
- Author
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IRAS OH Epidemiology Microbial Agents, IRAS – One Health Microbial, Marcato, F, Rebel, J M J, Kar, S K, Wouters, I M, Schokker, D, Bossers, A, Harders, F, van Riel, J W, Wolthuis-Fillerup, M, de Jong, I C, IRAS OH Epidemiology Microbial Agents, IRAS – One Health Microbial, Marcato, F, Rebel, J M J, Kar, S K, Wouters, I M, Schokker, D, Bossers, A, Harders, F, van Riel, J W, Wolthuis-Fillerup, M, and de Jong, I C
- Published
- 2023
4. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans
- Author
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Munnink, B.B.O. (Bas B. Oude), Sikkema, R.S. (Reina S.), Nieuwenhuijse, D.F. (David F.), Molenaar, R.J. (Robert Jan), Munger, E. (Emmanuelle), Molenkamp, R. (Richard), Van Der Spek, A. (Arco), Tolsma, P. (Paulien), Rietveld, A. (Ariene), Brouwer, M. (Miranda), Bouwmeester-Vincken, N. (Noortje), Harders, F. (Frank), Der Honing, R.H.-V. (Renate Hakze-Van), Wegdam-Blans, M.C. (Marjolijn C.), Bouwstra, R.J. (Ruth J.), Geurts van Kessel, C.H. (Corine), Eijck, A.A. (Annemiek), Velkers, F.C. (Francisca C.), Smit, L.A.M., Stegeman, A. (Arjan), Poel, W.H.M. van der, Koopmans D.V.M., M.P.G. (Marion), Munnink, B.B.O. (Bas B. Oude), Sikkema, R.S. (Reina S.), Nieuwenhuijse, D.F. (David F.), Molenaar, R.J. (Robert Jan), Munger, E. (Emmanuelle), Molenkamp, R. (Richard), Van Der Spek, A. (Arco), Tolsma, P. (Paulien), Rietveld, A. (Ariene), Brouwer, M. (Miranda), Bouwmeester-Vincken, N. (Noortje), Harders, F. (Frank), Der Honing, R.H.-V. (Renate Hakze-Van), Wegdam-Blans, M.C. (Marjolijn C.), Bouwstra, R.J. (Ruth J.), Geurts van Kessel, C.H. (Corine), Eijck, A.A. (Annemiek), Velkers, F.C. (Francisca C.), Smit, L.A.M., Stegeman, A. (Arjan), Poel, W.H.M. van der, and Koopmans D.V.M., M.P.G. (Marion)
- Abstract
Animal experiments have shown that nonhuman primates, cats, ferrets, hamsters, rabbits, and bats can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, SARS-CoV-2 RNA has been detected in felids, mink, and dogs in the field. Here, we describe an in-depth investigation using whole-genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced by humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period, several weeks before detection. Despite enhanced biosecurity, early warning surveillance, and immediate culling of animals in affected farms, transmission occurred between mink farms in three large transmission clusters with unknown modes of transmission. Of the tested mink farm residents, employees, and/or individuals with whom they had been in contact, 68% had evidence of SARS-CoV-2 infection. Individuals for which whole genomes were available were shown to have been infected with strains with an animal sequence signature, providing evidence of animal-to-human transmission of SARS-CoV-2 within mink farms.
- Published
- 2021
- Full Text
- View/download PDF
5. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans
- Author
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Oude Munnink, Bas, Sikkema, Reina, Nieuwenhuijse, David, Molenaar, RJ, Münger, Emmanuelle, Molenkamp, Richard, Spek, A, Tolsma, P, Rietveld, A, Brouwer, M, Bouwmeester-Vincken, N, Harders, F, Der Honing, RHV, Wegdam-Blans, MCA, Bouwstra, RJ, Geurts van Kessel, Corine, Baltissen - van der Eijk, Annemiek, Velkers, FC, Smit, L A M, Stegeman, A, van der Poel, WHM, Koopmans, Marion, Oude Munnink, Bas, Sikkema, Reina, Nieuwenhuijse, David, Molenaar, RJ, Münger, Emmanuelle, Molenkamp, Richard, Spek, A, Tolsma, P, Rietveld, A, Brouwer, M, Bouwmeester-Vincken, N, Harders, F, Der Honing, RHV, Wegdam-Blans, MCA, Bouwstra, RJ, Geurts van Kessel, Corine, Baltissen - van der Eijk, Annemiek, Velkers, FC, Smit, L A M, Stegeman, A, van der Poel, WHM, and Koopmans, Marion
- Abstract
Animal experiments have shown that nonhuman primates, cats, ferrets, hamsters, rabbits, and bats can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, SARS-CoV-2 RNA has been detected in felids, mink, and dogs in the field. Here, we describe an in-depth investigation using whole-genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced by humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period, several weeks before detection. Despite enhanced biosecurity, early warning surveillance, and immediate culling of animals in affected farms, transmission occurred between mink farms in three large transmission clusters with unknown modes of transmission. Of the tested mink farm residents, employees, and/or individuals with whom they had been in contact, 68% had evidence of SARS-CoV-2 infection. Individuals for which whole genomes were available were shown to have been infected with strains with an animal sequence signature, providing evidence of animal-to-human transmission of SARS-CoV-2 within mink farms.
- Published
- 2021
6. Analyse der negativen Therapieevaluationen vor geplanter selektiver interner Radiotherapie bei primärem und sekundären Lebertumoren
- Author
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Masthoff, M, additional, Schindler, P, additional, Harders, F, additional, Heindel, W, additional, Rahbar, K, additional, Köhler, M, additional, and Wildgruber, M, additional
- Published
- 2021
- Full Text
- View/download PDF
7. SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020
- Author
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Oreshkova, N., Molenaar, R.J. (Remco), Vreman, S., Harders, F., Munnink, BBO, Hakze-van Der Honing, R.W., Gerhards, N., Tolsma, P., Bouwstra, R., Sikkema, R. S., Tacken, M.G.J., de Roolj, M.M.T., Weesendorp, E., Engelsma, M.Y., Bruschke, C.J.M., Smit, L. A. M., Koopmans D.V.M., M.P.G. (Marion), Poel, W.H.M. van der, Stegeman, A., Oreshkova, N., Molenaar, R.J. (Remco), Vreman, S., Harders, F., Munnink, BBO, Hakze-van Der Honing, R.W., Gerhards, N., Tolsma, P., Bouwstra, R., Sikkema, R. S., Tacken, M.G.J., de Roolj, M.M.T., Weesendorp, E., Engelsma, M.Y., Bruschke, C.J.M., Smit, L. A. M., Koopmans D.V.M., M.P.G. (Marion), Poel, W.H.M. van der, and Stegeman, A.
- Published
- 2020
- Full Text
- View/download PDF
8. SARS-CoV-2 infection in farmed minks, the Netherlands, April and May 2020
- Author
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Oreshkova, N, Molenaar, RJ, Vreman, S, Harders, F, Oude Munnink, Bas, Hakze-van Der Honing, RW, Gerhards, N, Tolsma, P, Bouwstra, R, Sikkema, Reina, Tacken, MGJ, de Roolj, MMT, Weesendorp, E, Engelsma, MY, Bruschke, CJM, Smit, L A M, Koopmans, Marion, van der Poel, WHM, Stegeman, A, Oreshkova, N, Molenaar, RJ, Vreman, S, Harders, F, Oude Munnink, Bas, Hakze-van Der Honing, RW, Gerhards, N, Tolsma, P, Bouwstra, R, Sikkema, Reina, Tacken, MGJ, de Roolj, MMT, Weesendorp, E, Engelsma, MY, Bruschke, CJM, Smit, L A M, Koopmans, Marion, van der Poel, WHM, and Stegeman, A
- Published
- 2020
9. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans
- Author
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Oude Munnink, B.B., Sikkema, R.S., Nieuwenhuijse, D.F., Molenaar, R.J., Munger, E., Molenkamp, R., Spek, A. van der, Tolsma, P., Rietveld, A., Brouwer, M., Bouwmeester-Vincken, N., Harders, F., Hakze-van der Honing, R., Wegdam-Blans, M.C.A., Bouwstra, R.J., GeurtsvanKessel, C., Eijk, A.A. van der, Velkers, F.C., Smit, L.A.M., Stegeman, A., Koopmans, M.P.G., Poel, W.H.M. van der, Oude Munnink, B.B., Sikkema, R.S., Nieuwenhuijse, D.F., Molenaar, R.J., Munger, E., Molenkamp, R., Spek, A. van der, Tolsma, P., Rietveld, A., Brouwer, M., Bouwmeester-Vincken, N., Harders, F., Hakze-van der Honing, R., Wegdam-Blans, M.C.A., Bouwstra, R.J., GeurtsvanKessel, C., Eijk, A.A. van der, Velkers, F.C., Smit, L.A.M., Stegeman, A., Koopmans, M.P.G., and Poel, W.H.M. van der
- Abstract
Animal experiments have shown that non-human primates, cats, ferrets, hamsters, rabbits and bats can be infected by SARS-CoV-2. In addition, SARS-CoV-2 RNA has been detected in felids, mink and dogs in the field. Here, we describe an in-depth investigation using whole genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced from humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period several weeks prior to detection. Despite enhanced biosecurity, early warning surveillance and immediate culling of infected farms, transmission occurred between mink farms in three big transmission clusters with unknown modes of transmission. Sixty-eight percent (68%) of the tested mink farm residents, employees and/or contacts had evidence of SARS-CoV-2 infection. Where whole genomes were available, these persons were infected with strains with an animal sequence signature, providing evidence of animal to human transmission of SARS-CoV-2 within mink farms.
