Abstract:
:Early passages of NIH 3T3 cells yield about 10 transformed foci for every 10(5) cells seeded after the cells multiply to confluence in a standardized 2-week assay. The question arose whether more cells would give rise to foci if given more time for their development. This question could not be answered simply by extending the incubation period, since the original foci spread to cover much of the area of the culture dish. Transformed cells can also detach into the medium from the original foci to initiate new foci by reattaching at a distance. These problems were averted by growing cells in multiwell plates which in effect simulated partitioned culture dishes. All the wells in a given plate were assayed for focus formation at successive intervals up to 14 weeks. The results indicated the spatial pattern and sequence of transformation on different parts of the "partitioned" dish. The number of multiwells containing focus-forming cells increased steadily with time, indicating that all parts of a dish eventually undergo transformation. Also, most of the transformations were recorded long after confluence in the multiwells was reached. Hence such a transformation is much more likely to occur in the nondividing state rather than in the dividing state of the cells and is thus inconsistent with a mutational basis. The results suggest that "spontaneous" transformation is a population-wide, epigenetic phenomenon. This agrees with the results from clonal analysis and other studies and is well described by the concept of progressive state selection, in which "spontaneous" transformation represents a heterogeneous, adaptive response of competent cells to moderate constraints on cell growth.
journal_name
Proc Natl Acad Sci U S Aauthors
Chow M,Yao A,Rubin Hdoi
10.1073/pnas.91.2.599subject
Has Abstractpub_date
1994-01-18 00:00:00pages
599-603issue
2eissn
0027-8424issn
1091-6490journal_volume
91pub_type
杂志文章abstract::In Caenorhabditis elegans, pre-mRNA for the essential splicing factor U2AF65 sometimes is spliced to produce an RNA that includes an extra 216-bp internal exon, exon 3. Inclusion of exon 3 inserts an in-frame stop codon, yet this RNA is not subject to SMG-mediated RNA surveillance. To test whether exon 3 causes RNA to...
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.96.7.3813
更新日期:1999-03-30 00:00:00
abstract::The binding of interferons to distinct cell surface receptors leads to the induction of synthesis of several unique polypeptides and their corresponding mRNAs (1-6). We have isolated two cDNAs that are complementary to nuclear RNA whose synthesis is induced from undetectable levels to maximal rates of transcription wi...
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.81.21.6733
更新日期:1984-11-01 00:00:00
abstract::Toll-like receptors (TLRs) play key roles in detecting pathogens and initiating inflammatory responses that, subsequently, prime specific adaptive responses. Several mechanisms control TLR activity to avoid excessive inflammation and consequent immunopathology, including the anti-inflammatory cytokine IL-10. Recently,...
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.1219852110
更新日期:2013-07-09 00:00:00
abstract::Calcicludine (CaC) is a 60-amino acid polypeptide from the venom of Dendroaspis angusticeps. It is structurally homologous to the Kunitz-type protease inhibitor, to dendrotoxins, which block K+ channels, and to the protease inhibitor domain of the amyloid beta protein that accumulates in Alzheimer disease. Voltage-cla...
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.91.3.878
更新日期:1994-02-01 00:00:00
abstract::Most B lymphocytes in normal individuals express two classes of cell-surface immunoglobulins, IgM and IgD. The specificity of the two antigen receptors is identical since they are produced by transcription and differential splicing of the same variable region gene segment to the heavy-chain constant region gene segmen...
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.91.4.1323
更新日期:1994-02-15 00:00:00
abstract::Inherited retinal degeneration (RD) is a devastating and currently untreatable neurodegenerative condition that leads to loss of photoreceptor cells and blindness. The vast genetic heterogeneity of RD, the lack of "druggable" targets, and the access-limiting blood-retinal barrier (BRB) present major hurdles toward eff...
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.1718792115
更新日期:2018-03-27 00:00:00
abstract::We have used a membrane-leak mass spectrometer to follow the time courses of H2 evolution and substrate reduction by nitrogenase [reduced ferredoxin:dinitrogen oxidoreductase (ATP-hydrolyzing), EC 1.18.6.1]. In the absence of added substrates, dinitrogenase passes all of its electrons to protons to form H2, but when a...
