Abstract:
:We have recently shown that the Alzheimer disease 40-residue amyloid beta-protein [A beta P-(1-40)] can form cation-selective channels when incorporated into planar lipid bilayers by fusion of liposomes containing the peptide. Since A beta P-(1-40) comprises portions of the putative extracellular and membrane-spanning domains of the amyloid precursor protein (APP751), we suggested that the channel-forming property could be the underlying cause of amyloid neurotoxicity. The peptide has been proposed to occur in vivo in both membrane-bound and soluble forms, and we now report that soluble A beta P-(1-40) can also form similar channels in solvent-free lipid bilayers formed at the tip of a patch pipet, as well as in the planar lipid bilayer system. As in the case of liposome-mediated incorporation, the amyloid channel activity in the patch pipet exhibits multiple conductance levels between 40 and 400 pS, cation selectivity, and sensitivity to tromethamine (Tris). Further studies with A beta P channels incorporated into planar lipid bilayers from the liposome complex have also revealed that the channel activity can express spontaneous transitions to a much higher range of conductances between 400 and 4000 pS. Under these conditions, the amyloid channel continues to be cation selective. Amyloid channels were insensitive to nitrendipine at either conductance range. We calculate that if such channels were expressed in cells, the ensuing ion fluxes down their electrochemical potential gradients would be homeostatically dissipative. We therefore interpret these data as providing further support for the concept that cell death in Alzheimer disease may be due to amyloid ion-channel activity.
journal_name
Proc Natl Acad Sci U S Aauthors
Arispe N,Pollard HB,Rojas Edoi
10.1073/pnas.90.22.10573subject
Has Abstractpub_date
1993-11-15 00:00:00pages
10573-7issue
22eissn
0027-8424issn
1091-6490journal_volume
90pub_type
杂志文章abstract::Origins of DNA replication in Schizosaccharomyces pombe lack a specific consensus sequence analogous to the Saccharomyces cerevisiae autonomously replicating sequence (ARS) consensus, raising the question of how they are recognized by the replication machinery. Because all well characterized S. pombe origins are locat...
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.0408811102
更新日期:2005-01-11 00:00:00
abstract::Heymann nephritis is an experimental autoimmune disease model for human membranous nephropathy. We have recently identified a pathogenic epitope, clone 14 (C14), responsible for formation and deposition of glomerular immune complexes that is contained within the small subunit of the Heymann nephritis antigenic complex...
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.89.23.11179
更新日期:1992-12-01 00:00:00
abstract::Intermolecular energy transfer between appropriately chosen pairs of dyes can be used to induce or enhance banding patterns in human metaphase chromosomes. Energy transfer, calibrated by fluorometric studies on soluble dye.DNA complexes, can also be detected by photometric measurements on cytological preparations of m...
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.75.11.5650
更新日期:1978-11-01 00:00:00
abstract::We have isolated a segment of DNA from the eukaryote Saccharomyces cerevisiae (baker's yeast) as a viable molecular hybrid of bacteriophage lambda DNA which, when integrated into the chromosome of an E. coli histidine auxotroph, allows this bacterium to grow in the absence of histidine. The nonrevertable, histidine au...
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.73.5.1471
更新日期:1976-05-01 00:00:00
abstract::Plants require metals for essential functions ranging from respiration to photosynthesis. These metals also contribute to the nutritional value of plants for both humans and livestock. Additionally, plants have the ability to accumulate nonessential metals such as cadmium and lead, and this ability could be harnessed ...
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.210214197
更新日期:2000-10-24 00:00:00
abstract::Structural protein 4.1, which has crucial interactions within the spectrin-actin lattice of the human red cell membrane skeleton, also is widely distributed at diverse intracellular sites in nucleated cells. We previously showed that 4.1 is essential for assembly of functional nuclei in vitro and that the capacity of ...
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.1934680100
更新日期:2003-09-16 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::Time-resolved optical measurements encompassing the femtoseconds to seconds time scales have been used to investigate Rhodobacter capsulatus reaction centers (RCs) in which the histidine residue at position 200 on the M polypeptide has been changed to a leucine by site-directed mutagenesis. The HisM200----Leu RC, whic...
