Abstract:
:Stroke is a major cause of serious disability due to the brain's limited capacity to regenerate damaged tissue and neuronal circuits. After ischemic injury, a multiphasic degenerative and inflammatory response is coupled with severely restricted vascular and neuronal repair, resulting in permanent functional deficits. Although clinical evidence indicates that revascularization of the ischemic brain regions is crucial for functional recovery, no therapeutics that promote angiogenesis after cerebral stroke are currently available. Besides vascular growth factors, guidance molecules have been identified to regulate aspects of angiogenesis in the central nervous system (CNS) and may provide targets for therapeutic angiogenesis. In this study, we demonstrate that genetic deletion of the neurite outgrowth inhibitor Nogo-A or one of its corresponding receptors, S1PR2, improves vascular sprouting and repair and reduces neurological deficits after cerebral ischemia in mice. These findings were reproduced in a therapeutic approach using intrathecal anti-Nogo-A antibodies; such a therapy is currently in clinical testing for spinal cord injury. These results provide a basis for a therapeutic blockage of inhibitory guidance molecules to improve vascular and neural repair after ischemic CNS injuries.
journal_name
Proc Natl Acad Sci U S Aauthors
Rust R,Grönnert L,Gantner C,Enzler A,Mulders G,Weber RZ,Siewert A,Limasale YDP,Meinhardt A,Maurer MA,Sartori AM,Hofer AS,Werner C,Schwab MEdoi
10.1073/pnas.1905309116subject
Has Abstractpub_date
2019-07-09 00:00:00pages
14270-14279issue
28eissn
0027-8424issn
1091-6490pii
1905309116journal_volume
116pub_type
杂志文章abstract::The super-enhancers (SEs) of lineage-specific genes in B cells are off-target sites of somatic hypermutation. However, the inability to detect sufficient numbers of mutations in normal human B cells has precluded the generation of a high-resolution mutational landscape of SEs. Here we captured and sequenced 12 B 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.1914163116
更新日期:2019-12-03 00:00:00
abstract::Previous studies have shown that the oxidants Cu(++), H(2)O(2), and diamide mimic the stimulatory effect of insulin on 3-O-methylglucose transport in isolated fat cells. The present experiments were designed to determine whether sulfhydryl oxidation plays a key role in the activation of the glucose transport system. 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.71.10.4173
更新日期:1974-10-01 00:00:00
abstract::The resonance Raman excitation profiles of a number of charge transfer transitions in electron donor/acceptor complexes with tetracyanoethylene as acceptor in solution at room temperature are reported and compared with absorption and fluorescence spectra of these complexes. All complexes show distinct anomalies which ...
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.72.11.4196
更新日期:1975-11-01 00:00:00
abstract::The polyamines, putrescine, spermidine, and spermine, are essential polycations, intimately involved in the regulation of cellular proliferation. Although polyamines exert dynamic effects on the conformation of nucleic acids and macromolecular synthesis in vitro, their specific functions in vivo are poorly understood....
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.1219002110
更新日期:2013-02-05 00:00:00
abstract::Nature is rife with networks that are functionally optimized to propagate inputs to perform specific tasks. Whether via genetic evolution or dynamic adaptation, many networks create functionality by locally tuning interactions between nodes. Here we explore this behavior in two contexts: strain propagation in mechanic...
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.1806790116
更新日期:2019-02-12 00:00:00
abstract::The functional consequences of interrupting in utero binocular interactions were studied by recording from single cells in area 17 of adult cats that had one eye removed at least 2 wk before birth. In these animals all cortical neurons could be driven by the remaining eye, and in tangential microelectrode penetrations...
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.82.11.3901
更新日期:1985-06-01 00:00:00
abstract::DPB11, a gene that suppresses mutations in two essential subunits of Saccharomyces cerevisiae DNA polymerase II(epsilon) encoded by POL2 and DPB2, was isolated on a multicopy plasmid. The nucleotide sequence of the DPB11 gene revealed an open reading frame predicting an 87-kDa protein. This protein is homologous to 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.92.25.11791
更新日期:1995-12-05 00:00:00
abstract::The growth of a small number of cells from each of two chemically induced BALB/c sarcomas was enhanced when x-irradiated (15,000 rads) cells of the same sarcoma were mixed with the tumor inoculum. This enhancement did not occur if the recipients had been given a total body x-irradiation of 450 rads. Tumor neutralizati...
