Abstract:
:The molecular and cellular basis of selective motor neuron (MN) vulnerability in amyotrophic lateral sclerosis (ALS) is not known. In genetically distinct mouse models of familial ALS expressing mutant superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS), we demonstrate selective degeneration of alpha MNs (α-MNs) and complete sparing of gamma MNs (γ-MNs), which selectively innervate muscle spindles. Resistant γ-MNs are distinct from vulnerable α-MNs in that they lack synaptic contacts from primary afferent (IA) fibers. Elimination of these synapses protects α-MNs in the SOD1 mutant, implicating this excitatory input in MN degeneration. Moreover, reduced IA activation by targeted reduction of γ-MNs in SOD1G93A mutants delays symptom onset and prolongs lifespan, demonstrating a pathogenic role of surviving γ-MNs in ALS. This study establishes the resistance of γ-MNs as a general feature of ALS mouse models and demonstrates that synaptic excitation of MNs within a complex circuit is an important determinant of relative vulnerability in ALS.
journal_name
Proc Natl Acad Sci U S Aauthors
Lalancette-Hebert M,Sharma A,Lyashchenko AK,Shneider NAdoi
10.1073/pnas.1605210113subject
Has Abstractpub_date
2016-12-20 00:00:00pages
E8316-E8325issue
51eissn
0027-8424issn
1091-6490pii
1605210113journal_volume
113pub_type
杂志文章abstract::The idea that the first living systems on earth were based on self-replicating RNA molecules has recently become popular as a result of the discovery of ribozymes. However, there are several major problems associated with the prebiotic synthesis of ribonucleotides. In addition, there is the newly recognized problem 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.84.13.4398
更新日期:1987-07-01 00:00:00
abstract::To improve the efficiency of liposome-mediated DNA transfer as a tool for gene therapy, we have developed a fusigenic liposome vector based on principles of viral cell fusion. The fusion proteins of hemagglutinating virus of Japan (HVJ; also Sendai virus) are complexed with liposomes that encapsulate oligodeoxynucleot...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 评论,杂志文章,评审
doi:10.1073/pnas.93.21.11421
更新日期:1996-10-15 00:00:00
abstract::Avian myelocytomatosis virus (MC29), a defective acute leukemia virus, has a broad oncogenic spectrum in vivo and transforms fibroblasts and hematopoietic target cells in vitro. We have used recombinant DNA technology to isolate and to characterize the sequences that are essential in the transformation process. Integr...
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.78.3.1518
更新日期:1981-03-01 00:00:00
abstract::Chaperones of the Hsp70 family bind to unfolded or partially folded polypeptides to facilitate many cellular processes. ATP hydrolysis and substrate binding, the two key molecular activities of this chaperone, are modulated by the cochaperone DnaJ. By using both genetic and biochemical approaches, we provide evidence ...
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.95.26.15223
更新日期:1998-12-22 00:00:00
abstract::The prediction of binding sites and the understanding of interfaces associated with protein complexation remains an open problem in molecular biophysics. This work shows that a crucial factor in predicting and rationalizing protein-protein interfaces can be inferred by assessing the extent of intramolecular desolvatio...
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.0136888100
更新日期:2003-01-07 00:00:00
abstract::The translocation from chromosome 8 to chromosome 21, t(8;21), associated with acute myeloid leukemia results in production of an AML1/MTG8(ETO) fusion transcript. The product of the AML1 gene contains an evolutionarily conserved 128-amino acid region referred to as the "Runt domain," which is necessary for binding to...
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.91.24.11723
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abstract::Microcin B17 (MccB17) is a 3.1-kDa Escherichia coli antibiotic that contains thiazole and oxazole heterocycles in a peptide backbone. MccB17 inhibits its cellular target, DNA gyrase, by trapping the enzyme in a complex that is covalently bound to double-strand cleaved DNA, in a manner similar to the well-known quinolo...
