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  • Proceedings of the National Academy of Sciences  (16)
  • English  (16)
  • 2000-2004  (16)
  • Biodiversity Research  (16)
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  • Proceedings of the National Academy of Sciences  (16)
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  • English  (16)
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  • 2000-2004  (16)
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  • 1
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2004
    In:  Proceedings of the National Academy of Sciences Vol. 101, No. 51 ( 2004-12-21), p. 17611-17615
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 101, No. 51 ( 2004-12-21), p. 17611-17615
    Abstract: The migratory locust is one of the most notorious agricultural pests that undergo a well known reversible, density-dependent phase transition from the solitary to the gregarious. To demonstrate the underlying molecular mechanisms of the phase change, we generated 76,012 ESTs from the whole body and dissected organs in the two phases. Comparing 12,161 unigene clusters, we identified 532 genes as phase-related ( P 〈 0.01). Comprehensive assessment of the phase-related expression revealed that, whereas most of the genes in various categories from hind legs and the midgut are down-regulated in the gregarious phase, several gene classes in the head are impressively up-regulated, including those with peptidase, receptor, and oxygen-binding activities and those related to development, cell growth, and responses to external stimuli. Among them, a superfamily of proteins, the JHPH super-family, which includes j uvenile hormone-binding protein, h examerins, p rophenoloxidase, and h emocyanins, were highly expressed in the heads of the gregarious hoppers and hind legs of the solitary hoppers. Quantitative PCR experiments confirmed in part the EST results. These differentially regulated genes have strong functional implications that numerous molecular activities are involved in phase plasticity. This study provides ample molecular markers and genomic information on hemimetabolous insects and insights into the genetic and molecular mechanisms of phase changes in locusts.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2004
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  • 2
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 6 ( 2002-03-19), p. 3872-3877
    Abstract: Essential hypertension has a heritability as high as 30–50%, but its genetic cause(s) has not been determined despite intensive investigation. The renal dopaminergic system exerts a pivotal role in maintaining fluid and electrolyte balance and participates in the pathogenesis of genetic hypertension. In genetic hypertension, the ability of dopamine and D 1 -like agonists to increase urinary sodium excretion is impaired. A defective coupling between the D 1 dopamine receptor and the G protein/effector enzyme complex in the proximal tubule of the kidney is the cause of the impaired renal dopaminergic action in genetic rodent and human essential hypertension. We now report that, in human essential hypertension, single nucleotide polymorphisms of a G protein-coupled receptor kinase, GRK4 γ, increase G protein-coupled receptor kinase (GRK) activity and cause the serine phosphorylation and uncoupling of the D 1 receptor from its G protein/effector enzyme complex in the renal proximal tubule and in transfected Chinese hamster ovary cells. Moreover, expressing GRK4 γ A142V but not the wild-type gene in transgenic mice produces hypertension and impairs the diuretic and natriuretic but not the hypotensive effects of D 1 -like agonist stimulation. These findings provide a mechanism for the D 1 receptor coupling defect in the kidney and may explain the inability of the kidney to properly excrete sodium in genetic hypertension.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2002
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 4 ( 2003-02-18), p. 1603-1608
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 4 ( 2003-02-18), p. 1603-1608
    Abstract: Understanding binding properties at protein–protein interfaces has been limited to structural and mutational analyses of natural binding partners or small peptides identified by phage display. Here, we present a high-resolution analysis of a nonpeptidyl small molecule, previously discovered by medicinal chemistry [Tilley, J. W., et al . (1997) J. Am. Chem. Soc. 119, 7589–7590], which binds to the cytokine IL-2. The small molecule binds to the same site that binds the IL-2 α receptor and buries into a groove not seen in the free structure of IL-2. Comparison of the bound and several free structures shows this site to be composed of two subsites: one is rigid, and the other is highly adaptive. Thermodynamic data suggest the energy barriers between these conformations are low. The subsites were dissected by using a site-directed screening method called tethering, in which small fragments were captured by disulfide interchange with cysteines introduced into IL-2 around these subsites. X-ray structures with the tethered fragments show that the subsite-binding interactions are similar to those observed with the original small molecule. Moreover, the adaptive subsite tethered many more compounds than did the rigid one. Thus, the adaptive nature of a protein–protein interface provides sites for small molecules to bind and underscores the challenge of applying structure-based design strategies that cannot accurately predict a dynamic protein surface.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2003
