| 1. |
- Anderson, Jenna
(författare)
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Development and evaluation of a subunit DIVA vaccine against bluetongue virus serotype 8 in cattle
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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. |
- Jacobsen, M, et al.
(författare)
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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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Ingår i: Animal Genetics. - : Wiley. - 0268-9146 .- 1365-2052. ; 41:1, s. 21-25
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Palsdottir, Vilborg, 1979, et al.
(författare)
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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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Ingår i: Prostaglandins, Leukotrienes and Essential Fatty Acids. - : Elsevier BV. - 1532-2823 .- 0952-3278. ; 84:3-4, s. 85-92
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Tidskriftsartikel (refereegranskat)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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| 5. |
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| 6. |
- Karlsson, Frida
(författare)
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Treponema spp. in porcine skin ulcers : clinical aspects
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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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| 7. |
- Blomström, Anne-Lie
(författare)
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Non-Structural Proteins of Arthropod-Borne Bunyaviruses: Roles and Functions
- 2013
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Ingår i: Viruses. - : MDPI AG. - 1999-4915. ; 5, s. 2447-2468
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Forskningsöversikt (refereegranskat)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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| 8. |
- Gunnarsson, Ulrika, et al.
(författare)
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The Dark brown plumage color in chickens is caused by an 8.3 kb deletion upstream of SOX10.
- 2011
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Ingår i: Pigment cell & melanoma research. - 1755-148X .- 1755-1471.
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Tidskriftsartikel (refereegranskat)abstract
- The Dark brown mutation in chickens reduces expression of black eumelanin and enhances expression of red pheomelanin but only in certain parts of the plumage. Here we present genetic evidence that an 8.3 kb deletion upstream of the SOX10 transcription start site is the causal mutation underlying the Dark brown phenotype. The SOX10 transcription factor has a well-established role in melanocyte biology and is essential for melanocyte migration and survival. Previous studies have demonstrated that the mouse homolog of a highly conserved element within the deleted region is a SOX10 enhancer. The mechanism of action of this mutation remains to be established but one possible scenario is that the deletion leads to reduced SOX10 expression which in turn down-regulates expression of key enzymes in pigment synthesis such as tyrosinase. Lower tyrosinase activity leads to a shift towards a more pheomelanistic (reddish) plumage color, which is the characteristic feature of the Dark brown phenotype.
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| 9. |
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| 10. |
- Östensson, Karin
(författare)
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Från manligt till kvinnligt
- 2010
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Ingår i: Veterinär - yrke i förvandling. - 9789163374425 ; , s. 83-110
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Bokkapitel (populärvet., debatt m.m.)
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| 11. |
- Östensson, Karin
(författare)
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Sveriges Veterinärförbund 150 år
- 2010
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Ingår i: Veterinär - yrke i förvandling. - 9789163374425 ; , s. 8-67
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Bokkapitel (populärvet., debatt m.m.)
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| 12. |
- Baranowska Körberg, Izabella, et al.
(författare)
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A Simple Repeat Polymorphism in the MITF-M Promoter Is a Key Regulator of White Spotting in Dogs
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8, s. e104363-
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Tidskriftsartikel (refereegranskat)abstract
- The white spotting locus (S) in dogs is colocalized with the MITF (microphtalmia-associated transcription factor) gene. The phenotypic effects of the four S alleles range from solid colour (S) to extreme white spotting (s(w)). We have investigated four candidate mutations associated with the s(w) allele, a SINE insertion, a SNP at a conserved site and a simple repeat polymorphism all associated with the MITF-M promoter as well as a 12 base pair deletion in exon 1B. The variants associated with white spotting at all four loci were also found among wolves and we conclude that none of these could be a sole causal mutation, at least not for extreme white spotting. We propose that the three canine white spotting alleles are not caused by three independent mutations but represent haplotype effects due to different combinations of causal polymorphisms. The simple repeat polymorphism showed extensive diversity both in dogs and wolves, and allele-sharing was common between wolves and white spotted dogs but was non-existent between solid and spotted dogs as well as between wolves and solid dogs. This finding was unexpected as Solid is assumed to be the wild-type allele. The data indicate that the simple repeat polymorphism has been a target for selection during dog domestication and breed formation. We also evaluated the significance of the three MITF-M associated polymorphisms with a Luciferase assay, and found conclusive evidence that the simple repeat polymorphism affects promoter activity. Three alleles associated with white spotting gave consistently lower promoter activity compared with the allele associated with solid colour. We propose that the simple repeat polymorphism affects cooperativity between transcription factors binding on either flanking sides of the repeat. Thus, both genetic and functional evidence show that the simple repeat polymorphism is a key regulator of white spotting in dogs.
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| 13. |
- Nilsson Sköld, Helen, 1970, et al.
(författare)
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Telomerase deficiency in a colonial ascidian after prolonged asexual propagation
- 2011
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Ingår i: Journal of experimental zoology B (Mol Dev Evol). ; 314B
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT In organisms that propagate by agametic cloning, the parental body is the reproductive unit and fitness increases with clonal size, so that colonial metazoans, despite lack of experimental data, have been considered potentially immortal. Using asexual propagation rate as a measure of somatic performance, and telomerase activity and relative telomere length as molecular markers of senescence, old (7-12 yr) asexual strains of a colonial ascidian, Diplosoma listerianum, were compared with their recent sexually produced progeny. We report for the first time evidence for long-term molecular senescence in asexual lineages of a metazoan, and that only passage between sexual generations provides total rejuvenation permitting indefinite propagation and growth. Thus, this colonial ascidian has not fully escaped ageing. The possibility of somatic replicative senescence also potentially helps to explain why metazoans with the capacity for asexual propagation through gametic cloning commonly undergo cycles of sexual reproduction in the wild.