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.85.20.7562
更新日期:1988-10-01 00:00:00
abstract::The protein encoded by the neu protooncogene (human gene symbol NGL for neuro/glioblastoma-derived) is a member of the surface receptor/tyrosine kinase family. Though its structure suggests that it can transduce a transmembrane signal, neither its extracellular ligand nor its critical intracellular substrates are know...
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.85.21.8057
更新日期:1988-11-01 00:00:00
abstract::The ultrastructure of the crystalline ferric mineral that forms the central core of ferritin macro-molecules has been examined by means of ultrahigh resolution electron microscopy at 100 kV. Very high magnification dark-field images reveal the presence of either a single large crystal or several smaller crystallites 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.70.12.3847
更新日期:1973-12-01 00:00:00
abstract::The origin recognition complex (ORC) binds sites from which DNA replication is initiated. We address ORC binding selectivity in vivo by mapping ∼52,000 ORC2 binding sites throughout the human genome. The ORC binding profile is broader than those of sequence-specific transcription factors, suggesting that ORC is not 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.1609060113
更新日期:2016-08-16 00:00:00
abstract::Larval fishes suffer prodigious mortality rates, eliminating 99% of the brood within a few days after first feeding. Hjort (1914) famously attributed this "critical period" of low survival to the larvae's inability to obtain sufficient food [Hjort (1914) Rapp P-v Réun Cons Int Explor Mer 20:1-228]. However, the cause ...
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.1323205111
更新日期:2014-06-03 00:00:00
abstract::DNA triple helices offer new perspectives toward oligonucleotide-directed gene regulation. However, the poor stability of some of these structures might limit their use under physiological conditions. Specific ligands can intercalate into DNA triple helices and stabilize them. Molecular modeling and thermal denaturati...
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.95.7.3591
更新日期:1998-03-31 00:00:00
abstract::Calcium oscillations suppress mitochondrial movements along the microtubules to support on-demand distribution of mitochondria. To activate this mechanism, Ca(2+) targets a yet unidentified cytoplasmic factor that does not seem to be a microtubular motor or a kinase/phosphatase. Here, we have studied the dependence of...
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.0808953105
更新日期:2008-12-30 00:00:00
abstract::DNA polymerases from Xenopus laevis oocytes, unfertilized eggs, and kidney cells grown in culture have been characterized. The same three major DNA polymerase activities are present in all cell types examined. We attempt to relate the characteristics of amphibian enzymes to those of mammalian polymerases. ...
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.71.9.3706
更新日期:1974-09-01 00:00:00
abstract::The switch from membrane-bound to secreted IgM is accomplished by producing alternative forms of mRNA from a single mu heavy-chain gene. This process might be controlled at any of three steps--transcription termination, RNA splicing, or RNA cleavage/poly(A) addition. To distinguish between these possibilities, we have...
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.82.24.8658
更新日期:1985-12-01 00:00:00
abstract::The dnaZX gene of Escherichia coli directs the synthesis of two proteins, DnaZ and DnaX. These products are confirmed as the gamma and tau subunits of DNA polymerase III because antibody to a synthetic peptide present in both the DnaZ and DnaX proteins reacts also with the gamma and tau subunits of holoenzyme. To char...
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.84.9.2713
更新日期:1987-05-01 00:00:00
abstract::The lack of genetic means has been a serious limitation in studying mosquito immunity. We generated Relish-mediated immune deficiency (RMID) by transforming Aedes aegypti with the Delta Rel transgene driven by the vitellogenin (Vg) promoter using the pBac[3xP3-EGFP, afm] vector. A stable transformed line had a single ...