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 14 ( 2003-07-08), p. 8314-8318
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 14 ( 2003-07-08), p. 8314-8318
    Abstract: Here we report the discovery of eight specimens of an Early Cambrian fossil tunicate Shankouclava near Kunming (South China). The tunicate identity of this organism is supported by the presence of a large and perforated branchial basket, a sac-like peri-pharyngeal atrium, an oral siphon with apparent oral tentacles at the basal end of the siphonal chamber, perhaps a dorsal atrial pore, and an elongated endostyle on the mid-ventral floor of the pharynx. As in most modern tunicates, the gut is simple and U-shaped, and is connected with posterior end of the pharynx at one end and with an atrial siphon at the other, anal end. Shankouclava differs from Cheungkongella , which was previously called a tunicate. Based on new, more complete “ Cheungkongella ” specimens that show branching tentacles, this form may be a lophophorate, and in any case is not a tunicate.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2003
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2002
    In:  Proceedings of the National Academy of Sciences Vol. 99, No. 20 ( 2002-10), p. 12747-12752
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 20 ( 2002-10), p. 12747-12752
    Abstract: Overproduction of the Her2 oncoprotein has been found in ≈30% of breast tumors, and patients who have Her2 excesses typically have more aggressive disease. Here we show that the expression of the Her2 gene can be decreased by inhibiting the interaction of the two cancer-linked proteins, DRIP130/CRSP130/Sur-2 (a Ras-linked subunit of human mediator complexes) and ESX (an epithelial-restricted transcription factor). Disruption of the interaction by a short cell-permeable peptide reduced the expression of the Her2 gene and specifically impaired the growth and viability of Her2-overexpressing breast cancer cells. The association of ESX with DRIP130 is mediated by a small hydrophobic face of an 8-aa helix in ESX, suggesting a therapeutic approach to incapacitating the Her2 gene by small organic molecules.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2002
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    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
    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
    RVK:
    RVK:
    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
    SSG: 11
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 9 ( 2003-04-29), p. 5103-5106
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 9 ( 2003-04-29), p. 5103-5106
    Abstract: RNA interference is an effective method to silence specific gene expression. Its application to mammalian cells, however, has been hampered by various shortcomings. Recently, it was reported that introduction of 22-bp double-stranded RNAs (dsRNAs) would specifically suppress expression of endogenous and heterogeneous genes in various mammalian cell lines. However, using this method, we failed to knock out proteins of interest effectively. Here we report the development of a stable and controllable method for generating dsRNA intracellularly. Tetracycline-responsive transactivator-containing cells were transfected with a vector capable of tetracycline-induced bidirectionally overexpressing sense and antisense RNA to form dsRNA in vivo . With this method, glutaredoxin, monitored by Western blot, was knocked out by overexpressing 290-base sense and antisense RNA in NIH 3T3 cells controlled by tetracycline or doxycycline. By using these glutaredoxin knocked-out cells, we have demonstrated that actin deglutathionylation plays a key role in growth factor-mediated actin polymerization, translocalization, and reorganization near the cell periphery.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2003
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2002
    In:  Proceedings of the National Academy of Sciences Vol. 99, No. 6 ( 2002-03-19), p. 3546-3551
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 6 ( 2002-03-19), p. 3546-3551
