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71.
72.
Recombination and linkage disequilibrium in Arabidopsis thaliana 总被引:4,自引:0,他引:4
Kim S Plagnol V Hu TT Toomajian C Clark RM Ossowski S Ecker JR Weigel D Nordborg M 《Nature genetics》2007,39(9):1151-1155
Linkage disequilibrium (LD) is a major aspect of the organization of genetic variation in natural populations. Here we describe the genome-wide pattern of LD in a sample of 19 Arabidopsis thaliana accessions using 341,602 non-singleton SNPs. LD decays within 10 kb on average, considerably faster than previously estimated. Tag SNP selection algorithms and 'hide-the-SNP' simulations suggest that genome-wide association mapping will require only 40%-50% of the observed SNPs, a reduction similar to estimates in a sample of African Americans. An Affymetrix genotyping array containing 250,000 SNPs has been designed based on these results; we demonstrate that it should have more than adequate coverage for genome-wide association mapping. The extent of LD is highly variable, and we find clear evidence of recombination hotspots, which seem to occur preferentially in intergenic regions. LD also reflects the action of selection, and it is more extensive between nonsynonymous polymorphisms than between synonymous polymorphisms. 相似文献
73.
Rogaeva E Meng Y Lee JH Gu Y Kawarai T Zou F Katayama T Baldwin CT Cheng R Hasegawa H Chen F Shibata N Lunetta KL Pardossi-Piquard R Bohm C Wakutani Y Cupples LA Cuenco KT Green RC Pinessi L Rainero I Sorbi S Bruni A Duara R Friedland RP Inzelberg R Hampe W Bujo H Song YQ Andersen OM Willnow TE Graff-Radford N Petersen RC Dickson D Der SD Fraser PE Schmitt-Ulms G Younkin S Mayeux R Farrer LA St George-Hyslop P 《Nature genetics》2007,39(2):168-177
The recycling of the amyloid precursor protein (APP) from the cell surface via the endocytic pathways plays a key role in the generation of amyloid beta peptide (Abeta) in Alzheimer disease. We report here that inherited variants in the SORL1 neuronal sorting receptor are associated with late-onset Alzheimer disease. These variants, which occur in at least two different clusters of intronic sequences within the SORL1 gene (also known as LR11 or SORLA) may regulate tissue-specific expression of SORL1. We also show that SORL1 directs trafficking of APP into recycling pathways and that when SORL1 is underexpressed, APP is sorted into Abeta-generating compartments. These data suggest that inherited or acquired changes in SORL1 expression or function are mechanistically involved in causing Alzheimer disease. 相似文献
74.
Risheg H Graham JM Clark RD Rogers RC Opitz JM Moeschler JB Peiffer AP May M Joseph SM Jones JR Stevenson RE Schwartz CE Friez MJ 《Nature genetics》2007,39(4):451-453
Opitz-Kaveggia syndrome (also known as FG syndrome) is an X-linked disorder characterized by mental retardation, relative macrocephaly, hypotonia and constipation. We report here that the original family for whom the condition is named and five other families have a recurrent mutation (2881C>T, leading to R961W) in MED12 (also called TRAP230 or HOPA), a gene located at Xq13 that functions as a thyroid receptor-associated protein in the Mediator complex. 相似文献
75.
Lindahl E Nyman U Melles E Sigmundsson K Ståhlberg M Wahren J Obrink B Shafqat J Joseph B Jörnvall H 《Cellular and molecular life sciences : CMLS》2007,64(4):479-486
Proinsulin C-peptide is known to bind specifically to cell membranes and to exert intracellular effects, but whether it is
internalized in target cells is unknown. In this study, using confocal microscopy and immunostained or rhodamine-labeled peptide,
we show that C-peptide is internalized and localized to the cytosol of Swiss 3T3 and HEK-293 cells. In addition, transport
into nuclei was found using the labeled peptide. The internalization was followed at 37°C for up to 1 h, and was reduced at
4°C and after preincubation with pertussis toxin. Hence, it is concluded to occur via an energy-dependent, pertussis toxin-sensitive
mechanism and without detectable degradation within the experimental time course. Surface plasmon resonance measurements demonstrated
binding of HEK-293 cell extract components to C-peptide, and subsequent elution of bound material revealed the components
to be intracellular proteins. The identification of C-peptide cellular internalization, intracellular binding proteins, absence
of rapid subsequent C-peptide degradation and apparent nuclear internalization support a maintained activity similar to that
of an intracrine peptide hormone. Hence, the data suggest the possibility of one further C-peptide site of action.