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.0537347100
更新日期:2003-03-04 00:00:00
abstract::Neural crest stem cells can be isolated from differentiated cultures of human pluripotent stem cells, but the process is inefficient and requires cell sorting to obtain a highly enriched population. No specific method for directed differentiation of human pluripotent cells toward neural crest stem cells has yet been 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.1113746108
更新日期:2011-11-29 00:00:00
abstract::Rapid development of genetic variability may contribute to the pathogenicity of lentiviruses as it may allow escape from immune surveillance and/or from suppression of virus replication. Although apathogenic in African green monkeys, simian immunodeficiency virus isolated from African green monkeys is shown to display...
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.88.18.8126
更新日期:1991-09-15 00:00:00
abstract::We have studied hepatic uptake of chylomicron retinyl ester. Chylomicrons were obtained from intestinal lymph of rats that were given retinol in groundnut oil by intraduodenal injection. When lymph was injected intravenously into normal rats, the radioactivity was cleared from blood with t1/2 approximately equal to 10...
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.79.23.7326
更新日期:1982-12-01 00:00:00
abstract::Steep topography, a tropical climate, and mafic lithologies contribute to efficient chemical weathering and carbon sequestration in the Southeast Asian islands. Ongoing arc-continent collision between the Sunda-Banda arc system and Australia has increased the area of subaerially exposed land in the region since the 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.2011033117
更新日期:2020-10-13 00:00:00
abstract::Mismatch repair contributes to genetic stability, and inactivation of the mammalian pathway leads to tumor development. Mismatch correction occurs by an excision-repair mechanism and has been shown to depend on the 5' to 3' hydrolytic activity exonuclease 1 (Exo1) in eukaryotic cells. However, genetic and biochemical ...
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.0903654106
更新日期:2009-05-26 00:00:00
abstract::We report the isolation and functional characterization of cDNAs encoding a Drosophila kainate-selective glutamate receptor. The deduced mature 964-residue protein (DGluR-I) is 108,482 Da and exhibits significant homology to mammalian glutamate receptor subunits. Injection of DGluR-I cRNA into Xenopus oocytes generate...
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.89.21.10484
更新日期:1992-11-01 00:00:00
abstract::A descriptive medium for the presentation of protein structure has been developed and used to evaluate the structure of the active site of bovine trypsin (EC 3.4.21.4). This technique, involving advanced computer graphics technology, permits the facile display of a representation of the molecular surface of proteins 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.75.11.5409
更新日期:1978-11-01 00:00:00
abstract::Previous studies have identified human breast tumor particles possessing many of the features characteristic of RNA tumor viruses. In addition to the expected size (600 S) and density (1.16 g/ml) these include possession of an outer membrane and an inner one surrounding a "core" containing a DNA polymerase and a large...
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.74.2.764
更新日期:1977-02-01 00:00:00
abstract::Based on the DNA sequence of the symbiotic plasmid of Rhizobium strain NGR234, we predicted potential rearrangements generated by homologous recombination. All predicted rearrangements were identified experimentally by using a PCR-based methodology. Thus, the predicted and the actual dynamic maps of the replicon coinc...
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.97.16.9138
更新日期:2000-08-01 00:00:00
abstract::In a subclone derived from mouse L(tk-) cells, we found a plasmid present in a high copy number (greater than 5000 copies per cell) that was stably maintained extrachromosomally without any cytopathic effect to the host cells. This plasmid, termed L factor, has two forms: 5.3 and 5.5 kilobase pairs. DNA sequencing and...
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.84.7.1789
更新日期:1987-04-01 00:00:00
abstract::The formation of social attachments is a critical component of human relationships. Infants begin to bond to their caregivers from the moment of birth, and these social bonds continue to provide regulatory emotional functions throughout adulthood. It is difficult to examine the interactions between social experience 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.0504767102
更新日期:2005-11-22 00:00:00
abstract::The activation of plant defensive genes in leaves of tomato plants in response to herbivore damage or mechanical wounding is mediated by a mobile 18-amino acid polypeptide signal called systemin. Systemin is derived from a larger, 200-amino acid precursor called prosystemin, similar to polypeptide hormones and soluble...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.93.22.12053
更新日期:1996-10-29 00:00:00