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- Anderson, Jenna
(author)
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Development and evaluation of a subunit DIVA vaccine against bluetongue virus serotype 8 in cattle
- 2014
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Doctoral thesis (other academic/artistic)abstract
- Bluetongue virus (BTV) causes the primarily vector-borne bluetongue disease of ruminants, which poses a permanent threat to Europe since new serotypes and strains are frequently introduced. Vaccination of cattle is essential to control BTV outbreaks. Commercial attenuated and inactivated vaccines are efficacious in reducing BTV spread and disease, but do not fulfil all safety, adaptability, or production requirements. Additionally, no current vaccines allow the differentiation of infected from vaccinated animals (DIVA). DIVA vaccines enable surveillance of BTV epidemiology and vaccine efficacy, and facilitate a quick return for countries to a BTV-free status. This thesis presents the development and evaluation of a novel subunit DIVA vaccine against BTV serotype 8 (BTV-8) in cattle. Five His-tagged recombinant BTV proteins (VP2, VP5 of BTV-8; NS1, NS2, NS3 of BTV-2) were produced in baculovirus or E. coli expression systems. Purification protocols were optimized for all but VP5. Based on the feasibility of protein production and the capability of the remaining four proteins to induce humoral or cellular immune responses in mice, VP2, NS1, and NS2 were selected to formulate an experimental vaccine combined to an ISCOM-matrix adjuvant (SubV). Next, cattle were immunized twice at a three-week interval with SubV, a commercial inactivated vaccine, or a placebo. SubV induced humoral immune responses, including virus-neutralizing antibodies, against all three proteins, as well as a cellular immune response directed against NS1. These responses were of similar type and comparable magnitude between both vaccines, suggesting that SubV might provide protection that is at least as effective as the commercial vaccine. Finally, the protective efficacy of SubV was evaluated and complete virological and clinical protection against virulent BTV-8 challenge was observed following vaccination in calves. This was likely due to the induction of virus-neutralizing antibodies directed against VP2 of BTV-8 and cross-serotype T cell responses directed against NS1 and NS2 of BTV-2. Furthermore, SubV was shown to be DIVA-compliant based on the detection of antibodies directed against VP7, by using commercially-available diagnostic assays. This novel BTV subunit vaccine is a promising candidate and should be further developed.
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| 2. |
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| 3. |
- Wiszmeg, Andréa, et al.
(author)
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Transforming trash to treasure Cultural ambiguity in foetal cell research
- 2021
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In: Philosophy Ethics and Humanities in Medicine. - : Springer Science and Business Media LLC. - 1747-5341. ; 16:1
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Journal article (peer-reviewed)abstract
- Background Rich in different kind of potent cells, embryos are used in modern regenerative medicine and research. Neurobiologists today are pushing the boundaries for what can be done with embryos existing in the transitory margins of medicine. Therefore, there is a growing need to develop conceptual frameworks for interpreting the transformative cultural, biological and technical processes involving these aborted, donated and marginal embryos. This article is a contribution to this development of frameworks. Methods This article examines different emotional, cognitive and discursive strategies used by neurobiologists in a foetal cell transplantation trial in Parkinson's disease research, using cells harvested from aborted embryos. Two interviews were analysed in the light of former observations in the processing laboratories, using the anthropologist Mary Douglas's concept of pollution behaviour and the linguist, philosopher, psychoanalyst and feminist Julia Kristeva's concept of the abjective to explain and make sense of the findings. Results The findings indicate that the labour performed by the researchers in the trial work involves transforming the foetal material practically, as well as culturally, from trash to treasure. The transformation process contains different phases, and in the interview material we observed that the foetal material or cells were considered objects, subjects or rejected as abject by the researchers handling them, depending on what phase of process or practice they referred to or had experience of. As demonstrated in the analysis, it is the human origin of the cell that makes it abjective and activates pollution discourse, when the researchers talk of their practice. Conclusions The marginal and ambiguous status of the embryo that emerges in the accounts turns the scientists handling foetal cells into liminal characters in modern medicine. Focusing on how practical as well as emotional and cultural strategies and rationalizations of the researchers emerge in interview accounts, this study adds insights on the rationale of practically procuring, transforming and utilizing the foetal material to the already existing studies focused on the donations. We also discuss why the use and refinement of a tissue, around which there is practical consensus but cultural ambiguity, deserves further investigation.
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| 4. |
- Hallberg, Ida, et al.