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| 14. |
- Kessler, Vadim
(författare)
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Facile non-hydrolytic synthesis of highly water dispersible, surfactant free nanoparticles of synthetic MFe2O4 (M-Mn2+, Fe2+, Co2+, Ni2+) ferrite spinel by a modified Bradley reaction
- 2013
-
Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 3, s. 12230-12243
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Tidskriftsartikel (refereegranskat)abstract
- A series of the highly crystalline MFe2O4 ferrite spinel nanoparticles were synthesized via a modified Bradley reaction using microwave stimulation. Particle size was estimated using theoretical calculations from the X-ray data (Scherrer and Rietveld methods) as well as by direct experimental techniques such as TEM, DLS and NTA. The calculated average grain size for dry powders is in the range 10 to 23 nm. Hydrodynamic size was measured using DLS on non-modified, surfactant free particles of the whole MFe2O4 series. Raman spectra used for additional verification of the structure features of the produced spinel phases showed strong asymmetric behavior of the A(1g) mode, which was deconvoluted revealing additional components. Among all the products the lowest site inversion was found for the manganese ferrite (MnFe2O4). The oxidation of Fe3O4 leading to the formation of the Fe2O3 hematite phase induced by laser irradiation was observed. Magnetic characterization of the MFe2O4 family was carried out, showing that superparamagnetic blocking temperatures and calculated anisotropy constants K are in good agreement with the data for similar fine-particle systems.
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| 15. |
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| 16. |
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| 17. |
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| 18. |
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| 19. |
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| 20. |
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| 21. |
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| 22. |
- Klütsch, Cornelya, et al.
(författare)
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Regional occurrence, high frequency but low diversity of mitochondrial DNA haplogroup d1 suggests a recent dog-wolf hybridization in Scandinavia
- 2011
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Ingår i: Animal Genetics. - : Wiley. - 0268-9146 .- 1365-2052. ; 42:1, s. 100-103
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Tidskriftsartikel (refereegranskat)abstract
- P>The domestic dog mitochondrial DNA (mtDNA)-gene pool consists of a homogenous mix of haplogroups shared among all populations worldwide, indicating that the dog originated at a single time and place. However, one small haplogroup, subclade d1, found among North Scandinavian/Finnish spitz breeds at frequencies above 30%, has a clearly separate origin. We studied the genetic and geographical diversity for this phylogenetic group to investigate where and when it originated and whether through independent domestication of wolf or dog-wolf crossbreeding. We analysed 582 bp of the mtDNA control region for 514 dogs of breeds earlier shown to harbour d1 and possibly related northern spitz breeds. Subclade d1 occurred almost exclusively among Swedish/Finnish Sami reindeer-herding spitzes and some Swedish/Norwegian hunting spitzes, at a frequency of mostly 60-100%. Genetic diversity was low, with only four haplotypes: a central, most frequent, one surrounded by two haplotypes differing by an indel and one differing by a substitution. The substitution was found in a single lineage, as a heteroplasmic mix with the central haplotype. The data indicate that subclade d1 originated in northern Scandinavia, at most 480-3000 years ago and through dog-wolf crossbreeding rather than a separate domestication event. The high frequency of d1 suggests that the dog-wolf hybrid phenotype had a selective advantage.
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| 23. |
- Johansson Wensman, Jonas, et al.
(författare)
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Borna disease virus infection in cats
- 2014
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Ingår i: Veterinary Journal. - : Elsevier BV. - 1090-0233 .- 1532-2971. ; 201, s. 142-149
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Forskningsöversikt (refereegranskat)abstract
- Bornaviruses are known to cause neurological disorders in a number of animal species. Avian Bornavirus (ABV) causes proventricular dilatation disease (PDD) in birds and Borna disease virus (BDV) causes Borna disease in horses and sheep. BDV also causes staggering disease in cats, characterised by ataxia, behavioural changes and loss of postural reactions. BDV-infection markers in cats have been reported throughout the world. This review summarizes the current knowledge of Borna disease viruses in cats, including etiological agent, clinical signs, pathogenesis, epidemiology and diagnostics, with comparisons to Bornavirus infections in other species.
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| 24. |
- Johansson Wensman, Jonas
(författare)
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Bornaviruses
- 2013
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Ingår i: Mononegaviruses of Veterinary Importance Vol. I: Pathobiology and Molecular Diagnosis. - UK : CABI. - 9781780641799 ; , s. 1-14
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 25. |
- Waern, Ida, et al.
(författare)
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PP-020-09 Protective role of mast cell chymase in house dust mite induced allergic airway inflammation
- 2010
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Ingår i: International Immunology. - : Oxford University Press (OUP). - 0953-8178 .- 1460-2377. ; 22, s. i134-
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Konferensbidrag (refereegranskat)abstract
- Mast cells release substantial amounts of active proteases, including chymase, upon activation and degranulation inresponse to e.g. IgE cross-linking. A chymase polymorphism has been associated with allergic asthma but the role of chymase in the pathogenesis is not fully understood. We recently showed that mouse mast cell protease 4 (mMCP-4) is the major chymotryptic enzyme in murine airways and that mMCP-4 can protect against bronchial hyperresponsiveness. We here assessed the role of chymase in a model of airway inflammation where mMCP-4 deficient (mMCP-4-/-) and wild type (WT) controls received repeated intranasal instillations of house dust mite (HDM). HDM-sensitization resulted in an accumulation of eosinophils and lymphocytes in the airways of both WT and mMCP-4-/- mice, but the numbers of eosinophils were approximately 5-fold higher in mMCP-4-/- mice. The airway inflammation correlated with the degree of T cell activation in draining lymph nodes. Moreover, the serum level of IgE was significantly higher in sensitized mMCP-4-/- mice than in WT mice. These results suggest a regulatory role for mMCP-4 in the early sensitization process when release of MC proteases in response to IgE cross-linking would be minimal. However, we found that HDM extract per se induced a low but significant degranulation in cultured MCs derived from both mMCP-4-/- and WT mice. Together these results suggest that MC chymase is released upon HDM exposure and that chymase has a protective role in HDM-induced airway inflammation by acting as a negative regulator of allergic sensitization.