- Published
- 2020
10. Functional analysis of inter-individual transcriptome differential expression in pig longissimus muscle
- Author
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Zhao, S., Hulsegge, B., Harders, F. L., Bossers, R., Keuning, E., Hoekman, A. J.W., Hoving-Bolink, R., and te Pas, M. F.W.
- Published
- 2013
- Full Text
- View/download PDF
11. PrP genotype frequencies of the most dominant sheep breed in a country free from scrapie
- Author
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Bossers, A., Harders, F. L., and Smits, M. A.
- Published
- 1999
- Full Text
- View/download PDF
12. Prognostische Faktoren für das Gesamtüberleben bei Patienten mit fortgeschrittenem intrahepatischem cholangiozellulärem Karzinom nach Yttrium-90 Radioembolisation
- Author
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Köhler, M, additional, Harders, F, additional, Lohöfer, F, additional, Paprottka, P, additional, Schaarschmidt, B, additional, Theysson, J, additional, Hermann, K, additional, Heindel, W, additional, Schmidt, H, additional, Pascher, A, additional, Stegger, L, additional, Rahbar, K, additional, and Wildgruber, M, additional
- Published
- 2020
- Full Text
- View/download PDF
13. Effektivität der selektiven internen Radiotherapie (SIRT) bei metastasiertem Kolonkarzinom in Abhängigkeit von der Lokalisation des Primärtumors
- Author
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Schindler, P, additional, Masthoff, M, additional, Harders, F, additional, Rhabar, K, additional, Wildgruber, M, additional, and Köhler, M, additional
- Published
- 2020
- Full Text
- View/download PDF
14. Genetic relationship between poultry and wild bird viruses during the highly pathogenic avian influenza H5N6 epidemic in the Netherlands, 2017–2018
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Beerens, N., Heutink, R., Pritz-Verschuren, S., Germeraad, E.A., Bergervoet, S.A., Harders, F., Bossers, A., Koch, G., Beerens, N., Heutink, R., Pritz-Verschuren, S., Germeraad, E.A., Bergervoet, S.A., Harders, F., Bossers, A., and Koch, G.
- Abstract
In the Netherlands, three commercial poultry farms and two hobby holdings were infected with highly pathogenic avian influenza (HPAI) H5N6 virus in the winter of 2017–2018. This H5N6 virus is a reassortant of HPAI H5N8 clade 2.3.4.4 group B viruses detected in Eurasia in 2016. H5N6 viruses were also detected in several dead wild birds during the winter. However, wild bird mortality was limited compared to the caused by the H5N8 group B virus in 2016–2017. H5N6 virus was not detected in wild birds after March, but in late summer infected wild birds were found again. In this study, the complete genome sequences of poultry and wild bird viruses were determined to study their genetic relationship. Genetic analysis showed that the outbreaks in poultry were not the result of farm-to-farm transmissions, but rather resulted from separate introductions from wild birds. Wild birds infected with viruses related to the first outbreak in poultry were found at short distances from the farm, within a short time frame. However, no wild bird viruses related to outbreaks 2 and 3 were detected. The H5N6 virus isolated in summer shares a common ancestor with the virus detected in outbreak 1. This suggests long-term circulation of H5N6 virus in the local wild bird population. In addition, the pathogenicity of H5N6 virus in ducks was determined, and compared to that of H5N8 viruses detected in 2014 and 2016. A similar high pathogenicity was measured for H5N6 and H5N8 group B viruses, suggesting that biological or ecological factors in the wild bird population may have affected the mortality rates during the H5N6 epidemic. These observations suggest different infection dynamics for the H5N6 and H5N8 group B viruses in the wild bird population.
- Published
- 2019
15. Genetic relationship between poultry and wild bird viruses during the highly pathogenic avian influenza H5N6 epidemic in the Netherlands, 2017–2018
- Author
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Beerens, N., primary, Heutink, R., additional, Pritz‐Verschuren, S., additional, Germeraad, E. A., additional, Bergervoet, S. A., additional, Harders, F., additional, Bossers, A., additional, and Koch, G., additional
- Published
- 2019
- Full Text
- View/download PDF
16. A dimorphic microsatellite in the porcine H-FABP gene at chromosome 6
- Author
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Gerbens, F, Harders, F L, Groenen, M A M, Veerkamp, J H, and te Pas, M F W
- Published
- 1998
17. Gene expression profiling of mesenteric lymph nodes from sheep with natural scrapie
- Author
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Filali, H., Martín-Burriel, I., Harders, F., Varona, L., Hedman, C., Mediano, D.R., Monzón, M., Bossers, A., Badiola, J.J., and Bolea, R.
- Abstract
Background: Prion diseases are characterized by the accumulation of the pathogenic PrPSc protein, mainly in the brain and the lymphoreticular system. Although prions multiply/accumulate in the lymph nodes without any detectable pathology, transcriptional changes in this tissue may reflect biological processes that contribute to the molecular pathogenesis of prion diseases. Little is known about the molecular processes that occur in the lymphoreticular system in early and late stages of prion disease. We performed a microarray-based study to identify genes that are differentially expressed at different disease stages in the mesenteric lymph node of sheep naturally infected with scrapie. Oligo DNA microarrays were used to identify gene-expression profiles in the early/middle (preclinical) and late (clinical) stages of the disease. Results: In the clinical stage of the disease, we detected 105 genes that were differentially expressed (=2-fold change in expression). Of these, 43 were upregulated and 62 downregulated as compared with age-matched negative controls. Fewer genes (50) were differentially expressed in the preclinical stage of the disease. Gene Ontology enrichment analysis revealed that the differentially expressed genes were largely associated with the following terms: glycoprotein, extracellular region, disulfide bond, cell cycle and extracellular matrix. Moreover, some of the annotated genes could be grouped into 3 specific signaling pathways: focal adhesion, PPAR signaling and ECM-receptor interaction. We discuss the relationship between the observed gene expression profiles and PrPSc deposition and the potential involvement in the pathogenesis of scrapie of 7 specific differentially expressed genes whose expression levels were confirmed by real time-PCR. Conclusions: The present findings identify new genes that may be involved in the pathogenesis of natural scrapie infection in the lymphoreticular system, and confirm previous reports describing scrapie-induced alterations in the expression of genes involved in protein misfolding, angiogenesis and the oxidative stress response. Further studies will be necessary to determine the role of these genes in prion replication, dissemination and in the response of the organism to this disease.
- Published
- 2017
18. Gene expression profiling of mesenteric lymph nodes from sheep with natural scrapie
- Author
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Filali, H., Martín-Burriel, I., Harders, F., Varona, L., Hedman, C., Mediano, D.R., Monzón, M., Bossers, A., Badiola, J.J., and Bolea, R.
