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  • 1
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    The highly expressed methionine synthase gene of Neurospora crassa is positively regulated by its proximal heterochromatic region (2014)
    Oxford University Press
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    Publication Date: 2014-06-03
    Description: In Neurospora crassa , the methionine synthase gene met-8 plays a key role in methionine synthesis. In this study, we found that MET-8 protein levels were compromised in several mutants defective in proper heterochromatin formation. Bioinformatics analysis revealed a 50-kb AT-rich region adjacent to the met-8 promoter. ChIP assays confirmed that trimethylated H3K9 was enriched in this region, indicating that heterochromatin may form upstream of met-8 . In an H3K9R mutant strain, the output of met-8 was dramatically reduced, similar to what we observed in mutant strains that had defective heterochromatin formation. Furthermore, the production of ectopically expressed met-8 at the his-3 locus in the absence of a normal heterochromatin environment was inefficient, whereas ectopic expression of met -8 downstream of two other heterochromatin domains was efficient. In addition, our data show that the expression of mig-6 was also controlled by an upstream 4.2-kb AT-rich region similar to that of the met-8 gene, and we demonstrate that the AT-rich regions adjacent to met-8 or mig-6 are required for their peak expression. Our study indicates that met-8 and mig-6 may represent a novel type of gene, whose expression relies on the proper formation of a nearby heterochromatin region.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 2
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    A competitive formation of DNA:RNA hybrid G-quadruplex is responsible to the mitochondrial transcription termination at the DNA replication priming site (2014)
    Oxford University Press
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    Publication Date: 2014-11-12
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 3
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    A competitive formation of DNA:RNA hybrid G-quadruplex is responsible to the mitochondrial transcription termination at the DNA replication priming site (2014)
    Oxford University Press
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    Publication Date: 2014-09-17
    Description: Human mitochondrial DNA contains a distinctive guanine-rich motif denoted conserved sequence block II (CSB II) that stops RNA transcription, producing prematurely terminated transcripts to prime mitochondrial DNA replication. Recently, we reported a general phenomenon that DNA:RNA hybrid G-quadruplexes (HQs) readily form during transcription when the non-template DNA strand is guanine-rich and such HQs in turn regulate transcription. In this work, we show that transcription of mitochondrial DNA leads to the formation of a stable HQ or alternatively an unstable intramolecular DNA G-quadruplex (DQ) at the CSB II. The HQ is the dominant species and contributes to the majority of the premature transcription termination. Manipulating the stability of the DQ has little effect on the termination even in the absence of HQ; however, abolishing the formation of HQs by preventing the participation of either DNA or RNA abolishes the vast majority of the termination. These results demonstrate that the type of G-quadruplexes (HQ or DQ) is a crucial determinant in directing the transcription termination at the CSB II and suggest a potential functionality of the co-transcriptionally formed HQ in DNA replication initiation. They also suggest that the competition/conversion between an HQ and a DQ may regulate the function of a G-quadruplex-forming sequence.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    Performance of protein-structure predictions with the physics-based UNRES force field in CASP11 (2016)
    Oxford University Press
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    Publication Date: 2016-10-26
    Description: : Participating as the Cornell-Gdansk group, we have used our physics-based coarse-grained UNited RESidue (UNRES) force field to predict protein structure in the 11th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP11). Our methodology involved extensive multiplexed replica exchange simulations of the target proteins with a recently improved UNRES force field to provide better reproductions of the local structures of polypeptide chains. All simulations were started from fully extended polypeptide chains, and no external information was included in the simulation process except for weak restraints on secondary structure to enable us to finish each prediction within the allowed 3-week time window. Because of simplified UNRES representation of polypeptide chains, use of enhanced sampling methods, code optimization and parallelization and sufficient computational resources, we were able to treat, for the first time, all 55 human prediction targets with sizes from 44 to 595 amino acid residues, the average size being 251 residues. Complete structures of six single-domain proteins were predicted accurately, with the highest accuracy being attained for the T0769, for which the CαRMSD was 3.8 Å for 97 residues of the experimental structure. Correct structures were also predicted for 13 domains of multi-domain proteins with accuracy comparable to that of the best template-based modeling methods. With further improvements of the UNRES force field that are now underway, our physics-based coarse-grained approach to protein-structure prediction will eventually reach global prediction capacity and, consequently, reliability in simulating protein structure and dynamics that are important in biochemical processes. Availability and Implementation: Freely available on the web at http://www.unres.pl/ . Contact: has5@cornell.edu