    Abstract: The migration of vascular endothelial cells (ECs) is critical in vascular remodeling. We showed that fluid shear stress enhanced EC migration in flow direction and called this “mechanotaxis.” To visualize the molecular dynamics of focal adhesion kinase (FAK) at focal adhesions (FAs), FAK tagged with green fluorescence protein (GFP) was expressed in ECs. Within 10 min of shear stress application, lamellipodial protrusion was induced at cell periphery in the flow direction, with the recruitment of FAK at FAs. ECs under flow migrated with polarized formation of new FAs in flow direction, and these newly formed FAs subsequently disassembled after the rear of the cell moved over them. The cells migrating under flow had a decreased number of FAs. In contrast to shear stress, serum did not significantly affect the speed of cell migration. Serum induced lamellipodia and FAK recruitment at FAs without directional preference. FAK(Y397) phosphorylation colocalized with GFP-FAK at FAs in both shear stress and serum experiments. The total level of FAK(Y397) phosphorylation after shear stress was lower than that after serum treatment, suggesting that the polarized change at cell periphery rather than the total level of FAK(Y397) phosphorylation is important for directional migration. Our results demonstrate the dynamics of FAK at FAs during the directional migration of EC in response to mechanical force, and suggest that mechanotaxis is an important mechanism controlling EC migration.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2002
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2003
    In:  Proceedings of the National Academy of Sciences Vol. 100, No. 19 ( 2003-09-16), p. 10635-10640
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 100, No. 19 ( 2003-09-16), p. 10635-10640
    Abstract: ATRX syndrome is characterized by X-linked mental retardation associated with α-thalassemia. The gene mutated in this disease, ATRX , encodes a plant homeodomain-like finger and a SWI2/SNF2-like ATPase motif, both of which are often found in chromatin-remodeling enzymes, but ATRX has not been characterized biochemically. By immunoprecipitation from HeLa extract, we found that ATRX is in a complex with transcription cofactor Daxx. The following evidence supports that ATRX and Daxx are components of an ATP-dependent chromatin-remodeling complex: ( i ) Daxx and ATRX can be coimmunoisolated by antibodies specific for each protein; ( ii ) a proportion of Daxx cofractionates with ATRX as a complex of 1 MDa by gel-filtration analysis; ( iii ) in extract from cells of a patient with ATRX syndrome, the level of the Daxx–ATRX complex is correspondingly reduced; ( iv ) a proportion of ATRX and Daxx colocalize in promyelocytic leukemia nuclear bodies, with which Daxx had previously been located; and ( v ) the ATRX complex displays ATP-dependent activities that resemble those of other chromatin-remodeling complexes, including triple-helix DNA displacement and alteration of mononucleosome disruption patterns. But unlike the previously described SWI/SNF or NURD complexes, the ATRX complex does not randomize DNA phasing of the mononucleosomes, suggesting that it may remodel chromatin differently. Taken together, the results suggest that ATRX functions in conjunction with Daxx in a novel chromatin-remodeling complex. The defects in ATRX syndrome may result from inappropriate expression of genes controlled by this complex.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2003
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 10
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2002
    In:  Proceedings of the National Academy of Sciences Vol. 99, No. 6 ( 2002-03-19), p. 4091-4096
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 99, No. 6 ( 2002-03-19), p. 4091-4096
    Abstract: The peripheral accessory chlorophylls (Chls) of the photosystem II (PSII) reaction center (RC) are coordinated by a pair of symmetry-related histidine residues (D1-H118 and D2-H117). These Chls participate in energy transfer from the proximal antennae complexes (CP43 and CP47) to the RC core chromophores. In addition, one or both of the peripheral Chls are redox-active and participate in a low-quantum-yield electron transfer cycle around PSII. We demonstrate that conservative mutations of the D2-H117 residue result in decreased Chl fluorescence quenching efficiency attributed to reduced accumulation of the peripheral accessory Chl cation, Chl \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{Z}^{+}}}\end{equation*}\end{document} . In contrast, identical symmetry-related mutations at residue D1-H118 had no effect on Chl fluorescence yield or quenching kinetics. Mutagenesis of the D2-H117 residue also altered the line width of the Chl \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}{\mathrm{_{Z}^{+}}}\end{equation*}\end{document} EPR signal, but the line shape of the D1-H118Q mutant remained unchanged. The D1-H118 and D2-H117 mutations also altered energy transfer properties in PSII RCs. Unlike wild type or the D1-H118Q mutant, D2-H117N RCs exhibited a reduced CD doublet in the red region of Chl absorbance band, indicative of reduced energetic coupling between P680 and the peripheral accessory Chl. In addition, transient absorption measurements of D2-H117N RCs, excited on the blue side of the Chl absorbance band, exhibited a (≈400 fs) pheophytin Q X band bleach lifetime component not seen in wild-type or D1-H118Q RCs. The origin of this component may be related to delayed fast-energy equilibration of the excited state between the core pigments of this mutant.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2002
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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