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Träfflista för sökning "WFRF:(Fredholm B B) srt2:(2010-2014)"

Search: WFRF:(Fredholm B B) > (2010-2014)

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1.
  • Groenen, M. A., et al. (author)
  • Analyses of pig genomes provide insight into porcine demography and evolution
  • 2012
  • In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 491:7424, s. 393-398
  • Journal article (peer-reviewed)abstract
    • For 10,000 years pigs and humans have shared a close and complex relationship. From domestication to modern breeding practices, humans have shaped the genomes of domestic pigs. Here we present the assembly and analysis of the genome sequence of a female domestic Duroc pig (Sus scrofa) and a comparison with the genomes of wild and domestic pigs from Europe and Asia. Wild pigs emerged in South East Asia and subsequently spread across Eurasia. Our results reveal a deep phylogenetic split between European and Asian wild boars approximately 1 million years ago, and a selective sweep analysis indicates selection on genes involved in RNA processing and regulation. Genes associated with immune response and olfaction exhibit fast evolution. Pigs have the largest repertoire of functional olfactory receptor genes, reflecting the importance of smell in this scavenging animal. The pig genome sequence provides an important resource for further improvements of this important livestock species, and our identification of many putative disease-causing variants extends the potential of the pig as a biomedical model.
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2.
  • Fredholm, B. B., et al. (author)
  • Fuels for transportation
  • 2010
  • In: Ambio. - : Springer Science and Business Media LLC. - 0044-7447 .- 1654-7209. ; 39:suppl. 1, s. 31-35
  • Journal article (peer-reviewed)abstract
    • There is a need to reduce the amount of fossil energy used for transport, both because of the easily available fossil fuel is becoming sparser and because of climate concerns. In this article, the concept of "peak oil" is briefly presented. Second, a practical approach to reduction of fossil fuel use for transport elaborated by two British commissions is presented. A key feature is the introduction of electric cars. This raises the third issue covered in this article: namely, how battery technology is going to meet the increasing needs posed by the transport sector
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4.
  • Saellstroem, J., et al. (author)
  • Inhibition of sodium-linked glucose reabsorption normalizes diabetes-induced glomerular hyperfiltration in conscious adenosine A(1)-receptor deficient mice
  • 2014
  • In: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 210:2, s. 440-445
  • Journal article (peer-reviewed)abstract
    • AimGlomerular hyperfiltration is commonly observed in diabetics early after the onset of the disease and predicts the progression of nephropathy. Sustained hyperglycaemia is also closely associated with kidney hypertrophy and increased electrolyte and glucose reabsorption in the proximal tubule. In this study, we investigated the role of the increased tubular sodium/glucose cotransport for diabetes-induced glomerular hyperfiltration. To eliminate any potential confounding effect of the tubuloglomerular feedback (TGF) mechanism, we used adenosine A(1)-receptor deficient (A(1)AR(-/-)) mice known to lack a functional TGF mechanism and compared the results to corresponding wild-type animals (A(1)AR(+/+)). MethodsDiabetes was induced by an intravenous bolus injection of alloxan. Glomerular filtration rate (GFR) was determined in conscious mice by a single bolus injection of inulin. The sodium/glucose cotransporters were inhibited by phlorizin 30min prior to GFR measurements. ResultsNormoglycaemic animals had a similar GFR independent of genotype (A(1)AR(+/+) 23311 vs. A(1)AR(-/-) 241 +/- 25Lmin(-1)), and induction of diabetes resulted in glomerular hyperfiltration in both groups (A(1)AR(+/+) 380 +/- 25 vs. A(1)AR(-/-) 336 +/- 35Lmin(-1); both Pless than0.05). Phlorizin had no effect on GFR in normoglycaemic mice, whereas it reduced GFR in both genotypes during diabetes (A(1)AR(+/+) 365 +/- 18 to 295 +/- 19, A(1)AR(-/-) 354 +/- 38 to 199 +/- 15Lmin(-1); both Pless than0.05). Notably, the reduction was more pronounced in the A(1)AR(-/-) (Pless than0.05). ConclusionThis study demonstrates that increased tubular sodium/glucose reabsorption is important for diabetes-induced hyperfiltration, and that the TGF mechanism is not involved in these alterations, but rather functions to reduce any deviations from a new set-point.
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5.
  • Fredholm, B, et al. (author)
  • Purines - 80 years and very much alive
  • 2010
  • In: Acta physiologica (Oxford, England). - : Wiley. - 1748-1716 .- 1748-1708. ; 199:2, s. 91-92
  • Journal article (other academic/artistic)
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6.