- Abstract
Background: Prion diseases are characterized by the accumulation of the pathogenic PrPSc protein, mainly in the brain and the lymphoreticular system. Although prions multiply/accumulate in the lymph nodes without any detectable pathology, transcriptional changes in this tissue may reflect biological processes that contribute to the molecular pathogenesis of prion diseases. Little is known about the molecular processes that occur in the lymphoreticular system in early and late stages of prion disease. We performed a microarray-based study to identify genes that are differentially expressed at different disease stages in the mesenteric lymph node of sheep naturally infected with scrapie. Oligo DNA microarrays were used to identify gene-expression profiles in the early/middle (preclinical) and late (clinical) stages of the disease. Results: In the clinical stage of the disease, we detected 105 genes that were differentially expressed (=2-fold change in expression). Of these, 43 were upregulated and 62 downregulated as compared with age-matched negative controls. Fewer genes (50) were differentially expressed in the preclinical stage of the disease. Gene Ontology enrichment analysis revealed that the differentially expressed genes were largely associated with the following terms: glycoprotein, extracellular region, disulfide bond, cell cycle and extracellular matrix. Moreover, some of the annotated genes could be grouped into 3 specific signaling pathways: focal adhesion, PPAR signaling and ECM-receptor interaction. We discuss the relationship between the observed gene expression profiles and PrPSc deposition and the potential involvement in the pathogenesis of scrapie of 7 specific differentially expressed genes whose expression levels were confirmed by real time-PCR. Conclusions: The present findings identify new genes that may be involved in the pathogenesis of natural scrapie infection in the lymphoreticular system, and confirm previous reports describing scrapie-induced alterations in the expression of genes involved in protein misfolding, angiogenesis and the oxidative stress response. Further studies will be necessary to determine the role of these genes in prion replication, dissemination and in the response of the organism to this disease.
- Published
- 2014
19. Phylogenetic analysis of highly pathogenic avian influenza A(H5N8) virus outbreak strains provides evidence for four separate introductions and one between-poultry farm transmission in the Netherlands, November 2014
- Author
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Bouwstra, R J, primary, Koch, G, additional, Heutink, R, additional, Harders, F, additional, van der Spek, A, additional, Elbers, A R, additional, and Bossers, A, additional
- Published
- 2015
- Full Text
- View/download PDF
20. Complete genome sequences of Incl1 Plasmids carrying extended-spectrum B-Lactamase genes
- Author
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Brouwer, M.S.M., Bossers, A., Harders, F., van Essen-Zandbergen, A., Mevius, D.J., Smith, H.E., Brouwer, M.S.M., Bossers, A., Harders, F., van Essen-Zandbergen, A., Mevius, D.J., and Smith, H.E.
- Abstract
Extended spectrum beta-lactamases (ESBLs) confer resistance to clinically relevant antibiotics. Often, the resistance genes are carried by conjugative plasmids which are responsible for dissemination. Five IncI1 plasmids carrying ESBLs from commensal and clinical Escherichia coli isolates were completely sequenced and annotated along with a non-ESBL carrying IncI1 plasmid.
- Published
- 2014
21. Medulla oblongata transcriptome changes during presymptomatic natural scrapie and their associaition with prion-related lesions.
- Author
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Filali, H., Martin-Burriel, I., Harders, F., Varona, L., Serrano, C., Acín, C., Badiola, J.J., Bossers, A., Bolea, R., Filali, H., Martin-Burriel, I., Harders, F., Varona, L., Serrano, C., Acín, C., Badiola, J.J., Bossers, A., and Bolea, R.
- Abstract
Background The pathogenesis of natural scrapie and other prion diseases is still poorly understood. Determining the variations in the transcriptome in the early phases of the disease might clarify some of the molecular mechanisms of the prion-induced pathology and allow for the development of new biomarkers for diagnosis and therapy. This study is the first to focus on the identification of genes regulated during the preclinical phases of natural scrapie in the ovine medulla oblongata (MO) and the association of these genes with prion deposition, astrocytosis and spongiosis. Results A custom microarray platform revealed that 86 significant probes had expression changes greater than 2-fold. From these probes, we identified 32 genes with known function; the highest number of regulated genes was included in the phosphoprotein-encoding group. Genes encoding extracellular marker proteins and those involved in the immune response and apoptosis were also differentially expressed. In addition, we investigated the relationship between the gene expression profiles and the appearance of the main scrapie-associated brain lesions. Quantitative Real-time PCR was used to validate the expression of some of the regulated genes, thus showing the reliability of the microarray hybridization technology. Conclusions Genes involved in protein and metal binding and oxidoreductase activity were associated with prion deposition. The expression of glial fibrillary acidic protein (GFAP) was associated with changes in the expression of genes encoding proteins with oxidoreductase and phosphatase activity, and the expression of spongiosis was related to genes encoding extracellular matrix components or transmembrane transporters. This is the first genome-wide expression study performed in naturally infected sheep with preclinical scrapie. As in previous studies, our findings confirm the close relationship between scrapie and other neurodegenerative diseases.
- Published
- 2012
22. Genetics of scrapie susceptibility and selection for resistance
- Author
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Smits, Mari, Barillet, Francis, Harders, F., Boscher, M.Y., Vellema, P., Aguerre, X., Hellinga, M., McLean, A.R., Baylis, Matthew, Elsen, Jean Michel, Station d'Amélioration Génétique des Animaux (SAGA), Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration
- Subjects
[SDV] Life Sciences [q-bio] ,GENETIQUE ANIMALE ,[SDV]Life Sciences [q-bio] ,RESISTANCE GENETIQUE ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2000
23. The effect of adipocyte and heart fatty acid-binding protein genes on intramuscular fat and backfat content in Meishan crossbred pigs
- Author
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Gerbens, F, de Koning, D J, Harders, F L, Meuwissen, T H, Janss, L L, Groenen, M A, Veerkamp, J H, Van Arendonk, J A, and te Pas, M F
- Subjects
Male ,Meat ,Swine ,Myocardium ,Chromosome Mapping ,Fatty Acid-Binding Proteins ,Myelin P2 Protein ,Neoplasm Proteins ,Quantitative Trait, Heritable ,Adipocytes ,Animals ,lipids (amino acids, peptides, and proteins) ,Female ,Carrier Proteins ,Alleles ,Microsatellite Repeats - Abstract
Effects of genetic variation in porcine adipocyte and heart fatty acid-binding protein genes, A-FABP and H-FABP, respectively, on intramuscular fat (IMF) content and backfat thickness (BFT) were examined in F2 crossbreds of Meishan and Western pigs. The involvement of each FABP gene in IMF accretion was studied to confirm previous results for Duroc pigs. The F2 crossbred pigs were genotyped for various markers including microsatellite sequences situated within both FABP genes. Linkage analysis assigned the A-FABP and H-FABP genes to marker intervals S0001-S0217 (20 cM) on SSC4 and Sw316-S0003 (16.6 cM) on SSC6, respectively, refining previous chromosomal assignments. Next, the role of both chromosome regions/genes on genetic variation in IMF content and BFT was studied by 1) screening SSC4 and SSC6 for QTL affecting both traits by performing a line-cross analysis and 2) estimation of the effect of individual A-FABP and H-FABP alleles on both traits. In the first analysis, suggestive and chromosome-wise significant evidence for a QTL affecting IMF was detected on SSC6. The H-FABP gene is a candidate gene for this effect because it resides within the large region containing this putative QTL. The second analysis showed a considerable but nonsignificant effect of H-FABP microsatellite alleles on IMF content. Suggestive evidence for a QTL affecting BFT was found on SSC6, but H-FABP was excluded as a candidate gene. In conclusion, present and previous results support involvement of H-FABP gene polymorphisms in IMF accretion independently from BFT in pigs. Therefore, implementation of these polymorphisms in marker-assisted selection to control IMF content independently from BFT may be considered. In contrast to previous findings for Duroc pigs, no evidence was found for an effect of the A-FABP gene on IMF or BFT in this population.
- Published
- 2000
24. Gene expression profiling en association with prion-related lesions in the medulla oblongata of symptomatic natural scrapie animals.
