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Sample records for intron rna circles

  1. The ability to form full-length intron RNA circles is a general property of nuclear group I introns

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Fiskaa, Tonje; Birgisdottir, Asa Birna

    2003-01-01

    at the expense of the host. The circularization pathway has distinct structural requirements that differ from those of splicing and appears to be specifically suppressed in vivo. The ability to form full-length circles is found in all types of nuclear group I introns, including those from the Tetrahymena...... ribosomal DNA. The biological function of the full-length circles is not known, but the fact that the circles contain the entire genetic information of the intron suggests a role in intron mobility....

  2. Archaeal rRNA operons, intron splicing and homing endonucleases, RNA polymerase operons and phylogeny

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    Garrett, Roger Antony; Aagaard, Claus Sindbjerg; Andersen, Morten

    1994-01-01

    Over the past decade our laboratory has had a strong interest in defining the phylogenetic status of the archaea. This has involved determining and analysing the sequences of operons of both rRNAs and RNA polymerases and it led to the discovery of the first archaeal rRNA intron. What follows...

  3. Characterization of the molecular basis of group II intron RNA recognition by CRS1-CRM domains.

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    Keren, Ido; Klipcan, Liron; Bezawork-Geleta, Ayenachew; Kolton, Max; Shaya, Felix; Ostersetzer-Biran, Oren

    2008-08-22

    CRM (chloroplast RNA splicing and ribosome maturation) is a recently recognized RNA-binding domain of ancient origin that has been retained in eukaryotic genomes only within the plant lineage. Whereas in bacteria CRM domains exist as single domain proteins involved in ribosome maturation, in plants they are found in a family of proteins that contain between one and four repeats. Several members of this family with multiple CRM domains have been shown to be required for the splicing of specific plastidic group II introns. Detailed biochemical analysis of one of these factors in maize, CRS1, demonstrated its high affinity and specific binding to the single group II intron whose splicing it facilitates, the plastid-encoded atpF intron RNA. Through its association with two intronic regions, CRS1 guides the folding of atpF intron RNA into its predicted "catalytically active" form. To understand how multiple CRM domains cooperate to achieve high affinity sequence-specific binding to RNA, we analyzed the RNA binding affinity and specificity associated with each individual CRM domain in CRS1; whereas CRM3 bound tightly to the RNA, CRM1 associated specifically with a unique region found within atpF intron domain I. CRM2, which demonstrated only low binding affinity, also seems to form specific interactions with regions localized to domains I, III, and IV. We further show that CRM domains share structural similarities and RNA binding characteristics with the well known RNA recognition motif domain.

  4. Group II intron inhibits conjugative relaxase expression in bacteria by mRNA targeting

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    Piazza, Carol Lyn; Smith, Dorie

    2018-01-01

    Group II introns are mobile ribozymes that are rare in bacterial genomes, often cohabiting with various mobile elements, and seldom interrupting housekeeping genes. What accounts for this distribution has not been well understood. Here, we demonstrate that Ll.LtrB, the group II intron residing in a relaxase gene on a conjugative plasmid from Lactococcus lactis, inhibits its host gene expression and restrains the naturally cohabiting mobile element from conjugative horizontal transfer. We show that reduction in gene expression is mainly at the mRNA level, and results from the interaction between exon-binding sequences (EBSs) in the intron and intron-binding sequences (IBSs) in the mRNA. The spliced intron targets the relaxase mRNA and reopens ligated exons, causing major mRNA loss. Taken together, this study provides an explanation for the distribution and paucity of group II introns in bacteria, and suggests a potential force for those introns to evolve into spliceosomal introns. PMID:29905149

  5. The distribution, diversity, and importance of 16S rRNA gene introns in the order Thermoproteales.

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    Jay, Zackary J; Inskeep, William P

    2015-07-09

    Intron sequences are common in 16S rRNA genes of specific thermophilic lineages of Archaea, specifically the Thermoproteales (phylum Crenarchaeota). Environmental sequencing (16S rRNA gene and metagenome) from geothermal habitats in Yellowstone National Park (YNP) has expanded the available datasets for investigating 16S rRNA gene introns. The objectives of this study were to characterize and curate archaeal 16S rRNA gene introns from high-temperature habitats, evaluate the conservation and distribution of archaeal 16S rRNA introns in geothermal systems, and determine which "universal" archaeal 16S rRNA gene primers are impacted by the presence of intron sequences. Several new introns were identified and their insertion loci were constrained to thirteen locations across the 16S rRNA gene. Many of these introns encode homing endonucleases, although some introns were short or partial sequences. Pyrobaculum, Thermoproteus, and Caldivirga 16S rRNA genes contained the most abundant and diverse intron sequences. Phylogenetic analysis of introns revealed that sequences within the same locus are distributed biogeographically. The most diverse set of introns were observed in a high-temperature, circumneutral (pH 6) sulfur sediment environment, which also contained the greatest diversity of different Thermoproteales phylotypes. The widespread presence of introns in the Thermoproteales indicates a high probability of misalignments using different "universal" 16S rRNA primers employed in environmental microbial community analysis.

  6. Natural RNA circles function as efficient microRNA sponges

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    Hansen, Thomas Birkballe; Jensen, Trine I; Clausen, Bettina Hjelm

    2013-01-01

    MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so-called comp......MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that act by direct base pairing to target sites within untranslated regions of messenger RNAs. Recently, miRNA activity has been shown to be affected by the presence of miRNA sponge transcripts, the so......-called competing endogenous RNA in humans and target mimicry in plants. We previously identified a highly expressed circular RNA (circRNA) in human and mouse brain. Here we show that this circRNA acts as a miR-7 sponge; we term this circular transcript ciRS-7 (circular RNA sponge for miR-7). ciRS-7 contains more...... sponge, suggesting that miRNA sponge effects achieved by circRNA formation are a general phenomenon. This study serves as the first, to our knowledge, functional analysis of a naturally expressed circRNA....

  7. An intronic microRNA silences genes that are functionally antagonistic to its host gene.

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    Barik, Sailen

    2008-09-01

    MicroRNAs (miRNAs) are short noncoding RNAs that down-regulate gene expression by silencing specific target mRNAs. While many miRNAs are transcribed from their own genes, nearly half map within introns of 'host' genes, the significance of which remains unclear. We report that transcriptional activation of apoptosis-associated tyrosine kinase (AATK), essential for neuronal differentiation, also generates miR-338 from an AATK gene intron that silences a family of mRNAs whose protein products are negative regulators of neuronal differentiation. We conclude that an intronic miRNA, transcribed together with the host gene mRNA, may serve the interest of its host gene by silencing a cohort of genes that are functionally antagonistic to the host gene itself.

  8. High-throughput sequencing of human plasma RNA by using thermostable group II intron reverse transcriptases

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    Qin, Yidan; Yao, Jun; Wu, Douglas C.; Nottingham, Ryan M.; Mohr, Sabine; Hunicke-Smith, Scott; Lambowitz, Alan M.

    2016-01-01

    Next-generation RNA-sequencing (RNA-seq) has revolutionized transcriptome profiling, gene expression analysis, and RNA-based diagnostics. Here, we developed a new RNA-seq method that exploits thermostable group II intron reverse transcriptases (TGIRTs) and used it to profile human plasma RNAs. TGIRTs have higher thermostability, processivity, and fidelity than conventional reverse transcriptases, plus a novel template-switching activity that can efficiently attach RNA-seq adapters to target RNA sequences without RNA ligation. The new TGIRT-seq method enabled construction of RNA-seq libraries from RNA in RNA in 1-mL plasma samples from a healthy individual revealed RNA fragments mapping to a diverse population of protein-coding gene and long ncRNAs, which are enriched in intron and antisense sequences, as well as nearly all known classes of small ncRNAs, some of which have never before been seen in plasma. Surprisingly, many of the small ncRNA species were present as full-length transcripts, suggesting that they are protected from plasma RNases in ribonucleoprotein (RNP) complexes and/or exosomes. This TGIRT-seq method is readily adaptable for profiling of whole-cell, exosomal, and miRNAs, and for related procedures, such as HITS-CLIP and ribosome profiling. PMID:26554030

  9. The mitochondrial LSU rRNA group II intron of Ustilago maydis encodes an active homing endonuclease likely involved in intron mobility.

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    Anja Pfeifer

    Full Text Available BACKGROUND: The a2 mating type locus gene lga2 is critical for uniparental mitochondrial DNA inheritance during sexual development of Ustilago maydis. Specifically, the absence of lga2 results in biparental inheritance, along with efficient transfer of intronic regions in the large subunit rRNA gene between parental molecules. However, the underlying role of the predicted LAGLIDADG homing endonuclease gene I-UmaI located within the group II intron LRII1 has remained unresolved. METHODOLOGY/PRINCIPAL FINDINGS: We have investigated the enzymatic activity of I-UmaI in vitro based on expression of a tagged full-length and a naturally occurring mutant derivative, which harbors only the N-terminal LAGLIDADG domain. This confirmed Mg²⁺-dependent endonuclease activity and cleavage at the LRII1 insertion site to generate four base pair extensions with 3' overhangs. Specifically, I-UmaI recognizes an asymmetric DNA sequence with a minimum length of 14 base pairs (5'-GACGGGAAGACCCT-3' and tolerates subtle base pair substitutions within the homing site. Enzymatic analysis of the mutant variant indicated a correlation between the activity in vitro and intron homing. Bioinformatic analyses revealed that putatively functional or former functional I-UmaI homologs are confined to a few members within the Ustilaginales and Agaricales, including the phylogenetically distant species Lentinula edodes, and are linked to group II introns inserted into homologous positions in the LSU rDNA. CONCLUSIONS/SIGNIFICANCE: The present data provide strong evidence that intron homing efficiently operates under conditions of biparental inheritance in U. maydis. Conversely, uniparental inheritance may be critical to restrict the transmission of mobile introns. Bioinformatic analyses suggest that I-UmaI-associated introns have been acquired independently in distant taxa and are more widespread than anticipated from available genomic data.

  10. Use of a Fluorescent Aptamer RNA as an Exonic Sequence to Analyze Self-Splicing Ability of a Group I Intron from Structured RNAs

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    Airi Furukawa

    2016-11-01

    Full Text Available Group I self-splicing intron constitutes an important class of functional RNA molecules that can promote chemical transformation. Although the fundamental mechanism of the auto-excision from its precursor RNA has been established, convenient assay systems for its splicing activity are still useful for a further understanding of its detailed mechanism and of its application. Because some host RNA sequences, to which group I introns inserted form stable three-dimensional (3D structures, the effects of the 3D structures of exonic elements on the splicing efficiency of group I introns are important but not a fully investigated issue. We developed an assay system for group I intron self-splicing by employing a fluorescent aptamer RNA (spinach RNA as a model exonic sequence inserted by the Tetrahymena group I intron. We investigated self-splicing of the intron from spinach RNA, serving as a model exonic sequence with a 3D structure.

  11. Diversity in mRNA expression of the serine-type carboxypeptidase ocpG in Aspergillus oryzae through intron retention.

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    Ishida, Ken; Kuboshima, Megumi; Morita, Hiroto; Maeda, Hiroshi; Okamoto, Ayako; Takeuchi, Michio; Yamagata, Youhei

    2014-01-01

    Alternative splicing is thought to be a means for diversification of products by mRNA modification. Although some intron retentions are predicted by transcriptome analysis in Aspergillus oryzae, its physiological significance remains unknown. We found that intron retention occurred occasionally in the serine-type carboxypeptidase gene, ocpG. Analysis under various culture conditions revealed that extracellular nitrogen conditions influence splicing patterns; this suggested that there might be a correlation between splicing efficiency and the necessity of OcpG activity for obtaining a nitrogen source. Since further analysis showed that splicing occurred independently in each intron, we constructed ocpG intron-exchanging strain by interchanging the positions of intron-1 and intron-2. The splicing pattern indicated the probability that ocpG intron retention was affected by the secondary structures of intronic mRNA.

  12. Regulation of mRNA Levels by Decay-Promoting Introns that Recruit the Exosome Specificity Factor Mmi1

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    Cornelia Kilchert

    2015-12-01

    Full Text Available In eukaryotic cells, inefficient splicing is surprisingly common and leads to the degradation of transcripts with retained introns. How pre-mRNAs are committed to nuclear decay is unknown. Here, we uncover a mechanism by which specific intron-containing transcripts are targeted for nuclear degradation in fission yeast. Sequence elements within these “decay-promoting” introns co-transcriptionally recruit the exosome specificity factor Mmi1, which induces degradation of the unspliced precursor and leads to a reduction in the levels of the spliced mRNA. This mechanism negatively regulates levels of the RNA helicase DDX5/Dbp2 to promote cell survival in response to stress. In contrast, fast removal of decay-promoting introns by co-transcriptional splicing precludes Mmi1 recruitment and relieves negative expression regulation. We propose that decay-promoting introns facilitate the regulation of gene expression. Based on the identification of multiple additional Mmi1 targets, including mRNAs, long non-coding RNAs, and sn/snoRNAs, we suggest a general role in RNA regulation for Mmi1 through transcript degradation.

  13. Recruitment of Staufen2 Enhances Dendritic Localization of an Intron-Containing CaMKIIα mRNA

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    Raúl Ortiz

    2017-07-01

    Full Text Available Regulation of mRNA localization is a conserved cellular process observed in many types of cells and organisms. Asymmetrical mRNA distribution plays a particularly important role in the nervous system, where local translation of localized mRNA represents a key mechanism in synaptic plasticity. CaMKIIα is a very abundant mRNA detected in neurites, consistent with its crucial role at glutamatergic synapses. Here, we report the presence of CaMKIIα mRNA isoforms that contain intron i16 in dendrites, RNA granules, and synaptoneurosomes from primary neurons and brain. This subpopulation of unspliced mRNA preferentially localizes to distal dendrites in a synaptic-activity-dependent manner. Staufen2, a well-established marker of RNA transport in dendrites, interacts with intron i16 sequences and enhances its distal dendritic localization, pointing to the existence of intron-mediated mechanisms in the molecular pathways that modulate dendritic transport and localization of synaptic mRNAs.

  14. A Two-Piece Derivative of a Group I Intron RNA as a Platform for Designing Self-Assembling RNA Templates to Promote Peptide Ligation

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    Takahiro Tanaka

    2012-01-01

    Full Text Available Multicomponent RNA-peptide complexes are attractive from the viewpoint of artificial design of functional biomacromolecular systems. We have developed self-folding and self-assembling RNAs that serve as templates to assist chemical ligation between two reactive peptides with RNA-binding capabilities. The design principle of previous templates, however, can be applied only to limited classes of RNA-binding peptides. In this study, we employed a two-piece derivative of a group I intron RNA from the Tetrahymena large subunit ribosomal RNA (LSU rRNA as a platform for new template RNAs. In this group I intron-based self-assembling platform, modules for the recognition of substrate peptides can be installed independently from modules holding the platform structure. The new self-assembling platform allows us to expand the repertoire of substrate peptides in template RNA design.

  15. Biotechnological applications of mobile group II introns and their reverse transcriptases: gene targeting, RNA-seq, and non-coding RNA analysis.

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    Enyeart, Peter J; Mohr, Georg; Ellington, Andrew D; Lambowitz, Alan M

    2014-01-13

    Mobile group II introns are bacterial retrotransposons that combine the activities of an autocatalytic intron RNA (a ribozyme) and an intron-encoded reverse transcriptase to insert site-specifically into DNA. They recognize DNA target sites largely by base pairing of sequences within the intron RNA and achieve high DNA target specificity by using the ribozyme active site to couple correct base pairing to RNA-catalyzed intron integration. Algorithms have been developed to program the DNA target site specificity of several mobile group II introns, allowing them to be made into 'targetrons.' Targetrons function for gene targeting in a wide variety of bacteria and typically integrate at efficiencies high enough to be screened easily by colony PCR, without the need for selectable markers. Targetrons have found wide application in microbiological research, enabling gene targeting and genetic engineering of bacteria that had been intractable to other methods. Recently, a thermostable targetron has been developed for use in bacterial thermophiles, and new methods have been developed for using targetrons to position recombinase recognition sites, enabling large-scale genome-editing operations, such as deletions, inversions, insertions, and 'cut-and-pastes' (that is, translocation of large DNA segments), in a wide range of bacteria at high efficiency. Using targetrons in eukaryotes presents challenges due to the difficulties of nuclear localization and sub-optimal magnesium concentrations, although supplementation with magnesium can increase integration efficiency, and directed evolution is being employed to overcome these barriers. Finally, spurred by new methods for expressing group II intron reverse transcriptases that yield large amounts of highly active protein, thermostable group II intron reverse transcriptases from bacterial thermophiles are being used as research tools for a variety of applications, including qRT-PCR and next-generation RNA sequencing (RNA-seq). The

  16. Enzyme engineering through evolution: thermostable recombinant group II intron reverse transcriptases provide new tools for RNA research and biotechnology.

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    Collins, Kathleen; Nilsen, Timothy W

    2013-08-01

    Current investigation of RNA transcriptomes relies heavily on the use of retroviral reverse transcriptases. It is well known that these enzymes have many limitations because of their intrinsic properties. This commentary highlights the recent biochemical characterization of a new family of reverse transcriptases, those encoded by group II intron retrohoming elements. The novel properties of these enzymes endow them with the potential to revolutionize how we approach RNA analyses.

  17. A distant cis acting intronic element induces site-selective RNA editing

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    Daniel, Chammiran; Venø, Morten Trillingsgaard; Ekdahl, Ylva

    2012-01-01

    Transcripts have been found to be site selectively edited from adenosine-to-inosine (A-to-I) in the mammalian brain, mostly in genes involved in neurotransmission. While A-to-I editing occurs at double-stranded structures, other structural requirements are largely unknown. We have investigated...... shown to be important for A-to-I editing. We demonstrate that the element also can induce editing in related but normally not edited RNA sequences. In human, thousands of genes are edited in duplexes formed by inverted repeats in non-coding regions. It is likely that numerous such duplexes can induce...... the requirements for editing at the I/M site in the Gabra-3 transcript of the GABA(A) receptor. We identify an evolutionarily conserved intronic duplex, 150 nt downstream of the exonic hairpin where the I/M site resides, which is required for its editing. This is the first time a distant RNA structure has been...

  18. The fission yeast RNA binding protein Mmi1 regulates meiotic genes by controlling intron specific splicing and polyadenylation coupled RNA turnover.

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    Huei-Mei Chen

    Full Text Available The polyA tails of mRNAs are monitored by the exosome as a quality control mechanism. We find that fission yeast, Schizosaccharomyces pombe, adopts this RNA quality control mechanism to regulate a group of 30 or more meiotic genes at the level of both splicing and RNA turnover. In vegetative cells the RNA binding protein Mmi1 binds to the primary transcripts of these genes. We find the novel motif U(U/C/GAAAC highly over-represented in targets of Mmi1. Mmi1 can specifically regulate the splicing of particular introns in a transcript: it inhibits the splicing of introns that are in the vicinity of putative Mmi1 binding sites, while allowing the splicing of other introns that are far from such sites. In addition, binding of Mmi1, particularly near the 3' end, alters 3' processing to promote extremely long polyA tails of up to a kilobase. The hyperadenylated transcripts are then targeted for degradation by the nuclear exonuclease Rrp6. The nuclear polyA binding protein Pab2 assists this hyperadenylation-mediated RNA decay. Rrp6 also targets other hyperadenylated transcripts, which become hyperadenylated in an unknown, but Mmi1-independent way. Thus, hyperadenylation may be a general signal for RNA degradation. In addition, binding of Mmi1 can affect the efficiency of 3' cleavage. Inactivation of Mmi1 in meiosis allows meiotic expression, through splicing and RNA stabilization, of at least 29 target genes, which are apparently constitutively transcribed.

  19. The Mitochondrial Genome of the Prasinophyte Prasinoderma coloniale Reveals Two Trans-Spliced Group I Introns in the Large Subunit rRNA Gene

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    Pombert, Jean-François; Otis, Christian; Turmel, Monique; Lemieux, Claude

    2013-01-01

    Organelle genes are often interrupted by group I and or group II introns. Splicing of these mobile genetic occurs at the RNA level via serial transesterification steps catalyzed by the introns'own tertiary structures and, sometimes, with the help of external factors. These catalytic ribozymes can be found in cis or trans configuration, and although trans-arrayed group II introns have been known for decades, trans-spliced group I introns have been reported only recently. In the course of sequencing the complete mitochondrial genome of the prasinophyte picoplanktonic green alga Prasinoderma coloniale CCMP 1220 (Prasinococcales, clade VI), we uncovered two additional cases of trans-spliced group I introns. Here, we describe these introns and compare the 54,546 bp-long mitochondrial genome of Prasinoderma with those of four other prasinophytes (clades II, III and V). This comparison underscores the highly variable mitochondrial genome architecture in these ancient chlorophyte lineages. Both Prasinoderma trans-spliced introns reside within the large subunit rRNA gene (rnl) at positions where cis-spliced relatives, often containing homing endonuclease genes, have been found in other organelles. In contrast, all previously reported trans-spliced group I introns occur in different mitochondrial genes (rns or coxI). Each Prasinoderma intron is fragmented into two pieces, forming at the RNA level a secondary structure that resembles those of its cis-spliced counterparts. As observed for other trans-spliced group I introns, the breakpoint of the first intron maps to the variable loop L8, whereas that of the second is uniquely located downstream of P9.1. The breakpoint In each Prasinoderma intron corresponds to the same region where the open reading frame (ORF) occurs when present in cis-spliced orthologs. This correlation between the intron breakpoint and the ORF location in cis-spliced orthologs also holds for other trans-spliced introns; we discuss the possible implications

  20. The mitochondrial genome of the prasinophyte Prasinoderma coloniale reveals two trans-spliced group I introns in the large subunit rRNA gene.

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    Jean-François Pombert

    Full Text Available Organelle genes are often interrupted by group I and or group II introns. Splicing of these mobile genetic occurs at the RNA level via serial transesterification steps catalyzed by the introns'own tertiary structures and, sometimes, with the help of external factors. These catalytic ribozymes can be found in cis or trans configuration, and although trans-arrayed group II introns have been known for decades, trans-spliced group I introns have been reported only recently. In the course of sequencing the complete mitochondrial genome of the prasinophyte picoplanktonic green alga Prasinoderma coloniale CCMP 1220 (Prasinococcales, clade VI, we uncovered two additional cases of trans-spliced group I introns. Here, we describe these introns and compare the 54,546 bp-long mitochondrial genome of Prasinoderma with those of four other prasinophytes (clades II, III and V. This comparison underscores the highly variable mitochondrial genome architecture in these ancient chlorophyte lineages. Both Prasinoderma trans-spliced introns reside within the large subunit rRNA gene (rnl at positions where cis-spliced relatives, often containing homing endonuclease genes, have been found in other organelles. In contrast, all previously reported trans-spliced group I introns occur in different mitochondrial genes (rns or coxI. Each Prasinoderma intron is fragmented into two pieces, forming at the RNA level a secondary structure that resembles those of its cis-spliced counterparts. As observed for other trans-spliced group I introns, the breakpoint of the first intron maps to the variable loop L8, whereas that of the second is uniquely located downstream of P9.1. The breakpoint In each Prasinoderma intron corresponds to the same region where the open reading frame (ORF occurs when present in cis-spliced orthologs. This correlation between the intron breakpoint and the ORF location in cis-spliced orthologs also holds for other trans-spliced introns; we discuss the

  1. The function of introns

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    Liran eCarmel

    2012-04-01

    Full Text Available The intron-exon architecture of many eukaryotic genes raises the intriguing question of whether this unique organization serves any function, or is it simply a result of the spread of functionless introns in eukaryotic genomes. In this review, we show that introns in contemporary species fulfill a broad spectrum of functions, and are involved in virtually every step of mRNA processing. We propose that this great diversity of intronic functions supports the notion that introns were indeed selfish elements in early eukaryotes, but then independently gained numerous functions in different eukaryotic lineages. We suggest a novel criterion of evolutionary conservation, dubbed intron positional conservation, which can identify functional introns.

  2. Degradation of YRA1 Pre-mRNA in the cytoplasm requires translational repression, multiple modular intronic elements, Edc3p, and Mex67p.

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    Shuyun Dong

    2010-04-01

    Full Text Available Intron-containing pre-mRNAs are normally retained and processed in the nucleus but are sometimes exported to the cytoplasm and degraded by the nonsense-mediated mRNA decay (NMD pathway as a consequence of their inclusion of intronic in-frame termination codons. When shunted to the cytoplasm by autoregulated nuclear export, the intron-containing yeast YRA1 pre-mRNA evades NMD and is targeted by a cytoplasmic decay pathway mediated by the decapping activator Edc3p. Here, we have elucidated this transcript-specific decay mechanism, showing that Edc3p-mediated YRA1 pre-mRNA degradation occurs independently of translation and is controlled through five structurally distinct but functionally interdependent modular elements in the YRA1 intron. Two of these elements target the pre-mRNA as an Edc3p substrate and the other three mediate transcript-specific translational repression. Translational repression of YRA1 pre-mRNA also requires the heterodimeric Mex67p/Mtr2p general mRNA export receptor, but not Edc3p, and serves to enhance Edc3p substrate specificity by inhibiting the susceptibility of this pre-mRNA to NMD. Collectively, our data indicate that YRA1 pre-mRNA degradation is a highly regulated process that proceeds through translational repression, substrate recognition by Edc3p, recruitment of the Dcp1p/Dcp2p decapping enzyme, and activation of decapping.

  3. Modulation of mdm2 pre-mRNA splicing by 9-aminoacridine-PNA (peptide nucleic acid conjugates targeting intron-exon junctions

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    Nielsen Peter E

    2010-06-01

    Full Text Available Abstract Background Modulation of pre-mRNA splicing by antisense molecules is a promising mechanism of action for gene therapeutic drugs. In this study, we have examined the potential of peptide nucleic acid (PNA 9-aminoacridine conjugates to modulate the pre-mRNA splicing of the mdm2 human cancer gene in JAR cells. Methods We screened 10 different 15 mer PNAs targeting intron2 at both the 5' - and the 3'-splice site for their effects on the splicing of mdm2 using RT-PCR analysis. We also tested a PNA (2512 targeting the 3'-splice site of intron3 with a complementarity of 4 bases to intron3 and 11 bases to exon4 for its splicing modulation effect. This PNA2512 was further tested for the effects on the mdm2 protein level as well as for inhibition of cell growth in combination with the DNA damaging agent camptothecin (CPT. Results We show that several of these PNAs effectively inhibit the splicing thereby producing a larger mRNA still containing intron2, while skipping of exon3 was not observed by any of these PNAs. The most effective PNA (PNA2406 targeting the 3'-splice site of intron2 had a complementarity of 4 bases to intron2 and 11 bases to exon3. PNA (2512 targeting the 3'-splice site of intron3 induced both splicing inhibition (intron3 skipping and skipping of exon4. Furthermore, treatment of JAR cells with this PNA resulted in a reduction in the level of MDM2 protein and a concomitant increase in the level of tumor suppressor p53. In addition, a combination of this PNA with CPT inhibited cell growth more than CPT alone. Conclusion We have identified several PNAs targeting the 5'- or 3'-splice sites in intron2 or the 3'-splice site of intron3 of mdm2 pre-mRNA which can inhibit splicing. Antisense targeting of splice junctions of mdm2 pre-mRNA may be a powerful method to evaluate the cellular function of MDM2 splice variants as well as a promising approach for discovery of mdm2 targeted anticancer drugs.

  4. Intronic microRNAs

    International Nuclear Information System (INIS)

    Ying, S.-Y.; Lin, S.-L.

    2005-01-01

    MicroRNAs (miRNAs), small single-stranded regulatory RNAs capable of interfering with intracellular mRNAs that contain partial complementarity, are useful for the design of new therapies against cancer polymorphism and viral mutation. MiRNA was originally discovered in the intergenic regions of the Caenorhabditis elegans genome as native RNA fragments that modulate a wide range of genetic regulatory pathways during animal development. However, neither RNA promoter nor polymerase responsible for miRNA biogenesis was determined. Recent findings of intron-derived miRNA in C. elegans, mouse, and human have inevitably led to an alternative pathway for miRNA biogenesis, which relies on the coupled interaction of Pol-II-mediated pre-mRNA transcription and intron excision, occurring in certain nuclear regions proximal to genomic perichromatin fibrils

  5. Alteration of introns in a hyaluronan synthase 1 (HAS1 minigene convert Pre-mRNA [corrected] splicing to the aberrant pattern in multiple myeloma (MM: MM patients harbor similar changes.

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    Jitra Kriangkum

    Full Text Available Aberrant pre-mRNA splice variants of hyaluronan synthase 1 (HAS1 have been identified in malignant cells from cancer patients. Bioinformatic analysis suggests that intronic sequence changes can underlie aberrant splicing. Deletions and mutations were introduced into HAS1 minigene constructs to identify regions that can influence aberrant intronic splicing, comparing the splicing pattern in transfectants with that in multiple myeloma (MM patients. Introduced genetic variations in introns 3 and 4 of HAS1 as shown here can promote aberrant splicing of the type detected in malignant cells from MM patients. HAS1Vd is a novel intronic splice variant first identified here. HAS1Vb, an intronic splice variant previously identified in patients, skips exon 4 and utilizes the same intron 4 alternative 3'splice site as HAS1Vd. For transfected constructs with unaltered introns 3 and 4, HAS1Vd transcripts are readily detectable, frequently to the exclusion of HAS1Vb. In contrast, in MM patients, HAS1Vb is more frequent than HAS1Vd. In the HAS1 minigene, combining deletion in intron 4 with mutations in intron 3 leads to a shift from HAS1Vd expression to HAS1Vb expression. The upregulation of aberrant splicing, exemplified here by the expression of HAS1Vb, is shown here to be influenced by multiple genetic changes in intronic sequences. For HAS1Vb, this includes enhanced exon 4 skipping and increased usage of alternative 3' splice sites. Thus, the combination of introduced mutations in HAS1 intron3 with introduced deletions in HAS1 intron 4 promoted a shift to an aberrant splicing pattern previously shown to be clinically significant. Most MM patients harbor genetic variations in intron 4, and as shown here, nearly half harbor recurrent mutations in HAS1 intron 3. Our work suggests that aberrant intronic HAS1 splicing in MM patients may rely on intronic HAS1 deletions and mutations that are frequent in MM patients but absent from healthy donors.

  6. Splicing analysis for exonic and intronic mismatch repair gene variants associated with Lynch syndrome confirms high concordance between minigene assays and patient RNA analyses

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    van der Klift, Heleen M; Jansen, Anne M L; van der Steenstraten, Niki; Bik, Elsa C; Tops, Carli M J; Devilee, Peter; Wijnen, Juul T

    2015-01-01

    A subset of DNA variants causes genetic disease through aberrant splicing. Experimental splicing assays, either RT-PCR analyses of patient RNA or functional splicing reporter minigene assays, are required to evaluate the molecular nature of the splice defect. Here, we present minigene assays performed for 17 variants in the consensus splice site regions, 14 exonic variants outside these regions, and two deep intronic variants, all in the DNA mismatch-repair (MMR) genes MLH1, MSH2, MSH6, and PMS2, associated with Lynch syndrome. We also included two deep intronic variants in APC and PKD2. For one variant (MLH1 c.122A>G), our minigene assay and patient RNA analysis could not confirm the previously reported aberrant splicing. The aim of our study was to further investigate the concordance between minigene splicing assays and patient RNA analyses. For 30 variants results from patient RNA analyses were available, either performed by our laboratory or presented in literature. Some variants were deliberately included in this study because they resulted in multiple aberrant transcripts in patient RNA analysis, or caused a splice effect other than the prevalent exon skip. While both methods were completely concordant in the assessment of splice effects, four variants exhibited major differences in aberrant splice patterns. Based on the present and earlier studies, together showing an almost 100% concordance of minigene assays with patient RNA analyses, we discuss the weight given to minigene splicing assays in the current criteria proposed by InSiGHT for clinical classification of MMR variants. PMID:26247049

  7. Altered Pre-mRNA Splicing Caused by a Novel Intronic Mutation c.1443+5G>A in the Dihydropyrimidinase (DPYS) Gene.

    Science.gov (United States)

    Nakajima, Yoko; Meijer, Judith; Zhang, Chunhua; Wang, Xu; Kondo, Tomomi; Ito, Tetsuya; Dobritzsch, Doreen; Van Kuilenburg, André B P

    2016-01-12

    Dihydropyrimidinase (DHP) deficiency is an autosomal recessive disease caused by mutations in the DPYS gene. Patients present with highly elevated levels of dihydrouracil and dihydrothymine in their urine, blood and cerebrospinal fluid. The analysis of the effect of mutations in DPYS on pre-mRNA splicing is hampered by the fact that DHP is primarily expressed in liver and kidney cells. The minigene approach can detect mRNA splicing aberrations using cells that do not express the endogenous mRNA. We have used a minigene-based approach to analyze the effects of a presumptive pre-mRNA splicing mutation in two newly identified Chinese pediatric patients with DHP deficiency. Mutation analysis of DPYS showed that both patients were compound heterozygous for a novel intronic mutation c.1443+5G>A in intron 8 and a previously described missense mutation c.1001A>G (p.Q334R) in exon 6. Wild-type and the mutated minigene constructs, containing exons 7, 8 and 9 of DPYS, yielded different splicing products after expression in HEK293 cells. The c.1443+5G>A mutation resulted in altered pre-mRNA splicing of the DPYS minigene construct with full skipping of exon 8. Analysis of the DHP crystal structure showed that the deletion of exon 8 severely affects folding, stability and homooligomerization of the enzyme as well as disruption of the catalytic site. Thus, the analysis suggests that the c.1443+5G>A mutation results in aberrant splicing of the pre-mRNA encoding DHP, underlying the DHP deficiency in two unrelated Chinese patients.

  8. Altered Pre-mRNA Splicing Caused by a Novel Intronic Mutation c.1443+5G>A in the Dihydropyrimidinase (DPYS Gene

    Directory of Open Access Journals (Sweden)

    Yoko Nakajima

    2016-01-01

    Full Text Available Dihydropyrimidinase (DHP deficiency is an autosomal recessive disease caused by mutations in the DPYS gene. Patients present with highly elevated levels of dihydrouracil and dihydrothymine in their urine, blood and cerebrospinal fluid. The analysis of the effect of mutations in DPYS on pre-mRNA splicing is hampered by the fact that DHP is primarily expressed in liver and kidney cells. The minigene approach can detect mRNA splicing aberrations using cells that do not express the endogenous mRNA. We have used a minigene-based approach to analyze the effects of a presumptive pre-mRNA splicing mutation in two newly identified Chinese pediatric patients with DHP deficiency. Mutation analysis of DPYS showed that both patients were compound heterozygous for a novel intronic mutation c.1443+5G>A in intron 8 and a previously described missense mutation c.1001A>G (p.Q334R in exon 6. Wild-type and the mutated minigene constructs, containing exons 7, 8 and 9 of DPYS, yielded different splicing products after expression in HEK293 cells. The c.1443+5G>A mutation resulted in altered pre-mRNA splicing of the DPYS minigene construct with full skipping of exon 8. Analysis of the DHP crystal structure showed that the deletion of exon 8 severely affects folding, stability and homooligomerization of the enzyme as well as disruption of the catalytic site. Thus, the analysis suggests that the c.1443+5G>A mutation results in aberrant splicing of the pre-mRNA encoding DHP, underlying the DHP deficiency in two unrelated Chinese patients.

  9. The full-length microRNA cluster in the intron of large latency transcript is associated with the virulence of pseudorabies virus.

    Science.gov (United States)

    Wang, Xin; Zhang, Mei-Mei; Yan, Kai; Tang, Qi; Wu, Yi-Quan; He, Wen-Bo; Chen, Huan-Chun; Liu, Zheng-Fei

    2018-07-01

    Pseudorabies virus (PRV), the etiological pathogen of Aujeszky's disease, belongs to the Alphaherpesvirus subfamily. Large latency transcript (LLT), the most abundant PRV transcript, harbors a ~ 4.6 kb microRNA (miRNA) cluster-encoding intron. To investigate the function of the LLT miRNA cluster during the life cycle of PRV, we generated a miRNA cluster mutation virus (PRV-∆miR cluster) and revertant virus. Analysis of the growth kinetics of PRV-ΔmiR cluster-infected cells revealed significantly smaller plaques and lower titers than the wild-type and revertant viruses. The mutation virus exhibited increased IE180 and decreased EP0 expression. The clinical symptoms observed in mice infected with PRV-ΔmiR cluster revealed that the miRNA cluster is involved in the pathogenesis of PRV. Physical parameters, virus shedding assays, and the SN 50 titers revealed that the miRNA cluster enhances PRV virulence in pigs. Collectively, our findings suggest that the full-length miRNA cluster is involved in PRV replication and virulence. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Effects of secondary structure on pre-mRNA splicing: hairpins sequestering the 5' but not the 3' splice site inhibit intron processing in Nicotiana plumbaginifolia.

    Science.gov (United States)

    Liu, H X; Goodall, G J; Kole, R; Filipowicz, W

    1995-01-16

    We have performed a systematic study of the effect of artificial hairpins on pre-mRNA splicing in protoplasts of a dicot plant, Nicotiana plumbaginifolia. Hairpins with a potential to form 18 or 24 bp stems strongly inhibit splicing when they sequester the 5' splice site or are placed in the middle of short introns. However, similar 24 bp hairpins sequestering the 3' splice site do not prevent this site from being used as an acceptor. Utilization of the stem-located 3' site requires that the base of the stem is separated from the upstream 5' splice site by a minimum of approximately 45 nucleotides and that another 'helper' 3' splice site is present downstream of the stem. The results indicate that the spliceosome or factors associated with it may have a potential to unfold secondary structure present in the downstream portion of the intron, prior to or at the step of the 3' splice site selection. The finding that the helper 3' site is required for utilization of the stem-located acceptor confirms and extends previous observations, obtained with HeLa cell in vitro splicing systems, indicating that the 3' splice site may be recognized at least twice during spliceosome assembly.

  11. DIVERSITY OF THE TYPE 1 INTRON-ITS REGION OF THE 18S rRNA GENE IN PSEUDOGYMNOASCUS SPECIES FROM THE RED HILLS OF KANSAS.

    Science.gov (United States)

    Chen, Xi; Crupper, Scott S

    2016-09-01

    Gypsum caves found throughout the Red Hills of Kansas have the state's most diverse and largest population of cave-roosting bats. White-nose syndrome (WNS), a disease caused by the fungus Pseudogymnoascus destructans, which threatens all temperate bat species, has not been previously detected in the gypsum caves as this disease moves westward from the eastern United States. Cave soil was obtained from the gypsum caves, and using the polymerase chain reaction, a 624-nucleotide DNA fragment specific to the Type 1 intron-internal transcribed spacer region of the 18S rRNA gene from Pseudogymnoascus species was amplified. Subsequent cloning and DNA sequencing indicated P. destructans DNA was present, along with 26 uncharacterized Pseudogymnoascus DNA variants. However, no evidence of WNS was observed in bat populations residing in these caves.

  12. An intronic ncRNA-dependent regulation of SORL1 expression affecting Aβ formation is upregulated in post-mortem Alzheimer's disease brain samples

    Directory of Open Access Journals (Sweden)

    Eleonora Ciarlo

    2013-03-01

    Recent studies indicated that sortilin-related receptor 1 (SORL1 is a risk gene for late-onset Alzheimer's disease (AD, although its role in the aetiology and/or progression of this disorder is not fully understood. Here, we report the finding of a non-coding (nc RNA (hereafter referred to as 51A that maps in antisense configuration to intron 1 of the SORL1 gene. 51A expression drives a splicing shift of SORL1 from the synthesis of the canonical long protein variant A to an alternatively spliced protein form. This process, resulting in a decreased synthesis of SORL1 variant A, is associated with impaired processing of amyloid precursor protein (APP, leading to increased Aβ formation. Interestingly, we found that 51A is expressed in human brains, being frequently upregulated in cerebral cortices from individuals with Alzheimer's disease. Altogether, these findings document a novel ncRNA-dependent regulatory pathway that might have relevant implications in neurodegeneration.

  13. Structure and conformational dynamics of the domain 5 RNA hairpin of a bacterial group II intron revealed by solution nuclear magnetic resonance and molecular dynamics simulations.

    Science.gov (United States)

    Pechlaner, Maria; Sigel, Roland K O; van Gunsteren, Wilfred F; Dolenc, Jožica

    2013-10-08

    Nuclear magnetic resonance (NMR) nuclear Overhauser enhancement (NOE) data obtained for a 35-nucleotide RNA segment of a bacterial group II intron indicate a helical hairpin structure in which three parts, a terminal pentaloop, a bulge, and a G-A mismatch, display no Watson-Crick base pairing. The 668 NOE upper distance bounds for atom pairs are insufficient to uniquely determine the conformation of these segments. Therefore, molecular dynamics simulations including time-averaged distance restraints have been used to obtain a conformational ensemble compatible with the observed NMR data. The ensemble shows alternating hydrogen bonding patterns for the mentioned segments. In particular, in the pentaloop and in the bulge, the hydrogen bonding networks correspond to distinct conformational clusters that could not be captured by using conventional single-structure refinement techniques. This implies that, to obtain a realistic picture of the conformational ensemble of such flexible biomolecules, it is necessary to properly account for the conformational variability in the structure refinement of RNA fragments.

  14. Phylogenetic evidence for the acquisition of ribosomal RNA introns subsequent to the divergence of some of the major Tetrahymena groups

    DEFF Research Database (Denmark)

    Sogin, M L; Ingold, A; Karlok, M

    1986-01-01

    . In an attempt to evaluate the evolutionary origins of the intervening sequences, we have now determined complete small subunit ribosomal RNA gene sequences from 13 species of Tetrahymena and the absolute number of nucleotide differences between the sequences was used to construct a phylogenetic tree...

  15. The Trypanosoma brucei La protein is a candidate poly(U) shield that impacts spliced leader RNA maturation and tRNA intron removal

    Czech Academy of Sciences Publication Activity Database

    Trantírková, Silvie; Paris, Zdeněk; Sturm, N. R.; Campbell, D. A.; Lukeš, Julius

    2005-01-01

    Roč. 35, č. 4 (2005), s. 359-366 ISSN 0020-7519 R&D Projects: GA AV ČR IAA5022302 Grant - others:NIH(US) AI34536; NIH(US) AI056034 Institutional research plan: CEZ:AV0Z60220518 Keywords : splicing * Trypanosoma * RNA interference Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.346, year: 2005

  16. Evolution of the Exon-Intron Structure in Ciliate Genomes.

    Directory of Open Access Journals (Sweden)

    Vladyslav S Bondarenko

    Full Text Available A typical eukaryotic gene is comprised of alternating stretches of regions, exons and introns, retained in and spliced out a mature mRNA, respectively. Although the length of introns may vary substantially among organisms, a large fraction of genes contains short introns in many species. Notably, some Ciliates (Paramecium and Nyctotherus possess only ultra-short introns, around 25 bp long. In Paramecium, ultra-short introns with length divisible by three (3n are under strong evolutionary pressure and have a high frequency of in-frame stop codons, which, in the case of intron retention, cause premature termination of mRNA translation and consequent degradation of the mis-spliced mRNA by the nonsense-mediated decay mechanism. Here, we analyzed introns in five genera of Ciliates, Paramecium, Tetrahymena, Ichthyophthirius, Oxytricha, and Stylonychia. Introns can be classified into two length classes in Tetrahymena and Ichthyophthirius (with means 48 bp, 69 bp, and 55 bp, 64 bp, respectively, but, surprisingly, comprise three distinct length classes in Oxytricha and Stylonychia (with means 33-35 bp, 47-51 bp, and 78-80 bp. In most ranges of the intron lengths, 3n introns are underrepresented and have a high frequency of in-frame stop codons in all studied species. Introns of Paramecium, Tetrahymena, and Ichthyophthirius are preferentially located at the 5' and 3' ends of genes, whereas introns of Oxytricha and Stylonychia are strongly skewed towards the 5' end. Analysis of evolutionary conservation shows that, in each studied genome, a significant fraction of intron positions is conserved between the orthologs, but intron lengths are not correlated between the species. In summary, our study provides a detailed characterization of introns in several genera of Ciliates and highlights some of their distinctive properties, which, together, indicate that splicing spellchecking is a universal and evolutionarily conserved process in the biogenesis of short

  17. A Novel Heterozygous Intronic Mutation in the FBN1 Gene Contributes to FBN1 RNA Missplicing Events in the Marfan Syndrome

    Directory of Open Access Journals (Sweden)

    Mario Torrado

    2018-01-01

    Full Text Available Marfan syndrome (MFS is an autosomal dominantly inherited connective tissue disorder, mostly caused by mutations in the fibrillin-1 (FBN1 gene. We, by using targeted next-generation sequence analysis, identified a novel intronic FBN1 mutation (the c.2678-15C>A variant in a MFS patient with aortic dilatation. The computational predictions showed that the heterozygous c.2678-15C>A intronic variant might influence the splicing process by differentially affecting canonical versus cryptic splice site utilization within intron 22 of the FBN1 gene. RT-PCR and Western blot analyses, using FBN1 minigenes transfected into HeLa and COS-7 cells, revealed that the c.2678-15C>A variant disrupts normal splicing of intron 22 leading to aberrant 13-nt intron 22 inclusion, frameshift, and premature termination codon. Collectively, the results strongly suggest that the c.2678-15C>A variant could lead to haploinsufficiency of the FBN1 functional protein and structural connective tissue fragility in MFS complicated by aorta dilation, a finding that further expands on the genetic basis of aortic pathology.

  18. Characterization of intronic uridine-rich sequence elements acting as possible targets for nuclear proteins during pre-mRNA splicing in Nicotiana plumbaginifolia.

    Science.gov (United States)

    Gniadkowski, M; Hemmings-Mieszczak, M; Klahre, U; Liu, H X; Filipowicz, W

    1996-02-15

    Introns of nuclear pre-mRNAs in dicotyledonous plants, unlike introns in vertebrates or yeast, are distinctly rich in A+U nucleotides and this feature is essential for their processing. In order to define more precisely sequence elements important for intron recognition in plants, we investigated the effects of short insertions, either U-rich or A-rich, on splicing of synthetic introns in transfected protoplast of Nicotiana plumbaginifolia. It was found that insertions of U-rich (sequence UUUUUAU) but not A-rich (AUAAAAA) segments can activate splicing of a GC-rich synthetic infron, and that U-rich segments, or multimers thereof, can function irrespective of the site of insertion within the intron. Insertions of multiple U-rich segments, either at the same or different locations, generally had an additive, stimulatory effect on splicing. Mutational analysis showed that replacement of one or two U residues in the UUUUUAU sequence with A or C residues had only a small effect on splicing, but replacement with G residues was strongly inhibitory. Proteins that interact with fragments of natural and synthetic pre-mRNAs in vitro were identified in nuclear extracts of N.plumbaginifolia by UV cross- linking. The profile of cross-linked plant proteins was considerably less complex than that obtained with a HeLa cell nuclear extract. Two major cross-linkable plant proteins had apparent molecular mass of 50 and 54 kDa and showed affinity for oligouridilates present in synGC introns or for poly(U).

  19. An "off-on" electrochemiluminescent biosensor based on DNAzyme-assisted target recycling and rolling circle amplifications for ultrasensitive detection of microRNA.

    Science.gov (United States)

    Zhang, Pu; Wu, Xiaoyan; Yuan, Ruo; Chai, Yaqin

    2015-03-17

    In this study, an off-on switching of a dual amplified electrochemiluminescence (ECL) biosensor based on Pb(2+)-induced DNAzyme-assisted target recycling and rolling circle amplification (RCA) was constructed for microRNA (miRNA) detection. First, the primer probe with assistant probe and miRNA formed Y junction which was cleaved with the addition of Pb(2+) to release miRNA. Subsequently, the released miRNA could initiate the next recycling process, leading to the generation of numerous intermediate DNA sequences (S2). Afterward, bare glassy carbon electrode (GCE) was immersed into HAuCl4 solution to electrodeposit a Au nanoparticle layer (depAu), followed by the assembly of a hairpin probe (HP). Then, dopamine (DA)-modified DNA sequence (S1) was employed to hybridize with HP, which switching off the sensing system. This is the first work that employs DA to quench luminol ECL signal, possessing the biosensor ultralow background signal. Afterward, S2 produced by the target recycling process was loaded onto the prepared electrode to displace S1 and served as an initiator for RCA. With rational design, numerous repeated DNA sequences coupling with hemin to form hemin/G-quadruplex were generated, which could exhibit strongly catalytic toward H2O2, thus amplified the ECL signal and switched the ON state of the sensing system. The liner range for miRNA detection was from 1.0 fM to 100 pM with a low detection limit down to 0.3 fM. Moreover, with the high sensitivity and specificity induced by the dual signal amplification, the proposed miRNA biosensor holds great potential for analysis of other interesting tumor markers.

  20. Frequency of intron loss correlates with processed pseudogene abundance: a novel strategy to test the reverse transcriptase model of intron loss.

    Science.gov (United States)

    Zhu, Tao; Niu, Deng-Ke

    2013-03-05

    Although intron loss in evolution has been described, the mechanism involved is still unclear. Three models have been proposed, the reverse transcriptase (RT) model, genomic deletion model and double-strand-break repair model. The RT model, also termed mRNA-mediated intron loss, suggests that cDNA molecules reverse transcribed from spliced mRNA recombine with genomic DNA causing intron loss. Many studies have attempted to test this model based on its predictions, such as simultaneous loss of adjacent introns, 3'-side bias of intron loss, and germline expression of intron-lost genes. Evidence either supporting or opposing the model has been reported. The mechanism of intron loss proposed in the RT model shares the process of reverse transcription with the formation of processed pseudogenes. If the RT model is correct, genes that have produced more processed pseudogenes are more likely to undergo intron loss. In the present study, we observed that the frequency of intron loss is correlated with processed pseudogene abundance by analyzing a new dataset of intron loss obtained in mice and rats. Furthermore, we found that mRNA molecules of intron-lost genes are mostly translated on free cytoplasmic ribosomes, a feature shared by mRNA molecules of the parental genes of processed pseudogenes and long interspersed elements. This feature is likely convenient for intron-lost gene mRNA molecules to be reverse transcribed. Analyses of adjacent intron loss, 3'-side bias of intron loss, and germline expression of intron-lost genes also support the RT model. Compared with previous evidence, the correlation between the abundance of processed pseudogenes and intron loss frequency more directly supports the RT model of intron loss. Exploring such a correlation is a new strategy to test the RT model in organisms with abundant processed pseudogenes.

  1. Research circles

    DEFF Research Database (Denmark)

    Nordentoft, Helle Merete; Thomsen, Rie; Möller, Jonas

    lifelong guidance policies. This paper presents `research circles´ as a way to develop guidance practices through long-term research relationships between practice and research. Research circles support a bottom up approach to policy development just like ELGPN considers to be necessary and required...... of their habitual pedagogical role and enables them to observe and analyze their own practice. In conclusion, this methodological approach to the development of guidance practices introduces a combination between theory and practice that meets current needs of practice, policy and research....

  2. Characteristics of binding sites of intergenic, intronic and exonic ...

    African Journals Online (AJOL)

    user

    2013-03-06

    Mar 6, 2013 ... miR-1587). Such part of mRNA is very important for its regulation via several miRNA. Interaction of intronic miRNAs with mRNAs genes coding in-miRNA. Oncogenes (51) are host genes and target genes for in-. miRNAs. Majority of these in-miRNAs are encoded in intron. Five of the studied genes (ATF2, ...

  3. Origin of introns by 'intronization' of exonic sequences

    DEFF Research Database (Denmark)

    Irimia, Manuel; Rukov, Jakob Lewin; Penny, David

    2008-01-01

    The mechanisms of spliceosomal intron creation have proved elusive. Here we describe a new mechanism: the recruitment of internal exonic sequences ('intronization') in Caenorhabditis species. The numbers of intronization events and introns gained by other mechanisms are similar, suggesting that i...

  4. Family of autocatalytic group I introns in bacteriophage T4

    International Nuclear Information System (INIS)

    Shub, D.A.; Xu, M.Q.; Gott, J.M.; Zeeh, A.; Wilson, L.D.

    1987-01-01

    The discovery of an intron in phage T4 encouraged the authors to look for additional group I introns in the T4 genome. Further examples would permit sequence and structural comparisons that might lend insight into their evolutionary origin. Additionally, they hoped that their locations within the T4 genome would infer a possible regulatory function in prokaryotic gene expression. They took advantage of the fact that, since G is added to the 5' end of the intron, autocatalytic group I introns could be specifically labeled in vitro for use as probes for DNA blotting experiments. If Group I introns were in more than just the td gene, multiple RNA species should be labeled when total RNA is extracted from T4-infected cells and incubated with [α- 32 P]GTP in vitro. When used as a probe for a Southern blot of T4 DNA, this RNA should hybridize to several DNA bands

  5. On-Particle Rolling Circle Amplification-Based Core-Satellite Magnetic Superstructures for MicroRNA Detection

    DEFF Research Database (Denmark)

    Tian, Bo; Qiu, Zhen; Ma, Jing

    2018-01-01

    -specific nuclease in the presence of target microRNA, resulting in a release of MNPs that can be quantified in an optomagnetic sensor. The proposed biosensor has a simple mix-separate-measure strategy. For let-7b detection, the proposed biosensor offers a wide linear detection range of approximately 5 orders...

  6. Host Factors Influencing the Retrohoming Pathway of Group II Intron RmInt1, Which Has an Intron-Encoded Protein Naturally Devoid of Endonuclease Activity.

    Directory of Open Access Journals (Sweden)

    Rafael Nisa-Martínez

    Full Text Available Bacterial group II introns are self-splicing catalytic RNAs and mobile retroelements that have an open reading frame encoding an intron-encoded protein (IEP with reverse transcriptase (RT and RNA splicing or maturase activity. Some IEPs carry a DNA endonuclease (En domain, which is required to cleave the bottom strand downstream from the intron-insertion site for target DNA-primed reverse transcription (TPRT of the inserted intron RNA. Host factors complete the insertion of the intron. By contrast, the major retrohoming pathway of introns with IEPs naturally lacking endonuclease activity, like the Sinorhizobium meliloti intron RmInt1, is thought to involve insertion of the intron RNA into the template for lagging strand DNA synthesis ahead of the replication fork, with possible use of the nascent strand to prime reverse transcription of the intron RNA. The host factors influencing the retrohoming pathway of such introns have not yet been described. Here, we identify key candidates likely to be involved in early and late steps of RmInt1 retrohoming. Some of these host factors are common to En+ group II intron retrohoming, but some have different functions. Our results also suggest that the retrohoming process of RmInt1 may be less dependent on the intracellular free Mg2+ concentration than those of other group II introns.

  7. The peculiarities of large intron splicing in animals.

    Directory of Open Access Journals (Sweden)

    Samuel Shepard

    Full Text Available In mammals a considerable 92% of genes contain introns, with hundreds and hundreds of these introns reaching the incredible size of over 50,000 nucleotides. These "large introns" must be spliced out of the pre-mRNA in a timely fashion, which involves bringing together distant 5' and 3' acceptor and donor splice sites. In invertebrates, especially Drosophila, it has been shown that larger introns can be spliced efficiently through a process known as recursive splicing-a consecutive splicing from the 5'-end at a series of combined donor-acceptor splice sites called RP-sites. Using a computational analysis of the genomic sequences, we show that vertebrates lack the proper enrichment of RP-sites in their large introns, and, therefore, require some other method to aid splicing. We analyzed over 15,000 non-redundant, large introns from six mammals, 1,600 from chicken and zebrafish, and 560 non-redundant large introns from five invertebrates. Our bioinformatic investigation demonstrates that, unlike the studied invertebrates, the studied vertebrate genomes contain consistently abundant amounts of direct and complementary strand interspersed repetitive elements (mainly SINEs and LINEs that may form stems with each other in large introns. This examination showed that predicted stems are indeed abundant and stable in the large introns of mammals. We hypothesize that such stems with long loops within large introns allow intron splice sites to find each other more quickly by folding the intronic RNA upon itself at smaller intervals and, thus, reducing the distance between donor and acceptor sites.

  8. Modulation of mdm2 pre-mRNA splicing by 9-aminoacridine-PNA (peptide nucleic acid) conjugates targeting intron-exon junctions

    DEFF Research Database (Denmark)

    Shiraishi, Takehiko; Eysturskard, Jonhard; Nielsen, Peter E

    2010-01-01

    ABSTRACT: BACKGROUND: Modulation of pre-mRNA splicing by antisense molecules is a promising mechanism of action for gene therapeutic drugs. In this study, we have examined the potential of peptide nucleic acid (PNA) 9-aminoacridine conjugates to modulate the pre-mRNA splicing of the mdm2 human ca...

  9. A site-specific endonuclease encoded by a typical archaeal intron

    DEFF Research Database (Denmark)

    Dalgaard, Jacob; Garrett, Roger Antony; Belfort, Malene

    1993-01-01

    The protein encoded by the archaeal intron in the 23S rRNA gene of the hyperthermophile Desulfurococcus mobilis is a double-strand DNase that, like group I intron homing endonucleases, is capable of cleaving an intronless allele of the gene. This enzyme, I-Dmo I, is unusual among the intron...

  10. Intron retention in mRNA encoding ancillary subunit of insect voltage-gated sodium channel modulates channel expression, gating regulation and drug sensitivity.

    Directory of Open Access Journals (Sweden)

    Céline M Bourdin

    Full Text Available Insect voltage-gated sodium (Nav channels are formed by a well-known pore-forming α-subunit encoded by para-like gene and ancillary subunits related to TipE from the mutation "temperature-induced-paralysis locus E." The role of these ancillary subunits in the modulation of biophysical and pharmacological properties of Na(+ currents are not enough documented. The unique neuronal ancillary subunit TipE-homologous protein 1 of Drosophila melanogaster (DmTEH1 strongly enhances the expression of insect Nav channels when heterologously expressed in Xenopus oocytes. Here we report the cloning and functional expression of two neuronal DmTEH1-homologs of the cockroach, Periplaneta americana, PaTEH1A and PaTEH1B, encoded by a single bicistronic gene. In PaTEH1B, the second exon encoding the last 11-amino-acid residues of PaTEH1A is shifted to 3'UTR by the retention of a 96-bp intron-containing coding-message, thus generating a new C-terminal end. We investigated the gating and pharmacological properties of the Drosophila Nav channel variant (DmNav1-1 co-expressed with DmTEH1, PaTEH1A, PaTEH1B or a truncated mutant PaTEH1Δ(270-280 in Xenopus oocytes. PaTEH1B caused a 2.2-fold current density decrease, concomitant with an equivalent α-subunit incorporation decrease in the plasma membrane, compared to PaTEH1A and PaTEH1Δ(270-280. PaTEH1B positively shifted the voltage-dependences of activation and slow inactivation of DmNav1-1 channels to more positive potentials compared to PaTEH1A, suggesting that the C-terminal end of both proteins may influence the function of the voltage-sensor and the pore of Nav channel. Interestingly, our findings showed that the sensitivity of DmNav1-1 channels to lidocaine and to the pyrazoline-type insecticide metabolite DCJW depends on associated TEH1-like subunits. In conclusion, our work demonstrates for the first time that density, gating and pharmacological properties of Nav channels expressed in Xenopus oocytes can be

  11. The Ia-2β intronic miRNA, miR-153, is a negative regulator of insulin and dopamine secretion through its effect on the Cacna1c gene in mice.

    Science.gov (United States)

    Xu, Huanyu; Abuhatzira, Liron; Carmona, Gilberto N; Vadrevu, Suryakiran; Satin, Leslie S; Notkins, Abner L

    2015-10-01

    miR-153 is an intronic miRNA embedded in the genes that encode IA-2 (also known as PTPRN) and IA-2β (also known as PTPRN2). Islet antigen (IA)-2 and IA-2β are major autoantigens in type 1 diabetes and are important transmembrane proteins in dense core and synaptic vesicles. miR-153 and its host genes are co-regulated in pancreas and brain. The present experiments were initiated to decipher the regulatory network between miR-153 and its host gene Ia-2β (also known as Ptprn2). Insulin secretion was determined by ELISA. Identification of miRNA targets was assessed using luciferase assays and by quantitative real-time PCR and western blots in vitro and in vivo. Target protector was also employed to evaluate miRNA target function. Functional studies revealed that miR-153 mimic suppresses both glucose- and potassium-induced insulin secretion (GSIS and PSIS, respectively), whereas miR-153 inhibitor enhances both GSIS and PSIS. A similar effect on dopamine secretion also was observed. Using miRNA target prediction software, we found that miR-153 is predicted to target the 3'UTR region of the calcium channel gene, Cacna1c. Further studies confirmed that Cacna1c mRNA and protein are downregulated by miR-153 mimics and upregulated by miR-153 inhibitors in insulin-secreting freshly isolated mouse islets, in the insulin-secreting mouse cell line MIN6 and in the dopamine-secreting cell line PC12. miR-153 is a negative regulator of both insulin and dopamine secretion through its effect on Cacna1c expression, which suggests that IA-2β and miR-153 have opposite functional effects on the secretory pathway.

  12. Small circles

    DEFF Research Database (Denmark)

    Ling, Richard; Bjelland, Johannes; Sundsøy, Pål

    2014-01-01

    and spatial movement is highly predictable and that the majority of calls and text messages are sent to only four to six different persons. This article extends this research by examining both tie strength and the distance between the interlocutors in urban and rural settings. The findings show that even......This article examines how we use mobile telephony to maintain our physically and socially closest social circle. The analysis is based on traffic data gathered from Norway using approximately 24 million calls and texts made by private individuals. Previous research has shown that our temporal...... as information and communication technologies (ICTs) potentially put the world at our fingertips, the mobile phone is an instrument of a more limited geographical and social sphere. Approximately two-thirds of our calls/texts go to strong ties that are within a 25-km radius....

