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  • 1
    Online Resource
    Online Resource
    A Draft Sequence for the Genome of the Domesticated Silkworm ( Bombyx mori )
    American Association for the Advancement of Science (AAAS) ; 2004
    In:  Science Vol. 306, No. 5703 ( 2004-12-10), p. 1937-1940
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 306, No. 5703 ( 2004-12-10), p. 1937-1940
    Abstract: We report a draft sequence for the genome of the domesticated silkworm ( Bombyx mori ), covering 90.9% of all known silkworm genes. Our estimated gene count is 18,510, which exceeds the 13,379 genes reported for Drosophila melanogaster . Comparative analyses to fruitfly, mosquito, spider, and butterfly reveal both similarities and differences in gene content.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1102210
    RVK:
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2004
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
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  • 2
    Online Resource
    Online Resource
    All-trans retinoic acid/As 2 O 3 combination yields a high quality remission and survival in newly diagnosed acute promyelocytic leukemia
    Proceedings of the National Academy of Sciences ; 2004
    In:  Proceedings of the National Academy of Sciences Vol. 101, No. 15 ( 2004-04-13), p. 5328-5335
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 101, No. 15 ( 2004-04-13), p. 5328-5335
    Abstract: Both all-trans retinoic acid (ATRA) and arsenic trioxide (As 2 O 3 ) have proven to be very effective in obtaining high clinical complete remission (CR) rates in acute promyelocytic leukemia (APL), but they had not been used jointly in an integrated treatment protocol for remission induction or maintenance among newly diagnosed APL patients. In this study, 61 newly diagnosed APL subjects were randomized into three treatment groups, namely by ATRA, As 2 O 3 , and the combination of the two drugs. CR was determined by hematological analysis, tumor burden was examined with real-time quantitative RT-PCR of the PML-RAR α (promyelocytic leukemia - retinoic acid receptor α) fusion transcripts, and side effects were evaluated by means of clinical examinations. Mechanisms possibly involved were also investigated with cellular and molecular biology methods. Although CR rates in three groups were all high (≥90%), the time to achieve CR differed significantly, with that of the combination group being the shortest one. Earlier recovery of platelet count was also found in this group. The disease burden as reflected by fold change of PML-RARα transcripts at CR decreased more significantly in combined therapy as compared with ATRA or As 2 O 3 mono-therapy ( P 〈 0.01). This difference persisted after consolidation ( P 〈 0.05). Importantly, all 20 cases in the combination group remained in CR whereas 7 of 37 cases treated with mono-therapy relapsed ( P 〈 0.05) after a follow-up of 8–30 months (median: 18 months). Synergism of ATRA and As 2 O 3 on apoptosis and degradation of PML-RARα oncoprotein might provide a plausible explanation for superior efficacy of combinative therapy in clinic. In conclusion, the ATRA/As 2 O 3 combination for remission/maintenance therapy of APL brings much better results than either of the two drugs used alone in terms of the quality of CR and the status of the disease-free survival.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0400053101
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2004
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  • 3
    Online Resource
    Online Resource
    A Draft Sequence of the Rice Genome ( Oryza sativa L. ssp. indica )
    American Association for the Advancement of Science (AAAS) ; 2002
    In:  Science Vol. 296, No. 5565 ( 2002-04-05), p. 79-92
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 296, No. 5565 ( 2002-04-05), p. 79-92
    Abstract: We have produced a draft sequence of the rice genome for the most widely cultivated subspecies in China, Oryza sativa L. ssp. indica , by whole-genome shotgun sequencing. The genome was 466 megabases in size, with an estimated 46,022 to 55,615 genes. Functional coverage in the assembled sequences was 92.0%. About 42.2% of the genome was in exact 20-nucleotide oligomer repeats, and most of the transposons were in the intergenic regions between genes. Although 80.6% of predicted Arabidopsis thaliana genes had a homolog in rice, only 49.4% of predicted rice genes had a homolog in A. thaliana . The large proportion of rice genes with no recognizable homologs is due to a gradient in the GC content of rice coding sequences.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1068037
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2002
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  • 4
    Online Resource
    Online Resource
    Loss of presenilin 1 is associated with enhanced β-catenin signaling and skin tumorigenesis
    Proceedings of the National Academy of Sciences ; 2001
    In:  Proceedings of the National Academy of Sciences Vol. 98, No. 19 ( 2001-09-11), p. 10863-10868
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 19 ( 2001-09-11), p. 10863-10868