- Author
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Filali, H., Martin-Burriel, I., Harders, F., Varona, L., Lyahyai, J., Zaragoza, P., Pumarola, M., Badiola, J.J., Bossers, A., Bolea, R., Filali, H., Martin-Burriel, I., Harders, F., Varona, L., Lyahyai, J., Zaragoza, P., Pumarola, M., Badiola, J.J., Bossers, A., and Bolea, R.
- Abstract
The pathogenesis of natural scrapie and other prion diseases remains unclear. Examining transcriptome variations in infected versus control animals may highlight new genes potentially involved in some of the molecular mechanisms of prion-induced pathology. The aim of this work was to identify disease-associated alterations in the gene expression profiles of the caudal medulla oblongata (MO) in sheep presenting the symptomatic phase of natural scrapie. The gene expression patterns in the MO from 7 sheep that had been naturally infected with scrapie were compared with 6 controls using a Central Veterinary Institute (CVI) custom designed 4×44K microarray. The microarray consisted of a probe set on the previously sequenced ovine tissue library by CVI and was supplemented with all of the Ovis aries transcripts that are currently publicly available. Over 350 probe sets displayed greater than 2-fold changes in expression. We identified 148 genes from these probes, many of which encode proteins that are involved in the immune response, ion transport, cell adhesion, and transcription. Our results confirm previously published gene expression changes that were observed in murine models with induced scrapie. Moreover, we have identified new genes that exhibit differential expression in scrapie and could be involved in prion neuropathology. Finally, we have investigated the relationship between gene expression profiles and the appearance of the main scrapie-related lesions, including prion protein deposition, gliosis and spongiosis. In this context, the potential impacts of these gene expression changes in the MO on scrapie development are discussed.
- Published
- 2011
25. Myogenin and porcine lean meat growth
- Author
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te Pas, M.F.W., Galesloot, P., Harders, F., Meuwissen, T.H.E., and Soumillion, A.
- Subjects
ID-Lelystad, Instituut voor Dierhouderij en Diergezondheid ,ID Lelystad, Institute for Animal Science and Health ,Life Science - Published
- 1997
26. The effect of adipocyte and heart fatty acid-binding protein genes on intramuscular fat and backfat content in Meishan crossbred pigs.
- Author
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Gerbens, F, primary, de Koning, D J, additional, Harders, F L, additional, Meuwissen, T H, additional, Janss, L L, additional, Groenen, M A, additional, Veerkamp, J H, additional, Van Arendonk, J A, additional, and te Pas, M F, additional
- Published
- 2000
- Full Text
- View/download PDF
27. Effect of genetic variants of the heart fatty acid-binding protein gene on intramuscular fat and performance traits in pigs.
- Author
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Gerbens, F, primary, van Erp, A J, additional, Harders, F L, additional, Verburg, F J, additional, Meuwissen, T H, additional, Veerkamp, J H, additional, and te Pas, M F, additional
- Published
- 1999
- Full Text
- View/download PDF
28. Influences of myogenin genotypes on birth weight, growth rate, carcass weight, backfat thickness, and lean weight of pigs.
- Author
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te Pas, M F, primary, Soumillion, A, additional, Harders, F L, additional, Verburg, F J, additional, van den Bosch, T J, additional, Galesloot, P, additional, and Meuwissen, T H, additional
- Published
- 1999
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29. Selection for growth rate or against back fat thickness in pigs is associated with changes in growth hormone axis plasma protein concentration and mRNA level
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Pas, M. F. te, Freriksen, J. W., Bijnen, A. J. van, Gerritsen, C. L., Bosch, T. J. van den, Harders, F. H., Verburg, F. J., Visscher, A. H., and Greef, K. H. de
- Published
- 2001
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30. Influences of myogeningenotypes on birth weight, growth rate, carcass weight, backfat thickness, and lean weight of pigs
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te Pas, M.F.W., Soumillion, A., Harders, F. L., Verburg, F. J., van den Bosch, T. J., Galesloot, P., and Meuwissen, T.H.E.
- Abstract
Lean weight is related to muscle fiber number. Muscle fiber formation (myogenesis) occurs only during embryonic development when it is under the control of the MyoD gene family consisting of myogenin, MyoD1, myf-5, and myf-6. Myogeninhas a central position within the MyoDgene family because myogenin expression abrogates myoblast proliferation potential and regulates the differentiation of single nucleated myoblasts into multinucleated myofibers. Thus, myogenin genotype could be related to variation in the number of muscle fibers formed, leading to variation in muscle mass and, thus, lean weight. A polymorphism at the porcine myogeninlocus was associated with birth weight, growth rate, lean weight at 200 d, and backfat thickness. Yorkshire pigs from two commercial lines were genotyped, and crosses between heterozygous pigs and heterozygous and homozygous pigs were made. Resulting litters were genotyped, and phenotypic data were collected. Significant differences were found between the two homozygous myogeningenotypes for birth weight, growth rate, and lean weight, but not for backfat thickness. Variation at the myogenin locus explained 4% of the total phenotypic variation in birth weight, growth rate, and carcass weight, and 5.8% of the total variation in lean weight. We conclude that myogenin genotype influences porcine growth rate and muscle mass.
- Published
- 1999
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31. Effect of genetic variants of the heart fatty acid-binding proteingene on intramuscular fat and performance traits in pigs
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Gerbens, F., van Erp, A.J.M., Harders, F. L., Verburg, F. J., Meuwissen, T.H.E., Veerkamp, J. H., and te Pas, M.F.W.
- Abstract
In order to find genetic markers to improve the meat quality of pigs by breeding we studied the relationship between variation in the heart fatty acid-binding protein (H-FABP)gene (FABP3) and intramuscular fat (IMF) content. To estimate the effect of H-FABP, pigs from two Duroc populations were selectively mated in such a way that at least two genotypes were present in each litter. In total, data from 983 pigs and pedigree information from three preceding generations were analyzed. Offspring were tested for IMF content as well as backfat thickness (BFT), BW, and drip loss of the meat (DRIP). All pigs were assigned to H-FABP RFLP genotype classes either by the assessed genotype (75%) or based on a probability score determined according to genotypic information of their relatives (25%). Contrasts were detected between homozygous H-FABP RFLP genotype classes for IMF content (.4%, P< .05), BFT (.6 mm, P< .01), and BW (2.4 kg, P< .10). No significant contrasts were detected for DRIP. Results for IMF content, BFT, and BW were confirmed when only genotyped animals were analyzed. Variation in BFT partially explained the effect on IMF content. Although other closely linked genes on porcine chromosome 6 might be responsible for the observed effect, interference of the halothane gene was excluded because all parental animals were noncarriers. In conclusion, H-FABP RFLP can be used as markers to select for increased IMF content and growth in breeding programs.
- Published
- 1999
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32. Development of a whole genome sequencing method for Hepatitis E Virus
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Hakze - van der Honing, R. W., Harders, F, and van der Poel, W.H.M.
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Hepatitis E Virus ,viruses ,Whole genome sequencing ,virus diseases ,digestive system diseases ,3. Good health - Abstract
Hepatitis E virus (HEV) genotype 3 is a zoonotic virus. HEV has a relatively high genetic diversity and its classification can best be done by whole genome sequencing. So far, to obtain the virus complete sequence a high concentration of HEV is needed. Our aim is to develop a sample processing protocol for recovery of enough RNA from HEV positive target samples of different origin and concentrations.
33. Development of a whole genome sequencing method for Hepatitis E Virus
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Hakze - van der Honing, R. W., Harders, F, and van der Poel, W.H.M.
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Hepatitis E Virus ,viruses ,Whole genome sequencing ,virus diseases ,digestive system diseases ,3. Good health - Abstract
Hepatitis E virus (HEV) genotype 3 is a zoonotic virus. HEV has a relatively high genetic diversity and its classification can best be done by whole genome sequencing. So far, to obtain the virus complete sequence a high concentration of HEV is needed. Our aim is to develop a sample processing protocol for recovery of enough RNA from HEV positive target samples of different origin and concentrations.