  13. Introns: The Functional Benefits of Introns in Genomes

    Directory of Open Access Journals (Sweden)

    Bong-Seok Jo

    2015-12-01

    Full Text Available The intron has been a big biological mystery since it was first discovered in several aspects. First, all of the completely sequenced eukaryotes harbor introns in the genomic structure, whereas no prokaryotes identified so far carry introns. Second, the amount of total introns varies in different species. Third, the length and number of introns vary in different genes, even within the same species genome. Fourth, all introns are copied into RNAs by transcription and DNAs by replication processes, but intron sequences do not participate in protein-coding sequences. The existence of introns in the genome should be a burden to some cells, because cells have to consume a great deal of energy to copy and excise them exactly at the correct positions with the help of complicated spliceosomal machineries. The existence throughout the long evolutionary history is explained, only if selective advantages of carrying introns are assumed to be given to cells to overcome the negative effect of introns. In that regard, we summarize previous research about the functional roles or benefits of introns. Additionally, several other studies strongly suggesting that introns should not be junk will be introduced.

  14. Introns: The Functional Benefits of Introns in Genomes.

    Science.gov (United States)

    Jo, Bong-Seok; Choi, Sun Shim

    2015-12-01

    The intron has been a big biological mystery since it was first discovered in several aspects. First, all of the completely sequenced eukaryotes harbor introns in the genomic structure, whereas no prokaryotes identified so far carry introns. Second, the amount of total introns varies in different species. Third, the length and number of introns vary in different genes, even within the same species genome. Fourth, all introns are copied into RNAs by transcription and DNAs by replication processes, but intron sequences do not participate in protein-coding sequences. The existence of introns in the genome should be a burden to some cells, because cells have to consume a great deal of energy to copy and excise them exactly at the correct positions with the help of complicated spliceosomal machineries. The existence throughout the long evolutionary history is explained, only if selective advantages of carrying introns are assumed to be given to cells to overcome the negative effect of introns. In that regard, we summarize previous research about the functional roles or benefits of introns. Additionally, several other studies strongly suggesting that introns should not be junk will be introduced.

  15. Introns Protect Eukaryotic Genomes from Transcription-Associated Genetic Instability.

    Science.gov (United States)

    Bonnet, Amandine; Grosso, Ana R; Elkaoutari, Abdessamad; Coleno, Emeline; Presle, Adrien; Sridhara, Sreerama C; Janbon, Guilhem; Géli, Vincent; de Almeida, Sérgio F; Palancade, Benoit

    2017-08-17

    Transcription is a source of genetic instability that can notably result from the formation of genotoxic DNA:RNA hybrids, or R-loops, between the nascent mRNA and its template. Here we report an unexpected function for introns in counteracting R-loop accumulation in eukaryotic genomes. Deletion of endogenous introns increases R-loop formation, while insertion of an intron into an intronless gene suppresses R-loop accumulation and its deleterious impact on transcription and recombination in yeast. Recruitment of the spliceosome onto the mRNA, but not splicing per se, is shown to be critical to attenuate R-loop formation and transcription-associated genetic instability. Genome-wide analyses in a number of distant species differing in their intron content, including human, further revealed that intron-containing genes and the intron-richest genomes are best protected against R-loop accumulation and subsequent genetic instability. Our results thereby provide a possible rationale for the conservation of introns throughout the eukaryotic lineage. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Altered Pre-mRNA Splicing Caused by a Novel Intronic Mutation c.1443+5G>A in the Dihydropyrimidinase (DPYS) Gene

    NARCIS (Netherlands)

    Nakajima, Yoko; Meijer, Judith; Zhang, Chunhua; Wang, Xu; Kondo, Tomomi; Ito, Tetsuya; Dobritzsch, Doreen; van Kuilenburg, André B. P.

    2016-01-01

    Dihydropyrimidinase (DHP) deficiency is an autosomal recessive disease caused by mutations in the DPYS gene. Patients present with highly elevated levels of dihydrouracil and dihydrothymine in their urine, blood and cerebrospinal fluid. The analysis of the effect of mutations in DPYS on pre-mRNA

  17. The Biology of Intron Gain and Loss

    DEFF Research Database (Denmark)

    Jeffares, Daniel C; Mourier, Tobias; Penny, David

    2006-01-01

    Intron density in eukaryote genomes varies by more than three orders of magnitude, so there must have been extensive intron gain and/or intron loss during evolution. A favored and partial explanation for this range of intron densities has been that introns have accumulated stochastically in large...... on introns depending on the biology of the organism and the gene involved....

  18. Class I self-splicing introns are found in the T-even bacteriophage family

    International Nuclear Information System (INIS)

    Chu, F.K.; Maley, F.; Maley, G.F.

    1987-01-01

    The thymidylate synthase gene (td) and ribonucleotide reductase B2 subunit gene (nrdB) EMBO both of bacteriophage T4 in origin, are procaryotic intron-containing protein-encoding genes. To screen for other procaryotic introns, southern hybridization analysis of several procaryotic genomes was carried out, using T4 phage td DNA restriction fragments and synthetic oligodeoxynucleotides defining strategic td exon and intron regions. Furthermore, the labeling pattern of total RNA with [α- 32 P]GTP, a typical reaction of self-splicing RNAs (class I), was examined. Experimental data implicate multiple self-splicing introns only in the T-even phages: five (1, 0.9, 0.83, 0.75 and 0.6 kb) in T4 and three (1, 0.9 and 0.75 kb) each in T2 and T6 phages. Northern hybridization analysis of total RNA extracted from T-even phage-infected cells confirms that the 1 kb RNA from each phage is in fact the excised intron segment from the precursor RNA transcribed from an intron-containing td gene in each case. This RNA cyclizes to form a contiguous circular molecule. The 0.6 kb RNA is most likely the T4 phage nrdB intron which seems to be absent from the corresponding gene in T2 and T6. The remaining RNA species are candidates for other self-splicing introns in these phages

  19. Localized Retroprocessing as a Model of Intron Loss in the Plant Mitochondrial Genome.

    Science.gov (United States)

    Cuenca, Argelia; Ross, T Gregory; Graham, Sean W; Barrett, Craig F; Davis, Jerrold I; Seberg, Ole; Petersen, Gitte

    2016-08-03

    Loss of introns in plant mitochondrial genes is commonly explained by retroprocessing. Under this model, an mRNA is reverse transcribed and integrated back into the genome, simultaneously affecting the contents of introns and edited sites. To evaluate the extent to which retroprocessing explains intron loss, we analyzed patterns of intron content and predicted RNA editing for whole mitochondrial genomes of 30 species in the monocot order Alismatales. In this group, we found an unusually high degree of variation in the intron content, even expanding the hitherto known variation among angiosperms. Some species have lost some two-third of the cis-spliced introns. We found a strong correlation between intron content and editing frequency, and detected 27 events in which intron loss is consistent with the presence of nucleotides in an edited state, supporting retroprocessing. However, we also detected seven cases of intron loss not readily being explained by retroprocession. Our analyses are also not consistent with the entire length of a fully processed cDNA copy being integrated into the genome, but instead indicate that retroprocessing usually occurs for only part of the gene. In some cases, several rounds of retroprocessing may explain intron loss in genes completely devoid of introns. A number of taxa retroprocessing seem to be very common and a possibly ongoing process. It affects the entire mitochondrial genome. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  20. Remarkable sequence conservation of the last intron in the PKD1 gene.

    Science.gov (United States)

    Rodova, Marianna; Islam, M Rafiq; Peterson, Kenneth R; Calvet, James P

    2003-10-01

    The last intron of the PKD1 gene (intron 45) was found to have exceptionally high sequence conservation across four mammalian species: human, mouse, rat, and dog. This conservation did not extend to the comparable intron in pufferfish. Pairwise comparisons for intron 45 showed 91% identity (human vs. dog) to 100% identity (mouse vs. rat) for an average for all four species of 94% identity. In contrast, introns 43 and 44 of the PKD1 gene had average pairwise identities of 57% and 54%, and exons 43, 44, and 45 and the coding region of exon 46 had average pairwise identities of 80%, 84%, 82%, and 80%. Intron 45 is 90 to 95 bp in length, with the major region of sequence divergence being in a central 4-bp to 9-bp variable region. RNA secondary structure analysis of intron 45 predicts a branching stem-loop structure in which the central variable region lies in one loop and the putative branch point sequence lies in another loop, suggesting that the intron adopts a specific stem-loop structure that may be important for its removal. Although intron 45 appears to conform to the class of small, G-triplet-containing introns that are spliced by a mechanism utilizing intron definition, its high sequence conservation may be a reflection of constraints imposed by a unique mechanism that coordinates splicing of this last PKD1 intron with polyadenylation.

  1. Introns in the genome of bacteriophage T4

    International Nuclear Information System (INIS)

    Gott, J.M.

    1987-01-01

    RNA from T4-infected cells yields multiple end-labeled species when incubated with [α- 32 P]GTP under self-splicing conditions. One of these corresponds to the previously characterized intron from the T4 td gene and, as shown in this work, the others represent additional group I introns in T4. Two loci distinct from the td gene were found to hybridize to the mixed GTP-labeled T4 RNA probe. These were mapped to the unlinked genes nrdB and sunY. Cloned DNA from the nrdB region that contained the intron was shown to generate characteristic group I splice products with RNA synthesized in vivo or in vitro. The splice junction of the nrdB gene was determined and the nature of the RNA reaction products characterized. In vivo expression of the nrdB gene and the open reading frame within the intron was studied using in-frame lacZ fusions and primer extension analyses. The data suggest that expression of the intron open reading frame is highly regulated during T4 infection. Possible regulatory mechanisms are discussed

  2. Accumulation of Stable Full-Length Circular Group I Intron RNAs during Heat-Shock

    DEFF Research Database (Denmark)

    Andersen, Kasper L.; Beckert, Bertrand; Masquida, Benoit

    2016-01-01

    the potential to linearize the circle. To understand the structural features that maintain circle integrity, we performed chemical and enzymatic probing of the splicing ribozyme combined with molecular modeling to arrive at models of the inactive circular form and its active linear counterpart. We show...... integration and thus supports the notion that the circular form is a biologically significant molecule possibly with a role in intron mobility...

  3. Circle diffeomorphisms forced by expanding circle maps

    NARCIS (Netherlands)

    Homburg, A.J.

    2012-01-01

    We discuss the dynamics of skew product maps defined by circle diffeomorphisms forced by expanding circle maps. We construct an open class of such systems that are robustly topologically mixing and for which almost all points in the same fiber converge under iteration. This property follows from the

  4. 50/50 Expressional Odds of Retention Signifies the Distinction between Retained Introns and Constitutively Spliced Introns in Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Rui Mao

    2017-10-01

    Full Text Available Intron retention, one of the most prevalent alternative splicing events in plants, can lead to introns retained in mature mRNAs. However, in comparison with constitutively spliced introns (CSIs, the relevantly distinguishable features for retained introns (RIs are still poorly understood. This work proposes a computational pipeline to discover novel RIs from multiple next-generation RNA sequencing (RNA-Seq datasets of Arabidopsis thaliana. Using this pipeline, we detected 3,472 novel RIs from 18 RNA-Seq datasets and re-confirmed 1,384 RIs which are currently annotated in the TAIR10 database. We also use the expression of intron-containing isoforms as a new feature in addition to the conventional features. Based on these features, RIs are highly distinguishable from CSIs by machine learning methods, especially when the expressional odds of retention (i.e., the expression ratio of the RI-containing isoforms relative to the isoforms without RIs for the same gene reaches to or larger than 50/50. In this case, the RIs and CSIs can be clearly separated by the Random Forest with an outstanding performance of 0.95 on AUC (the area under a receiver operating characteristics curve. The closely related characteristics to the RIs include the low strength of splice sites, high similarity with the flanking exon sequences, low occurrence percentage of YTRAY near the acceptor site, existence of putative intronic splicing silencers (ISSs, i.e., AG/GA-rich motifs and intronic splicing enhancers (ISEs, i.e., TTTT-containing motifs, and enrichment of Serine/Arginine-Rich (SR proteins and heterogeneous nuclear ribonucleoparticle proteins (hnRNPs.

  5. Parallel loss of plastid introns and their maturase in the genus Cuscuta.

    Science.gov (United States)

    McNeal, Joel R; Kuehl, Jennifer V; Boore, Jeffrey L; Leebens-Mack, Jim; dePamphilis, Claude W

    2009-06-19

    Plastid genome content and arrangement are highly conserved across most land plants and their closest relatives, streptophyte algae, with nearly all plastid introns having invaded the genome in their common ancestor at least 450 million years ago. One such intron, within the transfer RNA trnK-UUU, contains a large open reading frame that encodes a presumed intron maturase, matK. This gene is missing from the plastid genomes of two species in the parasitic plant genus Cuscuta but is found in all other published land plant and streptophyte algal plastid genomes, including that of the nonphotosynthetic angiosperm Epifagus virginiana and two other species of Cuscuta. By examining matK and plastid intron distribution in Cuscuta, we add support to the hypothesis that its normal role is in splicing seven of the eight group IIA introns in the genome. We also analyze matK nucleotide sequences from Cuscuta species and relatives that retain matK to test whether changes in selective pressure in the maturase are associated with intron deletion. Stepwise loss of most group IIA introns from the plastid genome results in substantial change in selective pressure within the hypothetical RNA-binding domain of matK in both Cuscuta and Epifagus, either through evolution from a generalist to a specialist intron splicer or due to loss of a particular intron responsible for most of the constraint on the binding region. The possibility of intron-specific specialization in the X-domain is implicated by evidence of positive selection on the lineage leading to C. nitida in association with the loss of six of seven introns putatively spliced by matK. Moreover, transfer RNA gene deletion facilitated by parasitism combined with an unusually high rate of intron loss from remaining functional plastid genes created a unique circumstance on the lineage leading to Cuscuta subgenus Grammica that allowed elimination of matK in the most species-rich lineage of Cuscuta.

  6. Parallel loss of plastid introns and their maturase in the genus Cuscuta.

    Directory of Open Access Journals (Sweden)

    Joel R McNeal

    2009-06-01

    Full Text Available Plastid genome content and arrangement are highly conserved across most land plants and their closest relatives, streptophyte algae, with nearly all plastid introns having invaded the genome in their common ancestor at least 450 million years ago. One such intron, within the transfer RNA trnK-UUU, contains a large open reading frame that encodes a presumed intron maturase, matK. This gene is missing from the plastid genomes of two species in the parasitic plant genus Cuscuta but is found in all other published land plant and streptophyte algal plastid genomes, including that of the nonphotosynthetic angiosperm Epifagus virginiana and two other species of Cuscuta. By examining matK and plastid intron distribution in Cuscuta, we add support to the hypothesis that its normal role is in splicing seven of the eight group IIA introns in the genome. We also analyze matK nucleotide sequences from Cuscuta species and relatives that retain matK to test whether changes in selective pressure in the maturase are associated with intron deletion. Stepwise loss of most group IIA introns from the plastid genome results in substantial change in selective pressure within the hypothetical RNA-binding domain of matK in both Cuscuta and Epifagus, either through evolution from a generalist to a specialist intron splicer or due to loss of a particular intron responsible for most of the constraint on the binding region. The possibility of intron-specific specialization in the X-domain is implicated by evidence of positive selection on the lineage leading to C. nitida in association with the loss of six of seven introns putatively spliced by matK. Moreover, transfer RNA gene deletion facilitated by parasitism combined with an unusually high rate of intron loss from remaining functional plastid genes created a unique circumstance on the lineage leading to Cuscuta subgenus Grammica that allowed elimination of matK in the most species-rich lineage of Cuscuta.

  7. The brown algae Pl.LSU/2 group II intron-encoded protein has functional reverse transcriptase and maturase activities.

    Directory of Open Access Journals (Sweden)

    Madeleine Zerbato

    Full Text Available Group II introns are self-splicing mobile elements found in prokaryotes and eukaryotic organelles. These introns propagate by homing into precise genomic locations, following assembly of a ribonucleoprotein complex containing the intron-encoded protein (IEP and the spliced intron RNA. Engineered group II introns are now commonly used tools for targeted genomic modifications in prokaryotes but not in eukaryotes. We speculate that the catalytic activation of currently known group II introns is limited in eukaryotic cells. The brown algae Pylaiella littoralis Pl.LSU/2 group II intron is uniquely capable of in vitro ribozyme activity at physiological level of magnesium but this intron remains poorly characterized. We purified and characterized recombinant Pl.LSU/2 IEP. Unlike most IEPs, Pl.LSU/2 IEP displayed a reverse transcriptase activity without intronic RNA. The Pl.LSU/2 intron could be engineered to splice accurately in Saccharomyces cerevisiae and splicing efficiency was increased by the maturase activity of the IEP. However, spliced transcripts were not expressed. Furthermore, intron splicing was not detected in human cells. While further tool development is needed, these data provide the first functional characterization of the PI.LSU/2 IEP and the first evidence that the Pl.LSU/2 group II intron splicing occurs in vivo in eukaryotes in an IEP-dependent manner.

  8. General minisum circle location

    DEFF Research Database (Denmark)

    Körner, Mark; Brimberg, Jack; Juel, Henrik

    2009-01-01

    In our paper we approximate a set of given points by a general circle. More precisely, we consider the problem of locating and scaling the unit ball of some given norm k1 with respect to xed points on the plane such that the sum of weighted distances between the circle and the xed points is minim......In our paper we approximate a set of given points by a general circle. More precisely, we consider the problem of locating and scaling the unit ball of some given norm k1 with respect to xed points on the plane such that the sum of weighted distances between the circle and the xed points...

  9. Vicious Circles in Organizations.

    Science.gov (United States)

    Masuch, Michael

    1985-01-01

    After examining some elementary notions of action theory and cybernetics, this article analyzes the dynamics, clustering, and survival chances of vicious circles. It argues that the action perspective implies that many structural suboptimalities of organizations are caused by vicious circles. Eleven figures and 105 references are provided. (DCS)

  10. Polygons and Their Circles

    Science.gov (United States)

    Stephenson, Paul

    2009-01-01

    In order to find its circumference, Archimedes famously boxed the circle between two polygons. Ending the first of a series of articles (MT179) with an aside, Francis Lopez-Real reverses the situation to ask: Which polygons can be boxed between two circles? (The official term for such polygons is "bicentric".) The sides of these polygons are…

  11. Two CRM protein subfamilies cooperate in the splicing of group IIB introns in chloroplasts.

    Science.gov (United States)

    Asakura, Yukari; Bayraktar, Omer Ali; Barkan, Alice

    2008-11-01

    Chloroplast genomes in angiosperms encode approximately 20 group II introns, approximately half of which are classified as subgroup IIB. The splicing of all but one of the subgroup IIB introns requires a heterodimer containing the peptidyl-tRNA hydrolase homolog CRS2 and one of two closely related proteins, CAF1 or CAF2, that harbor a recently recognized RNA binding domain called the CRM domain. Two CRS2/CAF-dependent introns require, in addition, a CRM domain protein called CFM2 that is only distantly related to CAF1 and CAF2. Here, we show that CFM3, a close relative of CFM2, associates in vivo with those CRS2/CAF-dependent introns that are not CFM2 ligands. Mutant phenotypes in rice and Arabidopsis support a role for CFM3 in the splicing of most of the introns with which it associates. These results show that either CAF1 or CAF2 and either CFM2 or CFM3 simultaneously bind most chloroplast subgroup IIB introns in vivo, and that the CAF and CFM subunits play nonredundant roles in splicing. These results suggest that the expansion of the CRM protein family in plants resulted in two subfamilies that play different roles in group II intron splicing, with further diversification within a subfamily to accommodate multiple intron ligands.

  12. The three circle method

    International Nuclear Information System (INIS)

    Garncarek, Z.

    1989-01-01

    The three circle method in its general form is presented. The method is especially useful for investigation of shapes of agglomerations of objects. An example of its applications to investigation of galaxies distribution is given. 17 refs. (author)

  13. A CRM domain protein functions dually in group I and group II intron splicing in land plant chloroplasts.

    Science.gov (United States)

    Asakura, Yukari; Barkan, Alice

    2007-12-01

    The CRM domain is a recently recognized RNA binding domain found in three group II intron splicing factors in chloroplasts, in a bacterial protein that associates with ribosome precursors, and in a family of uncharacterized proteins in plants. To elucidate the functional repertoire of proteins with CRM domains, we studied CFM2 (for CRM Family Member 2), which harbors four CRM domains. RNA coimmunoprecipitation assays showed that CFM2 in maize (Zea mays) chloroplasts is associated with the group I intron in pre-trnL-UAA and group II introns in the ndhA and ycf3 pre-mRNAs. T-DNA insertions in the Arabidopsis thaliana ortholog condition a defective-seed phenotype (strong allele) or chlorophyll-deficient seedlings with impaired splicing of the trnL group I intron and the ndhA, ycf3-int1, and clpP-int2 group II introns (weak alleles). CFM2 and two previously described CRM proteins are bound simultaneously to the ndhA and ycf3-int1 introns and act in a nonredundant fashion to promote their splicing. With these findings, CRM domain proteins are implicated in the activities of three classes of catalytic RNA: group I introns, group II introns, and 23S rRNA.

  14. The Half-Life of the HSV-1 1.5 kb LAT Intron is similar to the half-Life of the 2.0 kb LAT Intron

    Science.gov (United States)

    Brinkman, Kerry K.; Mishra, Prakhar; Fraser, Nigel W.

    2013-01-01

    Herpes Simplex Virus type 1 (HSV-1) establishes a latent infection in the sensory neurons of the peripheral nervous system of humans. Although about 80 genes are expressed during the lytic cycle of the virus infection, essentially only one gene is expressed during the latent cycle. This gene is known as the latency associated transcript (LAT) and it appears to play a role in the latency cycle through an anti-apoptotic function in the 5’ end of the gene and miRNA encoded along the length of the transcript which down regulate some of the viral immediate early (IE) gene products. The LAT gene is about 8.3 kb long and consists of two exons separated by an unusual intron. The intron between the exons consists of two nested introns. This arrangement of introns has been called a twintron. Furthermore, the larger (2 kb) intron has been shown to be very stable. In this study we measure the stability of the shorter 1.5 kb nested intron and find its half-life is similar to the longer intron. This was achieved by deleting the 0.5 kb overlapping intron from a plasmid construct designed to express the LAT transcript from a tet-inducible promoter, and measuring the half-life of the 1.5 kb intron in tissue culture cells. This finding supports the hypothesis that it is the common branch-point region of these nested introns that is responsible for their stability. PMID:23335177

  15. The Inner Circle Revisited

    DEFF Research Database (Denmark)

    Grau Larsen, Anton; Ellersgaard, Christoph

    2018-01-01

    in social networks, we identify a cohesive core group of 171 individuals within a corporate elite of 6154 board members of the top 1037 Danish corporations. A high degree of social homogeneity in gender, social background, education and career position underlines the cohesion of the inner circle. By mapping...

  16. Inside Larry's Circle

    Science.gov (United States)

    Arnold, Alice

    2009-01-01

    Last spring, students from several North Carolina middle schools were invited to participate in the annual Celebrate the Arts festival in Columbus Country. Larry Hewett, a local art teacher, had been selected to instruct the middle-school students. Larry's River Rock Circles project was made as the starting point for the Celebrate the Arts…

  17. Dynamics on the Circle

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 8; Issue 11. Dynamics on the Circle - Interval Dynamics and Rotation Number. Siddhartha Gadgil. General Article Volume 8 Issue 11 November 2003 pp 25-36. Fulltext. Click here to view fulltext PDF. Permanent link:

  18. Circles, Materiality and Movement

    Science.gov (United States)

    Chorney, Sean

    2017-01-01

    This paper approaches the concept of the circle through the framework of mathematics-as-becoming. This paper focuses specifically on how a concept can be thought of as a process, and on the implications that this might have for mathematics learning. Contrary to long-standing assumptions about mathematical concepts as ideal, inert, Platonic forms,…

  19. Polymorphism in Mitochondrial Group I Introns among Cryptococcus neoformans and Cryptococcus gattii Genotypes and Its Association with Drug Susceptibility

    Directory of Open Access Journals (Sweden)

    Felipe E. E. S. Gomes

    2018-02-01

    Full Text Available Cryptococcosis, one of the most important systemic mycosis in the world, is caused by different genotypes of Cryptococcus neoformans and Cryptococcus gattii, which differ in their ecology, epidemiology, and antifungal susceptibility. Therefore, the search for new molecular markers for genotyping, pathogenicity and drug susceptibility is necessary. Group I introns fulfill the requisites for such task because (i they are polymorphic sequences; (ii their self-splicing is inhibited by some drugs; and (iii their correct splicing under parasitic conditions is indispensable for pathogen survival. Here, we investigated the presence of group I introns in the mitochondrial LSU rRNA gene in 77 Cryptococcus isolates and its possible relation to drug susceptibility. Sequencing revealed two new introns in the LSU rRNA gene. All the introns showed high sequence similarity to other mitochondrial introns from distinct fungi, supporting the hypothesis of an ancient non-allelic invasion. Intron presence was statistically associated with those genotypes reported to be less pathogenic (p < 0.001. Further virulence assays are needed to confirm this finding. In addition, in vitro antifungal tests indicated that the presence of LSU rRNA introns may influence the minimum inhibitory concentration (MIC of amphotericin B and 5-fluorocytosine. These findings point to group I introns in the mitochondrial genome of Cryptococcus as potential molecular markers for antifungal resistance, as well as therapeutic targets.

  20. Reenacting the birth of an intron

    Energy Technology Data Exchange (ETDEWEB)

    Hellsten, Uffe; Aspden, Julie L.; Rio, Donald C.; Rokhsar, Daniel S.

    2011-07-01

    An intron is an extended genomic feature whose function requires multiple constrained positions - donor and acceptor splice sites, a branch point, a polypyrimidine tract and suitable splicing enhancers - that may be distributed over hundreds or thousands of nucleotides. New introns are therefore unlikely to emerge by incremental accumulation of functional sub-elements. Here we demonstrate that a functional intron can be created de novo in a single step by a segmental genomic duplication. This experiment recapitulates in vivo the birth of an intron that arose in the ancestral jawed vertebrate lineage nearly half a billion years ago.

  1. Exon sequence requirements for excision in vivo of the bacterial group II intron RmInt1

    Directory of Open Access Journals (Sweden)

    Toro Nicolás

    2011-05-01

    Full Text Available Abstract Background Group II intron splicing proceeds through two sequential transesterification reactions in which the 5' and 3'-exons are joined together and the lariat intron is released. The intron-encoded protein (IEP assists the splicing of the intron in vivo and remains bound to the excised intron lariat RNA in a ribonucleoprotein particle (RNP that promotes intron mobility. Exon recognition occurs through base-pairing interactions between two guide sequences on the ribozyme domain dI known as EBS1 and EBS2 and two stretches of sequence known as IBS1 and IBS2 on the 5' exon, whereas the 3' exon is recognized through interaction with the sequence immediately upstream from EBS1 [(δ-δ' interaction (subgroup IIA] or with a nucleotide [(EBS3-IBS3 interaction (subgroup IIB and IIC] located in the coordination-loop of dI. The δ nucleotide is involved in base pairing with another intron residue (δ' in subgroup IIB introns and this interaction facilitates base pairing between the 5' exon and the intron. Results In this study, we investigated nucleotide requirements in the distal 5'- and 3' exon regions, EBS-IBS interactions and δ-δ' pairing for excision of the group IIB intron RmInt1 in vivo. We found that the EBS1-IBS1 interaction was required and sufficient for RmInt1 excision. In addition, we provide evidence for the occurrence of canonical δ-δ' pairing and its importance for the intron excision in vivo. Conclusions The excision in vivo of the RmInt1 intron is a favored process, with very few constraints for sequence recognition in both the 5' and 3'-exons. Our results contribute to understand how group II introns spread in nature, and might facilitate the use of RmInt1 in gene targeting.

  2. RNA.

    Science.gov (United States)

    Darnell, James E., Jr.

    1985-01-01

    Ribonucleic acid (RNA) converts genetic information into protein and usually must be processed to serve its function. RNA types, chemical structure, protein synthesis, translation, manufacture, and processing are discussed. Concludes that the first genes might have been spliced RNA and that humans might be closer than bacteria to primitive…

  3. A game magically circling

    DEFF Research Database (Denmark)

    Ejsing-Duun, Stine

    2011-01-01

    This chapter analyses the relationship between players, the game world, and the ordinary world in alternative reality games (ARGs) and location-based games (LBGs). These games use technology to create a game world in the everyday scene. The topic of this chapter is the concept of the 'magic circle......', which defines the relationship between play and the ordinary world, and how this concept relates to a new kind of game....

  4. Euglena gracilis chloroplast DNA: analysis of a 1.6 kb intron of the psb C gene containing an open reading frame of 458 codons.

    Science.gov (United States)

    Montandon, P E; Vasserot, A; Stutz, E

    1986-01-01

    We retrieved a 1.6 kbp intron separating two exons of the psb C gene which codes for the 44 kDa reaction center protein of photosystem II. This intron is 3 to 4 times the size of all previously sequenced Euglena gracilis chloroplast introns. It contains an open reading frame of 458 codons potentially coding for a basic protein of 54 kDa of yet unknown function. The intron boundaries follow consensus sequences established for chloroplast introns related to class II and nuclear pre-mRNA introns. Its 3'-terminal segment has structural features similar to class II mitochondrial introns with an invariant base A as possible branch point for lariat formation.

  5. Recumbent Stone Circles

    Science.gov (United States)

    Ruggles, Clive L. N.

    During the 1970s and early 1980s, British archaeoastronomers were striving to bridge the interpretative gulf between the "megalithic observatories" of Alexander Thom and an archaeological mainstream that, generally speaking, was hostile to any mention of astronomy in relation to the megalithic monuments of Neolithic and Early Bronze Age Britain. The Scottish recumbent stone circles (RSCs) came to represent an example where sounder methodology could overcome many of the data selection issues that had beset earlier studies and, with due restraint, produce credible interpretations. Systematic studies of their orientations consistently concluded that the RSCs had a strong lunar connection, and it was widely envisaged that they were the setting for ceremonies associated with the appearance of the moon over the recumbent stone. Other evidence such as the presence of white quartz and the spatial distribution of cupmarks appeared to back up this conclusion. New archaeological investigations since 1999 have challenged and modified these conclusions, confirming in particular that the circles were built to enclose cairns rather than to demarcate open spaces. Yet the restricted pattern of orientations of these structures could only have been achieved by reference to the basic diurnal motions of the skies, and orientation in relation to simple observations of the midsummer moon remains the most likely reading of the alignment evidence taken as a whole. On the other hand, a consideration of the broader context, which includes the nearby Clava cairns, highlights instead the symbolic importance of the sun.

  6. Imprecise intron losses are less frequent than precise intron losses but are not rare in plants.

    Science.gov (United States)

    Ma, Ming-Yue; Zhu, Tao; Li, Xue-Nan; Lan, Xin-Ran; Liu, Heng-Yuan; Yang, Yu-Fei; Niu, Deng-Ke

    2015-05-27

    In this study, we identified 19 intron losses, including 11 precise intron losses (PILs), six imprecise intron losses (IILs), one de-exonization, and one exon deletion in tomato and potato, and 17 IILs in Arabidopsis thaliana. Comparative analysis of related genomes confirmed that all of the IILs have been fixed during evolution. Consistent with previous studies, our results indicate that PILs are a major type of intron loss. However, at least in plants, IILs are unlikely to be as rare as previously reported. This article was reviewed by Jun Yu and Zhang Zhang. For complete reviews, see the Reviewers' Reports section.

  7. Architecture and Distribution of Introns in Core Genes of Four Fusarium Species

    Directory of Open Access Journals (Sweden)

    Mmatshepho M. Phasha

    2017-11-01

    Full Text Available Removal of introns from transcribed RNA represents a crucial step during the production of mRNA in eukaryotes. Available whole-genome sequences and expressed sequence tags (ESTs have increased our knowledge of this process and revealed various commonalities among eukaryotes. However, certain aspects of intron structure and diversity are taxon-specific, which can complicate the accuracy of in silico gene prediction methods. Using core genes, we evaluated the distribution and architecture of Fusarium circinatum spliceosomal introns, and linked these characteristics to the accuracy of the predicted gene models of the genome of this fungus. We also evaluated intron distribution and architecture in F. verticillioides, F. oxysporum, and F. graminearum, and made comparisons with F. circinatum. Results indicated that F. circinatum and the three other Fusarium species have canonical 5′ and 3′ splice sites, but with subtle differences that are apparently not shared with those of other fungal genera. The polypyrimidine tract of Fusarium introns was also found to be highly divergent among species and genes. Furthermore, the conserved adenosine nucleoside required during the first step of splicing is contained within unique branch site motifs in certain Fusarium introns. Data generated here show that introns of F. circinatum, as well as F. verticillioides, F. oxysporum, and F. graminearum, are characterized by a number of unique features such as the CTHAH and ACCAT motifs of the branch site. Incorporation of such information into genome annotation software will undoubtedly improve the accuracy of gene prediction methods used for Fusarium species and related fungi.

  8. Updating rDNA restriction enzyme maps of Tetrahymena reveals four new intron-containing species

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Simon, E M; Engberg, J

    1985-01-01

    an intron in the 26s rRNA coding region. The evolutionary relationship among the species of the T. pyriformis complex was examined on the basis of the rDNA maps with emphasis on similarities between two of the new species and the widely studied T. thermophila and T. pigmentosa. Examination of a large number...

  9. Domestication of self-splicing introns during eukaryogenesis : the rise of the complex spliceosomal machinery

    NARCIS (Netherlands)

    Vosseberg, Julian; Snel, Berend

    2017-01-01

    ᅟ: The spliceosome is a eukaryote-specific complex that is essential for the removal of introns from pre-mRNA. It consists of five small nuclear RNAs (snRNAs) and over a hundred proteins, making it one of the most complex molecular machineries. Most of this complexity has emerged during

  10. Sequence comparison of the rDNA introns from six different species of Tetrahymena

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Engberg, J

    1985-01-01

    model for the intron RNA of Cech et al. (Proc. Natl. Acad. Sci. U.S.A. 80, 3903 (83)). Most of the sequence variation in the four new sequences reported here is found in single stranded loops in the model. However, in four cases we found nucleotide substitutions in duplex stem regions, two of them...

  11. Genomewide analysis of intronic microRNAs in rice and Arabidopsis

    Indian Academy of Sciences (India)

    2012-12-13

    Dec 13, 2012 ... Seventy-five miRNA stem– loop sequences for rice came from ... The A. thaliana genotype used in this study was Columbia. (Col-0) wildtype. ... sense strand of intronic regions of protein-coding gene, 40 were located in the ...

  12. Domain Discretization and Circle Packings

    DEFF Research Database (Denmark)

    Dias, Kealey

    A circle packing is a configuration of circles which are tangent with one another in a prescribed pattern determined by a combinatorial triangulation, where the configuration fills a planar domain or a two-dimensional surface. The vertices in the triangulation correspond to centers of circles...... to domain discretization problems such as triangulation and unstructured mesh generation techniques. We wish to ask ourselves the question: given a cloud of points in the plane (we restrict ourselves to planar domains), is it possible to construct a circle packing preserving the positions of the vertices...... and constrained meshes having predefined vertices as constraints. A standard method of two-dimensional mesh generation involves conformal mapping of the surface or domain to standardized shapes, such as a disk. Since circle packing is a new technique for constructing discrete conformal mappings, it is possible...

  13. Macronuclear genome structure of the ciliate Nyctotherus ovalis: Single-gene chromosomes and tiny introns

    Directory of Open Access Journals (Sweden)

    Landweber Laura F

    2008-12-01

    Full Text Available Abstract Background Nyctotherus ovalis is a single-celled eukaryote that has hydrogen-producing mitochondria and lives in the hindgut of cockroaches. Like all members of the ciliate taxon, it has two types of nuclei, a micronucleus and a macronucleus. N. ovalis generates its macronuclear chromosomes by forming polytene chromosomes that subsequently develop into macronuclear chromosomes by DNA elimination and rearrangement. Results We examined the structure of these gene-sized macronuclear chromosomes in N. ovalis. We determined the telomeres, subtelomeric regions, UTRs, coding regions and introns by sequencing a large set of macronuclear DNA sequences (4,242 and cDNAs (5,484 and comparing them with each other. The telomeres consist of repeats CCC(AAAACCCCn, similar to those in spirotrichous ciliates such as Euplotes, Sterkiella (Oxytricha and Stylonychia. Per sequenced chromosome we found evidence for either a single protein-coding gene, a single tRNA, or the complete ribosomal RNAs cluster. Hence the chromosomes appear to encode single transcripts. In the short subtelomeric regions we identified a few overrepresented motifs that could be involved in gene regulation, but there is no consensus polyadenylation site. The introns are short (21–29 nucleotides, and a significant fraction (1/3 of the tiny introns is conserved in the distantly related ciliate Paramecium tetraurelia. As has been observed in P. tetraurelia, the N. ovalis introns tend to contain in-frame stop codons or have a length that is not dividable by three. This pattern causes premature termination of mRNA translation in the event of intron retention, and potentially degradation of unspliced mRNAs by the nonsense-mediated mRNA decay pathway. Conclusion The combination of short leaders, tiny introns and single genes leads to very minimal macronuclear chromosomes. The smallest we identified contained only 150 nucleotides.

  14. Functional characterisation of an intron retaining K+ transporter of barley reveals intron-mediated alternate splicing

    KAUST Repository

    Shahzad, K.; Rauf, M.; Ahmed, M.; Malik, Z. A.; Habib, I.; Ahmed, Z.; Mahmood, K.; Ali, R.; Masmoudi, K.; Lemtiri-Chlieh, Fouad; Gehring, Christoph A; Berkowitz, G. A.; Saeed, N. A.

    2015-01-01

    Intron retention in transcripts and the presence of 5 and 3 splice sites within these introns mediate alternate splicing, which is widely observed in animals and plants. Here, functional characterisation of the K+ transporter, HvHKT2;1, with stably

  15. Towards barcode markers in Fungi: an intron map of Ascomycota mitochondria.

    Science.gov (United States)

    Santamaria, Monica; Vicario, Saverio; Pappadà, Graziano; Scioscia, Gaetano; Scazzocchio, Claudio; Saccone, Cecilia

    2009-06-16

    A standardized and cost-effective molecular identification system is now an urgent need for Fungi owing to their wide involvement in human life quality. In particular the potential use of mitochondrial DNA species markers has been taken in account. Unfortunately, a serious difficulty in the PCR and bioinformatic surveys is due to the presence of mobile introns in almost all the fungal mitochondrial genes. The aim of this work is to verify the incidence of this phenomenon in Ascomycota, testing, at the same time, a new bioinformatic tool for extracting and managing sequence databases annotations, in order to identify the mitochondrial gene regions where introns are missing so as to propose them as species markers. The general trend towards a large occurrence of introns in the mitochondrial genome of Fungi has been confirmed in Ascomycota by an extensive bioinformatic analysis, performed on all the entries concerning 11 mitochondrial protein coding genes and 2 mitochondrial rRNA (ribosomal RNA) specifying genes, belonging to this phylum, available in public nucleotide sequence databases. A new query approach has been developed to retrieve effectively introns information included in these entries. After comparing the new query-based approach with a blast-based procedure, with the aim of designing a faithful Ascomycota mitochondrial intron map, the first method appeared clearly the most accurate. Within this map, despite the large pervasiveness of introns, it is possible to distinguish specific regions comprised in several genes, including the full NADH dehydrogenase subunit 6 (ND6) gene, which could be considered as barcode candidates for Ascomycota due to their paucity of introns and to their length, above 400 bp, comparable to the lower end size of the length range of barcodes successfully used in animals. The development of the new query system described here would answer the pressing requirement to improve drastically the bioinformatics support to the DNA Barcode

  16. CIRCLE Enhancement After Myopic SMILE.

    Science.gov (United States)

    Siedlecki, Jakob; Luft, Nikolaus; Mayer, Wolfgang J; Siedlecki, Martin; Kook, Daniel; Meyer, Bertram; Bechmann, Martin; Wiltfang, Rainer; Priglinger, Siegfried G; Dirisamer, Martin

    2018-05-01

    To report the outcomes of enhancement after small incision lenticule extraction (SMILE) using the VisuMax CIRCLE option (Carl Zeiss Meditec AG, Jena, Germany), which converts the SMILE cap into a femtosecond LASIK flap for secondary excimer laser application. Of 2,065 SMILE procedures, 22 eyes (1.1%) re-treated with CIRCLE with a follow-up of 3 months were included in the analysis. SMILE was performed in the usual manner. For re-treatment, the CIRCLE procedure was performed with pattern D flap creation on the VisuMax system and subsequent excimer laser ablation with a Zeiss MEL 90 laser (Carl Zeiss Meditec) with plano target in all cases. Spherical equivalent was -5.56 ± 2.22 diopters (D) before SMILE and -0.51 ± 1.08 D before CIRCLE. CIRCLE enhancement was performed after a mean of 10.0 ± 7.9 months, allowed for safe flap lifting in all eyes, and resulted in a final manifest refraction spherical equivalent of 0.18 ± 0.31 D at 3 months (P line of UDVA. Corrected distance visual acuity (CDVA) remained unchanged at all time points (before vs after CIRCLE, P = .40). Two eyes (9.1 %) lost one line of CDVA; no eye lost two or more lines. The safety and efficacy indices were 1.03 and 0.97 at 3 months. The CIRCLE procedure represents an effective re-treatment option after SMILE. Compared to surface ablation re-treatment after SMILE, CIRCLE seems to offer advantages in respect to speed of visual recovery, safety, and predictability, but at the price of flap creation. [J Refract Surg. 2018;34(5):304-309.]. Copyright 2018, SLACK Incorporated.

  17. Functional characterisation of an intron retaining K+ transporter of barley reveals intron-mediated alternate splicing

    KAUST Repository

    Shahzad, K.

    2015-01-01

    Intron retention in transcripts and the presence of 5 and 3 splice sites within these introns mediate alternate splicing, which is widely observed in animals and plants. Here, functional characterisation of the K+ transporter, HvHKT2;1, with stably retained introns from barley (Hordeum vulgare) in yeast (Saccharomyces cerevisiae), and transcript profiling in yeast and transgenic tobacco (Nicotiana tabacum) is presented. Expression of intron-retaining HvHKT2;1 cDNA (HvHKT2;1-i) in trk1, trk2 yeast strain defective in K+ uptake restored growth in medium containing hygromycin in the presence of different concentrations of K+ and mediated hypersensitivity to Na+. HvHKT2;1-i produces multiple transcripts via alternate splicing of two regular introns and three exons in different compositions. HKT isoforms with retained introns and exon skipping variants were detected in relative expression analysis of (i) HvHKT2;1-i in barley under native conditions, (ii) in transgenic tobacco plants constitutively expressing HvHKT2;1-i, and (iii) in trk1, trk2 yeast expressing HvHKT2;1-i under control of an inducible promoter. Mixed proportions of three HKT transcripts: HvHKT2;1-e (first exon region), HvHKT2;1-i1 (first intron) and HvHKT2;1-i2 (second intron) were observed. The variation in transcript accumulation in response to changing K+ and Na+ concentrations was observed in both heterologous and plant systems. These findings suggest a link between intron-retaining transcripts and different splice variants to ion homeostasis, and their possible role in salt stress.

  18. Evidence against the energetic cost hypothesis for the short introns in highly expressed genes

    Directory of Open Access Journals (Sweden)

    Niu Deng-Ke

    2008-05-01

    Full Text Available Abstract Background In animals, the moss Physcomitrella patens and the pollen of Arabidopsis thaliana, highly expressed genes have shorter introns than weakly expressed genes. A popular explanation for this is selection for transcription efficiency, which includes two sub-hypotheses: to minimize the energetic cost or to minimize the time cost. Results In an individual human, different organs may differ up to hundreds of times in cell number (for example, a liver versus a hypothalamus. Considered at the individual level, a gene specifically expressed in a large organ is actually transcribed tens or hundreds of times more than a gene with a similar expression level (a measure of mRNA abundance per cell specifically expressed in a small organ. According to the energetic cost hypothesis, the former should have shorter introns than the latter. However, in humans and mice we have not found significant differences in intron length between large-tissue/organ-specific genes and small-tissue/organ-specific genes with similar expression levels. Qualitative estimation shows that the deleterious effect (that is, the energetic burden of long introns in highly expressed genes is too negligible to be efficiently selected against in mammals. Conclusion The short introns in highly expressed genes should not be attributed to energy constraint. We evaluated evidence for the time cost hypothesis and other alternatives.

  19. Recurrent loss of specific introns during angiosperm evolution.

    Directory of Open Access Journals (Sweden)

    Hao Wang

    2014-12-01

    Full Text Available Numerous instances of presence/absence variations for introns have been documented in eukaryotes, and some cases of recurrent loss of the same intron have been suggested. However, there has been no comprehensive or phylogenetically deep analysis of recurrent intron loss. Of 883 cases of intron presence/absence variation that we detected in five sequenced grass genomes, 93 were confirmed as recurrent losses and the rest could be explained by single losses (652 or single gains (118. No case of recurrent intron gain was observed. Deep phylogenetic analysis often indicated that apparent intron gains were actually numerous independent losses of the same intron. Recurrent loss exhibited extreme non-randomness, in that some introns were removed independently in many lineages. The two larger genomes, maize and sorghum, were found to have a higher rate of both recurrent loss and overall loss and/or gain than foxtail millet, rice or Brachypodium. Adjacent introns and small introns were found to be preferentially lost. Intron loss genes exhibited a high frequency of germ line or early embryogenesis expression. In addition, flanking exon A+T-richness and intron TG/CG ratios were higher in retained introns. This last result suggests that epigenetic status, as evidenced by a loss of methylated CG dinucleotides, may play a role in the process of intron loss. This study provides the first comprehensive analysis of recurrent intron loss, makes a series of novel findings on the patterns of recurrent intron loss during the evolution of the grass family, and provides insight into the molecular mechanism(s underlying intron loss.

  20. Extensive intron gain in the ancestor of placental mammals

    Science.gov (United States)

    2011-01-01

    Background Genome-wide studies of intron dynamics in mammalian orthologous genes have found convincing evidence for loss of introns but very little for intron turnover. Similarly, large-scale analysis of intron dynamics in a few vertebrate genomes has identified only intron losses and no gains, indicating that intron gain is an extremely rare event in vertebrate evolution. These studies suggest that the intron-rich genomes of vertebrates do not allow intron gain. The aim of this study was to search for evidence of de novo intron gain in domesticated genes from an analysis of their exon/intron structures. Results A phylogenomic approach has been used to analyse all domesticated genes in mammals and chordates that originated from the coding parts of transposable elements. Gain of introns in domesticated genes has been reconstructed on well established mammalian, vertebrate and chordate phylogenies, and examined as to where and when the gain events occurred. The locations, sizes and amounts of de novo introns gained in the domesticated genes during the evolution of mammals and chordates has been analyzed. A significant amount of intron gain was found only in domesticated genes of placental mammals, where more than 70 cases were identified. De novo gained introns show clear positional bias, since they are distributed mainly in 5' UTR and coding regions, while 3' UTR introns are very rare. In the coding regions of some domesticated genes up to 8 de novo gained introns have been found. Intron densities in Eutheria-specific domesticated genes and in older domesticated genes that originated early in vertebrates are lower than those for normal mammalian and vertebrate genes. Surprisingly, the majority of intron gains have occurred in the ancestor of placentals. Conclusions This study provides the first evidence for numerous intron gains in the ancestor of placental mammals and demonstrates that adequate taxon sampling is crucial for reconstructing intron evolution. The

  1. Analysis of ribosomal protein gene structures: implications for intron evolution.

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available Many spliceosomal introns exist in the eukaryotic nuclear genome. Despite much research, the evolution of spliceosomal introns remains poorly understood. In this paper, we tried to gain insights into intron evolution from a novel perspective by comparing the gene structures of cytoplasmic ribosomal proteins (CRPs and mitochondrial ribosomal proteins (MRPs, which are held to be of archaeal and bacterial origin, respectively. We analyzed 25 homologous pairs of CRP and MRP genes that together had a total of 527 intron positions. We found that all 12 of the intron positions shared by CRP and MRP genes resulted from parallel intron gains and none could be considered to be "conserved," i.e., descendants of the same ancestor. This was supported further by the high frequency of proto-splice sites at these shared positions; proto-splice sites are proposed to be sites for intron insertion. Although we could not definitively disprove that spliceosomal introns were already present in the last universal common ancestor, our results lend more support to the idea that introns were gained late. At least, our results show that MRP genes were intronless at the time of endosymbiosis. The parallel intron gains between CRP and MRP genes accounted for 2.3% of total intron positions, which should provide a reliable estimate for future inferences of intron evolution.

  2. Interrupted thymidylate synthase gene of bacteriophages T2 and T6 and other potential self-splicing introns in the T-even bacteriophages

    International Nuclear Information System (INIS)

    Chu, F.K.; Maley, F.; Martinez, J.; Maley, G.F.

    1987-01-01

    Southern hybridization analyses of procaryotic DNA from Escherchia coli, λ bacteriophage, and T1 to T7 phages were carried out. The hybridization probes used consisted of DNA restriction fragments derived from the T4 phage intron-containing thymidylate synthase gene (td) and short synthetic oligodeoxynucleotides defining specific exon and intron regions of the gene. It was shown that intact as well as restricted DNA from the T-even phages hybridized not only to both T4 phage td intron- and exon-specific probes but also to probes defining the td 5' (exon I-intron) and 3' (intron-exon II) presplice junctions. These data strongly suggest that, analogous to the T4 phage, only the T2 and T6 phages among the procaryotes tested contain interrupted td genes. The td intervening sequence in each phage is roughly 1 kilobase pair (kb) in size and interrupts the td gene at a site analogous to that in the T4 phage. This was confirmed by data from Northern (RNA) hybridization analysis of td-specific in vitro transcripts of these phage DNAs. [α- 32 P]GTP in vitro labeling of total RNA from T4 phage-infected cells produced five species of labeled RNAs that were 1, 0.9, 0.83, 0.75, and 0.6 kb in size. Only the 1-, 0.9-, and 0.75-kb species were labeled in RNA from T2- or T6-infected cells. The commonly present 1-kb RNA is the excised td intron, which exists in both linear and circular forms in the respective T-even-phage-infected cells, while the 0.6-kb RNA unique to T4 may be the excised intron derived from the ribonucleotide reductase small subunit gene (nrdB) of the phage. The remaining labeled RNA species are likely candidates for other self-splicing introns

  3. Quality Circles and nuclear energy

    International Nuclear Information System (INIS)

    Wiesendanger, J.; Raveleau, G.

    1983-01-01

    A Circle of Quality is a small group of workers or employees made up of from five to ten volunteers from a given shop, office, or factory team, or sharing identical concerns. For every problem that is taken under advisement, these groups draft a solution, test its validity and propose its application, eventually monitoring its implementation and assessing the results achieved. The problems dealt with and the improvements introduced frequently concern details of the personnel's work routines, product quality, tool reliability. But these improvements become so numerous that, eventually, it is the efficiency of an entire office, shop, department or plant, and hence that of the company itself, that is enhanced thereby. Some of the features of a circle of quality are given. A Circle of quality is a contribution to the reliability of the individual, as also to innovation [fr

  4. Controlled Microwave Heating Accelerates Rolling Circle Amplification.

    Science.gov (United States)

    Yoshimura, Takeo; Suzuki, Takamasa; Mineki, Shigeru; Ohuchi, Shokichi

    2015-01-01

    Rolling circle amplification (RCA) generates single-stranded DNAs or RNA, and the diverse applications of this isothermal technique range from the sensitive detection of nucleic acids to analysis of single nucleotide polymorphisms. Microwave chemistry is widely applied to increase reaction rate as well as product yield and purity. The objectives of the present research were to apply microwave heating to RCA and indicate factors that contribute to the microwave selective heating effect. The microwave reaction temperature was strictly controlled using a microwave applicator optimized for enzymatic-scale reactions. Here, we showed that microwave-assisted RCA reactions catalyzed by either of the four thermostable DNA polymerases were accelerated over 4-folds compared with conventional RCA. Furthermore, the temperatures of the individual buffer components were specifically influenced by microwave heating. We concluded that microwave heating accelerated isothermal RCA of DNA because of the differential heating mechanisms of microwaves on the temperatures of reaction components, although the overall reaction temperatures were the same.

  5. 2. A Circle of ideas

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 2. Geometry A Circle of Ideas. Kapil H Paranjape. Series Article Volume 1 Issue 2 February 1996 pp 26-31. Fulltext. Click here to view fulltext PDF. Permanent link: https://www.ias.ac.in/article/fulltext/reso/001/02/0026-0031. Author Affiliations.

  6. On a Family of Circles

    Science.gov (United States)

    Feeman, Timothy G.

    2011-01-01

    We generalize a standard example from precalculus and calculus texts to give a simple description in polar coordinates of any circle that passes through the origin. We discuss an occurrence of this formula in the context of medical imaging. (Contains 1 figure.)

  7. Queuing systems on a circle

    NARCIS (Netherlands)

    Kroese, Dirk; Schmidt, Volker

    1993-01-01

    Consider a ring on which customers arrive according to a Poisson process. Arriving customers drop somewhere on the circle and wait there for a server who travels on the ring. Whenever this server encounters a customer, he stops and serves the customer according to an arbitrary service time

  8. Inheritance of the group I rDNA intron in Tetrahymena pigmentosa

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Simon, E M; Engberg, J

    1992-01-01

    - strains looking for a strong polarity in the inheritance of the intron (intron homing). Based on the genetic analysis we find that the intron in T. pigmentosa is inherited as a neutral character and that intron+ and intron- alleles segregate in a Mendelian fashion with no sign of intron homing...

  9. Mobile group II intron based gene targeting in Lactobacillus plantarum WCFS1.

    Science.gov (United States)

    Sasikumar, Ponnusamy; Paul, Eldho; Gomathi, Sivasamy; Abhishek, Albert; Sasikumar, Sundaresan; Selvam, Govindan Sadasivam

    2016-10-01

    The usage of recombinant lactic acid bacteria for delivery of therapeutic proteins to the mucosa has been emerging. In the present study, an attempt was made to engineer a thyA mutant of Lactobacillus plantarum (L. plantarum) using lactococcal group II intron Ll.LtrB for the development of biologically contained recombinant L. plantarum for prevention of calcium oxalate stone disease. The 3 kb Ll.LtrB intron donor cassettes from the source vector pACD4C was PCR amplified, ligated into pSIP series of lactobacillus vector pLp_3050sAmyA, yielding a novel vector pLpACD4C (8.6 kb). The quantitative real-time PCR experiment shows 94-fold increased expression of Ll.LtrB intron and 14-fold increased expression of ltrA gene in recombinant L. plantarum containing pLpACD4C. In order to target the thyA gene, the potential intron RNA binding sites in the thyA gene of L. plantarum was predicted with help of computer algorithm. The insertion location 188|189s of thyA gene (lowest E-0.134) was chosen and the wild type intron Ll.LtrB was PCR modified, yielding a retargeted intron of pLpACDthyA. The retargeted intron was expressed by using induction peptide (sppIP), subsequently the integration of intron in thyA gene was identified by PCR screening and finally ThyA - mutant of L. plantarum (ThyA18) was detected. In vitro growth curve result showed that in the absence of thymidine, colony forming units of mutant ThyA18 was decreased, whereas high thymidine concentration (10 μM) supported the growth of the culture until saturation. In conclusion, ThyA - mutant of L. plantarum (ThyA18) constructed in this study will be used as a biologically contained recombinant probiotic to deliver oxalate decarboxylase into the lumen for treatment of hyperoxaluria and calcium oxalate stone deposition. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Locating a circle on a sphere

    DEFF Research Database (Denmark)

    Brimberg, Jack; Juel, Henrik; Schöbel, Anita

    2003-01-01

    We consider the problem of locating a spherical circle with respect to existing facilities on a sphere, such that the sum of weighted distances between the circle and the facilities is minimized, or such that the maximum weighted distance is minimized. The problem properties are analyzed, and we...... give solution procedures. When the circle to be located is restricted to be a great circle, some simplifications are possible....

  11. Locating a minisum circle in the plane

    DEFF Research Database (Denmark)

    Brimberg, Jack; Juel, Henrik; Schöbel, Anita

    2009-01-01

    We consider the problem of locating a circle with respect to existing facilities in the plane such that the sum of weighted distances between the circle and the facilities is minimized, i.e., we approximate a set of given points by a circle regarding the sum of weighted distances. If the radius...

  12. Quantum localisation on the circle

    Science.gov (United States)

    Fresneda, Rodrigo; Gazeau, Jean Pierre; Noguera, Diego

    2018-05-01

    Covariant integral quantisation using coherent states for semi-direct product groups is implemented for the motion of a particle on the circle. In this case, the phase space is the cylinder, which is viewed as a left coset of the Euclidean group E(2). Coherent states issued from fiducial vectors are labeled by points in the cylinder and depend also on extra parameters. We carry out the corresponding quantisations of the basic classical observables, particularly the angular momentum and the 2π-periodic discontinuous angle function. We compute their corresponding lower symbols. The quantum localisation on the circle is examined through the properties of the angle operator yielded by our procedure, its spectrum and lower symbol, its commutator with the quantum angular momentum, and the resulting Heisenberg inequality. Comparison with other approaches to the long-standing question of the quantum angle is discussed.

  13. Patterns of intron gain and conservation in eukaryotic genes

    Directory of Open Access Journals (Sweden)

    Wolf Yuri I

    2007-10-01

    Full Text Available Abstract Background: The presence of introns in protein-coding genes is a universal feature of eukaryotic genome organization, and the genes of multicellular eukaryotes, typically, contain multiple introns, a substantial fraction of which share position in distant taxa, such as plants and animals. Depending on the methods and data sets used, researchers have reached opposite conclusions on the causes of the high fraction of shared introns in orthologous genes from distant eukaryotes. Some studies conclude that shared intron positions reflect, almost entirely, a remarkable evolutionary conservation, whereas others attribute it to parallel gain of introns. To resolve these contradictions, it is crucial to analyze the evolution of introns by using a model that minimally relies on arbitrary assumptions. Results: We developed a probabilistic model of evolution that allows for variability of intron gain and loss rates over branches of the phylogenetic tree, individual genes, and individual sites. Applying this model to an extended set of conserved eukaryotic genes, we find that parallel gain, on average, accounts for only ~8% of the shared intron positions. However, the distribution of parallel gains over the phylogenetic tree of eukaryotes is highly non-uniform. There are, practically, no parallel gains in closely related lineages, whereas for distant lineages, such as animals and plants, parallel gains appear to contribute up to 20% of the shared intron positions. In accord with these findings, we estimated that ancestral introns have a high probability to be retained in extant genomes, and conversely, that a substantial fraction of extant introns have retained their positions since the early stages of eukaryotic evolution. In addition, the density of sites that are available for intron insertion is estimated to be, approximately, one in seven basepairs. Conclusion: We obtained robust estimates of the contribution of parallel gain to the observed

  14. Josephson junctions and circle maps

    Energy Technology Data Exchange (ETDEWEB)

    Bak, P; Bohr, T; Jensen, M H; Christiansen, P V

    1984-01-01

    The return map of a differential equation for the current driven Josephson junction, or the damped driven pendulum, is shown numerically to be a circle map. Phase locking, noise and hysteresis, can thus be understood in a simple and coherent way. The transition to chaos is related to the development of a cubic inflection point. Recent theoretical results on universal behavior at the transition to chaos can readily be checked experimentally by studying I-V characteristics. 17 references, 1 figure.

  15. Circle activity of quality assurance in construction

    International Nuclear Information System (INIS)

    1982-05-01

    This book explains purpose, introduction 10 things to keep in mind, management and role of QC activity, TQC and QC circle activity in construction, introduction of the case of QC circle activity in a company like QC circle activity as TQC activity and QC circle for the bright future, case of experience of QC circle activity such as decreasing concrete loss, improvement of sleeve sticking on the ps wooden floor, overcoming handicap in field where one person works and point of QC 7 tools and order of improvement and management.

  16. The essential function of the Trypanosoma brucei Trl1 homolog in procyclic cells is maturation of the intron-containing tRNATyr

    Czech Academy of Sciences Publication Activity Database

    Lopes, R.R.S.; Silveira, G. de O.; Eitler, R.; Vidal, R.S.; Kessler, A.; Hinger, S.; Paris, Zdeněk; Alfonzo, J. D.; Polycarpo, C.

    2016-01-01

    Roč. 22, č. 8 (2016), s. 1190-1199 ISSN 1355-8382 R&D Projects: GA ČR GJ15-21450Y Institutional support: RVO:60077344 Keywords : Trypanosoma * tRNA * tRNA editing * splicing * intron Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.605, year: 2016

  17. Complex exon-intron marking by histone modifications is not determined solely by nucleosome distribution.

    Directory of Open Access Journals (Sweden)

    Pawandeep Dhami

    2010-08-01

    Full Text Available It has recently been shown that nucleosome distribution, histone modifications and RNA polymerase II (Pol II occupancy show preferential association with exons ("exon-intron marking", linking chromatin structure and function to co-transcriptional splicing in a variety of eukaryotes. Previous ChIP-sequencing studies suggested that these marking patterns reflect the nucleosomal landscape. By analyzing ChIP-chip datasets across the human genome in three cell types, we have found that this marking system is far more complex than previously observed. We show here that a range of histone modifications and Pol II are preferentially associated with exons. However, there is noticeable cell-type specificity in the degree of exon marking by histone modifications and, surprisingly, this is also reflected in some histone modifications patterns showing biases towards introns. Exon-intron marking is laid down in the absence of transcription on silent genes, with some marking biases changing or becoming reversed for genes expressed at different levels. Furthermore, the relationship of this marking system with splicing is not simple, with only some histone modifications reflecting exon usage/inclusion, while others mirror patterns of exon exclusion. By examining nucleosomal distributions in all three cell types, we demonstrate that these histone modification patterns cannot solely be accounted for by differences in nucleosome levels between exons and introns. In addition, because of inherent differences between ChIP-chip array and ChIP-sequencing approaches, these platforms report different nucleosome distribution patterns across the human genome. Our findings confound existing views and point to active cellular mechanisms which dynamically regulate histone modification levels and account for exon-intron marking. We believe that these histone modification patterns provide links between chromatin accessibility, Pol II movement and co-transcriptional splicing.

