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261.
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263.
A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene 总被引:18,自引:0,他引:18
Bitner-Glindzicz M Lindley KJ Rutland P Blaydon D Smith VV Milla PJ Hussain K Furth-Lavi J Cosgrove KE Shepherd RM Barnes PD O'Brien RE Farndon PA Sowden J Liu XZ Scanlan MJ Malcolm S Dunne MJ Aynsley-Green A Glaser B 《Nature genetics》2000,26(1):56-60
Usher syndrome type 1 describes the association of profound, congenital sensorineural deafness, vestibular hypofunction and childhood onset retinitis pigmentosa. It is an autosomal recessive condition and is subdivided on the basis of linkage analysis into types 1A through 1E. Usher type 1C maps to the region containing the genes ABCC8 and KCNJ11 (encoding components of ATP-sensitive K + (KATP) channels), which may be mutated in patients with hyperinsulinism. We identified three individuals from two consanguineous families with severe hyperinsulinism, profound congenital sensorineural deafness, enteropathy and renal tubular dysfunction. The molecular basis of the disorder is a homozygous 122-kb deletion of 11p14-15, which includes part of ABCC8 and overlaps with the locus for Usher syndrome type 1C and DFNB18. The centromeric boundary of this deletion includes part of a gene shown to be mutated in families with type 1C Usher syndrome, and is hence assigned the name USH1C. The pattern of expression of the USH1C protein is consistent with the clinical features exhibited by individuals with the contiguous gene deletion and with isolated Usher type 1C. 相似文献
264.
DNA computing on surfaces 总被引:68,自引:0,他引:68
DNA computing was proposed as a means of solving a class of intractable computational problems in which the computing time can grow exponentially with problem size (the 'NP-complete' or non-deterministic polynomial time complete problems). The principle of the technique has been demonstrated experimentally for a simple example of the hamiltonian path problem (in this case, finding an airline flight path between several cities, such that each city is visited only once). DNA computational approaches to the solution of other problems have also been investigated. One technique involves the immobilization and manipulation of combinatorial mixtures of DNA on a support. A set of DNA molecules encoding all candidate solutions to the computational problem of interest is synthesized and attached to the surface. Successive cycles of hybridization operations and exonuclease digestion are used to identify and eliminate those members of the set that are not solutions. Upon completion of all the multistep cycles, the solution to the computational problem is identified using a polymerase chain reaction to amplify the remaining molecules, which are then hybridized to an addressed array. The advantages of this approach are its scalability and potential to be automated (the use of solid-phase formats simplifies the complex repetitive chemical processes, as has been demonstrated in DNA and protein synthesis). Here we report the use of this method to solve a NP-complete problem. We consider a small example of the satisfiability problem (SAT), in which the values of a set of boolean variables satisfying certain logical constraints are determined. 相似文献
265.
Dominant modifier DFNM1 suppresses recessive deafness DFNB26 总被引:8,自引:0,他引:8
Riazuddin S Castelein CM Ahmed ZM Lalwani AK Mastroianni MA Naz S Smith TN Liburd NA Friedman TB Griffith AJ Riazuddin S Wilcox ER 《Nature genetics》2000,26(4):431-434
More than 50% of severe childhood deafness is genetically determined, approximately 70% of which occurs without other abnormalities and is thus termed nonsyndromic. So far, 30 nonsyndromic recessive deafness loci have been mapped and the defective genes at 6 loci, DFNB1, DFNB2, DFNB3, DFNB4, DFNB9 and DNFB21, have been identified, encoding connexin-26 (ref. 3), myosin VIIA (ref. 4), myosin XV (ref. 5), pendrin, otoferlin and alpha-tectorin, respectively. Here we map a new recessive nonsyndromic deafness locus, DFNB26, to a 1.5-cM interval of chromosome 4q31 in a consanguineous Pakistani family. A maximum lod score of 8.10 at theta=0 was obtained with D4S1610 when only the 8 affected individuals in this family were included in the calculation. There are seven unaffected family members who are also homozygous for the DFNB26-linked haplotype and thus are non-penetrant. A dominant modifier, DFNM1, that suppresses deafness in the 7 nonpenetrant individuals was mapped to a 5.6-cM region on chromosome 1q24 with a lod score of 4.31 at theta=0 for D1S2815. 相似文献
266.
