Abstract:
:Canavan's disease (CD) is a fatal, hereditary disorder of CNS development that has been linked to mutations in the gene for the enzyme aspartoacylase (ASPA) (EC 3.5.1.15). ASPA acts to hydrolyze N-acetylaspartate (NAA) into l-aspartate and acetate, but the connection between ASPA deficiency and the failure of proper CNS development is unclear. We hypothesize that one function of ASPA is to provide acetate for the increased lipid synthesis that occurs during postnatal CNS myelination. The gene encoding ASPA has been inactivated in the mouse model of CD, and here we show significant decreases in the synthesis of six classes of myelin-associated lipids, as well as reduced acetate levels, in the brains of these mice at the time of peak postnatal CNS myelination. Analysis of the lipid content of white matter from a human CD patient showed decreased cerebroside and sulfatide relative to normal white matter. These results demonstrate that myelin lipid synthesis is significantly compromised in CD and provide direct evidence that defective myelin synthesis, resulting from a deficiency of NAA-derived acetate, is involved in the pathogenesis of CD.
journal_name
Proc Natl Acad Sci U S Aauthors
Madhavarao CN,Arun P,Moffett JR,Szucs S,Surendran S,Matalon R,Garbern J,Hristova D,Johnson A,Jiang W,Namboodiri MAdoi
10.1073/pnas.0409184102keywords:
subject
Has Abstractpub_date
2005-04-05 00:00:00pages
5221-6issue
14eissn
0027-8424issn
1091-6490pii
0409184102journal_volume
102pub_type
杂志文章abstract::The twin-arginine transport (Tat) system is a protein-targeting pathway of prokaryotes and chloroplasts. Most Escherichia coli Tat substrates are complex metalloenzymes that must be correctly folded and assembled before transport, and a preexport chaperone-mediated "proofreading" process is therefore in operation. 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.0500737102
更新日期:2005-06-14 00:00:00
abstract::Transforming growth factor betas (TGF-betas) regulate key aspects of embryonic development and major human diseases. Although Smad2, Smad3, and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinases (MAPKs) have been proposed as key mediators in TGF-beta signaling, their functional specificities...
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.1834070100
更新日期:2003-09-02 00:00:00
abstract::We have found that poly(L-lysine) can be a very effective agent in preventing the growth of Ehrlich ascites tumors in mice. When given optimal doses of poly(L-lysine) (Mr 60 x 10(3)) intraperitoneally for 5 consecutive days, beginning on day 1 after inoculation with Ehrlich ascites cells. White Swiss mice show nearly ...
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.76.7.3246
更新日期:1979-07-01 00:00:00
abstract::Overexpression of ErbB-2/Neu has been causally associated with mammary epithelial transformation. Here we report that blockade of the epidermal growth factor receptor (EGFR) kinase with AG-1478 markedly delays breast tumor formation in mouse mammary tumor virus (MMTV)/Neu + MMTV/transforming growth factor alpha bigeni...
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.160564197
更新日期:2000-08-15 00:00:00
abstract::Experiments were designed with the aim of understanding the mechanism whereby the lambda repressor inhibits messenger RNA synthesis. Complexes containing lambda DNA and RNA polymerase were isolated from repressed and derepressed lysogens and analyzed for the relative amounts of RNA polymerase per phage genome. The dat...
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.64.3.962
更新日期:1969-11-01 00:00:00
abstract::The opportunistic pathogen Candida albicans can undergo phenotypic switching between a benign, unicellular phenotype and an invasive, multicellular form that causes candidiasis. Increasingly, strains of Candida are becoming resistant to antifungal drugs, making the treatment of candidiasis difficult, especially in imm...
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.0906145106
更新日期:2009-11-17 00:00:00
abstract::Resonance Raman and optical absorption spectra of ligand-free (deoxy) myoglobin and CO-bound myoglobin (MbCO) at pH 2.6 have been measured by using continuous-flow/rapid-mixing techniques. The spectra of deoxy myoglobin at low pH within 6 ms of the pH drop demonstrate that the iron-histidine bond has been ruptured but...
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.87.1.205
更新日期:1990-01-01 00:00:00
abstract::We explore the question of what are the best ligands for macromolecular targets. A survey of experimental data on a large number of the strongest-binding ligands indicates that the free energy of binding increases with the number of nonhydrogen atoms with an initial slope of approximately -1.5 kcal/mol (1 cal = 4.18 J...
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.96.18.9997
更新日期:1999-08-31 00:00:00
abstract::The conformational change in amyloid beta (Abeta) peptide from its monomeric form to aggregates is crucial in the pathogenesis of Alzheimer's disease (AD). In the healthy brain, some unidentified chaperones appear to prevent the aggregation of Abeta. Here we reported that lipocalin-type prostaglandin D synthase (L-PGD...
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.0701585104
更新日期:2007-04-10 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::Zooxanthellae are unicellular algae that occur as endosymbionts in many hundreds of common marine invertebrates. The issue of zooxanthella diversity has been difficult to address. Most zooxanthellae have been placed in the dinoflagellate genus Symbiodinium as one or several species that are not easily distinguished. 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.89.8.3639
更新日期:1992-04-15 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 x-ray crystal structures of the sulfide oxidase antibody 28B4 and of antibody 28B4 complexed with hapten have been solved at 2.2-angstrom and 1.9-angstrom resolution, respectively. To our knowledge, these structures are the highest resolution catalytic antibody structures to date and provide insight into the molec...
