Abstract:
:Thresholds are frequently thought to be involved in the development of discrete structures in response to a shallow, monotonic gradient of morphogenetic information. We propose a mechanism for threshold setting that incorporates two essential components: (i) determinator genes that produce intracellular "determinators" that control cellular differentiation during development and (ii) intracellular "inhibitors" that bind tightly and specifically to the determinators to form "determinator-inhibitor pairs" that are inactive with respect to determinator function. The interaction of these components amplifies the intracellular response to an extra-cellular morphogen, thus producing a sharp transition in determinator gene activity. This system could operate at either the RNA level with the determinator-inhibitor pairs taking the form of sense-antisense RNAs or at the protein level via a competitive inhibition mechanism. In either case this model suggests a possible role for pseudogenes in development as a source of the intracellular inhibitors.
journal_name
Proc Natl Acad Sci U S Aauthors
McCarrey JR,Riggs ADdoi
10.1073/pnas.83.3.679subject
Has Abstractpub_date
1986-02-01 00:00:00pages
679-83issue
3eissn
0027-8424issn
1091-6490journal_volume
83pub_type
杂志文章abstract::A biologically active vitamin D(3) metabolite ("peak V metabolite") more polar than 25-hydroxycholecalciferol has been isolated from chicken intestines in pure form as a mono(trimethylsilyl)ether derivative. The molecule has been identified as 1,25-dihydroxycholecalciferol by means of mass spectrometry, ultraviolet ab...
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.68.4.803
更新日期:1971-04-01 00:00:00
abstract::Whole-genome duplication (WGD) is believed to be a significant source of major evolutionary innovation. Redundant genes resulting from WGD are thought to be lost or acquire new functions. However, the rates of gene loss and thus temporal process of genome reshaping after WGD remain unclear. The WGD shared by all teleo...
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.1507669112
更新日期:2015-12-01 00:00:00
abstract::The effect of plasmin-derived fibrinogen fragments on the biosynthesis of fibrinogen was investigated in cultured monolayers of rat hepatocytes. Incubating the cells with several concentrations of either fibrinogen or fibrin fragment D or E had no effect on the synthesis and secretion of fibrinogen by these cells. How...
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.79.5.1530
更新日期:1982-03-01 00:00:00
abstract::IL-2-PE40 is a chimeric protein composed of human interleukin 2 (IL-2) genetically fused to the amino terminus of a modified form of Pseudomonas exotoxin lacking its cell recognition domain. IL-2-PE40, which is extremely cytotoxic to IL-2 receptor-positive cells, was examined for its ability to prevent graft rejection...
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.86.3.1008
更新日期:1989-02-01 00:00:00
abstract::The assembly of regional biotas and organismal responses to anthropogenic climate change both depend on the capacity of organisms to adapt to novel ecological conditions. Here we demonstrate the concept of evolutionary lag time, the time between when a climatic regime or habitat develops in a region and when it is col...
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.1308721110
更新日期:2013-07-09 00:00:00
abstract::Treatment with neuraminidase (NA) plus galactose oxidase (GalOxase) does not cause stimulation of human thymocytes. However, stimulation can be achieved by addition of exogenous interleukin 2 (IL-2). The IL-2-induced stimulation was inhibited with anti-Tac antibody, indicating that NA/GalOxase-oxidized cells can serve...
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.81.16.5209
更新日期:1984-08-01 00:00:00
abstract::Two subjects, of 11,000 healthy individuals screened, were found to be missing three and four immunoglobulin isotypes, respectively (IgA1, IgG2, and IgG4; IgA1, IgG2, IgG4, and IgE), and have been analyzed at the DNA level by means of Southern blotting and Ig heavy-chain-specific probes. A broad deletion within the he...
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.81.18.5811
更新日期:1984-09-01 00:00:00
abstract::Ca(2+) is known to have important roles in sperm chemotaxis, although the relationship between intracellular Ca(2+) concentration ([Ca(2+)](i)) and modulation of the swimming and chemotactic behavior of spermatozoa has not been elucidated. Using a high-speed Ca(2+) imaging system, we examined the chemotactic behavior ...