(author)
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Perfluorononanoic acid (PFNA) alters lipid accumulation in bovine blastocysts after oocyte exposure during in vitro maturation
- 2019
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In: Reproductive Toxicology. - : Elsevier BV. - 0890-6238 .- 1873-1708. ; 84, s. 1-8
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Journal article (peer-reviewed)abstract
- Perfluorononanoic acid (PFNA) is one of the perfluoroalkyl acids present in human tissues. In this study, effects on early embryo development after PFNA exposure were investigated using the bovine in vitro production system. Oocytes were exposed to PFNA during maturation in vitro (10 μg mL-1 and 0.1 μg mL-1), and then fertilized and cultured in parallel with control groups. Developmental parameters (cleavage, blastocyst formation) were followed and embryo quality evaluated (stage, grade). Embryos developed after exposure to 0.1 μg mL-1 were stained to distinguish nuclei, active mitochondria and neutral lipids. 10 μg mL-1 of PFNA had a severe negative effect on blastocyst formation (OR: 0.27 p < 0.05), an effect not observed at 0.1 μg mL-1. However, lipid droplet distribution was significantly altered in embryos exposed to 0.1 μg mL-1, suggesting a disturbance of lipid metabolism after exposure to sublethal levels of PFNA during oocyte maturation in vitro.
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| 5. |
- Jacobsen, M, et al.
(author)
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Refined candidate region specified by haplotype sharing for Escherichia coli F4ab/F4ac susceptibility alleles in pigs
- 2010
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In: Animal Genetics. - : Wiley. - 0268-9146 .- 1365-2052. ; 41:1, s. 21-25
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Journal article (peer-reviewed)abstract
- Infection of the small intestine by enterotoxigenic Escherichia coli F4ab/ac is a major welfare problem and financial burden for the pig industry. Natural resistance to this infection is inherited as a Mendelian recessive trait, and a polymorphism in the MUC4 gene segregating for susceptibility/resistance is presently used in a selection programme by the Danish pig breeding industry. To elucidate the genetic background involved in E. coli F4ab/ac susceptibility in pigs, a detailed haplotype map of the porcine candidate region was established. This region covers approximately 3.7 Mb. The material used for the study is a three generation family, where the founders are two Wild boars and eight Large White sows. All pigs have been phenotyped for susceptibility to F4ab/ac using an adhesion assay. Their haplotypes are known from segregation analysis using flanking markers. By a targeted approach, the candidate region was subjected to screening for polymorphisms, mainly focusing on intronic sequences. A total of 18 genes were partially sequenced, and polymorphisms were identified in GP5, CENTB2, APOD, PCYT1A, OSTalpha, ZDHHC19, TFRC, ACK1, MUC4, MUC20, KIAA0226, LRCH3 and MUC13. Overall, 227 polymorphisms were discovered in the founder generation. The analysis revealed a large haplotype block, spanning at least 1.5 Mb around MUC4, to be associated with F4ab/ac susceptibility.
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| 6. |
- Palsdottir, Vilborg, 1979, et al.
(author)
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Postnatal deficiency of essential fatty acids in mice results in resistance to diet-induced obesity and low plasma insulin during adulthood
- 2011
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In: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 1532-2823 .- 0952-3278. ; 84:3-4, s. 85-92
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Journal article (peer-reviewed)abstract
- Our objective was to investigate the long-term metabolic effects of postnatal essential fatty acid deficiency (EFAD). Mouse dams were fed an EFAD diet or an isoenergetic control diet 4 days before delivery and throughout lactation. The pups were weaned to standard diet (STD) and were later subdivided into two groups: receiving high fat diet (HFD) or STD. Body composition, energy expenditure, food intake and leptin levels were analyzed in adult offspring. Blood glucose and plasma insulin concentrations were measured before and during a glucose tolerance test. EFAD offspring fed STD were leaner with lower plasma leptin and insulin concentrations compared to controls. EFAD offspring fed HFD were resistant to diet-induced obesity, had higher energy expenditure and lower levels of plasma leptin and insulin compared to controls. These results indicate that the fatty acid composition during lactation is important for body composition and glucose tolerance in the adult offspring.
