| 1. |
- Abdallah, J, et al.
(författare)
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Bose-Einstein correlations in W+W- events at LEP2
- 2005
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Ingår i: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 44:2, s. 161-174
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Tidskriftsartikel (refereegranskat)abstract
- Bose-Einstein correlations (BEC) between final state particles in the reaction e(+)e(-) -> W+ W- -> q(1)(q(2)) over barq(3)(q(4)over bar>) over bar) have been studied. Data corresponding to a total integrated luminosity of 550 pb(-1), recorded by the DELPHI detector at centre-of-mass energies ranging from 189 to 209 GeV, were analysed. An indication for inter-W BEC between like-sign particles has been found at the level of 2.4 standard deviations of the combined statistical and systematic uncertainties.
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| 2. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 3. |
- Ding, Li, et al.
(författare)
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Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
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Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
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| 4. |
- Aksentijevich, Ivona, et al.
(författare)
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An Autoinflammatory Disease with Deficiency of the Interleukin-1-Receptor Antagonist
- 2009
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 360:23, s. 2426-2437
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T cells. We report a disorder caused by mutations of IL1RN, which encodes the interleukin-1-receptor antagonist, with prominent involvement of skin and bone. METHODS We studied nine children from six families who had neonatal onset of sterile multifocal osteomyelitis, periostitis, and pustulosis. Response to empirical treatment with the recombinant interleukin-1-receptor antagonist anakinra in the first patient prompted us to test for the presence of mutations and changes in proteins and their function in interleukin-1-pathway genes including IL1RN. RESULTS We identified homozygous mutations of IL1RN in nine affected children, from one family from Newfoundland, Canada, three families from the Netherlands, and one consanguineous family from Lebanon. A nonconsanguineous patient from Puerto Rico was homozygous for a genomic deletion that includes IL1RN and five other interleukin-1-family members. At least three of the mutations are founder mutations; heterozygous carriers were asymptomatic, with no cytokine abnormalities in vitro. The IL1RN mutations resulted in a truncated protein that is not secreted, thereby rendering cells hyperresponsive to interleukin-1 beta stimulation. Patients treated with anakinra responded rapidly. CONCLUSIONS We propose the term deficiency of the interleukin-1-receptor antagonist, or DIRA, to denote this autosomal recessive autoinflammatory disease caused by mutations affecting IL1RN. The absence of interleukin-1-receptor antagonist allows unopposed action of interleukin-1, resulting in life-threatening systemic inflammation with skin and bone involvement. (ClinicalTrials.gov number, NCT00059748.)
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| 5. |
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| 6. |
- Enfalt, AC, et al.
(författare)
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Effects of a second mutant allele (V199I) at the PRKAG3 (RN) locus on carcass composition in pigs
- 2006
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Ingår i: Livestock Science. - : Elsevier BV. - 1871-1413. ; 99:2-3, s. 131-139
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Tidskriftsartikel (refereegranskat)abstract
- The effect of a second mutant allele (V1991, here denoted rn*) at the PRKAG3 (RN) locus on carcass composition was determined in 334 pigs, entire males and females, from crosses between Swedish Hampshire (H) and Finnish Landrace (L) (H x LH; LH x H; LH x LH). Pigs were classified according to DNA test into the following PRKAG3 genotypes: RN-IRN- (23%), RN-/rn(-) (24%), RN-/rn* (33%), rn(+)/rn(+) (8%), rn/rn* (9%) and rn*/rn* (2%). The pigs were slaughtered at a commercial slaughterhouse and assessed 24 h postmortem. Right sides were fabricated into primary wholesale cuts, then further processed into defatted hams and loins, and a subset of hams (n = 122) was dissected into the five major individual muscles. The genotype frequencies for the subsample were RN-/RN- (27%), RN-/rn(+) (20%), RN-/rn* (35%), rn(+)/rn(+) (9%), rn(+)/rn* (8%) and rn*/rn* (M). Weights were recorded for meat and bone in ham and loin, fat in ham, back and shoulder and the individual dissected muscles. The genotype effect was significant (P < 0.05) for estimated lean meat content and the proportions of meat and bone and fat in ham and loin (of carcass weight). Also, the content of meat and bone in ham and loin, in proportion of whole ham and loin, respectively, differed significantly (P < 0.01) between genotypes. Estimated lean meat content was highest for RN-/RN- (63.0%) and RN-/rn(+) (63.1%) and lowest in the combined group rn*/(-) (rn(+)/rn* and rn*/rn*, 61.7%); RN-/rn* (62.5%) and rn(+)/rn(+)(62.1%) were intermediate. The same results were found for meat and bone in ham and loin, as a proportion of whole ham and loin, respectively. RN-/RN- and RN-/rn(+) did not differ in any trait; however, they produced carcasses with the lowest proportions of fat within loin and the major wholesale cuts (ham, loin and shoulder). The carcass percentage of meat and bone in ham was higher in the three RN-/ genotypes (RN-/RN-, RN-/rn(+) and RN-/rn*, P < 0.05) than in the rn*/(-) group, whereas rn(+)/rn(+) did not (P > 0.05) differ from any of the other genotypes. RN-/rn(+) and RN-/rn* had higher (P < 0.05) proportion of meat and bone in loin compared to the rn*/(-) group. We conclude that the second mutant allele found at the PRKAG3 (RN) locus, rn*, decreased the lean meat content compared with the two other alleles (RN-, rn(+)). The RN-/RN- and RN-/rn(+) genotypes were leanest, followed by RN-/rn* and rn(+)/rn(+), and rn(+)/rn* and rn*/rn* were the fattest. (c) 2005 Elsevier B.V All rights reserved.
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| 7. |
- Fang, Hsin-Yu, et al.
(författare)
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Hypoxia-inducible factors 1 and 2 are important transcriptional effectors in primary macrophages experiencing hypoxia
- 2009
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 114:4, s. 844-859
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Tidskriftsartikel (refereegranskat)abstract
- Ischemia exists in many diseased tissues, including arthritic joints, atherosclerotic plaques, and malignant tumors. Macrophages accumulate in these sites and up-regulate hypoxia-inducible transcription factors (HIFs) 1 and 2 in response to the hypoxia present. Here we show that the gene expression profile in primary human and murine macrophages changes markedly when they are exposed to hypoxia for 18 hours. For example, they were seen to up-regulate the cell surface receptors, CXCR4 and GLUT1, and the potent, tumor-promoting cytokines, vascular endothelial growth factor A, interleukin (IL)-1 beta and IL-8, adrenomedullin, CXCR4, and angiopoietin-2. Hypoxia also stimulated their expression and/or phosphorylation of various proteins in the nuclear factor-kappa B (NF-kappa B) signaling pathway. We then used both genetic and pharmacologic methods to manipulate the levels of HIFs-1 alpha and 2 alpha or NF-kappa B in primary macrophages to elucidate their role in the hypoxic induction of many of these key genes. These studies showed that both HIF-1 and -2, but not NF-kappa B, are important transcriptional effectors regulating the responses of macrophages to such a period of hypoxia. Further studies using experimental mouse models are now warranted to investigate the role of such macrophage responses in the progression of various diseased tissues, such as malignant tumors. (Blood. 2009; 114: 844-859)
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