Abstract:
:Agonist binding to the muscarinic receptor in rat cerebral cortex membranes was studied by using the neurotransmitter itself, [3H]acetylcholine [( 3H]AcCho). By using 10 microM atropine or oxotremorine to define specific binding, it was possible to demonstrate specific binding of [3H]AcCho that was sensitive to muscarinic but not to nicotinic ligands. Equilibrium binding experiments with 5-240 nM [3H]AcCho indicated specific binding of the ligand to a saturable population of muscarinic receptors (361 +/- 29 fmol/mg of protein; Kd = 76 +/- 17 nM). This value represented 25% of the available binding sites for a labeled antagonist in the same preparation and corresponds to the proportion of high-affinity agonist binding sites observed previously in competition experiments with labeled antagonists. Inclusion of transition metal ions (e.g., 2 mM Ni2+) in the assay increased the equilibrium binding of [3H]AcCho (628 +/- 38 fmol/mg of protein, Kd = 86 +/- 21 nM) but did not affect equilibrium binding of 3H-labeled antagonists, indicating conversion of low- into high-affinity muscarinic agonist binding sites. The increase developed slowly over 30 min of incubation at 25 degrees C but could be reversed rapidly (approximately equal to 2 min) by the chelating agent EDTA or by guanine nucleotides. These data directly reveal a slow though quickly reversible interconversion of low- into high-affinity muscarinic agonist binding sites.
journal_name
Proc Natl Acad Sci U S Aauthors
Gurwitz D,Kloog Y,Sokolovsky Mdoi
10.1073/pnas.81.12.3650subject
Has Abstractpub_date
1984-06-01 00:00:00pages
3650-4issue
12eissn
0027-8424issn
1091-6490journal_volume
81pub_type
杂志文章abstract::High-resolution single nucleotide polymorphism genomic microarray (SNP-chip) is a useful tool to define gene dosage levels over the whole genome, allowing precise detection of deletions and duplications/amplifications of chromosomes in cancer cells. We found that this new technology can also identify breakpoints of ch...
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.0711039105
更新日期:2008-08-19 00:00:00
abstract::We present a model describing how Mg(2+) binds and stabilizes specific RNA structures. In this model, RNA stabilization arises from two energetically distinct modes of Mg(2+) binding: diffuse- and site-binding. Diffusely bound Mg(2+) are electrostatically attracted to the strong anionic field around the RNA and are ac...
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.221234598
更新日期:2001-10-23 00:00:00
abstract::The molecular size and stability of the nerve growth factor (NGF) secreted in culture by L cells have been studied by sedimentation and gel filtration chromatography. Results indicate that L cell NGF has a molecular weight of 160,000. It contains as part of its structure a protein component that is biologically, immun...
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.74.4.1492
更新日期:1977-04-01 00:00:00
abstract::The temporal distribution of the major extinctions over the past 250 million years has been investigated statistically using various forms of time series analysis. The analyzed record is based on variation in extinction intensity for fossil families of marine vertebrates, invertebrates, and protozoans and contains 12 ...
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.81.3.801
更新日期:1984-02-01 00:00:00
abstract::Gene expression has a stochastic component because of the single-molecule nature of the gene and the small number of copies of individual DNA-binding proteins in the cell. We show how the statistics of such systems can be mapped onto quantum many-body problems. The dynamics of a single gene switch resembles the spin-b...
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.2627987100
更新日期:2003-03-04 00:00:00
abstract::The ability to be synchronized by light-dark cycles is a fundamental property of circadian clocks. Although there are indications that circadian clocks are extremely light-sensitive and that they can be set by the low irradiances that occur at dawn and dusk, this has not been shown on the cellular level. Here, we demo...
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.0606870104
更新日期:2007-02-27 00:00:00
abstract::Maintaining the fidelity of nascent peptide chain (NP) synthesis is essential for proteome integrity and cellular health. Ribosome-associated quality control (RQC) serves to resolve stalled translation, during which untemplated Ala/Thr residues are added C terminally to stalled peptide, as shown during C-terminal Ala ...
