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341.
342.
Isolation of a cDNA clone corresponding to an X-linked gene family (XLR) closely linked to the murine immunodeficiency disorder xid 总被引:1,自引:0,他引:1
D I Cohen S M Hedrick E A Nielsen P D'Eustachio F Ruddle A D Steinberg W E Paul M M Davis 《Nature》1985,314(6009):369-372
The striking number of human and murine immunodeficiency disorders which map to the X chromosome suggests that genes localized on this chromosome must have important roles in lymphocyte development. At least seven distinct disorders in the human and two in the mouse disrupt lymphocyte maturation, particularly that of B cells, at characteristic stages. As functional genes mapping to the X chromosome in one mammal are found on the X chromosome in all other mammals, the same genes regulating lymphocyte development are expected to be found on the X chromosome in mouse and man. Investigations into the possible mechanisms of these X-linked disorders have been hampered by the lack of molecular probes for the genes or gene products affected; because of this, and the possibility of correlating one or more of the several hundred B- or T-cell-specific genes with a specific mutation, we surveyed 15 different B- and T-cell-specific cDNA clones for localization to the X chromosome. We report here the characterization of one of these murine cDNA clones, which hybridizes with a large, X-linked gene family, designated XLR (X-linked, lymphocyte-regulated). We show that the XLR gene family is closely linked to the X-linked immunodeficiency described in the CBA/N mouse strain (xid), by restriction fragment length polymorphism (RFLP) analysis of DNA from mice congeneic for xid. This finding, together with data on the expression of the XLR locus in B cells, indicates that this gene family either includes the locus defined by the xid mutation or is adjacent to it in a gene complex which may be important in lymphocyte differentiation. 相似文献
343.
Regulation of transcription factor function by phosphorylation 总被引:1,自引:1,他引:0
344.
345.
Y chromosome sequence variation and the history of human populations 总被引:48,自引:0,他引:48
Underhill PA Shen P Lin AA Jin L Passarino G Yang WH Kauffman E Bonné-Tamir B Bertranpetit J Francalacci P Ibrahim M Jenkins T Kidd JR Mehdi SQ Seielstad MT Wells RS Piazza A Davis RW Feldman MW Cavalli-Sforza LL Oefner PJ 《Nature genetics》2000,26(3):358-361
Binary polymorphisms associated with the non-recombining region of the human Y chromosome (NRY) preserve the paternal genetic legacy of our species that has persisted to the present, permitting inference of human evolution, population affinity and demographic history. We used denaturing high-performance liquid chromatography (DHPLC; ref. 2) to identify 160 of the 166 bi-allelic and 1 tri-allelic site that formed a parsimonious genealogy of 116 haplotypes, several of which display distinct population affinities based on the analysis of 1062 globally representative individuals. A minority of contemporary East Africans and Khoisan represent the descendants of the most ancestral patrilineages of anatomically modern humans that left Africa between 35,000 and 89,000 years ago. 相似文献
346.
Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10 总被引:25,自引:0,他引:25
Matsuura T Yamagata T Burgess DL Rasmussen A Grewal RP Watase K Khajavi M McCall AE Davis CF Zu L Achari M Pulst SM Alonso E Noebels JL Nelson DL Zoghbi HY Ashizawa T 《Nature genetics》2000,26(2):191-194
Spinocerebellar ataxia type 10 (SCA10; MIM 603516; refs 1,2) is an autosomal dominant disorder characterized by cerebellar ataxia and seizures. The gene SCA10 maps to a 3.8-cM interval on human chromosome 22q13-qter (refs 1,2). Because several other SCA subtypes show trinucleotide repeat expansions, we examined microsatellites in this region. We found an expansion of a pentanucleotide (ATTCT) repeat in intron 9 of SCA10 in all patients in five Mexican SCA10 families. There was an inverse correlation between the expansion size, up to 22.5 kb larger than the normal allele, and the age of onset (r2=0.34, P=0.018). Analysis of 562 chromosomes from unaffected individuals of various ethnic origins (including 242 chromosomes from Mexican persons) showed a range of 10 to 22 ATTCT repeats with no evidence of expansions. Our data indicate that the new SCA10 intronic ATTCT pentanucleotide repeat in SCA10 patients is unstable and represents the largest microsatellite expansion found so far in the human genome. 相似文献
347.