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
    Published by Oxford University Press
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  • 5
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    Two-year interactions between invasive Solidago canadensis and soil decrease its subsequent growth and competitive ability (2015)
    Oxford University Press
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    Publication Date: 2015-11-24
    Description: Aims Plant–soil interaction (PSI) has been implicated as a causative mechanism promoting plant invasions, and some mechanisms underlying PSI effects remain unclear. Here, we attempted to address how altered soil microbes and nutrients influence PSI effects. Methods Soil was cultured by an invasive forb Solidago canadensis for two years. We conducted an experiment, in which S. canadensis and Chinese natives were grown either alone or together in control and cultured soils, and determined the growth of S. canadensis and five natives and the competitive ability of S. canadensis . We analyzed the microbial community composition and nutrients of two types of soils. Important Findings Compared to the control soil, the soil cultured by S. canadensis decreased the subsequent growth of S. canadensis and five Chinese natives, as well as the competitive ability of S. canadensis against Chinese natives. Soil microbial community composition was significantly altered due to soil culturing. Total fatty acids, bacteria, Gram-negative bacteria and Gram-positive bacteria had no responses to soil culturing; fungi, aerobic bacteria and fungi/bacteria ratio significantly decreased with soil culturing; anaerobes and Gram-negative/positive bacteria ratio greatly increased with soil culturing. Soil nitrogen (N) dramatically decreased with soil culturing, whereas soil phosphorus (P) was unchanged. These results suggest that negative PSI effects may be linked to decreases in soil fungi, aerobic bacteria and soil N and increases in soil anaerobic bacteria and the ratio of Gram-negative/positive bacteria. Our findings provide an initial indication that S. canadensis– soil interaction alone could exhibit limited contributions to its success in the early stage of invasion.
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    Recognition and cleavage of 5-methylcytosine DNA by bacterial SRA-HNH proteins (2015)
    Oxford University Press
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    Publication Date: 2015-01-24
    Description: SET and RING-finger-associated (SRA) domain is involved in establishment and maintenance of DNA methylation in eukaryotes. Proteins containing SRA domains exist in mammals, plants, even microorganisms. It has been established that mammalian SRA domain recognizes 5-methylcytosine (5mC) through a base-flipping mechanism. Here, we identified and characterized two SRA domain-containing proteins with the common domain architecture of N-terminal SRA domain and C-terminal HNH nuclease domain, Sco5333 from Streptomyces coelicolo r and Tbis1 from Thermobispora bispora . Both sco5333 and tbis1 cannot establish in methylated Escherichia coli hosts ( dcm + ), and this in vivo toxicity requires both SRA and HNH domain. Purified Sco5333 and Tbis1 displayed weak DNA cleavage activity in the presence of Mg 2+ , Mn 2+ and Co 2+ and the cleavage activity was suppressed by Zn 2+ . Both Sco5333 and Tbis1 bind to 5mC-containing DNA in all sequence contexts and have at least a preference of 100 folds in binding affinity for methylated DNA over non-methylated one. We suggest that linkage of methyl-specific SRA domain and weakly active HNH domain may represent a universal mechanism in competing alien methylated DNA but to maximum extent minimizing damage to its own chromosome.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    RAN translation at CGG repeats induces ubiquitin proteasome system impairment in models of fragile X-associated tremor ataxia syndrome (2015)
    Oxford University Press
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    Publication Date: 2015-07-07