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.2005506117
更新日期:2020-10-06 00:00:00
abstract::The growth of actin filament networks is a fundamental biological process that drives a variety of cellular and intracellular motions. During motility, eukaryotic cells and intracellular pathogens are propelled by actin networks organized by nucleation-promoting factors that trigger the formation of nascent filaments ...
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.0702601104
更新日期:2007-10-02 00:00:00
abstract::Severe combined immunodeficient (SCID) mice display an increased sensitivity to ionizing radiation compared with the parental, C.B-17, strain due to a deficiency in DNA double-strand break repair. The catalytic subunit of DNA-dependent protein kinase (DNA-PKCS) has previously been identified as a strong candidate for ...
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.93.24.13825
更新日期:1996-11-26 00:00:00
abstract::Damage to the protooncogene MYC has been implicated in the genesis of diverse human tumors, but the tumorigenic potential of the isolated gene has been disputed. Here we report the use of a retroviral vector to test the potency of human MYC for neoplastic transformation in avian cells. We found that sustained and abun...
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.87.6.2102
更新日期:1990-03-01 00:00:00
abstract::Na(+)-NQR is a unique respiratory enzyme that couples the free energy of electron transfer reactions to electrogenic pumping of sodium across the cell membrane. This enzyme is found in many marine and pathogenic bacteria where it plays an analogous role to the H(+)-pumping complex I. It has generally been assumed that...
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.1002866107
更新日期:2010-07-13 00:00:00
abstract::Molecular weights of the isolated proteins from the 30S and 50S ribosomal subunits of Escherichia coli were determined by two independent methods: polyacrylamide gel electrophoresis with sodium dodecylsulphate and equilibrium sedimentation. The values for the molecular weights determined by gel electrophoresis range 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.67.4.1909
更新日期:1970-12-01 00:00:00
abstract::Palmitoylation is a common lipid modification known to regulate the functional properties of various proteins and is a vital step in the biosynthesis of voltage-activated sodium (Nav) channels. We discovered a mutation in an intracellular loop of rNav1.2a (G1079C), which results in a higher apparent affinity for exter...
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.1108497108
更新日期:2011-12-13 00:00:00
abstract::Clean water is paramount to human health. In this article, we present a technique for detection of trace amounts of human or animal waste products in water using fluorescence emission cavity-enhanced spectroscopy. The detection of femtomolar concentrations of urobilin, a metabolic byproduct of heme metabolism that 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.1403175111
更新日期:2014-05-20 00:00:00
abstract::Recent experiments have shown that spreading epithelial sheets exhibit a long-range coordination of motility forces that leads to a buildup of tension in the tissue, which may enhance cell division and the speed of wound healing. Furthermore, the edges of these epithelial sheets commonly show finger-like protrusions w...
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.1219937110
更新日期:2013-02-12 00:00:00
abstract::Cysteine site-directed mutagenesis was used to create variants of Escherichia coli ribosomal protein L7/L12 that have single cysteine substitutions, at residues 63 or 89, located in different exposed loops in the structure of the globular C-terminal domain indicated by the crystallographic structure. That structure 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.90.21.9828
更新日期:1993-11-01 00:00:00
abstract::Emerging genetic and clinical evidence suggests a link between Gaucher disease and the synucleinopathies Parkinson disease and dementia with Lewy bodies. Here, we provide evidence that a mouse model of Gaucher disease (Gba1(D409V/D409V)) exhibits characteristics of synucleinopathies, including progressive accumulation...
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.1108197108
更新日期:2011-07-19 00:00:00
abstract::Fifteen tumor-containing specimens were obtained directly from patients with small cell carcinoma of the lung and tested for their ability to grow in serum-supplemented medium and in serum-free medium supplemented with hydrocortisone, insulin, transferrin, estrogen, and selenium (HITES). The tumor cells replicated in ...