Capaldi EA Smith AD Osborne JL Fahrbach SE Farris SM Reynolds DR Edwards AS Martin A Robinson GE Poppy GM Riley JR 《Nature》2000,403(6769):537-540
Cognitive ethology focuses on the study of animals under natural conditions to reveal ecologically adapted modes of learning. But biologists can more easily study what an animal learns than how it learns. For example, honeybees take repeated 'orientation' flights before becoming foragers at about three weeks of age. These flights are a prerequisite for successful homing. Little is known about these flights because orienting bees rapidly fly out of the range of human observation. Using harmonic radar, we show for the first time a striking ontogeny to honeybee orientation flights. With increased experience, bees hold trip duration constant but fly faster, so later trips cover a larger area than earlier trips. In addition, each flight is typically restricted to a narrow sector around the hive. Orientation flights provide honeybees with repeated opportunities to view the hive and landscape features from different viewpoints, suggesting that bees learn the local landscape in a progressive fashion. We also show that these changes in orientation flight are related to the number of previous flights taken instead of chronological age, suggesting a learning process adapted to changes in weather conditions, flower availability and the needs of bee colonies. 相似文献
267.
Do mussels take wooden steps to deep-sea vents? 总被引:1,自引:0,他引:1
268.
Retrotransposition of a bacterial group II intron 总被引:13,自引:0,他引:13
269.
Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1 总被引:26,自引:0,他引:26
Li YM Xu M Lai MT Huang Q Castro JL DiMuzio-Mower J Harrison T Lellis C Nadin A Neduvelil JG Register RB Sardana MK Shearman MS Smith AL Shi XP Yin KC Shafer JA Gardell SJ 《Nature》2000,405(6787):689-694
Cleavage of amyloid precursor protein (APP) by the beta- and gamma-secretases generates the amino and carboxy termini, respectively, of the A beta amyloidogenic peptides A beta40 and A beta42--the major constituents of the amyloid plaques in the brain parenchyma of Alzheimer's disease patients. There is evidence that the polytopic membrane-spanning proteins, presenilin 1 and 2 (PS1 and PS2), are important determinants of gamma-secretase activity: mutations in PS1 and PS2 that are associated with early-onset familial Alzheimer's disease increase the production of A beta42 (refs 4-6), the more amyloidogenic peptide; gamma-secretase activity is reduced in neuronal cultures derived from PS1-deficient mouse embryos; and directed mutagenesis of two conserved aspartates in transmembrane segments of PS1 inactivates the ability of gamma-secretase to catalyse processing of APP within its transmembrane domain. It is unknown, however, whether PS1 (which has little or no homology to any known aspartyl protease) is itself a transmembrane aspartyl protease or a gamma-secretase cofactor, or helps to colocalize gamma-secretase and APP. Here we report photoaffinity labelling of PS1 (and PS2) by potent gamma-secretase inhibitors that were designed to function as transition state analogue inhibitors directed to the active site of an aspartyl protease. This observation indicates that PS1 (and PS2) may contain the active site of gamma-secretase. Interestingly, the intact, single-chain form of wild-type PS1 is not labelled by an active-site-directed photoaffinity probe, suggesting that intact wild-type PS1 may be an aspartyl protease zymogen. 相似文献
270.
Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean 总被引:30,自引:0,他引:30
Clapham JC Arch JR Chapman H Haynes A Lister C Moore GB Piercy V Carter SA Lehner I Smith SA Beeley LJ Godden RJ Herrity N Skehel M Changani KK Hockings PD Reid DG Squires SM Hatcher J Trail B Latcham J Rastan S Harper AJ Cadenas S Buckingham JA Brand MD Abuin A 《Nature》2000,406(6794):415-418
Uncoupling protein-3 (UCP-3) is a recently identified member of the mitochondrial transporter superfamily that is expressed predominantly in skeletal muscle. However, its close relative UCP-1 is expressed exclusively in brown adipose tissue, a tissue whose main function is fat combustion and thermogenesis. Studies on the expression of UCP-3 in animals and humans in different physiological situations support a role for UCP-3 in energy balance and lipid metabolism. However, direct evidence for these roles is lacking. Here we describe the creation of transgenic mice that overexpress human UCP-3 in skeletal muscle. These mice are hyperphagic but weigh less than their wild-type littermates. Magnetic resonance imaging shows a striking reduction in adipose tissue mass. The mice also exhibit lower fasting plasma glucose and insulin levels and an increased glucose clearance rate. This provides evidence that skeletal muscle UCP-3 has the potential to influence metabolic rate and glucose homeostasis in the whole animal. 相似文献