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| 26. |
- Palsdottir, Vilborg, 1979, et al.
(författare)
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Prenatal essential fatty acid deficiency in mice results in long-term gender-specific effects on body weight and glucose metabolism
- 2011
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Ingår i: Molecular Medicine Reports. - : Spandidos Publications. - 1791-2997 .- 1791-3004. ; 4:4, s. 731-737
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Tidskriftsartikel (refereegranskat)abstract
- Essential fatty acids are important for normal growth and development in early life. However, the long-term effects of prenatal essential fatty acid deficiency (EFAD) on the adult metabolism remain to be determined. The aim of this study was to investigate the effects of an EFAD diet given to mice during late gestation on body weight and body composition, and metabolism in the adult offspring. Pregnant dams were given an EFAD or a control diet during the last 10 days of gestation. After delivery, all mice were fed normal chow and the body weight of the offspring was measured weekly. Furthermore, food intake, energy expenditure and intraperitoneal glucose tolera-nce were analysed in the adult offspring in addition to body composition (analysed by dual-energy X-ray absorptiometry), plasma levels of leptin, triglycerides and cholesterol. The body weight was lower in the EFAD offspring as compared to the controls during the first 4 weeks of age, and remained lower in the females throughout the study. Lean body mass and plasma leptin levels were also lower in the female EFAD offspring as compared to the controls. Male EFAD offspring were found to have higher fasting glucose and insulin levels as well as higher insulin levels during the glucose tolerance test compared to the controls. However, no differences were found in blood lipids, food intake or energy expenditure between EFAD and control mice of either gender. These results demonstrate that an EFAD diet given during the last 10 days of gestation results in long-term gender-specific effects on body weight and insulin sensitivity in the adult offspring.
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| 27. |
- Palsdottir, Vilborg, 1979, et al.
(författare)
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Long-term effects of perinatal essential fatty acid deficiency on anxiety-related behavior in mice.
- 2012
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Ingår i: Behavioral neuroscience. - : American Psychological Association (APA). - 1939-0084 .- 0735-7044. ; 126:2, s. 361-9
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Tidskriftsartikel (refereegranskat)abstract
- Dietary essential fatty acids have been shown to regulate behavioral and cognitive functions in rodents. However, the long-term effect on behavior, besides memory and learning, of essential fatty acid deficiency (EFAD), i.e., lack of n-3 and n-6 fatty acids, during the perinatal period has not been investigated. Therefore, pregnant C57Bl/6 mice were given either an EFAD or an isoenergetic control diet from gestational day 16 and throughout lactation. The female offspring were given standard chow from 3 weeks of age, and at 12 to 14 weeks of age, open-field, object recognition, light-dark transition, elevated plus maze, and social interaction tests were performed. The brain glycerophospholipid fatty acid composition was investigated in 3-week-old and adult offspring by gas chromatography. The differences observed in behavior were indicative of lower anxiety in the EFAD mice compared to controls illustrated by more time spent in the open arms of the elevated plus maze (+ 41%, p < .05) and in the light compartment in the light-dark transition test (+ 63%, p < .05). The proportion of total n-3 fatty acids, especially 22:6n-3 in the brain, was lower with a compensatory increase in the proportion of total n-6 fatty acids, foremost 22:5n-6, in the EFAD mice compared to controls at 3 weeks of age. In the adult brains the fatty acid composition was normalized. In conclusion, our data show that EFAD during the perinatal period results in short-term alterations of fatty acid composition in brain and decreased anxiety in adult life.
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| 28. |
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| 29. |
- Bansal, Ruby, et al.
(författare)
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Polybrominated diphenyl ether (DE-71) interferes with thyroid hormone action independent of effects on circulating levels of thyroid hormone in male rats
- 2014
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Ingår i: Endocrinology. - : Oxford University Press. - 0013-7227 .- 1945-7170. ; 155:10, s. 4104-4112
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Tidskriftsartikel (refereegranskat)abstract
- Polybrominated diphenyl ethers (PBDEs) are routinely found in human tissues including cord blood and breast milk. PBDEs may interfere with thyroid hormone (TH) during development, which could produce neurobehavioral deficits. An assumption in experimental and epidemiological studies is that PBDE effects on serum TH levels will reflect PBDE effects on TH action in tissues. To test whether this assumption is correct, we performed the following experiments. First, five concentrations of diphenyl ether (0-30 mg/kg) were fed daily to pregnant rats to postnatal day 21. PBDEs were measured in dam liver and heart to estimate internal dose. The results were compared with a separate study in which four concentrations of propylthiouracil (PTU; 0, 1, 2, and 3 ppm) was provided to pregnant rats in drinking water for the same duration as for diphenyl ether. PBDE exposure reduced serum T4 similar in magnitude to PTU, but serum TSH was not elevated by PBDE. PBDE treatment did not affect the expression of TH response genes in the liver or heart as did PTU treatment. PTU treatment reduced T4 in liver and heart, but PBDE treatment reduced T4 only in the heart. Tissue PBDEs were in the micrograms per gram lipid range, only slightly higher than observed in human fetal tissues. Thus, PBDE exposure reduces serum T4 but does not produce effects on tissues typical of low TH produced by PTU, demonstrating that the effects of chemical exposure on serum T4 levels may not always be a faithful proxy measure of chemical effects on the ability of thyroid hormone to regulate development and adult physiology.
