Abstract:
:Inheritance of specific apolipoprotein E (apoE) alleles determines, in large part, the risk and mean age of onset of late-onset familial and sporadic Alzheimer disease. The mechanism by which the apoE isoforms differentially contribute to disease expression is, however, unknown. Isoform-specific differences have been identified in the binding of apoE to the microtubule-associated protein tau, which forms the paired helical filament and neurofibrillary tangles, and to amyloid beta peptide, a major component of the neuritic plaque. These and other isoform-specific interactions of apoE give rise to testable hypotheses for the mechanism(s) of pathogenesis of Alzheimer disease. An unresolved issue of increasing importance is the relationship between the structural pathological lesions and the cellular pathogenesis responsible for the clinical disease phenotype, progressive dementia. The identification of apoE in the cytoplasm of human neurons and the characterization of isoform-specific binding of apoE to the microtubule-associated proteins tau and MAP-2 present the possibility that apoE may affect microtubule function in the Alzheimer brain.
journal_name
Proc Natl Acad Sci U S Aauthors
Strittmatter WJ,Roses ADdoi
10.1073/pnas.92.11.4725subject
Has Abstractpub_date
1995-05-23 00:00:00pages
4725-7issue
11eissn
0027-8424issn
1091-6490journal_volume
92pub_type
杂志文章,评审abstract::Cartilage collagen fibrils, which are characterized by their thin, uniform diameters, are formed of a multicomponent system of three collagen types (II, IX, and XI) and interacting proteoglycans. We have used a genetic approach to test whether the proper assembly of this multiprotein structure was altered by overexpre...
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.90.9.3825
更新日期:1993-05-01 00:00:00
abstract::Seasonal changes of daylength (photoperiod) affect the expression of hormonal and behavioral circadian rhythms in a variety of organisms. In mammals, such effects might reflect photoperiodic changes in the circadian pace-making system [located in the suprachiasmatic nucleus (SCN) of the hypothalamus] that governs thes...
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.92.17.7754
更新日期:1995-08-15 00:00:00
abstract::Recombinant human erythropoietin (rHuEpo) has been used successfully in the treatment of cancer-related anemia. Clinical observations with several patients with multiple-myeloma treated with rHuEpo has shown, in addition to the improved quality of life, a longer survival than expected, considering the poor prognostic ...
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.081275298
更新日期:2001-04-24 00:00:00
abstract::Metallo-β-lactamases (MBLs) hydrolyze almost all β-lactam antibiotics and are unaffected by clinically available β-lactamase inhibitors (βLIs). Active-site architecture divides MBLs into three classes (B1, B2, and B3), complicating development of βLIs effective against all enzymes. Bisthiazolidines (BTZs) are carboxyl...
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.1601368113
更新日期:2016-06-28 00:00:00
abstract::Although it is well described in model membranes, little is known about phase separation in biological membranes. Here, we provide evidence for a coexistence of at least two different lipid bilayer phases in the apical plasma membrane of epithelial cells. Phase connectivity was assessed by measuring long-range diffusi...
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.0509885103
更新日期:2006-01-10 00:00:00
abstract::Tumor-specific molecules are needed across diverse areas of oncology for use in early detection, diagnosis, prognosis and therapy. Large and growing public databases of transcriptome sequencing data (RNA-seq) derived from tumors and normal tissues hold the potential of yielding tumor-specific molecules, but because 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.1508057112
更新日期:2015-06-09 00:00:00
abstract::Molecular targeting of the two receptor interaction domains of the epigenetic repressor silencing mediator of retinoid and thyroid hormone receptors (SMRT(mRID)) produced a transplantable skeletal syndrome that reduced radial bone growth, increased numbers of bone-resorbing periosteal osteoclasts, and increased bone 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.1318974110
更新日期:2013-11-19 00:00:00
abstract::Although aquaporin 5 (AQP5) is the major water channel expressed in alveolar type I cells in the lung, its actual role in the lung is a matter of considerable speculation. By using immunohistochemical staining, we show that AQP5 expression in mouse lung is not restricted to type I cells, but is also detected in alveol...