Received 31 October 2006; received after revision 27 December 2006; accepted 30 December 2006 相似文献
76.
We have previously argued that historical cases must be rendered canonical before they can plausibly serve as evidence for philosophical claims, where canonicity is established through a process of negotiation among historians and philosophers of science (Bolinska and Martin, 2020). Here, we extend this proposal by exploring how that negotiation might take place in practice. The working stock of historical examples that philosophers tend to employ has long been established informally, and, as a result, somewhat haphazardly. The composition of the historical canon of philosophy of science is therefore path dependent, and cases often become stock examples for reasons tangential to their appropriateness for the purposes at hand. We show how the lack of rigor around the canonization of case studies has muddied the waters in selected philosophical debates. This, in turn, lays the groundwork for proposing ways in which they can be improved. 相似文献
77.
JosephO'Connor 《科技潮》2004,(11):10-11
主要是被描述为由院所、高校为中心的技术主导型的创新体制向以企业为中心的市场主导型的创新体制的转变。北京是中国的文化和科技中心,北京的高等学府吸引了全国最优秀的人才,同时高校的设施也为开展研究工作提供了支撑。 相似文献
78.
Based on introducing the concept of the metric induced by a set of vectors, as well as minimizing the maximum amplitude of
residual vibrations in the sense of this metric, an approach for determining the balance correction for flexible shafts is
presented. The advantages of the proposed method are two-fold. Firstly, the approach is available when upper bound constraints
on balance corrections exist, and the resulted balance correction is approximately optimal. Secondly, the balance correction
can be easily calculated by solving a linear programming problem. 相似文献
79.
Stomach contents of 650 clouded salamanders ( Aneides ferreus ), collected monthly throughout the year from Curry County, Oregon, were examined. Samples from three age classes were involved: (1) 489 adults, (2) 131 juveniles, and (3) 30 hatchlings. Foods did not vary by sex, but did vary by age and by season. Hatchlings ate small items, particularly mites, springtails, flies, and small beetles. Juveniles fed mainly on flies, isopods (sowbugs), beetles, mites, and centipedes in winter; beetles, ants, and isopods in spring; ants and beetles in summer; and isopods, beetles, and ants in fall. Adults ate isopods and beetles as their major foods in winter, spring, and fall and isopods, ants, beetles, and earwigs in summer. Four species were exceedingly important as foods for these salamanders: an unidentified isopod, the snout beetle ( Trachyphloeus bifoveatus ), the European earwig ( Forficula auricularia ), and an ant ( Lasius alienus ). 相似文献
80.
Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 st1\:*{behavior:url(#ieooui) } /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} In 1968 and 1973 in southwestern Idaho, 275 Uta stansburiana were collected. Uta occupies low hills with rocky outcrops and flat sparse vegetation consisting of the following shrubs: Artemisia tridentata, Grayia spinosa, Atriplex confertifolia, Chrysothamnus nauseosus, and Atriplex canescens. Emergence from hibernation occurs from mid-March to early April and the first yolked follicles appear in early April, with oviducal eggs present in late April. Testicular cycle begins with the emergence of males, and spermatozoa are produced from April through July. Uta reaches sexual maturity in one year at a SVL of 40.0 mm in males and 43 mm in females. Overall clutch size is 3.75 eggs (1–2 clutches per year). Fat body size at emergence is not known, but what is present shows a decline in males and females until July, when a substantial increase occurs. Sex ratios are about 1:1 in all months and seasons except June 1968, according to chi-square analysis. 相似文献