Abstract:
:Factors that elevate amyloid-beta (Abeta) peptide levels are associated with an increased risk for Alzheimer's disease. Insulysin has been identified as one of several proteases potentially involved in Abeta degradation based on its hydrolysis of Abeta peptides in vitro. In this study, in vivo levels of brain Abeta40 and Abeta42 peptides were found to be increased significantly (1.6- and 1.4-fold, respectively) in an insulysin-deficient gene-trap mouse model. A 6-fold increase in the level of the gamma-secretase-generated C-terminal fragment of the Abeta precursor protein in the insulysin-deficient mouse also was found. In mice heterozygous for the insulysin gene trap, in which insulysin activity levels were decreased approximately 50%, brain Abeta peptides were increased to levels intermediate between those in wild-type mice and homozygous insulysin gene-trap mice that had no detectable insulysin activity. These findings indicate that there is an inverse correlation between in vivo insulysin activity levels and brain Abeta peptide levels and suggest that modulation of insulysin activity may alter the risk for Alzheimer's disease.
journal_name
Proc Natl Acad Sci U S Aauthors
Miller BC,Eckman EA,Sambamurti K,Dobbs N,Chow KM,Eckman CB,Hersh LB,Thiele DLdoi
10.1073/pnas.1031520100keywords:
subject
Has Abstractpub_date
2003-05-13 00:00:00pages
6221-6issue
10eissn
0027-8424issn
1091-6490pii
1031520100journal_volume
100pub_type
杂志文章abstract::Despite immense variability across languages, people can learn to understand any human language, spoken or signed. What neural mechanisms allow people to comprehend language across sensory modalities? When people listen to speech, electrophysiological oscillations in auditory cortex entrain to slow ([Formula: see text...
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.1620350114
更新日期:2017-06-13 00:00:00
abstract::The anticancer peptide PNC-27, which contains an HDM-2-binding domain corresponding to residues 12-26 of p53 and a transmembrane-penetrating domain, has been found to kill cancer cells (but not normal cells) by inducing membranolysis. We find that our previously determined 3D structure of the p53 residues of PNC-27 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.0909364107
更新日期:2010-02-02 00:00:00
abstract::Monoclonal antibodies have been obtained that recognize either the A or B chain of human urinary urokinase. These antibodies identify human urokinase-producing cells and the product of urokinase mRNA. Anti-urokinase monoclonal antibodies precipitate an approximately equal to 54,000-dalton protein synthesized in vitro ...
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.81.1.110
更新日期:1984-01-01 00:00:00
abstract::Drug resistance testing has been shown to be beneficial for clinical management of HIV type 1 infected patients. Whereas phenotypic assays directly measure drug resistance, the commonly used genotypic assays provide only indirect evidence of drug resistance, the major challenge being the interpretation of the sequence...
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.112177799
更新日期:2002-06-11 00:00:00
abstract::Cellular and molecular signals involved in axon elongation versus collateral and arbor formation may be intrinsic to developing neurons, or they may derive from targets. To identify signals regulating axon growth modes, we have developed a culture system in which trigeminal ganglion cells are challenged by various tar...
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.90.15.7235
更新日期:1993-08-01 00:00:00
abstract::Galanin is a neuropeptide with a wide variety of biological functions, including that of a strong endogenous anticonvulsant. No nonpeptide ligands, capable of activating galanin receptors, are available today. Based on known pharmacophores of galanin, a combinatorial library was designed, synthesized, and screened at ...
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.102163499
更新日期:2002-05-14 00:00:00
abstract::HLA-I molecules play a central role in antigen presentation. They typically bind 9- to 12-mer peptides, and their canonical binding mode involves anchor residues at the second and last positions of their ligands. To investigate potential noncanonical binding modes, we collected in-depth and accurate HLA peptidomics da...
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.1717277115
更新日期:2018-05-15 00:00:00
abstract::The nucleoside triphosphates ATP, GTP, TTP, and CTP induce conformational changes in histone IV at concentrations that are of the same magnitude as the histone concentration. The purine nucleoside triphosphates are much more effective than the pyrimidine nucleoside triphosphates. ...
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.69.9.2687
更新日期:1972-09-01 00:00:00
abstract::Cloned DNA probes containing genes coding for the large subunit of ribulose-1,5-bisphosphate carboxylase (rbcA) of corn and of Chlamydomonas were used to identify, by heterologous hybridization, DNA fragments from Anabaena 7120 carrying the corresponding gene sequence. The same probes were used to isolate, from a reco...
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.80.7.1835
更新日期:1983-04-01 00:00:00
abstract::The importance of founder events in promoting evolutionary changes on islands has been a subject of long-running controversy. Resolution of this debate has been hindered by a lack of empirical evidence from naturally founded island populations. Here we undertake a genetic analysis of a series of historically documente...
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.102583399
更新日期:2002-06-11 00:00:00
abstract::The mechanical properties of engineering structures continuously weaken during service life because of material fatigue or degradation. By contrast, living organisms are able to strengthen their mechanical properties by regenerating parts of their structures. For example, plants strengthen their cell structures by tra...
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.2016524118
更新日期:2021-01-19 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::We demonstrate how a conventional confocal spinning-disk (CSD) microscope can be converted into a doubly resolving image scanning microscopy (ISM) system without changing any part of its optical or mechanical elements. Making use of the intrinsic properties of a CSD microscope, we illuminate stroboscopically, generati...
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.1315858110
更新日期:2013-12-24 00:00:00
abstract::Loss-of-function DJ-1 mutations can cause early-onset Parkinson's disease. The function of DJ-1 is unknown, but an acidic isoform accumulates after oxidative stress, leading to the suggestion that DJ-1 is protective under these conditions. We addressed whether this represents a posttranslational modification at cystei...