  18. Learning to live together: mutualism between self-splicing introns and their hosts

    Directory of Open Access Journals (Sweden)

    Chalamcharla Venkata R

    2011-04-01

    Full Text Available Abstract Group I and II introns can be considered as molecular parasites that interrupt protein-coding and structural RNA genes in all domains of life. They function as self-splicing ribozymes and thereby limit the phenotypic costs associated with disruption of a host gene while they act as mobile DNA elements to promote their spread within and between genomes. Once considered purely selfish DNA elements, they now seem, in the light of recent work on the molecular mechanisms regulating bacterial and phage group I and II intron dynamics, to show evidence of co-evolution with their hosts. These previously underappreciated relationships serve the co-evolving entities particularly well in times of environmental stress.

  19. Remarkable interkingdom conservation of intron positions and massive, lineage-specific intron loss and gain in eukaryotic evolution.

    Science.gov (United States)

    Rogozin, Igor B; Wolf, Yuri I; Sorokin, Alexander V; Mirkin, Boris G; Koonin, Eugene V

    2003-09-02

    Sequencing of eukaryotic genomes allows one to address major evolutionary problems, such as the evolution of gene structure. We compared the intron positions in 684 orthologous gene sets from 8 complete genomes of animals, plants, fungi, and protists and constructed parsimonious scenarios of evolution of the exon-intron structure for the respective genes. Approximately one-third of the introns in the malaria parasite Plasmodium falciparum are shared with at least one crown group eukaryote; this number indicates that these introns have been conserved through >1.5 billion years of evolution that separate Plasmodium from the crown group. Paradoxically, humans share many more introns with the plant Arabidopsis thaliana than with the fly or nematode. The inferred evolutionary scenario holds that the common ancestor of Plasmodium and the crown group and, especially, the common ancestor of animals, plants, and fungi had numerous introns. Most of these ancestral introns, which are retained in the genomes of vertebrates and plants, have been lost in fungi, nematodes, arthropods, and probably Plasmodium. In addition, numerous introns have been inserted into vertebrate and plant genes, whereas, in other lineages, intron gain was much less prominent.

  20. Sequence features responsible for intron retention in human

    Directory of Open Access Journals (Sweden)

    Sakabe Noboru

    2007-02-01

    Full Text Available Abstract Background One of the least common types of alternative splicing is the complete retention of an intron in a mature transcript. Intron retention (IR is believed to be the result of intron, rather than exon, definition associated with failure of the recognition of weak splice sites flanking short introns. Although studies on individual retained introns have been published, few systematic surveys of large amounts of data have been conducted on the mechanisms that lead to IR. Results TTo understand how sequence features are associated with or control IR, and to produce a generalized model that could reveal previously unknown signals that regulate this type of alternative splicing, we partitioned intron retention events observed in human cDNAs into two groups based on the relative abundance of both isoforms and compared relevant features. We found that a higher frequency of IR in human is associated with individual introns that have weaker splice sites, genes with shorter intron lengths, higher expression levels and lower density of both a set of exon splicing silencers (ESSs and the intronic splicing enhancer GGG. Both groups of retained introns presented events conserved in mouse, in which the retained introns were also short and presented weaker splice sites. Conclusion Although our results confirmed that weaker splice sites are associated with IR, they showed that this feature alone cannot explain a non-negligible fraction of events. Our analysis suggests that cis-regulatory elements are likely to play a crucial role in regulating IR and also reveals previously unknown features that seem to influence its occurrence. These results highlight the importance of considering the interplay among these features in the regulation of the relative frequency of IR.

  1. On a conjecture concerning helly circle graphs

    Directory of Open Access Journals (Sweden)

    Durán Guillermo

    2003-01-01

    Full Text Available We say that G is an e-circle graph if there is a bijection between its vertices and straight lines on the cartesian plane such that two vertices are adjacent in G if and only if the corresponding lines intersect inside the circle of radius one. This definition suggests a method for deciding whether a given graph G is an e-circle graph, by constructing a convenient system S of equations and inequations which represents the structure of G, in such a way that G is an e-circle graph if and only if S has a solution. In fact, e-circle graphs are exactly the circle graphs (intersection graphs of chords in a circle, and thus this method provides an analytic way for recognizing circle graphs. A graph G is a Helly circle graph if G is a circle graph and there exists a model of G by chords such that every three pairwise intersecting chords intersect at the same point. A conjecture by Durán (2000 states that G is a Helly circle graph if and only if G is a circle graph and contains no induced diamonds (a diamond is a graph formed by four vertices and five edges. Many unsuccessful efforts - mainly based on combinatorial and geometrical approaches - have been done in order to validate this conjecture. In this work, we utilize the ideas behind the definition of e-circle graphs and restate this conjecture in terms of an equivalence between two systems of equations and inequations, providing a new, analytic tool to deal with it.

  2. Modulation of splicing of the preceding intron by antisense oligonucleotide complementary to intra-exon sequence deleted in dystrophin Kobe

    Energy Technology Data Exchange (ETDEWEB)

    Takeshima, Y.; Matuso, M.; Sakamoto, H.; Nishio, H. [Kobe Univ. School of Medicine and Science (Japan)

    1994-09-01

    Molecular analysis of dystrophin Kobe showed that exon 19 of the dystrophin gene bearing a 52 bp deletion was skipped during splicing, although the known consensus sequences at the 5{prime} and 3{prime} splice site of exon 19 were maintained. These data suggest that the deleted sequence of exon 19 may function as a cis-acting factor for exact splicing for the upstream intron. To investigate this potential role, an in vitro splicing system using dystrophin precursors was established. A two-exon precursor containing exon 18, truncated intron 18, and exon 19 was accurately spliced. However, splicing of intron 18 was dramatically inhibited when wild exon 19 was replaced with mutated exon 19. Even though the length of exon 19 was restored to normal by replacing the deleted sequence with other sequence, splicing of intron 18 was not fully reactivated. Characteristically, splicing of intron 18 was inactivated more markedly when the replaced sequence contained less polypurine stretches. These data suggested that modification of the exon sequence would result in a splicing abnormality. Antisense 31 mer 2`-O-methyl ribonucleotide was targeted against 5{prime} end of deleted region of exon 19 to modulate splicing of the mRNA precursor. Splicing of intron 18 was inhibited in a dose- and time-dependent manner. This is the first in vitro evidence to show splicing of dystrophin pre-mRNA can be managed by antisense oligonucleotides. These experiments represent an approach in which antisense oligonucleotides are used to restore the function of a defective dystrophin gene in Duchenne muscular dystrophy by inducing skipping of certain exons during splicing.

  3. A Contracted DNA Repeat in LHX3 Intron 5 Is Associated with Aberrant Splicing and Pituitary Dwarfism in German Shepherd Dogs

    Science.gov (United States)

    Voorbij, Annemarie M. W. Y.; van Steenbeek, Frank G.; Vos-Loohuis, Manon; Martens, Ellen E. C. P.; Hanson-Nilsson, Jeanette M.; van Oost, Bernard A.; Kooistra, Hans S.; Leegwater, Peter A.

    2011-01-01

    Dwarfism in German shepherd dogs is due to combined pituitary hormone deficiency of unknown genetic cause. We localized the recessively inherited defect by a genome wide approach to a region on chromosome 9 with a lod score of 9.8. The region contains LHX3, which codes for a transcription factor essential for pituitary development. Dwarfs have a deletion of one of six 7 bp repeats in intron 5 of LHX3, reducing the intron size to 68 bp. One dwarf was compound heterozygous for the deletion and an insertion of an asparagine residue in the DNA-binding homeodomain of LHX3, suggesting involvement of the gene in the disorder. An exon trapping assay indicated that the shortened intron is not spliced efficiently, probably because it is too small. We applied bisulfite conversion of cytosine to uracil in RNA followed by RT-PCR to analyze the splicing products. The aberrantly spliced RNA molecules resulted from either skipping of exon 5 or retention of intron 5. The same splicing defects were observed in cDNA derived from the pituitary of dwarfs. A survey of similarly mutated introns suggests that there is a minimal distance requirement between the splice donor and branch site of 50 nucleotides. In conclusion, a contraction of a DNA repeat in intron 5 of canine LHX3 leads to deficient splicing and is associated with pituitary dwarfism. PMID:22132174

  4. A contracted DNA repeat in LHX3 intron 5 is associated with aberrant splicing and pituitary dwarfism in German shepherd dogs.

    Directory of Open Access Journals (Sweden)

    Annemarie M W Y Voorbij

    Full Text Available Dwarfism in German shepherd dogs is due to combined pituitary hormone deficiency of unknown genetic cause. We localized the recessively inherited defect by a genome wide approach to a region on chromosome 9 with a lod score of 9.8. The region contains LHX3, which codes for a transcription factor essential for pituitary development. Dwarfs have a deletion of one of six 7 bp repeats in intron 5 of LHX3, reducing the intron size to 68 bp. One dwarf was compound heterozygous for the deletion and an insertion of an asparagine residue in the DNA-binding homeodomain of LHX3, suggesting involvement of the gene in the disorder. An exon trapping assay indicated that the shortened intron is not spliced efficiently, probably because it is too small. We applied bisulfite conversion of cytosine to uracil in RNA followed by RT-PCR to analyze the splicing products. The aberrantly spliced RNA molecules resulted from either skipping of exon 5 or retention of intron 5. The same splicing defects were observed in cDNA derived from the pituitary of dwarfs. A survey of similarly mutated introns suggests that there is a minimal distance requirement between the splice donor and branch site of 50 nucleotides. In conclusion, a contraction of a DNA repeat in intron 5 of canine LHX3 leads to deficient splicing and is associated with pituitary dwarfism.

  5. Intron Retention and TE Exonization Events in ZRANB2

    Directory of Open Access Journals (Sweden)

    Sang-Je Park

    2012-01-01

    Full Text Available The Zinc finger, RAN-binding domain-containing protein 2 (ZRANB2, contains arginine/serine-rich (RS domains that mediate its function in the regulation of alternative splicing. The ZRANB2 gene contains 2 LINE elements (L3b, Plat_L3 between the 9th and 10th exons. We identified the exonization event of a LINE element (Plat_L3. Using genomic PCR, RT-PCR amplification, and sequencing of primate DNA and RNA samples, we analyzed the evolutionary features of ZRANB2 transcripts. The results indicated that 2 of the LINE elements were integrated in human and all of the tested primate samples (hominoids: 3 species; Old World monkey: 8 species; New World monkey: 6 species; prosimian: 1 species. Human, rhesus monkey, crab-eating monkey, African-green monkey, and marmoset harbor the exon derived from LINE element (Plat_L3. RT-PCR amplification revealed the long transcripts and their differential expression patterns. Intriguingly, these long transcripts were abundantly expressed in Old World monkey lineages (rhesus, crab-eating, and African-green monkeys and were expressed via intron retention (IR. Thus, the ZRANB2 gene produces 3 transcript variants in which the Cterminus varies by transposable elements (TEs exonization and IR mechanisms. Therefore, ZRANB2 is valuable for investigating the evolutionary mechanisms of TE exonization and IR during primate evolution.

  6. "Take Me to the Mathematical Circle!"

    OpenAIRE

    Veilande, Ingrida

    2012-01-01

    Preparing the students for various mathematical contests are the key goals of mathematical circles in Latvian schools. The reason why mathematical circles for students of primary schools are organised rather seldom is that problem sets of Olympiads are mainly created for students of 5th to 12th grades. The young participants of circles have to be introduced with the basic principles of Olimpiads mathematics too.

  7. Fairy circle landscapes under the sea

    KAUST Repository

    Ruiz-Reynés, Daniel

    2017-08-03

    Short-scale interactions yield large-scale vegetation patterns that, in turn, shape ecosystem function across landscapes. Fairy circles, which are circular patches bare of vegetation within otherwise continuous landscapes, are characteristic features of semiarid grasslands. We report the occurrence of submarine fairy circle seascapes in seagrass meadows and propose a simple model that reproduces the diversity of seascapes observed in these ecosystems as emerging from plant interactions within the meadow. These seascapes include two extreme cases, a continuous meadow and a bare landscape, along with intermediate states that range from the occurrence of persistent but isolated fairy circles, or solitons, to seascapes with multiple fairy circles, banded vegetation, and

  8. Locating a circle on a sphere

    DEFF Research Database (Denmark)

    Brimberg, Jack; Juel, Henrik; Schöbel, Anita

    2007-01-01

    We consider the problem of locating a spherical circle with respect to existing facilities on a sphere, such that the sum of distances between the circle and the facilities is minimized or such that the maximum distance is minimized. The problem properties are analyzed, and we give solution...... procedures. When the circle to be located is restricted to be a great circle, some simplifications are possible. The models may be used in preliminary studies on the location of large linear facilities on the earth's surface, such as superhighways, pipelines, and transmission lines, or in totally different...

  9. Information flow through the disaster circle

    DEFF Research Database (Denmark)

    Egedorf, Maren Marie; Villanueva Holm-Nielsen, Pablo

    The traditional view of the disaster circle is phase based. Disaster and development professionals recognize that the actions carried out in the various phases of the disaster management cycle are overlapping and build upon each other, having resilience as the overall goal. However information does...... not necessarily flow across the phases of the circle in an effective manner. This is particularly true for the information that crosses the disaster point of the circle. Organisations carry out assessments, surveys and baselines for various purposes, at various points of time in the disaster circle. Output...

  10. Fairy circle landscapes under the sea

    KAUST Repository

    Ruiz-Reyné s, Daniel; Gomila, Damià ; Sintes, Tomà s; Herná ndez-Garcí a, Emilio; Marbà , Nú ria; Duarte, Carlos M.

    2017-01-01

    Short-scale interactions yield large-scale vegetation patterns that, in turn, shape ecosystem function across landscapes. Fairy circles, which are circular patches bare of vegetation within otherwise continuous landscapes, are characteristic features of semiarid grasslands. We report the occurrence of submarine fairy circle seascapes in seagrass meadows and propose a simple model that reproduces the diversity of seascapes observed in these ecosystems as emerging from plant interactions within the meadow. These seascapes include two extreme cases, a continuous meadow and a bare landscape, along with intermediate states that range from the occurrence of persistent but isolated fairy circles, or solitons, to seascapes with multiple fairy circles, banded vegetation, and

  11. Controlled Microwave Heating Accelerates Rolling Circle Amplification.

    Directory of Open Access Journals (Sweden)

    Takeo Yoshimura

    Full Text Available Rolling circle amplification (RCA generates single-stranded DNAs or RNA, and the diverse applications of this isothermal technique range from the sensitive detection of nucleic acids to analysis of single nucleotide polymorphisms. Microwave chemistry is widely applied to increase reaction rate as well as product yield and purity. The objectives of the present research were to apply microwave heating to RCA and indicate factors that contribute to the microwave selective heating effect. The microwave reaction temperature was strictly controlled using a microwave applicator optimized for enzymatic-scale reactions. Here, we showed that microwave-assisted RCA reactions catalyzed by either of the four thermostable DNA polymerases were accelerated over 4-folds compared with conventional RCA. Furthermore, the temperatures of the individual buffer components were specifically influenced by microwave heating. We concluded that microwave heating accelerated isothermal RCA of DNA because of the differential heating mechanisms of microwaves on the temperatures of reaction components, although the overall reaction temperatures were the same.

  12. Activity know-how and doctrine of QC circle

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1976-09-15

    This books introduces activity know-how of QC circle giving descriptions of basic of QC circle activities, introduction operation and development and mind of QC circle activities, method for beginning of QC circle activity like, way order, motivation of introduction of QC circle activity, propel method of QC circle activities, such as leadership, brain storming, and rule of QC circle activity, management and propel method for improvement, development of QC circle activities. It also deals with doctrine of basic of QC circle, purpose, self improvement and group activity.

  13. Activity know-how and doctrine of QC circle

    International Nuclear Information System (INIS)

    1976-09-01

    This books introduces activity know-how of QC circle giving descriptions of basic of QC circle activities, introduction operation and development and mind of QC circle activities, method for beginning of QC circle activity like, way order, motivation of introduction of QC circle activity, propel method of QC circle activities, such as leadership, brain storming, and rule of QC circle activity, management and propel method for improvement, development of QC circle activities. It also deals with doctrine of basic of QC circle, purpose, self improvement and group activity.

  14. Darboux cyclides and webs from circles

    KAUST Repository

    Pottmann, Helmut; Shi, Ling; Skopenkov, Mikhail

    2012-01-01

    to these surfaces based on the spherical model of 3D Möbius geometry, we provide computational tools for the identification of circle families on a given cyclide and for the direct design of those. In particular, we show that certain triples of circle families may

  15. The circle equation over finite fields

    DEFF Research Database (Denmark)

    Aabrandt, Andreas; Hansen, Vagn Lundsgaard

    2017-01-01

    Interesting patterns in the geometry of a plane algebraic curve C can be observed when the defining polynomial equation is solved over the family of finite fields. In this paper, we examine the case of C the classical unit circle defined by the circle equation x2 + y2 = 1. As a main result, we es...

  16. Beyond Quality Circles: Self-Managing Teams.

    Science.gov (United States)

    Sims, Henry P., Jr.; Dean, James W., Jr.

    1985-01-01

    This article reviews the quality circle concept, shows why its characteristics appeal to American executives, and examines some of its limitations. It looks at self-managing teams and discusses the reasons that adoptions have been relatively few. It then shows what organizational conditions are necessary for quality circles to evolve into teams.…

  17. Exploring Factors That Influence Quality Literature Circles

    Science.gov (United States)

    Young, Chase; Mohr, Kathleen A. J.

    2018-01-01

    Research indicates that literature circles are an authentic means for literacy development that students typically enjoy. To better understand the potential value and to add to the research base regarding literature circles, this study, involving 17 fourth graders, explores factors that may influence the quality of literature discussions,…

  18. Developing Soft Skills Using "Literature Circles"

    Science.gov (United States)

    Azmi, Mohd Nazri Bin Latiff

    2013-01-01

    This study investigates the impact of the implementation of "Literature Circles" in an Active Learning classroom in relations to developing soft skills among university students. The use of Literature Circles is a well-known strategy in teaching the students to be more creative, independent, and think out of the box. A group of…

  19. Drosophila polytene chromosome bands formed by gene introns.

    Science.gov (United States)

    Zhimulev, I F; Boldyreva, L V; Demakova, O V; Poholkova, G V; Khoroshko, V A; Zykova, T Yu; Lavrov, S A; Belyaeva, E S

    2016-01-01

    Genetic organization of bands and interbands in polytene chromosomes has long remained a puzzle for geneticists. It has been recently demonstrated that interbands typically correspond to the 5'-ends of house-keeping genes, whereas adjacent loose bands tend to be composed of coding sequences of the genes. In the present work, we made one important step further and mapped two large introns of ubiquitously active genes on the polytene chromosome map. We show that alternative promoter regions of these genes map to interbands, whereas introns and coding sequences found between those promoters correspond to loose grey bands. Thus, a gene having its long intron "sandwiched" between to alternative promoters and a common coding sequence may occupy two interbands and one band in the context of polytene chromosomes. Loose, partially decompacted bands appear to host large introns.

  20. Circles of quality in radiological safety

    International Nuclear Information System (INIS)

    Gonzalez F, J.A.

    1991-01-01

    The concept of Circles of quality arose in Japan like an option to capitalize the enormous potential that the workers had developed as a result of its training in the statistical tools of quality. There are presented a series of steps that could be given with the purpose of implementing a program of ALARA circles. The radiological safety is in it finishes instance responsibility of each hard-working one and there won't be a protection program that can work among apathetic people, it is in this sense where the ALARA circles can provide its maximum contribution creating a conscience of responsibility and participation

  1. Intron loss from the NADH dehydrogenase subunit 4 gene of lettuce mitochondrial DNA: evidence for homologous recombination of a cDNA intermediate.

    Science.gov (United States)

    Geiss, K T; Abbas, G M; Makaroff, C A

    1994-04-01

    The mitochondrial gene coding for subunit 4 of the NADH dehydrogenase complex I (nad4) has been isolated and characterized from lettuce, Lactuca sativa. Analysis of nad4 genes in a number of plants by Southern hybridization had previously suggested that the intron content varied between species. Characterization of the lettuce gene confirms this observation. Lettuce nad4 contains two exons and one group IIA intron, whereas previously sequenced nad4 genes from turnip and wheat contain three group IIA introns. Northern analysis identified a transcript of 1600 nucleotides, which represents the mature nad4 mRNA and a primary transcript of 3200 nucleotides. Sequence analysis of lettuce and turnip nad4 cDNAs was used to confirm the intron/exon border sequences and to examine RNA editing patterns. Editing is observed at the 5' and 3' ends of the lettuce transcript, but is absent from sequences that correspond to exons two, three and the 5' end of exon four in turnip and wheat. In contrast, turnip transcripts are highly edited in this region, suggesting that homologous recombination of an edited and spliced cDNA intermediate was involved in the loss of introns two and three from an ancestral lettuce nad4 gene.

  2. Group I introns and associated homing endonuclease genes reveals a clinal structure for Porphyra spiralis var. amplifolia (Bangiales, Rhodophyta along the Eastern coast of South America

    Directory of Open Access Journals (Sweden)

    Matioli Sergio R

    2008-11-01

    Full Text Available Abstract Background Group I introns are found in the nuclear small subunit ribosomal RNA gene (SSU rDNA of some species of the genus Porphyra (Bangiales, Rhodophyta. Size polymorphisms in group I introns has been interpreted as the result of the degeneration of homing endonuclease genes (HEG inserted in peripheral loops of intron paired elements. In this study, intron size polymorphisms were characterized for different Porphyra spiralis var. amplifolia (PSA populations on the Southern Brazilian coast, and were used to infer genetic relationships and genetic structure of these PSA populations, in addition to cox2-3 and rbcL-S regions. Introns of different sizes were tested qualitatively for in vitro self-splicing. Results Five intron size polymorphisms within 17 haplotypes were obtained from 80 individuals representing eight localities along the distribution of PSA in the Eastern coast of South America. In order to infer genetic structure and genetic relationships of PSA, these polymorphisms and haplotypes were used as markers for pairwise Fst analyses, Mantel's test and median joining network. The five cox2-3 haplotypes and the unique rbcL-S haplotype were used as markers for summary statistics, neutrality tests Tajima's D and Fu's Fs and for median joining network analyses. An event of demographic expansion from a population with low effective number, followed by a pattern of isolation by distance was obtained for PSA populations with the three analyses. In vitro experiments have shown that introns of different lengths were able to self-splice from pre-RNA transcripts. Conclusion The findings indicated that degenerated HEGs are reminiscent of the presence of a full-length and functional HEG, once fixed for PSA populations. The cline of HEG degeneration determined the pattern of isolation by distance. Analyses with the other markers indicated an event of demographic expansion from a population with low effective number. The different degrees of

  3. Group I introns and associated homing endonuclease genes reveals a clinal structure for Porphyra spiralis var. amplifolia (Bangiales, Rhodophyta) along the Eastern coast of South America

    Science.gov (United States)

    2008-01-01

    Background Group I introns are found in the nuclear small subunit ribosomal RNA gene (SSU rDNA) of some species of the genus Porphyra (Bangiales, Rhodophyta). Size polymorphisms in group I introns has been interpreted as the result of the degeneration of homing endonuclease genes (HEG) inserted in peripheral loops of intron paired elements. In this study, intron size polymorphisms were characterized for different Porphyra spiralis var. amplifolia (PSA) populations on the Southern Brazilian coast, and were used to infer genetic relationships and genetic structure of these PSA populations, in addition to cox2-3 and rbcL-S regions. Introns of different sizes were tested qualitatively for in vitro self-splicing. Results Five intron size polymorphisms within 17 haplotypes were obtained from 80 individuals representing eight localities along the distribution of PSA in the Eastern coast of South America. In order to infer genetic structure and genetic relationships of PSA, these polymorphisms and haplotypes were used as markers for pairwise Fst analyses, Mantel's test and median joining network. The five cox2-3 haplotypes and the unique rbcL-S haplotype were used as markers for summary statistics, neutrality tests Tajima's D and Fu's Fs and for median joining network analyses. An event of demographic expansion from a population with low effective number, followed by a pattern of isolation by distance was obtained for PSA populations with the three analyses. In vitro experiments have shown that introns of different lengths were able to self-splice from pre-RNA transcripts. Conclusion The findings indicated that degenerated HEGs are reminiscent of the presence of a full-length and functional HEG, once fixed for PSA populations. The cline of HEG degeneration determined the pattern of isolation by distance. Analyses with the other markers indicated an event of demographic expansion from a population with low effective number. The different degrees of degeneration of the HEG

  4. Mutation of Rubie, a novel long non-coding RNA located upstream of Bmp4, causes vestibular malformation in mice.

    Directory of Open Access Journals (Sweden)

    Kristina A Roberts

    Full Text Available The vestibular apparatus of the vertebrate inner ear uses three fluid-filled semicircular canals to sense angular acceleration of the head. Malformation of these canals disrupts the sense of balance and frequently causes circling behavior in mice. The Epistatic circler (Ecl is a complex mutant derived from wildtype SWR/J and C57L/J mice. Ecl circling has been shown to result from the epistatic interaction of an SWR-derived locus on chromosome 14 and a C57L-derived locus on chromosome 4, but the causative genes have not been previously identified.We developed a mouse chromosome substitution strain (CSS-14 that carries an SWR/J chromosome 14 on a C57BL/10J genetic background and, like Ecl, exhibits circling behavior due to lateral semicircular canal malformation. We utilized CSS-14 to identify the chromosome 14 Ecl gene by positional cloning. Our candidate interval is located upstream of bone morphogenetic protein 4 (Bmp4 and contains an inner ear-specific, long non-coding RNA that we have designated Rubie (RNA upstream of Bmp4 expressed in inner ear. Rubie is spliced and polyadenylated, and is expressed in developing semicircular canals. However, we discovered that the SWR/J allele of Rubie is disrupted by an intronic endogenous retrovirus that causes aberrant splicing and premature polyadenylation of the transcript. Rubie lies in the conserved gene desert upstream of Bmp4, within a region previously shown to be important for inner ear expression of Bmp4. We found that the expression patterns of Bmp4 and Rubie are nearly identical in developing inner ears.Based on these results and previous studies showing that Bmp4 is essential for proper vestibular development, we propose that Rubie is the gene mutated in Ecl mice, that it is involved in regulating inner ear expression of Bmp4, and that aberrant Bmp4 expression contributes to the Ecl phenotype.

  5. Robust Circle Detection Using Harmony Search

    Directory of Open Access Journals (Sweden)

    Jaco Fourie

    2017-01-01

    Full Text Available Automatic circle detection is an important element of many image processing algorithms. Traditionally the Hough transform has been used to find circular objects in images but more modern approaches that make use of heuristic optimisation techniques have been developed. These are often used in large complex images where the presence of noise or limited computational resources make the Hough transform impractical. Previous research on the use of the Harmony Search (HS in circle detection showed that HS is an attractive alternative to many of the modern circle detectors based on heuristic optimisers like genetic algorithms and simulated annealing. We propose improvements to this work that enables our algorithm to robustly find multiple circles in larger data sets and still work on realistic images that are heavily corrupted by noisy edges.

  6. Area of Common Overlap of Three Circles

    National Research Council Canada - National Science Library

    Fewell, M. P

    2006-01-01

    .... The results presented here have general significance in the corpus of menstruation formulae, and could be of specific use in any quantitative application of the three-circle Venn diagram such as for...

  7. Darboux cyclides and webs from circles

    KAUST Repository

    Pottmann, Helmut

    2012-01-01

    Motivated by potential applications in architecture, we study Darboux cyclides. These algebraic surfaces of order ≤4 are a superset of Dupin cyclides and quadrics, and they carry up to six real families of circles. Revisiting the classical approach to these surfaces based on the spherical model of 3D Möbius geometry, we provide computational tools for the identification of circle families on a given cyclide and for the direct design of those. In particular, we show that certain triples of circle families may be arranged as so-called hexagonal webs, and we provide a complete classification of all possible hexagonal webs of circles on Darboux cyclides. © 2011 Elsevier B.V. All rights reserved.

  8. The magic circle and the puzzle piece

    OpenAIRE

    Juul, Jesper

    2008-01-01

    In a common description, to play a game is to step inside a concrete or metaphorical magic circle where special rules apply. In video game studies, this description has received an inordinate amount of criticism which the paper argues has two primary sources: 1. a misreading of the basic concept of the magic circle and 2. a somewhat rushed application of traditional theoretical concerns onto games. The paper argues that games studies must move beyond conventional criticisms of binary distinct...

  9. H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast

    Directory of Open Access Journals (Sweden)

    Shieh Grace S

    2011-12-01

    Full Text Available Abstract Background The packaging of DNA into chromatin regulates transcription from initiation through 3' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA. Results Here we provide evidence that H2B monoubiquitylation (H2BK123ub1 marks introns in Saccharomyces cerevisiae. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3, which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an htb-K123R mutation, leads to synthetic lethality. Conclusion These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.

  10. H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast

    LENUS (Irish Health Repository)

    Shieh, Grace S.

    2011-12-22

    Abstract Background The packaging of DNA into chromatin regulates transcription from initiation through 3\\' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA. Results Here we provide evidence that H2B monoubiquitylation (H2BK123ub1) marks introns in Saccharomyces cerevisiae. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3), which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an htb-K123R mutation, leads to synthetic lethality. Conclusion These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.

  11. Newly evolved introns in human retrogenes provide novel insights into their evolutionary roles

    Directory of Open Access Journals (Sweden)

    Kang Li-Fang

    2012-07-01

    Full Text Available Abstract Background Retrogenes generally do not contain introns. However, in some instances, retrogenes may recruit internal exonic sequences as introns, which is known as intronization. A retrogene that undergoes intronization is a good model with which to investigate the origin of introns. Nevertheless, previously, only two cases in vertebrates have been reported. Results In this study, we systematically screened the human (Homo sapiens genome for retrogenes that evolved introns and analyzed their patterns in structure, expression and origin. In total, we identified nine intron-containing retrogenes. Alignment of pairs of retrogenes and their parents indicated that, in addition to intronization (five cases, retrogenes also may have gained introns by insertion of external sequences into the genes (one case or reversal of the orientation of transcription (three cases. Interestingly, many intronizations were promoted not by base substitutions but by cryptic splice sites, which were silent in the parental genes but active in the retrogenes. We also observed that the majority of introns generated by intronization did not involve frameshifts. Conclusions Intron gains in retrogenes are not as rare as previously thought. Furthermore, diverse mechanisms may lead to intron creation in retrogenes. The activation of cryptic splice sites in the intronization of retrogenes may be triggered by the change of gene structure after retroposition. A high percentage of non-frameshift introns in retrogenes may be because non-frameshift introns do not dramatically affect host proteins. Introns generated by intronization in human retrogenes are generally young, which is consistent with previous findings for Caenorhabditis elegans. Our results provide novel insights into the evolutionary role of introns.

  12. Intronic L1 retrotransposons and nested genes cause transcriptional interference by inducing intron retention, exonization and cryptic polyadenylation.

    Directory of Open Access Journals (Sweden)

    Kristel Kaer

    Full Text Available Transcriptional interference has been recently recognized as an unexpectedly complex and mostly negative regulation of genes. Despite a relatively few studies that emerged in recent years, it has been demonstrated that a readthrough transcription derived from one gene can influence the transcription of another overlapping or nested gene. However, the molecular effects resulting from this interaction are largely unknown.Using in silico chromosome walking, we searched for prematurely terminated transcripts bearing signatures of intron retention or exonization of intronic sequence at their 3' ends upstream to human L1 retrotransposons, protein-coding and noncoding nested genes. We demonstrate that transcriptional interference induced by intronic L1s (or other repeated DNAs and nested genes could be characterized by intron retention, forced exonization and cryptic polyadenylation. These molecular effects were revealed from the analysis of endogenous transcripts derived from different cell lines and tissues and confirmed by the expression of three minigenes in cell culture. While intron retention and exonization were comparably observed in introns upstream to L1s, forced exonization was preferentially detected in nested genes. Transcriptional interference induced by L1 or nested genes was dependent on the presence or absence of cryptic splice sites, affected the inclusion or exclusion of the upstream exon and the use of cryptic polyadenylation signals.Our results suggest that transcriptional interference induced by intronic L1s and nested genes could influence the transcription of the large number of genes in normal as well as in tumor tissues. Therefore, this type of interference could have a major impact on the regulation of the host gene expression.

  13. Spliced RNA of woodchuck hepatitis virus.

    Science.gov (United States)

    Ogston, C W; Razman, D G

    1992-07-01

    Polymerase chain reaction was used to investigate RNA splicing in liver of woodchucks infected with woodchuck hepatitis virus (WHV). Two spliced species were detected, and the splice junctions were sequenced. The larger spliced RNA has an intron of 1300 nucleotides, and the smaller spliced sequence shows an additional downstream intron of 1104 nucleotides. We did not detect singly spliced sequences from which the smaller intron alone was removed. Control experiments showed that spliced sequences are present in both RNA and DNA in infected liver, showing that the viral reverse transcriptase can use spliced RNA as template. Spliced sequences were detected also in virion DNA prepared from serum. The upstream intron produces a reading frame that fuses the core to the polymerase polypeptide, while the downstream intron causes an inframe deletion in the polymerase open reading frame. Whereas the splicing patterns in WHV are superficially similar to those reported recently in hepatitis B virus, we detected no obvious homology in the coding capacity of spliced RNAs from these two viruses.

  14. Circulating microparticles: square the circle

    Science.gov (United States)

    2013-01-01

    Background The present review summarizes current knowledge about microparticles (MPs) and provides a systematic overview of last 20 years of research on circulating MPs, with particular focus on their clinical relevance. Results MPs are a heterogeneous population of cell-derived vesicles, with sizes ranging between 50 and 1000 nm. MPs are capable of transferring peptides, proteins, lipid components, microRNA, mRNA, and DNA from one cell to another without direct cell-to-cell contact. Growing evidence suggests that MPs present in peripheral blood and body fluids contribute to the development and progression of cancer, and are of pathophysiological relevance for autoimmune, inflammatory, infectious, cardiovascular, hematological, and other diseases. MPs have large diagnostic potential as biomarkers; however, due to current technological limitations in purification of MPs and an absence of standardized methods of MP detection, challenges remain in validating the potential of MPs as a non-invasive and early diagnostic platform. Conclusions Improvements in the effective deciphering of MP molecular signatures will be critical not only for diagnostics, but also for the evaluation of treatment regimens and predicting disease outcomes. PMID:23607880

  15. Packing circles and spheres on surfaces

    KAUST Repository

    Schiftner, Alexander; Hö binger, Mathias; Wallner, Johannes; Pottmann, Helmut

    2009-01-01

    Inspired by freeform designs in architecture which involve circles and spheres, we introduce a new kind of triangle mesh whose faces' incircles form a packing. As it turns out, such meshes have a rich geometry and allow us to cover surfaces with circle patterns, sphere packings, approximate circle packings, hexagonal meshes which carry a torsion-free support structure, hybrid tri-hex meshes, and others. We show how triangle meshes can be optimized so as to have the incircle packing property. We explain their relation to conformal geometry and implications on solvability of optimization. The examples we give confirm that this kind of meshes is a rich source of geometric structures relevant to architectural geometry. © 2009 ACM.

  16. Shock circle model for ejector performance evaluation

    International Nuclear Information System (INIS)

    Zhu, Yinhai; Cai, Wenjian; Wen, Changyun; Li, Yanzhong

    2007-01-01

    In this paper, a novel shock circle model for the prediction of ejector performance at the critical mode operation is proposed. By introducing the 'shock circle' at the entrance of the constant area chamber, a 2D exponential expression for velocity distribution is adopted to approximate the viscosity flow near the ejector inner wall. The advantage of the 'shock circle' analysis is that the calculation of ejector performance is independent of the flows in the constant area chamber and diffuser. Consequently, the calculation is even simpler than many 1D modeling methods and can predict the performance of critical mode operation ejectors much more accurately. The effectiveness of the method is validated by two experimental results reported earlier. The proposed modeling method using two coefficients is shown to produce entrainment ratio, efficiency and coefficient of performance (COP) accurately and much closer to experimental results than those of 1D analysis methods

  17. ENTREPRENEURSHIP EDUCATION AND THE ECONOMY VICIOUS CIRCLES

    Directory of Open Access Journals (Sweden)

    MEDAR LUCIAN ION

    2015-06-01

    Full Text Available Education for sustainable development, involves training honest, active, social and creative persons for ensuring the link between environment, society, economy and politics. Trained entrepreneurs in sustainable development, are the engine system which can bring an economic prosperity. Lack of entrepreneurial education in the last 25 years has led accentuated conditions to avoiding economic development in all reference fields where added value can be achieved. Running away from excessive taxation led to the establishment of vicious circles in the economy. Vicious circles of the economy can be found in saving, tax policy, productive investment and the informal economy. Through this study will present the importance of entrepreneurship education in the real economy and some specifications to exit entrepreneurs from vicious circles of the economy.

  18. Packing circles and spheres on surfaces

    KAUST Repository

    Schiftner, Alexander

    2009-12-01

    Inspired by freeform designs in architecture which involve circles and spheres, we introduce a new kind of triangle mesh whose faces\\' incircles form a packing. As it turns out, such meshes have a rich geometry and allow us to cover surfaces with circle patterns, sphere packings, approximate circle packings, hexagonal meshes which carry a torsion-free support structure, hybrid tri-hex meshes, and others. We show how triangle meshes can be optimized so as to have the incircle packing property. We explain their relation to conformal geometry and implications on solvability of optimization. The examples we give confirm that this kind of meshes is a rich source of geometric structures relevant to architectural geometry.

  19. Packing circles and spheres on surfaces

    KAUST Repository

    Schiftner, Alexander

    2009-01-01

    Inspired by freeform designs in architecture which involve circles and spheres, we introduce a new kind of triangle mesh whose faces\\' incircles form a packing. As it turns out, such meshes have a rich geometry and allow us to cover surfaces with circle patterns, sphere packings, approximate circle packings, hexagonal meshes which carry a torsion-free support structure, hybrid tri-hex meshes, and others. We show how triangle meshes can be optimized so as to have the incircle packing property. We explain their relation to conformal geometry and implications on solvability of optimization. The examples we give confirm that this kind of meshes is a rich source of geometric structures relevant to architectural geometry. © 2009 ACM.

  20. Students’ Scientific Circle of Obstetrics and Gynaecology

    Directory of Open Access Journals (Sweden)

    Ivan Polishchuk

    2017-06-01

    Full Text Available The students’ scientific circle is the kind of teaching obstetrics and gynaecology in a higher medical institution. The circle is an elective form of learning that allows the students to get deeper knowledge of a subject and to perfect themselves in the issues of diagnostics in obstetrics and gynaecology as well as to acquaint themselves with basic medical techniques. It helps identify students who are capable of scientific research and allows the students to improve their ability to analytical perception of professional information, the ability to present it to the audience, ask and answer the questions publicly. The article presents the results of practical and research activities of obstetric and gynaecologic section of the students’ scientific circle of Ivano-Frankivsk National Medical University.

  1. Packing circles and spheres on surfaces

    KAUST Repository

    Schiftner, Alexander; Hö binger, Mathias; Wallner, Johannes; Pottmann, Helmut

    2009-01-01

    Inspired by freeform designs in architecture which involve circles and spheres, we introduce a new kind of triangle mesh whose faces' incircles form a packing. As it turns out, such meshes have a rich geometry and allow us to cover surfaces with circle patterns, sphere packings, approximate circle packings, hexagonal meshes which carry a torsion-free support structure, hybrid tri-hex meshes, and others. We show how triangle meshes can be optimized so as to have the incircle packing property. We explain their relation to conformal geometry and implications on solvability of optimization. The examples we give confirm that this kind of meshes is a rich source of geometric structures relevant to architectural geometry.

  2. The Long Intron 1 of Growth Hormone Gene from Reeves’ Turtle (Chinemys reevesii Correlates with Negatively Regulated GH Expression in Four Cell Lines

    Directory of Open Access Journals (Sweden)

    Wen-Sheng Liu

    2016-04-01

    Full Text Available Turtles grow slowly and have a long lifespan. Ultrastructural studies of the pituitary gland in Reeves’ turtle (Chinemys reevesii have revealed that the species possesses a higher nucleoplasmic ratio and fewer secretory granules in growth hormone (GH cells than other animal species in summer and winter. C. reevesii GH gene was cloned and species-specific similarities and differences were investigated. The full GH gene sequence in C. reevesii contains 8517 base pairs (bp, comprising five exons and four introns. Intron 1 was found to be much longer in C. reevesii than in other species. The coding sequence (CDS of the turtle’s GH gene, with and without the inclusion of intron 1, was transfected into four cell lines, including DF-1 chicken embryo fibroblasts, Chinese hamster ovary (CHO cells, human embryonic kidney 293FT cells, and GH4C1 rat pituitary cells; the turtle growth hormone (tGH gene mRNA and protein expression levels decreased significantly in the intron-containing CDS in these cell lines, compared with that of the corresponding intronless CDS. Thus, the long intron 1 of GH gene in Reeves’ turtle might correlate with downregulated gene expression.

  3. CELF1 preferentially binds to exon-intron boundary and regulates alternative splicing in HeLa cells.

    Science.gov (United States)

    Xia, Heng; Chen, Dong; Wu, Qijia; Wu, Gang; Zhou, Yanhong; Zhang, Yi; Zhang, Libin

    2017-09-01

    The current RIP-seq approach has been developed for the identification of genome-wide interaction between RNA binding protein (RBP) and the bound RNA transcripts, but still rarely for identifying its binding sites. In this study, we performed RIP-seq experiments in HeLa cells using a monoclonal antibody against CELF1. Mapping of the RIP-seq reads showed a biased distribution at the 3'UTR and intronic regions. A total of 15,285 and 1384 CELF1-specific sense and antisense peaks were identified using the ABLIRC software tool. Our bioinformatics analyses revealed that 5' and 3' splice site motifs and GU-rich motifs were highly enriched in the CELF1-bound peaks. Furthermore, transcriptome analyses revealed that alternative splicing was globally regulated by CELF1 in HeLa cells. For example, the inclusion of exon 16 of LMO7 gene, a marker gene of breast cancer, is positively regulated by CELF1. Taken together, we have shown that RIP-seq data can be used to decipher RBP binding sites and reveal an unexpected landscape of the genome-wide CELF1-RNA interactions in HeLa cells. In addition, we found that CELF1 globally regulates the alternative splicing by binding the exon-intron boundary in HeLa cells, which will deepen our understanding of the regulatory roles of CELF1 in the pre-mRNA splicing process. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Naturally occuring nucleosome positioning signals in human exons and introns

    DEFF Research Database (Denmark)

    Baldi, Pierre; Brunak, Søren; Chauvin, Yves

    1996-01-01

    We describe the structural implications of a periodic pattern found in human exons and introns by hidden Markov models. We show that exons (besides the reading frame) have a specific sequential structure in the form of a pattern with triplet consensus non-T(A/T)G, and a minimal periodicity of rou...

  5. Identification of novel intronic BRCA1 variants of uncertain ...

    Indian Academy of Sciences (India)

    in a Thai hereditary breast cancer family. Adisorn Ratanaphan, Pornpen Panomwan, Bhutorn Canyuk and Tanaphon Maipang. J. Genet. 90, 327–331. Table 1. Oligodeoxyribonucleotide primers used for PCR amplification of BRCA1 exon–intron 7 boundary sequences. Primers. Nucleotide position. Primer sequence (5 –3 ).

  6. Frequent gain and loss of introns in fungal cytochrome b genes.

    Directory of Open Access Journals (Sweden)

    Liang-Fen Yin

    Full Text Available In this study, all available cytochrome b (Cyt b genes from the GOBASE database were compiled and the evolutionary dynamics of the Cyt b gene introns was assessed. Cyt b gene introns were frequently present in the fungal kingdom and some lower plants, but generally absent or rare in Chromista, Protozoa, and Animalia. Fungal Cyt b introns were found at 35 positions in Cyt b genes and the number of introns varied at individual positions from a single representative to 32 different introns at position 131, showing a wide and patchy distribution. Many homologous introns were present at the same position in distantly related species but absent in closely related species, suggesting that introns of the Cyt b genes were frequently lost. On the other hand, highly similar intron sequences were observed in some distantly related species rather than in closely related species, suggesting that these introns were gained independently, likely through lateral transfers. The intron loss-and-gain events could be mediated by transpositions that might have occurred between nuclear and mitochondria. Southern hybridization analysis confirmed that some introns contained repetitive sequences and might be transposable elements. An intron gain in Botryotinia fuckeliana prevented the development of QoI fungicide resistance, suggesting that intron loss-and-gain events were not necessarily beneficial to their host organisms.

  7. Quality circles: the nurse executive as mentor.

    Science.gov (United States)

    Flarey, D L

    1991-12-01

    Changes within and around the health care environment are forcing health care executives to reexamine their managerial and leadership styles to confront the resulting turbulence. The nurse executive is charged with the profound responsibility of directing the delivery of nursing care throughout the organization. Care delivered today must be of high quality. Declining financial resources as well as personnel shortages cause the executive to be an effective innovator in meeting the increasing demands. Quality circles offer the nurse executive an avenue of recourse. Circles have been effectively implemented in the health care setting, as has been consistently documented over time. By way of a participative management approach, quality circles may lead to increased employee morale and productivity, cost savings, and decreased employee turnover rates, as well as realization of socialization and self-actualization needs. A most effective approach to their introduction would be implementation at the first-line manager level. This promotes an acceptance of the concept at the management level as well as a training course for managers to implement the process at the unit level. The nurse executive facilitates the process at the first-line manager level. This facilitation will cause a positive outcome to diffuse throughout the entire organization. Quality circles offer the nurse executive the opportunity to challenge the existing environmental turmoil and effect a positive and lasting change.

  8. Waring's Problem and the Circle Method

    Indian Academy of Sciences (India)

    other interests include classical music and mountaineering. the problems they worked on. Their proof of a slightly. Keywords weaker form of Ramanujan's original formula was pub-. Waring's problem, circle method, ... arc is fairly simple while it is the minor arc estimation that accounts for the 'major' amount of work involved!

  9. Everything within a Circle Is One Thing

    Centers for Disease Control (CDC) Podcasts

    2017-12-19

    Byron Breedlove, EID managing editor, discuses and reads his December 2017 cover essay, Everything within a Circle is One Thing.  Created: 12/19/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 12/19/2017.

  10. The Prague Linguistic Circle and Dialectics

    Czech Academy of Sciences Publication Activity Database

    Sládek, Ondřej

    -, č. 19 (2017), s. 352-357 E-ISSN 2037-2426 Institutional support: RVO:68378068 Keywords : The Prague Linguistic Circle * Jan Mukařovský * Structuralism * Structural Poetics * Dialectics Subject RIV: AJ - Letters, Mass-media, Audiovision OBOR OECD: Specific literatures

  11. Dynamics and bifurcations of random circle diffeomorphisms

    NARCIS (Netherlands)

    Zmarrou, H.; Homburg, A.J.

    2008-01-01

    We discuss iterates of random circle diffeomorphisms with identically distributed noise, where the noise is bounded and absolutely continuous. Using arguments of B. Deroin, V.A. Kleptsyn and A. Navas, we provide precise conditions under which random attracting fixed points or random attracting

  12. On circle map coupled map lattice

    CERN Document Server

    Ahmed, E

    2002-01-01

    Circle map in one and two dimensions is studied. Both its stability, synchronization using bounded control and persistence is discussed. This work is expected to be applicable in ecology where spatial effects are known to be important. Also it will be relevant to systems where delay effects are not negligible.

  13. An intronic mutation c.6430-3C>G in the F8 gene causes splicing efficiency and premature termination in hemophilia A.

    Science.gov (United States)

    Xia, Zunjing; Lin, Jie; Lu, Lingping; Kim, Chol; Yu, Ping; Qi, Ming

    2018-06-01

    : Hemophilia A is a bleeding disorder caused by coagulation factor VIII protein deficiency or dysfunction, which is classified into severe, moderate, and mild according to factor clotting activity. An overwhelming majority of missense and nonsense mutations occur in exons of F8 gene, whereas mutations in introns can also be pathogenic. This study aimed to investigate the effect of an intronic mutation, c.6430-3C>G (IVS22-3C>G), on pre-mRNA splicing of the F8 gene. We applied DNA and cDNA sequencing in a Chinese boy with hemophilia A to search if any pathogenic mutation in the F8 gene. Functional analysis was performed to investigate the effect of an intronic mutation at the transcriptional level. Human Splicing Finder and PyMol were also used to predict its effect. We found the mutation c.6430-3C>G (IVS22-3C>G) in the F8 gene in the affected boy, with his mother being a carrier. cDNA from the mother and pSPL3 splicing assay showed that the mutation IVS22-3C>G results in a two-nucleotide AG inclusion at the 3' end of intron 22 and leads to a truncated coagulation factor VIII protein, with partial loss of the C1 domain and complete loss of the C2 domain. The in-silico tool predicted that the mutation induces altered pre-mRNA splicing by using a cryptic acceptor site in intron 22. The IVS22-3C>G mutation was confirmed to affect pre-mRNA splicing and produce a truncated protein, which reduces the stability of binding between the F8 protein and von Willebrand factor carrier protein due to the loss of an interaction domain.

  14. Solving nucleic acid structures by molecular replacement: examples from group II intron studies

    International Nuclear Information System (INIS)

    Marcia, Marco; Humphris-Narayanan, Elisabeth; Keating, Kevin S.; Somarowthu, Srinivas; Rajashankar, Kanagalaghatta; Pyle, Anna Marie

    2013-01-01

    Strategies for phasing nucleic acid structures by molecular replacement, using both experimental and de novo designed models, are discussed. Structured RNA molecules are key players in ensuring cellular viability. It is now emerging that, like proteins, the functions of many nucleic acids are dictated by their tertiary folds. At the same time, the number of known crystal structures of nucleic acids is also increasing rapidly. In this context, molecular replacement will become an increasingly useful technique for phasing nucleic acid crystallographic data in the near future. Here, strategies to select, create and refine molecular-replacement search models for nucleic acids are discussed. Using examples taken primarily from research on group II introns, it is shown that nucleic acids are amenable to different and potentially more flexible and sophisticated molecular-replacement searches than proteins. These observations specifically aim to encourage future crystallographic studies on the newly discovered repertoire of noncoding transcripts

  15. Deep intronic mutation and pseudo exon activation as a novel muscular hypertrophy modifier in cattle.

    Directory of Open Access Journals (Sweden)

    Claire Bouyer

    Full Text Available Myostatin is essential for proper regulation of myogenesis, and inactivation of Myostatin results in muscle hypertrophy. Here, we identified an unexpected mutation in the myostatin gene which is almost fixed in Blonde d'Aquitaine cattle. In skeletal muscle, the mutant allele was highly expressed leading to an abnormal transcript consisting of a 41-bp inclusion and premature termination codons and to residual levels of a correctly spliced transcript. This expression pattern, caused by a leaky intronic mutation with regard to spliceosome activity and its apparent stability with regard to surveillance mechanisms, could contribute to the moderate muscle hypertrophy in this cattle breed. This finding is of importance for genetic counseling for meat quantity and quality in livestock production and possibly to manipulate myostatin pre-mRNA in human muscle diseases.

  16. Molecular characterization of a new member of the lariat capping twin-ribozyme introns

    DEFF Research Database (Denmark)

    Tang, Yunjia; Nielsen, Henrik; Masquida, Benoît

    2014-01-01

    BACKGROUND: Twin-ribozyme introns represent a complex class of mobile group I introns that harbour a lariat capping (LC) ribozyme and a homing endonuclease gene embedded in a conventional self-splicing group I ribozyme (GIR2). Twin-ribozyme introns have so far been confined to nucleolar DNA in Na...

  17. Occurrence of Can-SINEs and intron sequence evolution supports robust phylogeny of pinniped carnivores and their terrestrial relatives.

    Science.gov (United States)

    Schröder, Christiane; Bleidorn, Christoph; Hartmann, Stefanie; Tiedemann, Ralph

    2009-12-15

    Investigating the dog genome we found 178965 introns with a moderate length of 200-1000 bp. A screening of these sequences against 23 different repeat libraries to find insertions of short interspersed elements (SINEs) detected 45276 SINEs. Virtually all of these SINEs (98%) belong to the tRNA-derived Can-SINE family. Can-SINEs arose about 55 million years ago before Carnivora split into two basal groups, the Caniformia (dog-like carnivores) and the Feliformia (cat-like carnivores). Genome comparisons of dog and cat recovered 506 putatively informative SINE loci for caniformian phylogeny. In this study we show how to use such genome information of model organisms to research the phylogeny of related non-model species of interest. Investigating a dataset including representatives of all major caniformian lineages, we analysed 24 randomly chosen loci for 22 taxa. All loci were amplifiable and revealed 17 parsimony-informative SINE insertions. The screening for informative SINE insertions yields a large amount of sequence information, in particular of introns, which contain reliable phylogenetic information as well. A phylogenetic analysis of intron- and SINE sequence data provided a statistically robust phylogeny which is congruent with the absence/presence pattern of our SINE markers. This phylogeny strongly supports a sistergroup relationship of Musteloidea and Pinnipedia. Within Pinnipedia, we see strong support from bootstrapping and the presence of a SINE insertion for a sistergroup relationship of the walrus with the Otariidae.

  18. The newest miracle drug: quality circles in hospitals.

    Science.gov (United States)

    McKinney, M M

    1984-01-01

    In recent years, a number of hospitals throughout the United States have been exploring the use of Japanese-style quality circles to reduce their operating expenses, improve productivity, and enhance the quality of work life for hospital employees. This article examines the organizational climate necessary for quality circles, methods used to implement quality circles, and management's role in guiding and responding to circle activities. Ideas for building and maintaining staff support are presented along with a cost/benefit analysis of quality circle programs. The author concludes that quality circles are most successful in hospitals where they are part of a larger organizational development effort. When administrators believe in their employees' ability to contribute to the institution and are willing to invest necessary time and resources in employee education and the measurement of quality circle achievements, quality circles can produce creative solutions to perplexing institutional problems.

  19. Locating a circle on the plane using the minimax criterion

    DEFF Research Database (Denmark)

    Brimberg, Jack; Juel, Henrik; Schoebel, Anita

    2006-01-01

    We consider the problem of locating a circle with respect to existing facilities on the plane, such that the largest weighted distance between the circle and the facilities is minimized. The problem properties are analyzed, and a solution procedure proposed.......We consider the problem of locating a circle with respect to existing facilities on the plane, such that the largest weighted distance between the circle and the facilities is minimized. The problem properties are analyzed, and a solution procedure proposed....

  20. Polymorphism of the aryl-hydrocarbon receptor gene in intron 10 of human cancers

    Directory of Open Access Journals (Sweden)

    M. Rocas

    2011-11-01

    Full Text Available Polychlorinated dibenzo-p-dioxins (PCDDs and related halogenated aromatic hydrocarbons (e.g., PCDFs, often called "dioxins", are ubiquitously present environmental contaminants. Some of them, notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, are among the most toxic synthetic compounds known. The biological effects of dioxins are mediated via the aryl hydrocarbon receptor (AhR. Mutations in the AhR transactivation domain are linked to sensitivity to the acute lethality of TCDD. We present here a study of AhR gene polymorphism in normal and cancer human tissues affecting pre-mRNA splicing in the AhR gene-coding transactivation domain region (exon 10, intron 10, exon 11 region, previously shown to be associated with AhR dysfunction. We tested 126 pairs of normal and cancer tissue samples from liver, lung, stomach, kidney, mucous, breast, and pancreas of 49 males and 77 females (45-70 years of age. We used in vitro splicing assay, RT-PCR and sequencing methods. Our results showed that in an in vitro system it is possible to reconstitute cellular pre-mRNA splicing events. Tested cancer tissues did not contain mutations in the AhR transactivation domain region when the DNA sequences were compared with those from normal tissues. There were also no differences in AhR mRNA splice variants between normal and malignant breast tissues and no polymorphisms in the studied regions or cDNA.

  1. Yoctomole electrochemical genosensing of Ebola virus cDNA by rolling circle and circle to circle amplification.

    Science.gov (United States)

    Carinelli, S; Kühnemund, M; Nilsson, M; Pividori, M I

    2017-07-15

    This work addresses the design of an Ebola diagnostic test involving a simple, rapid, specific and highly sensitive procedure based on isothermal amplification on magnetic particles with electrochemical readout. Ebola padlock probes were designed to detect a specific L-gene sequence present in the five most common Ebola species. Ebola cDNA was amplified by rolling circle amplification (RCA) on magnetic particles. Further re-amplification was performed by circle-to-circle amplification (C2CA) and the products were detected in a double-tagging approach using a biotinylated capture probe for immobilization on magnetic particles and a readout probe for electrochemical detection by square-wave voltammetry on commercial screen-printed electrodes. The electrochemical genosensor was able to detect as low as 200 ymol, corresponding to 120 cDNA molecules of L-gene Ebola virus with a limit of detection of 33 cDNA molecules. The isothermal double-amplification procedure by C2CA combined with the electrochemical readout and the magnetic actuation enables the high sensitivity, resulting in a rapid, inexpensive, robust and user-friendly sensing strategy that offers a promising approach for the primary care in low resource settings, especially in less developed countries. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Three distinct modes of intron dynamics in the evolution of eukaryotes.

    Science.gov (United States)

    Carmel, Liran; Wolf, Yuri I; Rogozin, Igor B; Koonin, Eugene V

    2007-07-01

    Several contrasting scenarios have been proposed for the origin and evolution of spliceosomal introns, a hallmark of eukaryotic genes. A comprehensive probabilistic model to obtain a definitive reconstruction of intron evolution was developed and applied to 391 sets of conserved genes from 19 eukaryotic species. It is inferred that a relatively high intron density was reached early, i.e., the last common ancestor of eukaryotes contained >2.15 introns/kilobase, and the last common ancestor of multicellular life forms harbored approximately 3.4 introns/kilobase, a greater intron density than in most of the extant fungi and in some animals. The rates of intron gain and intron loss appear to have been dropping during the last approximately 1.3 billion years, with the decline in the gain rate being much steeper. Eukaryotic lineages exhibit three distinct modes of evolution of the intron-exon structure. The primary, balanced mode, apparently, operates in all lineages. In this mode, intron gain and loss are strongly and positively correlated, in contrast to previous reports on inverse correlation between these processes. The second mode involves an elevated rate of intron loss and is prevalent in several lineages, such as fungi and insects. The third mode, characterized by elevated rate of intron gain, is seen only in deep branches of the tree, indicating that bursts of intron invasion occurred at key points in eukaryotic evolution, such as the origin of animals. Intron dynamics could depend on multiple mechanisms, and in the balanced mode, gain and loss of introns might share common mechanistic features.

  3. The Acoustic Reality of the Kachruvian Circles: A Rhythmic Perspective

    Science.gov (United States)

    Low, Ee Ling

    2010-01-01

    This paper investigates whether the rhythmic properties of varieties of English found in each of the concentric circles of Kachru's model can, in any way, be elucidated by the "Three Circles" model. A measurement and comparison of the rhythm of three varieties of English: British English (from the Inner Circle), Singapore English (from…

  4. Circles of Support and Personalization: Exploring the Economic Case

    Science.gov (United States)

    Wistow, Gerald; Perkins, Margaret; Knapp, Martin; Bauer, Annette; Bonin, Eva-Maria

    2016-01-01

    Circles of Support aim to enable people with learning disabilities (and others) to live full lives as part of their communities. As part of a wider study of the economic case for community capacity building conducted from 2012 to 2014, we conducted a mixed methods study of five Circles in North West England. Members of these Circles were…

  5. The "Us" in Discuss: Grouping in Literature Circles

    Science.gov (United States)

    Batchelor, Katherine

    2012-01-01

    This article describes one middle school teacher's use of literature circles using heterogeneous grouping. It begins with a brief rationale for using literature circles in the language arts classroom. Next, it describes techniques to form literature circles. Then, it shares how to build and establish a supportive environment within each group. It…

  6. Forming Circle Formations of Anonymous Mobile Agents With Order Preservation

    NARCIS (Netherlands)

    Wang, Chen; Xie, Guangming; Cao, Ming

    2013-01-01

    We propose distributed control laws for a group of anonymous mobile agents to form desired circle formations when the agents move in the one-dimensional space of a circle. The agents are modeled by kinematic points. They share the common knowledge of the orientation of the circle, but are oblivious

  7. Intronic deletions in the SLC34A3 gene: A cautionary tale for mutation analysis of hereditary hypophosphatemic rickets with hypercalciuria

    Science.gov (United States)

    Ichikawa, Shoji; Tuchman, Shamir; Padgett, Leah R.; Gray, Amie K.; Baluarte, H. Jorge; Econs, Michael J.

    2013-01-01

    Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare metabolic disorder, characterized by hypophosphatemia, variable degrees of rickets/osteomalacia, and hypercalciuria secondary to increased serum 1,25-dihydroxyvitamin D [1,25(OH)2D] levels. HHRH is caused by mutations in the SLC34A3 gene, which encodes sodium-phosphate co-transporter type IIc. A 6 ½-year-old female presented with a history of nephrolithiasis. Her metabolic evaluation revealed increased 24- hour urine calcium excretion with high serum calcium, low intact parathyroid hormone (PTH) levels, and elevated 1,25(OH)2D level. In addition, the patient had low to low-normal serum phosphorus with high urine phosphorus. The patient had normal stature; without rachitic or boney deformities or a history of fractures. Genetic analysis of SLC34A3 revealed the patient to be a compound heterozygote for a novel single base pair deletion in exon 12 (c.1304delG) and 30-base pair deletion in intron 6 (g.1440–1469del). The single-base pair mutation causes a frameshift, which results in premature stop codon. The intronic deletion is likely caused by misalignment of the 4-basepair homologous repeats and results in the truncation of an already small intron to 63 bp, which would impair proper RNA splicing of the intron. This is the fourth unique intronic deletion identified in patients with HHRH, suggesting the frequent occurrence of sequence misalignments in SLC34A3 and the importance of screening introns in patients with HHRH. PMID:24176905

  8. Non-Watson Crick base pairs might stabilize RNA structural motifs in ...

    Indian Academy of Sciences (India)

    Watson Crick base pairs, internal loops and pseudoknots have been the highlighting feature of recent structural determination of RNAs. The recent crystal structure of group-I introns has demonstrated that these might constitute RNA structural ...