  • Gao, Xiang, et al. (author)
  • Adenosine A(1)-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment
  • 2011
  • In: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 301:6, s. R1669-R1681
  • Journal article (peer-reviewed)abstract
    • Adenosine mediates tubuloglomerular feedback responses via activation of A(1)-receptors on the renal afferent arteriole. Increased preglomerular reactivity, due to reduced nitric oxide (NO) production or increased levels of ANG II and reactive oxygen species (ROS), has been linked to hypertension. Using A(1)-receptor knockout (A(1)(-/-)) and wild-type (A(1)(+/+)) mice we investigated the hypothesis that A(1)-receptors modulate arteriolar and blood pressure responses during NO synthase (NOS) inhibition or ANG II treatment. Blood pressure and renal afferent arteriolar responses were measured in nontreated mice and in mice with prolonged N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME) or ANG II treatment. The hypertensive responses to L-NAME and ANG II were clearly attenuated in A(1)(-/-) mice. Arteriolar contractions to L-NAME (10(-4) mol/l; 15 min) and cumulative ANG II application (10(-12) to 10(-6) mol/l) were lower in A(1)(-/-) mice. Simultaneous treatment with tempol (10(-4) mol/l; 15 min) attenuated arteriolar responses in A(1)(+/+) but not in A(1)(-/-) mice, suggesting differences in ROS formation. Chronic treatment with L-NAME or ANG II did not alter arteriolar responses in A(1)(-/-) mice, but enhanced maximal contractions in A(1)(+/+) mice. In addition, chronic treatments were associated with higher plasma levels of dimethylarginines (asymmetrical and symmetrical) and oxidative stress marker malondialdehyde in A(1)(+/+) mice, and gene expression analysis showed reduced upregulation of NOS-isoforms and greater upregulation of NADPH oxidases. In conclusion, adenosine A(1)-receptors enhance preglomerular responses during NO inhibition and ANG II treatment. Interruption of A(1)-receptor signaling blunts L-NAME and ANG II-induced hypertension and oxidative stress and is linked to reduced responsiveness of afferent arterioles.
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7.
  • Jacobsen, Mette, et al. (author)
  • Characterisation of five candidate genes within the ETEC F4ab/ac candidate region in pigs
  • 2011
  • In: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 4
  • Journal article (peer-reviewed)abstract
    • BackgroundEnterotoxigenic Escherichia coli (ETEC) that express the F4ab and F4ac fimbriae is a major contributor to diarrhoea outbreaks in the pig breeding industry, infecting both newborn and weaned piglets. Some pigs are resistant to this infection, and susceptibility is inherited as a simple dominant Mendelian trait. Indentifying the genetics behind this trait will greatly benefit pig welfare as well as the pig breeding industry by providing an opportunity to select against genetically susceptible animals, thereby reducing the number of diarrhoea outbreaks. The trait has recently been mapped by haplotype sharing to a 2.5 Mb region on pig chromosome 13, a region containing 18 annotated genes.FindingsThe coding regions of five candidate genes for susceptibility to ETEC F4ab/ac infection (TFRC, ACK1, MUC20, MUC4 and KIAA0226), all located in the 2.5 Mb region, were investigated for the presence of possible causative mutations. A total of 34 polymorphisms were identified in either coding regions or their flanking introns. The genotyping data for two of those were found to perfectly match the genotypes at the ETEC F4ab/ac locus, a G to C polymorphism in intron 11 of TFRC and a C to T silent polymorphism in exon 22 of KIAA0226. Transcriptional profiles of the five genes were investigated in a porcine tissue panel including various intestinal tissues. All five genes were expressed in intestinal tissues at different levels but none of the genes were found differentially expressed between ETEC F4ab/ac resistant and ETEC F4ab/ac susceptible animals in any of the tested tissues.ConclusionsNone of the identified polymorphisms are obvious causative mutations for ETEC F4ab/ac susceptibility, as they have no impact on the level of the overall mRNA expression nor predicted to influence the composition of the amino acids composition. However, we cannot exclude that the five tested genes are bona fide candidate genes for susceptibility to ETEC F4ab/ac infection since the identified polymorphism might affect the translational apparatus, alternative splice forms may exist and post translational mechanisms might contribute to disease susceptibility.
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8.
  • Jacobsen, M, et al. (author)
  • Refined candidate region specified by haplotype sharing for Escherichia coli F4ab/F4ac susceptibility alleles in pigs
  • 2010
  • In: Animal Genetics. - : Wiley. - 0268-9146 .- 1365-2052. ; 41:1, s. 21-25
  • 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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