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.78.5.3185
更新日期:1981-05-01 00:00:00
abstract::We used gene knockout mice to explore the role of Angiopoietin-like-4 (Angptl4) in lipid metabolism as well as to generate anti-Angptl4 mAbs with pharmacological activity. Angptl4 -/- mice had lower triglyceride (TG) levels resulting both from increased very low-density lipoprotein (VLDL) clearance and decreased VLDL ...
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.0705041104
更新日期:2007-07-10 00:00:00
abstract::Productive T cell recognition of antigen-presenting cells (APCs) is normally accompanied by the formation of a cell-cell contact called the "immunological synapse." Our understanding of the steps leading up to this formation has been limited by the absence of tools for analyzing 3D surfaces and surface distributions 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.192573999
更新日期:2002-11-12 00:00:00
abstract::The elucidation of the mechanisms of antigen presentation by major histocompatibility complex class I molecules has stimulated the search for nonreplicative vectors that could deliver CD8+ T cell epitopes to the cytosol of antigen-presenting cells to trigger the activation of specific cytotoxic T lymphocytes (CTLs) in...
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.94.7.3314
更新日期:1997-04-01 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::The 18O/16O of calcite fossils increased by ∼8‰ between the Cambrian and present. It has long been controversial whether this change reflects evolution in the δ18O of seawater, or a decrease in ocean temperatures, or greater extents of diagenesis of older strata. Here, we present measurements of the oxygen and ‟clumpe...
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.1719681115
更新日期:2018-06-26 00:00:00
abstract::Astrocytes can release glutamate in a calcium-dependent manner and consequently signal to adjacent neurons. Whether this glutamate release pathway is used during physiological signaling or is recruited only under pathophysiological conditions is not well defined. One reason for this lack of understanding is the limite...
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.97.15.8629
更新日期:2000-07-18 00:00:00
abstract::Cdc7 is an essential kinase required for the initiation of eukaryotic DNA replication. Previous studies in many species showed that the minichromosome maintenance complex is a major physiological target of this kinase. In this study, we have mapped the sites in human Mcm2 protein that are phosphorylated by Cdc7. The 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.0604990103
更新日期:2006-08-01 00:00:00
abstract::Overexpression of the receptor tyrosine kinase (RTK) erbB2 (also designated neu or HER2) was implicated in causing a variety of human cancers, including mammary and ovarian carcinomas. Ligand-induced receptor dimerization is critical for stimulation of the intrinsic protein tyrosine kinase (PTK) of RTKs. It was theref...
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.252640799
更新日期:2002-12-10 00:00:00
abstract::The involvement of methylation in the chemosensory response of bacteria to many attractants has been clearly established by studies in several laboratories. It has been assumed that adaptation of Salmonella typhimurium and Escherichia coli to all attractants involves methylation of a transmembrane methyl-accepting che...
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.79.1.11
更新日期:1982-01-01 00:00:00
abstract::Malignant spreading of cancer cells requires cell surface proteases that cleave the crosslinked collagenous matrix of connective tissues. From correlating the morphologically defined invasiveness of tumor cells with the presence of specific membrane-associated proteases, we have identified a malignant human melanoma c...
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.87.21.8296
更新日期:1990-11-01 00:00:00
abstract::Quinate:NAD(+) 3-oxidoreductase (EC 1.1.1.24) from carrot cell suspension cultures has previously been shown to be activated by phosphorylation and inactivated by dephosphorylation. Here it is shown that the reactivation of the inactivated quinate:NAD(+) oxidoreductase is an enzyme-mediated process that requires ATP 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.80.17.5222
更新日期:1983-09-01 00:00:00
abstract::F(o)F(1)-ATP synthase manufactures the energy "currency," ATP, of living cells. The soluble F(1) portion, called F(1)-ATPase, can act as a rotary motor, with ATP binding, hydrolysis, and product release, inducing a torque on the gamma-subunit. A coarse-grained plastic network model is used to show at a residue level o...
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.0708746105
更新日期:2008-01-29 00:00:00