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.231273398
更新日期:2001-11-20 00:00:00
abstract::Although aminoacyl-tRNA synthetases (ARSs) are essential for protein synthesis, they also function as regulators and signaling molecules in diverse biological processes. Here, we screened 11 different human ARSs to identify the enzyme that is secreted as a signaling molecule. Among them, we found that lysyl-tRNA synth...
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.0500226102
更新日期:2005-05-03 00:00:00
abstract::Axonal guidance is key to the formation of neuronal circuitry. Semaphorin 3A (Sema 3A; previously known as semaphorin III, semaphorin D, and collapsin-1), a secreted subtype of the semaphorin family, is an important axonal guidance molecule in vitro and in vivo. The molecular mechanisms of the repellent activity of se...
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.96.23.13501
更新日期:1999-11-09 00:00:00
abstract::A cDNA of the human terminal deoxynucleotidyltransferase (TdT; "terminal transferase," EC 2.7.7.31) was isolated from a human lymphoblastoid cell cDNA library in lambda gt 11 by using immunological procedures. Four inserts containing 723 to 939 base pairs were recloned in pBR322 for hybridization and preliminary 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.81.14.4363
更新日期:1984-07-01 00:00:00
abstract::The SKW-3 cell line, which was established from the malignant cells of a patient with T-cell chronic lymphocytic leukemia, is characterized by a translocation involving chromosome 8 (band q24) and chromosome 14 (band q11) [t(8;14)(q24;q11)]. To determine the position of the gene encoding the alpha chain of the T-cell ...
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.83.10.3439
更新日期:1986-05-01 00:00:00
abstract::By using clones of murine T cells reactive with alloantigens as well as soluble antigens, it has been possible to demonstrate that Ia antigens, Ir gene phenomena (defined as the ability of immune T cells to recognize antigen), and mixed lymphocyte reaction (MLR)-stimulating determinants encoded within the I-A subregio...
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.78.3.1853
更新日期:1981-03-01 00:00:00
abstract::Photolyzed rhodopsin catalyzes the exchange of GTP for FDP bound to a protein in retinal rod outer segments. We previously proposed that the GTP complex of this protein regulates the cyclic GMP phosphodiesterase and that it may be the first amplified intermediate in visual excitation [Fung, B. K.-K. & Stryer, L. (1980...
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.78.1.152
更新日期:1981-01-01 00:00:00
abstract::Changes in the amount, intensity, and timing of precipitation are increasing hydrologic variability in many regions, but we have little understanding of how these changes are affecting freshwater species. Stream-breeding amphibians-a diverse group in North America-may be particularly sensitive to hydrologic variabilit...
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.1908057116
更新日期:2019-09-24 00:00:00
abstract::To assess the effect of transforming growth factor beta 1 on the skin in vivo, we have targeted its expression to the epidermis of transgenic mice. To ensure that active TGF-beta 1 was expressed, we used a porcine TGF-beta 1 cDNA with mutations of Cys-223-->Ser and Cys-225-->Ser, which allow constitutive activation. 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.90.11.5237
更新日期:1993-06-01 00:00:00
abstract::Scientific and engineering innovation is vital for American competitiveness, quality of life, and national security. However, too few American students, especially women, pursue these fields. Although this problem has attracted enormous attention, rigorously tested interventions outside artificial laboratory settings ...
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.1613117114
更新日期:2017-06-06 00:00:00
abstract::A glnB gene is identified in the cyanobacterium Synechococcus sp. PCC 7942, and its gene product is found to be covalently modified as a result of imbalance in electron transfer in photosynthesis, where photosystem II is favored over photosystem I. The gene was cloned and sequenced and found to encode a polypeptide 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.88.11.4565
更新日期:1991-06-01 00:00:00
abstract::Let X = Omega/Gamma be a compact quotient of an irreducible bounded symmetric domain Omega of rank >/=2 by a discrete group omega of automorphisms without fixed points. It is well known that the Kähler-Einstein metric g on X carries seminegative curvature (in the sense of Griffiths). I show that any Hermitian metric h...
