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  • 1
    Online Resource
    Online Resource
    The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice
    American Association for the Advancement of Science (AAAS) ; 2011
    In:  Science Vol. 332, No. 6028 ( 2011-04-22), p. 478-484
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 332, No. 6028 ( 2011-04-22), p. 478-484
    Abstract: The growth factor progranulin (PGRN) has been implicated in embryonic development, tissue repair, tumorigenesis, and inflammation, but its receptors remain unidentified. We report that PGRN bound directly to tumor necrosis factor receptors (TNFRs) and disturbed the TNFα-TNFR interaction. PGRN-deficient mice were susceptible to collagen-induced arthritis, and administration of PGRN reversed inflammatory arthritis. Atsttrin, an engineered protein composed of three PGRN fragments, exhibited selective TNFR binding. PGRN and Atsttrin prevented inflammation in multiple arthritis mouse models and inhibited TNFα-activated intracellular signaling. Collectively, these findings demonstrate that PGRN is a ligand of TNFR, an antagonist of TNFα signaling, and plays a critical role in the pathogenesis of inflammatory arthritis in mice. They also suggest new potential therapeutic interventions for various TNFα-mediated pathologies and conditions, including rheumatoid arthritis.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1199214
    RVK:
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    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2011
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  • 2
    Online Resource
    Online Resource
    Testing Accommodation or Modification? : The Effects of Integrated Object Representation on Enhancing Geometry Performance in Children With and Without Geometry Difficulties
    SAGE Publications ; 2014
    In:  Journal of Learning Disabilities Vol. 47, No. 6 ( 2014-11), p. 569-583
    Details
    In: Journal of Learning Disabilities, SAGE Publications, Vol. 47, No. 6 ( 2014-11), p. 569-583
    Abstract: According to the National Council of Teachers of Mathematics, geometry and spatial sense are fundamental components of mathematics learning. However, learning disabilities (LD) research has shown that many K–12 students encounter particular geometry difficulties (GD). This study examined the effect of an integrated object representation (IOR) accommodation on the test performance of students with GD compared to students without GD. Participants were 118 elementary students who took a researcher-developed geometry problem solving test under both a standard testing condition and an IOR accommodation condition. A total of 36 students who were classified with GD scored below 40% correct in the geometry problem solving test in the standard testing condition, and 82 students who were classified without GD scored equal to or above 40% correct in the same test and condition. All students were tested in both standard testing condition and IOR accommodation condition. The results from both ANOVA and regression discontinuity (RD) analyses suggested that students with GD benefited more than students without GD from the IOR accommodation. Implications of the study are discussed in terms of providing accommodations for students with mathematics learning difficulties and recommending RD design in LD research.
    Type of Medium: Online Resource
    ISSN: 0022-2194 , 1538-4780
    URL: Article
    DOI: 10.1177/0022219413507602
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2014
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  • 3
    Online Resource
    Online Resource
    Observation and theory of nonlinear mode couplings between shear Alfvén wave and magnetic island in tokamak plasmas
    IOP Publishing ; 2014
    In:  EPL (Europhysics Letters) Vol. 107, No. 2 ( 2014-07-01), p. 25001-
    Details
    In: EPL (Europhysics Letters), IOP Publishing, Vol. 107, No. 2 ( 2014-07-01), p. 25001-
    Type of Medium: Online Resource
    ISSN: 0295-5075 , 1286-4854
    URL: Article
    DOI: 10.1209/0295-5075/107/25001
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2014
    detail.hit.zdb_id: 1465366-7
    detail.hit.zdb_id: 165776-8
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  • 4
    Online Resource
    Online Resource
    Rapid Automatized Naming and Immediate Memory Functions in Chinese Mandarin—Speaking Elementary Readers
    SAGE Publications ; 2010
    In:  Journal of Learning Disabilities Vol. 43, No. 1 ( 2010-01), p. 48-61
    Details
    In: Journal of Learning Disabilities, SAGE Publications, Vol. 43, No. 1 ( 2010-01), p. 48-61
