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1.
Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. 总被引:226,自引:0,他引:226
L A Donehower M Harvey B L Slagle M J McArthur C A Montgomery J S Butel A Bradley 《Nature》1992,356(6366):215-221
Mutations in the p53 tumour-suppressor gene are the most frequently observed genetic lesions in human cancers. To investigate the role of the p53 gene in mammalian development and tumorigenesis, a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear normal but are prone to the spontaneous development of a variety of neoplasms by 6 months of age. These observations indicate that a normal p53 gene is dispensable for embryonic development, that its absence predisposes the animal to neoplastic disease, and that an oncogenic mutant form of p53 is not obligatory for the genesis of many types of tumours. 相似文献
2.
Thirty-eight accessions of 20 taxa (species and subspecies) of Chrysothamnus from a range of environments were grown in a uniform garden. During mid-June, terminal and lateral leaves were removed, fixed, and processed for light-microscopy studies. Area and perimeter measurements of ink tracings of midleaf vein cross sections were measured using computer-scan techniques. Leaf area and perimeter were compared with vein perimeter and area measurements. Area and perimeter of these Chrysothamnus leaves varied in response to the environment at the collection location. Plants native to hot, dry conditions had small, thick leaves, whereas plants native to cooler, more mesic conditions had relatively large, thin leaves. Similarly, leaves with round veins were adapted to hot, dry environments and leaves with elliptical veins were adapted to cooler, more mesic environments. Both terminal (young) and lateral (older) leaves were sampled. Terminal leaves showed significant (p < .05) correlational responses to environmental parameters, whereas the lateral leaves, while fronding in the predicted morphological directions, did not generally show significant responses. The different responses of terminal and lateral leaves may have been due to canopy position and uniform environmental conditions of the garden. Leaves with large cross sections characteristically had large veins, and leaves with small cross sections characteristically had small veins. Large leaf cross sections were normally flat. Small leaf cross sections were normally round. Decreasing leaf size and increasing leaf thickness were correlated with aridity. 相似文献
3.
A new subspecies of Artemisia arbuscula is described, A. arbuscula ssp. longicaulis Winward & McArthur, ssp. Nov. This taxon is a landscape dominant in portions of northwestern Nevada and adjacent California and Oregon at elevations from 1050 to 2000 m on shallow or argillic (clayey) soils. It differs from A. arbuscula ssp. arbuscula in its long floral stalks and large leaves. Morphological, chemical, ecological, and cytological data suggest that it is of hybrid origin. It is hexaploid (6x). We hypothesize that 2x A. arbusucla ssp. arbusucla and 4x A. tridentata ssp. wyomingensis are its parents. 相似文献
4.
Wignall PB McArthur JM Little CT Hallam A 《Nature》2006,441(7093):E5; discussion E5-E5; discussion E6
Dramatic global warming, triggered by release of methane from clathrates, has been postulated to have occurred during the early Toarcian age in the Early Jurassic period. Kemp et al. claim that this methane was released at three points, as recorded by three sharp excursions of delta13C(org) of up to 3 per thousand magnitude. But they discount another explanation for the excursions: namely that some, perhaps all, of the rapid excursions could be a local signature of a euxinic basin caused by recycling of isotopically light carbon from the lower water column. This idea has been proposed previously (see ref. 3, for example) and is supported by the lack evidence for negative delta13C excursions in coeval belemnite rostra. Kemp et al. dismiss this alternative, claiming that each abrupt shift would have required the recycling of about double the amount of organic carbon that is currently present in the modern ocean; however, their measurements are not from an ocean but from a restricted, epicontinental seaway and so would not require whole-ocean mixing to achieve the excursions. 相似文献
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6.
