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131.
132.
OPCML at 11q25 is epigenetically inactivated and has tumor-suppressor function in epithelial ovarian cancer 总被引:12,自引:0,他引:12
133.
Late Cretaceous sediments from the Western Interior of North America yield exceptionally well preserved fossils that serve as proxies for the rapidly changing climate preceding the Cretaceous/Tertiary boundary (about 67-65 Myr ago). Here we reconstruct the ontogenetic history of a Maastrichtian-age fish, Vorhisia vulpes, by using the carbon, oxygen and strontium isotope ratios of four aragonite otoliths collected from the Fox Hills Formation of South Dakota. Individuals of V. vulpes spawned in brackish water (about 70-80% seawater) and during their first year migrated to open marine waters of the Western Interior Seaway, where they remained for 3 years before returning to the estuary, presumably to spawn and die. The mean delta(18)O from the marine growth phase of V. vulpes yields a seawater temperature of 18 degrees C, which is consistent with leaf physiognomy and general-circulation-model temperature estimates for the Western Interior during the latest Maastrichtian. 相似文献
134.
Hidden complexity in the mechanical properties of titin 总被引:2,自引:0,他引:2
Williams PM Fowler SB Best RB Toca-Herrera JL Scott KA Steward A Clarke J 《Nature》2003,422(6930):446-449
Individual molecules of the giant protein titin span the A-bands and I-bands that make up striated muscle. The I-band region of titin is responsible for passive elasticity in such muscle, and contains tandem arrays of immunoglobulin domains. One such domain (I27) has been investigated extensively, using dynamic force spectroscopy and simulation. However, the relevance of these studies to the behaviour of the protein under physiological conditions was not established. Force studies reveal a lengthening of I27 without complete unfolding, forming a stable intermediate that has been suggested to be an important component of titin elasticity. To develop a more complete picture of the forced unfolding pathway, we use mutant titins--certain mutations allow the role of the partly unfolded intermediate to be investigated in more depth. Here we show that, under physiological forces, the partly unfolded intermediate does not contribute to mechanical strength. We also propose a unified forced unfolding model of all I27 analogues studied, and conclude that I27 can withstand higher forces in muscle than was predicted previously. 相似文献
135.
Marie Morelato Mark Barash Lucas Blanes Scott Chadwick Jessirie Dilag Unnikrishnan Kuzhiumparambil Katie D. Nizio Xanthe Spindler Sebastien Moret 《Foundations of Science》2017,22(4):799-825
Forensic science and its influence on policing and the criminal justice system have increased since the beginning of the twentieth century. While the philosophies of the forensic science pioneers remain the pillar of modern practice, rapid advances in technology and the underpinning sciences have seen an explosion in the number of disciplines and tools. Consequently, the way in which we exploit and interpret the remnant of criminal activity are adapting to this changing environment. In order to best exploit the trace, an interdisciplinary approach to both research and investigation is required. In this paper, nine postdoctoral research fellows from a multidisciplinary team discuss their vision for the future of forensic science at the crime scene, in the laboratory and beyond. This paper does not pretend to be exhaustive of all fields of forensic science, but describes a portion of the postdoctoral fellows’ interests and skills. 相似文献
136.
Willer CJ Sanna S Jackson AU Scuteri A Bonnycastle LL Clarke R Heath SC Timpson NJ Najjar SS Stringham HM Strait J Duren WL Maschio A Busonero F Mulas A Albai G Swift AJ Morken MA Narisu N Bennett D Parish S Shen H Galan P Meneton P Hercberg S Zelenika D Chen WM Li Y Scott LJ Scheet PA Sundvall J Watanabe RM Nagaraja R Ebrahim S Lawlor DA Ben-Shlomo Y Davey-Smith G Shuldiner AR Collins R Bergman RN Uda M Tuomilehto J Cao A Collins FS Lakatta E Lathrop GM Boehnke M Schlessinger D Mohlke KL 《Nature genetics》2008,40(2):161-169
To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (ABCA1, the APOA5-APOA4-APOC3-APOA1 and APOE-APOC clusters, APOB, CETP, GCKR, LDLR, LPL, LIPC, LIPG and PCSK9) and also in several newly identified loci (near MVK-MMAB and GALNT2, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near SORT1, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near TRIB1, MLXIPL and ANGPTL3, with variants primarily associated with triglycerides; and a locus encompassing several genes near NCAN, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls. 相似文献
137.
Cabral WA Chang W Barnes AM Weis M Scott MA Leikin S Makareeva E Kuznetsova NV Rosenbaum KN Tifft CJ Bulas DI Kozma C Smith PA Eyre DR Marini JC 《Nature genetics》2007,39(3):359-365
A recessive form of severe osteogenesis imperfecta that is not caused by mutations in type I collagen has long been suspected. Mutations in human CRTAP (cartilage-associated protein) causing recessive bone disease have been reported. CRTAP forms a complex with cyclophilin B and prolyl 3-hydroxylase 1, which is encoded by LEPRE1 and hydroxylates one residue in type I collagen, alpha1(I)Pro986. We present the first five cases of a new recessive bone disorder resulting from null LEPRE1 alleles; its phenotype overlaps with lethal/severe osteogenesis imperfecta but has distinctive features. Furthermore, a mutant allele from West Africa, also found in African Americans, occurs in four of five cases. All proband LEPRE1 mutations led to premature termination codons and minimal mRNA and protein. Proband collagen had minimal 3-hydroxylation of alpha1(I)Pro986 but excess lysyl hydroxylation and glycosylation along the collagen helix. Proband collagen secretion was moderately delayed, but total collagen secretion was increased. Prolyl 3-hydroxylase 1 is therefore crucial for bone development and collagen helix formation. 相似文献
138.
Guo DC Pannu H Tran-Fadulu V Papke CL Yu RK Avidan N Bourgeois S Estrera AL Safi HJ Sparks E Amor D Ades L McConnell V Willoughby CE Abuelo D Willing M Lewis RA Kim DH Scherer S Tung PP Ahn C Buja LM Raman CS Shete SS Milewicz DM 《Nature genetics》2007,39(12):1488-1493
The major function of vascular smooth muscle cells (SMCs) is contraction to regulate blood pressure and flow. SMC contractile force requires cyclic interactions between SMC alpha-actin (encoded by ACTA2) and the beta-myosin heavy chain (encoded by MYH11). Here we show that missense mutations in ACTA2 are responsible for 14% of inherited ascending thoracic aortic aneurysms and dissections (TAAD). Structural analyses and immunofluorescence of actin filaments in SMCs derived from individuals heterozygous for ACTA2 mutations illustrate that these mutations interfere with actin filament assembly and are predicted to decrease SMC contraction. Aortic tissues from affected individuals showed aortic medial degeneration, focal areas of medial SMC hyperplasia and disarray, and stenotic arteries in the vasa vasorum due to medial SMC proliferation. These data, along with the previously reported MYH11 mutations causing familial TAAD, indicate the importance of SMC contraction in maintaining the structural integrity of the ascending aorta. 相似文献
139.
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus 总被引:1,自引:0,他引:1
Lee-Kirsch MA Gong M Chowdhury D Senenko L Engel K Lee YA de Silva U Bailey SL Witte T Vyse TJ Kere J Pfeiffer C Harvey S Wong A Koskenmies S Hummel O Rohde K Schmidt RE Dominiczak AF Gahr M Hollis T Perrino FW Lieberman J Hübner N 《Nature genetics》2007,39(9):1065-1067
TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE. 相似文献
140.