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.85.24.9446
更新日期:1988-12-01 00:00:00
abstract::Metabolic engineering seeks to reprogram microbial cells to efficiently and sustainably produce value-added compounds. Since chemical production can be at odds with the cell's natural objectives, strategies have been developed to balance conflicting goals. For example, dynamic regulation modulates gene expression to f...
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.1911144116
更新日期:2019-12-17 00:00:00
abstract::Ancient societies are often used to illustrate the potential problems stemming from unsustainable land-use practices because the past seems rife with examples of sociopolitical "collapse" associated with the exhaustion of finite resources. Just as frequently, and typically in response to such presentations, archaeolog...
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
doi:10.1073/pnas.1409646111
更新日期:2014-08-12 00:00:00
abstract::Nucleotide sequence analysis of one of several tRNA genes cloned from Tetrahymena thermophila macronuclear DNA indicated that it corresponds to a tRNA species having TTA as anticodon. Subsequently, the tRNA species corresponding to that gene was isolated and its nucleotide sequence was determined by post-labeling tech...
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.82.14.4758
更新日期:1985-07-01 00:00:00
abstract::PDZ domains are abundant protein interaction modules and typically recognize a short motif at the C terminus of their ligands, with a few residues in the motif endowing the binding specificity. The sequence-based rules, however, cannot fully account for the specificity between the vast number of PDZ domains and ligand...
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.1508931112
更新日期:2015-12-01 00:00:00
abstract::α-Dystroglycan (α-DG) is a highly glycosylated basement membrane receptor that is cleaved by the proprotein convertase furin, which releases its N-terminal domain (α-DGN). Before cleavage, α-DGN interacts with the glycosyltransferase LARGE1 and initiates functional O-glycosylation of the mucin-like domain of α-DG. Not...
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.1904493116
更新日期:2019-06-04 00:00:00
abstract::Oil-in-water emulsions are potent human adjuvants used for effective pandemic influenza vaccines; however, their mechanism of action is still unknown. By combining microarray and immunofluorescence analysis, we monitored the effects of the adjuvants MF59 oil-in-water emulsion, CpG, and alum in the mouse muscle. MF59 i...
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.0804699105
更新日期:2008-07-29 00:00:00
abstract::Volume changes associated with protein folding reactions contain valuable information about the folding mechanism and the nature of the transition state. However, meaningful interpretation of such data requires that overall volume changes be deconvoluted into individual contributions from different structural componen...
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.1317973110
更新日期:2013-12-24 00:00:00
abstract::One goal of regenerative medicine is to repair damaged tissue. This requires not only generating new cells of the proper phenotype, but also selecting for those that properly integrate into sites of injury. In our laboratory we are using a cell-migration-based in vivo selection system to generate antibodies that induc...
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.1719259115
更新日期:2018-01-16 00:00:00
abstract::We describe in this study punchless, a nonpathogenic mutant from the rice blast fungus M. grisea, obtained by plasmid-mediated insertional mutagenesis. As do most fungal plant pathogens, M. grisea differentiates an infection structure specialized for host penetration called the appressorium. We show that punchless dif...
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.111132998
更新日期:2001-06-05 00:00:00
abstract::This work argues that, in a polarized environment, scientists can minimize the likelihood that the audience's biased processing will lead to rejection of their message if they not only eschew advocacy but also, convey that they are sharers of knowledge faithful to science's way of knowing and respectful of the audienc...
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.1320868111
更新日期:2014-09-16 00:00:00
abstract::Sera from 30 patients with astrocytoma were tested for antibody reacting with cell surface antigens of cultured autologous astrocytoma cells. Ten percent of the patients had antibody detectable by mixed hemadsorption assays, approximately 50% by immune adherence and protein A assays, and 100% by anti-C3-mixed hemadsor...
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.75.10.5122
更新日期:1978-10-01 00:00:00
abstract::Reducible compounds that participate in crosslinking were analyzed in hydroxylysine-deficient collagens of patients with a heritable disorder of connective tissue. After treatment with [(3)H]sodium borohydride, new compounds, as well as a totally different pattern of tritiated compounds, were found in hydroxylysine-de...