  9. CHARACTERISTICS OF HYDROCARBON EXPLOITATION IN ARCTIC CIRCLE

    Directory of Open Access Journals (Sweden)

    Vanja Lež

    2013-12-01

    Full Text Available The existence of large quantities of hydrocarbons is supposed within the Arctic Circle. Assumed quantities are 25% of the total undiscovered hydrocarbon reserves on Earth, mostly natural gas. Over 500 major and minor gas accumulations within the Arctic Circle were discovered so far, but apart from Snøhvit gas field, there is no commercial exploitation of natural gas from these fields. Arctic gas projects are complicated, technically hard to accomplish, and pose a great threat to the return of investment, safety of people and equipment and for the ecosystem. Russia is a country that is closest to the realization of the Arctic gas projects that are based on the giant gas fields. The most extreme weather conditions in the seas around Greenland are the reason why this Arctic region is the least explored and furthest from the realization of any gas project (the paper is published in Croatian .

  10. A vicious circle in chronic lymphoedema pathophysiology?

    DEFF Research Database (Denmark)

    Cucchi, F; Rossmeislova, L; Simonsen, L

    2017-01-01

    Chronic lymphoedema is a disease caused by a congenital or acquired damage to the lymphatic system and characterized by complex chains of pathophysiologic events such as lymphatic fluid stasis, chronic inflammation, lymphatic vessels impairment, adipose tissue deposition and fibrosis. These event....... Together, these observations indicate strong reciprocal relationship between lymphatics and adipose tissue and suggest a possible key role of the adipocyte in the pathophysiology of chronic lymphoedema's vicious circle....

  11. Rolling circle amplification of metazoan mitochondrialgenomes

    Energy Technology Data Exchange (ETDEWEB)

    Simison, W. Brian; Lindberg, D.R.; Boore, J.L.

    2005-07-31

    Here we report the successful use of rolling circle amplification (RCA) for the amplification of complete metazoan mt genomes to make a product that is amenable to high-throughput genome sequencing techniques. The benefits of RCA over PCR are many and with further development and refinement of RCA, the sequencing of organellar genomics will require far less time and effort than current long PCR approaches.

  12. Stone circles: form and soil kinematics.

    Science.gov (United States)

    Hallet, Bernard

    2013-01-01

    Distinct surface patterns are ubiquitous and diverse in soils of polar and alpine regions, where the ground temperature oscillates about 0°C. They constitute some of the most striking examples of clearly visible, abiotic self-organization in nature. This paper outlines the interplay of frost-related physical processes that produce these patterns spontaneously and presents unique data documenting subsurface soil rotational motion and surface displacement spanning 20 years in well-developed circles of soil outlined by gravel ridges. These sorted circles are particularly attractive research targets for a number of reasons that provide focus for this paper: (i) their exceptional geometric regularity captures the attention of any observer; (ii) they are currently forming and evolving, hence the underlying processes can be monitored readily, especially because they are localized near the ground surface on a scale of metres, which facilitates comprehensive characterization; and (iii) a recent, highly successful numerical model of sorted circle development helps to draw attention to particular field observations that can be used to assess the model, its assumptions and parameter choices, and to the considerable potential for synergetic field and modelling studies.

  13. Novel viral vectors utilizing intron splice-switching to activate genome rescue, expression and replication in targeted cells

    Directory of Open Access Journals (Sweden)

    El Andaloussi Samir

    2011-05-01

    Full Text Available Abstract Background The outcome of virus infection depends from the precise coordination of viral gene expression and genome replication. The ability to control and regulate these processes is therefore important for analysis of infection process. Viruses are also useful tools in bio- and gene technology; they can efficiently kill cancer cells and trigger immune responses to tumors. However, the methods for constructing tissue- or cell-type specific viruses typically suffer from low target-cell specificity and a high risk of reversion. Therefore novel and universal methods of regulation of viral infection are also important for therapeutic application of virus-based systems. Methods Aberrantly spliced introns were introduced into crucial gene-expression units of adenovirus vector and alphavirus DNA/RNA layered vectors and their effects on the viral gene expression, replication and/or the release of infectious genomes were studied in cell culture. Transfection of the cells with splice-switching oligonucleotides was used to correct the introduced functional defect(s. Results It was demonstrated that viral gene expression, replication and/or the release of infectious genomes can be blocked by the introduction of aberrantly spliced introns. The insertion of such an intron into an adenovirus vector reduced the expression of the targeted gene more than fifty-fold. A similar insertion into an alphavirus DNA/RNA layered vector had a less dramatic effect; here, only the release of the infectious transcript was suppressed but not the subsequent replication and spread of the virus. However the insertion of two aberrantly spliced introns resulted in an over one hundred-fold reduction in the infectivity of the DNA/RNA layered vector. Furthermore, in both systems the observed effects could be reverted by the delivery of splice-switching oligonucleotide(s, which corrected the splicing defects. Conclusions Splice-switch technology, originally developed for

  14. Malonyl CoA decarboxylase deficiency: C to T transition in intron 2 of the MCD gene.

    Science.gov (United States)

    Surendran, S; Sacksteder, K A; Gould, S J; Coldwell, J G; Rady, P L; Tyring, S K; Matalon, R

    2001-09-15

    Malonyl CoA decarboxylase (MCD) is an enzyme involved in the metabolism of fatty acids synthesis. Based on reports of MCD deficiency, this enzyme is particular important in muscle and brain metabolism. Mutations in the MCD gene result in a deficiency of MCD activity, that lead to psychomotor retardation, cardiomyopathy and neonatal death. To date however, only a few patients have been reported with defects in MCD. We report here studies of a patient with MCD deficiency, who presented with hypotonia, cardiomyopathy and psychomotor retardation. DNA sequencing of MCD revealed a homozygous intronic mutation, specifically a -5 C to T transition near the acceptor site for exon 3. RT-PCR amplification of exons 2 and 3 revealed that although mRNA from a normal control sample yielded one major DNA band, the mutant mRNA sample resulted in two distinct DNA fragments. Sequencing of the patient's two RT-PCR products revealed that the larger molecular weight fragments contained exons 2 and 3 as well as the intervening intronic sequence. The smaller size band from the patient contained the properly spliced exons, similar to the normal control. Western blotting analysis of the expressed protein showed only a faint band in the patient sample in contrast to a robust band in the control. In addition, the enzyme activity of the mutant protein was lower than that of the control protein. The data indicate that homozygous mutation in intron 2 disrupt normal splicing of the gene, leading to lower expression of the MCD protein and MCD deficiency. Copyright 2001 Wiley-Liss, Inc.

  15. Sequencing of mitochondrial genomes of nine Aspergillus and Penicillium species identifies mobile introns and accessory genes as main sources of genome size variability.

    Science.gov (United States)

    Joardar, Vinita; Abrams, Natalie F; Hostetler, Jessica; Paukstelis, Paul J; Pakala, Suchitra; Pakala, Suman B; Zafar, Nikhat; Abolude, Olukemi O; Payne, Gary; Andrianopoulos, Alex; Denning, David W; Nierman, William C

    2012-12-12

    The genera Aspergillus and Penicillium include some of the most beneficial as well as the most harmful fungal species such as the penicillin-producer Penicillium chrysogenum and the human pathogen Aspergillus fumigatus, respectively. Their mitochondrial genomic sequences may hold vital clues into the mechanisms of their evolution, population genetics, and biology, yet only a handful of these genomes have been fully sequenced and annotated. Here we report the complete sequence and annotation of the mitochondrial genomes of six Aspergillus and three Penicillium species: A. fumigatus, A. clavatus, A. oryzae, A. flavus, Neosartorya fischeri (A. fischerianus), A. terreus, P. chrysogenum, P. marneffei, and Talaromyces stipitatus (P. stipitatum). The accompanying comparative analysis of these and related publicly available mitochondrial genomes reveals wide variation in size (25-36 Kb) among these closely related fungi. The sources of genome expansion include group I introns and accessory genes encoding putative homing endonucleases, DNA and RNA polymerases (presumed to be of plasmid origin) and hypothetical proteins. The two smallest sequenced genomes (A. terreus and P. chrysogenum) do not contain introns in protein-coding genes, whereas the largest genome (T. stipitatus), contains a total of eleven introns. All of the sequenced genomes have a group I intron in the large ribosomal subunit RNA gene, suggesting that this intron is fixed in these species. Subsequent analysis of several A. fumigatus strains showed low intraspecies variation. This study also includes a phylogenetic analysis based on 14 concatenated core mitochondrial proteins. The phylogenetic tree has a different topology from published multilocus trees, highlighting the challenges still facing the Aspergillus systematics. The study expands the genomic resources available to fungal biologists by providing mitochondrial genomes with consistent annotations for future genetic, evolutionary and population

  16. quatre-quart1 is an indispensable U12 intron-containing gene that plays a crucial role in Arabidopsis development.

    Science.gov (United States)

    Kwak, Kyung Jin; Kim, Bo Mi; Lee, Kwanuk; Kang, Hunseung

    2017-05-17

    Despite increasing understanding of the importance of the splicing of U12-type introns in plant development, the key question of which U12 intron-containing genes are essential for plant development has not yet been explored. Here, we assessed the functional role of the quatre-quart1 (QQT1) gene, one of the ~230 U12 intron-containing genes in Arabidopsis thaliana. Expression of QQT1 in the U11/U12-31K small nuclear ribonucleoprotein mutant (31k) rescued the developmental-defect phenotypes of the 31k mutant, whereas the miRNA-mediated qqt1 knockdown mutants displayed severe defects in growth and development, including severely arrested stem growth, small size, and the formation of serrated leaves. The structures of the shoot apical meristems in the qqt1 mutants were abnormal and disordered. Identification of QQT1-interacting proteins via a yeast two-hybrid screening and a firefly luciferase complementation-imaging assay revealed that a variety of proteins, including many chloroplast-targeted proteins, interacted with QQT1. Importantly, the levels of chloroplast-targeted proteins in the chloroplast were reduced, and the chloroplast structure was abnormal in the qqt1 mutant. Collectively, these results provide clear evidence that QQT1 is an indispensable U12 intron-containing gene whose correct splicing is crucial for the normal development of Arabidopsis. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  17. Differential GC Content between Exons and Introns Establishes Distinct Strategies of Splice-Site Recognition

    Directory of Open Access Journals (Sweden)

    Maayan Amit

    2012-05-01

    Full Text Available During evolution segments of homeothermic genomes underwent a GC content increase. Our analyses reveal that two exon-intron architectures have evolved from an ancestral state of low GC content exons flanked by short introns with a lower GC content. One group underwent a GC content elevation that abolished the differential exon-intron GC content, with introns remaining short. The other group retained the overall low GC content as well as the differential exon-intron GC content, and is associated with longer introns. We show that differential exon-intron GC content regulates exon inclusion level in this group, in which disease-associated mutations often lead to exon skipping. This group's exons also display higher nucleosome occupancy compared to flanking introns and exons of the other group, thus “marking” them for spliceosomal recognition. Collectively, our results reveal that differential exon-intron GC content is a previously unidentified determinant of exon selection and argue that the two GC content architectures reflect the two mechanisms by which splicing signals are recognized: exon definition and intron definition.

  18. Development and utilization of novel intron length polymorphic markers in foxtail millet (Setaria italica (L.) P. Beauv.).

    Science.gov (United States)

    Gupta, Sarika; Kumari, Kajal; Das, Jyotirmoy; Lata, Charu; Puranik, Swati; Prasad, Manoj

    2011-07-01

    Introns are noncoding sequences in a gene that are transcribed to precursor mRNA but spliced out during mRNA maturation and are abundant in eukaryotic genomes. The availability of codominant molecular markers and saturated genetic linkage maps have been limited in foxtail millet (Setaria italica (L.) P. Beauv.). Here, we describe the development of 98 novel intron length polymorphic (ILP) markers in foxtail millet using sequence information of the model plant rice. A total of 575 nonredundant expressed sequence tag (EST) sequences were obtained, of which 327 and 248 unique sequences were from dehydration- and salinity-stressed suppression subtractive hybridization libraries, respectively. The BLAST analysis of 98 EST sequences suggests a nearly defined function for about 64% of them, and they were grouped into 11 different functional categories. All 98 ILP primer pairs showed a high level of cross-species amplification in two millets and two nonmillets species ranging from 90% to 100%, with a mean of ∼97%. The mean observed heterozygosity and Nei's average gene diversity 0.016 and 0.171, respectively, established the efficiency of the ILP markers for distinguishing the foxtail millet accessions. Based on 26 ILP markers, a reasonable dendrogram of 45 foxtail millet accessions was constructed, demonstrating the utility of ILP markers in germplasm characterizations and genomic relationships in millets and nonmillets species.

  19. Splicing of goose parvovirus pre-mRNA influences cytoplasmic translation of the processed mRNA

    Energy Technology Data Exchange (ETDEWEB)

    Li, Long; Pintel, David J., E-mail: pinteld@missouri.edu

    2012-04-25

    Translation of goose parvovirus (GPV) 72 kDa Rep 1 is initiated from unspliced P9-generated mRNAs in ORF1 from the first in-frame AUG (537 AUG); however, this AUG is bypassed in spliced P9-generated RNA: translation of the 52 kDa Rep 2 protein from spliced RNA is initiated in ORF2 at the next AUG downstream (650 AUG). Usage of the 537 AUG was restored in spliced RNA when the GPV intron was replaced with a chimeric SV40 intron, or following specific mutations of the GPV intron which did not appear in the final spliced mRNA. Additionally, 650 AUG usage was gained in unspliced RNA when the GPV intron splice sites were debilitated. Splicing-dependent regulation of translation initiation was mediated in cis by GPV RNA surrounding the target AUGs. Thus, nuclear RNA processing of GPV P9-generated pre-mRNAs has a complex, but significant, effect on alternative translation initiation of the GPV Rep proteins.

  20. Splicing of goose parvovirus pre-mRNA influences cytoplasmic translation of the processed mRNA

    International Nuclear Information System (INIS)

    Li, Long; Pintel, David J.

    2012-01-01

    Translation of goose parvovirus (GPV) 72 kDa Rep 1 is initiated from unspliced P9-generated mRNAs in ORF1 from the first in-frame AUG (537 AUG); however, this AUG is bypassed in spliced P9-generated RNA: translation of the 52 kDa Rep 2 protein from spliced RNA is initiated in ORF2 at the next AUG downstream (650 AUG). Usage of the 537 AUG was restored in spliced RNA when the GPV intron was replaced with a chimeric SV40 intron, or following specific mutations of the GPV intron which did not appear in the final spliced mRNA. Additionally, 650 AUG usage was gained in unspliced RNA when the GPV intron splice sites were debilitated. Splicing-dependent regulation of translation initiation was mediated in cis by GPV RNA surrounding the target AUGs. Thus, nuclear RNA processing of GPV P9-generated pre-mRNAs has a complex, but significant, effect on alternative translation initiation of the GPV Rep proteins.

  1. Introducing Nine-Point Circle to Junior High School Students

    Science.gov (United States)

    Fiangga, S.; Azizah, M. A. N.; Rini, R. N. K.; Hidayanti, A. N.

    2018-01-01

    The concept of circles is an ancient concept that has appeared since Ancient Egypt from which this concept gives many significant contributions in mathematics’ development until now. Nevertheless, the concept of circles hides many uncover mysterious features that are of applications in mathematics. One of the mysterious features is the Nine-Point Circle. This Nine-point circle is also known as Euler’s circle, six-point circle, Feuerbach’s circle, the twelve-point circle, and many others. Because of these different names, there have been misunderstand among mathematicians about the Nine-Point Circle’s history. Besides, the discussion of Nine-Point Circle can be used to be an initial material to explain elementary geometry topic in junior high school’s level curriculum of 2013. Therefore, this concept needs to be delivered to the students as a geometry introduction. A possible form of the integration historical aspect of Nine-point circle is suggested in this paper as well as its importance in the curriculum of 2013.

  2. Circle Maps and C*-algebras

    DEFF Research Database (Denmark)

    Schmidt, Thomas Lundsgaard; Thomsen, Klaus

    2015-01-01

    We consider a construction of $C^*$-algebras from continuous piecewise monotone maps on the circle which generalizes the crossed product construction for homeomorphisms and more generally the construction of Renault, Deaconu and Anantharaman-Delaroche for local homeomorphisms. Assuming that the map...... is surjective and not locally injective we give necessary and sufficient conditions for the simplicity of the $C^*$-algebra and show that it is then a Kirchberg algebra. We provide tools for the calculation of the K-theory groups and turn them into an algorithmic method for Markov maps....

  3. The circling mutant Pcdh15roda is a new mouse model for hearing loss.

    Science.gov (United States)

    Torres, Adriana Amorim; Rzadzinska, Agnieszka K; Ribeiro, Andrea Frozino; Silva, Daniel Almeida da Silva E; Guénet, Jean-Louis; Massironi, Sílvia Maria Gomes; Godard, Ana Lúcia Brunialti

    2013-01-01

    Mouse mutagenesis is a key tool for studying gene function and several mutant alleles have been described and constitute mouse models for human hereditary diseases. Genetic hearing loss represents over 50% of all hearing loss cases in children and, due to the heterogeneity of the disorder, there is still a demand for the isolation and characterization of new genes and alleles. Here we report phenotypic and molecular characterization of a new mouse model for hereditary hearing loss. The mutant rodador, isolated by Massironi and colleagues in 2006, presents an autosomal recessive disorder characterized by deafness and balance dysfunction associated with abnormal stereocilia in the inner ear. The mutation was mapped to mouse chromosome 10, and characterization of the gene Pcdh15 revealed an AT-to-GC transition in intron 23 of mutant animals. The alteration led to the switch of a dinucleotide ApA for ApG, creating a novel intronic acceptor splice site, which leads to incorporation of eight intronic bases into the processed mRNA and alteration of the downstream reading frame. In silico analysis indicated that the mutated protein is truncated and lacks two cadherin domains, and the transmembrane and cytoplasmic domains. Real Time PCR analyses revealed a significantly reduced Pcdh15 mRNA level in the brain of mutant mice, which might be due to the mechanism of non-sense mediated decay. In man, mutations in the orthologue PCDH15 cause non-syndromic deafness and Usher Syndrome Type 1F, a genetic disorder characterized by hearing loss and retinitis pigmentosa. Rodador mouse constitutes a new model for studying deafness in these conditions and may help in the comprehension of the pathogeneses of the disease, as well as of the mechanisms involved in the morphogenesis and function of inner ear stereocilia. This is a new ENU-induced allele and the first isolated in a BALB/c background. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. The group II intron maturase: a reverse transcriptase and splicing factor go hand in hand.

    Science.gov (United States)

    Zhao, Chen; Pyle, Anna Marie

    2017-12-01

    The splicing of group II introns in vivo requires the assistance of a multifunctional intron encoded protein (IEP, or maturase). Each IEP is also a reverse-transcriptase enzyme that enables group II introns to behave as mobile genetic elements. During splicing or retro-transposition, each group II intron forms a tight, specific complex with its own encoded IEP, resulting in a highly reactive holoenzyme. This review focuses on the structural basis for IEP function, as revealed by recent crystal structures of an IEP reverse transcriptase domain and cryo-EM structures of an IEP-intron complex. These structures explain how the same IEP scaffold is utilized for intron recognition, splicing and reverse transcription, while providing a physical basis for understanding the evolutionary transformation of the IEP into the eukaryotic splicing factor Prp8. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. In the vicious circle of fear

    International Nuclear Information System (INIS)

    Zischka, A.

    1980-01-01

    Fear is the great driving force, the basic effect, without which there would be no adaption to new living conditions, and no provision for the future. But fear has a positive influence only as long as it does not gain the upper hand, for then it makes human beings blind and stifles activity. What is important, and will remain so, is the equilibrium between fear and courage, caution and the desire for action, optimism und pessimism. This equilibrium has now been disturbed in the western countries - and only here. Our present fears give rise to hardly any positive measures, but prevent provision for the future. We are threatened with failure due to the manipulated conversion of fear from the maintenance of life to an effect which destroys life. In this way we got into a vicious circle of fear: we must try to weaken the imagined dangers by emphasising the true conditions. The author discusses how the viscious circle can be broken. (orig.) 891 UA/orig. 892 MKO [de

  6. Characteristic differences between the promoters of intron-containing and intronless ribosomal protein genes in yeast

    Directory of Open Access Journals (Sweden)

    Vingron Martin

    2008-10-01

    Full Text Available Abstract Background More than two thirds of the highly expressed ribosomal protein (RP genes in Saccharomyces cerevisiae contain introns, which is in sharp contrast to the genome-wide five percent intron-containing genes. It is well established that introns carry regulatory sequences and that the transcription of RP genes is extensively and coordinately regulated. Here we test the hypotheses that introns are innately associated with heavily transcribed genes and that introns of RP genes contribute regulatory TF binding sequences. Moreover, we investigate whether promoter features are significantly different between intron-containing and intronless RP genes. Results We find that directly measured transcription rates tend to be lower for intron-containing compared to intronless RP genes. We do not observe any specifically enriched sequence motifs in the introns of RP genes other than those of the branch point and the two splice sites. Comparing the promoters of intron-containing and intronless RP genes, we detect differences in number and position of Rap1-binding and IFHL motifs. Moreover, the analysis of the length distribution and the folding free energies suggest that, at least in a sub-population of RP genes, the 5' untranslated sequences are optimized for regulatory function. Conclusion Our results argue against the direct involvement of introns in the regulation of transcription of highly expressed genes. Moreover, systematic differences in motif distributions suggest that RP transcription factors may act differently on intron-containing and intronless gene promoters. Thus, our findings contribute to the decoding of the RP promoter architecture and may fuel the discussion on the evolution of introns.

  7. Empirical Evaluation of Different Feature Representations for Social Circles Detection

    Science.gov (United States)

    2015-06-16

    study and compare the performance on the available labelled Facebook data from the Kaggle competition on learning social circles in networks . We...Kaggle competition on learning social circles in networks [5]. The data consist of hand- labelled friendship egonets from Facebook and a set of 57...16. SECURITY CLASSIFICATION OF: Social circles detection is a special case of community detection in social network that is currently attracting a

  8. Locating a circle on the plane using the minimax criterion

    DEFF Research Database (Denmark)

    Brimberg, Jack; Juel, Henrik; Schöbel, Anita

    2009-01-01

    We consider the problem of locating a circle with respect to existing facilities on the plane, such that the largest weighted distance between the circumference of the circle and the facilities is minimized. The problem properties are analyzed, and a solution procedure proposed......We consider the problem of locating a circle with respect to existing facilities on the plane, such that the largest weighted distance between the circumference of the circle and the facilities is minimized. The problem properties are analyzed, and a solution procedure proposed...

  9. Locating a general minisum 'circle' on a plane

    DEFF Research Database (Denmark)

    Brimberg, Jack; Juel, Henrik; Körner, Mark-Christoph

    2011-01-01

    We approximate a set of given points in the plane by the boundary of a convex and symmetric set which is the unit circle of some norm. This generalizes previous work on the subject which considers Euclidean circles only. More precisely, we examine the problem of locating and scaling the unit circle...... of some given norm k with respect to given points on the plane such that the sum of weighted distances (as measured by the same norm k) between the circumference of the circle and the points is minimized. We present general results and are able to identify a finite dominating set in the case that k...

  10. Quality Circles: Determination of Significant Factors for Success an a General Model for Implementing a Quality Circle Process.

    Science.gov (United States)

    1981-06-01

    receive for contributions to quality and productivity /4:Apdx-47. The initiative for the Quality Circle concept came from Dr Kaoru Ishikawa , a...eloquently summarized by the "Father of Quality Circles", Dr Kaoru Ishikawa . He sees that, although Japan started with the worst quality reputation among...Perceptions of Influence, Academy of Management Journal. December 1974, pp 649-bz. 49. Ishikawa , Kaoru . S.C. Circle Activities. Union of Japanese Scientists and

  11. An ancient spliceosomal intron in the ribosomal protein L7a gene (Rpl7a of Giardia lamblia

    Directory of Open Access Journals (Sweden)

    Gray Michael W

    2005-08-01

    Full Text Available Abstract Background Only one spliceosomal-type intron has previously been identified in the unicellular eukaryotic parasite, Giardia lamblia (a diplomonad. This intron is only 35 nucleotides in length and is unusual in possessing a non-canonical 5' intron boundary sequence, CT, instead of GT. Results We have identified a second spliceosomal-type intron in G. lamblia, in the ribosomal protein L7a gene (Rpl7a, that possesses a canonical GT 5' intron boundary sequence. A comparison of the two known Giardia intron sequences revealed extensive nucleotide identity at both the 5' and 3' intron boundaries, similar to the conserved sequence motifs recently identified at the boundaries of spliceosomal-type introns in Trichomonas vaginalis (a parabasalid. Based on these observations, we searched the partial G. lamblia genome sequence for these conserved features and identified a third spliceosomal intron, in an unassigned open reading frame. Our comprehensive analysis of the Rpl7a intron in other eukaryotic taxa demonstrates that it is evolutionarily conserved and is an ancient eukaryotic intron. Conclusion An analysis of the phylogenetic distribution and properties of the Rpl7a intron suggests its utility as a phylogenetic marker to evaluate particular eukaryotic groupings. Additionally, analysis of the G. lamblia introns has provided further insight into some of the conserved and unique features possessed by the recently identified spliceosomal introns in related organisms such as T. vaginalis and Carpediemonas membranifera.

  12. Meromorphic Vector Fields and Circle Packings

    DEFF Research Database (Denmark)

    Dias, Kealey

    The objective of the Ph.D. project is to initiate a classification of bifurcations of meromorphic vector fields and to clarify their relation to circle packings. Technological applications are to image analysis and to effective grid generation using discrete conformal mappings. The two branches...... of dynamical systems, continuous and discrete, correspond to the study of differential equations (vector fields) and iteration of mappings respectively. In holomorphic dynamics, the systems studied are restricted to those described by holomorphic (complex analytic) functions or meromorphic (allowing poles...... as singularities) functions. There already exists a well-developed theory for iterative holomorphic dynamical systems, and successful relations found between iteration theory and flows of vector fields have been one of the main motivations for the recent interest in holomorphic vector fields. Restricting...

  13. Squaring the circle of healthcare supplies.

    Science.gov (United States)

    Böhme, Tillmann; Williams, Sharon; Childerhouse, Paul; Deakins, Eric; Towill, Denis

    2014-01-01

    The purpose of this paper is to use a systems lens to assess the comparative performance of healthcare supply chains and provide guidance for their improvement. A well-established and rigorous multi-method audit methodology, based on the uncertainty circle model, yields an objective assessment of value stream performance in eight Australasian public sector hospitals. Cause-effect analysis identifies the major barriers to achieving smooth, seamless flows. Potentially high-leverage remedial actions identified using systems thinking are examined with the aid of an exemplar case. The majority of the healthcare value streams studied are underperforming compared with those in the European automotive industry. Every public hospital appears to be caught in the grip of vicious circles of system uncertainty, in large part being caused by problems of their own making. The single exception is making good progress towards seamless functional integration, which has been achieved by elevating supply chain management to a core competence; having a clearly articulated supply chain vision; adopting a systems approach; and, managing supplies with accurate information. The small number of cases limits the generalisability of the findings at this time. Hospital supply chain managers endeavouring to achieve smooth and seamless supply flows should attempt to elevate the status of supplies management within their organisation to that of a core competence, and should use accurate information to manage their value streams holistically as a set of interwoven processes. A four-level prism model is proposed as a useful framework for thus improving healthcare supply delivery systems. Material flow concepts originally developed to provide objective assessments of value stream performance in commercial settings are adapted for use in a healthcare setting. The ability to identify exemplar organisations via a context-free uncertainty measure, and to use systems thinking to identify high

  14. The rolling circle amplification and next generation sequencing ...

    African Journals Online (AJOL)

    Rolling circle amplification is a simple approach of enriching populations of single-stranded DNA plant begomovirus genomes (genus, Begomovirus; family, Geminiviridae). This is an innovative approach that utilizes the robustness of the bacteriophage phi29 DNA polymerase used in circle amplification, together with deep ...

  15. Quality Circles in Higher Education: Quality, Satisfaction, and Climate.

    Science.gov (United States)

    Kay, Carol; Healy, Margaret

    The effect of quality circles at Iowa State University on absenteeism, performance evaluation, perceptions of the organization climate, job satisfaction, and perceived opportunities for professional and personal growth was measured in this study. The process of quality circles is designed to promote job fulfillment and organizational productivity…

  16. D'Nealian Handwriting versus Circle-Stick Print.

    Science.gov (United States)

    Thurber, Donald N.

    This paper argues against teaching children to make letters using circle-stick writing. It contends that the circle-stick method requires continued pen/pencil lifts hindering rhythm or flow in the writing process and that there is little carry-over value into cursive writing as the two scripts are totally different. D'Nealian print, one type of…

  17. An Effective Time and Management Strategy in Quality Circles.

    Science.gov (United States)

    Halverson, Don E.

    Contending that participation in quality circles enhances effective time management by school administrators and teachers, this guide provides both a theoretical briefing and practical recommendations for better time management. A pre- posttest prefaces a review of basic concepts of quality circles with reference to the work of Abraham Maslow,…

  18. Building quality into academic programmes using quality circles | Ivy ...

    African Journals Online (AJOL)

    The use of teams or quality circles is a relatively new approach to quality improvement in higher education in South Africa. This article describes some of the advantages in using the approach and some of the pitfalls that need to be considered. The debate of the "quality circle life cycle", which culminates in the demise of the ...

  19. Growing a Circle of Courage Culture: One School's Journey

    Science.gov (United States)

    Espiner, Deborah; Guild, Diane

    2010-01-01

    Mt. Richmond Special School is the first Circle of Courage school in New Zealand. The school reflects the richness of the cultural and learning diversity found in many New Zealand schools. Located in the heart of South Auckland, the school's 130 students represent a wide range of ethnic backgrounds. The universal values in the Circle of Courage…

  20. Finding the Maximal Area of Bounded Polygons in a Circle

    Science.gov (United States)

    Rokach, Arie

    2005-01-01

    The article deals with the area of polygons that are inscribed in a given circle. Naturally, the following question arises: Among all n-polygons that are inscribed in a given circle, which one has the biggest area? Intuitively, it may be guessed that is suitable for secondary students, and without any use id calculus, but only using very…

  1. T. thermophila group I introns that cleave amide bonds

    Science.gov (United States)

    Joyce, Gerald F. (Inventor)

    1997-01-01

    The present invention relates to nucleic acid enzymes or enzymatic RNA molecules that are capable of cleaving a variety of bonds, including phosphodiester bonds and amide bonds, in a variety of substrates. Thus, the disclosed enzymatic RNA molecules are capable of functioning as nucleases and/or peptidases. The present invention also relates to compositions containing the disclosed enzymatic RNA molecule and to methods of making, selecting, and using such enzymes and compositions.

  2. U12 type introns were lost at multiple occasions during evolution

    Directory of Open Access Journals (Sweden)

    Bartschat Sebastian

    2010-02-01

    Full Text Available Abstract Background Two categories of introns are known, a common U2 type and a rare U12 type. These two types of introns are removed by distinct spliceosomes. The phylogenetic distribution of spliceosomal RNAs that are characteristic of the U12 spliceosome, i.e. the U11, U12, U4atac and U6atac RNAs, suggest that U12 spliceosomes were lost in many phylogenetic groups. We have now examined the distribution of U2 and U12 introns in many of these groups. Results U2 and U12 introns were predicted by making use of available EST and genomic sequences. The results show that in species or branches where U12 spliceosomal components are missing, also U12 type of introns are lacking. Examples are the choanoflagellate Monosiga brevicollis, Entamoeba histolytica, green algae, diatoms, and the fungal lineage Basidiomycota. Furthermore, whereas U12 splicing does not occur in Caenorhabditis elegans, U12 introns as well as U12 snRNAs are present in Trichinella spiralis, which is deeply branching in the nematode tree. A comparison of homologous genes in T. spiralis and C. elegans revealed different mechanisms whereby U12 introns were lost. Conclusions The phylogenetic distribution of U12 introns and spliceosomal RNAs give further support to an early origin of U12 dependent splicing. In addition, this distribution identifies a large number of instances during eukaryotic evolution where such splicing was lost.

  3. The strength of intron donor splice sites in human genes displays a bell-shaped pattern

    DEFF Research Database (Denmark)

    Wang, Kai; Wernersson, Rasmus; Brunak, Søren

    2011-01-01

    introns. Interestingly, when analysing the intron containing gene pool from mouse consisting of >15 000 genes, we found the convex pattern to be conserved despite >75 million years of evolutionary divergence between the two organisms. We also analysed an interesting, novel class of chimeric genes which...

  4. The splicing of tiny introns of Paramecium is controlled by MAGO.

    Science.gov (United States)

    Contreras, Julia; Begley, Victoria; Marsella, Laura; Villalobo, Eduardo

    2018-07-15

    The exon junction complex (EJC) is a key element of the splicing machinery. The EJC core is composed of eIF4A3, MAGO, Y14 and MLN51. Few accessory proteins, such as CWC22 or UPF3, bind transiently to the EJC. The EJC has been implicated in the control of the splicing of long introns. To ascertain whether the EJC controls the splicing of short introns, we used Paramecium tetraurelia as a model organism, since it has thousands of very tiny introns. To elucidate whether EJC affects intron splicing in P. tetraurelia, we searched for EJC protein-coding genes, and silenced those genes coding for eIF4A3, MAGO and CWC22. We found that P. tetraurelia likely assembles an active EJC with only three of the core proteins, since MLN51 is lacking. Silencing of eIF4A3 or CWC22 genes, but not that of MAGO, caused lethality. Silencing of the MAGO gene caused either an increase, decrease, or no change in intron retention levels of some intron-containing mRNAs used as reporters. We suggest that a fine-tuning expression of EJC genes is required for steady intron removal in P. tetraurelia. Taking into consideration our results and those published by others, we conclude that the EJC controls splicing independently of the intron size. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Functional comparison of three transformer gene introns regulating conditional female lethality

    Science.gov (United States)

    The trasformer gene plays a critical role in the sex determination pathways of many insects. We cloned two transformer gene introns from Anastrepha suspensa, the Caribbean fruit fly. These introns have sequences that putatively have a role in sex-specific splicing patterns that affect sex determinat...

  6. Comparative Analysis of Vertebrate Dystrophin Loci Indicate Intron Gigantism as a Common Feature

    Science.gov (United States)

    Pozzoli, Uberto; Elgar, Greg; Cagliani, Rachele; Riva, Laura; Comi, Giacomo P.; Bresolin, Nereo; Bardoni, Alessandra; Sironi, Manuela

    2003-01-01

    The human DMD gene is the largest known to date, spanning > 2000 kb on the X chromosome. The gene size is mainly accounted for by huge intronic regions. We sequenced 190 kb of Fugu rubripes (pufferfish) genomic DNA corresponding to the complete dystrophin gene (FrDMD) and provide the first report of gene structure and sequence comparison among dystrophin genomic sequences from different vertebrate organisms. Almost all intron positions and phases are conserved between FrDMD and its mammalian counterparts, and the predicted protein product of the Fugu gene displays 55% identity and 71% similarity to human dystrophin. In analogy to the human gene, FrDMD presents several-fold longer than average intronic regions. Analysis of intron sequences of the human and murine genes revealed that they are extremely conserved in size and that a similar fraction of total intron length is represented by repetitive elements; moreover, our data indicate that intron expansion through repeat accumulation in the two orthologs is the result of independent insertional events. The hypothesis that intron length might be functionally relevant to the DMD gene regulation is proposed and substantiated by the finding that dystrophin intron gigantism is common to the three vertebrate genes. [Supplemental material is available online at www.genome.org.] PMID:12727896

  7. Exonization of an Intronic LINE-1 Element Causing Becker Muscular Dystrophy as a Novel Mutational Mechanism in Dystrophin Gene.

    Science.gov (United States)

    Gonçalves, Ana; Oliveira, Jorge; Coelho, Teresa; Taipa, Ricardo; Melo-Pires, Manuel; Sousa, Mário; Santos, Rosário

    2017-10-03

    A broad mutational spectrum in the dystrophin ( DMD ) gene, from large deletions/duplications to point mutations, causes Duchenne/Becker muscular dystrophy (D/BMD). Comprehensive genotyping is particularly relevant considering the mutation-centered therapies for dystrophinopathies. We report the genetic characterization of a patient with disease onset at age 13 years, elevated creatine kinase levels and reduced dystrophin labeling, where multiplex-ligation probe amplification (MLPA) and genomic sequencing failed to detect pathogenic variants. Bioinformatic, transcriptomic (real time PCR, RT-PCR), and genomic approaches (Southern blot, long-range PCR, and single molecule real-time sequencing) were used to characterize the mutation. An aberrant transcript was identified, containing a 103-nucleotide insertion between exons 51 and 52, with no similarity with the DMD gene. This corresponded to the partial exonization of a long interspersed nuclear element (LINE-1), disrupting the open reading frame. Further characterization identified a complete LINE-1 (~6 kb with typical hallmarks) deeply inserted in intron 51. Haplotyping and segregation analysis demonstrated that the mutation had a de novo origin. Besides underscoring the importance of mRNA studies in genetically unsolved cases, this is the first report of a disease-causing fully intronic LINE-1 element in DMD , adding to the diversity of mutational events that give rise to D/BMD.

  8. Exonization of an Intronic LINE-1 Element Causing Becker Muscular Dystrophy as a Novel Mutational Mechanism in Dystrophin Gene

    Science.gov (United States)

    Gonçalves, Ana; Coelho, Teresa; Melo-Pires, Manuel; Sousa, Mário

    2017-01-01

    A broad mutational spectrum in the dystrophin (DMD) gene, from large deletions/duplications to point mutations, causes Duchenne/Becker muscular dystrophy (D/BMD). Comprehensive genotyping is particularly relevant considering the mutation-centered therapies for dystrophinopathies. We report the genetic characterization of a patient with disease onset at age 13 years, elevated creatine kinase levels and reduced dystrophin labeling, where multiplex-ligation probe amplification (MLPA) and genomic sequencing failed to detect pathogenic variants. Bioinformatic, transcriptomic (real time PCR, RT-PCR), and genomic approaches (Southern blot, long-range PCR, and single molecule real-time sequencing) were used to characterize the mutation. An aberrant transcript was identified, containing a 103-nucleotide insertion between exons 51 and 52, with no similarity with the DMD gene. This corresponded to the partial exonization of a long interspersed nuclear element (LINE-1), disrupting the open reading frame. Further characterization identified a complete LINE-1 (~6 kb with typical hallmarks) deeply inserted in intron 51. Haplotyping and segregation analysis demonstrated that the mutation had a de novo origin. Besides underscoring the importance of mRNA studies in genetically unsolved cases, this is the first report of a disease-causing fully intronic LINE-1 element in DMD, adding to the diversity of mutational events that give rise to D/BMD. PMID:28972564

  9. SATB1 regulates SPARC expression in K562 cell line through binding to a specific sequence in the third intron

    International Nuclear Information System (INIS)

    Li, K.; Cai, R.; Dai, B.B.; Zhang, X.Q.; Wang, H.J.; Ge, S.F.; Xu, W.R.; Lu, J.

    2007-01-01

    Special AT-rich binding protein 1 (SATB1), a cell type-specific nuclear matrix attachment region (MAR) DNA-binding protein, tethers to a specific DNA sequence and regulates gene expression through chromatin remodeling and HDAC (histone deacetylase complex) recruitment. In this study, a SATB1 eukaryotic expression plasmid was transfected into the human erythroleukemia K562 cell line and individual clones that stably over-expressed the SATB1 protein were isolated. Microarray analysis revealed that hundreds of genes were either up- or down-regulated in the SATB1 over-expressing K562 cell lines. One of these was the extra-cellular matrix glycoprotein, SPARC (human secreted protein acidic and rich in cysteine). siRNA knock-down of SATB1 also reduced SPARC expression, which was consistent with elevated SPARC levels in the SATB1 over-expressing cell line. Bioinformatics software Mat-inspector showed that a 17 bp DNA sequence in the third intron of SPARC possessed a high potential for SATB1 binding; a finding confirmed by Chromatin immunoprecipitation (ChIP) with anti-SATB1 antibody. Our results show for the first time that forced-expression of SATB1 in K562 cells triggers SPARC up-regulation by binding to a 17 bp DNA sequence in the third intron

  10. Evolution of the tRNALeu (UAA) Intron and Congruence of Genetic Markers in Lichen-Symbiotic Nostoc.

    Science.gov (United States)

    Kaasalainen, Ulla; Olsson, Sanna; Rikkinen, Jouko

    2015-01-01

    The group I intron interrupting the tRNALeu UAA gene (trnL) is present in most cyanobacterial genomes as well as in the plastids of many eukaryotic algae and all green plants. In lichen symbiotic Nostoc, the P6b stem-loop of trnL intron always involves one of two different repeat motifs, either Class I or Class II, both with unresolved evolutionary histories. Here we attempt to resolve the complex evolution of the two different trnL P6b region types. Our analysis indicates that the Class II repeat motif most likely appeared first and that independent and unidirectional shifts to the Class I motif have since taken place repeatedly. In addition, we compare our results with those obtained with other genetic markers and find strong evidence of recombination in the 16S rRNA gene, a marker widely used in phylogenetic studies on Bacteria. The congruence of the different genetic markers is successfully evaluated with the recently published software Saguaro, which has not previously been utilized in comparable studies.

  11. Evolution of the tRNALeu (UAA Intron and Congruence of Genetic Markers in Lichen-Symbiotic Nostoc.

    Directory of Open Access Journals (Sweden)

    Ulla Kaasalainen

    Full Text Available The group I intron interrupting the tRNALeu UAA gene (trnL is present in most cyanobacterial genomes as well as in the plastids of many eukaryotic algae and all green plants. In lichen symbiotic Nostoc, the P6b stem-loop of trnL intron always involves one of two different repeat motifs, either Class I or Class II, both with unresolved evolutionary histories. Here we attempt to resolve the complex evolution of the two different trnL P6b region types. Our analysis indicates that the Class II repeat motif most likely appeared first and that independent and unidirectional shifts to the Class I motif have since taken place repeatedly. In addition, we compare our results with those obtained with other genetic markers and find strong evidence of recombination in the 16S rRNA gene, a marker widely used in phylogenetic studies on Bacteria. The congruence of the different genetic markers is successfully evaluated with the recently published software Saguaro, which has not previously been utilized in comparable studies.

  12. Heritability in the efficiency of nonsense-mediated mRNA decay in humans.

    LENUS (Irish Health Repository)

    Seoighe, Cathal

    2010-01-01

    BACKGROUND: In eukaryotes mRNA transcripts of protein-coding genes in which an intron has been retained in the coding region normally result in premature stop codons and are therefore degraded through the nonsense-mediated mRNA decay (NMD) pathway. There is evidence in the form of selective pressure for in-frame stop codons in introns and a depletion of length three introns that this is an important and conserved quality-control mechanism. Yet recent reports have revealed that the efficiency of NMD varies across tissues and between individuals, with important clinical consequences. PRINCIPAL FINDINGS: Using previously published Affymetrix exon microarray data from cell lines genotyped as part of the International HapMap project, we investigated whether there are heritable, inter-individual differences in the abundance of intron-containing transcripts, potentially reflecting differences in the efficiency of NMD. We identified intronic probesets using EST data and report evidence of heritability in the extent of intron expression in 56 HapMap trios. We also used a genome-wide association approach to identify genetic markers associated with intron expression. Among the top candidates was a SNP in the DCP1A gene, which forms part of the decapping complex, involved in NMD. CONCLUSIONS: While we caution that some of the apparent inter-individual difference in intron expression may be attributable to different handling or treatments of cell lines, we hypothesize that there is significant polymorphism in the process of NMD, resulting in heritable differences in the abundance of intronic mRNA. Part of this phenotype is likely to be due to a polymorphism in a decapping enzyme on human chromosome 3.

  13. Heritability in the efficiency of nonsense-mediated mRNA decay in humans

    KAUST Repository

    Seoighe, Cathal

    2010-07-21

    Background: In eukaryotes mRNA transcripts of protein-coding genes in which an intron has been retained in the coding region normally result in premature stop codons and are therefore degraded through the nonsense-mediated mRNA decay (NMD) pathway. There is evidence in the form of selective pressure for in-frame stop codons in introns and a depletion of length three introns that this is an important and conserved quality-control mechanism. Yet recent reports have revealed that the efficiency of NMD varies across tissues and between individuals, with important clinical consequences. Principal Findings: Using previously published Affymetrix exon microarray data from cell lines genotyped as part of the International HapMap project, we investigated whether there are heritable, inter-individual differences in the abundance of intron-containing transcripts, potentially reflecting differences in the efficiency of NMD. We identified intronic probesets using EST data and report evidence of heritability in the extent of intron expression in 56 HapMap trios. We also used a genome-wide association approach to identify genetic markers associated with intron expression. Among the top candidates was a SNP in the DCP1A gene, which forms part of the decapping complex, involved in NMD. Conclusions: While we caution that some of the apparent inter-individual difference in intron expression may be attributable to different handling or treatments of cell lines, we hypothesize that there is significant polymorphism in the process of NMD, resulting in heritable differences in the abundance of intronic mRNA. Part of this phenotype is likely to be due to a polymorphism in a decapping enzyme on human chromosome 3. © 2010 Seoighe, Gehring.

  14. Becker muscular dystrophy due to an intronic splicing mutation inducing a dual dystrophin transcript.

    Science.gov (United States)

    Todeschini, Alice; Gualandi, Francesca; Trabanelli, Cecilia; Armaroli, Annarita; Ravani, Anna; Fanin, Marina; Rota, Silvia; Bello, Luca; Ferlini, Alessandra; Pegoraro, Elena; Padovani, Alessandro; Filosto, Massimiliano

    2016-10-01

    We describe a 29-year-old patient who complained of left thigh muscle weakness since he was 23 and of moderate proximal weakness of both lower limbs with difficulty in climbing stairs and running since he was 27. Mild weakness of iliopsoas and quadriceps muscles and muscle atrophy of both the distal forearm and thigh were observed upon clinical examination. He harboured a novel c.1150-3C>G substitution in the DMD gene, affecting the intron 10 acceptor splice site and causing exon 11 skipping and an out-of-frame transcript. However, protein of normal molecular weight but in reduced amounts was observed on Western Blot analysis. Reverse transcription analysis on muscle RNA showed production, via alternative splicing, of a transcript missing exon 11 as well as a low abundant full-length transcript which is enough to avoid the severe Duchenne phenotype. Our study showed that a reduced amount of full length dystrophin leads to a mild form of Becker muscular dystrophy. These results confirm earlier findings that low amounts of dystrophin can be associated with a milder phenotype, which is promising for therapies aiming at dystrophin restoration. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Analysis and recognition of 5 ' UTR intron splice sites in human pre-mRNA

    DEFF Research Database (Denmark)

    Eden, E.; Brunak, Søren

    2004-01-01

    Prediction of splice sites in non-coding regions of genes is one of the most challenging aspects of gene structure recognition. We perform a rigorous analysis of such splice sites embedded in human 5' untranslated regions (UTRs), and investigate correlations between this class of splice sites and...

  16. Phylogenetic distribution of intron positions in alpha-amylase genes of bilateria suggests numerous gains and losses.

    Directory of Open Access Journals (Sweden)

    Jean-Luc Da Lage

    Full Text Available Most eukaryotes have at least some genes interrupted by introns. While it is well accepted that introns were already present at moderate density in the last eukaryote common ancestor, the conspicuous diversity of intron density among genomes suggests a complex evolutionary history, with marked differences between phyla. The question of the rates of intron gains and loss in the course of evolution and factors influencing them remains controversial. We have investigated a single gene family, alpha-amylase, in 55 species covering a variety of animal phyla. Comparison of intron positions across phyla suggests a complex history, with a likely ancestral intronless gene undergoing frequent intron loss and gain, leading to extant intron/exon structures that are highly variable, even among species from the same phylum. Because introns are known to play no regulatory role in this gene and there is no alternative splicing, the structural differences may be interpreted more easily: intron positions, sizes, losses or gains may be more likely related to factors linked to splicing mechanisms and requirements, and to recognition of introns and exons, or to more extrinsic factors, such as life cycle and population size. We have shown that intron losses outnumbered gains in recent periods, but that "resets" of intron positions occurred at the origin of several phyla, including vertebrates. Rates of gain and loss appear to be positively correlated. No phase preference was found. We also found evidence for parallel gains and for intron sliding. Presence of introns at given positions was correlated to a strong protosplice consensus sequence AG/G, which was much weaker in the absence of intron. In contrast, recent intron insertions were not associated with a specific sequence. In animal Amy genes, population size and generation time seem to have played only minor roles in shaping gene structures.

  17. The Prague Linguistic Circle and Dialectics

    Directory of Open Access Journals (Sweden)

    Ondřej Sládek

    2017-12-01

    Full Text Available The study deals with dialectics in the context of the Prague Linguistic Circle, particularly in the context of Jan Mukařovský’s thinking. The essay presents 1 main sources of Mukařovský’s dialectics, and outlines 2 Mukařovský’s dialectical method. The notion of dialectics appears in Mukařovský’s scholarly work in a set of connections. He applied dialectics as a method, manner or form of rationality. It served as a means of gaining knowledge about the world, specific phenomena and objects, their essence, interconnectedness as well as development. Mukařovský also used it as a procedure for resolving contradictions (antinomies that he encountered in his scientific explorations and in ordinary practical activities. He understood dialectical thinking as dynamic, open, and pluralist thinking striving to reflect reality as a constant process. Gradual coming together of dialectics and materialism, evident in Mukařovský’s scholarly works from the mid-1930s, resulted, ten years later, in a public adoption of dialectical materialism.

  18. Quality circles--new wave or fad?

    Science.gov (United States)

    Herkimer, A G

    1984-07-01

    The American healthcare industry must avoid the dangers of commitment to bureaucratic organizational thinking and be willing to experiment with Theory Z and quality circles. Productivity depends on trust, subtlety and intimacy. The industry must acknowledge that management style and organizational form are nothing more than facets of the larger organization of society. The ultimate goal should be to understand how the structure of society and the management of healthcare organizations can be coordinated. The common thread in Japanese life is intimacy. The caring, support, and disciplined unselfishness which makes life possible come through close social relationships. Accordingly, there is (or at least, there should be) a common thread in this nation's healthcare industry--the desire to render quality health care in an effective and efficient manner. The underlying messages are many, but they are not overwhelming. Perhaps the first message to healthcare managers is that a healthcare delivery system can realize the full potential of its employees only if it invests in their training and then shares with them the power to influence decisions. Without training, the invitation to participate in decision making will lead only to frustration and conflict. Without a sharing of decision-making power, an investment in training will be both frustrating and wasteful.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Geršgorin and his circles

    CERN Document Server

    Varga, Richard S

    2004-01-01

    TheGer? sgorin CircleTheorem, averywell-known resultin linear algebra today, stems from the paper of S. Ger? sgorin in 1931 (which is reproduced in AppendixD)where,givenanarbitraryn×ncomplexmatrix,easyarithmetic operationsontheentriesofthematrixproducendisks,inthecomplexplane, whose union contains all eigenvalues of the given matrix. The beauty and simplicity of Ger? sgorin’s Theorem has undoubtedly inspired further research in this area, resulting in hundreds of papers in which the name “Ger? sgorin” appears. The goal of this book is to give a careful and up-to-date treatment of various aspects of this topic. The author ?rst learned of Ger? sgorin’s results from friendly conversations with Olga Taussky-Todd and John Todd, which inspired me to work in this area.Olgawasclearlypassionateaboutlinearalgebraandmatrixtheory,and her path-?nding results in these areas were like a magnet to many, including this author! It is the author’s hope that the results, presented here on topics related to Ger? sgorin...

  20. Androgen circle of polycystic ovary syndrome.

    Science.gov (United States)

    Homburg, Roy

    2009-07-01

    Although the aetiology of polycystic ovary syndrome (PCOS) is still not known and the search for causative genes is proving elusive, it is generally agreed that hyperandrogenism is at the heart of the syndrome. Here, it is proposed that excess androgens are the root cause of PCOS starting from their influence on the female fetus in programming gene expression, producing the characteristic signs and symptoms which are then exacerbated by a propagation of excess ovarian androgen production from multiple small follicles, anovulation and insulin resistance in the reproductive life-span, thus setting up a vicious perpetual circle of androgen excess. This opinion paper, rather than being a full-scale review, is intentionally biased in support of this hypothesis that androgen excess is the 'root of all evil' in PCOS; in the hope that its acceptance could lead to more direct treatment of the syndrome in all its facets rather than the symptomatic treatment of side effects of androgen excess that we are addressing today.

  1. RNA splicing in a new rhabdovirus from Culex mosquitoes.

    Science.gov (United States)

    Kuwata, Ryusei; Isawa, Haruhiko; Hoshino, Keita; Tsuda, Yoshio; Yanase, Tohru; Sasaki, Toshinori; Kobayashi, Mutsuo; Sawabe, Kyoko

    2011-07-01

    Among members of the order Mononegavirales, RNA splicing events have been found only in the family Bornaviridae. Here, we report that a new rhabdovirus isolated from the mosquito Culex tritaeniorhynchus replicates in the nuclei of infected cells and requires RNA splicing for viral mRNA maturation. The virus, designated Culex tritaeniorhynchus rhabdovirus (CTRV), shares a similar genome organization with other rhabdoviruses, except for the presence of a putative intron in the coding region for the L protein. Molecular phylogenetic studies indicated that CTRV belongs to the family Rhabdoviridae, but it is yet to be assigned a genus. Electron microscopic analysis revealed that the CTRV virion is extremely elongated, unlike virions of rhabdoviruses, which are generally bullet shaped. Northern hybridization confirmed that a large transcript (approximately 6,500 nucleotides [nt]) from the CTRV L gene was present in the infected cells. Strand-specific reverse transcription-PCR (RT-PCR) analyses identified the intron-exon boundaries and the 76-nt intron sequence, which contains the typical motif for eukaryotic spliceosomal intron-splice donor/acceptor sites (GU-AG), a predicted branch point, and a polypyrimidine tract. In situ hybridization exhibited that viral RNAs are primarily localized in the nucleus of infected cells, indicating that CTRV replicates in the nucleus and is allowed to utilize the host's nuclear splicing machinery. This is the first report of RNA splicing among the members of the family Rhabdoviridae.

  2. RNA Chimeras as a Gene Signature of Breast Cancer

    Science.gov (United States)

    2014-06-01

    in the human [26,27] and another one in the mouse [28]. Human mtDNA does not contain introns and thus Figure 4. Cis- or trans- spiced mtRNA in ESTs...Therefore, the exact nt numbers and locations might slightly differ from different publications. RT-PCR, T-A cloning and DNA sequencing We cultured HEK293

  3. Age and personal values: Similar value circles with shifting priorities.

    Science.gov (United States)

    Borg, Ingwer; Hertel, Guido; Hermann, Dieter

    2017-11-01

    This study examined the relationship of personal values to age using data from two representative surveys. We hypothesized that individuals organize personal values, regardless of their age, as a circle with the same order of values on this circle but that older persons are closer to conservation and more remote from openness to change and closer to self-transcendence and more distant from self-enhancement. The structural stability of the value circle over age was largely confirmed across and within individuals. Different age groups exhibited a tendency to more strongly cluster those values that they rated as relatively important. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  4. Geometric fit of a point set by generalized circles

    DEFF Research Database (Denmark)

    Körner, Mark-Christopher; Brimberg, Jack; Juel, Henrik

    2010-01-01

    In our paper we approximate a set of given points by a general circle. More precisely, given two norms k 1 and k 2 and a set of points in the plane, we consider the problem of locating and scaling the unit circle of norm k 1 such that the sum of weighted distances between the circumference...... of the circle and the given points is minimized, where the distance is measured by a norm k 2. We present results for the general case. In the case that k 1 and k 2 are both polyhedral norms, we are able to solve the problem by investigating a finite candidate set....

  5. Changes in exon–intron structure during vertebrate evolution affect the splicing pattern of exons

    Science.gov (United States)

    Gelfman, Sahar; Burstein, David; Penn, Osnat; Savchenko, Anna; Amit, Maayan; Schwartz, Schraga; Pupko, Tal; Ast, Gil

    2012-01-01

    Exon–intron architecture is one of the major features directing the splicing machinery to the short exons that are located within long flanking introns. However, the evolutionary dynamics of exon–intron architecture and its impact on splicing is largely unknown. Using a comparative genomic approach, we analyzed 17 vertebrate genomes and reconstructed the ancestral motifs of both 3′ and 5′ splice sites, as also the ancestral length of exons and introns. Our analyses suggest that vertebrate introns increased in length from the shortest ancestral introns to the longest primate introns. An evolutionary analysis of splice sites revealed that weak splice sites act as a restrictive force keeping introns short. In contrast, strong splice sites allow recognition of exons flanked by long introns. Reconstruction of the ancestral state suggests these phenomena were not prevalent in the vertebrate ancestor, but appeared during vertebrate evolution. By calculating evolutionary rate shifts in exons, we identified cis-acting regulatory sequences that became fixed during the transition from early vertebrates to mammals. Experimental validations performed on a selection of these hexamers confirmed their regulatory function. We additionally revealed many features of exons that can discriminate alternative from constitutive exons. These features were integrated into a machine-learning approach to predict whether an exon is alternative. Our algorithm obtains very high predictive power (AUC of 0.91), and using these predictions we have identified and successfully validated novel alternatively spliced exons. Overall, we provide novel insights regarding the evolutionary constraints acting upon exons and their recognition by the splicing machinery. PMID:21974994

  6. Similar Ratios of Introns to Intergenic Sequence across Animal Genomes.

    Science.gov (United States)

    Francis, Warren R; Wörheide, Gert

    2017-06-01

    One central goal of genome biology is to understand how the usage of the genome differs between organisms. Our knowledge of genome composition, needed for downstream inferences, is critically dependent on gene annotations, yet problems associated with gene annotation and assembly errors are usually ignored in comparative genomics. Here, we analyze the genomes of 68 species across 12 animal phyla and some single-cell eukaryotes for general trends in genome composition and transcription, taking into account problems of gene annotation. We show that, regardless of genome size, the ratio of introns to intergenic sequence is comparable across essentially all animals, with nearly all deviations dominated by increased intergenic sequence. Genomes of model organisms have ratios much closer to 1:1, suggesting that the majority of published genomes of nonmodel organisms are underannotated and consequently omit substantial numbers of genes, with likely negative impact on evolutionary interpretations. Finally, our results also indicate that most animals transcribe half or more of their genomes arguing against differences in genome usage between animal groups, and also suggesting that the transcribed portion is more dependent on genome size than previously thought. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  7. Parhelic-like circle from light scattering in Plateau borders

    Energy Technology Data Exchange (ETDEWEB)

    Tufaile, A., E-mail: tufaile@usp.br; Tufaile, A.P.B.

    2015-03-06

    We are reporting a new simple optical element to generate halos. We have observed interesting patterns of light scattering in Plateau borders in foams. In analogy to the atmospheric phenomena known as parhelic circle, sun dogs, and sun pillars, we have named the features of the patterns observed as parlaseric circle, laser dogs, and laser pillars. The triangular symmetry of the Plateau borders is analogous to the hexagonal symmetry of ice crystals which produce these atmospheric phenomena. Working with one Plateau border at a time, we have observed wave optics phenomena that are not perceived in the atmospheric phenomena, such as diffraction and interference. - Highlights: • We obtained halo formation from light scattering in a Plateau border using an experiment. • We explained halo formation using geometrical theory of diffraction. • An optical element based on a Plateau border is proposed. • We compared some aspects of the parhelic circle with the parlaseric circle.

  8. Quality Productivity Circle in Manufacture | Achi | Nigerian Journal of ...

    African Journals Online (AJOL)

    A brief history of quality control and productivity is hereby traced. ... Circle management technique are discussed in its relationship with productivity. ... so should be made sound in body (and spirit) through appropriate training and motivation.

  9. Research Circles - a method for developing guidance practices

    DEFF Research Database (Denmark)

    2012-01-01

    This video reports on our work with using research circles to improve our understanding of how to provide guidance and counseling to help young people in danger of dropping out of school. The video is based on the paper: Research Circles -- a method for developing guidance practices, and was pres......This video reports on our work with using research circles to improve our understanding of how to provide guidance and counseling to help young people in danger of dropping out of school. The video is based on the paper: Research Circles -- a method for developing guidance practices......, and was presented at the Conference for Social Justice, Prosperity and Sustainable Employment 2012 by assistant professor Helle Merete Nordentoft from DPU (http://edu.au.dk/). The film communicating the research paper was created by Mie Nørgaard...

  10. Squaring the Circle: Attempting Peace in Northern Ireland

    National Research Council Canada - National Science Library

    Marchi, Gina

    1997-01-01

    Finding a political framework for self-government in Northern Ireland that will be supported by both nationalists and unionists is referred to as a modern day attempt to do the impossible-to 'square the circle...