Parkhill J Achtman M James KD Bentley SD Churcher C Klee SR Morelli G Basham D Brown D Chillingworth T Davies RM Davis P Devlin K Feltwell T Hamlin N Holroyd S Jagels K Leather S Moule S Mungall K Quail MA Rajandream MA Rutherford KM Simmonds M Skelton J Whitehead S Spratt BG Barrell BG 《Nature》2000,404(6777):502-506
Neisseria meningitidis causes bacterial meningitis and is therefore responsible for considerable morbidity and mortality in both the developed and the developing world. Meningococci are opportunistic pathogens that colonize the nasopharynges and oropharynges of asymptomatic carriers. For reasons that are still mostly unknown, they occasionally gain access to the blood, and subsequently to the cerebrospinal fluid, to cause septicaemia and meningitis. N. meningitidis strains are divided into a number of serogroups on the basis of the immunochemistry of their capsular polysaccharides; serogroup A strains are responsible for major epidemics and pandemics of meningococcal disease, and therefore most of the morbidity and mortality associated with this disease. Here we have determined the complete genome sequence of a serogroup A strain of Neisseria meningitidis, Z2491. The sequence is 2,184,406 base pairs in length, with an overall G+C content of 51.8%, and contains 2,121 predicted coding sequences. The most notable feature of the genome is the presence of many hundreds of repetitive elements, ranging from short repeats, positioned either singly or in large multiple arrays, to insertion sequences and gene duplications of one kilobase or more. Many of these repeats appear to be involved in genome fluidity and antigenic variation in this important human pathogen. 相似文献
348.
Maoz E Newman JA Ferrarese L Stetson PB Zepf SE Davis M Freedman WL Madore BF 《Nature》1999,401(6751):351-354
Cepheid variable stars pulsate in a way that is correlated with their intrinsic luminosity, making them useful as 'standard candles' for determining distances to galaxies; the potential systematic uncertainties in the resulting distances have been estimated to be only 8-10%. They have played a crucial role in establishing the extragalactic distance scale and hence the value of the Hubble constant. Here we report observations of Cepheids in the nearby galaxy NGC4258; the distance calculated from the Cepheids is 8.1 +/- 0.4 Mpc, where the uncertainty does not include possible systematic errors. There is an independently determined geometric distance to this galaxy of 7.2 +/- 0.5 Mpc, based on the observed proper motions of water masers orbiting the central black hole; the distances differ by 1.3sigma. If the maser-based distance is adopted and the Cepheid distance scale revised accordingly, the derived value of the Hubble constant would increase by 12 +/- 9%, while the expansion age of the Universe would decrease by the same amount. 相似文献
349.
Xiao B Heath R Saiu P Leiper FC Leone P Jing C Walker PA Haire L Eccleston JF Davis CT Martin SR Carling D Gamblin SJ 《Nature》2007,449(7161):496-500
AMP-activated protein kinase (AMPK) regulates cellular metabolism in response to the availability of energy and is therefore a target for type II diabetes treatment. It senses changes in the ratio of AMP/ATP by binding both species in a competitive manner. Thus, increases in the concentration of AMP activate AMPK resulting in the phosphorylation and differential regulation of a series of downstream targets that control anabolic and catabolic pathways. We report here the crystal structure of the regulatory fragment of mammalian AMPK in complexes with AMP and ATP. The phosphate groups of AMP/ATP lie in a groove on the surface of the gamma domain, which is lined with basic residues, many of which are associated with disease-causing mutations. Structural and solution studies reveal that two sites on the gamma domain bind either AMP or Mg.ATP, whereas a third site contains a tightly bound AMP that does not exchange. Our binding studies indicate that under physiological conditions AMPK mainly exists in its inactive form in complex with Mg.ATP, which is much more abundant than AMP. Our modelling studies suggest how changes in the concentration of AMP ([AMP]) enhance AMPK activity levels. The structure also suggests a mechanism for propagating AMP/ATP signalling whereby a phosphorylated residue from the alpha and/or beta subunits binds to the gamma subunit in the presence of AMP but not when ATP is bound. 相似文献
350.
This article explores the impact of 16th and 17th-century developments in micrometry on the methods Antoni van Leeuwenhoek employed to measure the microscopic creatures he discovered in various samples collected from his acquaintances and from local water sources. While other publications have presented Leeuwenhoek's measurement methods, an examination of the context of his techniques is missing. These previous measurement methods, driven by the need to improve navigation, surveying, astronomy, and ballistics, may have had an impact on Leeuwenhoek's methods. Leeuwenhoek was educated principally in the mercantile guild system in Amsterdam and Delft. He rose to positions of responsibility within Delft municipal government. These were the years that led up to his first investigations using the single-lens microscopes he became expert at creating, and that led to his first letter to the Royal Society in 1673. He also took measures to train in surveying and liquid assaying practices existing in his time, disciplines that were influenced by Pedro Nunes, Pierre Vernier, Rene Descartes, and others. While we may never know what inspired Leeuwenhoek's methods, the argument is presented that there were sufficient influences in his life to shape his approach to measuring the invisible. 相似文献