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.69.9.2594
更新日期:1972-09-01 00:00:00
abstract::Continuous and intensive exploitation of wildlife resources by early agricultural societies had major ecological consequences in the ancient Near East. In particular, hunting strategies of post-Neolithic societies involving the mass killing of wild ungulates contributed to the eventual extirpation of a number of wild ...
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
doi:10.1073/pnas.1017647108
更新日期:2011-05-03 00:00:00
abstract::The betaalpha barrel is the common protein fold of numerous enzymes and was proposed recently to be the result of gene duplication and fusion of an ancient half-barrel. The initial enzyme of shikimate biosynthesis possesses the additional feature of feedback regulation. The crystal structure and kinetic studies on chi...
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.0337566100
更新日期:2003-02-04 00:00:00
abstract::Electron cryomicroscopy (cryo-EM) has been used to determine the atomic coordinates (models) from density maps of biological assemblies. These models can be assessed by their overall fit to the experimental data and stereochemical information. However, these models do not annotate the actual density values of the atom...
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.1621152114
更新日期:2017-03-21 00:00:00
abstract::Ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid have been attached covalently to the 5' terminus of the deoxynucleotide sequence C-A-C-A-A-T-T-C-C-A-C-A-C-A-A-C (16-mer) via an ethylenediamine linker. In the presence of Fe2+ and dithiothreitol, these reagents bring about the hybridization-depend...
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.82.4.963
更新日期:1985-02-01 00:00:00
abstract::The carboxy-terminal domain (CTD) code encrypted within the Y1S2P3T4S5P6S7 heptad repeats of RNA polymerase II (Pol2) is deeply rooted in eukaryal biology. Key steps to deciphering the code are identifying the events in gene expression that are governed by individual "letters" and then defining a vocabulary of multile...
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.1810711115
更新日期:2018-11-06 00:00:00
abstract::Transcription is an intrinsically dynamic process and requires the coordinated interplay of RNA polymerases (RNAPs) with nucleic acids and transcription factors. Classical structural biology techniques have revealed detailed snapshots of a subset of conformational states of the RNAP as they exist in crystals. A detail...
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.1515817113
更新日期:2016-03-29 00:00:00
abstract::Human diploid fibroblasts underwent lysis when resuspended in isotonic sucrose. After preparation of a granular fraction by differential centrifugation, lysosomes were almost completely purified by free-flow electrophoresis. Electron micrographs of the final fraction of fibroblast lysosomes (about 25-fold purified) sh...
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.77.10.6139
更新日期:1980-10-01 00:00:00
abstract::The approximately 30-kb coronavirus (+)RNA genome is replicated and transcribed by a membrane-bound replicase complex made up of 16 viral nonstructural proteins (nsp) with multiple enzymatic activities. The complex includes an RNA endonuclease, NendoU, that is conserved among nidoviruses but no other RNA virus, making...
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.0601708103
更新日期:2006-08-08 00:00:00
abstract::Development of effective chemopreventive agents against prostate cancer (CaP) for humans requires conclusive evidence of their efficacy in animal models that closely emulates human disease. The autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which spontaneously develops metastatic CaP, is ...
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.171326098
更新日期:2001-08-28 00:00:00
abstract::The Bacillus subtilis phage SP01, whose DNA contains 5-hydroxymethyluracil (hmUra) in place of thymine, codes for an abundant, small, basic protein called TF1. TF1 binds preferentially to hydroxymethyluracil-containing DNA and thereby selectively inhibits transcription of such DNA in vitro. The gene for TF1 has been s...
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.81.22.7031
更新日期:1984-11-01 00:00:00
abstract::The stoichiometry of J chain in pentamer IgM has been determined by measuring the radiolabeled thiols in the constituent chains after complete reduction and alkylation of the polymer. One mole of J was found to be disulfide bonded to 1 mol of pentamer. The linkage of J chain in IgM has been determined by correlating t...
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.71.3.657
更新日期:1974-03-01 00:00:00