  11. Crosstalk between Wnt Signaling and RNA Processing in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Michael Bordonaro

    2013-01-01

    Full Text Available RNA processing involves a variety of processes affecting gene expression, including the removal of introns through RNA splicing, as well as 3' end processing (cleavage and polyadenylation. Alternative RNA processing is fundamentally important for gene regulation, and aberrant processing is associated with the initiation and progression of cancer. Deregulated Wnt signaling, which is the initiating event in the development of most cases of human colorectal cancer (CRC, has been linked to modified RNA processing, which may contribute to Wnt-mediated colonic carcinogenesis. Crosstalk between Wnt signaling and alternative RNA splicing with relevance to CRC includes effects on the expression of Rac1b, an alternatively spliced gene associated with tumorigenesis, which exhibits alternative RNA splicing that is influenced by Wnt activity. In addition, Tcf4, a crucial component of Wnt signaling, also exhibits alternative splicing, which is likely involved in colonic tumorigenesis. Modulation of 3' end formation, including of the Wnt target gene COX-2, also can influence the neoplastic process, with implications for CRC. While many human genes are dependent on introns and splicing for normal levels of gene expression, naturally intronless genes exist with a unique metabolism that allows for intron-independent gene expression. Effects of Wnt activity on the RNA metabolism of the intronless Wnt-target gene c-jun is a likely contributor to cancer development. Further, butyrate, a breakdown product of dietary fiber and a histone deacetylase inhibitor, upregulates Wnt activity in CRC cells, and also modulates RNA processing; therefore, the interplay between Wnt activity, the modulation of this activity by butyrate, and differential RNA metabolism in colonic cells can significantly influence tumorigenesis. Determining the role played by altered RNA processing in Wnt-mediated neoplasia may lead to novel interventions aimed at restoring normal RNA metabolism for

  12. Crosstalk between Wnt Signaling and RNA Processing in Colorectal Cancer.

    Science.gov (United States)

    Bordonaro, Michael

    2013-01-01

    RNA processing involves a variety of processes affecting gene expression, including the removal of introns through RNA splicing, as well as 3' end processing (cleavage and polyadenylation). Alternative RNA processing is fundamentally important for gene regulation, and aberrant processing is associated with the initiation and progression of cancer. Deregulated Wnt signaling, which is the initiating event in the development of most cases of human colorectal cancer (CRC), has been linked to modified RNA processing, which may contribute to Wnt-mediated colonic carcinogenesis. Crosstalk between Wnt signaling and alternative RNA splicing with relevance to CRC includes effects on the expression of Rac1b, an alternatively spliced gene associated with tumorigenesis, which exhibits alternative RNA splicing that is influenced by Wnt activity. In addition, Tcf4, a crucial component of Wnt signaling, also exhibits alternative splicing, which is likely involved in colonic tumorigenesis. Modulation of 3' end formation, including of the Wnt target gene COX-2, also can influence the neoplastic process, with implications for CRC. While many human genes are dependent on introns and splicing for normal levels of gene expression, naturally intronless genes exist with a unique metabolism that allows for intron-independent gene expression. Effects of Wnt activity on the RNA metabolism of the intronless Wnt-target gene c-jun is a likely contributor to cancer development. Further, butyrate, a breakdown product of dietary fiber and a histone deacetylase inhibitor, upregulates Wnt activity in CRC cells, and also modulates RNA processing; therefore, the interplay between Wnt activity, the modulation of this activity by butyrate, and differential RNA metabolism in colonic cells can significantly influence tumorigenesis. Determining the role played by altered RNA processing in Wnt-mediated neoplasia may lead to novel interventions aimed at restoring normal RNA metabolism for therapeutic benefit

  13. Membandingkan Bilangan Pecahan Menggunakan Fraction Circle terhadap Pemahaman Konsep Siswa

    Directory of Open Access Journals (Sweden)

    Renny Sendra Wahyuni

    2017-03-01

    Full Text Available Penelitian bertujuan untuk mendeskripsikan lintasan belajar siswa dalam memahami konsep pembelajaran membandingkan bilangan pecahan dengan menggunakan fraction circle melalui pendekatan PMRI. Penelitian dilaksanakan di SD Negeri 146 Palembang. Metode yang digunakan adalah design research melalui tahap-tahap preparing for the experiment, teaching experiment, dan retrospective analysis. Penelitian ini menunjukkan peranan fraction circle sebagai model yang mendorong peserta didik menemukan pemahaman konsep membandingkan bilangan pecahan dengan menggunakan pendekatan PMRI. Kata Kunci: pecahan, fraction circle, design research, PMRI This study aims to design a learning trajectory to help students understand the concept of rational numbers through fashion context. The study aims to describe students learning trajectory in understanding the concept of comparing fractions through fraction circle with PMRI approach. The research was conducted in SD Negeri 146 Palembang. The method used in this research is design research which consists of three stages: preparing for the experiment, teaching experiment, and retrospective analysis. The result shows the role fraction circle as a model to encourage students to understand the concept of comparing fractions using PMRI approach. Keywords: fractions, fraction circle, design research, PMRI

  14. Circles South East: the first 10 years 2002-2012.

    Science.gov (United States)

    Bates, Andrew; Williams, Dominic; Wilson, Chris; Wilson, Robin J

    2014-07-01

    This article describes the first 10 years of the implementation of Circles of Support and Accountability (Circles) in the management of sexual offenders in South-East England by Circles South East (CSE). The Circles of 71 core members are reviewed in detail, with reference to demographic data, offense and sentencing histories, risk assessment data, and considerations regarding Multi-Agency Public Protection Arrangements. A group of 71 comparison subjects who were referred to CSE and deemed suitable for but did not receive the service was identified. Follow-up behaviors of both groups are examined (including all forms of reconviction, breach of orders, and prison recall). Over a comparable follow-up period of 55 months, the incidence of violent and contact sexual reconviction in the comparison group was significantly higher than for the Circles cohort. Comparisons are made between expected and actual levels of sexual reconviction, with the Circles cohort showing lower than expected rate of sexual reconviction but not to a statistically significant degree. © The Author(s) 2013.

  15. Models to support students’ understanding of measuring area of circles

    Science.gov (United States)

    Rejeki, S.; Putri, R. I. I.

    2018-01-01

    Many studies showed that enormous students got confused about the concepts of measuring area of circles. The main reason is because mathematics classroom practices emphasized on memorizing formulas rather than understanding concepts. Therefore, in this study, a set of learning activities were designed as an innovation in learning area measurement of circles. The activities involved two models namely grid paper and reshaping which are respectively as a means and a strategy to support students’ learning of area measurement of circles. Design research was used as the research approach to achieve the aim. Thirty-eight of 8th graders in Indonesia were involved in this study. In this study, together with the contextual problems, the grid paper and reshaping sectors, which used as the models in this learning, helped the students to gradually develop their understanding of the area measurement of circles. The grid papers plays important role in comparing and estimating areas. Whereas, the reshaping sectors might support students’ understanding of the circumference and the area measurement of circles. Those two models could be the tool for promoting the informal theory of area measurement. Besides, the whole activities gave important role on distinguishing the area and perimeter of circles.

  16. A new RNA branching activity: the GIR1 ribozyme

    DEFF Research Database (Denmark)

    Nielsen, Henrik; Johansen, Steinar D

    2006-01-01

    The formation of lariat intermediates during the first step of splicing of group II introns and spliceosomal introns is a well-studied fundamental reaction in molecular biology. Apart from this prominent example, there are surprisingly few occurrences of branched nucleotides or even 2......',5'-phosphodiester bonds in biology. We recently described a new ribozyme, the GIR1 branching ribozyme, which catalyzes the formation of a tiny lariat that caps an mRNA. This new example together with work on artificial branching ribozymes and deoxyribozymes shows that branching is facile and points...... to the possibility that branching reactions could be more prevalent than previously recognized....

  17. Accurate, model-based tuning of synthetic gene expression using introns in S. cerevisiae.

    Directory of Open Access Journals (Sweden)

    Ido Yofe

    2014-06-01

    Full Text Available Introns are key regulators of eukaryotic gene expression and present a potentially powerful tool for the design of synthetic eukaryotic gene expression systems. However, intronic control over gene expression is governed by a multitude of complex, incompletely understood, regulatory mechanisms. Despite this lack of detailed mechanistic understanding, here we show how a relatively simple model enables accurate and predictable tuning of synthetic gene expression system in yeast using several predictive intron features such as transcript folding and sequence motifs. Using only natural Saccharomyces cerevisiae introns as regulators, we demonstrate fine and accurate control over gene expression spanning a 100 fold expression range. These results broaden the engineering toolbox of synthetic gene expression systems and provide a framework in which precise and robust tuning of gene expression is accomplished.

  18. Multiple splicing defects in an intronic false exon.

    Science.gov (United States)

    Sun, H; Chasin, L A

    2000-09-01

    Splice site consensus sequences alone are insufficient to dictate the recognition of real constitutive splice sites within the typically large transcripts of higher eukaryotes, and large numbers of pseudoexons flanked by pseudosplice sites with good matches to the consensus sequences can be easily designated. In an attempt to identify elements that prevent pseudoexon splicing, we have systematically altered known splicing signals, as well as immediately adjacent flanking sequences, of an arbitrarily chosen pseudoexon from intron 1 of the human hprt gene. The substitution of a 5' splice site that perfectly matches the 5' consensus combined with mutation to match the CAG/G sequence of the 3' consensus failed to get this model pseudoexon included as the central exon in a dhfr minigene context. Provision of a real 3' splice site and a consensus 5' splice site and removal of an upstream inhibitory sequence were necessary and sufficient to confer splicing on the pseudoexon. This activated context also supported the splicing of a second pseudoexon sequence containing no apparent enhancer. Thus, both the 5' splice site sequence and the polypyrimidine tract of the pseudoexon are defective despite their good agreement with the consensus. On the other hand, the pseudoexon body did not exert a negative influence on splicing. The introduction into the pseudoexon of a sequence selected for binding to ASF/SF2 or its replacement with beta-globin exon 2 only partially reversed the effect of the upstream negative element and the defective polypyrimidine tract. These results support the idea that exon-bridging enhancers are not a prerequisite for constitutive exon definition and suggest that intrinsically defective splice sites and negative elements play important roles in distinguishing the real splicing signal from the vast number of false splicing signals.

  19. Novel intron markers to study the phylogeny of closely related mammalian species

    Directory of Open Access Journals (Sweden)

    Castresana Jose

    2010-11-01

    Full Text Available Abstract Background Multilocus phylogenies can be used to infer the species tree of a group of closely related species. In species trees, the nodes represent the actual separation between species, thus providing essential information about their evolutionary history. In addition, multilocus phylogenies can help in analyses of species delimitation, gene flow and genetic differentiation within species. However, few adequate markers are available for such studies. Results In order to develop nuclear markers that can be useful in multilocus studies of mammals, we analyzed the mammalian genomes of human, chimpanzee, macaque, dog and cow. Rodents were excluded due to their unusual genomic features. Introns were extracted from the mammalian genomes because of their greater genetic variability and ease of amplification from the flanking exons. To an initial set of more than 10,000 one-to-one orthologous introns we applied several filters to select introns that belong to single-copy genes, show neutral evolutionary rates and have an adequate length for their amplification. This analysis led to a final list of 224 intron markers randomly distributed along the genome. To experimentally test their validity, we amplified twelve of these introns in a panel of six mammalian species. The result was that seven of these introns gave rise to a PCR band of the expected size in all species. In addition, we sequenced these bands and analyzed the accumulation of substitutions in these introns in five pairs of closely related species. The results showed that the estimated genetic distances in the five species pairs was quite variable among introns and that this divergence cannot be directly predicted from the overall intron divergence in mammals. Conclusions We have designed a new set of 224 nuclear introns with optimal features for the phylogeny of closely related mammalian species. A large proportion of the introns tested experimentally showed a perfect amplification

  20. Comprehensive analysis of RNA-Seq data reveals extensive RNA editing in a human transcriptome

    DEFF Research Database (Denmark)

    Peng, Zhiyu; Cheng, Yanbing; Tan, Bertrand Chin-Ming

    2012-01-01

    a computational pipeline that carefully controls for false positives while calling RNA editing events from genome and whole-transcriptome data of the same individual. We identified 22,688 RNA editing events in noncoding genes and introns, untranslated regions and coding sequences of protein-coding genes. Most......RNA editing is a post-transcriptional event that recodes hereditary information. Here we describe a comprehensive profile of the RNA editome of a male Han Chinese individual based on analysis of ∼767 million sequencing reads from poly(A)(+), poly(A)(-) and small RNA samples. We developed...... changes (∼93%) converted A to I(G), consistent with known editing mechanisms based on adenosine deaminase acting on RNA (ADAR). We also found evidence of other types of nucleotide changes; however, these were validated at lower rates. We found 44 editing sites in microRNAs (miRNAs), suggesting a potential...

  1. Asthma and COPD in cystic fibrosis intron-8 5T carriers. A population-based study

    DEFF Research Database (Denmark)

    Dahl, Morten; Tybjaerg-Hansen, Anne; Lange, Peter

    2005-01-01

    Carriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD).......Carriers of cystic fibrosis intron-8 5T alleles with high exon-9 skipping could have increased annual lung function decline and increased risk for asthma or chronic obstructive pulmonary disease (COPD)....

  2. Three Concentric Circles: Young Chinese English Learners' Perceptions of Purposeful Audiences

    Science.gov (United States)

    Liu, Jack Jinghui

    2015-01-01

    English learners have more access to communicate with different purposeful audiences across the Three Concentric Circles of English (Kachu, 1985): the Inner Circle, the Outer Circle and the Expanding Circle. However, young language learners' purposeful audience as a focus of communication has not been emphasized as much as other linguistic…

  3. Evidence for intron length conservation in a set of mammalian genes associated with embryonic development

    LENUS (Irish Health Repository)

    2011-10-05

    Abstract Background We carried out an analysis of intron length conservation across a diverse group of nineteen mammalian species. Motivated by recent research suggesting a role for time delays associated with intron transcription in gene expression oscillations required for early embryonic patterning, we searched for examples of genes that showed the most extreme conservation of total intron content in mammals. Results Gene sets annotated as being involved in pattern specification in the early embryo or containing the homeobox DNA-binding domain, were significantly enriched among genes with highly conserved intron content. We used ancestral sequences reconstructed with probabilistic models that account for insertion and deletion mutations to distinguish insertion and deletion events on lineages leading to human and mouse from their last common ancestor. Using a randomization procedure, we show that genes containing the homeobox domain show less change in intron content than expected, given the number of insertion and deletion events within their introns. Conclusions Our results suggest selection for gene expression precision or the existence of additional development-associated genes for which transcriptional delay is functionally significant.

  4. Porcine calbindin-D9k gene: expression in endometrium, myometrium, and placenta in the absence of a functional estrogen response element in intron A.

    Science.gov (United States)

    Krisinger, J; Jeung, E B; Simmen, R C; Leung, P C

    1995-01-01

    The expression of Calbindin-D9k (CaBP-9k) in the pig uterus and placenta was measured by Northern blot analysis and reverse transcription polymerase chain reaction (PCR), respectively. Progesterone (P4) administration to ovariectomized pigs decreased CaBP-9k mRNA levels. Expression of endometrial CaBP-9k mRNA was high on pregnancy Days 10-12 and below the detection limit on Days 15 and 18. On Day 60, expression could be detected at low levels. In myometrium and placenta, CaBP-9k mRNA expression was not detectable by Northern analysis using total RNA. Reverse-transcribed RNA from both tissues demonstrated the presence of CaBP-9k transcripts by means of PCR. The partial CaBP-9k gene was amplified by PCR and cloned to determine the sequence of intron A. In contrast to the rat CaBP-9k gene, the pig gene does not contain a functional estrogen response element (ERE) within this region. A similar ERE-like sequence located at the identical location was examined by gel retardation analysis and failed to bind the estradiol receptor. A similar disruption of this ERE-like sequence has been described in the human CaBP-9k gene, which is not expressed at any level in placenta, myometrium, or endometrium. It is concluded that the pig CaBP-9k gene is regulated in these reproductive tissues in a manner distinct from that in rat and human tissues. The regulation is probably due to a regulatory region outside of intron A, which in the rat gene contains the key cis element for uterine expression of the CaBP-9k gene.

  5. An Intron 9 CYP19 Gene Variant (IVS9+5G>A), Present in an Aromatase-Deficient Girl, Affects Normal Splicing and Is Also Present in Normal Human Steroidogenic Tissues.

    Science.gov (United States)

    Saraco, Nora; Nesi-Franca, Suzana; Sainz, Romina; Marino, Roxana; Marques-Pereira, Rosana; La Pastina, Julia; Perez Garrido, Natalia; Sandrini, Romolo; Rivarola, Marco Aurelio; de Lacerda, Luiz; Belgorosky, Alicia

    2015-01-01

    Splicing CYP19 gene variants causing aromatase deficiency in 46,XX disorder of sexual development (DSD) patients have been reported in a few cases. A misbalance between normal and aberrant splicing variants was proposed to explain spontaneous pubertal breast development but an incomplete sex maturation progress. The aim of this study was to functionally characterize a novel CYP19A1 intronic homozygote mutation (IVS9+5G>A) in a 46,XX DSD girl presenting spontaneous breast development and primary amenorrhea, and to evaluate similar splicing variant expression in normal steroidogenic tissues. Genomic DNA analysis, splicing prediction programs, splicing assays, and in vitro protein expression and enzyme activity analyses were carried out. CYP19A1 mRNA expression in human steroidogenic tissues was also studied. A novel IVS9+5G>A homozygote mutation was found. In silico analysis predicts the disappearance of the splicing donor site in intron 9, confirmed by patient peripheral leukocyte cP450arom and in vitro studies. Protein analysis showed a shorter and inactive protein. The intron 9 transcript variant was also found in human steroidogenic tissues. The mutation IVS9+5G>A generates a splicing variant that includes intron 9 which is also present in normal human steroidogenic tissues, suggesting that a misbalance between normal and aberrant splicing variants might occur in target tissues, explaining the clinical phenotype in the affected patient. © 2015 S. Karger AG, Basel.

  6. Evolution of red algal plastid genomes: ancient architectures, introns, horizontal gene transfer, and taxonomic utility of plastid markers.

    Directory of Open Access Journals (Sweden)

    Jan Janouškovec

    Full Text Available Red algae have the most gene-rich plastid genomes known, but despite their evolutionary importance these genomes remain poorly sampled. Here we characterize three complete and one partial plastid genome from a diverse range of florideophytes. By unifying annotations across all available red algal plastid genomes we show they all share a highly compact and slowly-evolving architecture and uniquely rich gene complements. Both chromosome structure and gene content have changed very little during red algal diversification, and suggest that plastid-to nucleus gene transfers have been rare. Despite their ancient character, however, the red algal plastids also contain several unprecedented features, including a group II intron in a tRNA-Met gene that encodes the first example of red algal plastid intron maturase - a feature uniquely shared among florideophytes. We also identify a rare case of a horizontally-acquired proteobacterial operon, and propose this operon may have been recruited for plastid function and potentially replaced a nucleus-encoded plastid-targeted paralogue. Plastid genome phylogenies yield a fully resolved tree and suggest that plastid DNA is a useful tool for resolving red algal relationships. Lastly, we estimate the evolutionary rates among more than 200 plastid genes, and assess their usefulness for species and subspecies taxonomy by comparison to well-established barcoding markers such as cox1 and rbcL. Overall, these data demonstrates that red algal plastid genomes are easily obtainable using high-throughput sequencing of total genomic DNA, interesting from evolutionary perspectives, and promising in resolving red algal relationships at evolutionarily-deep and species/subspecies levels.

  7. Three-charge black holes on a circle

    International Nuclear Information System (INIS)

    Harmark, Troels; Obers, Niels A.; Roenne, Peter B.; Kristjansson, Kristjan R.

    2007-01-01

    We study phases of five-dimensional three-charge black holes with a circle in their transverse space. In particular, when the black hole is localized on the circle we compute the corrections to the metric and corresponding thermodynamics in the limit of small mass. When taking the near-extremal limit, this gives the corrections to the finite entropy of the extremal three-charge black hole as a function of the energy above extremality. For the partial extremal limit with two charges sent to infinity and one finite we show that the first correction to the entropy is in agreement with the microscopic entropy by taking into account that the number of branes shift as a consequence of the interactions across the transverse circle. Beyond these analytical results, we also numerically obtain the entire phase of non- and near-extremal three- and two-charge black holes localized on a circle. More generally, we find in this paper a rich phase structure, including a new phase of three-charge black holes that are non-uniformly distributed on the circle. All these three-charge black hole phases are found via a map that relates them to the phases of five-dimensional neutral Kaluza-Klein black holes

  8. Talking Circles for Adolescent Girls in an Urban High School

    Directory of Open Access Journals (Sweden)

    Ann Schumacher

    2014-10-01

    Full Text Available Restorative Practices (RP in schools is a new and emerging field. Meeting in Circles to build friendships, develop emotional literacy skills, resolve conflict, or learn interactively are some of the core components of these programs. This article describes a 2-year study of 12 weekly Talking Circles organized under the auspices of a RP program in an urban high school with 60 adolescent girls. Primary data sources included 257 hr of participant observations in Talking Circles and individual, semi-structured interviews with 31 students. The Relational Cultural model, rooted in the work of Jean Baker Miller, served as the conceptual framework for understanding teens’ interactions within the Circle’s unique set of social conditions in a school environment. Findings demonstrated that Talking Circles provided a safe space for peers helping peers, and that the girls improved their listening, anger management, and empathic skills, which led to greater self-efficacy. It appears that Talking Circles could provide another venue for developing social-emotional literacy skills and growth-fostering relationships in schools.

  9. [A design of refractometer based on blur circle].

    Science.gov (United States)

    Zhang, Yikui; Huang, Shenghai; Ye, Huifang; Zou, Ruitao; Tong, Gengmin; Zhuo, Ran

    2011-03-01

    Design a convenient and stable eye refractometer based on the theory of blur circle. Analyze the retinal blur circle in both Emsly reduced eye model and Liou & Brennan 1997 eye model by ZEMAX. Design the coefficients including PD (pupil diameter) and NO' (length between node point and fovea) with the purpose of improving the accuracy. At last, compare the clinical optometry data from this refractor with the data obtained from optometry hospital in Wenzhou. The blur circle diameters are nearly the same in both reduced eye model and the Liou & Brennan 1997 eye model. With the PD = 4 mm and NO' = 20 mm, the refractor shows a fine accuracy in optometry. The paired t test shows that the myopia group and the astigmatism axial direction group have no statistical difference between the data from the blur circle refractor and the hospital (P > 0.05), while the astigmatism degree group has the result of P = 0.41 which may be caused by the poor cooperation of pediatric patients. 80% of the astigmatism degree data differ from the data from the hospital in less than 0.75D. The blur circle refractor, with the features of convenience and fine accuracy, is promised to be a new style of refractometer in the future.

  10. Effect of stern hull shape on turning circle of ships

    Science.gov (United States)

    Jaswar, Maimun, A.; Wahid, M. A.; Priyanto, A.; Zamani, Pauzi, Saman

    2012-06-01

    Many factors such as: stern hull shape, length, draught, trim, propulsion system and external forces affecting the drift angle influence rate of turn and size of turning circle of ships. This paper discusses turning circle characteristics of U and V stern hull shape of Very Large Crude Oil Carrier (VLCC) ships. The ships have same principal dimension such as length, beam, and draught. The turning circle characteristics of the VLCC ships are simulated at 35 degree of rudder angle. In the analysis, firstly, turning circle performance of U-type VLCC ship is simulated. In the simulation, initial ship speed is determined using given power and rpm. Hydrodynamic derivatives coefficients are determined by including effect of fullness of aft run. Using the obtained, speed and hydrodynamic coefficients, force and moment acting on hull, force and moment induced by propeller, force and moment induced by rudder are determined. Finally, ship trajectory, ratio of speed, yaw angle and drift angle are determined. Results of simulation results of the VLCC ship are compared with the experimental one as validation. Using the same method, V-type VLCC is simulated and the simulation results are compared with U-type VLCC ship. Results shows the turning circle of U-type is larger than V-type due to effect stern hul results of simulation are.

  11. Deletions in cox2 mRNA result in loss of splicing and RNA editing and gain of novel RNA editing sites.

    Directory of Open Access Journals (Sweden)

    Stefanie Grüttner

    Full Text Available As previously demonstrated, the maize cox2 RNA is fully edited in cauliflower mitochondria. Use of constructs with a deleted cox2 intron, however, led to a loss of RNA editing at almost all editing sites, with only a few sites still partially edited. Likewise, one deletion in exon 1 and three in exon 2 abolish RNA editing at all cox2 sites analyzed. Furthermore, intron splicing is abolished using these deletions. Mutation of a cytosine residue, which is normally edited and localized directly adjacent to the intron, to thymidine did not result in restoration of splicing, indicating that the loss of splicing was not due to loss of RNA editing. One deletion in exon 2 did not lead to loss of splicing. Instead, most editing sites were found to be edited, only three were not edited. Unexpectedly, we observed additional RNA editing events at new sites. Thus it appears that deletions in the cox2 RNA sequence can have a strong effect on RNA processing, leading to loss of splicing, loss of editing at all sites, or even to a gain of new editing sites. As these effects are not limited to the vicinity of the respective deletions, but appear to be widespread or even affect all editing sites, they may not be explained by the loss of PPR binding sites. Instead, it appears that several parts of the cox2 transcript are required for proper RNA processing. This indicates the roles of the RNA sequence and structural elements in the recognition of the editing sites.

  12. Modulation of RNA function by aminoglycoside antibiotics.

    Science.gov (United States)

    Schroeder, R; Waldsich, C; Wank, H

    2000-01-04

    One of the most important families of antibiotics are the aminoglycosides, including drugs such as neomycin B, paromomycin, gentamicin and streptomycin. With the discovery of the catalytic potential of RNA, these antibiotics became very popular due to their RNA-binding capacity. They serve for the analysis of RNA function as well as for the study of RNA as a potential therapeutic target. Improvements in RNA structure determination recently provided first insights into the decoding site of the ribosome at high resolution and how aminoglycosides might induce misreading of the genetic code. In addition to inhibiting prokaryotic translation, aminoglycosides inhibit several catalytic RNAs such as self-splicing group I introns, RNase P and small ribozymes in vitro. Furthermore, these antibiotics interfere with human immunodeficiency virus (HIV) replication by disrupting essential RNA-protein contacts. Most exciting is the potential of many RNA-binding antibiotics to stimulate RNA activities, conceiving small-molecule partners for the hypothesis of an ancient RNA world. SELEX (systematic evolution of ligands by exponential enrichment) has been used in this evolutionary game leading to small synthetic RNAs, whose NMR structures gave valuable information on how aminoglycosides interact with RNA, which could possibly be used in applied science.

  13. Circles Disturbed The Interplay of Mathematics and Narrative

    CERN Document Server

    Doxiadis, Apostolos

    2012-01-01

    Circles Disturbed brings together important thinkers in mathematics, history, and philosophy to explore the relationship between mathematics and narrative. The book's title recalls the last words of the great Greek mathematician Archimedes before he was slain by a Roman soldier--"Don't disturb my circles"--words that seem to refer to two radically different concerns: that of the practical person living in the concrete world of reality, and that of the theoretician lost in a world of abstraction. Stories and theorems are, in a sense, the natural languages of these two worlds--stories represent

  14. The core of C*-algebras associated with circle maps

    DEFF Research Database (Denmark)

    Johannesen, Benjamin Randeris

    2017-01-01

    The relationship between dynamical systems and operator algebras is one that has been fruitful and mutually beneficial and is by now both well-established, -aged and -matured. This thesis contribute in developing the relationship between dynamical systems, groupoids and operator algebra for circle...... dynamics. Another aspect of this thesis are the results solely about dynamics on the unit circle. The reader is supposed to be well versed in C*-algebras and K-theory (and classification). The reader is not assumed to be familiar with dynamical system theory nor with groupoids....

  15. The Existence and Structure of Rotational Systems in the Circle

    OpenAIRE

    Ramanathan, Jayakumar

    2018-01-01

    By a rotational system, we mean a closed subset X of the circle, T=R/Z, together with a continuous transformation f:X→X with the requirements that the dynamical system (X,f) be minimal and that f respect the standard orientation of T. We show that infinite rotational systems (X,f), with the property that map f has finite preimages, are extensions of irrational rotations of the circle. Such systems have been studied when they arise as invariant subsets of certain specific mappings, F:T→T. Beca...

  16. CP violation in Z circle → τ+τ-

    International Nuclear Information System (INIS)

    Lopez, J.M.

    1998-01-01

    Test of CP invariance in the reaction Z circle → τ + τ - on the Z circle peak is performed using the data sample recorded by the four Collaboration at LEP and SLD. From the non-observation of CP violation upper limits on the real (vertical stroke Re(d r W ) vertical stroke) and imaginary (vertical stroke Im(d r W ) vertical stroke) parts of the weak dipole moment of the τ lepton at 95% C.L. are derived. Results on measurements on weak magnetic moment is also reported. (orig.)

  17. A simple algorithm for computing the smallest enclosing circle

    DEFF Research Database (Denmark)

    Skyum, Sven

    1991-01-01

    Presented is a simple O(n log n) algorithm for computing the smallest enclosing circle of a convex polygon. It can be easily extended to algorithms that compute the farthest-and the closest-point Voronoi diagram of a convex polygon within the same time bound.......Presented is a simple O(n log n) algorithm for computing the smallest enclosing circle of a convex polygon. It can be easily extended to algorithms that compute the farthest-and the closest-point Voronoi diagram of a convex polygon within the same time bound....

  18. Environmental Assessment: Disposition of Chiefs’ Circle Residential Structures

    Science.gov (United States)

    2012-04-27

    five structures ranged from Page 4 of 5  $200,000 (with bricks removed) to $500,000 (with bricks intact). Mike Ford, CEO of NewTown Macon, echoed Mr...feasibility 25-Jul-08 and practicality of moving the Chief’s Circle duplexes Mike Ford NewTown Macon 23-Jul-08 478-722-9909 President of NewTown Macon...Daniel.Chavira@ Gave a tour of Chiefs’ Circle huntcompanies.com Not interested in using the houses Bob Sharples RAFB 26-Oct-10 robert.sharples

  19. Types of the cerebral arterial circle (circle of Willis in a Sri Lankan Population

    Directory of Open Access Journals (Sweden)

    Gunasekera WSL

    2011-01-01

    Full Text Available Abstract Background The variations of the circle of Willis (CW are clinically important as patients with effective collateral circulations have a lower risk of transient ischemic attack and stroke than those with ineffective collaterals. The aim of the present cadaveric study was to investigate the anatomical variations of the CW and to compare the frequency of prevalence of the different variations with previous autopsy studies as variations in the anatomy of the CW as a whole have not been studied in the Indian subcontinent. Methods The external diameter of all the arteries forming the CW in 225 normal Sri Lankan adult cadaver brains was measured using a calibrated grid to determine the prevalence in the variation in CW. Chisquared tests and a correspondence analysis were performed to compare the relative frequencies of prevalence of anatomical variations in the CW across 6 studies of diverse ethnic populations. Results We report 15 types of variations of CW out of 22 types previously described and one additional type: hypoplastic precommunicating part of the anterior cerebral arteries (A1 and contralateral posterior communicating arteries (PcoA 5(2%. Statistically significant differences (p Conclusion The present study reveals that there are significant variations in the CW among intra and inter ethnic groups (Caucasian, African and Asian: Iran and Sri Lanka dominant populations, and warrants further studies keeping the methods of measurements, data assessment, and the definitions of hypoplasia the same.

  20. RNA Crystallization

    Science.gov (United States)

    Golden, Barbara L.; Kundrot, Craig E.

    2003-01-01

    RNA molecules may be crystallized using variations of the methods developed for protein crystallography. As the technology has become available to syntheisize and purify RNA molecules in the quantities and with the quality that is required for crystallography, the field of RNA structure has exploded. The first consideration when crystallizing an RNA is the sequence, which may be varied in a rational way to enhance crystallizability or prevent formation of alternate structures. Once a sequence has been designed, the RNA may be synthesized chemically by solid-state synthesis, or it may be produced enzymatically using RNA polymerase and an appropriate DNA template. Purification of milligram quantities of RNA can be accomplished by HPLC or gel electrophoresis. As with proteins, crystallization of RNA is usually accomplished by vapor diffusion techniques. There are several considerations that are either unique to RNA crystallization or more important for RNA crystallization. Techniques for design, synthesis, purification, and crystallization of RNAs will be reviewed here.

  1. Inclusive Teaching Circles: Mechanisms for Creating Welcoming Classrooms

    Science.gov (United States)

    Moore, Sharon; Wallace, Sherri L.; Schack, Gina; Thomas, M. Shelley; Lewis, Linda; Wilson, Linda; Miller, Shawnise; D'Antoni, Joan

    2010-01-01

    This essay examines the Inclusive Teaching Circle (ITC) as a mechanism for faculty development in creating instructional tools that embrace an inclusive pedagogy reflecting diversity, cultural competence and social justice. We describe one group's year-long participation in an ITC at a large, metropolitan research university in the south. Next, we…

  2. Scaling laws for mode lockings in circle maps

    International Nuclear Information System (INIS)

    Cvitanovic, P.; Shraiman, B.; Soederberg, B.

    1985-06-01

    The self-similar structure of mode lockings for circle maps is studied by means of the associated Farey trees. We investigate numerically several classes of scaling relations implicit in the Farey organization of mode lockings and discuss the extent to which they lead to universal scaling laws. (orig.)

  3. Penerapan Model Beyond Centers and Circle Tme SD Kelas Satu

    OpenAIRE

    FITRIA, EVY

    2014-01-01

    Penelitian bertujuan mengkaji pelaksanaan penerapan model pembelajaran Sentra Model pembelajaran sentra (Beyond Centers and Circle Time) dilaksanakan pada siswa kelas satu SD Islam Jayawinata Kota Tangerang 2013. Penelitian menggunakan metode kualitatitf dengan analisis model Miles and Huberman. Hasil penelitian mengungkapkan bahwa kegiatan SD kelas satu menggunakan model pembelajaran sentra atau BCCT pada tahun ajaran baru sehingga guru memiliki panduan ketika membuat rencana pembelajaran; p...

  4. Uncertainty budget for optical coordinate measurements of circle diameter

    DEFF Research Database (Denmark)

    Morace, Renate Erica; Hansen, Hans Nørgaard; De Chiffre, Leonardo

    2004-01-01

    An uncertainty analysis for circle diameter measurements using a coordinate measuring machine (CMM) equipped with an optical probe is presented in this paper. A mathematical model for data evaluation and uncertainty assessment was formulated in accordance with Guide to the Expression of Uncertain...

  5. Full circle? Renato Amato's literary antipodes 1 | Hill | Italian Studies ...

    African Journals Online (AJOL)

    Il titolo stesso dell'opera di Amato The Full Circle of the Travelling Cuckoo (1967) rivela il senso di dislocazione dello scrittore migrante ma, al contempo, ne indica la capacità di riconciliarsi con il proprio difficile passato e di adattarsi alla sua patria adottiva, la Nuova Zelanda. Amato (1928-1964) ha dato un contribuito ...

  6. The Quality Control Circle: Is It for Education?

    Science.gov (United States)

    Land, Arthur J.

    From its start in Japan after World War II, the Quality Control Circle (Q.C.) approach to management and organizational operation evolved into what it is today: people doing similar work meeting regularly to identify, objectively analyze, and develop solutions to problems. The Q.C. approach meets Maslow's theory of motivation by inviting…

  7. Revisiting Cyberbullying in Schools Using the Quality Circle Approach

    Science.gov (United States)

    Paul, Simone; Smith, Peter K.; Blumberg, Herbert H.

    2012-01-01

    An earlier study reported the use of Quality Circles (QC) in a UK school in the context of understanding and reducing bullying and cyberbullying. Here, we report further work in the same school setting. The QC approach allows explorative analysis of problems in school settings, whereby students embark on a problem-solving exercise over a period of…

  8. Is Russell's vicious circle principle false or meaningless?

    NARCIS (Netherlands)

    Fleischhacker, L.E.

    1979-01-01

    P. Vardy asserts the thesis that the vicious circle principle has the same structure as Russell's paradox. But structure is not the thing itself. It is the thing objectivated from the wiewpoint of a mathematician. So this structure can be expressed in a mathematical formalism, e. g. the Λ-calculus.

  9. Random walks of a quantum particle on a circle

    International Nuclear Information System (INIS)

    Fjeldsoe, N.; Midtdal, J.; Ravndal, F.

    1987-07-01

    When the quantum planar rotor is put on a lattice, its dynamics can be approximated by random walks on a circle. This allows for fast and accurate Monto Carlo simulations to determine the topological charge of different configurations of the system and thereby the Θ-dependency of the lowest energy levels

  10. Come together – research circles as learning arenas

    DEFF Research Database (Denmark)

    Skovhus, Randi Boelskifte

    A presentation of an example of training through research circles. A training project that include teachers in compulsory school and researchers from Aarhus University and VIA University College. The presentation is based on a practice development project. First a short presentation of the projec...

  11. Circle Maps and the Devil's Staircase in a Chemical Oscillator

    DEFF Research Database (Denmark)

    Brøns, Morten; Gross, P.; Bar-Eli, K.

    1996-01-01

    We explain numerical results on a periodically perturbed Oregonator by Markman and Bar-Eli (J. Phys. Chem. 98 12248 (1994)). If the dynamics of the system is governed by a family of diffeomorphisms of a circle with a Devil's staircase one will expect the observed behavior, i.e. (1) Only periodic...

  12. Defining Leadership: Collegiate Women's Learning Circles: A Qualitative Approach

    Science.gov (United States)

    Preston-Cunningham, Tammie; Elbert, Chanda D.; Dooley, Kim E.

    2017-01-01

    The researchers employed qualitative methods to evaluate first-year female students' definition of "leadership" through involvement in the Women's Learning Circle. The findings revealed that students defined leadership in two dimensions: traits and behaviors. The qualitative findings explore a multidimensional approach to the voices of…

  13. The 253-kb inversion and deep intronic mutations in UNC13D are present in North American patients with familial hemophagocytic lymphohistiocytosis 3.

    Science.gov (United States)

    Qian, Yaping; Johnson, Judith A; Connor, Jessica A; Valencia, C Alexander; Barasa, Nathaniel; Schubert, Jeffery; Husami, Ammar; Kissell, Diane; Zhang, Ge; Weirauch, Matthew T; Filipovich, Alexandra H; Zhang, Kejian

    2014-06-01

    The mutations in UNC13D are responsible for familial hemophagocytic lymphohistiocytosis (FHL) type 3. A 253-kb inversion and two deep intronic mutations, c.118-308C > T and c.118-307G > A, in UNC13D were recently reported in European and Asian FHL3 patients. We sought to determine the prevalence of these three non-coding mutations in North American FHL patients and evaluate the significance of examining these new mutations in genetic testing. We performed DNA sequencing of UNC13D and targeted analysis of these three mutations in 1,709 North American patients with a suspected clinical diagnosis of hemophagocytic lymphohistiocytosis (HLH). The 253-kb inversion, intronic mutations c.118-308C > T and c.118-307G > A were found in 11, 15, and 4 patients, respectively, in which the genetic basis (bi-allelic mutations) explained 25 additional patients. Taken together with previously diagnosed FHL3 patients in our HLH patient registry, these three non-coding mutations were found in 31.6% (25/79) of the FHL3 patients. The 253-kb inversion, c.118-308C > T and c.118-307G > A accounted for 7.0%, 8.9%, and 1.3% of mutant alleles, respectively. Significantly, eight novel mutations in UNC13D are being reported in this study. To further evaluate the expression level of the newly reported intronic mutation c.118-307G > A, reverse transcription PCR and Western blot analysis revealed a significant reduction of both RNA and protein levels suggesting that the c.118-307G > A mutation affects transcription. These specified non-coding mutations were found in a significant number of North American patients and inclusion of them in mutation analysis will improve the molecular diagnosis of FHL3. © 2014 Wiley Periodicals, Inc.

  14. Intron-exon organization of the active human protein S gene PS. alpha. and its pseudogene PS. beta. : Duplication and silencing during primate evolution

    Energy Technology Data Exchange (ETDEWEB)

    Ploos van Amstel, H.; Reitsma, P.H.; van der Logt, C.P.; Bertina, R.M. (University Hospital, Leiden (Netherlands))

    1990-08-28

    The human protein S locus on chromosome 3 consists of two protein S genes, PS{alpha} and PS{beta}. Here the authors report the cloning and characterization of both genes. Fifteen exons of the PS{alpha} gene were identified that together code for protein S mRNA as derived from the reported protein S cDNAs. Analysis by primer extension of liver protein S mRNA, however, reveals the presence of two mRNA forms that differ in the length of their 5{prime}-noncoding region. Both transcripts contain a 5{prime}-noncoding region longer than found in the protein S cDNAs. The two products may arise from alternative splicing of an additional intron in this region or from the usage of two start sites for transcription. The intron-exon organization of the PS{alpha} gene fully supports the hypothesis that the protein S gene is the product of an evolutional assembling process in which gene modules coding for structural/functional protein units also found in other coagulation proteins have been put upstream of the ancestral gene of a steroid hormone binding protein. The PS{beta} gene is identified as a pseudogene. It contains a large variety of detrimental aberrations, viz., the absence of exon I, a splice site mutation, three stop codons, and a frame shift mutation. Overall the two genes PS{alpha} and PS{beta} show between their exonic sequences 96.5% homology. Southern analysis of primate DNA showed that the duplication of the ancestral protein S gene has occurred after the branching of the orangutan from the African apes. A nonsense mutation that is present in the pseudogene of man also could be identified in one of the two protein S genes of both chimpanzee and gorilla. This implicates that silencing of one of the two protein S genes must have taken place before the divergence of the three African apes.

  15. RNA Origami

    DEFF Research Database (Denmark)

    Sparvath, Steffen Lynge

    introducerede vores gruppe den enkeltstrengede RNA-origami metode, der giver mulighed for cotranscriptional foldning af veldefinerede nanostrukturer, og er en central del af arbejdet præsenteret heri. Denne ph.d.-afhandling udforsker potentielle anvendelser af RNA-origami nanostrukturer, som nanomedicin eller...... biosensorer. Afhandlingen består af en introduktion til RNA-nanoteknologi feltet, en introduktion af enkeltstrenget RNA-origami design, og fire studier, der beskriver design, produktion og karakterisering af både strukturelle og funktionelle RNA-origamier. Flere RNA-origami designs er blevet undersøgt, og...... projekterne, der indgår i denne afhandling, inkluderer de nyeste fremskridt indenfor strukturel RNA-nanoteknologi og udvikling af funktionelle RNA-baserede enheder. Det første studie beskriver konstruktion og karakterisering af en enkeltstrenget 6-helix RNA-origami stuktur, som er den første demonstration af...

  16. Innovation and Organizational Communication in Corporate America: The Rhetorical Visions of Managers, Facilitators, and Employees on Quality Circles.

    Science.gov (United States)

    Eyo, Bassey A.

    1992-01-01

    Examines the dynamics of organizational communication following corporate implementation of quality circles. Describes the rhetorical visions of people at three organizational levels closely associated with quality circles: (1) managers; (2) facilitators who organize the quality circles; and (3) employees. (SR)

  17. Are Namibian "fairy circles" the consequence of self-organizing spatial vegetation patterning?

    Directory of Open Access Journals (Sweden)

    Michael D Cramer

    Full Text Available Causes of over-dispersed barren "fairy circles" that are often surrounded by ca. 0.5 m tall peripheral grasses in a matrix of shorter (ca. 0.2 m tall grasses in Namibian grasslands remain mysterious. It was hypothesized that the fairy circles are the consequence of self-organizing spatial vegetation patterning arising from resource competition and facilitation. We examined the edaphic properties of fairy circles and variation in fairy circle size, density and landscape occupancy (% land surface with edaphic properties and water availability at a local scale (<50 km and with climate and vegetation characteristics at a regional scale. Soil moisture in the barren fairy circles declines from the center towards the periphery and is inversely correlated with soil organic carbon, possibly indicating that the peripheral grass roots access soil moisture that persists into the dry season within fairy circles. Fairy circle landscape occupancy is negatively correlated with precipitation and soil [N], consistent with fairy circles being the product of resource-competition. Regional fairy circle presence/absence is highly predictable using an empirical model that includes narrow ranges of vegetation biomass, precipitation and temperature seasonality as predictor variables, indicating that fairy circles are likely a climate-dependent emergent phenomenon. This dependence of fairy circle occurrence on climate explains why fairy circles in some locations may appear and disappear over time. Fairy circles are only over-dispersed at high landscape occupancies, indicating that inter-circle competition may determine their spacing. We conclude that fairy circles are likely to be an emergent arid-grassland phenomenon that forms as a consequence of peripheral grass resource-competition and that the consequent barren circle may provide a resource-reservoir essential for the survival of the larger peripheral grasses and provides a habitat for fossicking fauna.

  18. BIALLELIC POLYMORPHISM IN THE INTRON REGION OF B-TUBULIN GENE OF CRYPTOSPORIDIUM PARASITES

    Science.gov (United States)

    Nucleotide sequencing of polymerase chain reaction-amplified intron region of the Cryptosporidium parvum B-tubulin gene in 26 human and 15 animal isolates revealed distinct genetic polymorphism between the human and bovine genotypes. The separation of 2 genotypes of C. parvum is...

  19. Functional understanding of the diverse exon-intron structures of human GPCR genes.

    Science.gov (United States)

    Hammond, Dorothy A; Olman, Victor; Xu, Ying

    2014-02-01

    The GPCR genes have a variety of exon-intron structures even though their proteins are all structurally homologous. We have examined all human GPCR genes with at least two functional protein isoforms, totaling 199, aiming to gain an understanding of what may have contributed to the large diversity of the exon-intron structures of the GPCR genes. The 199 genes have a total of 808 known protein splicing isoforms with experimentally verified functions. Our analysis reveals that 1301 (80.6%) adjacent exon-exon pairs out of the total of 1,613 in the 199 genes have either exactly one exon skipped or the intron in-between retained in at least one of the 808 protein splicing isoforms. This observation has a statistical significance p-value of 2.051762 * e(-09), assuming that the observed splicing isoforms are independent of the exon-intron structures. Our interpretation of this observation is that the exon boundaries of the GPCR genes are not randomly determined; instead they may be selected to facilitate specific alternative splicing for functional purposes.

  20. Selection-driven extinction dynamics for group II introns in Enterobacteriales.

    Directory of Open Access Journals (Sweden)

    Sébastien Leclercq

    Full Text Available Transposable elements (TEs are one of the major driving forces of genome evolution, raising the question of the long-term dynamics underlying their evolutionary success. Some TEs were proposed to evolve under a pattern of periodic extinctions-recolonizations, in which elements recurrently invade and quickly proliferate within their host genomes, then start to disappear until total extinction. Depending on the model, TE extinction is assumed to be driven by purifying selection against colonized host genomes (Sel-DE model or by saturation of host genomes (Sat-DE model. Bacterial group II introns are suspected to follow an extinction-recolonization model of evolution, but whether they follow Sel-DE or Sat-DE dynamics is not known. Our analysis of almost 200 group II intron copies from 90 sequenced Enterobacteriales genomes confirms their extinction-recolonization dynamics: patchy element distributions among genera and even among strains within genera, acquisition of new group II introns through plasmids or other mobile genetic elements, and evidence for recent proliferations in some genomes. Distributions of recent and past proliferations and of their respective homing sites further provide strong support for the Sel-DE model, suggesting that group II introns are deleterious to their hosts. Overall, our observations emphasize the critical impact of host properties on TE dynamics.

  1. Genic regions of a large salamander genome contain long introns and novel genes

    Directory of Open Access Journals (Sweden)

    Bryant Susan V

    2009-01-01

    Full Text Available Abstract Background The basis of genome size variation remains an outstanding question because DNA sequence data are lacking for organisms with large genomes. Sixteen BAC clones from the Mexican axolotl (Ambystoma mexicanum: c-value = 32 × 109 bp were isolated and sequenced to characterize the structure of genic regions. Results Annotation of genes within BACs showed that axolotl introns are on average 10× longer than orthologous vertebrate introns and they are predicted to contain more functional elements, including miRNAs and snoRNAs. Loci were discovered within BACs for two novel EST transcripts that are differentially expressed during spinal cord regeneration and skin metamorphosis. Unexpectedly, a third novel gene was also discovered while manually annotating BACs. Analysis of human-axolotl protein-coding sequences suggests there are 2% more lineage specific genes in the axolotl genome than the human genome, but the great majority (86% of genes between axolotl and human are predicted to be 1:1 orthologs. Considering that axolotl genes are on average 5× larger than human genes, the genic component of the salamander genome is estimated to be incredibly large, approximately 2.8 gigabases! Conclusion This study shows that a large salamander genome has a correspondingly large genic component, primarily because genes have incredibly long introns. These intronic sequences may harbor novel coding and non-coding sequences that regulate biological processes that are unique to salamanders.

  2. Deep intronic GPR143 mutation in a Japanese family with ocular albinism.

    Science.gov (United States)

    Naruto, Takuya; Okamoto, Nobuhiko; Masuda, Kiyoshi; Endo, Takao; Hatsukawa, Yoshikazu; Kohmoto, Tomohiro; Imoto, Issei

    2015-06-10

    Deep intronic mutations are often ignored as possible causes of human disease. Using whole-exome sequencing, we analysed genomic DNAs of a Japanese family with two male siblings affected by ocular albinism and congenital nystagmus. Although mutations or copy number alterations of coding regions were not identified in candidate genes, the novel intronic mutation c.659-131 T > G within GPR143 intron 5 was identified as hemizygous in affected siblings and as heterozygous in the unaffected mother. This mutation was predicted to create a cryptic splice donor site within intron 5 and activate a cryptic acceptor site at 41nt upstream, causing the insertion into the coding sequence of an out-of-frame 41-bp pseudoexon with a premature stop codon in the aberrant transcript, which was confirmed by minigene experiments. This result expands the mutational spectrum of GPR143 and suggests the utility of next-generation sequencing integrated with in silico and experimental analyses for improving the molecular diagnosis of this disease.

  3. A localization algorithm of adaptively determining the ROI of the reference circle in image

    Science.gov (United States)

    Xu, Zeen; Zhang, Jun; Zhang, Daimeng; Liu, Xiaomao; Tian, Jinwen

    2018-03-01

    Aiming at solving the problem of accurately positioning the detection probes underwater, this paper proposed a method based on computer vision which can effectively solve this problem. The theory of this method is that: First, because the shape information of the heat tube is similar to a circle in the image, we can find a circle which physical location is well known in the image, we set this circle as the reference circle. Second, we calculate the pixel offset between the reference circle and the probes in the picture, and adjust the steering gear through the offset. As a result, we can accurately measure the physical distance between the probes and the under test heat tubes, then we can know the precise location of the probes underwater. However, how to choose reference circle in image is a difficult problem. In this paper, we propose an algorithm that can adaptively confirm the area of reference circle. In this area, there will be only one circle, and the circle is the reference circle. The test results show that the accuracy of the algorithm of extracting the reference circle in the whole picture without using ROI (region of interest) of the reference circle is only 58.76% and the proposed algorithm is 95.88%. The experimental results indicate that the proposed algorithm can effectively improve the efficiency of the tubes detection.

  4. Guided Discovery of the Nine-Point Circle Theorem and Its Proof

    Science.gov (United States)

    Buchbinder, Orly

    2018-01-01

    The nine-point circle theorem is one of the most beautiful and surprising theorems in Euclidean geometry. It establishes an existence of a circle passing through nine points, all of which are related to a single triangle. This paper describes a set of instructional activities that can help students discover the nine-point circle theorem through…

  5. The Value of the Math Circle for Gifted Middle School Students

    Science.gov (United States)

    Burns, Barbara; Henry, Julie; McCarthy, Dianne; Tripp, Jennifer

    2017-01-01

    Math Circles are designed to allow students to explore mathematics using a problem-solving/inquiry approach. Many of the students attending our Math Circle are mathematically talented and curious. This study examines the perspectives of the students and their families in determining why students attend Math Circle, what they enjoy about Math…

  6. The Chicken and the Egg: Inviting Response and Talk through Socratic Circles

    Science.gov (United States)

    Styslinger, Mary E.; Pollock, Timothy

    2010-01-01

    This collaborative inquiry answers the following questions: 1) What is the nature of talk during Socratic Circles? 2) What is student response to talk? 3) How might knowing more about student response to talk and the nature of talk improve teaching during Socratic Circles? The article first describes the process of implementing Socratic Circles,…

  7. Circling motion and screen edges as an alternative input method for on-screen target manipulation.

    Science.gov (United States)

    Ka, Hyun W; Simpson, Richard C

    2017-04-01

    To investigate a new alternative interaction method, called circling interface, for manipulating on-screen objects. To specify a target, the user makes a circling motion around the target. To specify a desired pointing command with the circling interface, each edge of the screen is used. The user selects a command before circling the target. To evaluate the circling interface, we conducted an experiment with 16 participants, comparing the performance on pointing tasks with different combinations of selection method (circling interface, physical mouse and dwelling interface) and input device (normal computer mouse, head pointer and joystick mouse emulator). A circling interface is compatible with many types of pointing devices, not requiring physical activation of mouse buttons, and is more efficient than dwell-clicking. Across all common pointing operations, the circling interface had a tendency to produce faster performance with a head-mounted mouse emulator than with a joystick mouse. The performance accuracy of the circling interface outperformed the dwelling interface. It was demonstrated that the circling interface has the potential as another alternative pointing method for selecting and manipulating objects in a graphical user interface. Implications for Rehabilitation A circling interface will improve clinical practice by providing an alternative pointing method that does not require physically activating mouse buttons and is more efficient than dwell-clicking. The Circling interface can also work with AAC devices.

  8. Absent collateral function of the circle of Willis as risk factor for ischemic stroke

    NARCIS (Netherlands)

    Hoksbergen, A. W. J.; Legemate, D. A.; Csiba, L.; Csáti, G.; Síró, P.; Fülesdi, B.

    2003-01-01

    Background. Autopsy studies show a higher prevalence of circle of Willis anomalies in brains with signs of ischemic infarction. Our goal was to examine the collateral function of the circle of Willis in ischemic stroke patients and to assess in a case-control study if a collateral deficient circle

  9. Proliferation of group II introns in the chloroplast genome of the green alga Oedocladium carolinianum (Chlorophyceae

    Directory of Open Access Journals (Sweden)

    Jean-Simon Brouard

    2016-10-01

    Full Text Available Background The chloroplast genome sustained extensive changes in architecture during the evolution of the Chlorophyceae, a morphologically and ecologically diverse class of green algae belonging to the Chlorophyta; however, the forces driving these changes are poorly understood. The five orders recognized in the Chlorophyceae form two major clades: the CS clade consisting of the Chlamydomonadales and Sphaeropleales, and the OCC clade consisting of the Oedogoniales, Chaetophorales, and Chaetopeltidales. In the OCC clade, considerable variations in chloroplast DNA (cpDNA structure, size, gene order, and intron content have been observed. The large inverted repeat (IR, an ancestral feature characteristic of most green plants, is present in Oedogonium cardiacum (Oedogoniales but is lacking in the examined members of the Chaetophorales and Chaetopeltidales. Remarkably, the Oedogonium 35.5-kb IR houses genes that were putatively acquired through horizontal DNA transfer. To better understand the dynamics of chloroplast genome evolution in the Oedogoniales, we analyzed the cpDNA of a second representative of this order, Oedocladium carolinianum. Methods The Oedocladium cpDNA was sequenced and annotated. The evolutionary distances separating Oedocladium and Oedogonium cpDNAs and two other pairs of chlorophycean cpDNAs were estimated using a 61-gene data set. Phylogenetic analysis of an alignment of group IIA introns from members of the OCC clade was performed. Secondary structures and insertion sites of oedogonialean group IIA introns were analyzed. Results The 204,438-bp Oedocladium genome is 7.9 kb larger than the Oedogonium genome, but its repertoire of conserved genes is remarkably similar and gene order differs by only one reversal. Although the 23.7-kb IR is missing the putative foreign genes found in Oedogonium, it contains sequences coding for a putative phage or bacterial DNA primase and a hypothetical protein. Intergenic sequences are 1.5-fold

  10. A construct with fluorescent indicators for conditional expression of miRNA

    Directory of Open Access Journals (Sweden)

    Xia Xugang

    2008-10-01

    Full Text Available Abstract Background Transgenic RNAi holds promise as a simple, low-cost, and fast method for reverse genetics in mammals. It may be particularly useful for producing animal models for hypomorphic gene function. Inducible RNAi that permits spatially and temporally controllable gene silencing in vivo will enhance the power of transgenic RNAi approach. Furthermore, because microRNA (miRNA targeting specific genes can be expressed simultaneously with protein coding genes, incorporation of fluorescent marker proteins can simplify the screening and analysis of transgenic RNAi animals. Results We sought to optimally express a miRNA simultaneously with a fluorescent marker. We compared two construct designs. One expressed a red fluorescent protein (RFP and a miRNA placed in its 3' untranslated region (UTR. The other expressed the same RFP and miRNA, but the precursor miRNA (pre-miRNA coding sequence was placed in an intron that was inserted into the 3'-UTR. We found that the two constructs expressed comparable levels of miRNA. However, the intron-containing construct expressed a significantly higher level of RFP than the intron-less construct. Further experiments indicate that the 3'-UTR intron enhances RFP expression by its intrinsic gene-expression-enhancing activity and by eliminating the inhibitory effect of the pre-miRNA on the expression of RFP. Based on these findings, we incorporated the intron-embedded pre-miRNA design into a conditional expression construct that employed the Cre-loxP system. This construct initially expressed EGFP gene, which was flanked by loxP sites. After exposure to Cre recombinase, the transgene stopped EGFP expression and began expression of RFP and a miRNA, which silenced the expression of specific cellular genes. Conclusion We have designed and tested a conditional miRNA-expression construct and showed that this construct expresses both the marker genes strongly and can silence the target gene efficiently upon Cre

  11. Influenza polymerase encoding mRNAs utilize atypical mRNA nuclear export.

    Science.gov (United States)

    Larsen, Sean; Bui, Steven; Perez, Veronica; Mohammad, Adeba; Medina-Ramirez, Hilario; Newcomb, Laura L

    2014-08-28

    Influenza is a segmented negative strand RNA virus. Each RNA segment is encapsulated by influenza nucleoprotein and bound by the viral RNA dependent RNA polymerase (RdRP) to form viral ribonucleoproteins responsible for RNA synthesis in the nucleus of the host cell. Influenza transcription results in spliced mRNAs (M2 and NS2), intron-containing mRNAs (M1 and NS1), and intron-less mRNAs (HA, NA, NP, PB1, PB2, and PA), all of which undergo nuclear export into the cytoplasm for translation. Most cellular mRNA nuclear export is Nxf1-mediated, while select mRNAs utilize Crm1. Here we inhibited Nxf1 and Crm1 nuclear export prior to infection with influenza A/Udorn/307/1972(H3N2) virus and analyzed influenza intron-less mRNAs using cellular fractionation and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). We examined direct interaction between Nxf1 and influenza intron-less mRNAs using immuno purification of Nxf1 and RT-PCR of associated RNA. Inhibition of Nxf1 resulted in less influenza intron-less mRNA export into the cytoplasm for HA and NA influenza mRNAs in both human embryonic kidney cell line (293 T) and human lung adenocarcinoma epithelial cell line (A549). However, in 293 T cells no change was observed for mRNAs encoding the components of the viral ribonucleoproteins; NP, PA, PB1, and PB2, while in A549 cells, only PA, PB1, and PB2 mRNAs, encoding the RdRP, remained unaffected; NP mRNA was reduced in the cytoplasm. In A549 cells NP, NA, HA, mRNAs were found associated with Nxf1 but PA, PB1, and PB2 mRNAs were not. Crm1 inhibition also resulted in no significant difference in PA, PB1, and PB2 mRNA nuclear export. These results further confirm Nxf1-mediated nuclear export is functional during the influenza life cycle and hijacked for select influenza mRNA nuclear export. We reveal a cell type difference for Nxf1-mediated nuclear export of influenza NP mRNA, a reminder that cell type can influence molecular mechanisms. Importantly, we

  12. Nuclear pre-mRNA processing in plants

    Energy Technology Data Exchange (ETDEWEB)

    Reddy, A.S.N. [Colorado State Univ., Fort Collins, CO (United States). Dept. of Biology and Program in Molecular Plant Biology; Golovkin, M. (eds.) [Thomas Jefferson Univ., Philadelphia, PA (United States). Dept. of Microbiology

    2008-07-01

    This volume of CTMI, entitled Nuclear premRNA Processing in Plants, with 16 chapters from leading scientists in this area, summarizes recent advances in nuclear pre-mRNA processing and its role in plant growth and development. It provides researchers in the field, as well as those in related areas, with an up-to-date and comprehensive, yet concise, overview of the current status and future potential of this research in understanding plant biology. The first four chapters focus on spliceosome composition, genome-wide alternative splicing, and splice site requirements for U1 and U12 introns using computational and empirical approaches. Analysis of sequenced plant genomes has revealed that 80% of all protein-coding nuclear genes contain one or more introns. The lack of an in vitro plant splicing system has made it difficult to identify general and plant-specific components of splicing machinery in plants. The next three chapters focus on serine/arginine-rich (SR) proteins, a family of highly conserved proteins, which are known to play key roles in constitutive and regulated splicing of pre-mRNA and other aspects of RNA metabolism in metazoans. These proteins engage both in RNA binding and protein.protein interactions and function as splicing regulators at multiple stages of spliceosome assembly. This family of proteins has expanded considerably in plants with several plant-specific SR proteins. Several serendipitous discoveries made using forward genetics are indicating that RNA metabolism (alternative splicing, alternative polyadenylation, mRNA transport) plays an important role in many aspects of plant growth and development and in plant responses to biotic and abiotic stresses. The next seven chapters focus on these aspects of RNA metabolism. The plant hormone abscisic acid (ABA) regulates a number of physiological processes during plant growth and development. The next chapter or A.B. Rose discusses the ways introns affect gene expression both positively and

  13. Nuclear pre-mRNA processing in plants

    International Nuclear Information System (INIS)

    Reddy, A.S.N.; Golovkin, M.

