Abstract:
:Na(+)-channel inactivation is proposed to occur by binding of an intracellular inactivation gate to a hydrophobic inactivation gate receptor in the intracellular mouth of the pore. Amino acid residues in transmembrane segment S6 of domain IV (IVS6) that are critical for fast inactivation were identified by alanine-scanning mutagenesis. Mutant VIL1774-6AAA, in which three adjacent residues (Val-Ile-Leu) at the intracellular end of segment IVS6 were converted to alanine, had substantial (> 85%) sustained Na+ currents remaining 15 ms after depolarization, while a nearby mutation of three residues to alanine had no effect. Single-channel analysis revealed continued reopenings late in 40-ms depolarizing pulses indicating that inactivation was substantially impaired compared to wild type. The mean open time for VIL1774-6AAA was longer than wild type, suggesting that this mutation also decreases the rate of entry into the fast inactivated state. These results suggest that residues near the intracellular end of segment IVS6 are critical for fast Na(+)-channel inactivation and may form part of the hydrophobic receptor site for the fast inactivation gate.
journal_name
Proc Natl Acad Sci U S Aauthors
McPhee JC,Ragsdale DS,Scheuer T,Catterall WAdoi
10.1073/pnas.91.25.12346subject
Has Abstractpub_date
1994-12-06 00:00:00pages
12346-50issue
25eissn
0027-8424issn
1091-6490journal_volume
91pub_type
杂志文章abstract::Human T cell clones were analyzed for their susceptibility to activation-induced cell death (AICD) in response to CD3/T cell receptor ligation. AICD was observed only in Th1 clones and was Fas-mediated, whereas Th2 clones resisted AICD. Analysis of a panel of Th0 clones, characterized by their ability to secrete both ...
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.94.11.5778
更新日期:1997-05-27 00:00:00
abstract::The tumor microenvironment restrains conventional T cell (Tconv) activation while facilitating the expansion of Tregs. Here we showed that Tregs' advantage in the tumor milieu relies on supplemental energetic routes involving lipid metabolism. In murine models, tumor-infiltrating Tregs displayed intracellular lipid 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.1720113115
更新日期:2018-07-10 00:00:00
abstract::Macrophage migration inhibition factor (MIF) is one of a class of lymphocyte-derived mediator substances (lymphokines) which plays a role in the mechanism of cellular immunity. A variety of other soluble factors produced by non-lymphoid cells have been shown to have effects on macrophage mobility similar to that of MI...
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.72.4.1641
更新日期:1975-04-01 00:00:00
abstract::According to the Dobzhansky-Muller model, hybrid sterility is a consequence of the independent evolution of related taxa resulting in incompatible genomic interactions of their hybrids. The model implies that the incompatibilities evolve randomly, unless a particular gene or nongenic sequence diverges much faster than...
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.1219126110
更新日期:2013-02-05 00:00:00
abstract::The type 6 secretion system (T6SS) is a nanomachine used by many Gram-negative bacteria, including Vibrio cholerae, to deliver toxic effector proteins into adjacent eukaryotic and bacterial cells. Because the activity of the T6SS is dependent on direct contact between cells, its activity is limited to bacteria growing...
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.1808469115
更新日期:2018-07-31 00:00:00
abstract::The polycystic kidney diseases (PKDs) are a group of disorders characterized by the growth of epithelial cysts from the nephrons and collecting ducts of kidney tubules. The diseases can be inherited or can be provoked by environmental factors. To investigate the molecular basis of the abnormal cell growth associated 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.84.23.8394
更新日期:1987-12-01 00:00:00
abstract::Controlling topological defects in 3D liquid crystal phases is a crucial element in the development of novel devices, from blue-phase displays to passive biochemical sensors. However, it remains challenging to realize the 3D topological conditions necessary to robustly and arbitrarily direct the formation of defects. ...
