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  • Oxford University Press  (128)
  • Wiley  (100)
  • American Geophysical Union  (20)
  • 1
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    GS-align for glycan structure alignment and similarity measurement (2015)
    Oxford University Press
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    Publication Date: 2015-08-08
    Description: Motivation: Glycans play critical roles in many biological processes, and their structural diversity is key for specific protein-glycan recognition. Comparative structural studies of biological molecules provide useful insight into their biological relationships. However, most computational tools are designed for protein structure, and despite their importance, there is no currently available tool for comparing glycan structures in a sequence order- and size-independent manner. Results: A novel method, GS-align, is developed for glycan structure alignment and similarity measurement. GS-align generates possible alignments between two glycan structures through iterative maximum clique search and fragment superposition. The optimal alignment is then determined by the maximum structural similarity score, GS-score, which is size-independent. Benchmark tests against the Protein Data Bank (PDB) N -linked glycan library and PDB homologous/non-homologous N -glycoprotein sets indicate that GS-align is a robust computational tool to align glycan structures and quantify their structural similarity. GS-align is also applied to template-based glycan structure prediction and monosaccharide substitution matrix generation to illustrate its utility. Availability and implementation: http://www.glycanstructure.org/gsalign . Contact: wonpil@ku.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 2
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    PINK1 positively regulates HDAC3 to suppress dopaminergic neuronal cell death (2015)
    Oxford University Press
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    Publication Date: 2015-01-25
    Description: Deciphering the molecular basis of neuronal cell death is a central issue in the etiology of neurodegenerative diseases, such as Parkinson's and Alzheimer's. Dysregulation of p53 levels has been implicated in neuronal apoptosis. The role of histone deacetylase 3 (HDAC3) in suppressing p53-dependent apoptosis has been recently emphasized; however, the molecular basis of modulation of p53 function by HDAC3 remains unclear. Here we show that PTEN-induced putative kinase 1 ( PINK1 ), which is linked to autosomal recessive early-onset familial Parkinson's disease, phosphorylates HDAC3 at Ser-424 to enhance its HDAC activity in a neural cell-specific manner. PINK1 prevents H 2 O 2 -induced C-terminal cleavage of HDAC3 via phosphorylation of HDAC3 at Ser-424, which is reversed by protein phosphatase 4c. PINK1-mediated phosphorylation of HDAC3 enhances its direct association with p53 and causes subsequent hypoacetylation of p53. Genetic deletion of PINK1 partly impaired the suppressive role of HDAC3 in regulating p53 acetylation and transcriptional activity. However, depletion of HDAC3 fully abolished the PINK1-mediated p53 inhibitory loop. Finally, ectopic expression of phosphomometic-HDAC3 S424E substantially overcomes the defective action of PINK1 against oxidative stress in dopaminergic neuronal cells. Together, our results uncovered a mechanism by which PINK1–HDAC3 network mediates p53 inhibitory loop in response to oxidative stress-induced damage.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 3
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    Global transcription network incorporating distal regulator binding reveals selective cooperation of cancer drivers and risk genes (2015)
    Oxford University Press
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    Publication Date: 2015-07-12
    Description: Global network modeling of distal regulatory interactions is essential in understanding the overall architecture of gene expression programs. Here, we developed a Bayesian probabilistic model and computational method for global causal network construction with breast cancer as a model. Whereas physical regulator binding was well supported by gene expression causality in general, distal elements in intragenic regions or loci distant from the target gene exhibited particularly strong functional effects. Modeling the action of long-range enhancers was critical in recovering true biological interactions with increased coverage and specificity overall and unraveling regulatory complexity underlying tumor subclasses and drug responses in particular. Transcriptional cancer drivers and risk genes were discovered based on the network analysis of somatic and genetic cancer-related DNA variants. Notably, we observed that the risk genes were functionally downstream of the cancer drivers and were selectively susceptible to network perturbation by tumorigenic changes in their upstream drivers. Furthermore, cancer risk alleles tended to increase the susceptibility of the transcription of their associated genes. These findings suggest that transcriptional cancer drivers selectively induce a combinatorial misregulation of downstream risk genes, and that genetic risk factors, mostly residing in distal regulatory regions, increase transcriptional susceptibility to upstream cancer-driving somatic changes.
