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  • 1
    Publication Date: 2016-10-08
    Description: Retinoic acid-inducible gene I (RIG-I) recognizes specific molecular patterns of viral RNAs for inducing type I interferon. The C-terminal domain (CTD) of RIG-I binds to double-stranded RNA (dsRNA) with the 5'-triphosphate (5'-PPP), which induces a conformational change in RIG-I to an active form. It has been suggested that RIG-I detects infection of influenza A virus by recognizing the 5'-triphosphorylated panhandle structure of the viral RNA genome. Influenza panhandle RNA has a unique structure with a sharp helical bending. In spite of extensive studies of how viral RNAs activate RIG-I, whether the structural elements of the influenza panhandle RNA confer the ability to activate RIG-I signaling has been poorly explored. Here, we investigated the dynamics of the influenza panhandle RNA in complex with RIG-I CTD using NMR spectroscopy and showed that the bending structure of the panhandle RNA negates the requirement of a 5'-PPP moiety for RIG-I activation.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 2
    Publication Date: 2016-05-27
    Description: Vibrio parahaemolyticus is a Gram-negative, motile, nonspore-forming pathogen that causes foodborne illness associated with the consumption of contaminated seafoods. Although many cases of foodborne outbreaks caused by V. parahaemolyticus have been reported, the genomes of only five strains have been completely sequenced and analyzed using bioinformatics. In order to characterize overall virulence factors and pathogenesis of V. parahaemolyticus associated with foodborne outbreak in South Korea, a new strain FORC_008 was isolated from flounder fish and its genome was completely sequenced. The genomic analysis revealed that the genome of FORC_008 consists of two circular DNA chromosomes of 3266 132 bp (chromosome I) and 1772 036 bp (chromosome II) with a GC content of 45.36% and 45.53%, respectively. The entire genome contains 4494 predicted open reading frames, 129 tRNAs and 31 rRNA genes. While the strain FORC_008 does not have genes encoding thermostable direct hemolysin (TDH) and TDH-related hemolysin (TRH), its genome encodes many other virulence factors including hemolysins, pathogenesis-associated secretion systems and iron acquisition systems, suggesting that it may be a potential pathogen. This report provides an extended understanding on V. parahaemolyticus in genomic level and would be helpful for rapid detection, epidemiological investigation and prevention of foodborne outbreak in South Korea.
    Print ISSN: 0928-8244
    Topics: Biology , Medicine
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  • 3
    Publication Date: 2014-08-27
    Description: Motivation: Time-evolving differential protein–protein interaction (PPI) networks are essential to understand serial activation of differentially regulated (up- or downregulated) cellular processes (DRPs) and their interplays over time. Despite developments in the network inference, current methods are still limited in identifying temporal transition of structures of PPI networks, DRPs associated with the structural transition and the interplays among the DRPs over time. Results: Here, we present a probabilistic model for estimating Time-Evolving differential PPI networks with MultiPle Information (TEMPI). This model describes probabilistic relationships among network structures, time-course gene expression data and Gene Ontology biological processes (GOBPs). By maximizing the likelihood of the probabilistic model, TEMPI estimates jointly the time-evolving differential PPI networks (TDNs) describing temporal transition of PPI network structures together with serial activation of DRPs associated with transiting networks. This joint estimation enables us to interpret the TDNs in terms of temporal transition of the DRPs. To demonstrate the utility of TEMPI, we applied it to two time-course datasets. TEMPI identified the TDNs that correctly delineated temporal transition of DRPs and time-dependent associations between the DRPs. These TDNs provide hypotheses for mechanisms underlying serial activation of key DRPs and their temporal associations. Availability and implementation: Source code and sample data files are available at http://sbm.postech.ac.kr/tempi/sources.zip . Contact: seungjin@postech.ac.kr or dhwang@dgist.ac.kr Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 4
    Publication Date: 2015-05-24
    Description: We study the early stage of the formation of seed supermassive black holes via direct collapse in dark matter (DM) haloes, in the cosmological context. We perform high-resolution zoom-in simulations of such collapse at high z . Using the adaptive mesh refinement code enzo , we resolve the formation and growth of a DM halo, until its virial temperature reaches ~10 4  K, atomic cooling turns on, and collapse ensues. We demonstrate that direct collapse proceeds in two stages, although they are not well separated. The first stage is triggered by the onset of atomic cooling, and leads to rapidly increasing accretion rate with radius, from $\dot{M}\sim 0.1\,\mathrm{M}_{\odot }\,{\rm yr^{-1}}$ at the halo virial radius to few M yr –1 , around the scale radius R s ~ 30 pc of the NFW DM density profile. The second stage of the collapse commences when the gas density takes precedence over the DM density. This is associated with the gas decoupling from the DM gravitational potential. The ensuing collapse approximates that of an isothermal sphere with $\dot{M}{(r)}\sim$  const. We confirm that the gas loses its angular momentum through non-axisymmetric perturbations and gravitational torques, to overcome the centrifugal barrier. During the course of the collapse, this angular momentum transfer process happens on nearly all spatial scales, and the angular momentum vector of the gas varies with position and time. Collapsing gas also exhibits supersonic turbulent motions which suppress gas fragmentation, and are characterized by density PDF consisting of a lognormal part and a high-density power-law tail.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 5
