Abstract:
:Down syndrome (DS) caused by trisomy of chromosome 21 is the most common genetic cause of intellectual disability. Although the prenatal diagnosis of DS has become feasible, there are no therapies available for the rescue of DS-related neurocognitive impairment. A growth inducer newly identified in our screen of neural stem cells (NSCs) has potent inhibitory activity against dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) and was found to rescue proliferative deficits in Ts65Dn-derived neurospheres and human NSCs derived from individuals with DS. The oral administration of this compound, named ALGERNON (altered generation of neurons), restored NSC proliferation in murine models of DS and increased the number of newborn neurons. Moreover, administration of ALGERNON to pregnant dams rescued aberrant cortical formation in DS mouse embryos and prevented the development of abnormal behaviors in DS offspring. These data suggest that the neurogenic phenotype of DS can be prevented by ALGERNON prenatal therapy.
journal_name
Proc Natl Acad Sci U S Aauthors
Nakano-Kobayashi A,Awaya T,Kii I,Sumida Y,Okuno Y,Yoshida S,Sumida T,Inoue H,Hosoya T,Hagiwara Mdoi
10.1073/pnas.1704143114subject
Has Abstractpub_date
2017-09-19 00:00:00pages
10268-10273issue
38eissn
0027-8424issn
1091-6490pii
1704143114journal_volume
114pub_type
杂志文章abstract::After more than two decades of study, many fundamental questions remain unanswered about the dynamics of glass-forming materials confined to thin films. Experiments and simulations indicate that free interfaces enhance dynamics over length scales larger than molecular sizes, and this effect strengthens at lower temper...
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.2006703117
更新日期:2020-10-13 00:00:00
abstract::Heparin preparations from pig intestinal mucosa and from bovine lung were separated by chromatography on antithrombin-Sepharose into a high-affinity fraction (with high anticoagulant activity) and a low-affinity fraction (with low anticoagulant). Antithrombin-binding heparin fragments (12-16 monosaccharide units) were...
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.76.7.3198
更新日期:1979-07-01 00:00:00
abstract::We have measured the angle-resolved transverse resistivity (ARTR), a sensitive indicator of electronic anisotropy, in high-quality thin films of the unconventional superconductor Sr2RuO4 grown on various substrates. The ARTR signal, heralding the electronic nematicity or a large nematic susceptibility, is present 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.1921713117
更新日期:2020-05-19 00:00:00
abstract::Managing excess nutrients remains a major obstacle to improving ecosystem service benefits of urban waters. To inform more ecologically based landscape nutrient management, we compared watershed inputs, outputs, and retention for nitrogen (N) and phosphorus (P) in seven subwatersheds of the Mississippi River in St. Pa...
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.1618536114
更新日期:2017-04-18 00:00:00
abstract::Protein kinases are important mediators of much of the signal transduction that occurs in eukaryotic cells. Unfortunately, the identification of protein kinase substrates has proven to be a difficult task, and we generally know few, if any, of the physiologically relevant targets of any particular kinase. Here, we des...
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.0501046102
更新日期:2005-09-27 00:00:00
abstract::We construct counterexamples to classical calculus facts such as the inverse and implicit function theorems in scale calculus-a generalization of multivariable calculus to infinite-dimensional vector spaces, in which the reparameterization maps relevant to symplectic geometry are smooth. Scale calculus is a corner sto...
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.1811701116
更新日期:2019-04-30 00:00:00
abstract::Transmission electron microscopy studies have been used to argue that magnetite crystals in carbonate from Martian meteorite ALH84001 have a composition and morphology indistinguishable from that of magnetotactic bacteria. It has even been claimed from scanning electron microscopy imaging that some ALH84001 magnetite ...
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.0402292101
更新日期:2004-06-01 00:00:00
abstract::During response of budding yeast to peptide mating pheromone, the cell becomes markedly polarized and MAPK scaffold protein Ste5 localizes to the resulting projection (shmoo tip). We demonstrated before that this recruitment is essential for sustained MAPK signaling and requires interaction of a pleckstrin homology (P...
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.1005817107
更新日期:2010-06-29 00:00:00
abstract::The role of protein farnesylation in lamin A biogenesis and the pathogenesis of progeria has been studied in considerable detail, but the importance of farnesylation for the B-type lamins, lamin B1 and lamin B2, has received little attention. Lamins B1 and B2 are expressed in nearly every cell type from the earliest s...
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.1303916110
更新日期:2013-05-21 00:00:00
abstract::delta-Aminolevulinic acid (ALA) synthase [succinyl-CoA:glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37] activity was detected in cell extracts of the unicellular green flagellate alga Euglena gracilis. The enzyme was identified by substrate and cofactor requirements, and activity was proportional to numbe...
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.78.3.1666
更新日期:1981-03-01 00:00:00
abstract::Physical activity increases energy metabolism in exercising muscle. Whether acute exercise elicits metabolic changes in nonexercising muscles remains unclear. We show that one of the few genes that is more highly induced in nonexercising muscle than in exercising human muscle during acute exercise encodes angiopoietin...
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.1400889111
更新日期:2014-03-18 00:00:00
abstract::Chronic stress is known to promote inflammatory bowel disease (IBD), but the underlying mechanism remains largely unresolved. Here, we found chronic stress to sensitize mice to dextran sulfate sodium (DSS)-induced colitis; to increase the infiltration of B cells, neutrophils, and proinflammatory ly6Chi macrophages in ...
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.1720696115
更新日期:2018-03-27 00:00:00
abstract::During the last several decades corals have been in decline and at least one-third of all coral species are now threatened with extinction. Coral disease has been a major contributor to this threat, but little is known about the responsible pathogens. To date most research has focused on bacterial and fungal diseases;...