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.1214708109
更新日期:2013-01-02 00:00:00
abstract::The effects of UV irradiation on the incorporation of [3H]uridine in HeLa (human) cell mRNA, rRNA, heterogeneous nuclear RNA (hnRNA) and early mRNA from adenovirus type 2 have been compared. The UV target size of cell mRNA is at least 3 times larger than the average size of the mRNA itself and larger than the adenovir...
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.74.10.4520
更新日期:1977-10-01 00:00:00
abstract::We have examined the effect of diphtheria toxin, Pseudomonas aeruginosa exotoxin A, and cycloheximide on the CV-1 cell cytoskeleton. Within a few hours after producing an inhibition of cellular protein synthesis, all these agents specifically disrupted the organization of the vimentin filament system with no discernab...
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.77.12.7267
更新日期:1980-12-01 00:00:00
abstract::Efficient and reliable classification of visual stimuli requires that their representations reside a low-dimensional and, therefore, computationally manageable feature space. We investigated the ability of the human visual system to derive such representations from the sensory input-a highly nontrivial task, given 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.93.21.12046
更新日期:1996-10-15 00:00:00
abstract::For the design of potent subunit vaccines, it is of paramount importance to identify all antigens immunologically recognized by a patient population infected with a pathogen. We have developed a rapid and efficient procedure to identify such commonly recognized antigens, and here we provide a comprehensive in vivo ant...
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.092569199
更新日期:2002-05-14 00:00:00
abstract::We have shown that 3-nitropropionate, an isoelectronic analogue of succinate, is a suicide inactivator of succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1] as follows. (i) When rat liver mitochondria oxidize succinate in the presence of 3-nitropropionate carbanion, the rate of O(2) consumption...
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.74.9.3767
更新日期:1977-09-01 00:00:00
abstract::The trinucleotide CCA sequence is present at the 3' terminus of all mature tRNAs. Despite this high degree of conservation, we have been able to prepare in vitro transcripts of Escherichia coli tRNA(Val) with altered 3' termini that are readily aminoacylated and can function in polypeptide synthesis. Replacement of th...
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.91.22.10389
更新日期:1994-10-25 00:00:00
abstract::Biological soil crusts (biocrusts)—communities of mosses, lichens, cyanobacteria, and heterotrophs living at the soil surface—are fundamental components of drylands worldwide, and destruction of biocrusts dramatically alters biogeochemical processes, hydrology, surface energy balance, and vegetation cover. Although th...
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.1509150112
更新日期:2015-09-29 00:00:00
abstract::Many cancers have substantial genomic heterogeneity within a given tumor, and to fully understand that diversity requires the ability to perform single cell analysis. We performed targeted sequencing of a panel of single nucleotide variants (SNVs), deletions, and IgH sequences in 1,479 single tumor cells from six acut...
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.1420822111
更新日期:2014-12-16 00:00:00
abstract::Chemokines and their receptors are key factors in the onset and progression of AIDS. Among them, accumulating evidence strongly indicates the involvement of IL-8 and its receptors, CXCR1 and CXCR2, in AIDS-related conditions. Through extensive investigation of genetic variations of the human CXCR1-CXCR2 locus, we iden...
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.0611670104
更新日期:2007-02-27 00:00:00
abstract::An electrophoretic karyotype of Aspergillus nidulans has been obtained using contour-clamped homogeneous electric field gel electrophoresis. Six chromosomal bands were separated, with two of the bands migrating as doublets. Using the Schizosaccharomyces pombe and Saccharomyces cerevisiae chromosomes as size standards,...
