Abstract:
:Using the Luria-Delbrück fluctuation analysis, we have examined the lung tumor-forming ability of a series of parallel clones derived from the KHT tumor, grown to small defined sizes. From these studies, we conclude that metastatic variants arise spontaneously in the clonal lines during their growth, at an apparent rate of approximately 10(-5) per cell per generation. This rapid rate has implications for our understanding of tumor heterogeneity and the process of tumor progression. Previous results have suggested that heterogeneity observed in cloning experiments reflects stable subpopulations of cells in the original tumor. We propose here an alternative "dynamic heterogeneity" model, in which metastatic variants arise at a high rate (as detected in the cloning experiments) but need not be stable mutations in order to effectively produce metastases.
journal_name
Proc Natl Acad Sci U S Aauthors
Harris JF,Chambers AF,Hill RP,Ling Vdoi
10.1073/pnas.79.18.5547subject
Has Abstractpub_date
1982-09-01 00:00:00pages
5547-51issue
18eissn
0027-8424issn
1091-6490journal_volume
79pub_type
杂志文章abstract::On the basis of task-related imaging studies in normal human subjects, it has been suggested that two attention systems exist in the human brain: a bilateral dorsal attention system involved in top-down orienting of attention and a right-lateralized ventral attention system involved in reorienting attention in respons...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0604187103
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abstract::The embryonic sites in which progenitors of the hematopoietic lineages first emerge are ideal regions to characterize both the cells and environment needed to initiate blood cell development. For a number of years both the murine yolk sac and embryo have been recognized to contain progenitors of B lymphocytes. However...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.14.6429
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abstract::Transgenic mice harboring the int-2/Fgf-3 protooncogene under transcriptional control of the mouse mammary tumor virus (MMTV) promoter/enhancer exhibit a dramatic, benign hyperplasia of the mammary gland. In one int-2 transgenic line (TG.NX), this growth disturbance is evoked by pregnancy and regresses after parturiti...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.92.6.2268
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abstract::Inactivation of the retinoblastoma gene (RB gene) is associated with the development of several human malignancies including retinoblastomas, some osteo- and soft tissue sarcomas, small cell lung cancer, and possibly breast and bladder cancers. To our knowledge, this gene has not been evaluated in human germ-cell mali...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.88.15.6662
更新日期:1991-08-01 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.16.5947
更新日期:1987-08-01 00:00:00
abstract::Most transmissible spongiform encephalopathies arise either spontaneously or by infection. Mutations of PRNP, which encodes the prion protein, PrP, segregate with phenotypically similar diseases. Here we report that moderate overexpression in transgenic mice of mPrP(170N,174T), a mouse PrP with two point mutations tha...
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.10.4562
更新日期:1977-10-01 00:00:00
abstract::The marine nitrogen fixing microorganisms (diazotrophs) are a major source of nitrogen to open ocean ecosystems and are predicted to be limited by iron in most marine environments. Here we use global and targeted proteomic analyses on a key unicellular marine diazotroph Crocosphaera watsonii to reveal large scale diel...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2011-02-08 00:00:00
abstract::The deadly symptoms of malaria occur as Plasmodium parasites replicate within blood cells. Members of several variant surface protein families are expressed on infected blood cell surfaces. Of these, the largest and most ubiquitous are the Plasmodium-interspersed repeat (PIR) proteins, with more than 1,000 variants in...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.22.7891
更新日期:1987-11-01 00:00:00
abstract::The thyroid hormone and retinoid X receptors form a heterodimer with each other and mediate thyroid hormone (T3)-dependent transcription. Retinoid X receptor, in addition, forms a homodimer and mediates 9-cis-retinoic acid-dependent transcription. Here, recombinant thyroid hormone receptor and recombinant retinoid X r...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.91.5.1647
更新日期:1994-03-01 00:00:00
abstract::Small molecules produced by Actinobacteria have played a prominent role in both drug discovery and organic chemistry. As part of a larger study of the actinobacterial symbionts of fungus-growing ants, we discovered a small family of three previously unreported piperazic acid-containing cyclic depsipeptides, gerumycins...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2015-10-27 00:00:00
abstract::Despite structural knowledge of broadly neutralizing monoclonal antibodies (NMAbs) complexed to HIV-1 gp120 and gp41 envelope glycoproteins, virus inactivation mechanisms have been difficult to prove, in part because neutralization assays are complex and were previously not understood. Concordant with recent evidence ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1109728109
更新日期:2012-05-15 00:00:00
abstract::Irrigation of the dog's oxyntic glandular mucosa contained in a chronically prepared, vagally denervated, separated pouch of the dog's stomach with a solution (0.5 mg ml-1) of lyophilized venom of the hooded cobra (Naja naja) increases the permeability of the mucosa. If irrigation with venom solution is repeated at we...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.73.3.968
更新日期:1976-03-01 00:00:00
abstract::IL-17-producing CD4(+) T helper (Th17) cells have recently been defined as a unique subset of proinflammatory helper cells whose development depends on signaling initiated by IL-6 and TGF-beta, autocrine activity of IL-21, activation of STAT3, and induction of the orphan nuclear receptor RORgammat. The maintenance, ex...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0900408106
