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Many tumours are composed of genetically diverse cells; however, little is known about how diversity evolves or the impact that diversity has on functional properties. Here, using xenografting and DNA copy number alteration (CNA) profiling of human BCR-ABL1 lymphoblastic leukaemia, we demonstrate that genetic diversity occurs in functionally defined leukaemia-initiating cells and that many diagnostic patient samples contain multiple genetically distinct leukaemia-initiating cell subclones. Reconstructing the subclonal genetic ancestry of several samples by CNA profiling demonstrated a branching multi-clonal evolution model of leukaemogenesis, rather than linear succession. For some patient samples, the predominant diagnostic clone repopulated xenografts, whereas in others it was outcompeted by minor subclones. Reconstitution with the predominant diagnosis clone was associated with more aggressive growth properties in xenografts, deletion of CDKN2A and CDKN2B, and a trend towards poorer patient outcome. Our findings link clonal diversity with leukaemia-initiating-cell function and underscore the importance of developing therapies that eradicate all intratumoral subclones.  相似文献   
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Bryophytes were found to be abundant as components of microbiotic soil crusts on the calcareous soils of Mungo National Park, an arid area of southern central Australia. Six sites that reflected differences in soils, topography, and vascular plant vegetation were studied. At each site bryophytes were abundant, both in terms of number of species present and percent ground cover. Number of species present did not differ significantly between sites, but percent bryophyte cover was lower at a site on sand dunes in mallee woodland and a site on a silcrete ridge than at the four other sites. Environmental factors (soil texture, pH, conductivity, nutrient status, vascular plant vegetation, light level, leaf litter, and fire frequency) appear to play a significant part in determining bryophyte distribution. Mosses that occur at Mungo are also widespread on calcareous substrates throughout arid southern Australia. Many of the bryophyte species present at Mungo also occur on limestones in high rainfall areas of eastern Australia. Environmental factors favoring bryophytic soil crusts in arid Australia are also present on limestones in high rainfall areas of eastern Australia and may account for tile presence of many arid zone bryophyte species on limestones. In Australia there appears to be a relationship between rainfall and the ratios of acrocarpous to pleurocarpous mosses, and thallose to leafy liverworts. Recognition of calcareous soils, widespread in arid areas of southern Australia, may be possible by assessing a combination of characteristics of bryophyte assemblages.  相似文献   
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MicroRNA expression profiles classify human cancers   总被引:13,自引:0,他引:13  
Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.  相似文献   
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Effects of biodiversity on the functioning of trophic groups and ecosystems   总被引:22,自引:0,他引:22  
Over the past decade, accelerating rates of species extinction have prompted an increasing number of studies to reduce species diversity experimentally and examine how this alters the efficiency by which communities capture resources and convert those into biomass. So far, the generality of patterns and processes observed in individual studies have been the subjects of considerable debate. Here we present a formal meta-analysis of studies that have experimentally manipulated species diversity to examine how it affects the functioning of numerous trophic groups in multiple types of ecosystem. We show that the average effect of decreasing species richness is to decrease the abundance or biomass of the focal trophic group, leading to less complete depletion of resources used by that group. At the same time, analyses reveal that the standing stock of, and resource depletion by, the most species-rich polyculture tends to be no different from that of the single most productive species used in an experiment. Of the known mechanisms that might explain these trends, results are most consistent with what is called the 'sampling effect', which occurs when diverse communities are more likely to contain and become dominated by the most productive species. Whether this mechanism is widespread in natural communities is currently controversial. Patterns we report are remarkably consistent for four different trophic groups (producers, herbivores, detritivores and predators) and two major ecosystem types (aquatic and terrestrial). Collectively, our analyses suggest that the average species loss does indeed affect the functioning of a wide variety of organisms and ecosystems, but the magnitude of these effects is ultimately determined by the identity of species that are going extinct.  相似文献   
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