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91.
92.
Gilbert SL Zhang L Forster ML Anderson JR Iwase T Soliven B Donahue LR Sweet HO Bronson RT Davisson MT Wollmann RL Lahn BT 《Nature genetics》2006,38(2):245-250
Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases. 相似文献
93.
Valdar W Solberg LC Gauguier D Burnett S Klenerman P Cookson WO Taylor MS Rawlins JN Mott R Flint J 《Nature genetics》2006,38(8):879-887
Difficulties in fine-mapping quantitative trait loci (QTLs) are a major impediment to progress in the molecular dissection of complex traits in mice. Here we show that genome-wide high-resolution mapping of multiple phenotypes can be achieved using a stock of genetically heterogeneous mice. We developed a conservative and robust bootstrap analysis to map 843 QTLs with an average 95% confidence interval of 2.8 Mb. The QTLs contribute to variation in 97 traits, including models of human disease (asthma, type 2 diabetes mellitus, obesity and anxiety) as well as immunological, biochemical and hematological phenotypes. The genetic architecture of almost all phenotypes was complex, with many loci each contributing a small proportion to the total variance. Our data set, freely available at http://gscan.well.ox.ac.uk, provides an entry point to the functional characterization of genes involved in many complex traits. 相似文献
94.
95.
5-Methylcytosine localised in mammalian constitutive heterochromatin 总被引:26,自引:0,他引:26
96.
Along shore sediment transport that is driven by waves is generally assumed to smooth a coastline. This assumption is valid for small angles between the wave crest lines and the shore, as has been demonstrated in shoreline models. But when the angle between the waves and the shoreline is sufficiently large, small perturbations to a straight shoreline will grow. Here we use a numerical model to investigate the implications of this instability mechanism for large-scale morphology over long timescales. Our simulations show growth of coastline perturbations that interact with each other to produce large-scale features that resemble various kinds of natural landforms, including the capes and cuspate forelands observed along the Carolina coast of southeastern North America. Wind and wave data from this area support our hypothesis that such an instability mechanism could be responsible for the formation of shoreline features at spatial scales up to hundreds of kilometres and temporal scales up to millennia. 相似文献
97.
Complex patterns formed by motile cells of Escherichia coli 总被引:6,自引:0,他引:6
When chemotactic strains of the bacterium Escherichia coli are inoculated on semi-solid agar containing mixtures of amino acids or sugars, the cells swarm outwards in a series of concentric rings: they respond to spatial gradients of attractants generated by uptake and catabolism. Cells also drift up gradients generated artificially, for example by diffusion from the tip of a capillary tube or by mixing. Here we describe conditions under which cells aggregate in response to gradients of attractant which they excrete themselves. When cells are grown in semi-solid agar on intermediates of the tricarboxylic acid cycle, they form symmetrical arrays of spots or stripes that arise sequentially. When cells in a thin layer of liquid culture are exposed to these compounds, spots appear synchronously, more randomly arrayed. In either case, the patterns are stationary. The attractant is a chemical sensed by the aspartate receptor. Its excretion can be triggered by oxidative stress. As oxygen is limiting at high cell densities, aggregation might serve as a mechanism for collective defence. 相似文献
98.
Non-indigenous African honey bees have invaded most of South and Central America in just over 30 years. The genetic composition of this population and the means by which it rapidly colonizes new territory remain controversial. In particular, it has been unclear whether this 'Africanized' population has resulted from interbreeding between African and domestic European bees, or is an essentially pure African population. Also, it has not been known whether this population expanded primarily by female or by male migration. Restriction site mapping of 62 mitochondrial DNAs of African bees from Brazil, Venezuela and Mexico reveals that 97% were of African (Apis mellifera scutellata) type. Although neotropical European apiary populations are rapidly Africanized by mating with neotropical African males, there is little reciprocal gene flow to the neotropical African population through European females. These are the first genetic data to indicate that the neotropical African population could be expanding its range by female migration. 相似文献
99.
Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs 总被引:108,自引:0,他引:108
The aminoacyl-transfer RNA synthetases (aaRS) catalyse the attachment of an amino acid to its cognate transfer RNA molecule in a highly specific two-step reaction. These proteins differ widely in size and oligomeric state, and have limited sequence homology. Out of the 18 known aaRS, only 9 referred to as class I synthetases (GlnRS, TyrRS, MetRS, GluRS, ArgRS, ValRS, IleRS, LeuRS, TrpRS), display two short common consensus sequences ('HIGH' and 'KMSKS') which indicate, as observed in three crystal structures, the presence of a structural domain (the Rossman fold) that binds ATP. We report here the sequence of Escherichia coli ProRS, a dimer of relative molecular mass 127,402, which is homologous to both ThrRS and SerRS. These three latter aaRS share three new sequence motifs with AspRS, AsnRS, LysRS, HisRS and the beta subunit of PheRS. These three motifs (motifs 1, 2 and 3), in a search through the entire data bank, proved to be specific for this set of aaRS (referred to as class II). Class II may also contain AlaRS and GlyRS, because these sequences have a typical motif 3. Surprisingly, this partition of aaRS in two classes is found to be strongly correlated on the functional level with the acylation occurring either on the 2' OH (class I) or 3' OH (class II) of the ribose of the last nucleotide of tRNA. 相似文献
100.
A truncated human chromosome 16 associated with alpha thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n 总被引:39,自引:0,他引:39
The instability of chromosomes with breaks induced by X-irradiation led to the proposal that the natural ends of chromosomes are capped by a specialized structure, the telomere. Telomeres prevent end-to-end fusions and exonucleolytic degradation, enable the end of the linear DNA molecule to replicate, and function in cell division. Human telomeric DNA comprises approximately 2-20 kilobases (kb) of the tandemly repeated sequence (TTAGGG)n oriented 5'----3' in towards the end of the chromosome, interspersed with variant repeats in the proximal region. Immediately subtelomeric lie families of unrelated repeat motifs (telomere-associated sequences) whose function, if any, is unknown. In lower eukaryotes the formation and maintenance of telomeres may be mediated enzymatically (by telomerase) or by recombination; in man the mechanisms are poorly understood, although telomerase has been identified in HeLa cells. Here we describe an alpha thalassaemia mutation associated with terminal truncation of the short arm of chromosome 16 (within band 16p13-3) to a site 50 kb distal to the alpha globin genes, and show that (TTAGGG)n has been added directly to the site of the break. The mutation is stably inherited, proving that telomeric DNA alone is sufficient to stabilize the broken chromosome end. This mechanism may occur in any genetic disease associated with chromosome truncation. 相似文献