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.0808580105
更新日期:2008-12-09 00:00:00
abstract::The ability of cocaine to inhibit the dopamine transporter (DAT) appears to be crucial for its reinforcing properties. The potential use of drugs that produce long-lasting inhibition of the DAT as a mean of preventing the "high" and reducing drug-seeking behavior has become a major strategy in medication development. ...
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.93.19.10388
更新日期:1996-09-17 00:00:00
abstract::A muscarone-binding material has been found in Torpedo electroplax. The material behaves in several ways as one would expect of the binding component of the acetylcholine receptor, especially in its high affinity for muscarone (approximate K = 7 x 10(-6)M), acetylcholine (approximate K = 1.1 x 10(-6)M), curare, and ni...
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.63.2.496
更新日期:1969-06-01 00:00:00
abstract::The goal of the current study was to investigate the role of exogenous and endogenous hydrogen sulfide (H(2)S) on neovascularization and wound healing in vitro and in vivo. Incubation of endothelial cells (ECs) with H(2)S enhanced their angiogenic potential, evidenced by accelerated cell growth, migration, and capilla...
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.0908047106
更新日期:2009-12-22 00:00:00
abstract::When a mutant of Saccharomyces cerevisiae (spe2 delta) that cannot make spermidine or spermine was incubated in a polyamine-deficient medium in oxygen, there was a rapid cessation of cell growth and associated cell death. In contrast, when the mutant cells were incubated in the polyamine-deficient medium in air or ana...
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.90.10.4693
更新日期:1993-05-15 00:00:00
abstract::Diabetes is now the most common cause of progressive kidney failure leading to dialysis or transplantation. The central pathological feature of diabetic nephropathy is accumulation of extracellular matrix within the glomeruli. The factors in the diabetic milieu responsible for extracellular matrix accumulation are 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.90.5.1814
更新日期:1993-03-01 00:00:00
abstract::Transfer RNA is one of the most richly modified biological molecules. Biosynthetic pathways that introduce these modifications are underexplored, largely because their absence does not lead to obvious phenotypes under normal growth conditions. Queuosine (Q) is a hypermodified base found in the wobble positions of tRNA...
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.1018636108
更新日期:2011-05-03 00:00:00
abstract::Inherited single gene defects have been identified in both humans and mice that lead to loss of developmental control over the left-right asymmetry of the heart and viscera. In mice the recessively inherited mutation iv leads to such apparent loss of control over situs: 50% of iv/iv mice exhibit situs inversus and 50%...
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.86.13.5035
更新日期:1989-07-01 00:00:00
abstract::In the wake of the COVID-19 pandemic many countries implemented containment measures to reduce disease transmission. Studies using digital data sources show that the mobility of individuals was effectively reduced in multiple countries. However, it remains unclear whether these reductions caused deeper structural chan...
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.2012326117
更新日期:2020-12-29 00:00:00
abstract::Hox genes are located in highly conserved clusters. The significance of this organization is unclear, but one possibility is that regulatory regions for individual genes are dispersed throughout the cluster and shared with other Hox genes. This hypothesis is supported by studies on several Hox genes in which even larg...
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.93.6.2426
更新日期:1996-03-19 00:00:00
abstract::A Drosophila cDNA encoding a human transcription factor TFIIB homologue was isolated by PCR methods. The deduced amino acid sequence indicates 85% sequence similarity with human TFIIB, and the corresponding cDNA product expressed in Escherichia coli is interchangeable with human TFIIB for both basal and GAL4-VP16-indu...
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.89.7.2839
更新日期:1992-04-01 00:00:00
abstract::Established T cell dysfunction is a barrier to antitumor responses, and checkpoint blockade presumably reverses this. Many patients fail to respond to treatment and/or develop autoimmune adverse events. The underlying reason for T cell responsiveness remains elusive. Here, we show that susceptibility to checkpoint blo...