    Abstract: The purpose of this study was to evaluate rapid automatized naming skills (RAN) and immediate memory processes in 243 Chinese Mandarin—speaking elementary readers (ranging from Grade 1 to Grade 5). For RAN subtests, the mean naming time decreased monotonically with grade level in good and average readers, and a similar trajectory was found in poor readers, even though they were generally slower in rapid naming. Regardless of grouping methods (counting all participants or counting good readers only), RAN Character emerged as a significant predictor of various Chinese reading measures. Different from classical findings in English readers indicating that RAN Number was a better correlate of reading than RAN Object, RAN Object outperformed RAN Number and became a significant predictor of Chinese reading speed and spelling, suggesting that the differences in predictive power of RAN tasks may be language specific. Comparison of memory profiles for good, average, and poor readers revealed that the patterns varied depending on mode of stimulus presentation or response. Poor readers performed poorly on subtests involving a visual component and did relatively better on subtests involving verbal cues only, whereas a reversed pattern was shown in the group of good readers. The findings were interpreted to suggest that good and poor Chinese readers may be essentially different in applying visual strategies and verbal mediation during visual-verbal intra- and intermodal processing, and visual skills appear to be particularly important in reading of Chinese.
    Type of Medium: Online Resource
    ISSN: 0022-2194 , 1538-4780
    URL: Article
    DOI: 10.1177/0022219409345016
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
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  • 5
    Online Resource
    Online Resource
    A Memory Retrieval-Extinction Procedure to Prevent Drug Craving and Relapse
    American Association for the Advancement of Science (AAAS) ; 2012
    In:  Science Vol. 336, No. 6078 ( 2012-04-13), p. 241-245
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 336, No. 6078 ( 2012-04-13), p. 241-245
    Abstract: Drug use and relapse involve learned associations between drug-associated environmental cues and drug effects. Extinction procedures in the clinic can suppress conditioned responses to drug cues, but the extinguished responses typically reemerge after exposure to the drug itself (reinstatement), the drug-associated environment (renewal), or the passage of time (spontaneous recovery). We describe a memory retrieval-extinction procedure that decreases conditioned drug effects and drug seeking in rat models of relapse, and drug craving in abstinent heroin addicts. In rats, daily retrieval of drug-associated memories 10 minutes or 1 hour but not 6 hours before extinction sessions attenuated drug-induced reinstatement, spontaneous recovery, and renewal of conditioned drug effects and drug seeking. In heroin addicts, retrieval of drug-associated memories 10 minutes before extinction sessions attenuated cue-induced heroin craving 1, 30, and 180 days later. The memory retrieval-extinction procedure is a promising nonpharmacological method for decreasing drug craving and relapse during abstinence.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1215070
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2012
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  • 6
    Online Resource
    Online Resource
    Rapid Automatized Naming and Immediate Memory Functions in Chinese Children Who Read English as a Second Language
    SAGE Publications ; 2013
    In:  Journal of Learning Disabilities Vol. 46, No. 4 ( 2013-07), p. 347-362
    Details
    In: Journal of Learning Disabilities, SAGE Publications, Vol. 46, No. 4 ( 2013-07), p. 347-362
    Abstract: This study examined reading performance of 102 Chinese Mandarin-speaking 4th graders in their second language (L2, English) as a function of performance in their first language (L1, Chinese). The results revealed that for Rapid Automatized Naming (RAN) and Rapid Alternating Stimulus (RAS) measures, the mean naming time decreased monotonically in high-achieving, average, and low-achieving readers. RAN and RAS differentiated poor readers from good and average readers but failed to differentiate between good and average readers. RAN deficits occurred in poor readers in both languages. Comparison of memory profiles revealed that patterns varied depending on the mode of stimulus presentation or response. Low-achieving readers performed poorly on a subtest involving visual components only and did relatively better on a subtest involving verbal components only. Poor readers in Chinese also encountered difficulties in learning English as a L2. RAN-character accounted for unique variance in two Chinese reading measures. RAN-letter explained unique variance in English mid-term reading grade. The unique variance captured by the Color Span Subtest 1 (visual-visual) was found in Chinese reading comprehension but not in English reading comprehension. Reading performance in L1 was predictive of reading performance in L2 and vice versa.