34. Medulla oblongata transcriptome changes during presymptomatic natural scrapie and their association with prion-related lesions
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Filali Hicham, Martin-Burriel Inmaculada, Harders Frank, Varona Luis, Serrano Carmen, Acín Cristina, Badiola Juan J, Bossers Alex, and Bolea Rosa
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Natural scrapie ,Preclinical sheep ,Microarray ,Genetic expression ,Real time PCR ,Prion ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background The pathogenesis of natural scrapie and other prion diseases is still poorly understood. Determining the variations in the transcriptome in the early phases of the disease might clarify some of the molecular mechanisms of the prion-induced pathology and allow for the development of new biomarkers for diagnosis and therapy. This study is the first to focus on the identification of genes regulated during the preclinical phases of natural scrapie in the ovine medulla oblongata (MO) and the association of these genes with prion deposition, astrocytosis and spongiosis. Results A custom microarray platform revealed that 86 significant probes had expression changes greater than 2-fold. From these probes, we identified 32 genes with known function; the highest number of regulated genes was included in the phosphoprotein-encoding group. Genes encoding extracellular marker proteins and those involved in the immune response and apoptosis were also differentially expressed. In addition, we investigated the relationship between the gene expression profiles and the appearance of the main scrapie-associated brain lesions. Quantitative Real-time PCR was used to validate the expression of some of the regulated genes, thus showing the reliability of the microarray hybridization technology. Conclusions Genes involved in protein and metal binding and oxidoreductase activity were associated with prion deposition. The expression of glial fibrillary acidic protein (GFAP) was associated with changes in the expression of genes encoding proteins with oxidoreductase and phosphatase activity, and the expression of spongiosis was related to genes encoding extracellular matrix components or transmembrane transporters. This is the first genome-wide expression study performed in naturally infected sheep with preclinical scrapie. As in previous studies, our findings confirm the close relationship between scrapie and other neurodegenerative diseases.
- Published
- 2012
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35. Transmission of Brucella canis in a canine kennel following introduction of an infected dog.
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Graham H, van der Most M, Kampfraath AA, Visser V, Dinkla A, Harders F, Ruuls R, van Essen-Zandbergen A, van den Esker MH, van der Heide R, van Keulen L, and Koets A
- Subjects
- Dogs, Animals, Male, Netherlands epidemiology, Whole Genome Sequencing, Antibodies, Bacterial blood, Brucella canis isolation & purification, Brucella canis genetics, Dog Diseases microbiology, Dog Diseases transmission, Dog Diseases epidemiology, Brucellosis veterinary, Brucellosis transmission, Brucellosis epidemiology, Brucellosis microbiology, Disease Outbreaks veterinary
- Abstract
Brucella canis is a zoonotic pathogen and the main causative agent of canine brucellosis. In the Netherlands, B. canis had previously only been detected in individual cases of imported dogs. However, an outbreak of B. canis occurred for the first time in a cohort of autochthonous dogs in a breeding kennel in 2019. The outbreak began with a positive serological test result of an imported intact male dog showing clinical symptoms of brucellosis. Consequently, urine and blood samples were collected and tested positive for B. canis by culture, matrix-assisted laser desorption/ionization - time of flight mass spectrometry (MALDI-TOF MS) and whole-genome-sequencing (WGS). Screening of the contact dogs in the kennel where the index case was kept, revealed that antibodies against B. canis could be detected in 23 out of 69 dogs (34 %) by serum agglutination test (SAT). Of the 23 seropositive dogs, B. canis could be cultured from the urine and/or heparin samples of 19 dogs (83 %). This outbreak represents the first documented case of transmission of B. canis to autochthonous contact dogs in the Netherlands. WGS revealed all B. canis isolates belonged to the same cluster, which means the transmission of B. canis in the breeding kennel was most likely caused by the introduction of one infected dog. Comparing this cluster with data from other B. canis isolates, it also appears that characteristic clusters of B. canis are present in several endemic countries. These clusters seem to remain stable over time and may help in locating the origin of new isolates found. This outbreak showed that the international movement of dogs from endemic countries poses a threat to the canine population, while serological screening and WGS proved to be valuable tools for respectively screening and the epidemiological investigation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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36. Emergence of Bluetongue Virus Serotype 3, the Netherlands, September 2023.
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Holwerda M, Santman-Berends IMGA, Harders F, Engelsma M, Vloet RPM, Dijkstra E, van Gennip RGP, Mars MH, Spierenburg M, Roos L, van den Brom R, and van Rijn PA
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- Animals, Netherlands epidemiology, Sheep, Cattle, Disease Outbreaks, Phylogeny, Communicable Diseases, Emerging epidemiology, Communicable Diseases, Emerging virology, History, 21st Century, Retrospective Studies, Bluetongue virus classification, Bluetongue virus genetics, Bluetongue virus isolation & purification, Bluetongue epidemiology, Bluetongue virology, Serogroup
- Abstract
Since 1998, notifiable bluetongue virus (BTV) serotypes 1-4, 6, 8, 9, 11, and 16 have been reported in Europe. In August 2006, a bluetongue (BT) outbreak caused by BTV serotype 8 began in northwestern Europe. The Netherlands was declared BT-free in February 2012, and annual monitoring continued. On September 3, 2023, typical BT clinical manifestations in sheep were notified to the Netherlands Food and Product Safety Consumer Authority. On September 6, we confirmed BTV infection through laboratory diagnosis; notifications of clinical signs in cattle were also reported. We determined the virus was serotype 3 by whole-genome sequencing. Retrospective analysis did not reveal BTV circulation earlier than September. The virus source and introduction route into the Netherlands remains unknown. Continuous monitoring and molecular diagnostic testing of livestock will be needed to determine virus spread, and new prevention strategies will be required to prevent BTV circulation within the Netherlands and Europe.
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- 2024
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37. Diet-induced changes in the jejunal microbiota of developing broilers reduce the abundance of Enterococcus hirae and Enterococcus faecium.
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Stege PB, Schokker D, Harders F, Kar SK, Stockhofe N, Perricone V, Rebel JMJ, de Jong IC, and Bossers A
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- Animals, Diet veterinary, Metagenomics methods, Dietary Supplements, Chickens microbiology, Chickens growth & development, Enterococcus faecium genetics, Gastrointestinal Microbiome drug effects, Jejunum microbiology, Enterococcus hirae, Animal Feed
- Abstract
Modern broiler breeds allow for high feed efficiency and rapid growth, which come at a cost of increased susceptibility to pathogens and disease. Broiler growth rate, feed efficiency, and health are affected by the composition of the gut microbiota, which in turn is influenced by diet. In this study, we therefore assessed how diet composition can affect the broiler jejunal gut microbiota. A total of 96 broiler chickens were divided into four diet groups: control, coated butyrate supplementation, medium-chain fatty acid supplementation, or a high-fibre low-protein content. Diet groups were sub-divided into age groups (4, 12 and 33 days of age) resulting in groups of 8 broilers per diet per age. The jejunum content was used for metagenomic shotgun sequencing to determine the microbiota taxonomic composition at species level. The composed diets resulted in a total of 104 differentially abundant bacterial species. Most notably were the butyrate-induced changes in the jejunal microbiota of broilers 4 days post-hatch, resulting in the reduced relative abundance of mainly Enterococcus faecium (-1.8 l2fc, P
adj = 9.9E-05) and the opportunistic pathogen Enterococcus hirae (-2.9 l2fc, Padj = 2.7E-08), when compared to the control diet. This effect takes place during early broiler development, which is critical for broiler health, thus exemplifying the importance of how diet can influence the microbiota composition in relation to broiler health. Future studies should therefore elucidate how diet can be used to promote a beneficial microbiota in the early stages of broiler development., (© 2024. The Author(s).)- Published
- 2024
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38. Molecular Characterization of Serratia marcescens Strain Isolated from Yellow Mealworms, Tenebrio molitor , in The Netherlands.
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Bello Gonzalez TDJ, van Gelderen B, Harders F, Vloet R, Voorbergen-Laarman M, de Ruiter B, and Haenen OLM
- Abstract
Insect culture has developed rapidly worldwide; it faces important security and safety control issues, including animal infections and disease development. In the Netherlands, in 2021, a ~30% mortality of mealworms, Tenebrio molitor , occurred at one farm, where over-humid sites in the substrate were observed. Bacterial cultures from both the external and internal partsof fry and larger mealworms were identified by MALDI-TOF to predominantly Serratia marcescens, Staphylococcus xylosus and Staphylococus saprofyticus . Due to the important role of S. marcescens as a potential zoonotic bacterium, we performed a molecular characterization of the isolated strain. Genomic analysis showed a multidrug-resistant S. marcescens isolate carrying a tet (41), aac (6')- Ic , and bla SST-1 chromosomal class C beta-lactamase-resistantgenes, all located on the chromosome. Additionally, several virulence genes were identified. The phylogenetic tree revealed that the S. marcescens strain from this study was similar to other S. marcescens strains from different ecological niches. Although the entomopathogenic activity was not confirmed, this case demonstrates that T. molitor can act as a reservoir and as an alternative path for exposing clinically important antibiotic-resistant bacteria that can affect animals and humans. It underlines the need to keep management factors optimal, before insects and their products enter the feed and food chain.