    Description: Fragile X-associated tremor ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a CGG trinucleotide repeat expansion in the 5' UTR of the Fragile X gene, FMR1 . FXTAS is thought to arise primarily from an RNA gain-of-function toxicity mechanism. However, recent studies demonstrate that the repeat also elicits production of a toxic polyglycine protein, FMRpolyG, via repeat-associated non-AUG (RAN)-initiated translation. Pathologically, FXTAS is characterized by ubiquitin-positive intranuclear neuronal inclusions, raising the possibility that failure of protein quality control pathways could contribute to disease pathogenesis. To test this hypothesis, we used Drosophila - and cell-based models of CGG-repeat-associated toxicity. In Drosophila , ubiquitin proteasome system (UPS) impairment led to enhancement of CGG-repeat-induced degeneration, whereas overexpression of the chaperone protein HSP70 suppressed this toxicity. In transfected mammalian cells, CGG repeat expression triggered accumulation of a UPS reporter in a length-dependent fashion. To delineate the contributions from CGG repeats as RNA from RAN translation-associated toxicity, we enhanced or impaired the production of FMRpolyG in these models. Driving expression of FMRpolyG enhanced induction of UPS impairment in cell models, while prevention of RAN translation attenuated UPS impairment in cells and suppressed the genetic interaction with UPS manipulation in Drosophila. Taken together, these findings suggest that CGG repeats induce UPS impairment at least in part through activation of RAN translation.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 8
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    Variation in plant diversity and dominance across dune fixation stages in the Chinese steppe zone (2012)
    Oxford University Press
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    Publication Date: 2012-07-10
    Description: Aims Our aim was to study how diversity and dominance of plant species and plant functional types (PFTs) change and covary across three dune fixation stages in the Chinese steppe zone. Methods In the Chinese steppe zone, we measured coverage, mean height and density of each plant species in three types of dunes (mobile, semi-fixed and fixed dunes) in four sites (Mu Us, Otindag, Hulunbeir and Horqin). Plant species were grouped into 24 PFTs according to their lifespan, photosynthetic pathway, reproductive mode and life form. Dominance of each plant species and PFT were determined, and species diversity and PFT diversity were quantified using Shannon–Wiener index. Important Findings PFT diversity was positively related to plant species diversity in each dune stage, but PFT diversity increased more with increasing plant species diversity in the mobile and semi-fixed dunes than in the fixed dunes. Dune fixation stage explained 87.2% of the variation in plant species diversity and 84.8% of the variation in PFT diversity. Dominant species and PFTs differed among the three dune fixation stages; the more fixed the dunes were, the more perennial, shrubby, clonal and C 3 species co-dominated. Specifically, in mobile dunes annual C 4 non-clonal herbs were the most dominant, and in semi-fixed and fixed dunes perennial C 3 clonal shrubs were most dominant.
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    External Sorting on Flash Memory Via Natural Page Run Generation (2011)
    Oxford University Press
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    Publication Date: 2011-11-24
    Description: The increasing popularity of flash memory means more database systems will run on flash memory in the future. One of the most important database operations is the external sort. Hence, this paper is focused on studying the problem of efficient external sorting on flash memory. In contrast to most previous work, we target the situation where previously sorted data have become progressively unsorted due to data updates. Accordingly, we call this ‘partially’ sorted data. We focus on re-sorting partially sorted data by taking advantage of the partial sorted nature of the data to speed up the run generation phase of the traditional external merge sort. We do this by finding ‘naturally occurring’ page runs in the partially sorted data. Our algorithm can perform up to a factor of 1024 less write IO compared with a traditional external merge sort during the run generation phase. We map the problem of finding naturally occurring runs into the shortest distance problem in a directed acyclic graph (DAG). Accordingly, we propose an optimal solution to the problem using the well-known DAG-Shortest-Paths algorithm. However, we found that the optimal solution was too slow for even moderate-sized data sets and accordingly propose a fast heuristic solution that—we experimentally show—finds a high percentage of page runs using a minimum of computational overhead. Experiments using both real and synthetic data sets show that our heuristic algorithm can halve the external sorting time when compared with three likely competing external sorting algorithms.
    Print ISSN: 0010-4620
    Electronic ISSN: 1460-2067
    Topics: Computer Science
    Published by Oxford University Press
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  • 10
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    The multitude of biodiversity: methods, theories and applications (2012)
    Oxford University Press
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    Publication Date: 2012-01-13
    Print ISSN: 1752-993X
    Electronic ISSN: 1752-9921
    Topics: Biology
    Published by Oxford University Press
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