    Keywords: Computational Methods, Genomics, Transcriptome Mapping - Monitoring Gene Expression
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    DJ-1 Associates with lipid rafts by palmitoylation and regulates lipid rafts-dependent endocytosis in astrocytes (2013)
    Oxford University Press
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    Publication Date: 2013-11-08
    Description: Parkinson's disease (PD) is the second most common progressive neurodegenerative disease. Several genes have been associated with familial type PD, providing tremendous insights into the pathogenesis of PD. Gathering evidence supports the view that these gene products may operate through common molecular pathways. Recent reports suggest that many PD-associated gene products, such as α-synuclein, LRRK2, parkin and PINK1, associate with lipid rafts and lipid rafts may be associated with neurodegeneration. Here, we observed that DJ-1 protein also associated with lipid rafts. Palmitoylation of three cysteine residues (C46/53/106) and C-terminal region of DJ-1 were required for this association. Lipopolysaccharide (LPS) induced the localization of DJ-1 into lipid rafts in astrocytes. The LPS-TLR4 signaling was more augmented in DJ-1 knock-out astrocytes by the impairment of TLR4 endocytosis. Furthermore, lipid rafts-dependent endocytosis including the endocytosis of CD14, which play a major role in regulating TLR4 endocytosis was also impaired, but clathrin-dependent endocytosis was not. This study provides a novel function of DJ-1 in lipid rafts, which may contribute the pathogenesis of PD. Moreover, it also provides the possibility that many PD-related proteins may operate through common molecular pathways in lipid rafts.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 5
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    Morphological indicators of a mascon beneath Ceres' largest crater, Kerwan (2018)
    Wiley
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    Publication Date: 2018-01-30
    Description: Gravity data of Ceres returned by NASA's Dawn spacecraft is consistent with a lower density crust of variable thickness overlying a higher density mantle. Crustal thickness variations can affect the long-term, post-impact modification of impact craters on Ceres. Here we show that the unusual morphology of the 280-km diameter crater Kerwan may result from viscous relaxation in an outer layer that thins substantially beneath the crater floor. We propose that such a structure is consistent with either impact-induced uplift of the high-density mantle beneath the crater or from volatile loss during the impact event. In either case, the subsurface structure inferred from the crater morphology is superisostatic, and the mass excess would result in a positive Bouguer anomaly beneath the crater, consistent with the highest-degree gravity data from Dawn. Ceres joins the Moon, Mars, and Mercury in having basin-associated gravity anomalies, although their origin may differ substantially.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 6
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    Plasmapause location under quiet geomagnetic conditions (Kp≤ 1): THEMIS observations (2015)
    Wiley
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    Publication Date: 2015-09-13
    Description: We statistically examined the plasmapause location ( L pp ) under quiet geomagnetic conditions ( K p ≤ 1) using the electron density inferred from the THEMIS spacecraft potential for two-year period (2008 and 2009). 543 L pp samples were identified under steady quiet conditions with K p values ≤ 1 during 12 hours prior to the plasmapause crossing. From our large data set, we determined the medians and means of L pp in L and MLT. They are located near geosynchronous orbit and nearly circular. The L pp medians show a slight bulge located in post-dusk sector. Comparing with previous models, our median or mean L pp is extended ∼1-2 L from the earth than the model L pp along the local time from 0800 to 2400 MLT. That is, L pp locations in the previous models are underestimated during quiet geomagnetic conditions.
    Print ISSN: 0094-8276
    Electronic ISSN: 1944-8007
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 7
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    Comprehensive analysis of the flux dropout during 7–8 November 2008 storm using multi-satellites observations and RBE model (2015)
    Wiley
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    Publication Date: 2015-05-09
    Description: We investigate an electron flux dropout during a weak storm on November 7–8, 2008, with Dst minimum value being −37 nT. During this period, two clear dropouts were observed on GOES-11 〉 2MeV electrons. We also find a simultaneous dropout in the sub-relativistic electrons recorded by THEMIS probes in the outer radiation belt. Using the Radiation Belt Environment (RBE) model, we try to reproduce the observed dropout features in both relativistic and sub-relativistic electrons. We found that there are local time dependences in the dropout for both observation and simulation in sub-relativistic electrons; (1) particle loss begins from nightside and propagates into dayside, and (2) resupply starts from near dawn MLT and propagates into the dayside following electron drift direction. That resupply of the particles might be caused by substorm injections due to enhanced convection. We found a significant precipitation in hundreds keV electrons during the dropout. We observe electromagnetic ion cyclotron (EMIC) and chorus waves both on the ground and in space. We find the drift shells are opened near the beginning of the first dropout. The dropout in MeV electrons at GEO might therefore be initiated due to the magnetopause shadowing and the followed dropout in hundreds keV electrons might be the result of the combination of magnetopause shadowing and precipitation loss into the earth's atmosphere.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 8