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| 30. |
- Andaloussi, Mounir, et al.
(författare)
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Design, Synthesis, and X-ray Crystallographic Studies of alpha-Aryl Substituted Fosmidomycin Analogues as Inhibitors of Mycobacterium tuberculosis 1-Deoxy-D-xylulose 5-Phosphate Reductoisomerase
- 2011
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 54:14, s. 4964-4976
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Tidskriftsartikel (refereegranskat)abstract
- The natural antibiotic fosmidomycin acts via inhibition of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. Fosmidomycin is active on Mycobacterium tuberculosis DXR (MtDXR), but it lacks antibacterial activity probably because of poor uptake. alpha-Aryl substituted fosmidomycin analogues have more favorable physicochemical properties and are also more active in inhibiting malaria parasite growth. We have solved crystal structures of MtDXR in complex with 3,4-dichlorophenyl substituted fosmidomycin analogues; these show important differences compared to our previously described forsmidomycin-DXR complex. Our best inhibitor has an IC(50) = 0.15 mu M on MtDXR but still lacked activity in a mycobacterial growth assay (MIC > 32 mu g/mL). The combined results, however, provide insights into how DXR accommodates the new inhibitors and serve as an excellent starting point for the design of other novel and more potent inhibitors, particularly against pathogens where uptake is less of a problem, such as the malaria parasite.
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| 31. |
- Bergman, Ingrid-Maria, et al.
(författare)
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European wild boars and domestic pigs display different polymorphic patterns in the Toll-like receptor (TLR)1, TLR2, TLR6, and TLR10 genes.
- 2010
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Ingår i: International Symposium on Animal Genomics for Animal Health Paris, France, 31 May – 2 June 2010. ; , s. 35-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The Toll-like receptors (TLR) are vitally important pattern recognition receptors linking innate and adaptive immunity. Several single nucleotide polymorphisms (SNP) in human TLR genes have been associated with disease. There are few studies on associations between polymorphisms in TLR genes and disease in pigs, but the TLR2/TLR6 heterodimer is activated by Mycoplasma hyopneumoniae, and the expression of TLR2, TLR4, and TLR9 is modulated in the presence of different Salmonella serovars. Porcine TLR1, TLR6, and TLR10 are located in a cluster on the p arm of chromosome 8, while TLR2 resides on the q arm. Previously, we identified quantitative trait loci (QTL) for immune-related traits on pig chromosome 8, close to the KIT gene and the microsatellite S0225, respectively. In order to explore polymorphism in some TLR genes in European wild boars and domestic pigs, TLR1, TLR2, and TLR6 were sequenced in 25 wild boars, representing three populations, and in 15 domestic pigs of Hampshire, Landrace, and Large White origin. Similarly, TLR10 was sequenced in 15 wild boars and 15 domestic pigs. In TLR1 and TLR2, more SNP were present in the domestic pigs than in the wild boars. In TLR6, SNP numbers were similar in both animal groups, but the level of heterozygosity was higher in the domestic pigs than in the wild boars. In TLR10, again, more SNP were present in the domestic pigs, and a higher number of nonsynonymous SNP were detected in TLR10 compared to the other genes. This may suggest redundancy for TLR10 in pigs.
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| 32. |
- Egenvall, Agneta, et al.
(författare)
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Days-lost to training and competition in relation to workload in 263 elite show-jumping horses in four European countries
- 2013
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Ingår i: Preventive Veterinary Medicine. - : Elsevier BV. - 0167-5877 .- 1873-1716. ; 112, s. 387-400
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Tidskriftsartikel (refereegranskat)abstract
- Orthopaedic, or other, injuries in sports medicine can be quantified using the ‘days-lost to training’ concept. Both the training regimen and the surface used in training and racing can affect the health of racehorses. Our aim was to associate ‘days-lost to training’ in elite-level show-jumpers to horse characteristics, training and management strategies, and the time spent working on various training and competition surfaces. We designed a longitudinal study of professional riders in four European countries. Data were recorded using training diaries. Reasons for days-lost were classified into non-acute and acute orthopaedic, medical, hoof-related, and undefined. We produced descriptive statistics of training durations, relative to type of training, surfaces used, and days-lost. We created zero-inflated negative-binomial random-effects models using the overall days-lost as outcome. In the whole dataset, duration variables related to training surfaces were analysed as independent. The Swedish data only were also used to test whether duration variables were related to competition surfaces. Thirty-one riders with 263 horses provided data on 39,028 days at risk. Of these, 2357 (6.0%) were days-lost (55% and 22% of these were due to non-acute and acute orthopaedic injuries, respectively) in 126 horses. In the all-country model, controlling for season, a significant variable was country. Switzerland and the UK had lower incidence-rate ratios (IR) compared to Sweden (IRs 0.2 and 0.03, respectively). Horses with previous orthopaedic problems had almost a doubled IR (1.8) of days-lost due to orthopaedic injury, compared to baseline. If the horse had jumping training more than 1 minute per day at risk the IRs were 6.9-7 (compared to less than this amount of time); this was, however, likely an effect of a small baseline. Variation in training was a protective factor with a dose-response relationship; the category with the highest variation had an IR of 0.1. In the Swedish model, controlling for season, there was an association of year (IR 2.8 year 2010). Further, if the horse rested >17-25% of the days at risk, or >33% of the DAR2, had IRs 3.5 and 3,0, compared to less time. Horses ≥6 years had IRs of 1.8-2.0, compared to younger horses. Limited training use of sand surface was a risk-factor (IR 2.2; >4≤12 min/day at risk), compared to not training on sand. Training/competing on sand-wood was a protective factor (IRs 0.4-0.5) compared to not using this surface.