- Published
- 2023
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39. Implementation of WGS analysis of ESBL-producing Escherichia coli within EU AMR monitoring in livestock and meat.
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Brouwer MSM, Zandbergen Van Essen A, Kant A, Rapallini M, Harders F, Bossers A, Wullings B, Wit B, and Veldman KT
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- Animals, Humans, Livestock, beta-Lactamases genetics, Anti-Bacterial Agents pharmacology, Meat, Escherichia coli, Escherichia coli Infections epidemiology, Escherichia coli Infections veterinary
- Abstract
Background: As WGS comes of age, changes in EU legislation implemented in 2021 allow its usage for systematic monitoring of ESBL-producing Escherichia coli from livestock and meat, replacing phenotypic testing. Presently, phenotypic testing correlates well with antimicrobial resistance predicted from WGS data. WGS has added value in the wealth of additional information that is present in the data., Objectives: In this study we have detected the resistance phenotypes for a panel of antimicrobials while also analysing the molecular epidemiology of ESBL-producing E. coli., Methods: Susceptibility testing was performed with broth microdilution of selectively isolated E. coli. Short-read WGS was performed in parallel and phenotypes predicted based on the sequence data, which was also used to determine the phylogeny of the isolates., Results: The phenotypically determined resistance and the predicted resistance correlated 90%-100% for the different antimicrobial classes. Furthermore, clonal relationships were detected amongst ESBL-producing E. coli within livestock sectors and the meat produced by this sector., Conclusions: Further implementation of WGS analysis of ESBL/AmpC-producing E. coli within the AMR monitoring programme of EU member states and global surveillance programmes will contribute to determining the attribution of livestock in the prevalence of ESBL/AmpC-encoding E. coli in humans., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)
- Published
- 2023
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40. Emergence of biased hypermutation in a heterologous additional transcription unit in recombinant lentogenic Newcastle disease virus.
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de Buhr H, de Leeuw OS, Harders F, Peeters BP, and de Swart RL
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- Animals, Humans, Newcastle disease virus genetics, COVID-19 Vaccines, Pandemics, SARS-CoV-2 genetics, Chickens, Vaccines, Synthetic, RNA, COVID-19, Viral Vaccines, Newcastle Disease
- Abstract
Recombinant Newcastle disease virus (rNDV) strains engineered to express foreign genes from an additional transcription unit (ATU) are considered as candidate live-attenuated vector vaccines for human and veterinary use. Early during the COVID-19 pandemic we and others generated COVID-19 vaccine candidates based on rNDV expressing a partial or complete SARS-CoV-2 spike (S) protein. In our studies, a number of the rNDV constructs did not show high S expression levels in cell culture or seroconversion in immunized hamsters. Sanger sequencing showed the presence of frequent A-to-G transitions characteristic of adenosine deaminase acting on RNA (ADAR). Subsequent whole genome rNDV sequencing revealed that this biased hypermutation was exclusively localized in the ATU expressing the spike gene, and was related to deamination of adenosines in the negative strand viral genome RNA. The biased hypermutation was found both after virus rescue in chicken cell line DF-1 followed by passaging in embryonated chicken eggs, and after direct virus rescue and subsequent passaging in Vero E6 cells. Levels of biased hypermutation were higher in constructs containing codon-optimized as compared to native S gene sequences, suggesting potential association with increased GC content. These data show that deep sequencing of candidate recombinant vector vaccine constructs in different phases of development is of crucial importance in the development of NDV-based vaccines.
- Published
- 2023
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41. Immune Responses and Pathogenesis following Experimental SARS-CoV-2 Infection in Domestic Cats.
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Vreman S, van der Heijden EMDL, Ravesloot L, Ludwig IS, van den Brand JMA, Harders F, Kampfraath AA, Egberink HF, Gonzales JL, Oreshkova N, Broere F, van der Poel WHM, and Gerhards NM
- Subjects
- Animals, Cats, SARS-CoV-2, Lung, Immunity, Humoral, COVID-19 pathology
- Abstract
Several reports demonstrated the susceptibility of domestic cats to SARS-CoV-2 infection. Here, we describe a thorough investigation of the immune responses in cats after experimental SARS-CoV-2 inoculation, along with the characterization of infection kinetics and pathological lesions. Specific pathogen-free domestic cats ( n = 12) were intranasally inoculated with SARS-CoV-2 and subsequently sacrificed on DPI (days post-inoculation) 2, 4, 7 and 14. None of the infected cats developed clinical signs. Only mild histopathologic lung changes associated with virus antigen expression were observed mainly on DPI 4 and 7. Viral RNA was present until DPI 7, predominantly in nasal and throat swabs. The infectious virus could be isolated from the nose, trachea and lungs until DPI 7. In the swab samples, no biologically relevant SARS-CoV-2 mutations were observed over time. From DPI 7 onwards, all cats developed a humoral immune response. The cellular immune responses were limited to DPI 7. Cats showed an increase in CD8+ cells, and the subsequent RNA sequence analysis of CD4+ and CD8+ subsets revealed a prominent upregulation of antiviral and inflammatory genes on DPI 2. In conclusion, infected domestic cats developed a strong antiviral response and cleared the virus within the first week after infection without overt clinical signs and relevant virus mutations., Competing Interests: The authors declare no conflicts of interest.
- Published
- 2023
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42. Zoonotic Mutation of Highly Pathogenic Avian Influenza H5N1 Virus Identified in the Brain of Multiple Wild Carnivore Species.
- Author
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Vreman S, Kik M, Germeraad E, Heutink R, Harders F, Spierenburg M, Engelsma M, Rijks J, van den Brand J, and Beerens N
- Abstract
Wild carnivore species infected with highly pathogenic avian influenza (HPAI) virus subtype H5N1 during the 2021-2022 outbreak in the Netherlands included red fox ( Vulpes vulpes ), polecat ( Mustela putorius ), otter ( Lutra lutra ), and badger ( Meles meles ). Most of the animals were submitted for testing because they showed neurological signs. In this study, the HPAI H5N1 virus was detected by PCR and/or immunohistochemistry in 11 animals and was primarily present in brain tissue, often associated with a (meningo) encephalitis in the cerebrum. In contrast, the virus was rarely detected in the respiratory tract and intestinal tract and associated lesions were minimal. Full genome sequencing followed by phylogenetic analysis demonstrated that these carnivore viruses were related to viruses detected in wild birds in the Netherlands. The carnivore viruses themselves were not closely related, and the infected carnivores did not cluster geographically, suggesting that they were infected separately. The mutation PB2-E627K was identified in most carnivore virus genomes, providing evidence for mammalian adaptation. This study showed that brain samples should be included in wild life surveillance programs for the reliable detection of the HPAI H5N1 virus in mammals. Surveillance of the wild carnivore population and notification to the Veterinary Authority are important from a one-heath perspective, and instrumental to pandemic preparedness.
- Published
- 2023
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43. SARS-CoV-2 infection in cats and dogs in infected mink farms.