    2008-01-01

    This volume of CTMI, entitled Nuclear premRNA Processing in Plants, with 16 chapters from leading scientists in this area, summarizes recent advances in nuclear pre-mRNA processing and its role in plant growth and development. It provides researchers in the field, as well as those in related areas, with an up-to-date and comprehensive, yet concise, overview of the current status and future potential of this research in understanding plant biology. The first four chapters focus on spliceosome composition, genome-wide alternative splicing, and splice site requirements for U1 and U12 introns using computational and empirical approaches. Analysis of sequenced plant genomes has revealed that 80% of all protein-coding nuclear genes contain one or more introns. The lack of an in vitro plant splicing system has made it difficult to identify general and plant-specific components of splicing machinery in plants. The next three chapters focus on serine/arginine-rich (SR) proteins, a family of highly conserved proteins, which are known to play key roles in constitutive and regulated splicing of pre-mRNA and other aspects of RNA metabolism in metazoans. These proteins engage both in RNA binding and protein.protein interactions and function as splicing regulators at multiple stages of spliceosome assembly. This family of proteins has expanded considerably in plants with several plant-specific SR proteins. Several serendipitous discoveries made using forward genetics are indicating that RNA metabolism (alternative splicing, alternative polyadenylation, mRNA transport) plays an important role in many aspects of plant growth and development and in plant responses to biotic and abiotic stresses. The next seven chapters focus on these aspects of RNA metabolism. The plant hormone abscisic acid (ABA) regulates a number of physiological processes during plant growth and development. The next chapter or A.B. Rose discusses the ways introns affect gene expression both positively and

  14. RNA Splicing in a New Rhabdovirus from Culex Mosquitoes▿†

    Science.gov (United States)

    Kuwata, Ryusei; Isawa, Haruhiko; Hoshino, Keita; Tsuda, Yoshio; Yanase, Tohru; Sasaki, Toshinori; Kobayashi, Mutsuo; Sawabe, Kyoko

    2011-01-01

    Among members of the order Mononegavirales, RNA splicing events have been found only in the family Bornaviridae. Here, we report that a new rhabdovirus isolated from the mosquito Culex tritaeniorhynchus replicates in the nuclei of infected cells and requires RNA splicing for viral mRNA maturation. The virus, designated Culex tritaeniorhynchus rhabdovirus (CTRV), shares a similar genome organization with other rhabdoviruses, except for the presence of a putative intron in the coding region for the L protein. Molecular phylogenetic studies indicated that CTRV belongs to the family Rhabdoviridae, but it is yet to be assigned a genus. Electron microscopic analysis revealed that the CTRV virion is extremely elongated, unlike virions of rhabdoviruses, which are generally bullet shaped. Northern hybridization confirmed that a large transcript (approximately 6,500 nucleotides [nt]) from the CTRV L gene was present in the infected cells. Strand-specific reverse transcription-PCR (RT-PCR) analyses identified the intron-exon boundaries and the 76-nt intron sequence, which contains the typical motif for eukaryotic spliceosomal intron-splice donor/acceptor sites (GU-AG), a predicted branch point, and a polypyrimidine tract. In situ hybridization exhibited that viral RNAs are primarily localized in the nucleus of infected cells, indicating that CTRV replicates in the nucleus and is allowed to utilize the host's nuclear splicing machinery. This is the first report of RNA splicing among the members of the family Rhabdoviridae. PMID:21507977

  15. Exon-primed intron-crossing (EPIC markers for non-model teleost fishes

    Directory of Open Access Journals (Sweden)

    Riethoven Jean-Jack M

    2010-03-01

    Full Text Available Abstract Background Exon-primed intron-crossing (EPIC markers have three advantages over anonymous genomic sequences in studying evolution of natural populations. First, the universal primers designed in exon regions can be applied across a broad taxonomic range. Second, the homology of EPIC-amplified sequences can be easily determined by comparing either their exon or intron portion depending on the genetic distance between the taxa. Third, having both the exon and intron fragments could help in examining genetic variation at the intraspecific and interspecific level simultaneously, particularly helpful when studying species complex. However, the paucity of EPIC markers has hindered multilocus studies using nuclear gene sequences, particularly in teleost fishes. Results We introduce a bioinformatics pipeline for developing EPIC markers by comparing the whole genome sequences between two or more species. By applying this approach on five teleost fishes whose genomes were available in the Ensembl database http://www.ensembl.org, we identified 210 EPIC markers that have single-copy and conserved exon regions with identity greater than 85% among the five teleost fishes. We tested 12 randomly chosen EPIC markers in nine teleost species having a wide phylogenetic range. The success rate of amplifying and sequencing those markers varied from 44% to 100% in different species. We analyzed the exon sequences of the 12 EPIC markers from 13 teleosts. The resulting phylogeny contains many traditionally well-supported clades, indicating the usefulness of the exon portion of EPIC markers in reconstructing species phylogeny, in addition to the value of the intron portion of EPIC markers in interrogating the population history. Conclusions This study illustrated an effective approach to develop EPIC markers in a taxonomic group, where two or more genome sequences are available. The markers identified could be amplified across a broad taxonomic range of teleost

  16. Optimal weights for circle fitting with discrete granular data

    International Nuclear Information System (INIS)

    Chernov, N.; Kolganova, E.; Ososkov, G.

    1995-01-01

    The problem of the data approximation measured along a circle by modern detectors in high energy physics, as for example, RICH (Ring Imaging Cherenkov) is considered. Such detectors having the discrete cell structure register the energy dissipation produced by a passing elementary particle not in a single point, but in several adjacent cells where all this energy is distributed. The presence of background hits makes inapplicable circle fitting methods based on the least square fit due to their noise sensitivity. In this paper it's shown that the efficient way to overcome these problems of the curve fitting is the robust fitting technique based on a reweighted least square method with optimally chosen weights, obtained by the use of maximum likelihood estimates. Results of numerical experiments are given proving the high efficiency of the suggested method. 9 refs., 5 figs., 1 tab

  17. Handwriting: three-dimensional kinetic synergies in circle drawing movements.

    Science.gov (United States)

    Hooke, Alexander W; Karol, Sohit; Park, Jaebum; Kim, Yoon Hyuk; Shim, Jae Kun

    2012-07-01

    The purpose of this study was to investigate central nervous system (CNS) strategies for controlling multifinger forces during a circle-drawing task. Subjects drew 30 concentric, discontinuous clockwise and counter clockwise circles, at self and experimenter-set paces. The three-dimensional trajectory of the pen's center of mass and the three-dimensional forces and moments of force at each contact between the hand and the pen were recorded. Uncontrolled Manifold Analysis was used to quantify the synergies between pen-hand contact forces in radial, tangential and vertical directions. Results showed that synergies in the radial and tangential components were significantly stronger than in the vertical component. Synergies in the clockwise direction were significantly stronger than the counterclockwise direction in the radial and vertical components. Pace was found to be insignificant under any condition.

  18. Co-Constructing Knowledge through NGO-Driven Circle Work

    DEFF Research Database (Denmark)

    Agerbæk, Jonas

    This presentation revolves around the question of what degree of control, if any, the users participating in NGO-driven development programs may have over their own development. Based on a multi-sited ethnography of NGO organizing and communication that I conducted in the period of 2010 to 2015......, and with a special analytical focus on the facilitating role of frontline NGO workers in rural East Africa, this presentation discusses enabling and constraining aspects of using circle work to co-produce knowledge in international development. More particularly I am focusing an approach to circle work called......, then participatory approaches such as REFLECT can be used not only to drive changes locally but also bolster the global participatory agenda of defining development practices and politics from the bottom and up...

  19. Content-aware photo collage using circle packing.

    Science.gov (United States)

    Yu, Zongqiao; Lu, Lin; Guo, Yanwen; Fan, Rongfei; Liu, Mingming; Wang, Wenping

    2014-02-01

    In this paper, we present a novel approach for automatically creating the photo collage that assembles the interest regions of a given group of images naturally. Previous methods on photo collage are generally built upon a well-defined optimization framework, which computes all the geometric parameters and layer indices for input photos on the given canvas by optimizing a unified objective function. The complex nonlinear form of optimization function limits their scalability and efficiency. From the geometric point of view, we recast the generation of collage as a region partition problem such that each image is displayed in its corresponding region partitioned from the canvas. The core of this is an efficient power-diagram-based circle packing algorithm that arranges a series of circles assigned to input photos compactly in the given canvas. To favor important photos, the circles are associated with image importances determined by an image ranking process. A heuristic search process is developed to ensure that salient information of each photo is displayed in the polygonal area resulting from circle packing. With our new formulation, each factor influencing the state of a photo is optimized in an independent stage, and computation of the optimal states for neighboring photos are completely decoupled. This improves the scalability of collage results and ensures their diversity. We also devise a saliency-based image fusion scheme to generate seamless compositive collage. Our approach can generate the collages on nonrectangular canvases and supports interactive collage that allows the user to refine collage results according to his/her personal preferences. We conduct extensive experiments and show the superiority of our algorithm by comparing against previous methods.

  20. Quantum mechanics on the circle and W1+∞

    International Nuclear Information System (INIS)

    Floreanini, R.; Percacci, R.; Sezgin, E.

    1991-08-01

    The algebra W 1+∞ , with central charge c = 0, can be identified with the algebra of quantum observables of a particle moving on a circle. Mathematically, it is the universal enveloping algebra of the Euclidean algebra in two dimensions. Similarly, the super-W ∞ algebra is found to be the universal enveloping algebra of the super-Euclidean algebra in two dimensions. (author). 14 refs

  1. High accurate time system of the Low Latitude Meridian Circle.

    Science.gov (United States)

    Yang, Jing; Wang, Feng; Li, Zhiming

    In order to obtain the high accurate time signal for the Low Latitude Meridian Circle (LLMC), a new GPS accurate time system is developed which include GPS, 1 MC frequency source and self-made clock system. The second signal of GPS is synchronously used in the clock system and information can be collected by a computer automatically. The difficulty of the cancellation of the time keeper can be overcomed by using this system.

  2. Normal Isocurvature Surfaces and Special Isocurvature Circles (SIC)

    Science.gov (United States)

    Manoussakis, Gerassimos; Delikaraoglou, Demitris

    2010-05-01

    An isocurvature surface of a gravity field is a surface on which the value of the plumblines' curvature is constant. Here we are going to study the isocurvature surfaces of the Earth's normal gravity field. The normal gravity field is a symmetric gravity field therefore the isocurvature surfaces are surfaces of revolution. But even in this case the necessary relations for their study are not simple at all. Therefore to study an isocurvature surface we make special assumptions to form a vector equation which will hold only for a small coordinate patch of the isocurvature surface. Yet from the definition of the isocurvature surface and the properties of the normal gravity field is possible to express very interesting global geometrical properties of these surfaces without mixing surface differential calculus. The gradient of the plumblines' curvature function is vertical to an isocurvature surface. If P is a point of an isocurvature surface and "Φ" is the angle of the gradient of the plumblines' curvature with the equatorial plane then this direction points to the direction along which the curvature of the plumbline decreases / increases the most, and therefore is related to the strength of the normal gravity field. We will show that this direction is constant along a line of curvature of the isocurvature surface and this line is an isocurvature circle. In addition we will show that at each isocurvature surface there is at least one isocurvature circle along which the direction of the maximum variation of the plumblines' curvature function is parallel to the equatorial plane of the ellipsoid of revolution. This circle is defined as a Special Isocurvature Circle (SIC). Finally we shall prove that all these SIC lye on a special surface of revolution, the so - called SIC surface. That is to say, a SIC is not an isolated curve in the three dimensional space.

  3. CS Circles: An In-Browser Python Course for Beginners

    OpenAIRE

    Pritchard, David; Vasiga, Troy

    2012-01-01

    Computer Science Circles is a free programming website for beginners that is designed to be fun, easy to use, and accessible to the broadest possible audience. We teach Python since it is simple yet powerful, and the course content is well-structured but written in plain language. The website has over one hundred exercises in thirty lesson pages, plus special features to help teachers support their students. It is available in both English and French. We discuss the philosophy behind the cour...

  4. BANQUET SPEECH Full Circle: Star Ferry to Stardust

    Science.gov (United States)

    Matthews, Clifford N.

    2008-10-01

    Good evening. I'd like to invite you to join me on a journey that could be entitled “Full Circle: Star Ferry to Stardust”. “Star Ferry” represents Hong Kong, my home town, and especially its university - Hong Kong University - as I knew it during the years of World War II. “Stardust” refers to our gathering here to report on our research on possible organic chemistry in space.

  5. Social Circles Detection from Ego Network and Profile Information

    Science.gov (United States)

    2014-12-19

    way of organizing contacts in personal networks . They are therefore currently implemented in the major social net- working systems, such as Facebook ...0704-0188 3. DATES COVERED (From - To) - UU UU UU UU Approved for public release; distribution is unlimited. Social Circles Detection from Ego Network ...structural network information but also the contents of social interactions, with the aim to detect copying communities. The views, opinions and/or findings

  6. Discovering Social Circles in Ego Networks (Author’s Manuscript)

    Science.gov (United States)

    2013-01-10

    refer to as social cir- cles. Practically all major social networks provide such functionality, for example, ‘circles’ on Google+, and ‘lists’ on Facebook ...Discovering Social Circles in Ego Networks Julian McAuley and Jure Leskovec Stanford jmcauley@cs.stanford.edu, jure@cs.stanford.edu January 11, 2013...Abstract People’s personal social networks are big and cluttered, and currently there is no good way to automatically organize them. Social networking

  7. Truncated Calogero-Sutherland models on a circle

    Science.gov (United States)

    Tummuru, Tarun R.; Jain, Sudhir R.; Khare, Avinash

    2017-12-01

    We investigate a quantum many-body system with particles moving in a circle and subject to two-body and three-body potentials. This class of models, in which the range of interaction r can be set to a certain number of neighbors, extrapolates from a system with interactions up to next-to-nearest neighbors and the celebrated Calogero-Sutherland model. The exact ground state energy and a part of the excitation spectrum have been obtained.

  8. Ghost circles in lattice Aubry-Mather theory

    Science.gov (United States)

    Mramor, Blaz; Rink, Bob

    Monotone lattice recurrence relations such as the Frenkel-Kontorova lattice, arise in Hamiltonian lattice mechanics, as models for ferromagnetism and as discretization of elliptic PDEs. Mathematically, they are a multi-dimensional counterpart of monotone twist maps. Such recurrence relations often admit a variational structure, so that the solutions x:Z→R are the stationary points of a formal action function W(x). Given any rotation vector ω∈R, classical Aubry-Mather theory establishes the existence of a large collection of solutions of ∇W(x)=0 of rotation vector ω. For irrational ω, this is the well-known Aubry-Mather set. It consists of global minimizers and it may have gaps. In this paper, we study the parabolic gradient flow {dx}/{dt}=-∇W(x) and we will prove that every Aubry-Mather set can be interpolated by a continuous gradient-flow invariant family, the so-called 'ghost circle'. The existence of these ghost circles is known in dimension d=1, for rational rotation vectors and Morse action functions. The main technical result of this paper is therefore a compactness theorem for lattice ghost circles, based on a parabolic Harnack inequality for the gradient flow. This implies the existence of lattice ghost circles of arbitrary rotation vectors and for arbitrary actions. As a consequence, we can give a simple proof of the fact that when an Aubry-Mather set has a gap, then this gap must be filled with minimizers, or contain a non-minimizing solution.

  9. RNA-SeQC: RNA-seq metrics for quality control and process optimization.

    Science.gov (United States)

    DeLuca, David S; Levin, Joshua Z; Sivachenko, Andrey; Fennell, Timothy; Nazaire, Marc-Danie; Williams, Chris; Reich, Michael; Winckler, Wendy; Getz, Gad

    2012-06-01

    RNA-seq, the application of next-generation sequencing to RNA, provides transcriptome-wide characterization of cellular activity. Assessment of sequencing performance and library quality is critical to the interpretation of RNA-seq data, yet few tools exist to address this issue. We introduce RNA-SeQC, a program which provides key measures of data quality. These metrics include yield, alignment and duplication rates; GC bias, rRNA content, regions of alignment (exon, intron and intragenic), continuity of coverage, 3'/5' bias and count of detectable transcripts, among others. The software provides multi-sample evaluation of library construction protocols, input materials and other experimental parameters. The modularity of the software enables pipeline integration and the routine monitoring of key measures of data quality such as the number of alignable reads, duplication rates and rRNA contamination. RNA-SeQC allows investigators to make informed decisions about sample inclusion in downstream analysis. In summary, RNA-SeQC provides quality control measures critical to experiment design, process optimization and downstream computational analysis. See www.genepattern.org to run online, or www.broadinstitute.org/rna-seqc/ for a command line tool.

  10. An integrative genomic approach reveals coordinated expression of intronic miR-335, miR-342, and miR-561 with deregulated host genes in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Agnelli Luca

    2008-08-01

    Full Text Available Abstract Background The role of microRNAs (miRNAs in multiple myeloma (MM has yet to be fully elucidated. To identify miRNAs that are potentially deregulated in MM, we investigated those mapping within transcription units, based on evidence that intronic miRNAs are frequently coexpressed with their host genes. To this end, we monitored host transcript expression values in a panel of 20 human MM cell lines (HMCLs and focused on transcripts whose expression varied significantly across the dataset. Methods miRNA expression was quantified by Quantitative Real-Time PCR. Gene expression and genome profiling data were generated on Affymetrix oligonucleotide microarrays. Significant Analysis of Microarrays algorithm was used to investigate differentially expressed transcripts. Conventional statistics were used to test correlations for significance. Public libraries were queried to predict putative miRNA targets. Results We identified transcripts specific to six miRNA host genes (CCPG1, GULP1, EVL, TACSTD1, MEST, and TNIK whose average changes in expression varied at least 2-fold from the mean of the examined dataset. We evaluated the expression levels of the corresponding intronic miRNAs and identified a significant correlation between the expression levels of MEST, EVL, and GULP1 and those of the corresponding miRNAs miR-335, miR-342-3p, and miR-561, respectively. Genome-wide profiling of the 20 HMCLs indicated that the increased expression of the three host genes and their corresponding intronic miRNAs was not correlated with local copy number variations. Notably, miRNAs and their host genes were overexpressed in a fraction of primary tumors with respect to normal plasma cells; however, this finding was not correlated with known molecular myeloma groups. The predicted putative miRNA targets and the transcriptional profiles associated with the primary tumors suggest that MEST/miR-335 and EVL/miR-342-3p may play a role in plasma cell homing and

  11. Sphalerons of O(3) nonlinear sigma model on a circle

    International Nuclear Information System (INIS)

    Funakubo, Koichi; Otsuki, Shoichiro; Toyoda, Fumihiko.

    1989-09-01

    A series of saddle point solutions of O(3) nonlinear sigma model with symmetry breaking term in 1 + 1 dimensions are obtained by imposing boundary condition either periodic or partially antiperiodic (O(3) sphalerons on a circle). Under the periodic boundary condition, classical features of the O(3) sphalerons are similar to scalar sphalerons of φ 4 model on a circle by Manton and Samols. Under the partially antiperiodic boundary condition, the lowest of the O(3) sphalerons coincides in the limit of infinite spatial domain with the O(3) sphaleron by Mottola and Wipf. In particular, zero and negative modes of them are examined in detail. An estimate of transition rate over the lowest O(3) sphaleron at finite temperature is made, and some remarks on simulating the transition on a lattice are given. One to one correspondence between these O(3) sphalerons on a circle and a series of (possible) classical solutions of SU(2) gauge-Higgs model, to which the electroweak sphaleron S and new sphaleron S* belong, is discussed. (author)

  12. [Data supporting quality circle management of inpatient depression treatment].

    Science.gov (United States)

    Brand, S; Härter, M; Sitta, P; van Calker, D; Menke, R; Heindl, A; Herold, K; Kudling, R; Luckhaus, C; Rupprecht, U; Sanner, Dirk; Schmitz, D; Schramm, E; Berger, M; Gaebel, W; Schneider, F

    2005-07-01

    Several quality assurance initiatives in health care have been undertaken during the past years. The next step consists of systematically combining single initiatives in order to built up a strategic quality management. In a German multicenter study, the quality of inpatient depression treatment was measured in ten psychiatric hospitals. Half of the hospitals received comparative feedback on their individual results in comparison to the other hospitals (bench marking). Those bench markings were used by each hospital as a statistic basis for in-house quality work, to improve the quality of depression treatment. According to hospital differences concerning procedure and outcome, different goals were chosen. There were also differences with respect to structural characteristics, strategies, and outcome. The feedback from participants about data-based quality circles in general and the availability of bench-marking data was positive. The necessity of carefully choosing quality circle members and professional moderation became obvious. Data-based quality circles including bench-marking have proven to be useful for quality management in inpatient depression care.

  13. Expression of RNA virus proteins by RNA polymerase II dependent expression plasmids is hindered at multiple steps

    Directory of Open Access Journals (Sweden)

    Überla Klaus

    2007-06-01

    Full Text Available Abstract Background Proteins of human and animal viruses are frequently expressed from RNA polymerase II dependent expression cassettes to study protein function and to develop gene-based vaccines. Initial attempts to express the G protein of vesicular stomatitis virus (VSV and the F protein of respiratory syncytial virus (RSV by eukaryotic promoters revealed restrictions at several steps of gene expression. Results Insertion of an intron flanked by exonic sequences 5'-terminal to the open reading frames (ORF of VSV-G and RSV-F led to detectable cytoplasmic mRNA levels of both genes. While the exonic sequences were sufficient to stabilise the VSV-G mRNA, cytoplasmic mRNA levels of RSV-F were dependent on the presence of a functional intron. Cytoplasmic VSV-G mRNA levels led to readily detectable levels of VSV-G protein, whereas RSV-F protein expression remained undetectable. However, RSV-F expression was observed after mutating two of four consensus sites for polyadenylation present in the RSV-F ORF. Expression levels could be further enhanced by codon optimisation. Conclusion Insufficient cytoplasmic mRNA levels and premature polyadenylation prevent expression of RSV-F by RNA polymerase II dependent expression plasmids. Since RSV replicates in the cytoplasm, the presence of premature polyadenylation sites and elements leading to nuclear instability should not interfere with RSV-F expression during virus replication. The molecular mechanisms responsible for the destabilisation of the RSV-F and VSV-G mRNAs and the different requirements for their rescue by insertion of an intron remain to be defined.

  14. Interactions between the HIV-1 Unspliced mRNA and Host mRNA Decay Machineries

    Directory of Open Access Journals (Sweden)

    Daniela Toro-Ascuy

    2016-11-01

    Full Text Available The human immunodeficiency virus type-1 (HIV-1 unspliced transcript is used both as mRNA for the synthesis of structural proteins and as the packaged genome. Given the presence of retained introns and instability AU-rich sequences, this viral transcript is normally retained and degraded in the nucleus of host cells unless the viral protein REV is present. As such, the stability of the HIV-1 unspliced mRNA must be particularly controlled in the nucleus and the cytoplasm in order to ensure proper levels of this viral mRNA for translation and viral particle formation. During its journey, the HIV-1 unspliced mRNA assembles into highly specific messenger ribonucleoproteins (mRNPs containing many different host proteins, amongst which are well-known regulators of cytoplasmic mRNA decay pathways such as up-frameshift suppressor 1 homolog (UPF1, Staufen double-stranded RNA binding protein 1/2 (STAU1/2, or components of miRNA-induced silencing complex (miRISC and processing bodies (PBs. More recently, the HIV-1 unspliced mRNA was shown to contain N6-methyladenosine (m6A, allowing the recruitment of YTH N6-methyladenosine RNA binding protein 2 (YTHDF2, an m6A reader host protein involved in mRNA decay. Interestingly, these host proteins involved in mRNA decay were shown to play positive roles in viral gene expression and viral particle assembly, suggesting that HIV-1 interacts with mRNA decay components to successfully accomplish viral replication. This review summarizes the state of the art in terms of the interactions between HIV-1 unspliced mRNA and components of different host mRNA decay machineries.

  15. Estrogen receptor alpha regulates expression of the breast cancer 1 associated ring domain 1 (BARD1) gene through intronic DNA sequence.

    Science.gov (United States)

    Creekmore, Amy L; Ziegler, Yvonne S; Bonéy, Jamie L; Nardulli, Ann M

    2007-03-15

    We have used a chromatin immunoprecipitation (ChIP)-based cloning strategy to isolate and identify genes associated with estrogen receptor alpha (ERalpha) in MCF-7 human breast cancer cells. One of the gene regions isolated was a 288bp fragment from the ninth intron of the breast cancer 1 associated ring domain (BARD1) gene. We demonstrated that ERalpha associated with this region of the endogenous BARD 1 gene in MCF-7 cells, that ERalpha bound to three of five ERE half sites located in the 288bp BARD1 region, and that this 288bp BARD1 region conferred estrogen responsiveness to a heterologous promoter. Importantly, treatment of MCF-7 cells with estrogen increased BARD1 mRNA and protein levels. These findings demonstrate that ChIP cloning strategies can be utilized to successfully isolate regulatory regions that are far removed from the transcription start site and assist in identifying cis elements involved in conferring estrogen responsiveness.

  16. Experimental study of circle grid fractal pattern on turbulent intensity in pipe flow

    International Nuclear Information System (INIS)

    Manshoor, B; Zaman, I; Othman, M F; Khalid, Amir

    2013-01-01

    Fractal turbulence is deemed much more efficient than grid turbulence in terms of a turbulence generation. In this paper, the hotwire experimental results for the circle grids fractal pattern as a turbulent generator will be presented. The self-similar edge characteristic of the circle grid fractal pattern is thought to play a vital role in the enhancement of turbulent intensity. Three different beta ratios of perforated plates based on circle grids fractal pattern were used in the experimental work and each paired with standard circle grids with similar porosity. The objectives were to study the fractal scaling influence on the flow and also to explore the potential of the circle grids fractal pattern in enhancing the turbulent intensity. The results provided an excellent insight of the fractal generated turbulence and the fractal flow physics. Across the circle grids fractal pattern, the pressure drop was lower but the turbulent intensity was higher than those across the paired standard circle grids

  17. Fox-2 Splicing Factor Binds to a Conserved Intron Motif to PromoteInclusion of Protein 4.1R Alternative Exon 16

    Energy Technology Data Exchange (ETDEWEB)

    Ponthier, Julie L.; Schluepen, Christina; Chen, Weiguo; Lersch,Robert A.; Gee, Sherry L.; Hou, Victor C.; Lo, Annie J.; Short, Sarah A.; Chasis, Joel A.; Winkelmann, John C.; Conboy, John G.

    2006-03-01

    Activation of protein 4.1R exon 16 (E16) inclusion during erythropoiesis represents a physiologically important splicing switch that increases 4.1R affinity for spectrin and actin. Previous studies showed that negative regulation of E16 splicing is mediated by the binding of hnRNP A/B proteins to silencer elements in the exon and that downregulation of hnRNP A/B proteins in erythroblasts leads to activation of E16 inclusion. This paper demonstrates that positive regulation of E16 splicing can be mediated by Fox-2 or Fox-1, two closely related splicing factors that possess identical RNA recognition motifs. SELEX experiments with human Fox-1 revealed highly selective binding to the hexamer UGCAUG. Both Fox-1 and Fox-2 were able to bind the conserved UGCAUG elements in the proximal intron downstream of E16, and both could activate E16 splicing in HeLa cell co-transfection assays in a UGCAUG-dependent manner. Conversely, knockdown of Fox-2 expression, achieved with two different siRNA sequences resulted in decreased E16 splicing. Moreover, immunoblot experiments demonstrate mouse erythroblasts express Fox-2, but not Fox-1. These findings suggest that Fox-2 is a physiological activator of E16 splicing in differentiating erythroid cells in vivo. Recent experiments show that UGCAUG is present in the proximal intron sequence of many tissue-specific alternative exons, and we propose that the Fox family of splicing enhancers plays an important role in alternative splicing switches during differentiation in metazoan organisms.

  18. An intronic deletion in the PROM1 gene leads to autosomal recessive cone-rod dystrophy.

    Science.gov (United States)

    Eidinger, Osnat; Leibu, Rina; Newman, Hadas; Rizel, Leah; Perlman, Ido; Ben-Yosef, Tamar

    2015-01-01

    To investigate the genetic basis for autosomal recessive cone-rod dystrophy (CRD) in a consanguineous Israeli Jewish family. Patients underwent a detailed ophthalmic evaluation, including eye examination, visual field testing, optical coherence tomography (OCT), and electrophysiological tests, electroretinography (ERG) and visual evoked potential (VEP). Genome-wide homozygosity mapping using a single nucleotide polymorphism (SNP) array was performed to identify homozygous regions shared among two of the affected individuals. Mutation screening of the underlying gene was performed with direct sequencing. In silico and in vitro analyses were used to predict the effect of the identified mutation on splicing. The affected family members are three siblings who have various degrees of progressive visual deterioration, glare, color vision abnormalities, and night vision difficulties. Visual field tests revealed central scotomas of different extension. Cone and rod ERG responses were reduced, with cones more severely affected. Homozygosity mapping revealed several homozygous intervals shared among two of the affected individuals. One included the PROM1 gene. Sequence analysis of the 26 coding exons of PROM1 in one affected individual revealed no mutations in the coding sequence or in intronic splice sites. However, in intron 21, proximate to the intron-exon junction, we observed a homozygous 10 bp deletion between positions -26 and -17 (c.2281-26_-17del). The deletion was linked to a known SNP, c.2281-6C>G. The deletion cosegregated with the disease in the family, and was not detected in public databases or in 101 ethnically-matched control individuals. In silico analysis predicted that this deletion would lead to altered intron 21 splicing. Bioinformatic analysis predicted that a recognition site for the SRSF2 splicing factor is located within the deleted sequence. The in vitro splicing assay demonstrated that c.2281-26_-17del leads to complete exon 22 skipping. A novel

  19. Stereoscopic Machine-Vision System Using Projected Circles

    Science.gov (United States)

    Mackey, Jeffrey R.

    2010-01-01

    A machine-vision system capable of detecting obstacles large enough to damage or trap a robotic vehicle is undergoing development. The system includes (1) a pattern generator that projects concentric circles of laser light forward onto the terrain, (2) a stereoscopic pair of cameras that are aimed forward to acquire images of the circles, (3) a frame grabber and digitizer for acquiring image data from the cameras, and (4) a single-board computer that processes the data. The system is being developed as a prototype of machine- vision systems to enable robotic vehicles ( rovers ) on remote planets to avoid craters, large rocks, and other terrain features that could capture or damage the vehicles. Potential terrestrial applications of systems like this one could include terrain mapping, collision avoidance, navigation of robotic vehicles, mining, and robotic rescue. This system is based partly on the same principles as those of a prior stereoscopic machine-vision system in which the cameras acquire images of a single stripe of laser light that is swept forward across the terrain. However, this system is designed to afford improvements over some of the undesirable features of the prior system, including the need for a pan-and-tilt mechanism to aim the laser to generate the swept stripe, ambiguities in interpretation of the single-stripe image, the time needed to sweep the stripe across the terrain and process the data from many images acquired during that time, and difficulty of calibration because of the narrowness of the stripe. In this system, the pattern generator does not contain any moving parts and need not be mounted on a pan-and-tilt mechanism: the pattern of concentric circles is projected steadily in the forward direction. The system calibrates itself by use of data acquired during projection of the concentric-circle pattern onto a known target representing flat ground. The calibration- target image data are stored in the computer memory for use as a

  20. Speciation of a group I intron into a lariat capping ribozyme

    DEFF Research Database (Denmark)

    Meyer, Mélanie; Nielsen, Henrik; Oliéric, Vincent

    2014-01-01

    The lariat-capping (LC) ribozyme is a natural ribozyme isolated from eukaryotic microorganisms. Despite apparent structural similarity to group I introns, the LC ribozyme catalyzes cleavage by a 2',5' branching reaction, leaving the 3' product with a 3-nt lariat cap that functionally substitutes ....... The structures also show how conserved interactions twist residues, forming the lariat to join chemical groups involved in branching....

  1. Differentiation and fiber type-specific activity of a muscle creatine kinase intronic enhancer

    Directory of Open Access Journals (Sweden)

    Tai Phillip WL

    2011-07-01

    Full Text Available Abstract Background Hundreds of genes, including muscle creatine kinase (MCK, are differentially expressed in fast- and slow-twitch muscle fibers, but the fiber type-specific regulatory mechanisms are not well understood. Results Modulatory region 1 (MR1 is a 1-kb regulatory region within MCK intron 1 that is highly active in terminally differentiating skeletal myocytes in vitro. A MCK small intronic enhancer (MCK-SIE containing a paired E-box/myocyte enhancer factor 2 (MEF2 regulatory motif resides within MR1. The SIE's transcriptional activity equals that of the extensively characterized 206-bp MCK 5'-enhancer, but the MCK-SIE is flanked by regions that can repress its activity via the individual and combined effects of about 15 different but highly conserved 9- to 24-bp sequences. ChIP and ChIP-Seq analyses indicate that the SIE and the MCK 5'-enhancer are occupied by MyoD, myogenin and MEF2. Many other E-boxes located within or immediately adjacent to intron 1 are not occupied by MyoD or myogenin. Transgenic analysis of a 6.5-kb MCK genomic fragment containing the 5'-enhancer and proximal promoter plus the 3.2-kb intron 1, with and without MR1, indicates that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers (types I and IIa, respectively, but is not required for expression in fast-twitch muscle fibers (types IIb and IId. Conclusions In this study, we discovered that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers and that MR1's positive transcriptional activity depends on a paired E-box MEF2 site motif within a SIE. This is the first study to delineate the DNA controls for MCK expression in different skeletal muscle fiber types.

  2. Voice of the voiceless: The legacy of the Circle of Concerned African Women Theologians

    Directory of Open Access Journals (Sweden)

    Hazel O. Ayanga

    2016-07-01

    Full Text Available The Circle of Concerned African Women Theologians (the Circle formally came into existence in 1989 in Accra, Ghana. Under the charismatic leadership of Mercy Amba Oduyoye, the Circle sought to be the voice of African Christian women at the grass roots level. To this end research and publication was and still is one of the major pillars and activities of the Circle. The main objective of the Circle is �to write and publish theological literature written by African women from their own experience of religion and culture on this continent�. In this regard the Circle has been and continues to be the voice for and on behalf of the African woman in religion, culture and theology. However, 25 years down the line there is need for an evaluation of the legacy of the Circle. How has the Circle been a voice for the voiceless, a mentoring instrument for women venturing into the academia? This article seeks to do this evaluation by examining the activities of the Circle including research publication.Intradisciplinary and/or interdisciplinary implications: This article seeks to evaluate the achievements of the Circle of Concerned African Women Theologians in relation to the Circle�s stated objectives. The article picks up the notion of the Circle theologians as the voice of the voiceless women of Africa. The general approach of the article brings together discussions on social issues like gender, poverty and marginalisation as well as language. Theological and religious perspectives on these issues are understood from a Circle point of view.Keywords: women; voice; voicelessness; poverty; gender; The Circle; theology

  3. First intron of nestin gene regulates its expression during C2C12 myoblast ifferentiation

    Institute of Scientific and Technical Information of China (English)

    Hua Zhong; Zhigang Jin; Yongfeng Chen; Ting Zhang; Wei Bian; Xing Cui; Naihe Jing

    2008-01-01

    Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China Nestin is an intermediate filament protein expressed in neural progenitor cells and in developing skeletal muscle. Nestin has been widely used as a neural progenitor cell marker. It is well established that the specific expression of the nestin gene in neural progenitor cells is conferred by the neural-specific enhancer located in the second intron of the nestin gene. However, the transcriptional mechanism of nestin expression in developing muscle is still unclear. In this study, we identified a muscle cell-specific enhancer in the first intron of mouse nestin gene in mouse myoblast C2C12 cells.We localized the core enhancer activity to the 291-661 region of the first intron, and showed that the two E-boxes in the core enhancer region were important for enhancer activity in differentiating C2C12 cells. We also showed that MyoD protein was involved in the regulation of nestin expression in the myogenic differentiation of C2C12 cells.

  4. Significant association of interleukin-4 gene intron 3 VNTR polymorphism with susceptibility to knee osteoarthritis.

    Science.gov (United States)

    Yigit, Serbulent; Inanir, Ahmet; Tekcan, Akın; Tural, Ercan; Ozturk, Gokhan Tuna; Kismali, Gorkem; Karakus, Nevin

    2014-03-01

    Interleukin-4 (IL-4) is a strong chondroprotective cytokine and polymorphisms within this gene may be a risk factor for osteoarthritis (OA). We aimed to investigate genotype and allele frequencies of IL-4 gene intron 3 variable number of tandem repeats (VNTR) polymorphism in patients with knee OA in a Turkish population. The study included 202 patients with knee OA and 180 healthy controls. Genomic DNA was isolated and IL-4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers followed by restriction fragment length polymorphism (RFLP) analysis. Our result show that there was statistically significant difference between knee OA patients and control group with respect to IL-4 genotype distribution and allele frequencies (p=0.000, OR: 0.20, 95% CI: 0.10-0.41, OR: 0.22, 95% CI: 0.12-0.42, respectively). Our findings suggest that there is an association of IL-4 gene intron 3 VNTR polymorphism with susceptibility of a person for development of knee OA. As a result, IL-4 gene intron 3 VNTR polymorphism could be a genetic marker in OA in a Turkish study population. This is the first association study that evaluates the associations between IL-4 gene VNTR polymorphism and knee OA. Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

  5. Un gene con intrones en vez de exones / Envejecimiento Prematuro de la Piel

    Directory of Open Access Journals (Sweden)

    Tobías Mojica

    1996-04-01

    Full Text Available Un gene con intrones en vez de exones. La noción de que los genes son discontinuos (compuestos de exones e intrones en forma alterna y en cuya organización los exones representan regiones presentes, por medio del código genético en las proteínas, y los intrones nadie sabe todavía que representan produjo una cierta cantidad de desasosiego entre los genetistas mayores de edad, pero hoy día es ampliamente aceptada, con poco o ningún dolor, y se ha convertido en parte del cánon científico. / Envejecimiento Prematuro de la Piel. La exposición a largo plazo de la piel a la luz ultravioleta proveniente del sol resulta en daño al colágeno de la piel y a la elastina de la matriz extracelular; se cree que este daño es responsable de la apariencia típicamente arrugadita de la piel expuesta al sol por mucho tiempo (como en los vaqueros de los comerciales de la televisión.

  6. The Human Nuclear Exosome Targeting Complex Is Loaded onto Newly Synthesized RNA to Direct Early Ribonucleolysis

    Directory of Open Access Journals (Sweden)

    Michal Lubas

    2015-01-01

    Full Text Available The RNA exosome complex constitutes the major nuclear eukaryotic 3′-5′ exonuclease. Outside of nucleoli, the human nucleoplasmic exosome is directed to some of its substrates by the nuclear exosome targeting (NEXT complex. How NEXT targets RNA has remained elusive. Using an in vivo crosslinking approach, we report global RNA binding sites of RBM7, a key component of NEXT. RBM7 associates broadly with RNA polymerase II-derived RNA, including pre-mRNA and short-lived exosome substrates such as promoter upstream transcripts (PROMPTs, enhancer RNAs (eRNAs, and 3′-extended products from snRNA and replication-dependent histone genes. Within pre-mRNA, RBM7 accumulates at the 3′ ends of introns, and pulse-labeling experiments demonstrate that RBM7/NEXT defines an early exosome-targeting pathway for 3′-extended snoRNAs derived from such introns. We propose that RBM7 is generally loaded onto newly synthesized RNA to accommodate exosome action in case of available unprotected RNA 3′ ends.

  7. DBR1 siRNA inhibition of HIV-1 replication

    Directory of Open Access Journals (Sweden)

    Naidu Yathi

    2005-10-01

    Full Text Available Abstract Background HIV-1 and all retroviruses are related to retroelements of simpler organisms such as the yeast Ty elements. Recent work has suggested that the yeast retroelement Ty1 replicates via an unexpected RNA lariat intermediate in cDNA synthesis. The putative genomic RNA lariat intermediate is formed by a 2'-5' phosphodiester bond, like that found in pre-mRNA intron lariats and it facilitates the minus-strand template switch during cDNA synthesis. We hypothesized that HIV-1 might also form a genomic RNA lariat and therefore that siRNA-mediated inhibition of expression of the human RNA lariat de-branching enzyme (DBR1 expression would specifically inhibit HIV-1 replication. Results We designed three short interfering RNA (siRNA molecules targeting DBR1, which were capable of reducing DBR1 mRNA expression by 80% and did not significantly affect cell viability. We assessed HIV-1 replication in the presence of DBR1 siRNA and found that DBR1 knockdown led to decreases in viral cDNA and protein production. These effects could be reversed by cotransfection of a DBR1 cDNA indicating that the inhibition of HIV-1 replication was a specific effect of DBR1 underexpression. Conclusion These data suggest that DBR1 function may be needed to debranch a putative HIV-1 genomic RNA lariat prior to completion of reverse transcription.

  8. Orthogonal polynomials on the unit circle part 2 spectral theory

    CERN Document Server

    Simon, Barry

    2013-01-01

    This two-part book is a comprehensive overview of the theory of probability measures on the unit circle, viewed especially in terms of the orthogonal polynomials defined by those measures. A major theme involves the connections between the Verblunsky coefficients (the coefficients of the recurrence equation for the orthogonal polynomials) and the measures, an analog of the spectral theory of one-dimensional Schrödinger operators. Among the topics discussed along the way are the asymptotics of Toeplitz determinants (Szegő's theorems), limit theorems for the density of the zeros of orthogonal po

  9. Orthogonal polynomials on the unit circle part 1 classical theory

    CERN Document Server

    2009-01-01

    This two-part book is a comprehensive overview of the theory of probability measures on the unit circle, viewed especially in terms of the orthogonal polynomials defined by those measures. A major theme involves the connections between the Verblunsky coefficients (the coefficients of the recurrence equation for the orthogonal polynomials) and the measures, an analog of the spectral theory of one-dimensional Schrodinger operators. Among the topics discussed along the way are the asymptotics of Toeplitz determinants (Szegő's theorems), limit theorems for the density of the zeros of orthogonal po

  10. The Function of Love in Solzhenitsyn's The First Circle

    Directory of Open Access Journals (Sweden)

    John Schillinger

    1977-01-01

    Full Text Available Aleksander Solzhenitsyn, like Boris Pasternak before him, insists upon the primacy of life over any socio-political system. To lead truly meaningful lives, his characters must comprehend that they are responsible for their own actions; that they are engaged in an existential struggle which pits individual freedom against the will of authority. In The First Circle , this struggle is clearly reflected in the theme of love which, when analyzed in terms of the suppression or triumph of its four basic elements ( sex, eros, philia, and agape , offers a convincing allegory of man's existential self-definition by free choice.

  11. Social Circles: A 3D User Interface for Facebook

    Science.gov (United States)

    Rodrigues, Diego; Oakley, Ian

    Online social network services are increasingly popular web applications which display large amounts of rich multimedia content: contacts, status updates, photos and event information. Arguing that this quantity of information overwhelms conventional user interfaces, this paper presents Social Circles, a rich interactive visualization designed to support real world users of social network services in everyday tasks such as keeping up with friends and organizing their network. It achieves this by using 3D UIs, fluid animations and a spatial metaphor to enable direct manipulation of a social network.

  12. Mutation analysis in Duchenne and Becker muscular dystrophy patients from Bulgaria shows a peculiar distribution of breakpoints by intron

    Energy Technology Data Exchange (ETDEWEB)

    Todorova, A.; Bronzova, J.; Kremensky, I. [Univ. Hospital of Obstetrics and Gynecology, Sofia (Bulgaria)] [and others

    1996-10-02

    For the first time in Bulgaria, a deletion/duplication screening was performed on a group of 84 unrelated Duchenne/Becker muscular dystrophy patients, and the breakpoint distribution in the dystrophin gene was analyzed. Intragenic deletions were detected in 67.8% of patients, and intragenic duplications in 2.4%. A peculiar distribution of deletion breakpoints was found. Only 13.2% of the deletion breakpoints fell in the {open_quotes}classical{close_quotes} hot spot in intron 44, whereas the majority (> 54%) were located within the segment encompassing introns 45-51, which includes intron 50, the richest in breakpoints (16%) in the Bulgarian sample. Comparison with data from Greece and Turkey points at the probable existence of a deletion hot spot within intron 50, which might be a characteristic of populations of the Balkan region. 17 refs., 2 figs.

  13. mRNA processing in yeast

    International Nuclear Information System (INIS)

    Stevens, A.

    1982-01-01

    Investigations in this laboratory center on basic enzymatic reactions of RNA. Still undefined are reactions involved in the conversion of precursors of mRA (pre-mRNA) to mRNA in eukaryotes. The pre-mRNA is called heterogeneous nuclear RNA and is 2 to 6 times larger than mRNA. The conversion, called splicing, involves a removal of internal sequences called introns by endoribonuclease action followed by a rejoining of the 3'- and 5'-end fragments, called exons, by ligating activity. It has not been possible yet to study the enzymes involved in vitro. Also undefined are reactions involved in the turnover or discarding of certain of the pre-mRNA molecules. Yeast is a simple eukaryote and may be expected to have the same, but perhaps simpler, processing reactions as the higher eukaryotes. Two enzymes involved in the processing of pre-mRNA and mRNA in yeast are under investigation. Both enzymes have been partially purified from ribonucleoprotein particles of yeast. The first is a unique decapping enzyme which cleaves [ 3 H]m 7 Gppp [ 14 C]RNA-poly (A) of yeast, yielding [ 3 H]m 7 GDP and is suggested by the finding that the diphosphate product, m 7 GpppA(G), and UDP-glucose are not hydrolyzed. The second enzyme is an endoribonuclease which converts both the [ 3 H] and [ 14 C] labels of [ 3 H]m 7 Gppp[ 14 C]RNA-poly(A) from an oligo(dT)-cellulose bound form to an unbound, acid-insoluble form. Results show that the stimulation involves an interaction of the labeled RNA with the small nuclear RNA. The inhibition of the enzyme by ethidium bromide and its stimulation by small nuclear RNA suggest that it may be a processing ribonuclease, requiring specific double-stranded features in its substrate. The characterization of the unique decapping enzyme and endoribonuclease may help to understand reactions involved in the processing of pre-mRNA and mRNA in eukaryotes

  14. Multiple group I introns in the small-subunit rDNA of Botryosphaeria dothidea: implication for intraspecific genetic diversity.

    Directory of Open Access Journals (Sweden)

    Chao Xu

    Full Text Available Botryosphaeria dothidea is a widespread and economically important pathogen on various fruit trees, and it often causes die-back and canker on limbs and fruit rot. In characterizing intraspecies genetic variation within this fungus, group I introns, rich in rDNA of fungi, may provide a productive region for exploration. In this research, we analysed complete small subunit (SSU ribosomal DNA (rDNA sequences of 37 B. dothidea strains, and found four insertions, designated Bdo.S943, Bdo.S1199-A, Bdo.S1199-B and Bdo.S1506, at three positions. Sequence analysis and structure prediction revealed that both Bdo.S943 and Bdo.S1506 belonged to subgroup IC1 of group I introns, whereas Bdo.S1199-A and Bdo.S1199-B corresponded to group IE introns. Moreover, Bdo.S1199-A was found to host an open reading frame (ORF for encoding the homing endonuclease (HE, whereas Bdo.S1199-B, an evolutionary descendant of Bdo.S1199-A, included a degenerate HE. The above four introns were novel, and were the first group I introns observed and characterized in this species. Differential distribution of these introns revealed that all strains could be separated into four genotypes. Genotype III (no intron and genotype IV (Bdo.S1199-B were each found in only one strain, whereas genotype I (Bdo.S1199-A and genotype II (Bdo.S943 and Bdo.S1506 occurred in 95% of the strains. There is a correlation between B. dothidea genotypes and hosts or geographic locations. Thus, these newly discovered group I introns can help to advance understanding of genetic differentiation within B. dothidea.

  15. Phylogenetic inferences of Nepenthes species in Peninsular Malaysia revealed by chloroplast (trnL intron) and nuclear (ITS) DNA sequences

    OpenAIRE

    Bunawan, Hamidun; Yen, Choong Chee; Yaakop, Salmah; Noor, Normah Mohd

    2017-01-01

    Background The chloroplastic trnL intron and the nuclear internal transcribed spacer (ITS) region were sequenced for 11 Nepenthes species recorded in Peninsular Malaysia to examine their phylogenetic relationship and to evaluate the usage of trnL intron and ITS sequences for phylogenetic reconstruction of this genus. Results Phylogeny reconstruction was carried out using neighbor-joining, maximum parsimony and Bayesian analyses. All the trees revealed two major clusters, a lowland group consi...

  16. Pre-big-bang cosmology and circles in the cosmic microwave background

    International Nuclear Information System (INIS)

    Nelson, William; Wilson-Ewing, Edward

    2011-01-01

    We examine the possibility that circles in the cosmic microwave background could be formed by the interaction of a gravitational wave pulse emitted in some pre-big-bang phase of the universe with the last scattering surface. We derive the expected size distribution of such circles, as well as their typical ring width and (for concentric circles) angular separation. We apply these results, in particular, to conformal cyclic cosmology, ekpyrotic cosmology as well as loop quantum cosmology with and without inflation in order to determine how the predicted geometric properties of these circles would vary from one model to the other, and thus, if detected, could allow us to differentiate between various pre-big-bang cosmological models. We also obtain a relation between the angular ring width and the angular radius of such circles that can be used in order to determine whether or not circles observed in the cosmic microwave background are due to energetic pre-big-bang events.

  17. Drawing Euler Diagrams with Circles: The Theory of Piercings.

    Science.gov (United States)

    Stapleton, Gem; Leishi Zhang; Howse, John; Rodgers, Peter

    2011-07-01

    Euler diagrams are effective tools for visualizing set intersections. They have a large number of application areas ranging from statistical data analysis to software engineering. However, the automated generation of Euler diagrams has never been easy: given an abstract description of a required Euler diagram, it is computationally expensive to generate the diagram. Moreover, the generated diagrams represent sets by polygons, sometimes with quite irregular shapes that make the diagrams less comprehensible. In this paper, we address these two issues by developing the theory of piercings, where we define single piercing curves and double piercing curves. We prove that if a diagram can be built inductively by successively adding piercing curves under certain constraints, then it can be drawn with circles, which are more esthetically pleasing than arbitrary polygons. The theory of piercings is developed at the abstract level. In addition, we present a Java implementation that, given an inductively pierced abstract description, generates an Euler diagram consisting only of circles within polynomial time.

  18. Development of EST Intron-Targeting SNP Markers for Panax ginseng and Their Application to Cultivar Authentication.

    Science.gov (United States)

    Wang, Hongtao; Li, Guisheng; Kwon, Woo-Saeng; Yang, Deok-Chun

    2016-06-04

    Panax ginseng is one of the most valuable medicinal plants in the Orient. The low level of genetic variation has limited the application of molecular markers for cultivar authentication and marker-assisted selection in cultivated ginseng. To exploit DNA polymorphism within ginseng cultivars, ginseng expressed sequence tags (ESTs) were searched against the potential intron polymorphism (PIP) database to predict the positions of introns. Intron-flanking primers were then designed in conserved exon regions and used to amplify across the more variable introns. Sequencing results showed that single nucleotide polymorphisms (SNPs), as well as indels, were detected in four EST-derived introns, and SNP markers specific to "Gopoong" and "K-1" were first reported in this study. Based on cultivar-specific SNP sites, allele-specific polymerase chain reaction (PCR) was conducted and proved to be effective for the authentication of ginseng cultivars. Additionally, the combination of a simple NaOH-Tris DNA isolation method and real-time allele-specific PCR assay enabled the high throughput selection of cultivars from ginseng fields. The established real-time allele-specific PCR assay should be applied to molecular authentication and marker assisted selection of P. ginseng cultivars, and the EST intron-targeting strategy will provide a potential approach for marker development in species without whole genomic DNA sequence information.

  19. Using Group II Introns for Attenuating the In Vitro and In Vivo Expression of a Homing Endonuclease.

    Directory of Open Access Journals (Sweden)

    Tuhin Kumar Guha

    Full Text Available In Chaetomium thermophilum (DSM 1495 within the mitochondrial DNA (mtDNA small ribosomal subunit (rns gene a group IIA1 intron interrupts an open reading frame (ORF encoded within a group I intron (mS1247. This arrangement offers the opportunity to examine if the nested group II intron could be utilized as a regulatory element for the expression of the homing endonuclease (HEase. Constructs were generated where the codon-optimized ORF was interrupted with either the native group IIA1 intron or a group IIB type intron. This study showed that the expression of the HEase (in vivo in Escherichia coli can be regulated by manipulating the splicing efficiency of the HEase ORF-embedded group II introns. Exogenous magnesium chloride (MgCl2 stimulated the expression of a functional HEase but the addition of cobalt chloride (CoCl2 to growth media antagonized the expression of HEase activity. Ultimately the ability to attenuate HEase activity might be useful in precision genome engineering, minimizing off target activities, or where pathways have to be altered during a specific growth phase.

  20. Circle of willis and its variations; morphometric study in adult human cadavers

    OpenAIRE

    Raghavendra, Shirol VS, Daksha Dixit, Anil Kumar Reddy Y, Desai SP

    2014-01-01

    Background and Objectives: Circle of Willis plays a vital role in collateral circulation and redistribution of blood to all areas of the brain. Variation in circle of Willis is known to cause grave disorders like cerebrovascular disorders, subarachnoid haemorrhage, cerebral aneurysm and schizophrenia. The objectives of the present study are to study the formation and branching pattern of circle of Willis and also to study the distribution of variations. MATERIALS & Methods: The study was cond...

  1. Genome-wide generation and use of informative intron-spanning and intron-length polymorphism markers for high-throughput genetic analysis in rice

    Science.gov (United States)

    Badoni, Saurabh; Das, Sweta; Sayal, Yogesh K.; Gopalakrishnan, S.; Singh, Ashok K.; Rao, Atmakuri R.; Agarwal, Pinky; Parida, Swarup K.; Tyagi, Akhilesh K.

    2016-01-01

    We developed genome-wide 84634 ISM (intron-spanning marker) and 16510 InDel-fragment length polymorphism-based ILP (intron-length polymorphism) markers from genes physically mapped on 12 rice chromosomes. These genic markers revealed much higher amplification-efficiency (80%) and polymorphic-potential (66%) among rice accessions even by a cost-effective agarose gel-based assay. A wider level of functional molecular diversity (17–79%) and well-defined precise admixed genetic structure was assayed by 3052 genome-wide markers in a structured population of indica, japonica, aromatic and wild rice. Six major grain weight QTLs (11.9–21.6% phenotypic variation explained) were mapped on five rice chromosomes of a high-density (inter-marker distance: 0.98 cM) genetic linkage map (IR 64 x Sonasal) anchored with 2785 known/candidate gene-derived ISM and ILP markers. The designing of multiple ISM and ILP markers (2 to 4 markers/gene) in an individual gene will broaden the user-preference to select suitable primer combination for efficient assaying of functional allelic variation/diversity and realistic estimation of differential gene expression profiles among rice accessions. The genomic information generated in our study is made publicly accessible through a user-friendly web-resource, “Oryza ISM-ILP marker” database. The known/candidate gene-derived ISM and ILP markers can be enormously deployed to identify functionally relevant trait-associated molecular tags by optimal-resource expenses, leading towards genomics-assisted crop improvement in rice. PMID:27032371

  2. Edges and vertices in a unique signed circle in a signed graph

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    Richard Behr

    2017-12-01

    Full Text Available We examine the conditions under which a signed graph contains an edge or a vertex that is contained in a unique negative circle or a unique positive circle. For an edge in a unique signed circle, the positive and negative case require the same structure on the underlying graph, but the requirements on the signature are different. We characterize the structure of the underlying graph necessary to support such an edge in terms of bridges of a circle. We then use the results from the edge version of the problem to help solve the vertex version.

  3. Antisense Oligonucleotide-based Splice Correction for USH2A-associated Retinal Degeneration Caused by a Frequent Deep-intronic Mutation

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    Radulfus WN Slijkerman

    2016-01-01

    Full Text Available Usher syndrome (USH is the most common cause of combined deaf-blindness in man. The hearing loss can be partly compensated by providing patients with hearing aids or cochlear implants, but the loss of vision is currently untreatable. In general, mutations in the USH2A gene are the most frequent cause of USH explaining up to 50% of all patients worldwide. The first deep-intronic mutation in the USH2A gene (c.7595-2144A>G was reported in 2012, leading to the insertion of a pseudoexon (PE40 into the mature USH2A transcript. When translated, this PE40-containing transcript is predicted to result in a truncated non-functional USH2A protein. In this study, we explored the potential of antisense oligonucleotides (AONs to prevent aberrant splicing of USH2A pre-mRNA as a consequence of the c.7595-2144A>G mutation. Engineered 2'-O-methylphosphorothioate AONs targeting the PE40 splice acceptor site and/or exonic splice enhancer regions displayed significant splice correction potential in both patient derived fibroblasts and a minigene splice assay for USH2A c.7595-2144A>G, whereas a non-binding sense oligonucleotide had no effect on splicing. Altogether, AON-based splice correction could be a promising approach for the development of a future treatment for USH2A-associated retinitis pigmentosa caused by the deep-intronic c.7595-2144A>G mutation.

  4. tRNA gene diversity in the three domains of life

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    Kosuke eFujishima

    2014-05-01

    Full Text Available Transfer RNA (tRNA is widely known for its key role in decoding mRNA into protein. Despite their necessity and relatively short nucleotide sequences, a large diversity of gene structures and RNA secondary structures of pre-tRNAs and mature tRNAs have recently been discovered in the three domains of life. Growing evidences of disrupted tRNA genes in the genomes of Archaea reveals unique gene structures such as, intron-containing tRNA, split tRNA, and permuted tRNA. Coding sequence for these tRNAs are either separated with introns, fragmented, or permuted at the genome level. Although evolutionary scenario behind the tRNA gene disruption is still unclear, diversity of tRNA structure seems to be co-evolved with their processing enzyme, so-called RNA splicing endonuclease. Metazoan mitochondrial tRNAs (mtRNAs are known for their unique lack of either one or two arms from the typical tRNA cloverleaf structure, while still maintaining functionality. Recently identified nematode-specific V-arm containing tRNAs (nev-tRNAs possess long variable arms that are specific to eukaryotic class II tRNASer and tRNALeu but also decode class I tRNA codons. Moreover, many tRNA-like sequences have been found in the genomes of different organisms and viruses. Thus this review is aimed to cover the latest knowledge on tRNA gene diversity and further recapitulate the evolutionary and biological aspects that caused such uniqueness.

  5. A novel point mutation (G[sup [minus]1] to T) in a 5[prime] splice donor site of intron 13 of the dystrophin gene results in exon skipping and is responsible for Becker Muscular Dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Hagiwara, Yoko; Nishio, Hisahide; Kitoh, Yoshihiko; Takeshima, Yasuhiro; Narita, Naoko; Wada, Hiroko; Yokoyama, Mitsuhiro; Nakamura, Hajime; Matsuo, Masafumi (Kobe Univ. School of Medicine (Japan))

    1994-01-01

    The mutations in one-third of Duchenne and Becker muscular dystrophy patients remain unknown, as they do not involve gross rearrangements of the dystrophin gene. The authors now report a defect in the splicing of precursor mRNA (pre-mRNA), resulting from a maternally inherited mutation of the dystrophin gene in a patient with Becker muscular dystrophy. This defect results from a G-to-T transversion at the terminal nucleotide of exon 13, within the 5[prime] splice site of intron 13, and causes complete skipping of exon 13 during processing of dystrophin pre-mRNA. The predicted polypeptide encoded by the aberrant mRNA is a truncated dystrophin lacking 40 amino acids from the amino-proximal end of the rod domain. This is the first report of an intraexon point mutation that completely inactivates a 5[prime] splice donor site in dystrophin pre-mRNA. Analysis of the genomic context of the G[sup [minus]1]-to-T mutation at the 5[prime] splice site supports the exon-definition model of pre-mRNA splicing and contributes to the understanding of splice-site selection. 48 refs., 5 figs.

  6. mCSF1, a nucleus-encoded CRM protein required for the processing of many mitochondrial introns, is involved in the biogenesis of respiratory complexes I and IV in Arabidopsis.

    Science.gov (United States)

    Zmudjak, Michal; Colas des Francs-Small, Catherine; Keren, Ido; Shaya, Felix; Belausov, Eduard; Small, Ian; Ostersetzer-Biran, Oren

    2013-07-01

    The coding regions of many mitochondrial genes in plants are interrupted by intervening sequences that are classified as group II introns. Their splicing is essential for the expression of the genes they interrupt and hence for respiratory function, and is facilitated by various protein cofactors. Despite the importance of these cofactors, only a few of them have been characterized. CRS1-YhbY domain (CRM) is a recently recognized RNA-binding domain that is present in several characterized splicing factors in plant chloroplasts. The Arabidopsis genome encodes 16 CRM proteins, but these are largely uncharacterized. Here, we analyzed the intracellular location of one of these hypothetical proteins in Arabidopsis, mitochondrial CAF-like splicing factor 1 (mCSF1; At4 g31010), and analyzed the growth phenotypes and organellar activities associated with mcsf1 mutants in plants. Our data indicated that mCSF1 resides within mitochondria and its functions are essential during embryogenesis. Mutant plants with reduced mCSF1 displayed inhibited germination and retarded growth phenotypes that were tightly associated with reduced complex I and IV activities. Analogously to the functions of plastid-localized CRM proteins, analysis of the RNA profiles in wildtype and mcsf1 plants showed that mCSF1 acts in the splicing of many of the group II intron RNAs in Arabidopsis mitochondria. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  7. Genome-wide identification and functional prediction of nitrogen-responsive intergenic and intronic long non-coding RNAs in maize (Zea mays L.).