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| 33. |
- Padra, János T, et al.
(författare)
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Aeromonas salmonicida Binds Differentially to Mucins Isolated from Skin and Intestinal Regions of Atlantic Salmon in an N-Acetylneuraminic Acid-Dependent Manner.
- 2014
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Ingår i: Infection and immunity. - 1098-5522. ; 82:12, s. 5235-45
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Tidskriftsartikel (refereegranskat)abstract
- Aeromonas salmonicida subsp. salmonicida infection, also known as furunculosis disease, is associated with high morbidity and mortality in salmonid aquaculture. The first line of defense the pathogen encounters is the mucus layer, which is predominantly comprised of secreted mucins. Here we isolated and characterized mucins from the skin and intestinal tract of healthy Atlantic salmon and studied how A. salmonicida bound to them. The mucins from the skin, pyloric ceca, and proximal and distal intestine mainly consisted of mucins soluble in chaotropic agents. The mucin density and mucin glycan chain length from the skin were lower than were seen with mucin from the intestinal tract. A. salmonicida bound to the mucins isolated from the intestinal tract to a greater extent than to the skin mucins. The mucins from the intestinal regions had higher levels of sialylation than the skin mucins. Desialylating intestinal mucins decreased A. salmonicida binding, whereas desialylation of skin mucins resulted in complete loss of binding. In line with this, A. salmonicida also bound better to mammalian mucins with high levels of sialylation, and N-acetylneuraminic acid appeared to be the sialic acid whose presence was imperative for binding. Thus, sialylated structures are important for A. salmonicida binding, suggesting a pivotal role for sialylation in mucosal defense. The marked differences in sialylation as well as A. salmonicida binding between the skin and intestinal tract suggest interorgan differences in the host-pathogen interaction and in the mucin defense against A. salmonicida.
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| 34. |
- Uvnäs-Moberg, Kerstin
(författare)
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Psychosocial and psychophysiological effects of human-animal interactions: the possible role of oxytocin
- 2012
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 3
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Forskningsöversikt (refereegranskat)abstract
- During the last decade it has become more widely accepted that pet ownership and animal assistance in therapy and education may have a multitude of positive effects on humans. Here, we review the evidence from 69 original studies on human-animal interactions (HAI) which met our inclusion criteria with regard to sample size, peer-review, and standard scientific research design. Among the well-documented effects of HAI in humans of different ages, with and without special medical, or mental health conditions are benefits for: social attention, social behavior, interpersonal interactions, and mood; stress-related parameters such as cortisol, heart rate, and blood pressure; self-reported fear and anxiety; and mental and physical health, especially cardiovascular diseases. Limited evidence exists for positive effects of HAI on: reduction of stress-related parameters such as epinephrine and norepinephrine; improvement of immune system functioning and pain management; increased trustworthiness of and trust toward other persons; reduced aggression; enhanced empathy and improved learning. We propose that the activation of the oxytocin system plays a key role in the majority of these reported psychological and psychophysiological effects of HAI. Oxytocin and HAI effects largely overlap, as documented by research in both, humans and animals, and first studies found that HAI affects the oxytocin system. As a common underlying mechanism, the activation of the oxytocin system does not only provide an explanation, but also allows an integrative view of the different effects of HAI.
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| 35. |
- Zsigmond, Peter, et al.
(författare)
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Neurotransmitter levels in basal ganglia during levodopa and deep brain stimulation treatment in Parkinson’s disease
- 2014
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Ingår i: Neurology and Clinical Neuroscience. - : John Wiley & Sons. - 2049-4173. ; 2:5, s. 149-155
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Tidskriftsartikel (refereegranskat)abstract
- Background The mechanism by which deep brain stimulation of the nucleus subthalamicus improves Parkinson’s disease symptoms remains unclear. In a previous perioperative study, we showed that there might be alterations of neurotransmitter levels in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus. Aim In this study, we examined whether deep brain stimulation of the nucleus subthalamicus and levodopa infusion interact and affect the levels of neurotransmitters. Methods Five patients with advanced Parkinson’s disease took part in the study. During subthalamic nucleus surgery, microdialysis catheters were inserted bilaterally in the globus pallidum interna and unilaterally in the right putamen. A study protocol was set up and was followed for 3 days. Levodopa infusion with and without concomitant bilateral deep brain stimulation of the nucleus subthalamicus was also carried out. Results The putaminal dopamine levels increased during deep brain stimulation of the nucleus subthalamicus. In addition, an increase of gamma amino buturic acid concentrations in the globus pallidum interna during deep brain stimulation of the nucleus subthalamicus and during levodopa infusion was found. Conclusions These findings provide evidence that the subthalamic nucleus has a direct action on the substantia nigra pars compacta, and that deep brain stimulation of the nucleus subthalamicus might indirectly release putaminal dopamine. There is also evidence that deep brain stimulation of the nucleus subthalamicus interferes with levodopa therapy resulting in higher levels of levodopa in the brain, explaining why it is possible to decrease levodopa medication after deep brain stimulation surgery.