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.83.8.2288
更新日期:1986-04-01 00:00:00
abstract::The x-ray crystal structure of the tetrameric T-antigen-binding lectin from peanut, M(r) 110,000, has been determined by using the multiple isomorphous replacement method and refined to an R value of 0.218 for 22,155 reflections within the 10- to 2.95-A resolution range. Each subunit has essentially the same character...
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.91.1.227
更新日期:1994-01-04 00:00:00
abstract::In vitro and in vivo triplet state electron paramagnetic resonance (epr) spectra of bacteriochlorophylls (Bchls) show important differences in (a) electron spin polarization (esp), and (b) zero field splitting (ZFS) parameters. The unusual esp and ZFS properties of the observed in vivo triplet state are best interpret...
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.72.9.3270
更新日期:1975-09-01 00:00:00
abstract::The recent emergence and reemergence of viruses in the human population has highlighted the need to develop broader panels of therapeutic molecules. High-throughput screening assays opening access to untargeted steps of the viral replication cycle will provide powerful leverage to identify innovative antiviral molecul...
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.2010524118
更新日期:2021-01-12 00:00:00
abstract::Fungi must recognize plant-specific signals to initiate subsequent morphogenetic events such as filamentation that lead to infection. Here we show that the plant hormone indoleacetic acid (IAA) induces adhesion and filamentation of Saccharomyces cerevisiae. Genome expression profiling of cells treated with IAA identif...
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.0400659101
更新日期:2004-03-23 00:00:00
abstract::A single-nucleotide polymorphism in the human arylamine N-acetyltransferase 2 (Nat2) gene has recently been identified as associated with insulin resistance in humans. To understand the cellular and molecular mechanisms by which alterations in Nat2 activity might cause insulin resistance, we examined murine ortholog N...
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.1716990115
更新日期:2017-12-26 00:00:00
abstract::The modern concept of neurogenesis in the adult brain is predicated on the premise that multipotent glial cells give rise to new neurons throughout life. Although extensive evidence exists indicating that this is the case, the transition from glial to neuronal phenotype remains poorly understood. A unique monolayer ce...
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.0503965102
更新日期:2005-06-28 00:00:00
abstract::The global configuration of individual, surface-adsorbed molecules of the giant muscle protein titin, labeled with rhodamine conjugates, was followed with confocal microscopy. Fluorescence-emission intensity was reduced because of self-quenching caused by the close spacing between rhodamine dye molecules that formed d...
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.191494098
更新日期:2001-12-04 00:00:00
abstract::Specific antibodies against types I and III collagens and procollagens were used to localize these proteins in cultured human cells. These studies indicate that the same cell makes both proteins. No type III procollagen synthesis was observed in cells from two patients with two patients with the Ehlers-Danlos type IV ...
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.73.11.4037
更新日期:1976-11-01 00:00:00
abstract::We have shown that rat glioma tumors contain a protein that crossreacts with antibody against mouse 2.5S nerve growth factor prepared in rabbit in microcomplement fixation assays and has analogous isoelectric points to all the hybrids of 2.5S nerve growth factor (a dimer). Partially purified protein preparations from ...
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.71.6.2347
更新日期:1974-06-01 00:00:00
abstract::In a search for a model cell system that might allow studies of the function of the Rho-related GTPase CDC42Hs in human cells, we measured the content and distribution of CDC42Hs in monocytes that were differentiating into macrophages. The total content of this protein increased 5- to 6-fold in phorbol ester-treated h...
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.91.10.4263
更新日期:1994-05-10 00:00:00
abstract::Herpesviruses must traverse the nuclear envelope to gain access to the cytoplasm and, ultimately, to exit cells. It is believed that herpesvirus nucleocapsids enter the perinuclear space by budding through the inner nuclear membrane (NM). To reach the cytoplasm these enveloped particles must fuse with the outer NM 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.0703790104
更新日期:2007-06-12 00:00:00