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  • Oxford University Press  (38)
  • American Association for the Advancement of Science (AAAS)  (11)
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  • 11
    Publication Date: 2015-12-16
    Description: Escherichia coli topoisomerase I has an essential function in preventing hypernegative supercoiling of DNA. A full length structure of E. coli topoisomerase I reported here shows how the C-terminal domains bind single-stranded DNA (ssDNA) to recognize the accumulation of negative supercoils in duplex DNA. These C-terminal domains of E. coli topoisomerase I are known to interact with RNA polymerase, and two flexible linkers within the C-terminal domains may assist in the movement of the ssDNA for the rapid removal of transcription driven negative supercoils. The structure has also unveiled for the first time how the 4-Cys zinc ribbon domain and zinc ribbon-like domain bind ssDNA with primarily -stacking interactions. This novel structure, in combination with new biochemical data, provides important insights into the mechanism of genome regulation by type IA topoisomerases that is essential for life, as well as the structures of homologous type IA TOP3α and TOP3β from higher eukaryotes that also have multiple 4-Cys zinc ribbon domains required for their physiological functions.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 12
    Publication Date: 2016-06-11
    Description: We study a geometric analogue of the Iwasawa Main Conjecture for constant ordinary abelian varieties over $\mathbb {Z}_p^d$ -extensions of function fields ramifying at a finite set of places.
    Print ISSN: 0024-6115
    Electronic ISSN: 1460-244X
    Topics: Mathematics
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  • 13
    Publication Date: 2016-09-02
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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  • 14
    Publication Date: 2015-02-18
    Description: The SOS response is a DNA damage response pathway that serves as a general safeguard of genome integrity in bacteria. Extensive studies of the SOS response in Escherichia coli have contributed to establishing the key concepts of cellular responses to DNA damage. However, how the SOS response impacts on the dynamics of DNA replication fork movement remains unknown. We found that inducing the SOS response decreases the mean speed of individual replication forks by 30–50% in E. coli cells, leading to a 20–30% reduction in overall DNA synthesis. dinB and recA belong to a group of genes that are upregulated during the SOS response, and encode the highly conserved proteins DinB (also known as DNA polymerase IV) and RecA, which, respectively, specializes in translesion DNA synthesis and functions as the central recombination protein. Both genes were independently responsible for the SOS-dependent slowdown of replication fork progression. Furthermore, fork speed was reduced when each gene was ectopically expressed in SOS-uninduced cells to the levels at which they are expressed in SOS-induced cells. These results clearly indicate that the increased expression of dinB and recA performs a novel role in restraining the progression of an unperturbed replication fork during the SOS response.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 15
    Publication Date: 2016-01-31
    Description: Superconductors with periodically ordered mesoporous structures are expected to have properties very different from those of their bulk counterparts. Systematic studies of such phenomena to date are sparse, however, because of a lack of versatile synthetic approaches to such materials. We demonstrate the formation of three-dimensionally continuous gyroidal mesoporous niobium nitride (NbN) superconductors from chiral ABC triblock terpolymer self-assembly–directed sol-gel–derived niobium oxide with subsequent thermal processing in air and ammonia gas. Superconducting materials exhibit a critical temperature ( T c ) of about 7 to 8 K, a flux exclusion of about 5% compared to a dense NbN solid, and an estimated critical current density ( J c ) of 440 A cm –2 at 100 Oe and 2.5 K. We expect block copolymer self-assembly–directed mesoporous superconductors to provide interesting subjects for mesostructure-superconductivity correlation studies.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 16
    Publication Date: 2011-11-24
    Print ISSN: 1367-0751
    Electronic ISSN: 1368-9894
    Topics: Mathematics
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  • 17
    Publication Date: 2019
    Description: 〈p〉Dynamic nuclear polarization (DNP) has evolved as the method of choice to enhance NMR signal intensities and to address a variety of otherwise inaccessible chemical, biological and physical questions. Despite its success, there is no detailed understanding of how the large electron polarization is transferred to the surrounding nuclei or where these nuclei are located relative to the polarizing agent. To address these questions we perform an analysis of the three-spin solid effect, and show that it is exquisitely sensitive to the electron-nuclear distances. We exploit this feature and determine that the size of the spin diffusion barrier surrounding the trityl radical in a glassy glycerol–water matrix is 1H ENDOR experiments indicate that polarization is then transferred in a second step to glycerol molecules in intimate contact with the trityl.〈/p〉