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.0402959101
更新日期:2004-06-15 00:00:00
abstract::Nitroxyl anion (HNONO(-)), the one-electron reduced form of nitric oxide (NO), induces positive cardiac inotropy and selective venodilation in the normal in vivo circulation. Here we tested whether HNO/NO(-) augments systolic and diastolic function of failing hearts, and whether contrary to NO/nitrates such modulation...
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.0937302100
更新日期:2003-04-29 00:00:00
abstract::Immediately after adsorption, phages T4 and T5 induce a partial depolarization of the host cytoplasmic membrane. Infected bacteria respond to this phage-induced effect by a repolarization that leads to a new steady state of reduced membrane potential. The rate and extent of repolarization are adjusted to the intensity...
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.78.1.215
更新日期:1981-01-01 00:00:00
abstract::Accurate protein folding is essential for proper cellular and organismal function. In the cell, protein folding is carefully regulated; changes in folding homeostasis (proteostasis) can disrupt many cellular processes and have been implicated in various neurodegenerative diseases and other pathologies. For many protei...
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.1610272113
更新日期:2016-11-22 00:00:00
abstract::This paper is a theoretical study of dynamic self assembly in a system of millimeter-sized magnetized disks floating at a liquid-air interface and spinning under the influence of a rotating magnetic field. Equations of motions are derived that account for the hydrodynamic and magnetic forces acting in the system. Nume...
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.062036699
更新日期:2002-04-02 00:00:00
abstract::The cytokines interleukin (IL) 4 and IL-13 induce many of the same biological responses, including class switching to IgE and induction of major histocompatibility complex class II antigens and CD23 on human B cells. It has recently been shown that IL-4 induces the tyrosine phosphorylation of a 170-kDa protein, a subs...
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.92.17.7681
更新日期:1995-08-15 00:00:00
abstract::Current theory indicates that mitochondria were obtained 1.5 billion years ago from an ancient prokaryote. The mitochondria provided the capacity for aerobic respiration, the creation of the eukaryotic cell, and eventually complex multicellular organisms. Recent reports have found that mitochondria play essential role...
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.0510511103
更新日期:2006-01-31 00:00:00
abstract::The restriction endonuclease, HindIII, gives rise to three fragments in each of the three mitochondrial DNAs isolated from the established mammalian cell lines LA9 (mouse), HeLa (human), and BSC-1 (African green monkey). The restriction endonuclease, EcoRI, gives rise to three fragments in mitochondrial DNA from HeLa ...
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.71.11.4617
更新日期:1974-11-01 00:00:00
abstract::Despite the proclamation of Lowenstam and Weiner that crustaceans are the "champions of mineral mobilization and deposition of the animal kingdom," relatively few proteins from the two main calcification sites in these animals, i.e., the exoskeleton and the transient calcium storage organs, have been identified, seque...
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.0800193105
更新日期:2008-05-20 00:00:00
abstract::We investigated the structural and functional alterations of active lamellae during initial cell-cell collision and establishment of cell-cell contacts in wounded cultures of nontransformed rat epitheliocytes (IAR-2 line) and their ras-transformed descendants (C4 line). Typically, the leading edges of nontransformed 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.94.3.879
更新日期:1997-02-04 00:00:00
abstract::Programmed cell death (apoptosis) is a normal physiological process, which could in principle be manipulated to play an important role in cancer therapy. The key importance of p53 expression in the apoptotic response to DNA-damaging agents has been stressed because mutant or deleted p53 is so common in most kinds of 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.92.17.7829
更新日期:1995-08-15 00:00:00
abstract::Stearoyl-acyl-carrier-protein-desaturase-mediated conversion of stearic acid (18:0) to oleic acid (18:1) is a key step, which regulates levels of unsaturated fatty acids in cells. We previously showed that stearoyl-acyl-carrier-protein-desaturase mutants ssi2/fab2 carrying a loss-of-function mutation in the plastidial...
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.0401315101
更新日期:2004-04-06 00:00:00
abstract::A full-length cDNA clone encoding a purified augmenter of liver regeneration (ALR) factor prepared from the cytosol of weanling rat livers was isolated. The 1.2-kb cDNA included a 299-bp 5' untranslated region, a 375-bp coding region, and a 550-bp 3' untranslated region. It encoded a protein consisting of 125 amino 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.91.17.8142
更新日期:1994-08-16 00:00:00
abstract::Larger brains have an increasingly folded cerebral cortex whose white matter scales up faster than the gray matter. Here we analyze the cellular composition of the subcortical white matter in 11 primate species, including humans, and one Scandentia, and show that the mass of the white matter scales linearly across spe...
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.1012590107
更新日期:2010-11-02 00:00:00
abstract::The catalytic power of enzymes containing coenzyme B12 has been, in some respects, the "last bastion" for the strain hypothesis. Our previous study of this system established by a careful sampling that the major part of the catalytic effect is due to the electrostatic interaction between the ribose of the ado group 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.1503828112
更新日期:2015-04-07 00:00:00
abstract::The covalent linkage of supramolecular monomers provides a powerful strategy for constructing dynamic polymeric materials whose properties can be readily tuned either by the selection of monomers or the choice of functional linkers. In this strategy, the stabilities of the supramolecular monomers and the reactions use...
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.1612898113
更新日期:2016-10-04 00:00:00
abstract::Stable structures of icosahedral symmetry can serve numerous functional roles, including chemical microencapsulation and delivery of drugs and biomolecules, epitope presentation to allow for an efficient immunization process, synthesis of nanoparticles of uniform size, observation of encapsulated reactive intermediate...
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.0709489104
更新日期:2007-12-26 00:00:00