| 1. |
- Kiemeney, Lambertus A, et al.
(författare)
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A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
- 2010
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 415-9
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
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| 2. |
- Rafnar, Thorunn, et al.
(författare)
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European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.
- 2011
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 20:21, s. 4268-81
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Tidskriftsartikel (refereegranskat)abstract
- Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
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| 3. |
- Rothman, Nathaniel, et al.
(författare)
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A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 978-984
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.
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| 4. |
- Austin, James D, et al.
(författare)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 February 2011-31 March 2011.
- 2011
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 11:4, s. 757-758
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 111 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Acipenser oxyrinchus desotoi, Anopheles nuneztovari sensu lato, Asellus aquaticus, Calopteryx splendens, Calopteryx virgo, Centaurea aspera, Centaurea seridis, Chilina dombeyana, Proctoeces cf. lintoni and Pyrenophora teres f. teres.
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| 5. |
- Benoît, Catherine, et al.
(författare)
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The Guidelines for Social Life Cycle Assessment of products: Just in time!
- 2010
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Ingår i: The International Journal of Life Cycle Assessment. - : Springer Science and Business Media LLC. - 0948-3349 .- 1614-7502. ; 15:2, s. 156-163
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Authors of different sustainability journals, including authors of articles in past issues of the International Journal of Life Cycle Assessment have acknowledged the rising interest and the pressing need for a social and socio-economic life cycle assessment methodology and identified challenges in its development and implementation. Social life cycle assessment (LCA) allows identification of key issues, assessing, and telling the story of social conditions in the production, use, and disposal of products. In this article, the United Nations Environment Programme/The Society of Environmental Toxicology and Chemistry Guidelines for Social Life Cycle Assessment of Products will be presented. Aim and scope The guidelines demystifies the assessment of product life cycle social impacts and presents an effective framework representing the consensus of an international group of experts leading research in this field. The guidelines complement those for environmental life cycle assessment and life cycle costing, and by doing so contribute to the full assessment of goods and services within the context of sustainable development. They enable a larger group of stakeholders to engage. Key aspects of the framework and the research needs identified in the guidelines will be summarized. Conclusions In a globalized world where transparency and information occupies a predominant place and where consumers and companies reach out to shed light on both the brightest and the darkest side of the economy and, when applicable, transform its condition, social LCA brings strong value. At a moment where major companies and initiatives are going forward with using LCA and are trying to track and communicate about the social impacts of their products they are increasingly held accountable for the guidelines for social life cycle assessment arrive just in time to inform their efforts.
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| 6. |
- Engström, Patrik, 1982-, et al.
(författare)
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Mutations in hemG Mediate Resistance to Salicylidene Acylhydrazides, Demonstrating a Novel Link between Protoporphyrinogen Oxidase (HemG) and Chlamydia trachomatis Infectivity
- 2013
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Ingår i: Journal of Bacteriology. - Washington DC, USA : American Society for Microbiology. - 0021-9193 .- 1098-5530. ; 195:18, s. 4221-4230
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Tidskriftsartikel (refereegranskat)abstract
- Salicylidene acylhydrazides (SAHs) inhibit the type III secretion system (T3S) of Yersinia and other Gram-negative bacteria. In addition, SAHs restrict the growth and development of Chlamydia species. However, since the inhibition of Chlamydia growth by SAH is suppressed by the addition of excess iron and since SAHs have an iron-chelating capacity, their role as specific T3S inhibitors is unclear. We investigated here whether SAHs exhibit a function on C. trachomatis that goes beyond iron chelation. We found that the iron-saturated SAH INP0341 (IS-INP0341) specifically affects C. trachomatis infectivity with reduced generation of infectious elementary body (EB) progeny. Selection and isolation of spontaneous SAH-resistant mutant strains revealed that mutations in hemG suppressed the reduced infectivity caused by IS-INP0341 treatment. Structural modeling of C. trachomatis HemG predicts that the acquired mutations are located in the active site of the enzyme, suggesting that IS-INP0341 inhibits this domain of HemG and that protoporphyrinogen oxidase (HemG) and heme metabolism are important for C. trachomatis infectivity.
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| 7. |
- Silverstein, Rebecca A., et al.
(författare)
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The Incorporation of 5-Fluorouracil into RNA Affects the Ribonucleolytic Activity of the Exosome Subunit Rrp6
- 2011
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Ingår i: Molecular Cancer Research. - 1541-7786 .- 1557-3125. ; 9:3, s. 332-340
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Tidskriftsartikel (refereegranskat)abstract
- 5-Fluorouracil (5FU) is a fluoropyrimidine used for the treatment of solid tumors. 5FU is a precursor of dTTP and UTP during biogenesis, and it interferes with both DNA and RNA metabolism. The RNA exosome, a multisubunit complex with ribonucleolytic activity, has been identified as one of the targets of 5FU in yeast. Studies in human cells have shown that the catalytic subunit of the nuclear exosome, Rrp6, is specifically targeted. Here, we have investigated the direct effect of 5FU on the activity of Rrp6 in Drosophila S2 cells, and we have identified two aspects of Rrp6 function that are altered by 5FU. First, gel filtration analysis revealed that the repertoire of multimolecular complexes that contain Rrp6 is modified by exposure to 5FU, which is consistent with the proposal that incorporation of 5FU into RNA leads to the sequestration of Rrp6 in ribonucleoprotein complexes. Second, the incorporation of 5FU into RNA renders the RNA less susceptible to degradation by Rrp6, as shown by Rrp6 activity assays in vitro. Our results imply that aberrant transcripts synthesized in 5FU-treated cells cannot be turned over efficiently by the surveillance machinery. Together with previous results on the mechanisms of action of 5FU, our findings suggest that the cytotoxicity of 5FU at the RNA level is the result of at least three different effects: the increased levels of retroviral transcripts with mutagenic potential, the reduced synthesis of ribosomes, and the inhibition of the nuclear RNA surveillance pathways. Drugs that reinforce any of these effects may boost the cytotoxicity of 5FU.
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| 8. |
- Zepeda-Romero, L. C., et al.
(författare)
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Prediction of Retinopathy of Prematurity Using the Screening Algorithm WINROP in a Mexican Population of Preterm Infants
- 2012
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Ingår i: Archives of Ophthalmology. - 0003-9950. ; 130:6, s. 720-723
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To retrospectively validate the WINROP (weight, insulin-like growth factor I, neonatal, retinopathy of prematurity [ROP]) algorithm in identification of type 1 ROP in a Mexican population of preterm infants. Methods: In infants admitted to the neonatal intensive care unit at Hospital Civil de Guadalajara from 2005 to 2010, weight measurements had been recorded once weekly for 192 very preterm infants (gestational age [GA] <32 weeks) and for 160 moderately preterm infants (GA >= 32 weeks). Repeated eye examinations had been performed and maximal ROP stage had been recorded. Data are part of a case-control database for severe ROP risk factors. Results: Type 1 ROP was found in 51.0% of very preterm and 35.6% of moderately preterm infants. The WINROP algorithm correctly identified type 1 ROP in 84.7% of very preterm infants but in only 5.3% of moderately preterm infants. For infants with GA less than 32 weeks, the specificity was 26.6%, and for those with GA 32 weeks or more, it was 88.3%. Conclusions: In this Mexican population of preterm infants, WINROP detected type 1 ROP early in 84.7% of very preterm infants and correctly identified 26.6% of infants who did not develop type 1 ROP. Uncertainties in dating of pregnancies and differences in postnatal conditions may be factors explaining the different outcomes of WINROP in this population.
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