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Significant Distortion (significant + distortion)
Selected AbstractsThe IBD international genetics consortium provides further evidence for linkage to IBD4 and shows gene-environment interactionINFLAMMATORY BOWEL DISEASES, Issue 1 2005Marie Pierik MD Abstract Background and Aims: The inflammatory bowel diseases (IBDs) Crohn's disease (CD) and ulcerative colitis are complex disorders with an important genetic determinant. One gene associated with CD has been identified: NOD2/CARD15. Two independent genome-wide scans found significant evidence (logarithm of odds [LOD] 3.6) and suggestive evidence (LOD 2.8) for linkage on locus 14q11-12, also known as the IBD4 locus. To further characterize this locus, we assessed gene-environment interaction (IBD4 × smoking) and phenotypic heterogeneity in a large cohort of IBD-affected sibling pairs as part of an ongoing international collaborative effort. Patients and Methods: A total of 733 IBD families, comprising 892 affected sibling pairs, were genotyped for microsatellites D14S261, D14S283, D14S972, and D14S275, spanning the IBD4 locus. Information on gender, ethnicity, age at onset, smoking at diagnosis, extraintestinal manifestations, and disease location was available. Results: A significant distortion in the mean allele sharing (MAS) between affected siblings was observed for CD patients only at each of the four markers (54.6%, 52.8%, 50.4%, and 53.3%, respectively). Maximum linkage for CD was observed at marker D14S261 (multipoint nonparametric linkage score 2.36; P , 0.01; MAS 54.6%). MAS was higher in CD families in which all siblings or at least one sibling smoked compared with nonsmoking CD families (MAS, 58.90%, 57.50%, and 52.80%, respectively). Conclusions: The IBD International Genetics Consortium replicated the IBD4 locus on chromosome 14q for CD and also showed evidence for a gene-environment interaction at this locus. Further studies are needed to explore the mechanism by which smoking influences IBD4. [source] Impact of BRCA mutations on female fertility and offspring sex ratio,AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 2 2010Roxana Moslehi Positive selection for inherited mutations in breast and ovarian cancer predisposing genes, BRCA1 and BRCA2, may contribute to the high frequency of BRCA mutations among the Ashkenazi Jewish population. Impact of BRCA mutations on fertility has not been generally explored in epidemiologic studies. There are reports of distorted sex ratios in BRCA carrier families but these findings have been attributed to bias. We investigated the effect of BRCA mutations on female fertility and offspring sex ratio in a study of 260 Ashkenazi Jewish women with ovarian cancer and 331 controls, unselected for age or family history of the disease. Pregnancy success was similar for 96 mutation carrier (0.84) and 164 noncarrier cases (0.87) and controls (0.83). After adjusting for covariates, there were no significant differences between BRCA carrier and noncarrier cases and controls with regards to fertility, despite lower pregnancy rates among all cases compared to controls (P = 0.0049). Male/female sex ratios were significantly lower among offspring of carriers (0.71) than offspring of noncarriers (0.95) or those of the controls (0.99). Comparisons among the three groups yielded statistically significant distortion against males among the offspring of known and obligate BRCA carriers compared to noncarriers (OR = 0.74, 95% CI:0.55,0.99) and controls (OR = 0.71, 95% CI:0.54,0.94). In conclusion, we did not find evidence for an effect of BRCA mutations on female fertility. We found a significant excess of females among the offspring of female carriers of BRCA1 and BRCA2 mutations. Potential contribution of observed sex ratio distortions to positive selection for BRCA mutations may warrant further investigation. Am. J. Hum. Biol., 2010. © 2009 Wiley-Liss, Inc. [source] Structure of the buffalo secretory signalling glycoprotein at 2.8,Å resolutionACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 4 2007Abdul S. Ethayathulla The crystal structure of a 40,kDa signalling glycoprotein from buffalo (SPB-40) has been determined at 2.8,Å resolution. SPB-40 acts as a protective signalling factor by binding to viable cells during the early phase of involution, during which extensive tissue remodelling occurs. It was isolated from the dry secretions of Murrah buffalo. It was purified and crystallized using the hanging-drop vapour-diffusion method with 19% ethanol as the precipitant. The protein was also cloned and its complete nucleotide and amino-acid sequences were determined. When compared with the sequences of other members of the family, the sequence of SPB-40 revealed two very important mutations in the sugar-binding region, in which Tyr120 changed to Trp120 and Glu269 changed to Trp269. The structure showed a significant distortion in the shape of the sugar-binding groove. The water structure in the groove is also drastically altered. The folding of the protein chain in the flexible region comprising segments His188,His197, Phe202,Arg212 and Tyr244,Pro260 shows large variations when compared with other proteins of the family. [source] Platinum Complexes of Naphthalene-1,8-dichalcogen and Related Polyaromatic Hydrocarbon LigandsCHEMISTRY - A EUROPEAN JOURNAL, Issue 7 2004Stephen M. Aucott Dr. Abstract Platinum bisphosphine complexes bearing dichalcogen-derivatised naphthalene, acenaphthene or phenanthrene ligands have been prepared by either oxidative addition to zero-valent platinum species or from [PtCl2(PPhR2)] (R=Ph or Me) and the disodium or dilithium salts of the parent disulfur, diselenide or mixed S/Se species. The parent naphthalene, acenaphthene and phenanthrene chalcogen compounds were treated with either [Pt(PPh3)4] or [Pt(C2H4)(PMe3)2] (prepared in situ from [PtCl2(PMe3)2], ethene and sodium naphthalide or super hydride [LiBEt3H]) to give the appropriate platinum(II) species. The dilithium salts of 1,8-E2 -naphthalene (E=S or Se) prepared in situ by reduction of the EE bond with [LiBEt3H] were treated with [PtCl2(PPh3)2] to give [Pt(1,8-E2 -nap)(PPh3)2]. The tetraoxides [Pt(1,8-(S(O)2)2 -nap)(PR3)2] (PR3=PPh3 or PMe2Ph) were prepared in a similar metathetical manner from the appropriate [PtCl2(PR3)] complexes and the disodium salt of naphthalene 1,8-disulfinic acid (1,8-(S(O)ONa)2 -nap). The X-ray structures of selected examples reveal bidentate coordination with the naphthalene-E2 unit hinged (111,137°) with respect to the coordination plane. The naphthalene ring suffers significant distortion from planarity. [source] Quantitative ASL muscle perfusion imaging using a FAIR-TrueFISP technique at 3.0,TNMR IN BIOMEDICINE, Issue 1 2006Andreas Boss Abstract The feasibility of muscle perfusion imaging with diagnostic image quality was demonstrated using the FAIR-TrueFISP arterial spin labeling technique on a clinical 3.0,T whole-body scanner. In eight healthy volunteers (24 to 42 years old), quantitative perfusion maps of the forearm musculature were acquired before and after intense exercise. All measurements were carried out in a 3.0,T whole-body MR unit in combination with an eight-channel head coil. Pulsed arterial spin labeling and data recording were performed with an adapted FAIR-TrueFISP technique and quantitative perfusion maps were calculated on a pixel-by-pixel basis by means of the extended Bloch equations. Perfusion images with an in-plane resolution of 1,mm showed no significant distortions or blurring. Perfusion,time curves could be recorded with a temporal resolution of 6.4,s. Maximum perfusion in the musculature was found ,2,min after exercise, reaching values of up to 220,mL/min per 100,g of tissue with good delineation between the active muscles and the musculature not involved in the exercise. In conclusion, the TrueFISP pulsed arterial spin labeling technique allows patient-friendly assessment of muscular perfusion in a clinical whole-body scanner. Copyright © 2006 John Wiley & Sons, Ltd. [source] | |||||||||||||