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.93.11.5363
更新日期:1996-05-28 00:00:00
abstract::Animal rabies control has been frustrated by the existence of multiple wildlife reservoirs and the lack of efficacious oral vaccines. In this investigation, raccoons fed a vaccinia-rabies glycoprotein recombinant virus in a sponge bait developed rabies virus-neutralizing antibody (0.6-54.0 units) and resisted street 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.83.20.7947
更新日期:1986-10-01 00:00:00
abstract::Human cytomegalovirus (HCMV) strains that have been passaged in vitro rapidly acquire mutations that impact viral growth. These laboratory-adapted strains of HCMV generally exhibit restricted tropism, produce high levels of cell-free virus, and develop susceptibility to natural killer cells. To permit experimentation ...
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.1704809114
更新日期:2017-06-06 00:00:00
abstract::Signaling pathways regulating proliferation, differentiation, and apoptosis are commonly mediated through protein-protein interactions as well as reversible phosphorylation of proteins. To facilitate the study of regulated protein-protein interactions in cells and living animals, we optimized firefly luciferase 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.0404041101
更新日期:2004-08-17 00:00:00
abstract::A fluorescence resonance energy transfer assay has been developed for monitoring Bacillus anthracis lethal factor (LF) protease activity. A fluorogenic 16-mer peptide based on the known LF protease substrate MEK1 was synthesized and found to be cleaved by the enzyme at the anticipated site. Extension of this work to 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.062171599
更新日期:2002-05-14 00:00:00
abstract::Escherichia coli DnaK acts as a molecular chaperone through its ATP-regulated binding and release of polypeptide substrates. Overexpressing a C-terminal fragment (CTF) of DnaK (Gly-384 to Lys-638) containing the polypeptide substrate binding domain is lethal in wild-type E. coli. This dominant-negative phenotype may 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.93.20.10632
更新日期:1996-10-01 00:00:00
abstract::A number of recent studies have shown that iron dissolution in Fe-containing dust aerosol can be linked to source material (mineral or anthropogenic), mineralogy, and iron speciation. All of these factors need to be incorporated into atmospheric chemistry models if these models are to accurately predict the impact 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.0910809107
更新日期:2010-04-13 00:00:00
abstract::Spectrin (betaISigma*) and ankyrin (AnkG119) associate with Golgi membranes and the dynactin complex, but their role in vesicle trafficking remains uncertain. We find that the actin-binding domain and membrane-association domain 1 (MAD1) of betaI spectrin together form a constitutive Golgi targeting signal in transfec...
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.94.20.10711
更新日期:1997-09-30 00:00:00
abstract::We report the development of a practical ultrafast allelic profiling assay for the analysis of short tandem repeats (STRs) by using a highly optimized microfluidic electrophoresis device. We have achieved baseline-resolved electrophoretic separations of single-locus STR samples in 30 sec. Analyses of PCR samples conta...
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.94.19.10273
更新日期:1997-09-16 00:00:00
abstract::Management of the diverse fisheries of the world has had mixed success. While managing single species in data-rich environments has been largely effective, perhaps the greatest challenge facing fishery managers is how to deal with mixed stocks of fish with a range of life histories that reside in the same location. Be...
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.1705169114
更新日期:2017-08-22 00:00:00
abstract::We have measured the fidelity of bidirectional, semiconservative DNA synthesis by a human DNA replication complex in vitro. Replication was performed by extracts of HeLa cells in the presence of simian virus 40 (SV40) large tumor antigen by using a double-stranded phage M13mp2 DNA template containing the SV40 origin 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.85.19.7064
更新日期:1988-10-01 00:00:00
abstract::Using Drosophila pseudoobscura, we tested the hypothesis that social constraints on the free expression of mate preferences, by both females and males, decrease offspring viability and reproductive success of mating pairs. Mate preference arenas eliminated intrasexual combat and intersexual coercion. The time female 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.0611152104
更新日期:2007-03-13 00:00:00
abstract::We used positron emission tomography (PET) to examine the role of the hippocampal formation in implicit and explicit memory. Human volunteers studied a list of familiar words, and then they either provided the first word that came to mind in response to three-letter cues (implicit memory) or tried to recall studied wo...
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.93.1.321
更新日期:1996-01-09 00:00:00
abstract::The rotational strengths of the four longer wavelength transitions, B(2u), B(1u), and the two E(1u), of adenosine derivatives constrained in the syn form have been investigated theoretically and experimentally. The theory combines a complete neglect of differential overlap version S (CNDO/S) description of the base wi...
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.77.6.3398
更新日期:1980-06-01 00:00:00
abstract::The kinetics of biomolecular isomerization processes, such as protein folding, is governed by a free-energy surface of high dimensionality and complexity. As an alternative to projections into one or two dimensions, the free-energy surface can be mapped into a weighted network where nodes and links are configurations ...
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.0608099104
更新日期:2007-02-06 00:00:00
abstract::Three genome-wide RNA interference screens were performed in Drosophila S2 cells to dissect the contribution of host processes to Listeria monocytogenes entry, vacuolar escape, and intracellular growth. Among the 116 genes identified, several host pathways previously unrecognized as playing a role in listerial pathoge...
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.0506461102
更新日期:2005-09-20 00:00:00
abstract::The exquisite selectivity and catalytic activity of enzymes have been shaped by the effects of positive and negative selection pressure during the course of evolution. In contrast, enzyme variants engineered by using in vitro screening techniques to accept novel substrates typically display a higher degree of catalyti...
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.0500063102
更新日期:2005-05-10 00:00:00
abstract::In vitro assembly of tobacco mosaic virus (TMV) from its constituent RNA and protein occurs in two steps: formation of the initial complex by interaction of the 5'-end of TMV-RNA with 20S protein aggregate, and growth of the helical rod by sequential addition of protein subunits.Such a process was also observed in 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.69.12.3680
更新日期:1972-12-01 00:00:00