    Abstract: Presenilin 1 (PS1) is required for the proteolytic processing of Notch and the β-amyloid precursor protein (APP), molecules that play pivotal roles in cell-fate determination during development and Alzheimer's disease pathogenesis, respectively. In addition, PS1 interacts with β-catenin and promotes its turnover through independent mechanisms. Consistent with this activity, we report here that PS1 is important in controlling epidermal cell proliferation in vivo . PS1 knockout mice that are rescued through neuronal expression of human PS1 transgene develop spontaneous skin cancers. PS1-null keratinocytes exhibit higher cytosolic β-catenin and β-catenin/lymphoid enhancer factor-1/T cell factor (β-catenin/LEF)-mediated signaling. This effect can be reversed by reintroducing wild-type PS1, but not a PS1 mutant active in Notch processing but defective in β-catenin binding. Nuclear β-catenin protein can be detected in tumors. Elevated β-catenin/LEF signaling is correlated with activation of its downstream target cyclin D1 and accelerated entry from G 1 into S phase of the cell cycle. This report demonstrates a function of PS1 in adult tissues, and our analysis suggests that deregulation of β-catenin pathway contributes to the skin tumor phenotype.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.191284198
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2001
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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  • 5
    Online Resource
    Online Resource
    Immunogene therapy of tumors with vaccine based on Xenopus homologous vascular endothelial growth factor as a model antigen
    Proceedings of the National Academy of Sciences ; 2001
    In:  Proceedings of the National Academy of Sciences Vol. 98, No. 20 ( 2001-09-25), p. 11545-11550
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 20 ( 2001-09-25), p. 11545-11550
    Abstract: Overcoming immune tolerance of the growth factors associated with tumor growth should be a useful approach to cancer therapy by active immunity. We used vascular endothelial growth factor (VEGF) as a model antigen to explore the feasibility of the immunogene tumor therapy with a vaccine based on a single xenogeneic homologous gene, targeting the growth factors associated with angiogenesis. To test this concept, we constructed a plasmid DNA encoding Xenopus homologous VEGF (XVEGF-p) and control vectors. We found that immunogene tumor therapy with a vaccine based on XVEGF was effective at both protective and therapeutic antitumor immunity in several tumor models in mice. VEGF-specific autoantibodies in sera of mice immunized with XVEGF-p could be found in Western blotting analysis and ELISA assay. The purified immunoglobulins were effective at the inhibition of VEGF-mediated endothelial cell proliferation in vitro , and at antitumor activity and the inhibition of angiogenesis by adoptive transfer in vivo . The elevation of VEGF in the sera of the tumor-bearing mice could be abrogated with XVEGF-p immunization. The antitumor activity and production of VEGF-specific autoantibodies, significantly elevated IgG1 and IgG2b, could be abrogated by the depletion of CD4 + T lymphocytes. The observations may provide a vaccine strategy for cancer therapy through the induction of autoimmunity against the growth factors associated with tumor growth in a cross reaction with single xenogeneic homologous gene and may be of importance in the further exploration of the applications of other xenogeneic homologous genes identified in human and other animal genome sequence projects in cancer therapy.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.191112198
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2001
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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  • 6
    Online Resource
    Online Resource
    Comprehensive human genome amplification using multiple displacement amplification
    Proceedings of the National Academy of Sciences ; 2002
    In:  Proceedings of the National Academy of Sciences Vol. 99, No. 8 ( 2002-04-16), p. 5261-5266
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 8 ( 2002-04-16), p. 5261-5266
    Abstract: Fundamental to most genetic analysis is availability of genomic DNA of adequate quality and quantity. Because DNA yield from human samples is frequently limiting, much effort has been invested in developing methods for whole genome amplification (WGA) by random or degenerate oligonucleotide-primed PCR. However, existing WGA methods like degenerate oligonucleotide-primed PCR suffer from incomplete coverage and inadequate average DNA size. We describe a method, termed multiple displacement amplification (MDA), which provides a highly uniform representation across the genome. Amplification bias among eight chromosomal loci was less than 3-fold in contrast to 4–6 orders of magnitude for PCR-based WGA methods. Average product length was 〉 10 kb. MDA is an isothermal, strand-displacing amplification yielding about 20–30 μg product from as few as 1–10 copies of human genomic DNA. Amplification can be carried out directly from biological samples including crude whole blood and tissue culture cells. MDA-amplified human DNA is useful for several common methods of genetic analysis, including genotyping of single nucleotide polymorphisms, chromosome painting, Southern blotting and restriction fragment length polymorphism analysis, subcloning, and DNA sequencing. MDA-based WGA is a simple and reliable method that could have significant implications for genetic studies, forensics, diagnostics, and long-term sample storage.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.082089499
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2002
    detail.hit.zdb_id: 209104-5
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  • 7
    Online Resource
    Online Resource
    Remarkably diastereoselective synthesis of a chiral biphenyl diphosphine ligand and its application in asymmetric hydrogenation
    Proceedings of the National Academy of Sciences ; 2004
    In:  Proceedings of the National Academy of Sciences Vol. 101, No. 16 ( 2004-04-20), p. 5815-5820
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 101, No. 16 ( 2004-04-20), p. 5815-5820