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.75.1.436
更新日期:1978-01-01 00:00:00
abstract::The A(2A)R is largely coexpressed with D(2)Rs and enkephalin mRNA in the striatum where it modulates dopaminergic activity. Activation of the A(2A)R antagonizes D(2)R-mediated behavioral and neurochemical effects in the basal ganglia through a mechanism that may involve direct A(2A)R-D(2)R interaction. However, whethe...
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.98.4.1970
更新日期:2001-02-13 00:00:00
abstract::This study demonstrates that significantly shortened telomeres are a hallmark of cardiomyocytes (CMs) from individuals with end-stage hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM) as a result of heritable defects in cardiac proteins critical to contractile function. Positioned at the ends of chromo...
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.1714538115
更新日期:2018-09-11 00:00:00
abstract::Macrophages use phagocytosis to control the spread of pathogens in the body, to clear apoptotic cells, and to aid in tissue remodeling. The phagosomal membrane is traditionally thought to originate from the plasmalemma and then go through a series of maturation steps involving sequential fusion with endosomal compartm...
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.0705801104
更新日期:2007-11-20 00:00:00
abstract::A brilliant, coarsely granular nuclear antigen was detected by anti-complement immunofluorescence in the nuclei of acute myeloid leukemia myeloblasts. Designated as LANA (leukemia-associated nuclear antigen), the reactivity differs from that of the Epstein-Barr-virus-determined nuclear antigen (EBNA) in immunological ...
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.71.3.685
更新日期:1974-03-01 00:00:00
abstract::Anti-idiotype antibodies (Ab2) were purified from a cancer patient treated with NP-4, a murine monoclonal antibody to carcinoembryonic antigen (CEA). These Ab2 were specific for NP-4 and inhibited the binding between NP-4 and CEA. BALB/c mice immunized with these human Ab2 produced anti-Ab2 antibodies that were also 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.88.8.3421
更新日期:1991-04-15 00:00:00
abstract::Many cell surface receptors are multimeric proteins, composed of several structural domains, some involved in ligand recognition, whereas others are responsible for signal transduction. In most cases, the mechanism of how ligand interaction in the extracellular domains leads to the activation of effector domains remai...
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.1107775108
更新日期:2011-09-13 00:00:00
abstract::Higher-level cognitive processes strongly depend on a complex interplay between mediodorsal thalamus nuclei and the prefrontal cortex (PFC). Alteration of thalamofrontal connectivity has been involved in cognitive deficits of schizophrenia. Prefrontal serotonin (5-HT)2A receptors play an essential role in cortical net...
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.1525586113
更新日期:2016-03-08 00:00:00
abstract::Electron microscopic techniques have been used to reveal two classes of subunits of tubulin in ordered arrays. Presumably the two classes correspond to the alpha and beta polypeptide chains of tubulin that have been distinguished by chemical criteria. The two types of subunits alternate along individual protofilaments...
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.75.10.5006
更新日期:1978-10-01 00:00:00
abstract::Humans reason about the mental states of others; this capacity is called Theory of Mind (ToM). In typically developing adults, ToM is supported by a consistent group of brain regions: the bilateral temporoparietal junction (TPJ), medial prefrontal cortex (MPFC), precuneus (PC), and anterior temporal sulci (aSTS). How ...
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.0900010106
更新日期:2009-07-07 00:00:00
abstract::The posterodorsal part of the medial nucleus of the amygdala (MeAp) receives its major sensory input from the accessory olfactory bulb and projects massively to the medial preoptic nucleus and other sexually dimorphic hypothalamic nuclei thought to play key roles in mediating steroid-sensitive reproductive functions. ...
