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  • 1
    Online Resource
    Online Resource
    Protein kinase LKB1 regulates polarized dendrite formation of adult hippocampal newborn neurons
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 1 ( 2014-01-07), p. 469-474
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 1 ( 2014-01-07), p. 469-474
    Abstract: Adult-born granule cells in the dentate gyrus of the rodent hippocampus are important for memory formation and mood regulation, but the cellular mechanism underlying their polarized development, a process critical for their incorporation into functional circuits, remains unknown. We found that deletion of the serine-threonine protein kinase LKB1 or overexpression of dominant-negative LKB1 reduced the polarized initiation of the primary dendrite from the soma and disrupted its oriented growth toward the molecular layer. This abnormality correlated with the dispersion of Golgi apparatus that normally accumulated at the base and within the initial segment of the primary dendrite, and was mimicked by disrupting Golgi organization via altering the expression of Golgi structural proteins GM130 or GRASP65. Thus, besides its known function in axon formation in embryonic pyramidal neurons, LKB1 plays an additional role in regulating polarized dendrite morphogenesis in adult-born granule cells in the hippocampus.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1321454111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
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  • 2
    Online Resource
    Online Resource
    Menin promotes hepatocellular carcinogenesis and epigenetically up-regulates Yap1 transcription
    Proceedings of the National Academy of Sciences ; 2013
    In:  Proceedings of the National Academy of Sciences Vol. 110, No. 43 ( 2013-10-22), p. 17480-17485
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 43 ( 2013-10-22), p. 17480-17485
    Abstract: Menin is a scaffold protein encoded by the multiple endocrine neoplasia type 1 ( MEN1 ) gene in humans, and it interacts with a variety of transcriptional proteins to control active or repressive cellular processes. Here, we show that heterozygous ablation of Men1 in female mice reduces chemical carcinogen-induced liver carcinogenesis and represses the activation of the inflammation pathway. Using ChIP-on-chip screens and ChIP assays, we find that menin occupancy frequently coincides with H3K4me3 at the promoter of many liver cancer-related genes, such as Yes-associated protein (Yap1). Increased menin and Yap1 expression in human hepatocellular carcinoma specimens was associated with poor prognosis. Our findings reveal that menin plays an important epigenetic role in promoting liver tumorigenesis, and support the notion that H3K4me3, which is regulated by the menin–mixed-lineage leukemia complex, is a potential therapeutic target in hepatocellular carcinoma.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1312022110
    RVK:
    TA 1000
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    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
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  • 3
    Online Resource
    Online Resource
    Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 41 ( 2014-10-14), p. 14806-14811
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 41 ( 2014-10-14), p. 14806-14811
    Abstract: Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor. PDGF-CC deficiency by genetic deletion exacerbated blood vessel regression/degeneration in various animal models. Importantly, treatment with PDGF-CC protein not only increased the survival of retinal blood vessels in a model of oxygen-induced blood vessel regression but also markedly rescued retinal and blood vessel degeneration in a disease model of retinitis pigmentosa. Mechanistically, we revealed that heme oxygenase-1 (HMOX1) activity is critically required for the vascular protective/survival effect of PDGF-CC, because blockade of HMOX1 completely abolished the protective effect of PDGF-CC in vitro and in vivo. We further found that both PDGF receptors, PDGFR-β and PDGFR-α, are required for the vasoprotective effect of PDGF-CC. Thus our data show that PDGF-CC plays a pivotal role in maintaining blood vessel survival and may be of therapeutic value in treating various types of degenerative diseases.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1404140111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
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  • 4
    Online Resource
    Online Resource
    Exposure to ambient black carbon derived from a unique inventory and high-resolution model
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 7 ( 2014-02-18), p. 2459-2463
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 7 ( 2014-02-18), p. 2459-2463