    Publication Date: 2014-12-11
    Description: Parametric study of a hydraulic centrifugal pump with backward curved blades has been performed numerically using three-dimensional Reynolds-averaged Navier-Stokes equations. The shear stress transport turbulence model was used for analysis of turbulence. The finite volume method and an unstructured grid system were used for the numerical solution. The optimal grid system in the computational domain was selected through a grid dependency test. Tested parameters were related to the geometry of the impeller and volute: seven variables defining the hub and shroud contours and the blades angle of impeller, and two variables defining the inlet width and expansion angle of volute. The effects of these parameters on the hydrodynamic performance of the centrifugal pump have been investigated. It was found that the centrifugal water pump with the twisted blades has the enhancing efficiency compared to the straight blades pump.
    Print ISSN: 1755-1307
    Electronic ISSN: 1755-1315
    Topics: Geography , Geosciences , Physics
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  • 6
    Publication Date: 2016-09-20
    Description: Cosmic reionization by starlight from early galaxies affected their evolution, thereby impacting reionization itself. Star formation suppression, for example, may explain the observed underabundance of Local Group dwarfs relative to N -body predictions for cold dark matter. Reionization modelling requires simulating volumes large enough [~ (100 Mpc) 3 ] to sample reionization ‘patchiness’, while resolving millions of galaxy sources above ~10 8 M combining gravitational and gas dynamics with radiative transfer. Modelling the Local Group requires initial cosmological density fluctuations pre-selected to form the well-known structures of the Local Universe today. Cosmic Dawn (‘CoDa’) is the first such fully coupled, radiation-hydrodynamics simulation of reionization of the Local Universe. Our new hybrid CPU-GPU code, ramses-cudaton , performs hundreds of radiative transfer and ionization rate-solver timesteps on the GPUs for each hydro-gravity timestep on the CPUs. CoDa simulated (91Mpc) 3 with 4096 3 particles and cells, to redshift 4.23, on ORNL supercomputer Titan, utilizing 8192 cores and 8192 GPUs. Global reionization ended slightly later than observed. However, a simple temporal rescaling which brings the evolution of ionized fraction into agreement with observations also reconciles ionizing flux density, cosmic star formation history, CMB electron scattering optical depth and galaxy UV luminosity function with their observed values. Photoionization heating suppressed the star formation of haloes below ~2  x  10 9 M , decreasing the abundance of faint galaxies around M AB 1600  = [–10, –12]. For most of reionization, star formation was dominated by haloes between 10 10 –10 11 M , so low-mass halo suppression was not reflected by a distinct feature in the global star formation history. Intergalactic filaments display sheathed structures, with hot envelopes surrounding cooler cores, but do not self-shield, unlike regions denser than 100 〈〉.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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  • 7
    Publication Date: 2014-02-28
    Description: The nucleotide excision repair pathway removes ultraviolet (UV) photoproducts from the human genome in the form of short oligonucleotides ~30 nt in length. Because there are limitations to many of the currently available methods for investigating UV photoproduct repair in vivo , we developed a convenient non-radioisotopic method to directly detect DNA excision repair events in human cells. The approach involves extraction of oligonucleotides from UV-irradiated cells, DNA end-labeling with biotin and streptavidin-mediated chemiluminescent detection of the excised UV photoproduct-containing oligonucleotides that are released from the genome during excision repair. Our novel approach is robust, with essentially no signal in the absence of UV or a functional excision repair system. Furthermore, our non-radioisotopic methodology allows for the sensitive detection of excision products within minutes following UV irradiation and does not require additional enrichment steps such as immunoprecipitation. Finally, this technique allows for quantitative measurements of excision repair in human cells. We suggest that the new techniques presented here will be a useful and powerful approach for studying the mechanism of human nucleotide excision repair in vivo .
