| 1. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 4. |
- Low, W C, et al.
(author)
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Hereditary multi-infarct dementia of the Swedish type is a novel disorder different from NOTCH3 causing CADASIL
- 2007
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In: Brain. - : Oxford University Press (OUP). - 0006-8950 .- 1460-2156. ; 130:Part 2, s. 357-367
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Journal article (peer-reviewed)abstract
- Several hereditary small vessel diseases (SVDs) of the brain have been reported in recent years. In 1977, Sourander and Wålinder described hereditary multi-infarct dementia (MID) in a Swedish family. In the same year, Stevens and colleagues reported chronic familial vascular encephalopathy in an English family bearing a similar phenotype. These disorders have invariably been suggested to be cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) but their genetic identities remain unknown. We used molecular, radiological and neuropathological methods to characterize these disorders. Direct DNA sequencing unexpectedly confirmed that affected members of the English family carried the R141C mutation in the NOTCH3 gene diagnostic of CADASIL. However, we did not detect any pathogenic mutations in the entire 8091 bp reading frame of NOTCH3 or find clear evidence for NOTCH3 gene linkage in the Swedish DNA. This was consistent with the lack of hyperintense signals in the anterior temporal pole and external capsule in Swedish subjects upon magnetic resonance imaging. We further found no evidence for granular osmiophilic material in skin biopsy or post-mortem brain samples of affected members in the Swedish family. In addition, there was distinct lack of NOTCH3 N-terminal fragments in the cerebral microvasculature of the Swedish hereditary MID subjects compared to the intense accumulation in the English family afflicted with CADASIL. Several differences in arteriosclerotic changes in both the grey and white matter were also noted between the disorders. The sclerotic index values, density of collagen IV immunoreactivity in the microvasculature and number of perivascular macrophages were greater in the English CADASIL samples compared to those from the Swedish brains. Multiple approaches suggest that the Swedish family with hereditary MID suspected to be CADASIL has a different novel disorder with dissimilar pathological features and belongs to the growing number of genetically uncharacterized familial SVDs.
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| 5. |
- Cox, Angela, et al.
(author)
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A common coding variant in CASP8 is associated with breast cancer risk
- 2007
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 352-358
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Journal article (peer-reviewed)abstract
- The Breast Cancer Association Consortium (BCAC) has been established to conduct combined case-control analyses with augmented statistical power to try to confirm putative genetic associations with breast cancer. We genotyped nine SNPs for which there was some prior evidence of an association with breast cancer: CASP8 D302H (rs1045485), IGFBP3 -202 C --> A (rs2854744), SOD2 V16A (rs1799725), TGFB1 L10P (rs1982073), ATM S49C (rs1800054), ADH1B 3' UTR A --> G (rs1042026), CDKN1A S31R (rs1801270), ICAM5 V301I (rs1056538) and NUMA1 A794G (rs3750913). We included data from 9-15 studies, comprising 11,391-18,290 cases and 14,753-22,670 controls. We found evidence of an association with breast cancer for CASP8 D302H (with odds ratios (OR) of 0.89 (95% confidence interval (c.i.): 0.85-0.94) and 0.74 (95% c.i.: 0.62-0.87) for heterozygotes and rare homozygotes, respectively, compared with common homozygotes; P(trend) = 1.1 x 10(-7)) and weaker evidence for TGFB1 L10P (OR = 1.07 (95% c.i.: 1.02-1.13) and 1.16 (95% c.i.: 1.08-1.25), respectively; P(trend) = 2.8 x 10(-5)). These results demonstrate that common breast cancer susceptibility alleles with small effects on risk can be identified, given sufficiently powerful studies.
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| 6. |
- Cui, Daqing, et al.
(author)
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Immobilization of radionuclides on iron canister material at simulated near-field conditions
- 2009
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In: Scientific Basis for Nuclear Waste Management XXXII. - Warrendale, Pa : Materials Research Society. - 9781605110967 ; 1124
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Conference paper (peer-reviewed)abstract
- This work is a continuation of a long-term spent fuel leaching and radionuclides immobilization (by iron canister) experiment under simulated near-field conditions, in deoxygenated 2 mM NaHCO3 solution with 1 Gy/h γ irradiation. The corrosion of iron canister material was investigated by electrochemical and microanalytical methods. Significant amounts of radionuclides (U, Np, Tc, Sr) were found to be immobilized on the corrosion layer of iron canister material by using SEM-WDS and SIMS methods. The observation is useful for bettering our understanding of near-field chemical processes at earlier canister failure conditions.
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| 7. |
- Cui, D., et al.
(author)
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On the behaviour of spent fuel under simulated early canister-failure conditions
- 2006
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In: Proceedings of the 11th International High Level Radioactive Waste Management Conference, IHLRWM. - 0894486918 - 9780894486913 ; , s. 925-932
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Conference paper (peer-reviewed)abstract
- This paper reports on the results of a long term experiment on spent fuel leaching, canister corrosion and radionuclide immobilization under repository conditions corresponding to early canister failure. A γ-dose of 850 mGy per hour, and Ar-flushed synthetic groundwater were used. During the first 287 days, the fractions of inventory in aqueous phase per day (f/d) increased nearly constantly for each radionuclide (except for 100Mo), with higher fractions for fission products than for actinides. After this initial stage, iron, cast iron and copper coupons (of̃30 mm2 size) were inserted into the leaching vessel: the concentrations of 238U, 237Np and 99Tc decreased by 80%, 97% and 88% to relatively stable levels (500ppb, 0.2ppb and 0.6ppb respectively). 239Pu concentrations slightly increased to the level of PuO2 solubility (0.5ppb). The leaching process for Cs, Mo and 90Sr was not influenced by the added metals. The pH and Eh values and corrosion potential were measured. The polarization resistance (Rp) was obtained from fitting of electrochemical impedance spectra, and then corrected by the surface area of the sample. The corrosion current density Icorr was calculated according to the Stern-Gary relationship, and using the same Tafel constants (26 mV)for all samples, i.e., Icorr = 0.026/Rp. The momentary corrosion rates of iron, cast iron and copper (Cu/Cu+) calculated based on the Faraday's law are in reasonable agreement with the values estimated from observation of thickness of corrosion layers using SEM microscope. The copper coupon appeared much more stable against corrosion than the other coupons. The corrosion layer and radionuclides deposited on corrosion products on iron coupons were analyzed by SEM-EDS and SIMS. Si was found to be coordinated with all iron corrosion products; however, redox sensitive elements U and Pu were mainly coordinated with the inner layer of iron corrosion products even though some 1-2 μm sized uranium-silica rich particles were found on the outer side of the iron corrosion layer. The findings of this work contribute to an improved understanding of the behaviour of spent fuel under near field repository conditions.
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| 8. |
- Garcia-Closas, Montserrat, et al.
(author)
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Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics
- 2008
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In: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 4:4, s. e1000054-
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Journal article (peer-reviewed)abstract
- A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
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