    Abstract: Black carbon (BC) is increasingly recognized as a significant air pollutant with harmful effects on human health, either in its own right or as a carrier of other chemicals. The adverse impact is of particular concern in those developing regions with high emissions and a growing population density. The results of recent studies indicate that BC emissions could be underestimated by a factor of 2–3 and this is particularly true for the hot-spot Asian region. Here we present a unique inventory at 10-km resolution based on a recently published global fuel consumption data product and updated emission factor measurements. The unique inventory is coupled to an Asia-nested (∼50 km) atmospheric model and used to calculate the global population exposure to BC with fully quantified uncertainty. Evaluating the modeled surface BC concentrations against observations reveals great improvement. The bias is reduced from −88% to −35% in Asia when the unique inventory and higher-resolution model replace a previous inventory combined with a coarse-resolution model. The bias can be further reduced to −12% by downscaling to 10 km using emission as a proxy. Our estimated global population-weighted BC exposure concentration constrained by observations is 2.14 μg⋅m −3 ; 130% higher than that obtained using less detailed inventories and low-resolution models.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1318763111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    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
    Palmitoylation-dependent CDKL5–PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine development
    Proceedings of the National Academy of Sciences ; 2013
    In:  Proceedings of the National Academy of Sciences Vol. 110, No. 22 ( 2013-05-28), p. 9118-9123
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 22 ( 2013-05-28), p. 9118-9123
    Abstract: The X-linked gene cyclin-dependent kinase-like 5 ( CDKL5 ) is mutated in severe neurodevelopmental disorders, including some forms of atypical Rett syndrome, but the function and regulation of CDKL5 protein in neurons remain to be elucidated. Here, we show that CDKL5 binds to the scaffolding protein postsynaptic density (PSD)-95, and that this binding promotes the targeting of CDKL5 to excitatory synapses. Interestingly, this binding is not constitutive, but governed by palmitate cycling on PSD-95. Furthermore, pathogenic mutations that truncate the C-terminal tail of CDKL5 diminish its binding to PSD-95 and synaptic accumulation. Importantly, down-regulation of CDKL5 by RNA interference (RNAi) or interference with the CDKL5–PSD-95 interaction inhibits dendritic spine formation and growth. These results demonstrate a critical role of the palmitoylation-dependent CDKL5–PSD-95 interaction in localizing CDKL5 to synapses for normal spine development and suggest that disruption of this interaction by pathogenic mutations may be implicated in the pathogenesis of CDKL5-related disorders.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1300003110
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
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  • 6
    Online Resource
    Online Resource
    A tick-borne segmented RNA virus contains genome segments derived from unsegmented viral ancestors
    Proceedings of the National Academy of Sciences ; 2014
    In:  Proceedings of the National Academy of Sciences Vol. 111, No. 18 ( 2014-05-06), p. 6744-6749
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 111, No. 18 ( 2014-05-06), p. 6744-6749
    Abstract: Although segmented and unsegmented RNA viruses are commonplace, the evolutionary links between these two very different forms of genome organization are unclear. We report the discovery and characterization of a tick-borne virus—Jingmen tick virus (JMTV)—that reveals an unexpected connection between segmented and unsegmented RNA viruses. The JMTV genome comprises four segments, two of which are related to the nonstructural protein genes of the genus Flavivirus (family Flaviviridae), whereas the remaining segments are unique to this virus, have no known homologs, and contain a number of features indicative of structural protein genes. Remarkably, homology searching revealed that sequences related to JMTV were present in the cDNA library from Toxocara canis (dog roundworm; Nematoda), and that shared strong sequence and structural resemblances. Epidemiological studies showed that JMTV is distributed in tick populations across China, especially Rhipicephalus and Haemaphysalis spp., and experiences frequent host-switching and genomic reassortment. To our knowledge, JMTV is the first example of a segmented RNA virus with a genome derived in part from unsegmented viral ancestors.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1324194111
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2014
    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
    Electron transfer-based combination therapy of cisplatin with tetramethyl- p -phenylenediamine for ovarian, cervical, and lung cancers
    Proceedings of the National Academy of Sciences ; 2012
    In:  Proceedings of the National Academy of Sciences Vol. 109, No. 26 ( 2012-06-26), p. 10175-10180
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 109, No. 26 ( 2012-06-26), p. 10175-10180