更新日期:2009-03-24 00:00:00
abstract::The human Thy-1 gene has been isolated and sequenced and compared to the rat and mouse Thy-1 genes. All three genes are organized in the same way: one exon encoding the majority of the signal peptide, another encoding the transmembrane segment, and a third encoding the remainder of the protein. One major structural di...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.19.6657
更新日期:1985-10-01 00:00:00
abstract::Type 2 diabetes mellitus (T2DM) is strongly associated with obesity in most, but not all, ethnic groups, suggesting important ethnic differences in disease susceptibility. Although it is clear that insulin resistance plays a major role in the pathogenesis of T2DM and that insulin resistance is strongly associated with...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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doi:10.1073/pnas.0608537103
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abstract::Argonaute and Piwi proteins are key players in the RNA silencing pathway, with the former interacting with micro-RNAs (miRNAs) and siRNAs, whereas the latter targets piwi-interacting RNAs (piRNAs) that are 2'-O-methylated (2(')-OCH(3)) at their 3' ends. Germline-specific piRNAs and Piwi proteins play a critical role i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2011-01-18 00:00:00
abstract::In the past 15 years, the adoption of subnational immigration policies in the United States, such as those established by individual states, has gone from nearly zero to over 300 per year. These include welcoming policies aimed at attracting and incorporating immigrants, as well as unwelcoming policies directed at den...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2018-01-30 00:00:00
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journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:2012-06-05 00:00:00
abstract::A predictive coarse-grained protein force field [associative memory, water-mediated, structure, and energy model for molecular dynamics (AWSEM)-MD] is used to study the energy landscapes and relative stabilities of amyloid-β protein (1-40) in the monomer and all of its oligomeric forms up to an octamer. We find that a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2016-10-18 00:00:00
abstract::Based on the hypothesis that features of the molecular program of normal wound healing might play an important role in cancer metastasis, we previously identified consistent features in the transcriptional response of normal fibroblasts to serum, and used this "wound-response signature" to reveal links between wound h...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2005-03-08 00:00:00
abstract::In this era of unprecedented biodiversity loss and increased zoonotic disease emergence, it is imperative to understand the effects of biodiversity on zoonotic pathogen dynamics in wildlife. Whether increasing biodiversity should lead to a decrease or increase in infection prevalence, termed the dilution and amplifica...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2018-07-31 00:00:00
abstract::The sparking of cut grape hemispheres in a household microwave oven has been a poorly explained Internet parlor trick for over two decades. By expanding this phenomenon to whole spherical dimers of various grape-sized fruit and hydrogel water beads, we demonstrate that the formation of plasma is due to electromagnetic...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1818350116
更新日期:2019-03-05 00:00:00
abstract::HIV-1 reverse transcriptase (RT) catalyzes the synthesis of DNA from DNA or RNA templates. During this process, it must transfer its primer from one template to another RNA or DNA template. Binary complexes made of RT and a primer/template bind an additional single-stranded RNA molecule of the same nucleotide sequence...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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abstract::Four new members of the fibroblast growth factor (FGF) family, referred to as fibroblast growth factor homologous factors (FHFs), have been identified by a combination of random cDNA sequencing, data base searches, and degenerate PCR. Pairwise comparisons between the four FHFs show between 58% and 71% amino acid seque...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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更新日期:1996-09-03 00:00:00
abstract::Island biogeography theory posits that species richness increases with island size and decreases with isolation. This logic underpins much conservation policy and regulation, with preference given to conserving large, highly connected areas, and relative ambivalence shown toward protecting small, isolated habitat patc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1813051115
更新日期:2019-01-15 00:00:00
abstract::Ancient DNA (aDNA) analysis provides a powerful means of investigating human migration, social organization, and a plethora of other crucial questions about humanity's past. Recently, specialists have suggested that the ideal research design involving aDNA would include multiple independent lines of evidence. In this ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
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更新日期:2020-08-04 00:00:00
abstract::Human activities have increased N availability dramatically in terrestrial and aquatic ecosystems. Extensive research demonstrates that local plant species diversity generally declines in response to nutrient enrichment, yet the mechanisms for this decline remain unclear. Based on an analysis of >900 species responses...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0408648102
更新日期:2005-03-22 00:00:00
abstract::Many cortical neurons combine the information ascending and descending the cortical hierarchy. In the classical view, this information is combined nonlinearly to give rise to a single firing-rate output, which collapses all input streams into one. We analyze the extent to which neurons can simultaneously represent mul...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1720995115
更新日期:2018-07-03 00:00:00