    Type of Medium: Online Resource
    ISSN: 0022-2194 , 1538-4780
    URL: Article
    DOI: 10.1177/0022219411424209
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2013
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  • 7
    Online Resource
    Online Resource
    Hepatitis B virus core antigen determines viral persistence in a C57BL/6 mouse model
    Proceedings of the National Academy of Sciences ; 2010
    In:  Proceedings of the National Academy of Sciences Vol. 107, No. 20 ( 2010-05-18), p. 9340-9345
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 107, No. 20 ( 2010-05-18), p. 9340-9345
    Abstract: We recently developed a mouse model of hepatitis B virus (HBV) persistence, in which a single i.v. hydrodynamic injection of HBV DNA to C57BL/6 mice allows HBV replication and induces a partial immune response, so that about 20–30% of the mice carry HBV for more than 6 months. The model was used to identify the viral antigen crucial for HBV persistence. We knocked out individual HBV genes by introducing a premature termination codon to the HBV core, HBeAg, HBx, and polymerase ORFs. The specific-gene-deficient HBV mutants were hydrodynamically injected into mice and the HBV profiles of the mice were monitored. About 90% of the mice that received the HBcAg-mutated HBV plasmid exhibited high levels of hepatitis B surface antigenemia and maintained HBsAg expression for more than 6 months after injection. To map the region of HBcAg essential for viral clearance, we constructed a set of serial HBcAg deletion mutants for hydrodynamic injection. We localized the essential region of HBcAg to the carboxyl terminus, specifically to the 10 terminal amino acids (HBcAg176–185). The majority of mice receiving this HBV mutant DNA did not elicit a proper HBcAg-specific IFN-γ response and expressed HBV virions for 6 months. These results indicate that the immune response triggered in mice by HBcAg during exposure to HBV is important in determining HBV persistence.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1004762107
    RVK:
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    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2010
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  • 8
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    Online Resource
    Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events
    Proceedings of the National Academy of Sciences ; 2010
    In:  Proceedings of the National Academy of Sciences Vol. 107, No. 39 ( 2010-09-28), p. 17017-17022
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 107, No. 39 ( 2010-09-28), p. 17017-17022
    Abstract: Chronic administration of high levels of selective COX-2 inhibitors (coxibs), particularly rofecoxib, valdecoxib, and parecoxib, increases risk for cardiovascular disease. Understanding the possibly multiple mechanisms underlying these adverse cardiovascular events is critical for evaluating the risks and benefits of coxibs and for development of safer coxibs. The current understanding of these mechanisms is likely incomplete. Using a metabolomics approach, we demonstrate that oral administration of rofecoxib for 3 mo results in a greater than 120-fold higher blood level of 20-hydroxyeicosatetraenoic acid (20-HETE), which correlates with a significantly shorter tail bleeding time in a murine model. We tested the hypothesis that this dramatic increase in 20-HETE is attributable to inhibition of its metabolism and that the shortened bleeding time following rofecoxib administration is attributable, in part, to this increase. The s.c. infusion of 20-HETE shortened the tail bleeding time dramatically. Neither 20-HETE biosynthesis nor cytochrome P4A-like immune reactivity was increased by rofecoxib administration, but 20-HETE production increased in vitro with the addition of coxib. 20-HETE is significantly more potent than its COX-mediated metabolites in shortening clotting time in vitro. Furthermore, 20-HETE but not rofecoxib significantly increases rat platelet aggregation in vitro in a dose-dependent manner. These data suggest 20-HETE as a marker of rofecoxib exposure and that inhibition of 20-HETE's degradation by rofecoxib is a partial explanation for its dramatic increase, the shortened bleeding time, and, possibly, the adverse cardiovascular events associated with rofecoxib.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1011278107
    RVK:
    TA 1000
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    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2010