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    AGO2 and SETDB1 cooperate in promoter-targeted transcriptional silencing of the androgen receptor gene (2014)
    Oxford University Press
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    Publication Date: 2014-12-17
    Description: In mammals, RNA interference is primarily a post-transcriptional mechanism. Evidence has accumulated for additional role in transcriptional gene silencing (TGS) but the question for a good paradigm for small interfering antigene RNA (agRNA)-induced chromatin modification remains unanswered. Here, we show that SETDB1, a histone H3-lysine 9 (H3K9)-specific methyltransferase, cooperates with Argonaute-2 (AGO2) and plays an essential role in agRNA-induced TGS. The androgen receptor ( AR ) gene was transcriptionally silenced by agRNA targeted to its promoter, and we show that this repression was mitigated by knockdown of SETDB1 or AGO2 . Chromatin immunoprecipitation demonstrated that agRNA-driven AGO2 was first targeted to the AR promoter, followed by SETDB1. SIN3A and HDAC1/2, the components of the SIN3-HDAC complex, immunoprecipitated with SETDB1, and localized at the agRNA-targeted promoter. Agreeing with the presence of SETDB1, trimethyl-H3K9 was enriched in the AR promoter. Both EZH2 and trimethyl-H3K27 were also present in the targeted locus; accordingly, EZH2 immunoprecipitated with SETDB1. DNA methylation level was not significantly changed, suggesting the absence of de novo methylating activity in agRNA-induced AR promoter. Our results demonstrate that SETDB1, together with AGO2, plays an essential role in TGS through recruiting chromatin remodeler and/or other modifiers, consequently creating a repressive chromatin milieu at the targeted promoter.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    Solution structure of the Z-DNA binding domain of PKR-like protein kinase from Carassius auratus and quantitative analyses of the intermediate complex during B-Z transition (2016)
    Oxford University Press
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    Publication Date: 2016-04-08
    Description: Z-DNA binding proteins (ZBPs) play important roles in RNA editing, innate immune response and viral infection. Structural and biophysical studies show that ZBPs initially form an intermediate complex with B-DNA for B–Z conversion. However, a comprehensive understanding of the mechanism of Z-DNA binding and B–Z transition is still lacking, due to the absence of structural information on the intermediate complex. Here, we report the solution structure of the Zα domain of the ZBP-containing protein kinase from Carassius auratus (caZα PKZ ). We quantitatively determined the binding affinity of caZα PKZ for both B-DNA and Z-DNA and characterized its B–Z transition activity, which is modulated by varying the salt concentration. Our results suggest that the intermediate complex formed by caZα PKZ and B-DNA can be used as molecular ruler, to measure the degree to which DNA transitions to the Z isoform.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 10
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    Effects of algal food quality on sexual reproduction of Daphnia magna (2016)
    Wiley
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    Publication Date: 2016-03-23
    Description: The objective of our study was to investigate sexual reproduction of Daphnia magna associated with mating behaviors and hatching rates, according to different algal food sources. Since a diatom is known to contain more abundant long-chain poly unsaturated fatty acids (PUFAs), we hypothesized that the diatom-consuming D. magna would exhibit more successful reproduction rates. Upon the hypothesis, we designed three experiments using two algal species, a green alga ( Chlorella vulgaris ) and a diatom ( Stephanodiscus hantzschii ). From the results, we found that the mating frequency and copulation duration increased in the treatment with S. hantzschii , resulting in a significant increase of hatching rates of resting eggs. In the other two repetitive mating strategies (e.g., one female vs. multiple males, and one male vs. multiple females), we found that the hatching rates of resting eggs were greater in the S. hantzschii treatment. In addition to the mating strategy, male body size significantly increased in the diatom treatment, hence average diameter of penis was also statistically different among the treatments (greater diameter in the S. hantzschii treatment). To examine the effect of algal food quality, we estimated quantity of fatty acids in the two algal species. Our result showed that S. hantzschii had a higher proportion of long-chain PUFAs than C. vulgaris . Furthermore, a stable isotope analysis revealed that carbon and nitrogen originated from S. hantzschii were more assimilated to D. magna . In summary, our study manifested that diatom consumption of D. magna leads to more successful sexual reproduction. We then discussed how the diatom consumption of zooplankton influences food web dynamics in a freshwater ecosystem. Algal food quality is important for daphniids’ sexual reproduction, and the grazers’ sexual reproduction activity are strongly enhanced when a diatom was consumed than a green alga.
    Electronic ISSN: 2045-7758
    Topics: Biology
    Published by Wiley
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