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| 36. |
- Appelgren, Lars-Erik
(författare)
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Mistel - inte bara för julkyssar?
- 2014
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Ingår i: Svensk Veterinärtidning. - 0346-2250. ; 66, s. 29-32
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 37. |
- Appelgren, Lars-Erik
(författare)
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Myrra: mytomspunnen medicin
- 2012
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Ingår i: Svensk Veterinärtidning. - 0346-2250. ; , s. 41-42
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 38. |
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| 39. |
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| 40. |
- Lai, H., et al.
(författare)
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A novel isotropic conductive adhesive with Ag flakes, BN and SiC nanoparticles
- 2010
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Ingår i: 2010 International Symposium on Advanced Packaging Materials: Microtech, APM '10. - 9781424467563 ; , s. 49-53
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Isotropic conductive adhesives (ICAs) with lower bonding temperature, higher resolution and environmental friendly have been used extensively in packaging process. In order to improve the electrical and thermal conductive properties of ICAs, two kinds of bimodal high temperature stable ICAs with matrix SHT6 and fillers with composition of macro silver flakes and boron nitride nanoparticles or macro silver flakes and silicon carbide nanoparticles were studied. In these two kinds of adhesives, the silver flakes were 75wt%, and the contents of nanoparticles were Owt%, 0.5wt%, 1.5wt%, 2.5wt%, 3wt%, 5wt% in weight. All the samples were cured at 150°C for 1 hour. SEM images and EDS results show the nanoparticles disperse randomly in the ICA. The electrical resistivity of these ICAs depends on the contents of silver flakes and is hardly affected by BN nanoparticles and SiC nanoparticles. The thermal conductivity of these ICAs increases firstly with the weight increase of the BN nanoparticles and SiC nanoparticles. And then it decreases when the content of the nanoparticles beyond a certain point. ©2010 IEEE.
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| 41. |
- Ley, Cecilia, et al.
(författare)
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Effects of high mobility group box protein-1, interleukin-1β, and interleukin-6 on cartilage matrix metabolism in three-dimensional equine chondrocyte cultures.
- 2011
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Ingår i: Connective tissue research. - : Informa UK Limited. - 1607-8438 .- 0300-8207. ; 52:4, s. 290-300
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Tidskriftsartikel (refereegranskat)abstract
- The effects of high mobility group box protein (HMGB)-1, interleukin (IL)-1β, and IL-6 on equine articular chondrocytes were investigated, with emphasis on detecting differences between anatomical sites exposed to different loading in vivo, using three-dimensional (3D) cell cultures established with chondrocytes from dorsal radial facet (DRF, highly loaded) and palmar condyle (PC, less loaded) of the third carpal bone (C3). Expression of important genes involved in cartilage metabolism, presence of glycosaminoglycans and cartilage oligomeric matrix protein (COMP) in pellets, and concentrations of matrix metalloproteinase (MMP)-13 and aggrecan epitope CS 846 were evaluated. Compared to controls, IL-1β treatment increased gene expression of versican, matrix-degrading enzymes, and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased aggrecan and collagen type I and type II expression. In addition, IL-1β-treated pellets showed decreased safranin O staining and increased COMP immunostaining and MMP-13 concentrations in culture supernatants. Effects of IL-6 and HMGB-1 on gene expression were variable, although upregulation of Sry-related high-mobility group box 9 (Sox9) was often present and statistically increased in HMGB-1-treated pellets. Response to cytokines rarely differed between DRF and PC pellets. Thus, site-associated cartilage deterioration in equine carpal osteoarthritis (OA) is not explained by topographically different responses to inflammatory mediators. Differences in gene expressions of structural matrix proteins in untreated DRF and PC pellets were noted in the youngest horses, which may indicate differences in the chondrocytes potential to produce matrix in vivo. Overall, a strong catabolic response was induced by IL-1β, whereas slight anabolic effects were induced by IL-6 and HMGB-1.
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| 42. |
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| 43. |
- Tyden, Eva, et al.
(författare)
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Differential gene expression of CYP3A isoforms in equine liver and intestines
- 2012
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Ingår i: Journal of Veterinary Pharmacology and Therapeutics. - : Wiley. - 0140-7783 .- 1365-2885. ; 35, s. 588-595
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Tidskriftsartikel (refereegranskat)abstract
- Tyden, E., Lofgren, M., Pegolo, S., Capolongo, F., Tjalve, H., Larsson, P. Differential gene expression of CYP3A isoforms in equine liver and intestines. J. vet. Pharmacol. Therap. 35, 588595. Recently, seven CYP3A isoforms CYP3A89, CYP3A93, CYP3A94, CYP3A95, CYP3A96, CYP3A97 and CYP129 have been isolated from the horse genome. In this study, we have examined the hepatic and intestinal gene expression of these CYP3A isoforms using TaqMan probes. We have also studied the enzyme activity using luciferin-isopropyl acetal (LIPA) as a substrate. The results show a differential gene expression of the CYP3A isoforms in the liver and intestines in horses. In the liver, CYP3A89, CYP3A94, CYP3A96 and CYP3A97 were highly expressed, while in the intestine there were only two dominating isoforms, CYP3A93 and CYP3A96. The isoform CYP3A129 was not detected in the liver or the intestine, although this gene consists of a complete set of exons and should therefore code for a functional protein. It is possible that this gene is expressed in tissues other than the liver and intestines. In the intestine, both CYP3A96 and CYP3A93 showed the highest gene expression in the duodenum and the proximal parts of the jejunum. This correlated with a high protein expression in these tissues. Studies of the enzyme activity showed the same Km for the LIPA substrate in the liver and the intestine, while the maximum velocity (Vmax) in the liver was higher than in the intestine. Our finding of a differential gene expression of the CYP3A isoforms in the liver and the intestines contributes to a better understanding of drug metabolism in horses.