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.86.12.4766
更新日期:1989-06-01 00:00:00
abstract::Viruses have unique lifestyles. To describe the pathogenesis and significance of viral infection in terms of host responses, resultant injury, and therapy, we focused on two RNA viruses: lymphocytic choriomeningitis (LCMV) and influenza (Flu). Many of the currently established concepts and consequences about viruses a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.1222025110
更新日期:2013-03-12 00:00:00
abstract::High-performance anion-exchange (HPAE) chromatography under alkaline conditions (pH congruent to 13) has been found to efficiently separate neutral oligosaccharides (triose to undecaose) according to molecular size, sugar composition, and linkage of monosaccharide units. The method was able to resolve 1----3, 1----4, ...
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.85.10.3289
更新日期:1988-05-01 00:00:00
abstract::The activated human Ha-ras oncogene was subjected to the control of the promoter region of the murine whey acidic protein (Wap) gene, which is expressed in mammary epithelial cells in response to lactogenic hormones. The Wap-ras gene was stably introduced into the mouse germ line of five transgenic mice (one male 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.84.5.1299
更新日期:1987-03-01 00:00:00
abstract::Src homology 2 (SH2) domains are phosphotyrosine-binding modules found within various signal-transducing proteins. We have determined by 125I competition assay and surface plasmon resonance that the SH2 domains of Src and Lck bind to a variety of phosphopeptides with similar affinity and specificity. Both bound with 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.90.11.4902
更新日期:1993-06-01 00:00:00
abstract::An efficient technique has been developed for performing in vivo site-directed mutagenesis in Drosophila melanogaster. This procedure involves directed repair of P-element-induced DNA lesions after injection of a modified DNA sequence into early embryos. An oligonucleotide of 50 base pairs, whose sequence spans the 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.89.5.1735
更新日期:1992-03-01 00:00:00
abstract::Using an antibody highly specific for D-serine conjugated to glutaraldehyde, we have localized endogenous D-serine in rat brain. Highest levels of D-serine immunoreactivity occur in the gray matter of the cerebral cortex, hippocampus, anterior olfactory nucleus, olfactory tubercle, and amygdala. Localizations of D-ser...
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.92.9.3948
更新日期:1995-04-25 00:00:00
abstract::Lipoxin B (LXB) was prepared by incubation of (15S)-15-hydroperoxy-5,8,11-cis-13-trans-icosatetraenoic acid (15-HPETE) with human leukocytes. Comparison with a number of trihydroxyicosatetraenes prepared by total synthesis showed that biologically derived LXB is (5S,14R,15S)-5,14,15-trihydroxy-6,10,12-trans-8-cis-icos...
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.83.7.1983
更新日期:1986-04-01 00:00:00
abstract::Secondary (i.e., heterotrophic or animal) production is a main pathway of energy flow through an ecosystem as it makes energy available to consumers, including humans. Its estimation can play a valuable role in the examination of linkages between ecosystem functions and services. We found that oil and gas platforms 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.1411477111
更新日期:2014-10-28 00:00:00
abstract::Vascular endothelial cells (ECs) sense and respond to hemodynamic shear stress, which is critical for circulatory homeostasis and the pathophysiology of vascular diseases. The mechanisms of shear stress mechanotransduction, however, remain elusive. We previously demonstrated a direct role of mitochondria in the purine...
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.2014029117
更新日期:2020-12-29 00:00:00
abstract::cDNAs made from polyadenylylated RNAs of the mouse lens were cloned by the G.C tailing procedure in the bacterial plasmid pBR322. Four recombinant DNAs containing gamma-crystallin sequences were identified by hybrid selection and translation. Sequence analysis of the in vivo-labeled gamma-crystallin polypeptides that ...
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.79.9.2783
更新日期:1982-05-01 00:00:00
abstract::Two strains that overproduce endonuclease III were found in a colony bank containing hybrid ColE1-Escherichia coli plasmids. The enzyme was identified in crude extracts by the degradation of partially depyrimidinated DNA in the presence of EDTA, by its sedimentation velocity, and by its associated thymine glycol-DNA g...
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.82.2.474
更新日期:1985-01-01 00:00:00
abstract::Multituberculates were the longest-lived order of the Class Mammalia and, during the Mesozoic and early Cenozoic, were among the most diverse and abundant representatives of the class. However, until the recent discovery of two Cretaceous teeth, one from South America and one from Africa, they were known only from nor...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.90.20.9379
更新日期:1993-10-15 00:00:00