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.141225698
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abstract::Biomimetic nanopores based on membrane-spanning single-walled carbon nanotubes have been designed to include selectivity filters based on combinations of anionic and cationic groups mimicking those present in bacterial porins and in voltage-gated sodium and calcium channels. The ion permeation and selectivity properti...
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.1119326109
更新日期:2012-05-01 00:00:00
abstract::The T-cell receptor (TCR) gamma gene product occurs in association with T3 (CD3) polypeptides on the surface of human T lymphocytes. TCR gamma lymphocytes express arrays of T3 polypeptides distinct from those typically observed on TCR alpha beta lymphocytes. This report demonstrates that identical T3 gamma, delta, 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.84.11.3817
更新日期:1987-06-01 00:00:00
abstract::Malaria control is threatened by a limited pipeline of effective pharmaceuticals against drug-resistant strains of Plasmodium falciparum Components of the mitochondrial electron transport chain (ETC) are attractive targets for drug development, owing to exploitable differences between the parasite and human ETC. Disru...
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.1804492115
更新日期:2018-06-12 00:00:00
abstract::We carried out a large-scale screen to identify interactions between integral membrane proteins of Saccharomyces cerevisiae by using a modified split-ubiquitin technique. Among 705 proteins annotated as integral membrane, we identified 1,985 putative interactions involving 536 proteins. To ascribe confidence levels to...
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.0505482102
更新日期:2005-08-23 00:00:00
abstract::The murine mast cell line PB-3c is dependent on interleukin 3 (IL-3) with respect to survival and proliferation. These cells also require IL-3 to display antigen-mediated serotonin release, which is coupled to a transient increase of cytosolic free calcium ([Ca2+]i). The antigen-mediated exocytosis is inhibited by pho...
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.84.5.1277
更新日期:1987-03-01 00:00:00
abstract::Recent analyses of high-throughput protein interaction data coupled with large-scale investigations of evolutionary properties of interaction networks have left some unanswered questions. To what extent do protein interactions act as constraints during evolution of the protein sequence? How does the type of interactio...
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.0502667102
更新日期:2005-08-02 00:00:00
abstract::Developing tools for investigating the cellular activity of glycans will help to delineate the molecular basis for aberrant glycosylation in pathological processes such as cancer. Metabolic oligosaccharide engineering, which inserts sugar-reporting groups into cellular glycoconjugates, represents a powerful method for...
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.0611307104
更新日期:2007-02-20 00:00:00
abstract::A gamma-trace variant protein is the major constituent of the amyloid fibrils in patients from Iceland with hereditary cerebral hemorrhage with amyloidosis. The protein consists of 110 residues and is similar to human urinary gamma-trace basic protein (or cystatin C) beginning at its 11th amino-terminal residue. It ha...
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.83.9.2974
更新日期:1986-05-01 00:00:00
abstract::Broken-cell preparations of Salmonella typhimurium rapidly incorporated 75Se from 75SeO3(2-) into tRNA by an ATP-dependent process. Selenium incorporation in the presence of 50 microM 75SeO3(2-) (0.8-1 pmol per A260 unit) was enhanced by the selenocysteine precursor, O-acetyl-L-serine (to 3.7 pmol per A260 unit). This...
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.87.16.6341
更新日期:1990-08-01 00:00:00
abstract::Relatively low concentrations of methylxanthines increase spontaneous twitching in cultured muscle fibers; they also cause a second activity, escalation, which is the initiation and undiminished propagation of visible waves. The effect on twitching is abolished by depolarizing concentrations of K(+) or by tetrodotoxin...
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.69.3.613
更新日期:1972-03-01 00:00:00
abstract::Beetle luciferases are thought to have evolved from fatty acyl-CoA synthetases present in all insects. Both classes of enzymes activate fatty acids with ATP to form acyl-adenylate intermediates, but only luciferases can activate and oxidize d-luciferin to emit light. Here we show that the Drosophila fatty acyl-CoA syn...