    Science.gov (United States)

    Lv, Yuanda; Liang, Zhikai; Ge, Min; Qi, Weicong; Zhang, Tifu; Lin, Feng; Peng, Zhaohua; Zhao, Han

    2016-05-11

    Nitrogen (N) is an essential and often limiting nutrient to plant growth and development. Previous studies have shown that the mRNA expressions of numerous genes are regulated by nitrogen supplies; however, little is known about the expressed non-coding elements, for example long non-coding RNAs (lncRNAs) that control the response of maize (Zea mays L.) to nitrogen. LncRNAs are a class of non-coding RNAs larger than 200 bp, which have emerged as key regulators in gene expression. In this study, we surveyed the intergenic/intronic lncRNAs in maize B73 leaves at the V7 stage under conditions of N-deficiency and N-sufficiency using ribosomal RNA depletion and ultra-deep total RNA sequencing approaches. By integration with mRNA expression profiles and physiological evaluations, 7245 lncRNAs and 637 nitrogen-responsive lncRNAs were identified that exhibited unique expression patterns. Co-expression network analysis showed that the nitrogen-responsive lncRNAs were enriched mainly in one of the three co-expressed modules. The genes in the enriched module are mainly involved in NADH dehydrogenase activity, oxidative phosphorylation and the nitrogen compounds metabolic process. We identified a large number of lncRNAs in maize and illustrated their potential regulatory roles in response to N stress. The results lay the foundation for further in-depth understanding of the molecular mechanisms of lncRNAs' role in response to nitrogen stresses.

  8. Correlation of PTPN11 polymorphism at intron 3 with gastric cancer

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    Li ZHANG

    2011-05-01

    Full Text Available Objective To explore the correlation of protein-tyrosine-phosphatase nonreceptor-type 11(PTPN11 polymorphism at intron 3 with gastric cancer in Chinese population,and the feasibility and accuracy of employing mastrix-assisted laser desorption ionization time-of-flight mass spectrogram(MALDI-TOF-MS in genotyping of this SNP.Methods Two hundred and forty-seven patients with gastric cancer,212 cancer-free patients and 160 cord blood samples were enrolled in present study.Genotypes of PTPN11 G/A polymorphism at intron 3 were determined by MALDI-TOF-MS analysis,and direct sequencing of PCR products with 20 samples of the gene locus was done for checking the accuracy of MALDI-TOF-MS.Histological examination,Helicobacter pylori culture,rapid urease test,serum anti-H.pylori antibodies(ELISA and urease colloidal gold test were performed to evaluate H.pylori infection.Results Direct sequencing of 20 random selected samples were well consistent with the MALDI-TOF-MS results.The rates of H.pylori infection were 73.68% in gastric cancer patients and 75.47% in cancer-free patients,implying no significant difference between the two groups.The distributions of genotypes were in Hardy Weinberg equilibrium in both gastric cancer patients and controls.There were no significant differences in the genotype frequencies between the 2 groups(P>0.05.Compared with the GG genotype,GA+AA genotype could not influence the risk of gastric cancer.When stratified for status,PTPN11 polymorphism was not associated with age,gender and H.pylori infection states in both cancer patients and controls.Conclusion It seems that PTPN11 G/A polymorphism at intron 3 has no affection on the risk of gastric cancer in Chinese population.

  9. Strong Signature of Natural Selection within an FHIT Intron Implicated in Prostate Cancer Risk

    Science.gov (United States)

    Ding, Yan; Larson, Garrett; Rivas, Guillermo; Lundberg, Cathryn; Geller, Louis; Ouyang, Ching; Weitzel, Jeffrey; Archambeau, John; Slater, Jerry; Daly, Mary B.; Benson, Al B.; Kirkwood, John M.; O'Dwyer, Peter J.; Sutphen, Rebecca; Stewart, James A.; Johnson, David; Nordborg, Magnus; Krontiris, Theodore G.

    2008-01-01

    Previously, a candidate gene linkage approach on brother pairs affected with prostate cancer identified a locus of prostate cancer susceptibility at D3S1234 within the fragile histidine triad gene (FHIT), a tumor suppressor that induces apoptosis. Subsequent association tests on 16 SNPs spanning approximately 381 kb surrounding D3S1234 in Americans of European descent revealed significant evidence of association for a single SNP within intron 5 of FHIT. In the current study, re-sequencing and genotyping within a 28.5 kb region surrounding this SNP further delineated the association with prostate cancer risk to a 15 kb region. Multiple SNPs in sequences under evolutionary constraint within intron 5 of FHIT defined several related haplotypes with an increased risk of prostate cancer in European-Americans. Strong associations were detected for a risk haplotype defined by SNPs 138543, 142413, and 152494 in all cases (Pearson's χ2 = 12.34, df 1, P = 0.00045) and for the homozygous risk haplotype defined by SNPs 144716, 142413, and 148444 in cases that shared 2 alleles identical by descent with their affected brothers (Pearson's χ2 = 11.50, df 1, P = 0.00070). In addition to highly conserved sequences encompassing SNPs 148444 and 152413, population studies revealed strong signatures of natural selection for a 1 kb window covering the SNP 144716 in two human populations, the European American (π = 0.0072, Tajima's D = 3.31, 14 SNPs) and the Japanese (π = 0.0049, Fay & Wu's H = 8.05, 14 SNPs), as well as in chimpanzees (Fay & Wu's H = 8.62, 12 SNPs). These results strongly support the involvement of the FHIT intronic region in an increased risk of prostate cancer. PMID:18953408

  10. Nonsynonymous substitution in abalone sperm fertilization genes exceeds substitution in introns and mitochondrial DNA

    Science.gov (United States)

    Metz, Edward C.; Robles-Sikisaka, Refugio; Vacquier, Victor D.

    1998-01-01

    Strong positive Darwinian selection acts on two sperm fertilization proteins, lysin and 18-kDa protein, from abalone (Haliotis). To understand the phylogenetic context for this dramatic molecular evolution, we obtained sequences of mitochondrial cytochrome c oxidase subunit I (mtCOI), and genomic sequences of lysin, 18-kDa, and a G protein subunit. Based on mtDNA differentiation, four north Pacific abalone species diverged within the past 2 million years (Myr), and remaining north Pacific species diverged over a period of 4–20 Myr. Between-species nonsynonymous differences in lysin and 18-kDa exons exceed nucleotide differences in introns by 3.5- to 24-fold. Remarkably, in some comparisons nonsynonymous substitutions in lysin and 18-kDa genes exceed synonymous substitutions in mtCOI. Lysin and 18-kDa intron/exon segments were sequenced from multiple red abalone individuals collected over a 1,200-km range. Only two nucleotide changes and two sites of slippage variation were detected in a total of >29,000 nucleotides surveyed. However, polymorphism in mtCOI and a G protein intron was found in this species. This finding suggests that positive selection swept one lysin allele and one 18-kDa allele to fixation. Similarities between mtCOI and lysin gene trees indicate that rapid adaptive evolution of lysin has occurred consistently through the history of the group. Comparisons with mtCOI molecular clock calibrations suggest that nonsynonymous substitutions accumulate 2–50 times faster in lysin and 18-kDa genes than in rapidly evolving mammalian genes. PMID:9724763

  11. Circle Hough transform implementation for dots recognition in braille cells

    Science.gov (United States)

    Jacinto Gómez, Edwar; Montiel Ariza, Holman; Martínez Sarmiento, Fredy Hernán.

    2017-02-01

    This paper shows a technique based on CHT (Circle Hough Transform) to achieve the optical Braille recognition (OBR). Unlike other papers developed around the same topic, this one is made by using Hough Transform to process the recognition and transcription of Braille cells, proving CHT to be an appropriate technique to go over different non-systematics factors who can affect the process, as the paper type where the text to traduce is placed, some lightning factors, input image resolution and some flaws derived from the capture process, which is realized using a scanner. Tests are performed with a local database using text generated by visual nondisabled people and some transcripts by sightless people; all of this with the support of National Institute for Blind People (INCI for their Spanish acronym) placed in Colombia.

  12. Asymptotically stable phase synchronization revealed by autoregressive circle maps

    Science.gov (United States)

    Drepper, F. R.

    2000-11-01

    A specially designed of nonlinear time series analysis is introduced based on phases, which are defined as polar angles in spaces spanned by a finite number of delayed coordinates. A canonical choice of the polar axis and a related implicit estimation scheme for the potentially underlying autoregressive circle map (next phase map) guarantee the invertibility of reconstructed phase space trajectories to the original coordinates. The resulting Fourier approximated, invertibility enforcing phase space map allows us to detect conditional asymptotic stability of coupled phases. This comparatively general synchronization criterion unites two existing generalizations of the old concept and can successfully be applied, e.g., to phases obtained from electrocardiogram and airflow recordings characterizing cardiorespiratory interaction.

  13. Training of students’ special endurance in ping pong sport circles

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    V.M. Grinko

    2017-04-01

    Full Text Available Urpose: to test experimentally influence of aerobic trainings (cross country training and basic aerobic on students’ special endurance in sport oriented groups (sport circles, ping pong. Material: 106 first year students (n=53 - control group and n=53 - experimental participated in experiment. For determination of temporal series’ trends R-S analysis was used. Prognostication of mistakes’ quantity per one set was fulfilled with the help of exponential smoothing method. Results: it was shown that exponential smoothing method permits to prognosticate by one set ahead with rather high accuracy. As initial predictor we found mean quantity of mistakes in all sets. It permits to average all internal and external factors, which influence on the next predicting indicators. Such approach increases confidence of mistakes’ calculation in prognostication. Criteria of prognostication methodic for possible indicators’ values were also determined. Conclusions: the recommended time distribution in program is as follows: ping pong - 75%; cross country training and basic aerobic - 25%.

  14. G2 cubic transition between two circles with shape control

    Science.gov (United States)

    Habib, Zulfiqar; Sakai, Manabu

    2009-01-01

    This paper describes a method for joining two circles with an S-shaped or with a broken back C-shaped transition curve, composed of at most two spiral segments. In highway and railway route design or car-like robot path planning, it is often desirable to have such a transition. It is shown that a single cubic curve can be used for blending or for a transition curve preserving G2 continuity with local shape control parameter and more flexible constraints. Provision of the shape parameter and flexibility provide freedom to modify the shape in a stable manner which is an advantage over previous work by Meek, Walton, Sakai and Habib.

  15. The Virtuous Circles of Clinical Information Systems: a Modern Utopia.

    Science.gov (United States)

    Degoulet, P

    2016-11-10

    Clinical information systems (CIS) are developed with the aim of improving both the efficiency and the quality of care. This position paper is based on the hypothesis that such vision is partly a utopian view of the emerging eSociety. Examples are drawn from 15 years of experience with the fully integrated Georges Pompidou University Hospital (HEGP) CIS and temporal data series extracted from the data warehouses of Assistance Publique - Hôpitaux de Paris (AP-HP) acute care hospitals which share the same administrative organization as HEGP. Three main virtuous circles are considered: user satisfaction vs. system use, system use vs. cost efficiency, and system use vs quality of care. In structural equation models (SEM), the positive bidirectional relationship between user satisfaction and use was only observed in the early HEGP CIS deployment phase (first four years) but disappeared in late post-adoption (≥8 years). From 2009 to 2013, financial efficiency of 20 AP-HP hospitals evaluated with stochastic frontier analysis (SFA) models diminished by 0.5% per year. The lower decrease of efficiency observed between the three hospitals equipped with a more mature CIS and the 17 other hospitals was of the same order of magnitude than the difference observed between pediatric and non-pediatric hospitals. Outcome quality benefits that would bring evidence to the system use vs. quality loop are unlikely to be obtained in a near future since they require integration with population-based outcome measures including mortality, morbidity, and quality of life that may not be easily available. Barriers to making the transformation of the utopian part of the CIS virtuous circles happen should be overcome to actually benefit the emerging eSociety.

  16. Differences in daily disposable circle lens performance characteristics

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    Schafer JM

    2014-04-01

    Full Text Available Jeffery M Schafer, William T Reindel, Marjorie J Rah, Osbert Chan, Lening Zhang Bausch & Lomb Incorporated, Rochester, NY, USA Purpose: The purpose of this evaluation was to compare the performance characteristics of two cosmetically tinted contact lenses in the circle lens category that differ in lens design, lens material, and pigment print pattern: etafilcon A (1-Day Acuvue Define; Johnson & Johnson Vision Care and hilafilcon B (Naturelle; Bausch & Lomb Incorporated. Methods: Two hundred Asian subjects (400 eyes were enrolled in this 1-month parallel, bilateral, randomized study at ten investigative sites. Study lenses were dispensed at a screening/dispensing visit, and follow-up visits occurred at 2 weeks and 1 month. Lenses were worn on a daily disposable basis. Fit characteristics were evaluated at each visit, and slit-lamp evaluations were completed at each follow-up visit. Results: Of the 200 patients enrolled, 172 (344 eyes completed the study. The proportion of eyes with fully centered lenses was statistically significantly higher for the hilafilcon B group at the 2-week and 1-month visits, P<0.05. Over all visits, 0.6% of hilafilcon B eyes demonstrated incomplete corneal coverage, whereas for the etafilcon A group, 8.5% of eyes demonstrated incomplete corneal coverage and/or edge lift. The proportion of eyes with adequate lens movement was statistically significantly higher for the hilafilcon B group, P<0.05. Over all visits, none of the hilafilcon B eyes was reported to have excessive movement, whereas for etafilcon A lenses, 10.2% of eyes were reported to have excessive movement. Conclusions: Etafilcon A lenses were significantly less likely to be fully centered and significantly more likely to have incomplete corneal coverage and/or edge lift compared with the hilafilcon B lenses. Keywords: cosmetic contact lens, circle contact lens

  17. The Dunaliella salina organelle genomes: large sequences, inflated with intronic and intergenic DNA

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    Tran Duc

    2010-05-01

    Full Text Available Abstract Background Dunaliella salina Teodoresco, a unicellular, halophilic green alga belonging to the Chlorophyceae, is among the most industrially important microalgae. This is because D. salina can produce massive amounts of β-carotene, which can be collected for commercial purposes, and because of its potential as a feedstock for biofuels production. Although the biochemistry and physiology of D. salina have been studied in great detail, virtually nothing is known about the genomes it carries, especially those within its mitochondrion and plastid. This study presents the complete mitochondrial and plastid genome sequences of D. salina and compares them with those of the model green algae Chlamydomonas reinhardtii and Volvox carteri. Results The D. salina organelle genomes are large, circular-mapping molecules with ~60% noncoding DNA, placing them among the most inflated organelle DNAs sampled from the Chlorophyta. In fact, the D. salina plastid genome, at 269 kb, is the largest complete plastid DNA (ptDNA sequence currently deposited in GenBank, and both the mitochondrial and plastid genomes have unprecedentedly high intron densities for organelle DNA: ~1.5 and ~0.4 introns per gene, respectively. Moreover, what appear to be the relics of genes, introns, and intronic open reading frames are found scattered throughout the intergenic ptDNA regions -- a trait without parallel in other characterized organelle genomes and one that gives insight into the mechanisms and modes of expansion of the D. salina ptDNA. Conclusions These findings confirm the notion that chlamydomonadalean algae have some of the most extreme organelle genomes of all eukaryotes. They also suggest that the events giving rise to the expanded ptDNA architecture of D. salina and other Chlamydomonadales may have occurred early in the evolution of this lineage. Although interesting from a genome evolution standpoint, the D. salina organelle DNA sequences will aid in the

  18. The Dunaliella salina organelle genomes: large sequences, inflated with intronic and intergenic DNA

    Energy Technology Data Exchange (ETDEWEB)

    Smith, David R.; Lee, Robert W.; Cushman, John C.; Magnuson, Jon K.; Tran, Duc; Polle, Juergen E.

    2010-05-07

    Abstract Background: Dunaliella salina Teodoresco, a unicellular, halophilic green alga belonging to the Chlorophyceae, is among the most industrially important microalgae. This is because D. salina can produce massive amounts of β-carotene, which can be collected for commercial purposes, and because of its potential as a feedstock for biofuels production. Although the biochemistry and physiology of D. salina have been studied in great detail, virtually nothing is known about the genomes it carries, especially those within its mitochondrion and plastid. This study presents the complete mitochondrial and plastid genome sequences of D. salina and compares them with those of the model green algae Chlamydomonas reinhardtii and Volvox carteri. Results: The D. salina organelle genomes are large, circular-mapping molecules with ~60% noncoding DNA, placing them among the most inflated organelle DNAs sampled from the Chlorophyta. In fact, the D. salina plastid genome, at 269 kb, is the largest complete plastid DNA (ptDNA) sequence currently deposited in GenBank, and both the mitochondrial and plastid genomes have unprecedentedly high intron densities for organelle DNA: ~1.5 and ~0.4 introns per gene, respectively. Moreover, what appear to be the relics of genes, introns, and intronic open reading frames are found scattered throughout the intergenic ptDNA regions -- a trait without parallel in other characterized organelle genomes and one that gives insight into the mechanisms and modes of expansion of the D. salina ptDNA. Conclusions: These findings confirm the notion that chlamydomonadalean algae have some of the most extreme organelle genomes of all eukaryotes. They also suggest that the events giving rise to the expanded ptDNA architecture of D. salina and other Chlamydomonadales may have occurred early in the evolution of this lineage. Although interesting from a genome evolution standpoint, the D. salina organelle DNA sequences will aid in the development of a viable

  19. Regulation of expression of two LY-6 family genes by intron retention and transcription induced chimerism

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    Mallya Meera

    2008-09-01

    Full Text Available Abstract Background Regulation of the expression of particular genes can rely on mechanisms that are different from classical transcriptional and translational control. The LY6G5B and LY6G6D genes encode LY-6 domain proteins, whose expression seems to be regulated in an original fashion, consisting of an intron retention event which generates, through an early premature stop codon, a non-coding transcript, preventing expression in most cell lines and tissues. Results The MHC LY-6 non-coding transcripts have shown to be stable and very abundant in the cell, and not subject to Nonsense Mediated Decay (NMD. This retention event appears not to be solely dependent on intron features, because in the case of LY6G5B, when the intron is inserted in the artificial context of a luciferase expression plasmid, it is fully spliced but strongly stabilises the resulting luciferase transcript. In addition, by quantitative PCR we found that the retained and spliced forms are differentially expressed in tissues indicating an active regulation of the non-coding transcript. EST database analysis revealed that these genes have an alternative expression pathway with the formation of Transcription Induced Chimeras (TIC. This data was confirmed by RT-PCR, revealing the presence of different transcripts that would encode the chimeric proteins CSNKβ-LY6G5B and G6F-LY6G6D, in which the LY-6 domain would join to a kinase domain and an Ig-like domain, respectively. Conclusion In conclusion, the LY6G5B and LY6G6D intron-retained transcripts are not subjected to NMD and are more abundant than the properly spliced forms. In addition, these genes form chimeric transcripts with their neighbouring same orientation 5' genes. Of interest is the fact that the 5' genes (CSNKβ or G6F undergo differential splicing only in the context of the chimera (CSNKβ-LY6G5B or G6F-LY6G6C and not on their own.

  20. Literature Circles in 18. Century; As a Cultural Centers of Istanbul: The Role of "Literature Circles" in the Transmission of The Cultural Heritage

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    Zehra ÖKSÜZ

    2015-08-01

    Full Text Available The aim of this study is to explore the particular examples of literature circles which were seen as wisdom centre and were influential in 18th century Ottoman social and cultural life. This study foc uses on the literature circles in the capital of Ottomans and examines their roles in the transmission of cultural heritage. Mahfil, which means the meeting place, became the centre of literature activities which are performed in a particular place. This li terature circles gained the status of being a prestigious literature and art centre which witnessed the creation of significant works in 18th. They functioned as a transmitter of culture in terms of the works studied and role model literary figures. Patron age tradition promoted the progress of literary activities in the circles. With regard to their significant contribution to the Ottoman culture and civilization, literature circles emerged at the patronage of Sultan III. Ahmed, Sultan III. Selim, Sadrazam Nevşehirli Damad İbrahim Paşa, Sadrazam Koca Râgıb Paşa, Hoca Neş’et Efendi, Şeyh Gâlib, Hoca Süleyman Vahyî. Therefore, it is essential to study these circles in terms of its importance as being home to important literary figures with a sophisticated sen se of art.

  1. On the minimal travel time needed to collect n items on a circle

    NARCIS (Netherlands)

    Litvak, Nelly; van Zwet, Willem R.

    2004-01-01

    Consider n items located randomly on a circle of length 1. The locations of the items are assumed to be independent and uniformly distributed on [0,1). A picker starts at point 0 and has to collect all n items by moving along the circle at unit speed in either direction. In this paper we study the

  2. On the minimal travel time needed to collect $n$ items on a circle

    NARCIS (Netherlands)

    Litvak, Nelli; van Zwet, Willem R.; van der Geer, Sarah; Wegkamp, Marten

    2012-01-01

    Consider $n$ items located randomly on a circle of length 1. The locations of the items are assumed to be independent and uniformly distributed on $[0,1)$. A picker starts at point 0 and has to collect all n items by moving along the circle at unit speed in either direction. In this paper we study

  3. On the minimal travel time needed to collect n items on a circle

    NARCIS (Netherlands)

    Litvak, Nelli; van Zwet, W.R.

    2002-01-01

    Consider n items located randomly on a circle of length 1. The locations of the items are assumed to be independent and uniformly distributed on [0, 1). A picker starts at point 0, and he has to collect all n items by moving along the circle at unit speed in either direction. In this paper we study

  4. Providing a Full Circle of Support to Teachers in an Inclusive Elementary School

    Science.gov (United States)

    Waldron, Nancy L.; Redd, Lacy

    2011-01-01

    Providing a full circle of support to teachers in an inclusive elementary school, the Newberry Elementary School (NES) principal and staff have worked for 5 years to ensure the inclusion of students with disabilities in general education classrooms. The authors would like to share their perceptions of how this full circle (the multiple systems) of…

  5. Quality Circles: How Effective Are They in Improving Employee Performance and Attitudes?

    Science.gov (United States)

    Buch, Kimberly; Raban, Amiram

    1990-01-01

    Used a quasi-experimental design to assess the effect of a quality circle intervention on behavior and attitudes of 88 employees at a large Midwestern organization. Results provide mixed support for the purported ability of circles to improve work behavior with no change for absenteeism and productivity but positive change for quality of work.…

  6. A surface containing a line and a circle through each point is a quadric

    KAUST Repository

    Nilov, Fedor K.; Skopenkov, Mikhail

    2012-01-01

    We prove that a surface in 3-dimensional Euclidean space containing a line and a circle through each point is a quadric. We also give some particular results on the classification of surfaces containing several circles through each point. © 2012 Springer Science+Business Media B.V.

  7. Exploring Writing Circles as Innovative, Collaborative Writing Structures with Teacher Candidates

    Science.gov (United States)

    Roberts, Sherron Killingsworth; Blanch, Norine; Gurjar, Nandita

    2017-01-01

    Writing circles are "small groups... meeting regularly to share drafts, choose common writing topics, practice positive response, and in general, help each other become better writers" (Vopat, 2009, p. 6). In this exploratory study, writing circles were employed with elementary teacher candidates in hopes of enhancing their perceptions…

  8. Comparing Interactions in Literature Circles in Both Online and in Class Discussions

    Science.gov (United States)

    Skeen, Christel Ghrist

    2014-01-01

    Discourse analysis of literature circles can lead educators to understand the different types of interactions taking place as students talk about text. Social and academic interactions exist in both face-to-face and online discussions of reading material. This study examines two different settings of literature circles and compares interactions of…

  9. 77 FR 55691 - Establishment of Class E Airspace; Circle Town, MT

    Science.gov (United States)

    2012-09-11

    ... (RNAV) Global Positioning System (GPS) standard instrument approach procedures at Circle Town County..., at Circle Town County Airport, to accommodate IFR aircraft executing new RNAV (GPS) standard..., Washington on August 30, 2012. Steven L. Vale, Acting Manager, Operations Support Group, Western Service...

  10. A surface containing a line and a circle through each point is a quadric

    KAUST Repository

    Nilov, Fedor K.

    2012-06-20

    We prove that a surface in 3-dimensional Euclidean space containing a line and a circle through each point is a quadric. We also give some particular results on the classification of surfaces containing several circles through each point. © 2012 Springer Science+Business Media B.V.

  11. The Revival of Research Circles: Meeting the Needs of Modern Aging and the Third Age

    Science.gov (United States)

    Ostlund, Britt

    2008-01-01

    This article provides evidence that it is worthwhile to reconsider the traditional research circle method as a means of involving people in the third age in fulfilling their needs to participate in learning activities and make their voices heard. The findings are based on three cases of research circles consistently driven by the interests of the…

  12. Linearly Recurrent Circle Map Subshifts and an Application to Schrödinger Operators

    CERN Document Server

    Adamczewski, B

    2001-01-01

    We discuss circle map sequences and subshifts generated by them. We give a characterization of those sequences among them which are linearly recurrent. As an application we deduce zero-measure spectrum for a class of discrete one-dimensional Schrödinger operators with potentials generated by circle maps.

  13. Migraine without aura is not associated with incomplete circle of Willis

    DEFF Research Database (Denmark)

    Ezzatian-Ahar, Shabnam; Amin, Faisal Mohammad; Obaid, Hayder Ghani

    2014-01-01

    the prevalence of incomplete circle of Willis in migraineurs and controls. In the present study we compared the prevalence of incomplete circle of Willis in female migraine patients without aura to female healthy non-migraine controls.Using 3-Tesla magnetic resonance angiography we recorded three...

  14. Genome-wide development and deployment of informative intron-spanning and intron-length polymorphism markers for genomics-assisted breeding applications in chickpea.

    Science.gov (United States)

    Srivastava, Rishi; Bajaj, Deepak; Sayal, Yogesh K; Meher, Prabina K; Upadhyaya, Hari D; Kumar, Rajendra; Tripathi, Shailesh; Bharadwaj, Chellapilla; Rao, Atmakuri R; Parida, Swarup K

    2016-11-01

    The discovery and large-scale genotyping of informative gene-based markers is essential for rapid delineation of genes/QTLs governing stress tolerance and yield component traits in order to drive genetic enhancement in chickpea. A genome-wide 119169 and 110491 ISM (intron-spanning markers) from 23129 desi and 20386 kabuli protein-coding genes and 7454 in silico InDel (insertion-deletion) (1-45-bp)-based ILP (intron-length polymorphism) markers from 3283 genes were developed that were structurally and functionally annotated on eight chromosomes and unanchored scaffolds of chickpea. A much higher amplification efficiency (83%) and intra-specific polymorphic potential (86%) detected by these markers than that of other sequence-based genetic markers among desi and kabuli chickpea accessions was apparent even by a cost-effective agarose gel-based assay. The genome-wide physically mapped 1718 ILP markers assayed a wider level of functional genetic diversity (19-81%) and well-defined phylogenetics among domesticated chickpea accessions. The gene-derived 1424 ILP markers were anchored on a high-density (inter-marker distance: 0.65cM) desi intra-specific genetic linkage map/functional transcript map (ICC 4958×ICC 2263) of chickpea. This reference genetic map identified six major genomic regions harbouring six robust QTLs mapped on five chromosomes, which explained 11-23% seed weight trait variation (7.6-10.5 LOD) in chickpea. The integration of high-resolution QTL mapping with differential expression profiling detected six including one potential serine carboxypeptidase gene with ILP markers (linked tightly to the major seed weight QTLs) exhibiting seed-specific expression as well as pronounced up-regulation especially in seeds of high (ICC 4958) as compared to low (ICC 2263) seed weight mapping parental accessions. The marker information generated in the present study was made publicly accessible through a user-friendly web-resource, "Chickpea ISM-ILP Marker Database

  15. A multiplexed miRNA and transgene expression platform for simultaneous repression and expression of protein coding sequences.

    Science.gov (United States)

    Seyhan, Attila A

    2016-01-01

    Knockdown of single or multiple gene targets by RNA interference (RNAi) is necessary to overcome escape mutants or isoform redundancy. It is also necessary to use multiple RNAi reagents to knockdown multiple targets. It is also desirable to express a transgene or positive regulatory elements and inhibit a target gene in a coordinated fashion. This study reports a flexible multiplexed RNAi and transgene platform using endogenous intronic primary microRNAs (pri-miRNAs) as a scaffold located in the green fluorescent protein (GFP) as a model for any functional transgene. The multiplexed intronic miRNA - GFP transgene platform was designed to co-express multiple small RNAs within the polycistronic cluster from a Pol II promoter at more moderate levels to reduce potential vector toxicity. The native intronic miRNAs are co-transcribed with a precursor GFP mRNA as a single transcript and presumably cleaved out of the precursor-(pre) mRNA by the RNA splicing machinery, spliceosome. The spliced intron with miRNA hairpins will be further processed into mature miRNAs or small interfering RNAs (siRNAs) capable of triggering RNAi effects, while the ligated exons become a mature messenger RNA for the translation of the functional GFP protein. Data show that this approach led to robust RNAi-mediated silencing of multiple Renilla Luciferase (R-Luc)-tagged target genes and coordinated expression of functional GFP from a single transcript in transiently transfected HeLa cells. The results demonstrated that this design facilitates the coordinated expression of all mature miRNAs either as individual miRNAs or as multiple miRNAs and the associated protein. The data suggest that, it is possible to simultaneously deliver multiple negative (miRNA or shRNA) and positive (transgene) regulatory elements. Because many cellular processes require simultaneous repression and activation of downstream pathways, this approach offers a platform technology to achieve that dual manipulation efficiently

  16. Determinism and randomness in the evolution of introns and sine inserts in mouse and human mitochondrial solute carrier and cytokine receptor genes.

    Science.gov (United States)

    Cianciulli, Antonia; Calvello, Rosa; Panaro, Maria A

    2015-04-01

    In the homologous genes studied, the exons and introns alternated in the same order in mouse and human. We studied, in both species: corresponding short segments of introns, whole corresponding introns and complete homologous genes. We considered the total number of nucleotides and the number and orientation of the SINE inserts. Comparisons of mouse and human data series showed that at the level of individual relatively short segments of intronic sequences the stochastic variability prevails in the local structuring, but at higher levels of organization a deterministic component emerges, conserved in mouse and human during the divergent evolution, despite the ample re-editing of the intronic sequences and the fact that processes such as SINE spread had taken place in an independent way in the two species. Intron conservation is negatively correlated with the SINE occupancy, suggesting that virus inserts interfere with the conservation of the sequences inherited from the common ancestor. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Hexanucleotide Repeats in ALS/FTD Form Length-Dependent RNA Foci, Sequester RNA Binding Proteins, and Are Neurotoxic

    Directory of Open Access Journals (Sweden)

    Youn-Bok Lee

    2013-12-01

    Full Text Available The GGGGCC (G4C2 intronic repeat expansion within C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Intranuclear neuronal RNA foci have been observed in ALS and FTD tissues, suggesting that G4C2 RNA may be toxic. Here, we demonstrate that the expression of 38× and 72× G4C2 repeats form intranuclear RNA foci that initiate apoptotic cell death in neuronal cell lines and zebrafish embryos. The foci colocalize with a subset of RNA binding proteins, including SF2, SC35, and hnRNP-H in transfected cells. Only hnRNP-H binds directly to G4C2 repeats following RNA immunoprecipitation, and only hnRNP-H colocalizes with 70% of G4C2 RNA foci detected in C9ORF72 mutant ALS and FTD brain tissues. We show that expanded G4C2 repeats are potently neurotoxic and bind hnRNP-H and other RNA binding proteins. We propose that RNA toxicity and protein sequestration may disrupt RNA processing and contribute to neurodegeneration.

  18. Circles of Support and Accountability for Sex Offenders: A Systematic Review of Outcomes.

    Science.gov (United States)

    Clarke, Martin; Brown, Susan; Völlm, Birgit

    2017-08-01

    We conducted a systematic review of studies reporting on the effectiveness of Circles of Support and Accountability (Circles). Circles use volunteers to provide support for sex offenders living in the community. We searched 10 databases up to the end of 2013 and identified 3 relevant outcome studies. An additional 12 papers or reports were identified by searching reference lists, Google, and contacting key authors and Circles providers to obtain unpublished data. These 15 studies comprised one randomized controlled trial, three retrospective cohorts with matched controls, and 11 case series. The majority reported measures of recidivism, particularly reconviction. The 4 studies with controls generally reported that participation in Circles was associated with lower recidivism although there were few statistically significant differences. Few studies examined changes in risk or psychosocial outcomes. A number of methodological issues are discussed. Longer term, prospective follow-up studies with control groups are required to address these issues.

  19. Length and GC content variability of introns among teleostean genomes in the light of the metabolic rate hypothesis.

    Directory of Open Access Journals (Sweden)

    Ankita Chaurasia

    Full Text Available A comparative analysis of five teleostean genomes, namely zebrafish, medaka, three-spine stickleback, fugu and pufferfish was performed with the aim to highlight the nature of the forces driving both length and base composition of introns (i.e., bpi and GCi. An inter-genome approach using orthologous intronic sequences was carried out, analyzing independently both variables in pairwise comparisons. An average length shortening of introns was observed at increasing average GCi values. The result was not affected by masking transposable and repetitive elements harbored in the intronic sequences. The routine metabolic rate (mass specific temperature-corrected using the Boltzmann's factor was measured for each species. A significant correlation held between average differences of metabolic rate, length and GC content, while environmental temperature of fish habitat was not correlated with bpi and GCi. Analyzing the concomitant effect of both variables, i.e., bpi and GCi, at increasing genomic GC content, a decrease of bpi and an increase of GCi was observed for the significant majority of the intronic sequences (from ∼ 40% to ∼ 90%, in each pairwise comparison. The opposite event, concomitant increase of bpi and decrease of GCi, was counter selected (from <1% to ∼ 10%, in each pairwise comparison. The results further support the hypothesis that the metabolic rate plays a key role in shaping genome architecture and evolution of vertebrate genomes.

  20. Length and GC content variability of introns among teleostean genomes in the light of the metabolic rate hypothesis.

    Science.gov (United States)

    Chaurasia, Ankita; Tarallo, Andrea; Bernà, Luisa; Yagi, Mitsuharu; Agnisola, Claudio; D'Onofrio, Giuseppe

    2014-01-01

    A comparative analysis of five teleostean genomes, namely zebrafish, medaka, three-spine stickleback, fugu and pufferfish was performed with the aim to highlight the nature of the forces driving both length and base composition of introns (i.e., bpi and GCi). An inter-genome approach using orthologous intronic sequences was carried out, analyzing independently both variables in pairwise comparisons. An average length shortening of introns was observed at increasing average GCi values. The result was not affected by masking transposable and repetitive elements harbored in the intronic sequences. The routine metabolic rate (mass specific temperature-corrected using the Boltzmann's factor) was measured for each species. A significant correlation held between average differences of metabolic rate, length and GC content, while environmental temperature of fish habitat was not correlated with bpi and GCi. Analyzing the concomitant effect of both variables, i.e., bpi and GCi, at increasing genomic GC content, a decrease of bpi and an increase of GCi was observed for the significant majority of the intronic sequences (from ∼ 40% to ∼ 90%, in each pairwise comparison). The opposite event, concomitant increase of bpi and decrease of GCi, was counter selected (from hypothesis that the metabolic rate plays a key role in shaping genome architecture and evolution of vertebrate genomes.

  1. Heritability of circle of Willis variations in families with intracranial aneurysms.

    Directory of Open Access Journals (Sweden)

    Mayte Sánchez van Kammen

    Full Text Available Intracranial aneurysms more often occur in the same arterial territory within families. Several aneurysm locations are associated with specific circle of Willis variations. We investigated whether the same circle of Willis variations are more likely to occur in first-degree relatives than in unrelated individuals.We assessed four circle of Willis variations (classical, A1-asymmetry, incomplete posterior communicating artery and fetal circulation in two independent groups of families with familial aneurysms and ≥2 first-degree relatives with circle of Willis imaging on MRA/CTA. In each (index family we determined the proportion of first-degree relatives with the same circle of Willis variation as the proband and compared it to the proportion of first-degree relatives of a randomly selected unrelated (comparison family who had the same circle of Willis variation as the index family's proband. Concordance in index families and comparison families was compared with a conditional logistic events/trials model. The analysis was simulated 1001 times; we report the median concordances, odds ratios (ORs, and 95% confidence intervals (95%CI. The groups were analysed separately and together by meta-analysis.We found a higher overall concordance in circle of Willis configuration in index families than in comparison families (meta-analysis, 244 families: OR 2.2, 95%CI 1.6-3.0 mostly attributable to a higher concordance in incomplete posterior communicating artery (meta-analysis: OR 2.8, 95%CI 1.8-4.3. No association was found for the other three circle of Willis variations.In two independent groups of families with familial aneurysms, the incomplete PcomA variation occurred more often within than between families suggesting heritability of this circle of Willis variation. Further studies should investigate genetic variants associated with circle of Willis formation.

  2. RNA oxidation

    DEFF Research Database (Denmark)

    Kjaer, L. K.; Cejvanovic, V.; Henriken, T.

    2015-01-01

    .9 significant hazard ratio for death compared with the quartile with the lowest 8oxoGuo excretion when adjusted for age, sex, BMI, smoker status, s-HbA1c, urine protein excretion and s-cholesterol. We conclude that it is now established that RNA oxidation is an independent risk factor for death in type 2...

  3. Phylogenetic inferences of Nepenthes species in Peninsular Malaysia revealed by chloroplast (trnL intron) and nuclear (ITS) DNA sequences.

    Science.gov (United States)

    Bunawan, Hamidun; Yen, Choong Chee; Yaakop, Salmah; Noor, Normah Mohd

    2017-01-26

    The chloroplastic trnL intron and the nuclear internal transcribed spacer (ITS) region were sequenced for 11 Nepenthes species recorded in Peninsular Malaysia to examine their phylogenetic relationship and to evaluate the usage of trnL intron and ITS sequences for phylogenetic reconstruction of this genus. Phylogeny reconstruction was carried out using neighbor-joining, maximum parsimony and Bayesian analyses. All the trees revealed two major clusters, a lowland group consisting of N. ampullaria, N. mirabilis, N. gracilis and N. rafflesiana, and another containing both intermediately distributed species (N. albomarginata and N. benstonei) and four highland species (N. sanguinea, N. macfarlanei, N. ramispina and N. alba). The trnL intron and ITS sequences proved to provide phylogenetic informative characters for deriving a phylogeny of Nepenthes species in Peninsular Malaysia. To our knowledge, this is the first molecular phylogenetic study of Nepenthes species occurring along an altitudinal gradient in Peninsular Malaysia.

  4. The role of Circle women in curbing violence against women and girls in Africa

    Directory of Open Access Journals (Sweden)

    Sylvia Owusu-Ansah

    2016-07-01

    Full Text Available The article looks at the role Circle of Concerned African Women Theologians (the Circle have played in the struggle to end or reduce the rate at which violence against women and girls occurs in West Africa by highlighting the contributions of older Circle women, especially the initiator of the Circle, Mercy Amba Oduyoye. The initiator of the Circle and other older Circle women have left a remarkable legacy that needs to continue by the current and future generations of the Circle. The background information examines the leadership and mentorship of Mercy Amba Oduyoye and the impact she has made in the lives of African women. The essay then looks at the types of violence that women face in West Africa with the specific contributions of Circle women in the struggle to end violence against women and girls. It then argues that Circle women have played very significant roles both in setting the pace and giving the platform for women activities to minimise gender-based violence against women and girls. Circle women have written and presented papers that have addressed many challenges including HIV and/or AIDS, Girl Child trafficking, Marriage of Minors, and almost all kinds of violence against women and girls. Currently, religious violence threatens the fabric of African nations causing insecurity and panic, women and girls being the most vulnerable. The challenge to the present and future Circle members is to contribute in significant ways towards religious harmony in Africa and beyond. The Circle acknowledges the leadership role of women and encourages them to spearhead the liberation of women as well as empower them to be able to aspire to get to the top or become independent. No one understands what someone else feels better than the person experiencing the ordeal. Women can better understand what they go through and also have the passion to strive towards liberation.Intradisciplinary and/or interdisciplinary implications: In this article, the

  5. CYP3A5 mRNA degradation by nonsense-mediated mRNA decay.

    Science.gov (United States)

    Busi, Florent; Cresteil, Thierry

    2005-09-01

    The total CYP3A5 mRNA level is significantly greater in carriers of the CYP3A5*1 allele than in CYP3A5*3 homozygotes. Most of the CYP3A5*3 mRNA includes an intronic sequence (exon 3B) containing premature termination codons (PTCs) between exons 3 and 4. Two models were used to investigate the degradation of CYP3A5 mRNA: a CYP3A5 minigene consisting of CYP3A5 exons and introns 3 to 6 transfected into MCF7 cells, and the endogenous CYP3A5 gene expressed in HepG2 cells. The 3'-untranslated region g.31611C>T mutation has no effect on CYP3A5 mRNA decay. Splice variants containing exon 3B were more unstable than wild-type (wt) CYP3A5 mRNA. Cycloheximide prevents the recognition of PTCs by ribosomes: in transfected MCF7 and HepG2 cells, cycloheximide slowed down the degradation of exon 3B-containing splice variants, suggesting the participation of nonsense-mediated decay (NMD). When PTCs were removed from pseudoexon 3B or when UPF1 small interfering RNA was used to impair the NMD mechanism, the decay of the splice variant was reduced, confirming the involvement of NMD in the degradation of CYP3A5 splice variants. Induction could represent a source of variability for CYP3A5 expression and could modify the proportion of splice variants. The extent of CYP3A5 induction was investigated after exposure to barbiturates or steroids: CYP3A4 was markedly induced in a pediatric population compared with untreated neonates. However, no effect could be detected in either the total CYP3A5 RNA, the proportion of splice variant RNA, or the protein level. Therefore, in these carriers, induction is unlikely to switch on the phenotypic CYP3A5 expression in carriers of CYP3A5*3/*3.

  6. Targeted Regression of Hepatocellular Carcinoma by Cancer-Specific RNA Replacement through MicroRNA Regulation.

    Science.gov (United States)

    Kim, Juhyun; Won, Ranhui; Ban, Guyee; Ju, Mi Ha; Cho, Kyung Sook; Young Han, Sang; Jeong, Jin-Sook; Lee, Seong-Wook

    2015-07-20

    Hepatocellular carcinoma (HCC) has a high fatality rate and limited therapeutic options with side effects and low efficacy. Here, we proposed a new anti-HCC approach based on cancer-specific post-transcriptional targeting. To this end, trans-splicing ribozymes from Tetrahymena group I intron were developed, which can specifically induce therapeutic gene activity through HCC-specific replacement of telomerase reverse transcriptase (TERT) RNA. To circumvent side effects due to TERT expression in regenerating liver tissue, liver-specific microRNA-regulated ribozymes were constructed by incorporating complementary binding sites for the hepatocyte-selective microRNA-122a (miR-122a), which is down-regulated in HCC. The ribozyme activity in vivo was assessed in mouse models orthotopically implanted with HCC. Systemic administration of adenovirus encoding the developed ribozymes caused efficient anti-cancer effect and the least hepatotoxicity with regulation of ribozyme expression by miR-122a in both xenografted and syngeneic orthotopic murine model of multifocal HCC. Of note, the ribozyme induced local and systemic antitumor immunity, thereby completely suppressing secondary tumor challenge in the syngeneic mouse. The cancer specific trans-splicing ribozyme system, which mediates tissue-specific microRNA-regulated RNA replacement, provides a clinically relevant, safe, and efficient strategy for HCC treatment.

  7. The Wigner semi-circle law in quantum electro dynamics

    International Nuclear Information System (INIS)

    Accardi, L.; Nagoya Univ.; Lu, Y.G.; Nagoya Univ.

    1996-01-01

    In the present paper, the basic ideas of the stochastic limit of quantum theory are applied to quantum electro-dynamics. This naturally leads to the study of a new type of quantum stochastic calculus on a Hilbert module. Our main result is that in the weak coupling limit of a system composed of a free particle (electron, atom,..) interacting, via the minimal coupling, with the quantum electromagnetic field, a new type of quantum noise arises, living on a Hilbert module rather than a Hilbert space. Moreover we prove that the vacuum distribution of the limiting field operator is not Gaussian, as usual, but a nonlinear deformation of the Wigner semi-circle law. A third new object arising from the present theory, is the so-called interacting Fock space. A kind of Fock space in which the n quanta, in the n-particle space, are not independent, but interact. The origin of all these new features is that we do not introduce the dipole approximation, but we keep the exponential response term, coupling the electron to the quantum electromagnetic field. This produces a nonlinear interaction among all the modes of the limit master field (quantum noise) whose explicit expression, that we find, can be considered as a nonlinear generalization of the Fermi golden rule. (orig.)

  8. Primer Extension Mutagenesis Powered by Selective Rolling Circle Amplification

    Science.gov (United States)

    Huovinen, Tuomas; Brockmann, Eeva-Christine; Akter, Sultana; Perez-Gamarra, Susan; Ylä-Pelto, Jani; Liu, Yuan; Lamminmäki, Urpo

    2012-01-01

    Primer extension mutagenesis is a popular tool to create libraries for in vitro evolution experiments. Here we describe a further improvement of the method described by T.A. Kunkel using uracil-containing single-stranded DNA as the template for the primer extension by additional uracil-DNA glycosylase treatment and rolling circle amplification (RCA) steps. It is shown that removal of uracil bases from the template leads to selective amplification of the nascently synthesized circular DNA strand carrying the desired mutations by phi29 DNA polymerase. Selective RCA (sRCA) of the DNA heteroduplex formed in Kunkel's mutagenesis increases the mutagenesis efficiency from 50% close to 100% and the number of transformants 300-fold without notable diversity bias. We also observed that both the mutated and the wild-type DNA were present in at least one third of the cells transformed directly with Kunkel's heteroduplex. In contrast, the cells transformed with sRCA product contained only mutated DNA. In sRCA, the complex cell-based selection for the mutant strand is replaced with the more controllable enzyme-based selection and less DNA is needed for library creation. Construction of a gene library of ten billion members is demonstrated with the described method with 240 nanograms of DNA as starting material. PMID:22355397

  9. End of the line to build a circle

    CERN Multimedia

    2006-01-01

    The installation of the cryogenic distribution line in the LHC tunnel is finally finished! All the sectors have undergone pressure and helium leak tests at room temperature, and one complete sector was cold tested in cryogenic conditions. Some of the QRL team in UJ22 of the LHC tunnel, where the last sector of the cryogenic distribution line was installed.It must have been a joyous moment in UJ22 of the LHC tunnel (near Point 2, Saint Genis Pouilly) on 19 October. This was where the last external weld of the cryogenic distribution line, also known as QRL, was made, thus completing the full distribution ring. The QRL is a circle built in 8 sectors, each approximately 3 km in length. It will circulate helium in liquid and gas phases, at different temperatures and pressures, to provide the cryogenic conditions for the superconducting magnets in the LHC tunnel. The last sector installed (sector 1-2) passed the pressure and helium leak tests at room temperature on 28 October. As part of the warm test, each sector...

  10. Kastor-Traschen black holes, null geodesics and conformal circles

    International Nuclear Information System (INIS)

    Casey, Stephen

    2012-01-01

    The Kastor-Traschen metric is a time-dependent solution of the Einstein-Maxwell equations with positive cosmological constant Λ which can be used to describe an arbitrary number of charged dynamical black holes. In this paper, we consider the null geodesic structure of this solution, in particular, focusing on the projection to the space of orbits of the timelike conformal retraction. It is found that these projected light rays arise as integral curves of a system of third-order ordinary differential equations. This system is not uniquely defined, however, and we use the inherent freedom to construct a new system whose integral curves coincide with the projection of distinguished null curves of Kastor-Traschen arising from a magnetic flow. We discuss our results in the one-centre case and demonstrate a link to conformal circles in the limit Λ → 0. We also show how to construct analytic expressions for the projected null geodesics of this metric by exploiting a well-known diffeomorphism between the K-T metric and extremal Reissner-Nordstrom-de Sitter. We make some remarks about the two-centre solution and demonstrate a link with the one-centre case. (paper)

  11. Molecular evolution of Adh and LEAFY and the phylogenetic utility of their introns in Pyrus (Rosaceae).

    Science.gov (United States)

    Zheng, Xiaoyan; Hu, Chunyun; Spooner, David; Liu, Jing; Cao, Jiashu; Teng, Yuanwen

    2011-09-14

    The genus Pyrus belongs to the tribe Pyreae (the former subfamily Maloideae) of the family Rosaceae, and includes one of the most important commercial fruit crops, pear. The phylogeny of Pyrus has not been definitively reconstructed. In our previous efforts, the internal transcribed spacer region (ITS) revealed a poorly resolved phylogeny due to non-concerted evolution of nrDNA arrays. Therefore, introns of low copy nuclear genes (LCNG) are explored here for improved resolution. However, paralogs and lineage sorting are still two challenges for applying LCNGs in phylogenetic studies, and at least two independent nuclear loci should be compared. In this work the second intron of LEAFY and the alcohol dehydrogenase gene (Adh) were selected to investigate their molecular evolution and phylogenetic utility. DNA sequence analyses revealed a complex ortholog and paralog structure of Adh genes in Pyrus and Malus, the pears and apples. Comparisons between sequences from RT-PCR and genomic PCR indicate that some Adh homologs are putatively nonfunctional. A partial region of Adh1 was sequenced for 18 Pyrus species and three subparalogs representing Adh1-1 were identified. These led to poorly resolved phylogenies due to low sequence divergence and the inclusion of putative recombinants. For the second intron of LEAFY, multiple inparalogs were discovered for both LFY1int2 and LFY2int2. LFY1int2 is inadequate for phylogenetic analysis due to lineage sorting of two inparalogs. LFY2int2-N, however, showed a relatively high sequence divergence and led to the best-resolved phylogeny. This study documents the coexistence of outparalogs and inparalogs, and lineage sorting of these paralogs and orthologous copies. It reveals putative recombinants that can lead to incorrect phylogenetic inferences, and presents an improved phylogenetic resolution of Pyrus using LFY2int2-N. Our study represents the first phylogenetic analyses based on LCNGs in Pyrus. Ancient and recent duplications lead

  12. Molecular evolution of Adh and LEAFY and the phylogenetic utility of their introns in Pyrus (Rosaceae

    Directory of Open Access Journals (Sweden)

    Cao Jiashu

    2011-09-01

    Full Text Available Abstract Background The genus Pyrus belongs to the tribe Pyreae (the former subfamily Maloideae of the family Rosaceae, and includes one of the most important commercial fruit crops, pear. The phylogeny of Pyrus has not been definitively reconstructed. In our previous efforts, the internal transcribed spacer region (ITS revealed a poorly resolved phylogeny due to non-concerted evolution of nrDNA arrays. Therefore, introns of low copy nuclear genes (LCNG are explored here for improved resolution. However, paralogs and lineage sorting are still two challenges for applying LCNGs in phylogenetic studies, and at least two independent nuclear loci should be compared. In this work the second intron of LEAFY and the alcohol dehydrogenase gene (Adh were selected to investigate their molecular evolution and phylogenetic utility. Results DNA sequence analyses revealed a complex ortholog and paralog structure of Adh genes in Pyrus and Malus, the pears and apples. Comparisons between sequences from RT-PCR and genomic PCR indicate that some Adh homologs are putatively nonfunctional. A partial region of Adh1 was sequenced for 18 Pyrus species and three subparalogs representing Adh1-1 were identified. These led to poorly resolved phylogenies due to low sequence divergence and the inclusion of putative recombinants. For the second intron of LEAFY, multiple inparalogs were discovered for both LFY1int2 and LFY2int2. LFY1int2 is inadequate for phylogenetic analysis due to lineage sorting of two inparalogs. LFY2int2-N, however, showed a relatively high sequence divergence and led to the best-resolved phylogeny. This study documents the coexistence of outparalogs and inparalogs, and lineage sorting of these paralogs and orthologous copies. It reveals putative recombinants that can lead to incorrect phylogenetic inferences, and presents an improved phylogenetic resolution of Pyrus using LFY2int2-N. Conclusions Our study represents the first phylogenetic analyses based

  13. An Intron 7 Polymorphism in APP Affects the Age of Onset of Dementia in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Emma L. Jones

    2011-01-01

    Full Text Available People with Down syndrome (DS develop Alzheimer's disease (AD with an early age of onset. A tetranucleotide repeat, attt5−8, in intron 7 of the amyloid precursor protein has been associated with the age of onset of AD in DS in a preliminary study. The authors examine the impact of this polymorphism in a larger cohort of individuals with DS. Adults with DS were genotyped for attt5−8 and APOE. The results were analysed with respect to the age of onset of dementia. The presence of three copies of the six-repeat allele resulted in onset of dementia seven years earlier than in the presence of other genotypes. Further study is essential to elucidate the mechanism by which this polymorphism functions, with an exciting opportunity to identify novel treatment targets relevant for people with DS and AD.

  14. Cytochrome oxidase subunit II gene in mitochondria of Oenothera has no intron

    Science.gov (United States)

    Hiesel, Rudolf; Brennicke, Axel

    1983-01-01

    The cytochrome oxidase subunit II gene has been localized in the mitochondrial genome of Oenothera berteriana and the nucleotide sequence has been determined. The coding sequence contains 777 bp and, unlike the corresponding gene in Zea mays, is not interrupted by an intron. No TGA codon is found within the open reading frame. The codon CGG, as in the maize gene, is used in place of tryptophan codons of corresponding genes in other organisms. At position 742 in the Oenothera sequence the TGG of maize is changed into a CGG codon, where Trp is conserved as the amino acid in other organisms. Homologous sequences occur more than once in the mitochondrial genome as several mitochondrial DNA species hybridize with DNA probes of the cytochrome oxidase subunit II gene. ImagesFig. 5. PMID:16453484

  15. An evolutionarily conserved intronic region controls the spatiotemporal expression of the transcription factor Sox10

    Directory of Open Access Journals (Sweden)

    Pavan William J

    2008-10-01

    Full Text Available Abstract Background A major challenge lies in understanding the complexities of gene regulation. Mutation of the transcription factor SOX10 is associated with several human diseases. The disease phenotypes reflect the function of SOX10 in diverse tissues including the neural crest, central nervous system and otic vesicle. As expected, the SOX10 expression pattern is complex and highly dynamic, but little is known of the underlying mechanisms regulating its spatiotemporal pattern. SOX10 expression is highly conserved between all vertebrates characterised. Results We have combined in vivo testing of DNA fragments in zebrafish and computational comparative genomics to identify the first regulatory regions of the zebrafish sox10 gene. Both approaches converged on the 3' end of the conserved 1st intron as being critical for spatial patterning of sox10 in the embryo. Importantly, we have defined a minimal region crucial for this function. We show that this region contains numerous binding sites for transcription factors known to be essential in early neural crest induction, including Tcf/Lef, Sox and FoxD3. We show that the identity and relative position of these binding sites are conserved between zebrafish and mammals. A further region, partially required for oligodendrocyte expression, lies in the 5' region of the same intron and contains a putative CSL binding site, consistent with a role for Notch signalling in sox10 regulation. Furthermore, we show that β-catenin, Notch signalling and Sox9 can induce ectopic sox10 expression in early embryos, consistent with regulatory roles predicted from our transgenic and computational results. Conclusion We have thus identified two major sites of sox10 regulation in vertebrates and provided evidence supporting a role for at least three factors in driving sox10 expression in neural crest, otic epithelium and oligodendrocyte domains.

  16. Complex group-I introns in nuclear SSU rDNA of red and green algae: evidence of homing-endonuclease pseudogenes in the Bangiophyceae

    DEFF Research Database (Denmark)

    Haugen, P; Huss, V A; Nielsen, Henrik

    1999-01-01

    on the complementary strand. A comparison between related group-I introns in the Bangiophyceae revealed homing-endonuclease-like pseudogenes due to frame-shifts and deletions in Porphyra and Bangia. The Scenedesmus and Porphyra introns provide new insights into the evolution and possible novel functions of nuclear...

  17. Blocking of an intronic splicing silencer completely rescues IKBKAP exon 20 splicing in familial dysautonomia patient cells

    DEFF Research Database (Denmark)

    Bruun, Gitte H; Bang, Jeanne Mv; Christensen, Lise L

    2018-01-01

    designed splice switching oligonucleotides (SSO) that blocks the intronic hnRNP A1 binding site, and demonstrate that this completely rescues splicing of IKBKAP exon 20 in FD patient fibroblasts and increases the amounts of IKAP protein. We propose that this may be developed into a potential new specific...

  18. A Conserved Splicing Silencer Dynamically Regulates O-GlcNAc Transferase Intron Retention and O-GlcNAc Homeostasis

    Directory of Open Access Journals (Sweden)

    Sung-Kyun Park

    2017-08-01

    Full Text Available Modification of nucleocytoplasmic proteins with O-GlcNAc regulates a wide variety of cellular processes and has been linked to human diseases. The enzymes O-GlcNAc transferase (OGT and O-GlcNAcase (OGA add and remove O-GlcNAc, but the mechanisms regulating their expression remain unclear. Here, we demonstrate that retention of the fourth intron of OGT is regulated in response to O-GlcNAc levels. We further define a conserved intronic splicing silencer (ISS that is necessary for OGT intron retention. Deletion of the ISS in colon cancer cells leads to increases in OGT, but O-GlcNAc homeostasis is maintained by concomitant increases in OGA protein. However, the ISS-deleted cells are hypersensitive to OGA inhibition in culture and in soft agar. Moreover, growth of xenograft tumors from ISS-deleted cells is compromised in mice treated with an OGA inhibitor. Thus, ISS-mediated regulation of OGT intron retention is a key component in OGT expression and maintaining O-GlcNAc homeostasis.

  19. Rich services in interoperable Learning Designs: can the circle be squared?

    OpenAIRE

    Griffiths, David

    2009-01-01

    Griffiths, D. (2009). Rich services in interoperable Learning Designs: Can the circle be squared?. Presented at Opening Up Learning Design, European LAMS and Learning Design Conference 2009. July, 6-9, 2009, Milton Keynes, United Kingdom.

  20. Pied de pulse: packing embroidered circles and coil actuators in pied de poule (houndstooth)

    NARCIS (Netherlands)

    Feijs, L.M.G.; Toeters, M.J.; Torrence, E.; Torrence, B.; Sequin, C.; McKenna, D.; Fenyvesi, K.; Sarhangi, R.

    2016-01-01

    We report on the integration of fractal-like structures inspired by Appolonian circles with pied de poule (houndstooth) fabric patterns, and on the use of electric actuators in garments made with digital embroidery techniques.

  1. Visual Thinking, Algebraic Thinking, and a Full Unit-Circle Diagram.

    Science.gov (United States)

    Shear, Jonathan

    1985-01-01

    The study of trigonometric functions in terms of the unit circle offer an example of how students can learn algebraic relations and operations while using visually oriented thinking. Illustrations are included. (MNS)

  2. College geometry an introduction to the modern geometry of the triangle and the circle

    CERN Document Server

    Altshiller-Court, Nathan

    2007-01-01

    The standard university-level text for decades, this volume offers exercises in construction problems, harmonic division, circle and triangle geometry, and other areas. 1952 edition, revised and enlarged by the author.

  3. Interference of guiding modes in 'traffic' circle waveguides composed of dielectric spherical particles

    International Nuclear Information System (INIS)

    Polishchuk, I.Ya.; Gozman, M.I.; Samoylova, O.M.; Burin, A.L.

    2009-01-01

    The interference of guiding polariton modes propagating through the waveguide composed of dielectric spherical particles forming a 'traffic' circle docked by two linear entrance and exit chains is investigated. The dependence of intensity of the polariton wave on the position of the particle on the circle was studied using the multisphere Mie scattering formalism. We show that, if the frequency of light belongs to the pass-band of the circular part of this waveguide, the electromagnetic waves may be considered as two optical beams running along the circle in opposite directions and interfering with each other. Indeed, the obtained intensity behavior can be represented as a simple superposition of two waves propagating along the circle in opposite directions. The applications of this interference are discussed

  4. Violence in the eye of adolescents: education intervention with Culture Circles.

    Science.gov (United States)

    Brandão Neto, Waldemar; Silva, Marta Angélica Iossi; de Aquino, Jael Maria; de Lima, Luciane Soares; Monteiro, Estela Maria Leite Meirelles

    2015-01-01

    to apply the methodology of Culture Circles on adolescents as a strategy for health education of nurses in the construction of the collective knowledge of the thematic violence. action research type and qualitative study. Participants were 11 adolescents from a public school in Recife, PE, Brazil. Data production in Culture Circles included the participant observation with field diary, photographic recording and filming, as well as the photovoice technique. The analysis was performed by triangulating data in dialogue with the literature. it was shown that the problematizing action provided by the Culture Circle made possible to create situations in which adolescents felt invited to critically refl ect on the phenomenon of violence in all its complexity. the health education intervention, performed by Culture Circles, added learning and mutual growth subsidizing nursing care actions that excel at leadership and autonomy of adolescents.

  5. Collateral Circles in Carotid Artery Occlusion. A Comparative Study between CW Doppler and contrast angiography

    Energy Technology Data Exchange (ETDEWEB)

    Giraldi, C; Marconi, F; Parenti, G; Lenzi, B; Canapicchi, R; Padolecchia, R

    1986-01-01

    In order to evaluate the presence and efficacy of the different collateral circles, 98 patients with occlusion of the internal carotid artery between its origin and the origin of the ophtalmic artery, has been examined. Before contrast angiography, each patients was submitted to a Doppler examination with test of compression on the exsternal and common carotid arteries. The information on the collateral circles (Willis and pre-Willis) deriving from the Doppler examination seems to be interesting and more accurate. On the contrary, angiography allows a better visualisation of the extention of intercranial circles. These data show that the Doppler and angiographic techniques are complementary one to the other in the study of the collateral circles.

  6. Fermi Coordinates of an Observer Moving in a Circle in Minkowski Space: Apparent Behavior of Clocks

    National Research Council Canada - National Science Library

    Bahder, Thomas

    2000-01-01

    Space-time coordinate transformations valid for arbitrarily long coordinate time are derived from global Minkowski coordinates to the Fermi coordinates of an observer moving in a circle in three-dimensional space...