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.86.16.6260
更新日期:1989-08-01 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
pub_type: 杂志文章
doi:10.1073/pnas.2016775117
更新日期:2020-12-15 00:00:00
abstract::Insertion of trocars, needles, and catheters into unintended tissues or tissue compartments results in hundreds of thousands of complications annually. Current methods for blood vessel cannulation or epidural, chest tube, and initial trocar placement often involve the blind pass of a needle through several layers of 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.0808274106
更新日期:2009-04-07 00:00:00
abstract::Maternal deletion of the NESP55 differentially methylated region (DMR) (delNESP55/ASdel3-4(m), delNAS(m)) from the GNAS locus in humans causes autosomal dominant pseudohypoparathyroidism type Ib (AD-PHP-Ib(delNASm)), a disorder of proximal tubular parathyroid hormone (PTH) resistance associated with loss of maternal G...
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.1117608109
更新日期:2012-04-24 00:00:00
abstract::We have used wild-type and variants of the T-lymphoma cell line S49 to explore internalization and down-regulation of adenylate cyclase-linked beta-adrenergic receptors. Internalization was defined by the loss in "surface receptors" detected at 4 degrees C on intact cells by the antagonists [3H]CGP-12177 or [125I]iodo...
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.82.1.129
更新日期:1985-01-01 00:00:00
abstract::If RNA editing could be rationally directed to mutated RNA sequences, genetic diseases caused by certain base substitutions could be treated. Here we use a synthetic complementary RNA oligonucleotide to direct the correction of a premature stop codon mutation in dystrophin RNA. The complementary RNA oligonucleotide wa...
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.92.18.8298
更新日期:1995-08-29 00:00:00
abstract::The callipyge mutation (CLPG) is an A to G transition that affects a muscle-specific long-range control element located in the middle of the 90-kb DLK1-GTL2 intergenic (IG) region. It causes ectopic expression of a 327-kb cluster of imprinted genes in skeletal muscle, resulting in the callipyge muscular hypertrophy 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.0602844103
更新日期:2006-05-23 00:00:00
abstract::Magnetic interactions between dissolved oxygen and nitroxide radical spin probes lead to broadening of the ESR lines. We have used a closed-chamber method based on this property to determine the maximum rate of O2 uptake per cell (Vmax per cell) in cultured mammalian cells. A suitable spin probe and a cell suspension ...
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.79.4.1166
更新日期:1982-02-01 00:00:00
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
更新日期:1995-03-14 00:00:00
abstract::The bryostatins are macrocyclic lactones, extracted from the marine bryozoan Bugula neritina, and have been reported to be potent antineoplastic agents. Results described here demonstrate that the bryostatins may also be useful as stimulators of normal human hematopoietic cells since they can (i) directly stimulate bo...
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.84.23.8483
更新日期:1987-12-01 00:00:00
abstract::We have analyzed the spectra of UV-induced mutations in the lacI gene of a wild-type and an mfd strain of Escherichia coli. mfd strains have been recently proposed to be deficient in a factor coupling DNA repair and transcription. Analysis of UV-induced mutations occurring at adjacent pyrimidines showed that mutations...
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.89.22.11036
更新日期:1992-11-15 00:00:00
abstract::The UV photodissociation kinetics of tryptophan amino acid, Trp, attached to the membrane of bacteria, Escherichia coli and Bacillus subtilis, have been studied by means of normal and synchronous fluorescence. Our experimental data suggest that the fluorescence intensity of Trp increases during the first minute of irr...
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.1909722116
更新日期:2019-09-17 00:00:00
abstract::We study the electrophoretic transport of single-stranded RNA molecules through 1.5-nm-wide pores of carbon nanotube membranes by molecular dynamics simulations. From approximately 170 individual RNA translocation events analyzed at full atomic resolution of solvent, membrane, and RNA, we identify key factors in membr...
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.0402699101
更新日期:2004-08-17 00:00:00
abstract::The structural analysis of the Fab' fragment of human myeloma immunoglobulin IgGl(lambda) New has been extended to a nominal resolution of 2.0 A. Each of the structural subunits corresponding to the variable and to the constant homology regions of the light and heavy chains contains two irregular beta-sheets which are...
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.71.9.3440
更新日期:1974-09-01 00:00:00