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| 44. |
- Andersson, Lisa
(författare)
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Equine trait mapping : from disease loci to the discovery of a major gene controlling vertebrate locomotion
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Assigning function to genes is essential for a better understanding of biological systems. To date, approximately half of the genes in the vertebrate genome have known function. Domestic animals are a rich source for trait mapping and in this thesis we have mapped three distinct equine phenotypes. The result provides increased knowledge regarding gene function and importantly, practical implications for horse welfare. In paper I and IV, we confirm that Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome is inherited as an incompletely dominant trait (p= 2.2x10-16). By first identifying a 208 kb identity-by decent (IBD) region and subsequently excluding polymorphic sites identified through Illumina sequencing, we conclude that the gene PMEL causes these defects in horse. Our findings, together with functional analyses recently published, support that the cause of MCOA syndrome is a missense mutation (Arg625Cys) near the transmembrane region of PMEL that results in altered biochemical properties. In paper II we show that variants in the MHC-II region influence the susceptibility to equine Insect Bite Hypersensitivity with the same marker risk allele identified in two distinct populations, OR 4.19 (p= 2.3x10-5) and 1.48 (p= 0.04) for Icelandic horses and Exmoor ponies respectively. In addition, homozygosity across the MHC-II region confers a higher risk of developing disease, OR= 2.67 (p= 1.3x10-3). Finally, in paper III we utilize the EquineSNP50 BeadChip to identify the first Gait locus in horse. A highly significant SNP (EMP2= 2.0x10-4) was identified to be consistent with a recessive mode of inheritance for the lateral gait pace in Icelandic horses, and confirmed in an independent sample set (p= 2.4x10-14). Illumina sequencing of an established IBD region identified a nonsense mutation in the gene DMRT3. A clearly dichotomous distribution in a panel of gaited and non-gaited breeds revealed that the DMRT3 mutation is permissive for a variety of alternate gaits. The mutation also has a favorable effect in harness racing horses. Functional characterization of the truncated protein demonstrated correct localization and an intact DNA binding profile. mRNA expression in a small population of commissural neurons from the spinal cord was confirmed in mutant and wild type horses. Further, a DMRT3 null mouse displayed a change in spinal cord circuit signaling and locomotion. These findings reveal a new molecule involved in the regulation of limb movement.
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| 45. |
- Jansson, Desirée, et al.
(författare)
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Northern fowl mite (Ornithonyssus sylviarum) in Sweden
- 2014
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Ingår i: Medical and Veterinary Entomology. - : Wiley. - 0269-283X .- 1365-2915. ; 28:4, s. 443-446
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Tidskriftsartikel (refereegranskat)abstract
- Haematophagous mites were collected from the vent region and plumage of chickens in six hobby flocks of ornamental breeds in Sweden, one of which included turkeys. Soiled vent skin and feathers, dermatitis, hyperkeratosis, skin necroses and ulcers were observed in 12 necropsied birds from two of the flocks. The mites were identified as the northern fowl mite Ornithonyssus sylviarum (Mesostigmata: Macronyssidae). This was supported by sequence analysis of a 642-bp region in the mitochondrial cytochrome oxidase subunit 1 (COI) gene (COI) in mites collected from five flocks, which showed 97–99% sequence similarity to O. sylviarum by blast analysis. Pairwise sequence comparisons revealed nucleotide variations in the range of 0–2.8%, whereas amino acid sequences were highly conserved. This paper represents one of very few records of O. sylviarum in European poultry, and is the first to report COI sequence data for O. sylviarum from poultry in Europe.
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| 46. |
- Waern, Ida
(författare)
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The role of mast cell proteases in allergic disease and apoptosis
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Mast cells (MCs) are key effector cells in allergic reactions, through the release of a wide variety of granule-stored and de novo synthesized inflammatory mediators. The MC secretory granules contain exceedingly high levels of serglycin proteoglycan and the heparin-binding proteases chymase, tryptase and carboxypeptidase A. In this thesis the contribution of mouse mast cell protease (mMCP)-4, which is thought to be the functional homolog to the human chymase, was studied in the context of allergic airway inflammation. Using two models of allergic airway inflammation, wild-type (WT) and mMCP-4 deficient (mMCP-4-/-) mice were treated with ovalbumin (OVA) or with house dust mite (HDM) extract. We found that the OVA challenged mMCP-4-/- mice displayed increased airway hyperreactivity and lung eosinophilia and in the HDM model they displayed increased serum IgE levels. Moreover, the level of IL-33, a pro-inflammatory cytokine, was enhanced in the lung tissue in mMCP-4-/- mice compared to WT mice after HDM-treatment. The active proteases stored in MC granules have the ability to cleave a number of components upon degranulation. We could demonstrate that proteolytic degradation of IL-13 by MCs is mediated by a serine protease, dependent on serglycin proteoglycan for its storage. Permeabilization of lysosomal membranes often leads to apoptosis and the released proteases take part in this process, activating pro-apoptotic compounds. We have found that serglycin-/- MCs are more resistant to apoptosis induced by secretory granule damage. We showed that serglycin-/- MCs exhibited reduced caspase-3 activity and protease activity in the cytosol compared to WT cells. Taken together, the studies in this thesis suggest that MCs chymase plays a protective role in the development of allergic airway inflammation and this could possibly be explained by chymases ability to degrade the pro-inflammatory cytokine, IL-33. In addition, we also suggest that serglycin proteoglycan and serglycin-dependent MC proteases participate in IL-13 degradation as well as in MC apoptosis induced by secretory granule damage.