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| 8. |
- Karlsson, Frida
(author)
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Treponema spp. in porcine skin ulcers : clinical aspects
- 2014
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Doctoral thesis (other academic/artistic)abstract
- The hypothesis tested in this work is that bacteria of genus Treponema play a main role when shoulder ulcers and ear necrosis occur in an infectious or severe form, and perhaps also in other skin conditions in the pig. Samples were collected from pigs in 19 Swedish herds 2010-2011. The sampled skin lesions included 52 shoulder ulcers, 57 ear necroses, 4 facial necroses and 5 other skin ulcers. Occurrence of spirochetes was detected by phase contrast microscopy, Warthin-Starry silver staining, PCR and Fluorescent In Situ Hybridization (FISH). Treponemal diversity was investigated by sequencing of 16S-23S rRNA intergenic spacer region 2 (ISR2) and high-throughput sequencing (HTS) of a part of the 16S rRNA gene. Culturing and characterization of treponemes by biochemical analyses, testing of antimicrobial susceptibility and fingerprinting by random amplified polymorphic DNA (RAPD) were carried out. A challenge study was performed to test if Treponema pedis induced skin lesions. Serological response towards TPE0673, a T. pedis protein, was tested with ELISA. Spirochetes were found in all types of skin ulcers and in all herds. The occurrence of Treponema spp. detected by PCR was 52% in shoulder ulcers, 46% in ear necrosis and 9.7% in gingiva. Treponemes were identified in 69% of the shoulder ulcers and in 59% of the ear necroses by FISH. A phylogenetic tree revealed a great variability of treponemes. Three main phylotypes were identified; T. pedis, Treponema parvum and one phylotype without designation. Twelve isolates of T. pedis, T. parvum, and one phylotype most similar to Treponema sp. OMZ 840 were obtained. All except two had unique RAPD fingerprints. Biochemical tests could not differentiate between the isolates and they were generally susceptible to tested antimicrobials. By FISH, treponemes were visualized deep in the ulcers and a predominance of T. pedis was noted, and confirmed by HTS. Challenged pigs did not develop any lesions or IgG response towards the T. pedis protein. Most sows with shoulder ulcers showed a strong, and most cases of ear necrosis a weak IgG response towards TPE0673. In conclusion, Treponema spp. are frequently abundant in ear necroses and shoulder ulcers in pigs. Identical phylotypes and ISR2 sequences from ulcers and gingiva indicate spreading from mouth to ulcer. A broad diversity of phylotypes was revealed, but the predominance of T. pedis suggests specific importance of this species. Our results point towards an important role of treponemes in chronic and severe skin ulcers in pigs.
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| 9. |
- Blomström, Anne-Lie
(author)
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Non-Structural Proteins of Arthropod-Borne Bunyaviruses: Roles and Functions
- 2013
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In: Viruses. - : MDPI AG. - 1999-4915. ; 5, s. 2447-2468
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Research review (peer-reviewed)abstract
- Viruses within the Bunyaviridae family are tri-segmented, negative-stranded RNA viruses. The family includes several emerging and re-emerging viruses of humans, animals and plants, such as Rift Valley fever virus, Crimean-Congo hemorrhagic fever virus, La Crosse virus, Schmallenberg virus and tomato spotted wilt virus. Many bunyaviruses are arthropod-borne, so-called arboviruses. Depending on the genus, bunyaviruses encode, in addition to the RNA-dependent RNA polymerase and the different structural proteins, one or several non-structural proteins. These non-structural proteins are not always essential for virus growth and replication but can play an important role in viral pathogenesis through their interaction with the host innate immune system. In this review, we will summarize current knowledge and understanding of insect-borne bunyavirus non-structural protein function(s) in vertebrate, plant and arthropod.
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| 10. |
- Gillman, Anna, et al.
(author)
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Oseltamivir-Resistant Influenza A (H1N1) Virus Strain with an H274Y Mutation in Neuraminidase Persists without Drug Pressure in Infected Mallards
- 2015
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In: Applied and Environmental Microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 81:7, s. 2378-2383
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Journal article (peer-reviewed)abstract
- Influenza A virus (IAV) has its natural reservoir in wild waterfowl, and emerging human IAVs often contain gene segments from avian viruses. The active drug metabolite of oseltamivir (oseltamivir carboxylate [OC]), stockpiled as Tamiflu for influenza pandemic preparedness, is not removed by conventional sewage treatment and has been detected in river water. There, it may exert evolutionary pressure on avian IAV in waterfowl, resulting in the development of resistant viral variants. A resistant avian IAV can circulate among wild birds only if resistance does not restrict viral fitness and if the resistant virus can persist without continuous drug pressure. In this in vivo mallard (Anas platyrhynchos) study, we tested whether an OC-resistant avian IAV (H1N1) strain with an H274Y mutation in the neuraminidase (NA-H274Y) could retain resistance while drug pressure was gradually removed. Successively infected mallards were exposed to decreasing levels of OC, and fecal samples were analyzed for the neuraminidase sequence and phenotypic resistance. No reversion to wild-type virus was observed during the experiment, which included 17 days of viral transmission among 10 ducks exposed to OC concentrations below resistance induction levels. We conclude that resistance in avian IAV that is induced by exposure of the natural host to OC can persist in the absence of the drug. Thus, there is a risk that human-pathogenic IAVs that evolve from IAVs circulating among wild birds may contain resistance mutations. An oseltamivir-resistant pandemic IAV would pose a substantial public health threat. Therefore, our observations underscore the need for prudent oseltamivir use, upgraded sewage treatment, and surveillance for resistant IAVs in wild birds.
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