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.1810326116
更新日期:2019-02-12 00:00:00
abstract::Although heparin and low-molecular-weight heparins (LMWH) have been widely used clinically as anticoagulants, their broader use has been limited by the lack of noninvasive delivery methods for this class of molecules. In this study, we demonstrate an efficient, rapid, and reproducible delivery system for heparin throu...
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.0402891101
更新日期:2004-06-29 00:00:00
abstract::An intact T/E1A-binding domain (the pocket) is necessary, but not sufficient, for the retinoblastoma protein (RB) to bind to DNA-protein complexes containing E2F and for RB to induce a G1/S block. Indirect evidence suggests that the binding of RB to E2F may, in addition to inhibiting E2F transactivation function, gene...
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.92.25.11544
更新日期:1995-12-05 00:00:00
abstract::Antibodies can be developed to directly inhibit almost any protein, but their inability to enter the cytosol limits inhibitory antibodies to membrane-associated or extracellular targets. Developing a cytosolic antibody delivery system would offer unique opportunities to directly inhibit and study intracellular protein...
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.1913973116
更新日期:2019-10-29 00:00:00
abstract::We have developed a defective herpes simplex virus (HSV) vector system that permits the introduction of virtually any gene into mammalian central nervous system neurons. The prototype vector, pHSVlac, contains a transcription unit that places the Escherichia coli lacZ gene under the control of the HSV-1 immediate earl...
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.87.3.1149
更新日期:1990-02-01 00:00:00
abstract::We developed a method for rapidly generating thermostable enzyme variants. Our strategy is to introduce the gene coding for a given enzyme from a mesophilic organism into a thermophile, Bacillus stearothermophilus. Variants that retain the enzymatic activity at the higher growth temperatures of the thermophile are the...
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.83.3.576
更新日期:1986-02-01 00:00:00
abstract::Proteasomes are the multi-subunit protease thought to play a key role in the generation of peptides presented by major histocompatibility complex (MHC) class I molecules. When cells are stimulated with interferon gamma, two MHC-encoded subunits, low molecular mass polypeptide (LMP) 2 and LMP7, and the MECL1 subunit en...
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.93.17.9096
更新日期:1996-08-20 00:00:00
abstract::Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal disease in critical need of new therapeutic strategies. Here, we report that the stress-inducible 78-kDa glucose-regulated protein (GRP78/HSPA5), a key regulator of endoplasmic reticulum homeostasis and PI3K/AKT signaling, is overexpressed in the acini an...
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.1616060114
更新日期:2017-05-16 00:00:00
abstract::Breast cancer is a genetically and clinically heterogeneous disease, and the contributions of different target cells and different oncogenic mutations to this heterogeneity are not well understood. Here we report that mammary tumors induced by components of the Wnt signaling pathway contain heterogeneous cell types an...
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.2136825100
更新日期:2003-12-23 00:00:00
abstract::Recently, it has been reported that there is a differential subcellular distribution of components of the minor U12-dependent and major U2-dependent spliceosome, and further that the minor spliceosome functions in the cytoplasm. To study the subcellular localization of the snRNA components of both the major and minor ...
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.0803646105
更新日期:2008-06-24 00:00:00
abstract::Intact squid axons were injected with aequorin and bathed in 3 mM Ca seawater (a concentration close to that of squid blood). Sodium and potassium currents were pharmacologically blocked and repetitive voltage-clamp pulses of a duration of 1.5 ms were applied (to simulate the duration of an action potential) at amplit...
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.82.6.1847
更新日期:1985-03-01 00:00:00
abstract::Type I (IFN-alpha/beta) and type III (IFN-lambdas) IFNs are important components of the host antiviral response. Although type III IFNs possess intrinsic antiviral activity similar to that of type I IFNs, they signal through a specific unique receptor complex, and their functional importance for antiviral resistance 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.0610352104
更新日期:2007-06-05 00:00:00