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| 47. |
- Wolinski, J., et al.
(författare)
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Effect of feeding colostrum versus exogenous immunoglobulin G on gastrointestinal structure and enteric nervous system in newborn pigs
- 2012
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Ingår i: Journal of Animal Science. - : Oxford University Press (OUP). - 1525-3163 .- 0021-8812. ; 90, s. 327-329
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Tidskriftsartikel (refereegranskat)abstract
- Colostrum is an indispensable source of antibodies (IgG) protecting the newborn pig against infection. We studied the effect of feeding colostrum and purified IgG on early structure and development of the gastrointestinal tract (GIT). Newborn littermate pigs were fed either colostrum, an elemental diet (ED), or an ED supplemented with purified serum IgG (ED + IgG) for 24 h or then only ED up to 72 h. Afterwards, pigs were slaughtered. Colostrum-fed pigs or ED supplemented with IgG (ED + IgG) increased thickness (P < 0.001) of stomach mucosa and muscularis (P < 0.05) compared to the ED group not receiving IgG. Feeding an ED supplemented with IgG improved morphology of the GIT towards that of colostrum-fed piglets and indicates a beneficial effect of IgG on GIT development in neonatal pigs. Immunohistochemical studies indicate that ED feeding may influence the expression of nitric oxide synthase in jejunal myenteric (but not submucous) neurons of newborn pigs.
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| 48. |
- Ågren, Joakim
(författare)
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Microevolution during an Anthrax Outbreak Leading to Clonal Heterogeneity and Penicillin Resistance
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Anthrax is a bacterial disease primarily affecting grazing animals but it can also cause severe disease in humans. We have used genomic epidemiology to study microevolution of the bacterium in a confined outbreak in cattle which involved emergence of an antibiotic-resistant phenotype. At the time of death, the animals contained a heterogeneous population of Single Nucleotide Variants (SNVs), some being clonal but most being subclonal. We found that independent isolates from the same carcass had similar levels of SNV differences as isolates from different animals. Furthermore the relative levels of subclonal populations were different in different locations in the same carcass. The heterogeneity appeared to be derived in part from heterogeneity in the infectious dose. The resistance phenotype was linked to clonal mutations in an anti-sigma factor gene and in one case was preceded by an acquisition of a hypermutator phenotype. In another animal, small subclonal populations were observed with counteracting mutations that had turned off the resistance genes. In summary, this study shows the importance of accounting for both acquired and inherited heterogeneity when doing high-resolution infection tracing and when estimating the risks associated with penicillin treatment.
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| 49. |
- Liu, Cheng, et al.
(författare)
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Gastric de novo Muc13 expression and spasmolytic polypeptide-expressing metaplasia during Helicobacter heilmannii infection.
- 2014
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Ingår i: Infection and immunity. - 1098-5522. ; 82:8, s. 3227-39
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter heilmannii is a zoonotic bacterium that has been associated with gastric disease in humans. In this study, the mRNA expression of mucins in the stomach of BALB/c mice was analyzed at several time points during a 1-year infection with this bacterium, during which gastric disease progressed in severity. Markers for acid production by parietal cells and mucous metaplasia were also examined. In the first 9 weeks postinfection, the mRNA expression of Muc6 was clearly upregulated in both the antrum and fundus of the stomach of H. heilmannii-infected mice. Interestingly, Muc13 was upregulated already at 1 day postinfection in the fundus of the stomach. Its expression level remained high in the stomach over the course of the infection. This mucin is, however, not expressed in a healthy stomach, and high expression of this mucin has so far only been described in gastric cancer. In the later stages of infection, mRNA expression of H(+)/K(+)-ATPase α/β and KCNQ1 decreased, whereas the expression of Muc4, Tff2, Dmbt1, and polymeric immunoglobulin receptor (pIgR) increased starting at 16 weeks postinfection onwards, suggesting the existence of spasmolytic polypeptide-expressing metaplasia in the fundus of the stomach. Mucous metaplasia present in the mucosa surrounding low-grade mucosa-associated lymphoid tissue (MALT) lymphoma-like lesions was also histologically confirmed. Our findings indicate that H. heilmannii infection causes severe gastric pathologies and alterations in the expression pattern of gastric mucins, such as Muc6 and Muc13, as well as disrupting gastric homeostasis by inducing the loss of parietal cells, resulting in the development of mucous metaplasia.
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| 50. |
- Waern, Ida, et al.
(författare)
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Interleukin-6 degradation by mast cells is mediated by serglycin-dependent serine proteases
- 2013
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Mast cells contain large amounts of fully active proteases, i.e. chymase, tryptase and carboxypeptidase A (CPA3), that are stored together with serglycin (a proteoglycan with heparin side chains) in secretory granules. Hence, mast cell proteases are massively released upon degranulation and they may have a large impact on the local inflammatory reaction, e.g. by degrading various bioactive proteins. The objective of this study was to investigate the possibility if mast cells could regulate the levels of IL-6, a cytokine with a wide variety of biological functions. We found that cultured peritoneal mast cells from wild type mice can efficiently degrade IL-6 upon degranulation, whereas MCs from serglycin-deficient mice totally lacked this ability. Moreover, the addition of a serine protease inhibitor significantly reduced the proteolytic degradation of IL-6. Our data suggest that degradation of IL-6 by mast cells is mediated by serglycin-dependent serine proteases.
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