- Author
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van Aart AE, Velkers FC, Fischer EAJ, Broens EM, Egberink H, Zhao S, Engelsma M, Hakze-van der Honing RW, Harders F, de Rooij MMT, Radstake C, Meijer PA, Oude Munnink BB, de Rond J, Sikkema RS, van der Spek AN, Spierenburg M, Wolters WJ, Molenaar RJ, Koopmans MPG, van der Poel WHM, Stegeman A, and Smit LAM
- Subjects
- Animals, Animals, Wild, Cats, Dogs, Farms, Humans, Mink, SARS-CoV-2, COVID-19 epidemiology, COVID-19 veterinary, Cat Diseases epidemiology, Dog Diseases epidemiology
- Abstract
Animals like mink, cats and dogs are susceptible to SARS-CoV-2 infection. In the Netherlands, 69 out of 127 mink farms were infected with SARS-CoV-2 between April and November 2020 and all mink on infected farms were culled after SARS-CoV-2 infection to prevent further spread of the virus. On some farms, (feral) cats and dogs were present. This study provides insight into the prevalence of SARS-CoV-2-positive cats and dogs in 10 infected mink farms and their possible role in transmission of the virus. Throat and rectal swabs of 101 cats (12 domestic and 89 feral cats) and 13 dogs of 10 farms were tested for SARS-CoV-2 using PCR. Serological assays were performed on serum samples from 62 adult cats and all 13 dogs. Whole Genome Sequencing was performed on one cat sample. Cat-to-mink transmission parameters were estimated using data from all 10 farms. This study shows evidence of SARS-CoV-2 infection in 12 feral cats and 2 dogs. Eleven cats (18%) and two dogs (15%) tested serologically positive. Three feral cats (3%) and one dog (8%) tested PCR-positive. The sequence generated from the cat throat swab clustered with mink sequences from the same farm. The calculated rate of mink-to-cat transmission showed that cats on average had a chance of 12% (95%CI 10%-18%) of becoming infected by mink, assuming no cat-to-cat transmission. As only feral cats were infected it is most likely that infections in cats were initiated by mink, not by humans. Whether both dogs were infected by mink or humans remains inconclusive. This study presents one of the first reports of interspecies transmission of SARS-CoV-2 that does not involve humans, namely mink-to-cat transmission, which should also be considered as a potential risk for spread of SARS-CoV-2., (© 2021 The Authors. Transboundary and Emerging Diseases published by Wiley-VCH GmbH.)
- Published
- 2022
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44. Has Epizootic Become Enzootic? Evidence for a Fundamental Change in the Infection Dynamics of Highly Pathogenic Avian Influenza in Europe, 2021.
- Author
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Pohlmann A, King J, Fusaro A, Zecchin B, Banyard AC, Brown IH, Byrne AMP, Beerens N, Liang Y, Heutink R, Harders F, James J, Reid SM, Hansen RDE, Lewis NS, Hjulsager C, Larsen LE, Zohari S, Anderson K, Bröjer C, Nagy A, Savič V, van Borm S, Steensels M, Briand FX, Swieton E, Smietanka K, Grund C, Beer M, and Harder T
- Subjects
- Animals, Animals, Wild, Birds, Europe epidemiology, Phylogeny, Poultry, Influenza A Virus, H5N1 Subtype genetics, Influenza A virus genetics, Influenza in Birds epidemiology
- Abstract
Phylogenetic evidence from the recent resurgence of high-pathogenicity avian influenza (HPAI) virus subtype H5N1, clade 2.3.4.4b, observed in European wild birds and poultry since October 2021, suggests at least two different and distinct reservoirs. We propose contrasting hypotheses for this emergence: (i) resident viruses have been maintained, presumably in wild birds, in northern Europe throughout the summer of 2021 to cause some of the outbreaks that are part of the most recent autumn/winter 2021 epizootic, or (ii) further virus variants were reintroduced by migratory birds, and these two sources of reintroduction have driven the HPAI resurgence. Viruses from these two principal sources can be distinguished by their hemagglutinin genes, which segregate into two distinct sublineages (termed B1 and B2) within clade 2.3.4.4b, as well as their different internal gene compositions. The evidence of enzootic HPAI virus circulation during the summer of 2021 indicates a possible paradigm shift in the epidemiology of HPAI in Europe.
- Published
- 2022
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45. Multiple Introductions of Reassorted Highly Pathogenic Avian Influenza H5Nx Viruses Clade 2.3.4.4b Causing Outbreaks in Wild Birds and Poultry in The Netherlands, 2020-2021.
- Author
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Engelsma M, Heutink R, Harders F, Germeraad EA, and Beerens N
- Subjects
- Animals, Animals, Wild, Chickens, Disease Outbreaks, Mammals, Netherlands epidemiology, Phylogeny, Poultry, Influenza A Virus, H5N1 Subtype genetics, Influenza A Virus, H5N8 Subtype genetics, Influenza A virus genetics, Influenza in Birds epidemiology, Poultry Diseases
- Abstract
Highly pathogenic avian influenza (HPAI) viruses of subtype H5Nx caused outbreaks in poultry, captive birds, and wild birds in the Netherlands between October 2020 and June 2021. The full genome sequences of 143 viruses were analyzed. HPAI viruses were mainly of subtype H5N8, followed by H5N1, but also viruses of subtypes H5N3, H5N4, and H5N5 were detected. At least seven distinct genotypes were found, carrying closely related H5 segments belonging to clade 2.3.4.4b. Molecular clock analysis suggests that the reassortments of the NA gene segments likely occurred before the introduction of these viruses into the Netherlands. Genetic analysis suggested that multiple independent introductions of HPAI H5N8 viruses occurred in the Netherlands, likely followed by local spread resulting in at least two clusters of related viruses. The analysis provided evidence for independent introductions from wild birds at 10 poultry farms, whereas for two outbreaks transmission between farms could not be excluded. HPAI H5Nx viruses were detected in dead wild birds of 33 species, but mostly infected geese and swans were found. The pathogenicity of the H5N8 virus was determined for chickens and Pekin ducks, showing reduced mortality for ducks. This study provides more insight into the genetic diversity of HPAI H5Nx viruses generated by reassortment and evolution, and the spread of these viruses between wild birds and poultry. The fast and continuing evolution of H5 clade 2.3.4.4b may provide opportunities for these viruses to adapt to specific bird species, or possibly mammalian species and humans. IMPORTANCE Highly pathogenic avian influenza (HPAI) viruses are spread by migratory wild birds. Viruses causing outbreaks in wild birds and poultry in the Netherlands in 2020-2021 were genetically analyzed, which suggested that multiple virus incursions occurred. The outbreaks in poultry were likely caused by independent introductions from wild birds; only in one case virus spread between farms could not be excluded. Viruses of subtype H5N8 were mainly observed, but also other subtypes were detected that likely evolved by exchange of genetic information before these viruses were introduced into the Netherlands. Viruses were detected in many species of dead wild birds, but mostly in geese and swans. We showed that the H5N8 virus causes a higher mortality in chickens compared to ducks. This is consistent with the fact that not many wild ducks were found dead. This study provides more insight in the evolution and spread of HPAI viruses in wild birds and poultry.
- Published
- 2022
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46. Occupational and environmental exposure to SARS-CoV-2 in and around infected mink farms.
- Author
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de Rooij MMT, Hakze-Van der Honing RW, Hulst MM, Harders F, Engelsma M, van de Hoef W, Meliefste K, Nieuwenweg S, Oude Munnink BB, van Schothorst I, Sikkema RS, van der Spek AN, Spierenburg M, Spithoven J, Bouwstra R, Molenaar RJ, Koopmans M, Stegeman A, van der Poel WHM, and Smit LAM
- Subjects
- Animals, Humans, Netherlands epidemiology, Dust analysis, Environmental Exposure, Farms, Mink virology, Occupational Exposure, RNA, Viral isolation & purification, SARS-CoV-2 isolation & purification
- Abstract
Objective: Unprecedented SARS-CoV-2 infections in farmed minks raised immediate concerns regarding transmission to humans and initiated intensive environmental investigations to assess occupational and environmental exposure., Methods: Air sampling was performed at infected Dutch mink farms, at farm premises and at nearby residential sites. A range of other environmental samples were collected from minks' housing units, including bedding materials. SARS-CoV-2 RNA was analysed in all samples by quantitative PCR., Results: Inside the farms, considerable levels of SARS-CoV-2 RNA were found in airborne dust, especially in personal inhalable dust samples (approximately 1000-10 000 copies/m
3 ). Most of the settling dust samples tested positive for SARS-CoV-2 RNA (82%, 75 of 92). SARS-CoV-2 RNA was not detected in outdoor air samples, except for those collected near the entrance of the most recently infected farm. Many samples of minks' housing units and surfaces contained SARS-CoV-2 RNA., Conclusions: Infected mink farms can be highly contaminated with SARS-CoV-2 RNA. This warns of occupational exposure, which was substantiated by considerable SARS-CoV-2 RNA concentrations in personal air samples. Dispersion of SARS-CoV-2 to outdoor air was found to be limited and SARS-CoV-2 RNA was not detected in air samples collected beyond farm premises, implying a negligible risk of environmental exposure to nearby communities. Our occupational and environmental risk assessment is in line with whole genome sequencing analyses showing mink-to-human transmission among farm workers, but no indications of direct zoonotic transmission events to nearby communities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)- Published
- 2021
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47. Highly Pathogenic Avian Influenza A(H5N1) Virus in Wild Red Foxes, the Netherlands, 2021.
