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71.
Rivas MA Beaudoin M Gardet A Stevens C Sharma Y Zhang CK Boucher G Ripke S Ellinghaus D Burtt N Fennell T Kirby A Latiano A Goyette P Green T Halfvarson J Haritunians T Korn JM Kuruvilla F Lagacé C Neale B Lo KS Schumm P Törkvist L;National Institute of Diabetes Digestive Kidney Diseases Inflammatory Bowel Disease Genetics Consortium 《Nature genetics》2011,43(11):1066-1073
More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 × 10(-16), odds ratio ≈ 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models. 相似文献
72.
This study examined the role of Rab5a GTPase in regulating hCG-induced internalization and trafficking of the hCG-LH receptor
complex in transfected 293T cells. Coexpression of wild-type Rab5a (WT) or constitutively active Rab5a (Q79L) with LHR significantly
increased hCG-induced LHR internalization. Conversely, coexpression of dominant negative Rab5a (S34N) with LHR reduced internalization.
Confocal microscopy showed LHR colocalizing with Rab5a (WT) and Rab5a (Q79L) in punctuate structures. Coexpression of Rab5a
(WT) and Rab5a (Q79L) with LHR significantly increased colocalization of LHR in early endosomes. Conversely, dominant negative
Rab5a (S34N) decreased this colocalization. While Rab5a stimulated internalization of LHR, it significantly decreased LHR
recycling to the cell surface and increased degradation. Dominant negative Rab5a (S34N) increased LHR recycling and decreased
degradation. These results suggest that Rab5a plays a role in LHR trafficking by facilitating internalization and fusion to
early endosomes, increasing the degradation of internalized receptor resulting in a reduction in LHR recycling. 相似文献
73.
74.
The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus) 总被引:1,自引:0,他引:1
Ming R Hou S Feng Y Yu Q Dionne-Laporte A Saw JH Senin P Wang W Ly BV Lewis KL Salzberg SL Feng L Jones MR Skelton RL Murray JE Chen C Qian W Shen J Du P Eustice M Tong E Tang H Lyons E Paull RE Michael TP Wall K Rice DW Albert H Wang ML Zhu YJ Schatz M Nagarajan N Acob RA Guan P Blas A Wai CM Ackerman CM Ren Y Liu C Wang J Wang J Na JK Shakirov EV Haas B Thimmapuram J Nelson D Wang X Bowers JE Gschwend AR Delcher AL Singh R Suzuki JY Tripathi S Neupane K Wei H Irikura B Paidi M Jiang N Zhang W 《Nature》2008,452(7190):991-996
Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3x draft genome sequence of 'SunUp' papaya, the first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica's distinguishing morpho-physiological, medicinal and nutritional properties. 相似文献
75.
Rendall M Couet C Lappegard T Robert-Bobée I Rønsen M Smallwood S 《Population trends》2005,(121):27-34
Progressively later starting of childbearing has been a feature of cohort change in fertility across Europe and elsewhere over recent decades. Growing differences in the age patterns of childbearing between the Anglo-American and continental European countries, however, have also been found. The present study uses large linked-record databases in Britain, France and Norway to analyse these differences in more detail, focussing on age at entry to motherhood (first childbearing) by level of educational attainment among women born in the 1950s and in the 1960s. The shift between these two cohorts towards a later pattern of first childbearing in Britain was confined to women with secondary school qualifications and above. For women born in the 1960s, the peak age for risk of first childbearing among those with secondary school qualifications grew to be between seven and eleven years later than among women without secondary school qualifications. In France and Norway, the peak ages for risk of first childbearing shifted more uniformly across education levels between the two cohorts. For these 1950s and 1960s cohorts, improvements in women's educational levels also occurred more uniformly in France and Norway, moving more women into education categories characterised by later patterns of first childbearing. 相似文献
76.
77.
Stephanie Chin Maurita Hung Christine E. Bear 《Cellular and molecular life sciences : CMLS》2017,74(1):57-66
Cystic fibrosis transmembrane conductance regulator (CFTR) channel gating is predominantly regulated by protein kinase A (PKA)-dependent phosphorylation. In addition to regulating CFTR channel activity, PKA phosphorylation is also involved in enhancing CFTR trafficking and mediating conformational changes at the interdomain interfaces of the protein. The major cystic fibrosis (CF)-causing mutation is the deletion of phenylalanine at position 508 (F508del); it causes many defects that affect CFTR trafficking, stability, and gating at the cell surface. Due to the multiple roles of PKA phosphorylation, there is growing interest in targeting PKA-dependent signaling for rescuing the trafficking and functional defects of F508del-CFTR. This review will discuss the effects of PKA phosphorylation on wild-type CFTR, the consequences of CF mutations on PKA phosphorylation, and the development of therapies that target PKA-mediated signaling. 相似文献
78.
79.
Frédérique Nolin Jean Michel Laurence Wortham Pavel Tchelidze Gérard Balossier Vincent Banchet Hélène Bobichon Nathalie Lalun Christine Terryn Dominique Ploton 《Cellular and molecular life sciences : CMLS》2013,70(13):2383-2394
The cell is a crowded volume, with estimated mean mass percentage of macromolecules and of water ranging from 7.5 to 45 and 55 to 92.5 %, respectively. However, the concentrations of macromolecules and water at the nanoscale within the various cell compartments are unknown. We recently developed a new approach, correlative cryo-analytical scanning transmission electron microscopy, for mapping the quantity of water within compartments previously shown to display GFP-tagged protein fluorescence on the same ultrathin cryosection. Using energy-dispersive X-ray spectrometry (EDXS), we then identified various elements (C, N, O, P, S, K, Cl, Mg) in these compartments and quantified them in mmol/l. Here, we used this new approach to quantify water and elements in the cytosol, mitochondria, condensed chromatin, nucleoplasm, and nucleolar components of control and stressed cancerous cells. The water content of the control cells was between 60 and 83 % (in the mitochondria and nucleolar fibrillar centers, respectively). Potassium was present at concentrations of 128–462 mmol/l in nucleolar fibrillar centers and condensed chromatin, respectively. The induction of nucleolar stress by treatment with a low dose of actinomycin-D to inhibit rRNA synthesis resulted in both an increase in water content and a decrease in the elements content in all cell compartments. We generated a nanoscale map of water and elements within the cell compartments, providing insight into their changes induced by nucleolar stress. 相似文献
80.
Damtew Elias van Mierlo Barbara Lie Rico Struik Paul Leeuwis Cees Lemaga Berga Smart Christine 《Systemic Practice and Action Research》2020,33(1):111-134
Systemic Practice and Action Research - There has been strong research interest in designing and testing learning approaches for enhancing and sustaining the capacity of communities to manage... 相似文献