    Keywords: Repair
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 8
    Publication Date: 2012-05-22
    Description: Motivation: Gene clusters are arrangements of functionally related genes on a chromosome. In bacteria, it is expected that evolutionary pressures would conserve these arrangements due to the functional advantages they provide. Visualization of conserved gene clusters across multiple genomes provides key insights into their evolutionary histories. Therefore, a software tool that enables visualization and functional analyses of gene clusters would be a great asset to the biological research community. Results: We have developed GeneclusterViz, a Java-based tool that allows for the visualization, exploration and downstream analyses of conserved gene clusters across multiple genomes. GeneclusterViz combines an easy-to-use exploration interface for gene clusters with a host of other analysis features such as multiple sequence alignments, phylogenetic analyses and integration with the KEGG pathway database. Availability: http://biohealth.snu.ac.kr/GeneclusterViz/ ; http://microbial.informatics.indiana.edu/GeneclusterViz/ Contact: sunkim.bioinfo@snu.ac.kr ; ybrun@indiana.edu Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 9
    Publication Date: 2014-04-03
    Description: In the present study, we investigated the 3' untranslated region (UTR) of the mouse core clock gene cryptochrome 1 ( Cry1 ) at the post-transcriptional level, particularly its translational regulation. Interestingly, the 3'UTR of Cry1 mRNA decreased its mRNA levels but increased protein amounts. The 3'UTR is widely known to function as a cis -acting element of mRNA degradation. The 3'UTR also provides a binding site for microRNA and mainly suppresses translation of target mRNAs. We found that AU-rich element RNA binding protein 1 (AUF1) directly binds to the Cry1 3'UTR and regulates translation of Cry1 mRNA. AUF1 interacted with eukaryotic translation initiation factor 3 subunit B and also directly associated with ribosomal protein S3 or ribosomal protein S14, resulting in translation of Cry1 mRNA in a 3'UTR-dependent manner. Expression of cytoplasmic AUF1 and binding of AUF1 to the Cry1 3'UTR were parallel to the circadian CRY1 protein profile. Our results suggest that the 3'UTR of Cry1 is important for its rhythmic translation, and AUF1 bound to the 3'UTR facilitates interaction with the 5' end of mRNA by interacting with translation initiation factors and recruiting the 40S ribosomal subunit to initiate translation of Cry1 mRNA.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 10
    Publication Date: 2014-03-21
    Description: Recent observations have indicated the existence of dust in high-redshift galaxies, however, the dust properties in them are still unknown. Here we present theoretical constraints on dust properties in Lyman-break galaxies (LBGs) at z  = 3 by post-processing a cosmological smoothed particle hydrodynamics simulation with radiative transfer calculations. We calculate the dust extinction in 2800 dark matter haloes using the metallicity information of individual gas particles in our simulation. We use only bright galaxies with rest-frame ultraviolet (UV) magnitude M 1700  〈 –20 mag, and study the dust size, dust-to-metal mass ratio, and dust composition. From the comparison of calculated colour excess between B and V band [i.e. E ( B  –  V )] and the observations, we constrain the typical dust size, and show that the best-fitting dust grain size is ~ 0.05 μm, which is consistent with the results of theoretical dust models for Type II supernova. Our simulation with the dust extinction effect can naturally reproduce the observed rest-frame UV luminosity function of LBGs at z  = 3 without assuming an ad hoc constant extinction value. In addition, in order to reproduce the observed mean E ( B  –  V ), we find that the dust-to-metal mass ratio needs to be similar to that of the local galaxies, and that the graphite dust is dominant or at least occupy half of dust mass.
    Print ISSN: 0035-8711
    Electronic ISSN: 1365-2966
    Topics: Physics
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