- Author
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Rijks JM, Hesselink H, Lollinga P, Wesselman R, Prins P, Weesendorp E, Engelsma M, Heutink R, Harders F, Kik M, Rozendaal H, van den Kerkhof H, and Beerens N
- Subjects
- Animals, Animals, Wild, Foxes, Netherlands epidemiology, Phylogeny, Influenza A Virus, H5N1 Subtype, Influenza A virus, Influenza in Birds epidemiology
- Abstract
We detected infection with highly pathogenic avian influenza A(H5N1) virus clade 2.3.4.4b in 2 red fox (Vulpes vulpes) cubs found in the wild with neurologic signs in the Netherlands. The virus is related to avian influenza viruses found in wild birds in the same area.
- Published
- 2021
- Full Text
- View/download PDF
48. Genetic and phenotypic analysis of the pathogenic potential of two novel Chlamydia gallinacea strains compared to Chlamydia psittaci.
- Author
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Heijne M, Jelocnik M, Umanets A, Brouwer MSM, Dinkla A, Harders F, van Keulen LJM, Roest HJ, Schaafsma F, Velkers FC, van der Goot JA, Pannekoek Y, and Koets AP
- Subjects
- Animals, Chick Embryo, Chickens microbiology, Chlamydia genetics, Chlamydia Infections microbiology, Chlamydophila psittaci genetics, Genetic Association Studies, Phylogeny, Psittacosis microbiology, Virulence genetics, Chlamydia pathogenicity, Chlamydia Infections veterinary, Chlamydophila psittaci pathogenicity, Poultry Diseases microbiology, Psittacosis veterinary
- Abstract
Chlamydia gallinacea is an obligate intracellular bacterium that has recently been added to the family of Chlamydiaceae. C. gallinacea is genetically diverse, widespread in poultry and a suspected cause of pneumonia in slaughterhouse workers. In poultry, C. gallinacea infections appear asymptomatic, but studies about the pathogenic potential are limited. In this study two novel sequence types of C. gallinacea were isolated from apparently healthy chickens. Both isolates (NL_G47 and NL_F725) were closely related to each other and have at least 99.5% DNA sequence identity to C. gallinacea Type strain 08-1274/3. To gain further insight into the pathogenic potential, infection experiments in embryonated chicken eggs and comparative genomics with Chlamydia psittaci were performed. C. psittaci is a ubiquitous zoonotic pathogen of birds and mammals, and infection in poultry can result in severe systemic illness. In experiments with embryonated chicken eggs, C. gallinacea induced mortality was observed, potentially strain dependent, but lower compared to C. psittaci induced mortality. Comparative analyses confirmed all currently available C. gallinacea genomes possess the hallmark genes coding for known and potential virulence factors as found in C. psittaci albeit to a reduced number of orthologues or paralogs. The presence of potential virulence factors and the observed mortality in embryonated eggs indicates C. gallinacea should rather be considered as an opportunistic pathogen than an innocuous commensal., (© 2021. The Author(s).)
- Published
- 2021
- Full Text
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49. Analysis of failed therapy evaluations in radioembolization of primary and secondary liver cancers.
- Author
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Masthoff M, Schindler P, Harders F, Heindel W, Wilms C, Schmidt HH, Pascher A, Stegger L, Rahbar K, Köhler M, and Wildgruber M
- Subjects
- Adult, Aged, Aged, 80 and over, Albumins metabolism, Embolization, Therapeutic methods, Female, Humans, Liver metabolism, Liver pathology, Liver Neoplasms metabolism, Male, Middle Aged, Organotechnetium Compounds administration & dosage, Radiopharmaceuticals administration & dosage, Retrospective Studies, Technetium administration & dosage, Tumor Burden physiology, Young Adult, Liver Neoplasms pathology
- Abstract
Purpose: To analyze patients' characteristics and reasons for not performing planned transarterial radioembolization (TARE) in liver cancer after
99m Tc-labeled macroaggregated albumin (99m Tc-MAA) evaluation., Methods: In this retrospective single-center cohort, all patients undergoing99m Tc-MAA evaluation prior to planned TARE for primary or secondary liver cancer between 2009 and 2018 were analyzed. Patients were assigned to either "TARE" or "no TARE" group. Patients' characteristics, arising reasons for not performing the planned TARE treatment as well as predictive factors for occurrence of these causes were analyzed., Results: 436 patients [male = 248, female = 188, median age 62 (23-88) years] with99m Tc-MAA evaluation prior to planned TARE of primary or secondary liver cancer were included in this study. 148 patients (33.9%) did not receive planned TARE. Patients with a hepatic tumor burden > 50%, no liver cirrhosis, no previous therapies and a higher bilirubin were significantly more frequent in "no TARE" compared to "TARE" group. Main reasons for not performing TARE were extrahepatic tracer accumulation (n = 70, 40.5%), non-target accumulation of99m Tc-MAA (n = 27, 15.6%) or a hepatopulmonary shunt fraction of more than 20% (n = 23, 13.3%). Independent preprocedural parameters for not performing planned TARE were elevated bilirubin (p = 0.021) and creatinine (p = 0.018) and lower MELD score (p = 0.031)., Conclusion: A substantial number of patients are precluded from TARE following99m Tc-MAA evaluation, which is, therefore, implicitly needed to determine contraindications to TARE and should not be refrained from in pretreatment process. However, a preceding careful patient selection is needed especially in patients with high hepatic tumor burden and alteration in lab parameters.- Published
- 2021
- Full Text
- View/download PDF
50. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans.
- Author
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Oude Munnink BB, Sikkema RS, Nieuwenhuijse DF, Molenaar RJ, Munger E, Molenkamp R, van der Spek A, Tolsma P, Rietveld A, Brouwer M, Bouwmeester-Vincken N, Harders F, Hakze-van der Honing R, Wegdam-Blans MCA, Bouwstra RJ, GeurtsvanKessel C, van der Eijk AA, Velkers FC, Smit LAM, Stegeman A, van der Poel WHM, and Koopmans MPG
- Subjects
- Animals, COVID-19 epidemiology, COVID-19 veterinary, Disease Outbreaks, Farms, Humans, Likelihood Functions, Mutation, Netherlands epidemiology, Phylogeny, RNA, Viral analysis, RNA, Viral genetics, SARS-CoV-2 classification, SARS-CoV-2 physiology, Whole Genome Sequencing, COVID-19 transmission, COVID-19 virology, Mink, SARS-CoV-2 genetics, SARS-CoV-2 isolation & purification, Zoonoses transmission, Zoonoses virology
- Abstract
Animal experiments have shown that nonhuman primates, cats, ferrets, hamsters, rabbits, and bats can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, SARS-CoV-2 RNA has been detected in felids, mink, and dogs in the field. Here, we describe an in-depth investigation using whole-genome sequencing of outbreaks on 16 mink farms and the humans living or working on these farms. We conclude that the virus was initially introduced by humans and has since evolved, most likely reflecting widespread circulation among mink in the beginning of the infection period, several weeks before detection. Despite enhanced biosecurity, early warning surveillance, and immediate culling of animals in affected farms, transmission occurred between mink farms in three large transmission clusters with unknown modes of transmission. Of the tested mink farm residents, employees, and/or individuals with whom they had been in contact, 68% had evidence of SARS-CoV-2 infection. Individuals for which whole genomes were available were shown to have been infected with strains with an animal sequence signature, providing evidence of animal-to-human transmission of SARS-CoV-2 within mink farms., (Copyright © 2021, American Association for the Advancement of Science.)
- Published
- 2021
- Full Text
- View/download PDF
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