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.0808985105
更新日期:2008-11-25 00:00:00
abstract::Simulations with a regional chemical transport model show that anthropogenic emissions of volatile organic compounds and nitrogen oxides (NO(x) = NO + NO(2)) lead to a dramatic diurnal variation of surface ozone (O(3)) in Houston, Texas. During the daytime, photochemical oxidation of volatile organic compounds catalyz...
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.0401484101
更新日期:2004-04-27 00:00:00
abstract::Small molecules that specifically bind with high affinity to any designated DNA sequence in the human genome would be useful tools in molecular biology and potentially in human medicine. Simple rules have been developed to rationally alter the sequence specificity of minor groove-binding polyamides containing N-methyl...
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.92.22.10389
更新日期:1995-10-24 00:00:00
abstract::Helper-dependent adenoviral vectors deleted of all viral coding sequences have shown an excellent gene expression profile in a variety of animal models, as well as a reduced toxicity after systemic delivery. What is still unclear is whether long-term expression and therapeutic dosages of these vectors can be obtained ...
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.101122498
更新日期:2001-05-22 00:00:00
abstract::The protective effects of estrogen in the cardiovascular system result from both systemic effects and direct actions of the hormone on the vasculature. Two estrogen receptors have been identified, ERalpha and ERbeta. We demonstrated previously that estrogen inhibits the response to vascular injury in both wild-type 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.96.26.15133
更新日期:1999-12-21 00:00:00
abstract::Efficient single nucleotide polymorphism (SNP) genotyping methods are necessary to accomplish many current gene discovery goals. A crucial element in large-scale SNP genotyping is the number of individual biochemical reactions that must be performed. An efficient method that can be used to simultaneously amplify a set...
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.261710699
更新日期:2002-03-05 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::Two cDNAs encoding two human receptors for retinoic acid (RA), RAR-alpha and RAR-beta, have been characterized recently. Synthetic peptides corresponding to the cDNA-deduced amino acid sequences unique to RAR-alpha and RAR-beta were used to generate anti-RAR-alpha antiserum (SP171) and anti-RAR-beta antisera (SP172 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.86.9.3089
更新日期:1989-05-01 00:00:00
abstract::Mutations in the dystrophin gene cause Duchenne muscular dystrophy (DMD) most commonly through loss of protein expression. In a small subpopulation of patients, missense mutations can cause DMD, Becker muscular dystrophy, or X-linked cardiomyopathy. Nearly one-half of disease-causing missense mutations are located in ...
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.1001517107
更新日期:2010-05-25 00:00:00
abstract::Recessive N-ethyl-N-nitrosourea (ENU)-induced mutations recovered at the fitness-1 (fit1) locus in mouse chromosome 7 cause hematopoietic abnormalities, growth retardation, and shortened life span, with varying severity of the defects in different alleles. Abnormal iron distribution and metabolism and frequent scolios...
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.1432634100
更新日期:2003-07-08 00:00:00
abstract::Although peroxynitrite is harmful to the host, the beneficial effects of peroxynitrite are less well understood. We explored the role of peroxynitrite in the host immune response to Coxsackievirus infection. Peroxynitrite inhibits viral replication in vitro, in part by inhibiting viral RNA entry into the host cell. Ni...
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.0400518101
更新日期:2004-08-10 00:00:00
abstract::(3)H-actinomycin D, a guanine-binding agent, labels fixed human chromosomes nonrandomly. Actinomycin D added in G2 inhibits secondary constrictions and breaks chromosomes. There is some tendency for label to be concentrated at the ends of chromosomes and near the centromere. Labeling with (3)H-thymidine in the late st...
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.65.3.585
更新日期:1970-03-01 00:00:00
abstract::Information concerning the dynamics of river meandering is embedded in their planforms. Here, we focus on how bend skewing varies with increasing sinuosity, and how flow direction is embedded in bend skewing. It has often been thought that upstream-skewed bends are dominant within a sufficiently long reach. These bend...
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.1910874116
更新日期:2019-11-19 00:00:00
abstract::E-Cadherin, a cell adhesion molecule, which plays a key role in maintaining the epithelial phenotype, is regarded as an invasion-suppressor gene in light of accumulating evidence from in vitro experiments and clinical observations. In an attempt to clarify the mechanism responsible for inactivation of this gene in car...
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.92.16.7416
更新日期:1995-08-01 00:00:00
abstract::The basic assumptions of van der Waals theory are contained in two well-known concepts: excluded volume (repulsive forces) and a homogeneous, isotropic field potential (attractive forces). We have superimposed on these, one more well-known concept: the existence of dimers, trimers, etc., at chemical equilibrium. With ...
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.73.6.1773
更新日期:1976-06-01 00:00:00
abstract::Methionine sulfoxide reductase A (MsrA) catalyzes the reduction of methionine sulfoxide to methionine and is specific for the S epimer of methionine sulfoxide. The enzyme participates in defense against oxidative stresses by reducing methionine sulfoxide residues in proteins back to methionine. Because oxidation of me...
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.1101275108
更新日期:2011-06-28 00:00:00
abstract::Friction is caused by dissipative lateral forces that act between macroscopic objects. An improved understanding of friction is therefore expected from measurements of dissipative lateral forces acting between individual atoms. Here we establish atomic resolution of both conservative and dissipative forces by lateral ...
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.182160599
更新日期:2002-09-17 00:00:00
abstract::The soybean genome hosts a family of several hundred, relatively homogeneous copies of a large, copia/Ty1-like retroelement designated SIRE-1. A copy of this element has been recovered from a Glycine max genomic library. DNA sequence analysis of two SIRE-1 subclones revealed that SIRE-1 contains a long, uninterrupted,...
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.95.12.6897
更新日期:1998-06-09 00:00:00