    Abstract: Essentially complete atropdiastereoselectivity was realized in the preparation of biaryl diphosphine dioxide by asymmetric intramolecular Ullmann coupling and oxidative coupling with central-to-axial chirality transfer. A bridged C 2 -symmetric biphenyl phosphine ligand possessing additional chiral centers on the linking unit of the biphenyl groups was synthesized. No resolution step was required for the preparation of the enantiomerically pure chiral ligand. These findings offer a general and practical tool for the development of previously uninvestigated atropdiastereomeric biaryl phosphine ligands. The diphosphine ligand was found to be highly effective in the asymmetric hydrogenation of α- and β-ketoesters, 2-(6′-methoxy-2′-naphthyl)propenoic acid, β-(acylamino)acrylates, and enol acetates.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0307774101
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2004
    detail.hit.zdb_id: 209104-5
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  • 8
    Online Resource
    Online Resource
    Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-α
    Proceedings of the National Academy of Sciences ; 2001
    In:  Proceedings of the National Academy of Sciences Vol. 98, No. 21 ( 2001-10-09), p. 11879-11884
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 21 ( 2001-10-09), p. 11879-11884
    Abstract: The binding of tumor necrosis factor alpha (TNF-α) to the type-1 TNF receptor (TNFRc1) plays an important role in inflammation. Despite the clinical success of biologics (antibodies, soluble receptors) for treating TNF-based autoimmune conditions, no potent small molecule antagonists have been developed. Our screening of chemical libraries revealed that N -alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones were antagonists of this protein–protein interaction. After chemical optimization, we discovered IW927, which potently disrupted the binding of TNF-α to TNFRc1 (IC 50 = 50 nM) and also blocked TNF-stimulated phosphorylation of Iκ-B in Ramos cells (IC 50 = 600 nM). This compound did not bind detectably to the related cytokine receptors TNFRc2 or CD40, and did not display any cytotoxicity at concentrations as high as 100 μM. Detailed evaluation of this and related molecules revealed that compounds in this class are “photochemically enhanced” inhibitors, in that they bind reversibly to the TNFRc1 with weak affinity ( ca. 40–100 μM) and then covalently modify the receptor via a photochemical reaction. We obtained a crystal structure of IV703 (a close analog of IW927) bound to the TNFRc1. This structure clearly revealed that one of the aromatic rings of the inhibitor was covalently linked to the receptor through the main-chain nitrogen of Ala-62, a residue that has already been implicated in the binding of TNF-α to the TNFRc1. When combined with the fact that our inhibitors are reversible binders in light-excluded conditions, the results of the crystallography provide the basis for the rational design of nonphotoreactive inhibitors of the TNF-α–TNFRc1 interaction.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.211178398
    RVK:
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2001
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
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  • 9
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    Online Resource
    Giant magnetoresistance in organic spin-valves
    Springer Science and Business Media LLC ; 2004
    In:  Nature Vol. 427, No. 6977 ( 2004-2), p. 821-824
    Details
    In: Nature, Springer Science and Business Media LLC, Vol. 427, No. 6977 ( 2004-2), p. 821-824
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    URL: Article
    DOI: 10.1038/nature02325
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2004
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
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  • 10
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    Loss of signaling through the G protein, G z , results in abnormal platelet activation and altered responses to psychoactive drugs
    Proceedings of the National Academy of Sciences ; 2000
    In:  Proceedings of the National Academy of Sciences Vol. 97, No. 18 ( 2000-08-29), p. 9984-9989
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 97, No. 18 ( 2000-08-29), p. 9984-9989
    Abstract: Heterotrimeric G proteins mediate the earliest step in cell responses to external events by linking cell surface receptors to intracellular signaling pathways. G z is a member of the G i family of G proteins that is prominently expressed in platelets and brain. Here, we show that deletion of the α subunit of G z in mice: ( i ) impairs platelet aggregation by preventing the inhibition of cAMP formation normally seen at physiologic concentrations of epinephrine, and ( ii ) causes the mice to be more resistant to fatal thromboembolism. Loss of G zα also results in greatly exaggerated responses to cocaine, reduces the analgesic effects of morphine, and abolishes the effects of widely used antidepressant drugs that act as catecholamine reuptake inhibitors. These changes occur despite the presence of other G iα family members in the same cells and are not accompanied by detectable compensatory changes in the level of expression of other G protein subunits. Therefore, these results provide insights into receptor selectivity among G proteins and a model for understanding platelet function and the effects of psychoactive drugs.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.180194597
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2000
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
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