Relationships within, between, and among the Anthemideae genera Sphaeromeria, Artemisia , and Tanacetum were investigated using 238 randomly amplified polymorphic DNA (RAPD) markers obtained from twenty 10-mer primers amplified on genomic DNA. Forty-one populations from 16 taxa (15 species) were studied. Jaccard's coefficient of similarity and UPGMA clustering analysis were used to construct phenograms. T tests were used to make comparisons between samples at various systematic levels. DNA markers were 75% similar for conspecific populations. Sixteen Sphaeromeria populations (5 species) showed an average interspecific similarity of 21%. Interspecific similarity among 23 Artemisia populations (8 species with 2 subspecies of A. tridentata included) averaged 27%. Two Tanacetum species (1 population each) were 89% similar. The high similarity of Tanacetum species was in the range of observed values for conspecific populations; indeed those 2 species ( T. vulgare and T. boreale ) have been considered conspecific by some authors. The 3 subgenera of Artemisia studied ( Artemisia, Dracunculus , and Tridentatae ) formed separate groups. In comparison among the genera, Sphaeromeria was 18% similar to Artemisia (more similar to subgenus Tridentatae than the other Artemisia subgenera); intergeneric comparisons of Sphaeromeria and Artemisia and Tanacetum , which supports previously established morphological distinctions. Sphaeromeria potentilloides may be misplaced in the genus Sphaeromeria based on DNA marker results. It is likely that North American Anthemideae are circumboreal derivatives of ancestral Eurasian stock and that Sphaeromeria is derived from an Artemisia -like ancestor. 相似文献
7.
Nazarian R Shi H Wang Q Kong X Koya RC Lee H Chen Z Lee MK Attar N Sazegar H Chodon T Nelson SF McArthur G Sosman JA Ribas A Lo RS 《Nature》2010,468(7326):973-977
Activating B-RAF(V600E) (also known as BRAF) kinase mutations occur in ~7% of human malignancies and ~60% of melanomas. Early clinical experience with a novel class I RAF-selective inhibitor, PLX4032, demonstrated an unprecedented 80% anti-tumour response rate among patients with B-RAF(V600E)-positive melanomas, but acquired drug resistance frequently develops after initial responses. Hypotheses for mechanisms of acquired resistance to B-RAF inhibition include secondary mutations in B-RAF(V600E), MAPK reactivation, and activation of alternative survival pathways. Here we show that acquired resistance to PLX4032 develops by mutually exclusive PDGFRβ (also known as PDGFRB) upregulation or N-RAS (also known as NRAS) mutations but not through secondary mutations in B-RAF(V600E). We used PLX4032-resistant sub-lines artificially derived from B-RAF(V600E)-positive melanoma cell lines and validated key findings in PLX4032-resistant tumours and tumour-matched, short-term cultures from clinical trial patients. Induction of PDGFRβ RNA, protein and tyrosine phosphorylation emerged as a dominant feature of acquired PLX4032 resistance in a subset of melanoma sub-lines, patient-derived biopsies and short-term cultures. PDGFRβ-upregulated tumour cells have low activated RAS levels and, when treated with PLX4032, do not reactivate the MAPK pathway significantly. In another subset, high levels of activated N-RAS resulting from mutations lead to significant MAPK pathway reactivation upon PLX4032 treatment. Knockdown of PDGFRβ or N-RAS reduced growth of the respective PLX4032-resistant subsets. Overexpression of PDGFRβ or N-RAS(Q61K) conferred PLX4032 resistance to PLX4032-sensitive parental cell lines. Importantly, MAPK reactivation predicts MEK inhibitor sensitivity. Thus, melanomas escape B-RAF(V600E) targeting not through secondary B-RAF(V600E) mutations but via receptor tyrosine kinase (RTK)-mediated activation of alternative survival pathway(s) or activated RAS-mediated reactivation of the MAPK pathway, suggesting additional therapeutic strategies. 相似文献
8.
Previously, physiological studies of rubber and resin production during the growing season of Chrysothamnus nausceosus ssp. turbinatus indicated a negative correlation between rubber and resin content. The resin was highest in the spring and lowest in the summer, whereas rubber was highest in the summer and lowest in the spring. Individual compounds were followed during the growing season to see if they correlated with the rubber or resin trend. The total compounds in the cyclohexane fraction followed the resin pattern. Individual compounds varied in their changes during the growing season. Limonene, for example, was negatively correlated with rubber production, whereas β cubebene was positively correlated. The possible metabolic pathways between resin and rubber are discussed. 相似文献
9.
Colonization of macroinvertebrates in a headwater mountain stream was monitored using basket and Surber samplers. Taxa showed differences in colonization ability based both on dispersal ability and feeding strategy. Collector - gatherer feeding groups that could actively enter the water, i.e., Baetis mayflies, were the first organisms to colonize bare or new substrate. The slowest colonizers were heptageniid mayflies that colonized primarily from upstream migration. All organisms examined increased drifting behavior in response to decreases in discharge. 相似文献