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    detail.hit.zdb_id: 1461794-8
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  • 9
    Online Resource
    Online Resource
    Virus infection triggers widespread silencing of host genes by a distinct class of endogenous siRNAs in Arabidopsis
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 40 ( 2014-10-07), p. 14613-14618
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 40 ( 2014-10-07), p. 14613-14618
    Abstract: Antiviral immunity controlled by RNA interference (RNAi) in plants and animals is thought to specifically target only viral RNAs by the virus-derived small interfering RNAs (siRNAs). Here we show that activation of antiviral RNAi in Arabidopsis plants is accompanied by the production of an abundant class of endogenous siRNAs mapped to the exon regions of more than 1,000 host genes and rRNA. These virus-activated siRNAs (vasiRNAs) are predominantly 21 nucleotides long with an approximately equal ratio of sense and antisense strands. Genetically, vasiRNAs are distinct from the known plant endogenous siRNAs characterized to date and instead resemble viral siRNAs by requiring Dicer-like 4 and RNA-dependent RNA polymerase 1 (RDR1) for biogenesis. However, loss of EXORIBONUCLEASE4/THYLENE-INSENSITIVE5 enhances vasiRNA biogenesis and virus resistance without altering the biogenesis of viral siRNAs. We show that vasiRNAs are active in directing widespread silencing of the target host genes and that Argonaute-2 binds to and is essential for the silencing activity of vasiRNAs. Production of vasiRNAs is readily detectable in Arabidopsis after infection by viruses from two distinct supergroups of plant RNA virus families and is targeted for inhibition by the silencing suppressor protein 2b of Cucumber mosaic virus. These findings reveal RDR1 production of Arabidopsis endogenous siRNAs and identify production of vasiRNAs to direct widespread silencing of host genes as a conserved response of plants to infection by diverse viruses. A possible function for vasiRNAs to confer broad-spectrum antiviral activity distinct to the virus-specific antiviral RNAi by viral siRNAs is discussed.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1407131111
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
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    detail.hit.zdb_id: 1461794-8
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  • 10
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    Online Resource
    Rapid growth of a hepatocellular carcinoma and the driving mutations revealed by cell-population genetic analysis of whole-genome data
    Proceedings of the National Academy of Sciences ; 2011
    In:  Proceedings of the National Academy of Sciences Vol. 108, No. 29 ( 2011-07-19), p. 12042-12047
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 108, No. 29 ( 2011-07-19), p. 12042-12047
    Abstract: We present the analysis of the evolution of tumors in a case of hepatocellular carcinoma. This case is particularly informative about cancer growth dynamics and the underlying driving mutations. We sampled nine different sections from three tumors and seven more sections from the adjacent nontumor tissues. Selected sections were subjected to exon as well as whole-genome sequencing. Putative somatic mutations were then individually validated across all 9 tumor and 7 nontumor sections. Among the mutations validated, 24 were amino acid changes; in addition, 22 large indels/copy number variants ( 〉 1 Mb) were detected. These somatic mutations define four evolutionary lineages among tumor cells. Separate evolution and expansion of these lineages were recent and rapid, each apparently having only one lineage-specific protein-coding mutation. Hence, by using a cell-population genetic definition, this approach identified three coding changes (CCNG1, P62, and an indel/fusion gene) as tumor driver mutations. These three mutations, affecting cell cycle control and apoptosis, are functionally distinct from mutations that accumulated earlier, many of which are involved in inflammation/immunity or cell anchoring. These distinct functions of mutations at different stages may reflect the genetic interactions underlying tumor growth.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1108715108
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2011
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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