    Abstract: The platinum-based chemotherapy is the standard treatment for several types of cancer. However, cancer cells often become refractory with time and most patients with serious cancers die of drug resistance. Recently, we have discovered a unique dissociative electron-transfer mechanism of action of cisplatin, the first and most widely used platinum-based anticancer drug. Here, we show that the combination of cisplatin with an exemplary biological electron donor, N , N , N ′, N ′-tetramethyl- p -phenylenediamine (TMPD), may overcome the resistance of cancer cells to cisplatin. Our steady-state absorption and fluorescence spectroscopic measurements confirm the effective dissociative electron-transfer reaction between TMPD and cisplatin. More significantly, we found that the combination of 100 μM TMPD with cisplatin enhances double-strand breaks of plasmid DNA by a factor of approximately 3.5 and dramatically reduces the viability of cisplatin-sensitive human cervical (HeLa) cancer cells and highly cisplatin-resistant human ovarian (NIH:OVCAR-3) and lung (A549) cancer cells. Furthermore, this combination enhances apoptosis and DNA fragmentation by factors of 2–5 compared with cisplatin alone. These results demonstrate that this combination treatment not only results in a strong synergetic effect, but also makes resistant cancer cells sensitive to cisplatin. Because cisplatin is the cornerstone agent for the treatment of a variety of human cancers (including testicular, ovarian, cervical, bladder, head/neck, and lung cancers), our results show both the potential to improve platinum-based chemotherapy of various human cancers and the promise of femtomedicine as an emerging frontier in advancing cancer therapy.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1203451109
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2012
    detail.hit.zdb_id: 209104-5
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  • 8
    Online Resource
    Online Resource
    Acetylation of Metabolic Enzymes Coordinates Carbon Source Utilization and Metabolic Flux
    American Association for the Advancement of Science (AAAS) ; 2010
    In:  Science Vol. 327, No. 5968 ( 2010-02-19), p. 1004-1007
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 327, No. 5968 ( 2010-02-19), p. 1004-1007
    Abstract: Lysine acetylation regulates many eukaryotic cellular processes, but its function in prokaryotes is largely unknown. We demonstrated that central metabolism enzymes in Salmonella were acetylated extensively and differentially in response to different carbon sources, concomitantly with changes in cell growth and metabolic flux. The relative activities of key enzymes controlling the direction of glycolysis versus gluconeogenesis and the branching between citrate cycle and glyoxylate bypass were all regulated by acetylation. This modulation is mainly controlled by a pair of lysine acetyltransferase and deacetylase, whose expressions are coordinated with growth status. Reversible acetylation of metabolic enzymes ensure that cells respond environmental changes via promptly sensing cellular energy status and flexibly altering reaction rates or directions. It represents a metabolic regulatory mechanism conserved from bacteria to mammals.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1179687
    RVK:
    TA 1000
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    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2010
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
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  • 9
    Online Resource
    Online Resource
    Giant surfactants provide a versatile platform for sub-10-nm nanostructure engineering
    Proceedings of the National Academy of Sciences ; 2013
    In:  Proceedings of the National Academy of Sciences Vol. 110, No. 25 ( 2013-06-18), p. 10078-10083
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 25 ( 2013-06-18), p. 10078-10083
    Abstract: The engineering of structures across different length scales is central to the design of novel materials with controlled macroscopic properties. Herein, we introduce a unique class of self-assembling materials, which are built upon shape- and volume-persistent molecular nanoparticles and other structural motifs, such as polymers, and can be viewed as a size-amplified version of the corresponding small-molecule counterparts. Among them, “giant surfactants” with precise molecular structures have been synthesized by “clicking” compact and polar molecular nanoparticles to flexible polymer tails of various composition and architecture at specific sites. Capturing the structural features of small-molecule surfactants but possessing much larger sizes, giant surfactants bridge the gap between small-molecule surfactants and block copolymers and demonstrate a duality of both materials in terms of their self-assembly behaviors. The controlled structural variations of these giant surfactants through precision synthesis further reveal that their self-assemblies are remarkably sensitive to primary chemical structures, leading to highly diverse, thermodynamically stable nanostructures with feature sizes around 10 nm or smaller in the bulk, thin-film, and solution states, as dictated by the collective physical interactions and geometric constraints. The results suggest that this class of materials provides a versatile platform for engineering nanostructures with sub-10-nm feature sizes. These findings are not only scientifically intriguing in understanding the chemical and physical principles of the self-assembly, but also technologically relevant, such as in nanopatterning technology and microelectronics.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1302606110
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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