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.1319300111
更新日期:2014-03-25 00:00:00
abstract::Inhibition of human purine nucleoside phosphorylase (PNP) stops growth of activated T-cells and the formation of 6-oxypurine bases, making it a target for leukemia, autoimmune disorders, and gout. Four generations of ribocation transition-state mimics bound to PNP are structurally characterized. Immucillin-H (K*i(1/4)...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
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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.81.23.7505
更新日期:1984-12-01 00:00:00
abstract::This report provides direct evidence that strigolactone (SL) positively regulates drought and high salinity responses in Arabidopsis. Both SL-deficient and SL-response [more axillary growth (max)] mutants exhibited hypersensitivity to drought and salt stress, which was associated with shoot- rather than root-related t...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
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更新日期:2014-01-14 00:00:00
abstract::The in vitro biological activities of several rabies virus-neutralizing monoclonal antibodies (mAbs) were compared with their ability to prevent a lethal rabies virus encephalomyelitis. The protective activity of a particular mAb in vivo did not correlate with its virus-neutralizing activity in vitro; rather it was re...
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.89.15.7252
更新日期:1992-08-01 00:00:00
abstract::During meiosis, homologous chromosomes recombine and become closely apposed along their lengths within the synaptonemal complex (SC). In part because Spo11 is required both to make the double-strand breaks (DSBs) that initiate recombination and to promote normal SC formation in many organisms, it is clear that these 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.0400843101
更新日期:2004-03-30 00:00:00
abstract::We previously reported that long-term cyclic estrogen (E) treatment reverses age-related impairment of cognitive function mediated by the dorsolateral prefrontal cortex (dlPFC) in ovariectomized (OVX) female rhesus monkeys, and that E induces a corresponding increase in spine density in layer III dlPFC pyramidal neuro...
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.0704757104
更新日期:2007-07-03 00:00:00
abstract::We performed the first genome-wide expression analysis directly comparing the expression profile of highly enriched normal human hematopoietic stem cells (HSC) and leukemic stem cells (LSC) from patients with acute myeloid leukemia (AML). Comparing the expression signature of normal HSC to that of LSC, we identified 3...
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.0900089106
更新日期:2009-03-03 00:00:00
abstract::All available complete mitochondrial genomes (21 species) are evaluated for dinucleotide over- and under-representation. The CpG dinucleotide is pervasively under-represented in all animal mitochondria, but it is of variable relative abundance in fungal, protist, and plant mitochondrial genomes. Interpretations and hy...
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.91.9.3799
更新日期:1994-04-26 00:00:00
abstract::Functional reconstitution of membrane proteins within lipid bilayers is crucial for understanding their biological function in living cells. While this strategy has been extensively used with liposomes, reconstitution of membrane proteins in lipidic cubic mesophases presents significant challenges related to the struc...
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.1603965113
更新日期:2016-07-05 00:00:00
abstract::We have cloned a murine cDNA encoding a tyrosine kinase receptor with about 90% similarity to the chicken fibroblast growth factor (FGF) receptor and the human fms-like gene (FLG) tyrosine kinase. This mouse receptor lacks 88 amino acids in the extracellular portion, leaving only two immunoglobulin-like domains compar...
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.87.11.4378
更新日期:1990-06-01 00:00:00
abstract::Artificially aminoacylated suppressor tRNAs were used to introduce photoreactive amino acids into model mitochondrial precursor proteins to probe the environment along the protein import pathway. Amino acids with benzophenone side chains of various lengths [DL-2-amino-3-(p-benzoylphenyl)propanoic acid (1) and DL-2-ami...
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.94.2.485
更新日期:1997-01-21 00:00:00
abstract::The circadian clock is based on a transcriptional feedback loop with an essential time delay before feedback inhibition. Previous work has shown that PERIOD (PER) proteins generate circadian time cues through rhythmic nuclear accumulation of the inhibitor complex and subsequent interaction with the activator complex i...
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.2003524117
更新日期:2020-11-10 00:00:00