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
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  • 18
    Publication Date: 2014-04-29
    Description: Direct observations using digital videography in an aquarium showed that hairs on the valve surfaces of Modiolus traillii are not periostracal in origin, as often assumed for similar features in other mussels, but are secreted and planted individually by the foot, so they are correctly termed ‘byssal hairs’. Deposition of byssal hair occurred most frequently just after dark, and the time taken to form a strand of serrated hair varied between slightly more than 1 min to almost 10 min, with a mean time of 4.4 min. We observed one individual deposit a total of 11 hairs in 3.5 h. The formation of some 25 hairs were successfully observed on video for six individuals, and about 3,000 individual hairs from 12 mussels were measured in relation to their position, size and density. While hairs varied considerably in length and width, they are consistently flattened, with one edge bearing serrations and the other edge being smooth. Long hair required more time to form compared with shorter hair, and longer hair was deposited farther away from the byssal gape towards the posterior end of the valves. However, a higher density of short hair was laid around the byssal gape. Smaller mussels tended to have an overall higher density of hair compared with larger individuals. There was no discernible pattern in the order in which long and short hairs were secreted on the periostracal surfaces of either valve. Byssal hair microstructure was generally consistent with the distal region of byssal threads, having a tough but thin outer cortex surrounding a ‘spongy’ honeycomb matrix.
    Print ISSN: 0260-1230
    Electronic ISSN: 1464-3766
    Topics: Biology
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  • 19
    Publication Date: 2014-02-28
    Description: Combinatorial interactions among transcription factors (TFs) are critical for integrating diverse intrinsic and extrinsic signals, fine-tuning regulatory output and increasing the robustness and plasticity of regulatory systems. Current knowledge about combinatorial regulation is rather limited due to the lack of suitable experimental technologies and bioinformatics tools. The rapid accumulation of ChIP-Seq data has provided genome-wide occupancy maps for a large number of TFs and chromatin modification marks for identifying enhancers without knowing individual TF binding sites. Integration of the two data types has not been researched extensively, resulting in underused data and missed opportunities. We describe a novel method for discovering frequent combinatorial occupancy patterns by multiple TFs at enhancers. Our method is based on probabilistic item set mining and takes into account uncertainty in both types of ChIP-Seq data. By joint analysis of 108 TFs in four human cell types, we found that cell–type-specific interactions among TFs are abundant and that the majority of enhancers have flexible architecture. We show that several families of transposable elements disproportionally overlap with enhancers with combinatorial patterns, suggesting that these transposable element families play an important role in the evolution of combinatorial regulation.
    Keywords: Computational Methods, Massively Parallel (Deep) Sequencing, Genomics
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 20
    Publication Date: 2014-08-06
    Description: Motivation : Disease progression is driven by dynamic changes in both the activity and connectivity of molecular pathways. Understanding these dynamic events is critical for disease prognosis and effective treatment. Compared with activity dynamics, connectivity dynamics is poorly explored. Results: We describe the M-module algorithm to identify gene modules with common members but varied connectivity across multiple gene co-expression networks (aka M-modules). We introduce a novel metric to capture the connectivity dynamics of an entire M-module. We find that M-modules with dynamic connectivity have distinct topological and biochemical properties compared with static M-modules and hub genes. We demonstrate that incorporation of module connectivity dynamics significantly improves disease stage prediction. We identify different sets of M-modules that are important for specific disease stage transitions and offer new insights into the molecular events underlying disease progression. Besides modeling disease progression, the algorithm and metric introduced here are broadly applicable to modeling dynamics of molecular pathways. Availability and implementation: M-module is implemented in R. The source code is freely available at http://www.healthcare.uiowa.edu/labs/tan/M-module.zip . Contact: kai-tan@uiowa.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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