  7. Quasi-human seniority-order algorithm for unequal circles packing

    International Nuclear Information System (INIS)

    Zhu, Dingju

    2016-01-01

    In the existing methods for solving unequal circles packing problems, the initial configuration is given arbitrarily or randomly, but the impact of different initial configurations for existing packing algorithm to the speed of existing packing algorithm solving unequal circles packing problems is very large. The quasi-human seniority-order algorithm proposed in this paper can generate a better initial configuration for existing packing algorithm to accelerate the speed of existing packing algorithm solving unequal circles packing problems. In experiments, the quasi-human seniority-order algorithm is applied to generate better initial configurations for quasi-physical elasticity methods to solve the unequal circles packing problems, and the experimental results show that the proposed quasi-human seniority-order algorithm can greatly improve the speed of solving the problem.

  8. Citizenship as individual responsibility through personal investment - an ethnographic study in a study circle

    Directory of Open Access Journals (Sweden)

    Annika Pastuhov

    2017-05-01

    Full Text Available The aim of this article is to shed light on how the democratic ideal of institutionalised Nordic popular education is realised through an ethnographic field study in an English as a foreign language study circle. The study focuses on how participants express their citizenship when taking part in the study circle. Citizenship is viewed as a dynamic concept comprising the aspects of 'being' and 'acting' and constructed in and through social interaction. The study circle is arranged as a classroom practice: The study circle leader organises the activities, while the participants engage in exercises and attempt to learn correct usage. Through their participation, the participants take individual responsibility for what they see as their lack of sufficient knowledge of English. The participants describe their participation as a personal and voluntary investment in themselves. In light of the study, the individual stance is discussed as limiting possibilities for responsibility and thus expressions of citizenship.

  9. Developing a set of strong intronic promoters for robust metabolic engineering in oleaginous Rhodotorula (Rhodosporidium) yeast species.

    Science.gov (United States)

    Liu, Yanbin; Yap, Sihui Amy; Koh, Chong Mei John; Ji, Lianghui

    2016-11-25

    Red yeast species in the Rhodotorula/Rhodosporidium genus are outstanding producers of triacylglyceride and cell biomass. Metabolic engineering is expected to further enhance the productivity and versatility of these hosts for the production of biobased chemicals and fuels. Promoters with strong activity during oil-accumulation stage are critical tools for metabolic engineering of these oleaginous yeasts. The upstream DNA sequences of 6 genes involved in lipid biosynthesis or accumulation in Rhodotorula toruloides were studied by luciferase reporter assay. The promoter of perilipin/lipid droplet protein 1 gene (LDP1) displayed much stronger activity (4-11 folds) than that of glyceraldehyde-3-phosphate dehydrogenase gene (GPD1), one of the strongest promoters known in yeasts. Depending on the stage of cultivation, promoter of acetyl-CoA carboxylase gene (ACC1) and fatty acid synthase β subunit gene (FAS1) exhibited intermediate strength, displaying 50-160 and 20-90% levels of GPD1 promoter, respectively. Interestingly, introns significantly modulated promoter strength at high frequency. The incorporation of intron 1 and 2 of LDP1 (LDP1in promoter) enhanced its promoter activity by 1.6-3.0 folds. Similarly, the strength of ACC1 promoter was enhanced by 1.5-3.2 folds if containing intron 1. The intron 1 sequences of ACL1 and FAS1 also played significant regulatory roles. When driven by the intronic promoters of ACC1 and LDP1 (ACC1in and LDP1in promoter, respectively), the reporter gene expression were up-regulated by nitrogen starvation, independent of de novo oil biosynthesis and accumulation. As a proof of principle, overexpression of the endogenous acyl-CoA-dependent diacylglycerol acyltransferase 1 gene (DGA1) by LDP1in promoter was significantly more efficient than GPD1 promoter in enhancing lipid accumulation. Intronic sequences play an important role in regulating gene expression in R. toruloides. Three intronic promoters, LDP1in, ACC1in and FAS1in, are

  10. Complex motion of elevators in piecewise map model combined with circle map

    Science.gov (United States)

    Nagatani, Takashi

    2013-11-01

    We study the dynamic behavior in the elevator traffic controlled by capacity when the inflow rate of passengers into elevators varies periodically with time. The dynamics of elevators is described by the piecewise map model combined with the circle map. The motion of the elevators depends on the inflow rate, its period, and the number of elevators. The motion in the piecewise map model combined with the circle map shows a complex behavior different from the motion in the piecewise map model.

  11. Discriminants and functional equations for polynomials orthogonal on the unit circle

    International Nuclear Information System (INIS)

    Ismail, M.E.H.; Witte, N.S.

    2000-01-01

    We derive raising and lowering operators for orthogonal polynomials on the unit circle and find second order differential and q-difference equations for these polynomials. A general functional equation is found which allows one to relate the zeros of the orthogonal polynomials to the stationary values of an explicit quasi-energy and implies recurrences on the orthogonal polynomial coefficients. We also evaluate the discriminants and quantized discriminants of polynomials orthogonal on the unit circle

  12. Multimodal determination of Rayleigh dispersion and attenuation curves using the circle fit method

    Science.gov (United States)

    Verachtert, R.; Lombaert, G.; Degrande, G.

    2018-03-01

    This paper introduces the circle fit method for the determination of multi-modal Rayleigh dispersion and attenuation curves as part of a Multichannel Analysis of Surface Waves (MASW) experiment. The wave field is transformed to the frequency-wavenumber (fk) domain using a discretized Hankel transform. In a Nyquist plot of the fk-spectrum, displaying the imaginary part against the real part, the Rayleigh wave modes correspond to circles. The experimental Rayleigh dispersion and attenuation curves are derived from the angular sweep of the central angle of these circles. The method can also be applied to the analytical fk-spectrum of the Green's function of a layered half-space in order to compute dispersion and attenuation curves, as an alternative to solving an eigenvalue problem. A MASW experiment is subsequently simulated for a site with a regular velocity profile and a site with a soft layer trapped between two stiffer layers. The performance of the circle fit method to determine the dispersion and attenuation curves is compared with the peak picking method and the half-power bandwidth method. The circle fit method is found to be the most accurate and robust method for the determination of the dispersion curves. When determining attenuation curves, the circle fit method and half-power bandwidth method are accurate if the mode exhibits a sharp peak in the fk-spectrum. Furthermore, simulated and theoretical attenuation curves determined with the circle fit method agree very well. A similar correspondence is not obtained when using the half-power bandwidth method. Finally, the circle fit method is applied to measurement data obtained for a MASW experiment at a site in Heverlee, Belgium. In order to validate the soil profile obtained from the inversion procedure, force-velocity transfer functions were computed and found in good correspondence with the experimental transfer functions, especially in the frequency range between 5 and 80 Hz.

  13. Pengaruh Penerapan Metode Socratic Circles Disertai Media Gambar Terhadap Kemampuan Berpikir Kreatif Siswa

    OpenAIRE

    Afidah, Ihda Nuria; Santosa, Slamet; Indrowati, Meti

    2012-01-01

    - This research aims to ascertain whether or not the application Socratic Circles method with images media affects the student's creative thinking skill.This research is considered quasi-experiment research. The research was designed using Posttest-Only Control Group Design by applying Socratic Circles method with images media in experimental group and lectures methods, discussions, and presentations in control group. The population of this research were all strudents in X grade of SMA Nege...

  14. The association between Interleukin (IL)-4 gene intron 3 VNTR polymorphism and alopecia areata (AA) in Turkish population.

    Science.gov (United States)

    Kalkan, Göknur; Karakus, Nevin; Baş, Yalçın; Takçı, Zennure; Ozuğuz, Pınar; Ateş, Omer; Yigit, Serbulent

    2013-09-25

    Alopecia areata (AA) is hypothesized to be an organ-specific autoimmune disease of hair follicles mediated by T cells. As immunological and genetic factors have been implicated in the pathogenesis of AA, the purpose of the present study was to investigate possible associations between the functional Interleukin (IL)-4 gene intron 3 VNTR polymorphism and AA susceptibility and disease progression in Turkish population. The study group consisted of 116 unrelated patients with AA and 125 unrelated healthy controls. Genomic DNA was isolated and IL-4 gene 70 bp VNTR polymorphism determined by using polymerase chain reaction (PCR) with specific primers. No association was observed between AA patients and controls according to genotype distribution (p=0.051). The allele distribution of IL-4 gene intron 3 VNTR polymorphism was statistically different between AA patients and control group (p=0.026). The frequency of P1 allele in patients was significantly higher than that in the control group. When the P2P2 genotype was compared with P1P2+P1P1 genotypes, a statistically significant difference was observed between patients and controls (p=0.036). Intron 3 VNTR polymorphism in the IL-4 gene was found to be associated with AA susceptibility in Turkish population. The results suggest that IL-4 VNTR polymorphism in the intron 3 region may be a risk factor for the development of AA among Turkish population. This is the first to report that intron 3 VNTR polymorphism in the IL-4 gene is associated with AA susceptibility. © 2013.

  15. Mutations in the Lactococcus lactis Ll.LtrB group II intron that retain mobility in vivo

    Directory of Open Access Journals (Sweden)

    D'Souza Lisa M

    2002-12-01

    Full Text Available Abstract Background Group II introns are mobile genetic elements that form conserved secondary and tertiary structures. In order to determine which of the conserved structural elements are required for mobility, a series of domain and sub-domain deletions were made in the Lactococcus lactis group II intron (Ll.LtrB and tested for mobility in a genetic assay. Point mutations in domains V and VI were also tested. Results The largest deletion that could be made without severely compromising mobility was 158 nucleotides in DIVb(1–2. This mutant had a mobility frequency comparable to the wild-type Ll.LtrB intron (ΔORF construct. Hence, all subsequent mutations were done in this mutant background. Deletion of DIIb reduced mobility to approximately 18% of wild-type, while another deletion in domain II (nts 404–459 was mobile to a minor extent. Only two deletions in DI and none in DIII were tolerated. Some mobility was also observed for a DIVa deletion mutant. Of the three point mutants at position G3 in DV, only G3A retained mobility. In DVI, deletion of the branch-point nucleotide abolished mobility, but the presence of any nucleotide at the branch-point position restored mobility to some extent. Conclusions The smallest intron capable of efficient retrohoming was 725 nucleotides, comprising the DIVb(1–2 and DII(iia,b deletions. The tertiary elements found to be nonessential for mobility were alpha, kappa and eta. In DV, only the G3A mutant was mobile. A branch-point residue is required for intron mobility.

  16. Immunoregulation by interference RNA (iRNA – mechanisms, role, perspective

    Directory of Open Access Journals (Sweden)

    Emilia Sikora

    2011-08-01

    Full Text Available The functioning of an organism depends on the precise control mechanisms, constantly adjusted to the actual state. Therefore, there is a need for efficient communication between both adjacent and distant cells, which may be executed by proteins such as hormones, neurotransmitters and cytokines. Recently another means of regulation has emerged – short regulatory RNAs (srRNAs. Although discovered only a couple of years ago, the mechanism of RNA interference has already become a topic of thousands of publications, defining its roles in both physiological and pathological processes, such as cancerogenesis and autoimmunization.RNAs regulating cell function may be coded in its genome (both exons and introns or be introduced from the external environment. In mammals microRNAs (miRNAs cooperate with proteins from the Ago/PIWI family to form effector ribonucleoprotein complexes, and owing to their complementarity to the target mRNA, control genes’ expression at the posttranscriptional level, either through the suppression of mRNA translation or through mRNA degradation.SrRNAs are crucial regulators throughout the development of immune cells, starting from hematopoietic stem cells, up to the effector cells of the adaptive immune response. Moreover, some of the regulatory cells perform their function by releasing miRNAs, which are then transported to the target cells, possibly enclosed in the exosomes.

  17. Striatal output markers do not alter in response to circling behaviour in 6-OHDA lesioned rats produced by acute or chronic administration of the monoamine uptake inhibitor BTS 74 398.

    Science.gov (United States)

    Lane, E L; Cheetham, S; Jenner, P

    2008-01-01

    The monoamine uptake inhibitor BTS 74 398 induces ipsilateral circling in 6-hydroxydopamine (6-OHDA) lesioned rats without induction of abnormal motor behaviours associated with L-dopa administration. We examined whether this was reflected in the expression of peptide mRNA in the direct and indirect striatal output pathways.6-OHDA lesioning of the nigrostriatal pathway increased striatal expression of PPE-A mRNA and decreased levels of PPT mRNA with PPE-B mRNA expression remaining unchanged. Acute L-dopa administration normalised PPE-A mRNA and elevated PPT mRNA while PPE-B mRNA expression remained unchanged. Acute administration of BTS 74 398 did not alter striatal peptide mRNA levels. Following chronic treatment with L-dopa, PPE-A mRNA expression in the lesioned striatum continued to be normalised and PPT mRNA was increased compared to the intact side. PPE-B mRNA expression was also markedly increased relative to the non-lesioned striatum. Chronic BTS 74 398 administration did not alter mRNA expression in the 6-OHDA lesioned striatum although small increases in PPT mRNA expression in the intact and sham lesioned striatum were observed. The failure of BTS 74 398 to induce changes in striatal neuropeptide mRNA correlated with its failure to induce abnormal motor behaviours or behavioural sensitisation but does not explain how it produces a reversal of motor deficits. An action in another area of the brain appears likely and may explain the subsequent failure of BTS 74 398 and related compounds to exert anti-parkinsonian actions in man.

  18. Screening for duplications, deletions and a common intronic mutation detects 35% of second mutations in patients with USH2A monoallelic mutations on Sanger sequencing.

    Science.gov (United States)

    Steele-Stallard, Heather B; Le Quesne Stabej, Polona; Lenassi, Eva; Luxon, Linda M; Claustres, Mireille; Roux, Anne-Francoise; Webster, Andrew R; Bitner-Glindzicz, Maria

    2013-08-08

    Usher Syndrome is the leading cause of inherited deaf-blindness. It is divided into three subtypes, of which the most common is Usher type 2, and the USH2A gene accounts for 75-80% of cases. Despite recent sequencing strategies, in our cohort a significant proportion of individuals with Usher type 2 have just one heterozygous disease-causing mutation in USH2A, or no convincing disease-causing mutations across nine Usher genes. The purpose of this study was to improve the molecular diagnosis in these families by screening USH2A for duplications, heterozygous deletions and a common pathogenic deep intronic variant USH2A: c.7595-2144A>G. Forty-nine Usher type 2 or atypical Usher families who had missing mutations (mono-allelic USH2A or no mutations following Sanger sequencing of nine Usher genes) were screened for duplications/deletions using the USH2A SALSA MLPA reagent kit (MRC-Holland). Identification of USH2A: c.7595-2144A>G was achieved by Sanger sequencing. Mutations were confirmed by a combination of reverse transcription PCR using RNA extracted from nasal epithelial cells or fibroblasts, and by array comparative genomic hybridisation with sequencing across the genomic breakpoints. Eight mutations were identified in 23 Usher type 2 families (35%) with one previously identified heterozygous disease-causing mutation in USH2A. These consisted of five heterozygous deletions, one duplication, and two heterozygous instances of the pathogenic variant USH2A: c.7595-2144A>G. No variants were found in the 15 Usher type 2 families with no previously identified disease-causing mutations. In 11 atypical families, none of whom had any previously identified convincing disease-causing mutations, the mutation USH2A: c.7595-2144A>G was identified in a heterozygous state in one family. All five deletions and the heterozygous duplication we report here are novel. This is the first time that a duplication in USH2A has been reported as a cause of Usher syndrome. We found that 8 of

  19. Safety, dose optimisation and security: the quadrature of the circle

    Energy Technology Data Exchange (ETDEWEB)

    Hardeman, Frank; Vermeersch, Fernand [Belgian Nuclear Research Centre (SCK.CEN), Boeretang 200, BE-2400 Mol (Belgium)

    2010-07-01

    The growing concern for potential terrorist acts has lead to a number of new ideas about storing radiological and nuclear materials that are not always compatible with existing practices or infrastructures. This is valid in routine circumstances, but especially poses problems in case of accidents. As such, the management of nuclear safety, radiological protection and security within an evolving world such as a nuclear research centre sometimes looks like implementing the quadrature of the circle. International guidance exists, but is not always easily converted into an adequate policy comprehensible to all levels in a plant, from management to the work floor. Some examples. 1. infrastructure related problems: from a security point of view, fuels are better stored in the heart of a protected zone, while in case of criticality, fire... a more peripheral location is appropriate. 2. Safety related problems: Protection infrastructure may lead to difficulties of evacuation in case of emergencies; access limitations may be a burden in the management of safety interventions, maintenance... 3. Administrative contradictions: inventories of fuel storages and high active sealed sources are a cornerstone of inspections and verifications; yet, this information is a treasure for terrorists aiming at actions to obtain special materials. 4. Dose management: measures taken to secure sources may lead to a dose increase (e.g. labelling of old sources). However, the main difficulty is related to the 'cultural' aspect. There are synergies between safety culture, 'ALARA' culture and security culture. An individual aspect of desirable behaviour (e.g. questioning attitude), complemented with an organisational dimension (e.g. training, raising awareness) are obviously common. The objective is also in line: to avoid reduction of well-being of people, to protect the environment, to prevent damage to facilities. The main difficulties arise however because of the fundamental

  20. Experimental study of hemodynamics in the Circle of Willis.

    Science.gov (United States)

    Zhu, Guangyu; Yuan, Qi; Yang, Jian; Yeo, Joon

    2015-01-01

    The Circle of Willis (CoW) is an important collateral pathway of the cerebral blood flow. An experimental study of the cerebral blood flow (CBF) distribution in different anatomical variations may help to a better understanding of the collateral mechanism of the CoW. An in-vitro test rig was developed to simulate the physiological cerebral blood flow in the CoW. Ten anatomical variations were considered in this study, include a set of different degrees of stenosis in L-ICA and L-ICA occlusion coexist with common anatomical variations. Volume flow rates of efferent arteries and pressure signals at the end of communicating arteries of each case were recorded. Physiological pressure waveforms were applied as inlet boundary condition. In the development of L-ICA stenosis, the total CBF decreases with the increase of stenosis degree. The blood supply of ipsilateral middle cerebral artery (MCA) was affected most by the stenosis of L-ICA. Anterior communicating artery (ACoA) and ipsilateral posterior communicating artery (PCoA) function as important collateral pathways of cerebral collateral circulation when unilateral stenosis occurred. The blood supply of anterior cerebral circulation was compensated by the posterior cerebral circulation through ipsilateral PCoA when L-ICA stenosis degree is greater than 40% and the affected side was compensated immediately by the unaffected side through ACoA. Blood flow of the anterior circulation and the total CBF reached the minimum among all cases studied when L-ICA occlusion coexist with the absence of PCoA. The results demonstrated the flow distribution patterns of the CoW under anatomical variations and clarified the collateral mechanism of the CoW. The flow ACoA is the most sensitive indexes to the morphology change of ipsilateral ICA. The relative independence of the circulation in anterior and posterior sections of the CoW is not broken and the function of ipsilateral PCoA is not activated until a severe stenosis of unilateral

  1. Safety, dose optimisation and security: the quadrature of the circle

    International Nuclear Information System (INIS)

    Hardeman, Frank; Vermeersch, Fernand

    2010-01-01

    The growing concern for potential terrorist acts has lead to a number of new ideas about storing radiological and nuclear materials that are not always compatible with existing practices or infrastructures. This is valid in routine circumstances, but especially poses problems in case of accidents. As such, the management of nuclear safety, radiological protection and security within an evolving world such as a nuclear research centre sometimes looks like implementing the quadrature of the circle. International guidance exists, but is not always easily converted into an adequate policy comprehensible to all levels in a plant, from management to the work floor. Some examples. 1. infrastructure related problems: from a security point of view, fuels are better stored in the heart of a protected zone, while in case of criticality, fire... a more peripheral location is appropriate. 2. Safety related problems: Protection infrastructure may lead to difficulties of evacuation in case of emergencies; access limitations may be a burden in the management of safety interventions, maintenance... 3. Administrative contradictions: inventories of fuel storages and high active sealed sources are a cornerstone of inspections and verifications; yet, this information is a treasure for terrorists aiming at actions to obtain special materials. 4. Dose management: measures taken to secure sources may lead to a dose increase (e.g. labelling of old sources). However, the main difficulty is related to the 'cultural' aspect. There are synergies between safety culture, 'ALARA' culture and security culture. An individual aspect of desirable behaviour (e.g. questioning attitude), complemented with an organisational dimension (e.g. training, raising awareness) are obviously common. The objective is also in line: to avoid reduction of well-being of people, to protect the environment, to prevent damage to facilities. The main difficulties arise however because of the fundamental differences being

  2. Anatomical variations of the circle of Willis and cerebrovascular accidents in transitional Albania

    Directory of Open Access Journals (Sweden)

    Edlira Harizi (Shemsi

    2015-12-01

    Full Text Available Aim: The purpose of this study was twofold: i in a case-control design, to determine the relationship between anatomical variations of the circle of Willis and cerebrovascular accidents; ii to assess the association between anatomical variations of the circle of Willis and aneurisms among patients with subarachnoid hemorrhage. Methods: A case-control study was conducted in Albania in 2013-2014, including 100 patients with subarachnoid hemorrhage and 100 controls (individuals without cerebrovascular accidents. Patients with subarachnoid hemorrhage underwent a CT angiography procedure, whereas individuals in the control group underwent a magnetic resonance angiography procedure. Binary logistic regression was used to assess the association between cerebrovascular accidents and the anatomical variations of the circle of Willis. Conversely, Fisher’s exact test was used to compare the prevalence of aneurisms between subarachnoid hemorrhage patients with and without anatomical variations of the circle of Willis. Results: Among patients, there were 22 (22% cases with anatomical variations of the circle of Willis compared with 10 (10% individuals in the control group (P=0.033. There was no evidence of a statistically significant difference in the types of the anatomical variations of the circle of Willis between patients and controls (P=0.402. In age- and-sex adjusted logistic regression models, there was evidence of a significant positive association between cerebrovascular accidents and the anatomical variations of the circle of Willis (OR=1.87, 95%CI=1.03-4.68, P=0.048. Within the patients’ group, of the 52 cases with aneurisms, there were 22 (42.3% individuals with anatomical variations of the circle of Willis compared with no individuals with anatomical variations among the 48 patients without aneurisms (P<0.001. Conclusion: This study provides useful evidence on the association between anatomical variations of the circle of Willis and

  3. SplicingTypesAnno: annotating and quantifying alternative splicing events for RNA-Seq data.

    Science.gov (United States)

    Sun, Xiaoyong; Zuo, Fenghua; Ru, Yuanbin; Guo, Jiqiang; Yan, Xiaoyan; Sablok, Gaurav

    2015-04-01

    Alternative splicing plays a key role in the regulation of the central dogma. Four major types of alternative splicing have been classified as intron retention, exon skipping, alternative 5 splice sites or alternative donor sites, and alternative 3 splice sites or alternative acceptor sites. A few algorithms have been developed to detect splice junctions from RNA-Seq reads. However, there are few tools targeting at the major alternative splicing types at the exon/intron level. This type of analysis may reveal subtle, yet important events of alternative splicing, and thus help gain deeper understanding of the mechanism of alternative splicing. This paper describes a user-friendly R package, extracting, annotating and analyzing alternative splicing types for sequence alignment files from RNA-Seq. SplicingTypesAnno can: (1) provide annotation for major alternative splicing at exon/intron level. By comparing the annotation from GTF/GFF file, it identifies the novel alternative splicing sites; (2) offer a convenient two-level analysis: genome-scale annotation for users with high performance computing environment, and gene-scale annotation for users with personal computers; (3) generate a user-friendly web report and additional BED files for IGV visualization. SplicingTypesAnno is a user-friendly R package for extracting, annotating and analyzing alternative splicing types at exon/intron level for sequence alignment files from RNA-Seq. It is publically available at https://sourceforge.net/projects/splicingtypes/files/ or http://genome.sdau.edu.cn/research/software/SplicingTypesAnno.html. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  4. An Approach to Detect and Study DNA Double-Strand Break Repair by Transcript RNA Using a Spliced-Antisense RNA Template.

    Science.gov (United States)

    Keskin, Havva; Storici, Francesca

    2018-01-01

    A double-strand break (DSB) is one of the most dangerous DNA lesion, and its repair is crucial for genome stability. Homologous recombination is considered the safest way to repair a DNA DSB and requires an identical or nearly identical DNA template, such as a sister chromatid or a homologous chromosome for accurate repair. Can transcript RNA serve as donor template for DSB repair? Here, we describe an approach that we developed to detect and study DNA repair by transcript RNA. Key features of the method are: (i) use of antisense (noncoding) RNA as template for DSB repair by RNA, (ii) use of intron splicing to distinguish the sequence of the RNA template from that of the DNA that generates the RNA template, and (iii) use of a trans and cis system to study how RNA repairs a DSB in homologous but distant DNA or in its own DNA, respectively. This chapter provides details on how to use a spliced-antisense RNA template to detect and study DSB repair by RNA in trans or cis in yeast cells. Our approach for detection of DSB repair by RNA in cells can be applied to cell types other than yeast, such as bacteria, mammalian cells, or other eukaryotic cells. © 2018 Elsevier Inc. All rights reserved.

  5. The RNA-binding protein HOS5 and serine/arginine-rich proteins RS40 and RS41 participate in miRNA biogenesis in Arabidopsis

    KAUST Repository

    Chen, Tao

    2015-07-30

    MicroRNAs are a class of small regulatory RNAs that are generated from primary miRNA (pri-miRNA) transcripts with a stem-loop structure. Accuracy of the processing of pri-miRNA into mature miRNA in plants can be enhanced by SERRATE (SE) and HYPONASTIC LEAVES 1 (HYL1). HYL1 activity is regulated by the FIERY2 (FRY2)/RNA polymerase II C-terminal domain phosphatase-like 1 (CPL1). Here, we discover that HIGH OSMOTIC STRESS GENE EXPRESSION 5 (HOS5) and two serine/arginine-rich splicing factors RS40 and RS41, previously shown to be involved in pre-mRNA splicing, affect the biogenesis of a subset of miRNA. These proteins are required for correct miRNA strand selection and the maintenance of miRNA levels. FRY2 dephosphorylates HOS5 whose phosphorylation status affects its subnuclear localization. HOS5 and the RS proteins bind both intronless and intron-containing pri-miRNAs. Importantly, all of these splicing-related factors directly interact with both HYL1 and SE in nuclear splicing speckles. Our results indicate that these splicing factors are directly involved in the biogenesis of a group of miRNA.

  6. Pre-mRNA splicing repression triggers abiotic stress signaling in plants

    KAUST Repository

    Ling, Yu

    2016-09-24

    Alternative splicing (AS) of precursor RNAs enhances transcriptome plasticity and proteome diversity in response to diverse growth and stress cues. Recent work has shown that AS is pervasive across plant species, with more than 60% of intron-containing genes producing different isoforms. Mammalian cell-based assays have discovered various inhibitors of AS. Here, we show that the macrolide pladienolide B (PB) inhibits constitutive splicing and AS in plants. Also, our RNA sequencing (RNA-seq) data revealed that PB mimics abiotic stress signals including salt, drought and abscisic acid (ABA). PB activates the abiotic stress- and ABA-responsive reporters RD29A

  7. Pre-mRNA splicing repression triggers abiotic stress signaling in plants

    KAUST Repository

    Ling, Yu; Alshareef, Sahar; Butt, Haroon; Lozano-Juste, Jorge; Li, Lixin; Galal, Aya A.; Moustafa, Ahmed; Momin, Afaque Ahmad Imtiyaz; Tashkandi, Manal; Richardson, Dale N.; Fujii, Hiroaki; Arold, Stefan T.; Rodriguez, Pedro L.; Duque, Paula; Mahfouz, Magdy M.

    2016-01-01

    Alternative splicing (AS) of precursor RNAs enhances transcriptome plasticity and proteome diversity in response to diverse growth and stress cues. Recent work has shown that AS is pervasive across plant species, with more than 60% of intron-containing genes producing different isoforms. Mammalian cell-based assays have discovered various inhibitors of AS. Here, we show that the macrolide pladienolide B (PB) inhibits constitutive splicing and AS in plants. Also, our RNA sequencing (RNA-seq) data revealed that PB mimics abiotic stress signals including salt, drought and abscisic acid (ABA). PB activates the abiotic stress- and ABA-responsive reporters RD29A

  8. PPARA intron polymorphism associated with power performance in 30-s anaerobic Wingate Test.

    Directory of Open Access Journals (Sweden)

    Miroslav Petr

    Full Text Available To date, polymorphisms in several genes have been associated with a strength/power performance including alpha 3 actinin, ciliary neurotrophic factor, vitamin D receptor, or angiotensin I converting enzyme, underlining the importance of genetic component of the multifactorial strength/power-related phenotypes. The single nucleotide variation in peroxisome proliferator-activated receptor alpha gene (PPARA intron 7 G/C (rs4253778; g.46630634G>C has been repeatedly found to play a significant role in response to different types of physical activity. We investigated the effect of PPARA intron 7 G/C polymorphism specifically on anaerobic power output in a group of 77 elite male Czech ice hockey players (18-36 y. We determined the relative peak power per body weight (Pmax.kg(-1 and relative peak power per fat free mass (W.kg(-1FFM during the 30-second Wingate Test (WT30 on bicycle ergometer (Monark 894E Peak bike, MONARK, Sweden. All WT30s were performed during the hockey season. Overall genotype frequencies were 50.6% GG homozygotes, 40.3% CG heterozygotes, and 9.1% CC homozygotes. We found statistically significant differences in Pmax.kg(-1 and marginally significant differences in Pmax.kg(-1FFM values in WT30 between carriers and non-carriers for C allele (14.6 ± 0.2 vs. 13.9 ± 0.3 W.kg(-1 and 15.8 ± 0.2 vs. 15.2 ± 0.3 W.kg(-1FFM, P = 0.036 and 0.12, respectively. Furthermore, Pmax.kg(-1FFM strongly positively correlated with the body weight only in individuals with GG genotypes (R = 0.55; p<0.001. Our results indicate that PPARA 7C carriers exhibited higher speed strength measures in WT30. We hypothesize that C allele carriers within the cohort of trained individuals may possess a metabolic advantage towards anaerobic metabolism.

  9. An intronic LINE-1 insertion in MERTK is strongly associated with retinopathy in Swedish Vallhund dogs.

    Directory of Open Access Journals (Sweden)

    Richard Everson

    Full Text Available The domestic dog segregates a significant number of inherited progressive retinal diseases, several of which mirror human retinal diseases and which are collectively termed progressive retinal atrophy (PRA. In 2014, a novel form of PRA was reported in the Swedish Vallhund breed, and the disease was mapped to canine chromosome 17. The causal mutation was not identified, but expression analyses of the retinas of affected Vallhunds demonstrated a 6-fold increased expression of the MERTK gene compared to unaffected dogs. Using 24 retinopathy cases and 97 controls with no clinical signs of retinopathy, we replicated the chromosome 17 association in Swedish Vallhunds from the UK and aimed to elucidate the causal variant underlying this association using whole genome sequencing (WGS of an affected dog. This revealed a 6-8 kb insertion in intron 1 of MERTK that was not present in WGS of 49 dogs of other breeds. Sequencing and BLASTN analysis of the inserted segment was consistent with the insertion comprising a full-length intact LINE-1 retroelement. Testing of the LINE-1 insertion for association with retinopathy in the UK set of 24 cases and 97 controls revealed a strong statistical association (P-value 6.0 x 10-11 that was subsequently replicated in the original Finnish study set (49 cases and 89 controls (P-value 4.3 x 10-19. In a pooled analysis of both studies (73 cases and 186 controls, the LINE-1 insertion was associated with a ~20-fold increased risk of retinopathy (odds ratio 23.41, 95% confidence intervals 10.99-49.86, P-value 1.3 x 10-27. Our study adds further support for regulatory disruption of MERTK in Swedish Vallhund retinopathy; however, further work is required to establish a functional overexpression model. Future work to characterise the mechanism by which this intronic mutation disrupts gene regulation will further improve the understanding of MERTK biology and its role in retinal function.

  10. Study Circles as a Method of Informing the Adult Population on Radioactivity

    International Nuclear Information System (INIS)

    Kralj, M.

    2002-01-01

    Public acceptance of the radioactive waste disposal facilities is difficult to achieve. Analysis of the reasons that underlie public rejection of radioactive waste disposal facilities shows that people are not adequately informed about the proposal. They also have a lot of prejudices due to the lack of knowledge and understanding about basic facts on radioactivity and environmental processes. ARAO has proposed that the topic of radioactivity and radioactive waste be included in the program of study circles in order to promote knowledge and understanding of these issues among the adult population in several Slovenian communities. Study circles are self-organized adult learning groups in the local community environment. Two study circles were initially proposed: one in Krsko, the community with a nuclear facility, and one in Radovljica, a community without a nuclear facility. Because of troubles with the unexpected politicization of nuclear issues, the study circle in Krsko was postponed to the later term, so that only the study circle in the community without the nuclear installation was active. The members were found by personal invitations. They worked on different issues dealing with radiation, mainly with the application of radiation and radioactive substances in medicine. Through the study circle activities the interest in radiation issues increased. The members reported that they disseminated their interest and acquired knowledge to their family members and friends. Our experience shows that self-learning in small groups, promoting discussions and the confrontation of different opinions, results in an increase in objective knowledge. Therefore, study circles can provide a good basis for confidence building in the nuclear technology.(author)

  11. Molecular evolution and diversification of snake toxin genes, revealed by analysis of intron sequences.

    Science.gov (United States)

    Fujimi, T J; Nakajyo, T; Nishimura, E; Ogura, E; Tsuchiya, T; Tamiya, T

    2003-08-14

    The genes encoding erabutoxin (short chain neurotoxin) isoforms (Ea, Eb, and Ec), LsIII (long chain neurotoxin) and a novel long chain neurotoxin pseudogene were cloned from a Laticauda semifasciata genomic library. Short and long chain neurotoxin genes were also cloned from the genome of Laticauda laticaudata, a closely related species of L. semifasciata, by PCR. A putative matrix attached region (MAR) sequence was found in the intron I of the LsIII gene. Comparative analysis of 11 structurally relevant snake toxin genes (three-finger-structure toxins) revealed the molecular evolution of these toxins. Three-finger-structure toxin genes diverged from a common ancestor through two types of evolutionary pathways (long and short types), early in the course of evolution. At a later stage of evolution in each gene, the accumulation of mutations in the exons, especially exon II, by accelerated evolution may have caused the increased diversification in their functions. It was also revealed that the putative MAR sequence found in the LsIII gene was integrated into the gene after the species-level divergence.

  12. A STAT6 Intronic Single-Nucleotide Polymorphism is Associated with Clinical Malaria in Ghanaian Children

    Directory of Open Access Journals (Sweden)

    Daniel Amoako-Sakyi

    2016-01-01

    Full Text Available Malaria pathogenesis may be influenced by IgE responses and cytokine cross-regulation. Several mutations in the IL-4/STAT6 signaling pathway can alter cytokine cross-regulation and IgE responses during a Plasmodium falciparum malarial infection. This study investigated the relationship between a STAT6 intronic single-nucleotide polymorphism (rs3024974, total IgE, cytokines, and malaria severity in 238 Ghanaian children aged between 0.5 and 13 years. Total IgE and cytokine levels were measured by ELISA, while genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (RFLP. Compared with healthy controls, heterozygosity protected against clinical malaria: uncomplicated malaria (odds ratios [OR] = 0.13, P < 0.001, severe malarial anemia (OR = 0.18, P < 0.001, and cerebral malaria (OR = 0.39, P = 0.022. Levels of total IgE significantly differed among malaria phenotypes (P = 0.044 and rs3024974 genotypes (P = 0.037. Neither cytokine levels nor IL-6/IL-10 ratios were associated with malaria phenotypes or rs3024974 genotypes. This study suggests a role for rs3024974 in malaria pathogenesis and offers further insights into an IL-4/STAT6 pathway mutation in malaria pathogenesis.

  13. Homogeneous and label-free detection of microRNAs using bifunctional strand displacement amplification-mediated hyperbranched rolling circle amplification.

    Science.gov (United States)

    Zhang, Li-rong; Zhu, Guichi; Zhang, Chun-yang

    2014-07-01

    MicroRNAs (miRNAs) are an emerging class of biomarkers and therapeutic targets for various diseases including cancers. Here, we develop a homogeneous and label-free method for sensitive detection of let-7a miRNA based on bifunctional strand displacement amplification (SDA)-mediated hyperbranched rolling circle amplification (HRCA). The binding of target miRNA with the linear template initiates the bifunctional SDA reaction, generating two different kinds of triggers which can hybridize with the linear template to initiate new rounds of SDA reaction for the production of more and more triggers. In the meantime, the released two different kinds of triggers can function as the first and the second primers, respectively, to initiate the HRCA reaction whose products can be simply monitored by a standard fluorometer with SYBR Green I as the fluorescent indicator. The proposed method exhibits high sensitivity with a detection limit of as low as 1.8 × 10(-13) M and a large dynamic range of 5 orders of magnitude from 0.1 pM to 10 nM, and it can even discriminate the single-base difference among the miRNA family members. Moreover, this method can be used to analyze the total RNA samples from the human lung tissues and might be further applied for sensitive detection of various proteins, small molecules, and metal ions in combination with specific aptamers.

  14. Accurate episomal HIV 2-LTR circles quantification using optimized DNA isolation and droplet digital PCR.

    Science.gov (United States)

    Malatinkova, Eva; Kiselinova, Maja; Bonczkowski, Pawel; Trypsteen, Wim; Messiaen, Peter; Vermeire, Jolien; Verhasselt, Bruno; Vervisch, Karen; Vandekerckhove, Linos; De Spiegelaere, Ward

    2014-01-01

    In HIV-infected patients on combination antiretroviral therapy (cART), the detection of episomal HIV 2-LTR circles is a potential marker for ongoing viral replication. Quantification of 2-LTR circles is based on quantitative PCR or more recently on digital PCR assessment, but is hampered due to its low abundance. Sample pre-PCR processing is a critical step for 2-LTR circles quantification, which has not yet been sufficiently evaluated in patient derived samples. We compared two sample processing procedures to more accurately quantify 2-LTR circles using droplet digital PCR (ddPCR). Episomal HIV 2-LTR circles were either isolated by genomic DNA isolation or by a modified plasmid DNA isolation, to separate the small episomal circular DNA from chromosomal DNA. This was performed in a dilution series of HIV-infected cells and HIV-1 infected patient derived samples (n=59). Samples for the plasmid DNA isolation method were spiked with an internal control plasmid. Genomic DNA isolation enables robust 2-LTR circles quantification. However, in the lower ranges of detection, PCR inhibition caused by high genomic DNA load substantially limits the amount of sample input and this impacts sensitivity and accuracy. Moreover, total genomic DNA isolation resulted in a lower recovery of 2-LTR templates per isolate, further reducing its sensitivity. The modified plasmid DNA isolation with a spiked reference for normalization was more accurate in these low ranges compared to genomic DNA isolation. A linear correlation of both methods was observed in the dilution series (R2=0.974) and in the patient derived samples with 2-LTR numbers above 10 copies per million peripheral blood mononuclear cells (PBMCs), (R2=0.671). Furthermore, Bland-Altman analysis revealed an average agreement between the methods within the 27 samples in which 2-LTR circles were detectable with both methods (bias: 0.3875±1.2657 log10). 2-LTR circles quantification in HIV-infected patients proved to be more

  15. Model for an RNA tertiary interaction from the structure of an intermolecular complex between a GAAA tetraloop and an RNA helix.

    Science.gov (United States)

    Pley, H W; Flaherty, K M; McKay, D B

    1994-11-03

    In large structured RNAs, RNA hairpins in which the strands of the duplex stem are connected by a tetraloop of the consensus sequence 5'-GNRA (where N is any nucleotide, and R is either G or A) are unusually frequent. In group I introns there is a covariation in sequence between nucleotides in the third and fourth positions of the loop with specific distant base pairs in putative RNA duplex stems: GNAA loops correlate with successive 5'-C-C.G-C base pairs in stems, whereas GNGA loops correlate with 5'-C-U.G-A. This has led to the suggestion that GNRA tetraloops may be involved in specific long-range tertiary interactions, with each A in position 3 or 4 of the loop interacting with a C-G base pair in the duplex, and G in position 3 interacting with a U-A base pair. This idea is supported experimentally for the GAAA loop of the P5b extension of the group I intron of Tetrahymena thermophila and the L9 GUGA terminal loop of the td intron of bacteriophage T4 (ref. 4). NMR has revealed the overall structure of the tetraloop for 12-nucleotide hairpins with GCAA and GAAA loops and models have been proposed for the interaction of GNRA tetraloops with base pairs in the minor groove of A-form RNA. Here we describe the crystal structure of an intermolecular complex between a GAAA tetraloop and an RNA helix. The interactions we observe correlate with the specificity of GNRA tetraloops inferred from phylogenetic studies, suggesting that this complex is a legitimate model for intramolecular tertiary interactions mediated by GNRA tetraloops in large structured RNAs.

  16. Promoting retention, enabling success: Discovering the potential of student support circles.

    Science.gov (United States)

    Bass, Janice; Walters, Caroline; Toohill, Jocelyn; Sidebotham, Mary

    2016-09-01

    Retention of students is critical to education programs and future workforce. A mixed methods study evaluated student engagement within a Bachelor of Midwifery program and connection with career choice through participation in student support circles. Centred on the Five Senses of Success Framework (sense of capability, purpose, identity, resourcefulness and connectedness) and including four stages of engagement (creating space, preparing self, sharing stories, focused conversations), the circles support and develop student and professional identity. Of 80 students 43 (54%) provided responses to a two item survey assessed against a five point Likert scale to determine utility. Using a nominal group technique, student's voices gave rich insight into the personal and professional growth that participation in the student support circles provided. Evaluated as helpful to first year students in orientating to university study and early socialisation into the profession, the circles appear to influence the development of a strong sense of professional identity and personal midwifery philosophy based on the relational nature of the midwife being with woman rather than doing midwifery. This suggests that student support circles positively influence perceptions and expectations, contributing to a shared sense of purpose and discipline connection, for enhancing student retention and future workforce participation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Automatic Detection and Quantification of WBCs and RBCs Using Iterative Structured Circle Detection Algorithm

    Directory of Open Access Journals (Sweden)

    Yazan M. Alomari

    2014-01-01

    Full Text Available Segmentation and counting of blood cells are considered as an important step that helps to extract features to diagnose some specific diseases like malaria or leukemia. The manual counting of white blood cells (WBCs and red blood cells (RBCs in microscopic images is an extremely tedious, time consuming, and inaccurate process. Automatic analysis will allow hematologist experts to perform faster and more accurately. The proposed method uses an iterative structured circle detection algorithm for the segmentation and counting of WBCs and RBCs. The separation of WBCs from RBCs was achieved by thresholding, and specific preprocessing steps were developed for each cell type. Counting was performed for each image using the proposed method based on modified circle detection, which automatically counted the cells. Several modifications were made to the basic (RCD algorithm to solve the initialization problem, detecting irregular circles (cells, selecting the optimal circle from the candidate circles, determining the number of iterations in a fully dynamic way to enhance algorithm detection, and running time. The validation method used to determine segmentation accuracy was a quantitative analysis that included Precision, Recall, and F-measurement tests. The average accuracy of the proposed method was 95.3% for RBCs and 98.4% for WBCs.

  18. Nuclear introns outperform mitochondrial DNA in inter-specific phylogenetic reconstruction: Lessons from horseshoe bats (Rhinolophidae: Chiroptera).

    Science.gov (United States)

    Dool, Serena E; Puechmaille, Sebastien J; Foley, Nicole M; Allegrini, Benjamin; Bastian, Anna; Mutumi, Gregory L; Maluleke, Tinyiko G; Odendaal, Lizelle J; Teeling, Emma C; Jacobs, David S

    2016-04-01

    Despite many studies illustrating the perils of utilising mitochondrial DNA in phylogenetic studies, it remains one of the most widely used genetic markers for this purpose. Over the last decade, nuclear introns have been proposed as alternative markers for phylogenetic reconstruction. However, the resolution capabilities of mtDNA and nuclear introns have rarely been quantified and compared. In the current study we generated a novel ∼5kb dataset comprising six nuclear introns and a mtDNA fragment. We assessed the relative resolution capabilities of the six intronic fragments with respect to each other, when used in various combinations together, and when compared to the traditionally used mtDNA. We focused on a major clade in the horseshoe bat family (Afro-Palaearctic clade; Rhinolophidae) as our case study. This old, widely distributed and speciose group contains a high level of conserved morphology. This morphological stasis renders the reconstruction of the phylogeny of this group with traditional morphological characters complex. We sampled multiple individuals per species to represent their geographic distributions as best as possible (122 individuals, 24 species, 68 localities). We reconstructed the species phylogeny using several complementary methods (partitioned Maximum Likelihood and Bayesian and Bayesian multispecies-coalescent) and made inferences based on consensus across these methods. We computed pairwise comparisons based on Robinson-Foulds tree distance metric between all Bayesian topologies generated (27,000) for every gene(s) and visualised the tree space using multidimensional scaling (MDS) plots. Using our supported species phylogeny we estimated the ancestral state of key traits of interest within this group, e.g. echolocation peak frequency which has been implicated in speciation. Our results revealed many potential cryptic species within this group, even in taxa where this was not suspected a priori and also found evidence for mt

  19. Site-specific, insertional inactivation of incA in Chlamydia trachomatis using a group II intron.

    Science.gov (United States)

    Johnson, Cayla M; Fisher, Derek J

    2013-01-01

    Chlamydia trachomatis is an obligate, intracellular bacterial pathogen that has until more recently remained recalcitrant to genetic manipulation. However, the field still remains hindered by the absence of tools to create selectable, targeted chromosomal mutations. Previous work with mobile group II introns demonstrated that they can be retargeted by altering DNA sequences within the intron's substrate recognition region to create site-specific gene insertions. This platform (marketed as TargeTron™, Sigma) has been successfully employed in a variety of bacteria. We subsequently modified TargeTron™ for use in C. trachomatis and as proof of principle used our system to insertionally inactivate incA, a chromosomal gene encoding a protein required for homotypic fusion of chlamydial inclusions. C. trachomatis incA::GII(bla) mutants were selected with ampicillin and plaque purified clones were then isolated for genotypic and phenotypic analysis. PCR, Southern blotting, and DNA sequencing verified proper GII(bla) insertion, while continuous passaging in the absence of selection demonstrated that the insertion was stable. As seen with naturally occurring IncA(-) mutants, light and immunofluorescence microscopy confirmed the presence of non-fusogenic inclusions in cells infected with the incA::GII(bla) mutants at a multiplicity of infection greater than one. Lack of IncA production by mutant clones was further confirmed by Western blotting. Ultimately, the ease of retargeting the intron, ability to select for mutants, and intron stability in the absence of selection makes this method a powerful addition to the growing chlamydial molecular toolbox.

  20. Functional examination of MLH1, MSH2, and MSH6 intronic mutations identified in Danish colorectal cancer patients.

    Science.gov (United States)

    Petersen, Sanne M; Dandanell, Mette; Rasmussen, Lene J; Gerdes, Anne-Marie; Krogh, Lotte N; Bernstein, Inge; Okkels, Henrik; Wikman, Friedrik; Nielsen, Finn C; Hansen, Thomas V O

    2013-10-03

    Germ-line mutations in the DNA mismatch repair genes MLH1, MSH2, and MSH6 predispose to the development of colorectal cancer (Lynch syndrome or hereditary nonpolyposis colorectal cancer). These mutations include disease-causing frame-shift, nonsense, and splicing mutations as well as large genomic rearrangements. However, a large number of mutations, including missense, silent, and intronic variants, are classified as variants of unknown clinical significance. Intronic MLH1, MSH2, or MSH6 variants were investigated using in silico prediction tools and mini-gene assay to asses the effect on splicing. We describe in silico and in vitro characterization of nine intronic MLH1, MSH2, or MSH6 mutations identified in Danish colorectal cancer patients, of which four mutations are novel. The analysis revealed aberrant splicing of five mutations (MLH1 c.588 + 5G > A, MLH1 c.677 + 3A > T, MLH1 c.1732-2A > T, MSH2 c.1276 + 1G > T, and MSH2 c.1662-2A > C), while four mutations had no effect on splicing compared to wild type (MLH1 c.117-34A > T, MLH1 c.1039-8 T > A, MSH2 c.2459-18delT, and MSH6 c.3439-16C > T). In conclusion, we classify five MLH1/MSH2 mutations as pathogenic, whereas four MLH1/MSH2/MSH6 mutations are classified as neutral. This study supports the notion that in silico prediction tools and mini-gene assays are important for the classification of intronic variants, and thereby crucial for the genetic counseling of patients and their family members.

  1. Characterization of a Canine Tetranucleotide Microsatellite Marker Located in the First Intron of the Tumor Necrosis Factor Alpha Gene

    OpenAIRE

    WATANABE, Masashi; TANAKA, Kazuaki; TAKIZAWA, Tatsuya; SEGAWA, Kazuhito; NEO, Sakurako; TSUCHIYA, Ryo; MURATA, Michiko; MURAKAMI, Masaru; HISASUE, Masaharu

    2013-01-01

    ABSTRACT A polymorphic tetranucleotide (GAAT)n microsatellite in the first intron of the canine tumor necrosis factor alpha (TNFA) gene was characterized in this study; 139 dogs were analyzed: 22 Beagles, 26 Chihuahuas, 20 Miniature Dachshunds, 24 Miniature Poodles, 22 Pembroke Welsh Corgis and 25 Shiba Inus. We detected the presence of the 4 alleles (GAAT)5, (GAAT)6, (GAAT)7 and (GAAT)8, including 9 of the 10 expected genotypes. The expected heterozygosity (He) and the polymorphic informatio...

  2. AML1/ETO trans-activates c-KIT expression through the long range interaction between promoter and intronic enhancer.

    Science.gov (United States)

    Tian, Ying; Wang, Genjie; Hu, Qingzhu; Xiao, Xichun; Chen, Shuxia

    2018-04-01

    The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT. Gene expression analyses verify that c-KIT expression is significantly high in t(8;21) AML. Further ChIP-seq analysis and motif scanning identify two regulatory regions located in the promoter and intronic enhancer region of c-KIT, respectively. Both regions are enriched by co-factors of AML1/ETO, such as AML1, CEBPe, c-Jun, and c-Fos. Further luciferase reporter assays show that AML1/ETO trans-activates c-KIT promoter activity through directly recognizing the AML1 motif and the co-existence of co-factors. The induction of c-KIT promoter activity is reinforced with the existence of intronic enhancer region. Furthermore, ChIP-3C-qPCR assays verify that AML1/ETO mediates the formation of DNA-looping between the c-KIT promoter and intronic enhancer region through the long-range interaction. Collectively, our data uncover a novel transcriptional activity mechanism of AML1/ETO and enrich our knowledge of the onco-fusion protein mediated transcription regulation. © 2017 Wiley Periodicals, Inc.

  3. Virtual Genome Walking across the 32 Gb Ambystoma mexicanum genome; assembling gene models and intronic sequence.

    Science.gov (United States)

    Evans, Teri; Johnson, Andrew D; Loose, Matthew

    2018-01-12

    Large repeat rich genomes present challenges for assembly using short read technologies. The 32 Gb axolotl genome is estimated to contain ~19 Gb of repetitive DNA making an assembly from short reads alone effectively impossible. Indeed, this model species has been sequenced to 20× coverage but the reads could not be conventionally assembled. Using an alternative strategy, we have assembled subsets of these reads into scaffolds describing over 19,000 gene models. We call this method Virtual Genome Walking as it locally assembles whole genome reads based on a reference transcriptome, identifying exons and iteratively extending them into surrounding genomic sequence. These assemblies are then linked and refined to generate gene models including upstream and downstream genomic, and intronic, sequence. Our assemblies are validated by comparison with previously published axolotl bacterial artificial chromosome (BAC) sequences. Our analyses of axolotl intron length, intron-exon structure, repeat content and synteny provide novel insights into the genic structure of this model species. This resource will enable new experimental approaches in axolotl, such as ChIP-Seq and CRISPR and aid in future whole genome sequencing efforts. The assembled sequences and annotations presented here are freely available for download from https://tinyurl.com/y8gydc6n . The software pipeline is available from https://github.com/LooseLab/iterassemble .

  4. Extracellular RNA Communication (ExRNA)

    Data.gov (United States)

    Federal Laboratory Consortium — Until recently, scientists believed RNA worked mostly inside the cell that produced it. Some types of RNA help translate genes into proteins that are necessary for...

  5. Characterization of bacteriophage KVP40 and T4 RNA ligase 2

    International Nuclear Information System (INIS)

    Yin Shenmin; Kiong Ho, C.; Miller, Eric S.; Shuman, Stewart

    2004-01-01

    Bacteriophage T4 RNA ligase 2 (Rnl2) exemplifies a subfamily of RNA strand-joining enzymes that includes the trypanosome RNA editing ligases. A homolog of T4 Rnl2 is encoded in the 244-kbp DNA genome of vibriophage KVP40. We show that the 335-amino acid KVP40 Rnl2 is a monomeric protein that catalyzes RNA end-joining through ligase-adenylate and RNA-adenylate (AppRNA) intermediates. In the absence of ATP, pre-adenylated KVP40 Rnl2 reacts with an 18-mer 5'-PO 4 single-strand RNA (pRNA) to form an 18-mer RNA circle. In the presence of ATP, Rnl2 generates predominantly AppRNA. Isolated AppRNA can be circularized by KVP40 Rnl2 in the absence of ATP. The reactivity of phage Rnl2 and the distribution of the products are affected by the length of the pRNA substrate. Whereas 18-mer and 15-mer pRNAs undergo intramolecular sealing by T4 Rnl2 to form monomer circles, a 12-mer pRNA is ligated intermolecularly to form dimers, and a 9-mer pRNA is unreactive. In the presence of ATP, the 15-mer and 12-mer pRNAs are converted to AppRNAs, but the 9-mer pRNA is not. A single 5' deoxynucleotide substitution of an 18-mer pRNA substrate has no apparent effect on the 5' adenylation or circularization reactions of T4 Rnl2. In contrast, a single deoxyribonucleoside at the 3' terminus strongly and selectively suppresses the sealing step, thereby resulting in accumulation of high levels of AppRNA in the absence of ATP. The ATP-dependent 'capping' of RNA with AMP by Rnl2 is reminiscent of the capping of eukaryotic mRNA with GMP by GTP:RNA guanylyltransferase and suggests an evolutionary connection between bacteriophage Rnl2 and eukaryotic RNA capping enzymes

  6. A SEARCH FOR CONCENTRIC CIRCLES IN THE 7 YEAR WILKINSON MICROWAVE ANISOTROPY PROBE TEMPERATURE SKY MAPS

    International Nuclear Information System (INIS)

    Wehus, I. K.; Eriksen, H. K.

    2011-01-01

    In this Letter, we search for concentric circles with low variance in cosmic microwave background sky maps. The detection of such circles would hint at new physics beyond the current cosmological concordance model, which states that the universe is isotropic and homogeneous, and filled with Gaussian fluctuations. We first describe a set of methods designed to detect such circles, based on matched filters and χ 2 statistics, and then apply these methods to the best current publicly available data, the 7 year Wilkinson Microwave Anisotropy Probe (WMAP) temperature sky maps. We compare the observations with an ensemble of 1000 Gaussian ΛCDM simulations. Based on these tests, we conclude that the WMAP sky maps are fully compatible with the Gaussian and isotropic hypothesis as measured by low-variance ring statistics.

  7. Great circle solution to polarization-based quantum communication (QC) in optical fiber

    Science.gov (United States)

    Nordholt, Jane Elizabeth; Peterson, Charles Glen; Newell, Raymond Thorson; Hughes, Richard John

    2016-03-15

    Birefringence in optical fibers is compensated by applying polarization modulation at a receiver. Polarization modulation is applied so that a transmitted optical signal has states of polarization (SOPs) that are equally spaced on the Poincare sphere. Fiber birefringence encountered in propagation between a transmitter and a receiver rotates the great circle on the Poincare sphere that represents the polarization bases used for modulation. By adjusting received polarizations, polarization components of the received optical signal can be directed to corresponding detectors for decoding, regardless of the magnitude and orientation of the fiber birefringence. A transmitter can be configured to transmit in conjugate polarization bases whose SOPs can be represented as equidistant points on a great circle so that the received SOPs are mapped to equidistant points on a great circle and routed to corresponding detectors.

  8. Circle Solutions, a philosophy and pedagogy for learning positive relationships: What promotes and inhibits sustainable outcomes?

    Directory of Open Access Journals (Sweden)

    Florence McCarthy

    2013-04-01

    Full Text Available Educators are increasingly aware that the efficacy of social and emotional learning (SEL is dependent on implementation factors, not just program content. These include the philosophy underpinning an intervention, the beliefs as well as the skills of facilitators, and the classroom/whole school context in which the intervention takes place. This article outlines the philosophy and pedagogy of Circle Solutions and presents findings from research where 18 undergraduate students supported and developed ‘Circle Time’ in 8 Greater Western Sydney primary schools for a university module on community service. The study indicates that when there is full teacher participation within the principles of the Circle philosophy, together with activeschool support that promotes relational values, the learning outcomes for positive relationship building are more sustainable.

  9. Experimental research on energy circled fraction of continuous phase plates in focal spot

    International Nuclear Information System (INIS)

    Zhang Yuanhang; Yang Chunlin; Wen Shenglin; Shi Qikai; Wang Jian

    2013-01-01

    In inertial confinement fusion (ICF) research process, the form of focal spot is extremely crucial. Especially in the indirect driven implosion, energy circled fraction is higher than 95% in focal spot. Based on the offline test platform, the focusing spot of continuous phase plates with different application error is clearly imaged on CCD. By experimental analysis, it is found that the beam rotation error, caliber error, translational error and inclination error have a high tolerance in affecting focal plane of CPP. Energy circled fraction is higher than 95%, the range is less than 0.5%. Nevertheless, the waterfront aberration seriously affects the shaping ability of the CPP. Clearly, the main factor of reducing energy circled fraction to less than 90% is waterfront aberration. (authors)

  10. RNA regulatory elements and polyadenylation in plants

    Directory of Open Access Journals (Sweden)

    Arthur G. Hunt

    2012-01-01

    Full Text Available Alternative poly(A site choice (also known as alternative polyadenylation, or APA has the potential to affect gene expression in qualitative and quantitative ways. Alternative polyadenylation may affect as many as 82% of all expressed genes in a plant. The consequences of APA include the generation of transcripts with differing 3’-UTRs (and thus differing potential regulatory potential and of transcripts with differing protein-coding potential. Genome-wide studies of possible APA suggest a linkage with pre-mRNA splicing, and indicate a coincidence of and perhaps cooperation between RNA regulatory elements that affect splicing efficiency and the recognition of novel intronic poly(A sites. These studies also raise the possibility of the existence of a novel class of polyadenylation-related cis elements that are distinct from the well-characterized plant polyadenylation signal. Many potential APA events, however, have not been associated with identifiable cis elements. The present state of the field reveals a broad scope of APA, and also numerous opportunities for research into mechanisms that govern both choice and regulation of poly(A sites in plants.

  11. Molecular study in children with hemophilia A in Colombia: analysis of Intron 1 and 22 inversion using long-distance PCR technique

    Directory of Open Access Journals (Sweden)

    María Fernanda Garcés

    2017-04-01

    Conclusions: Inversions of intron 22 and 1 were found in half of this group of patients. These results are reproducible and useful to identify the two most frequent mutations in severe hemophilia A patients.

  12. Circles-in-the-sky searches and observable cosmic topology in a flat universe

    International Nuclear Information System (INIS)

    Mota, B.; Reboucas, M. J.; Tavakol, R.

    2010-01-01

    In a universe with a detectable nontrivial spatial topology, the last scattering surface contains pairs of matching circles with the same distribution of temperature fluctuations--the so-called circles-in-the-sky. Searches for nearly antipodal circles-in-the-sky in maps of cosmic microwave background radiation have so far been unsuccessful. This negative outcome, along with recent theoretical results concerning the detectability of nearly flat compact topologies, is sufficient to exclude a detectable nontrivial topology for most observers in very nearly flat positively and negatively curved universes, whose total matter-energy density satisfies 0 tot -1| -5 . Here, we investigate the consequences of these searches for observable nontrivial topologies if the Universe turns out to be exactly flat (Ω tot =1). We demonstrate that in this case, the conclusions deduced from such searches can be radically different. We show that, although there is no characteristic topological scale in the flat manifolds, for all multiply-connected orientable flat manifolds, it is possible to directly study the action of the holonomies in order to obtain a general upper bound on the angle that characterizes the deviation from antipodicity of pairs of matching circles associated with the shortest closed geodesic. This bound is valid for all observers and all possible values of the compactification length parameters. We also show that in a flat universe, there are observers for whom the circles-in-the-sky searches already undertaken are insufficient to exclude the possibility of a detectable nontrivial spatial topology. It is remarkable how such small variations in the spatial curvature of the Universe, which are effectively indistinguishable geometrically, can have such a drastic effect on the detectability of cosmic topology. Another important outcome of our results is that they offer a framework with which to make statistical inferences from future circles-in-the-sky searches on whether

  13. Circle of willis and its variations; morphometric study in adult human cadavers

    Directory of Open Access Journals (Sweden)

    Raghavendra, Shirol VS, Daksha Dixit, Anil Kumar Reddy Y, Desai SP

    2014-04-01

    Full Text Available Background and Objectives: Circle of Willis plays a vital role in collateral circulation and redistribution of blood to all areas of the brain. Variation in circle of Willis is known to cause grave disorders like cerebrovascular disorders, subarachnoid haemorrhage, cerebral aneurysm and schizophrenia. The objectives of the present study are to study the formation and branching pattern of circle of Willis and also to study the distribution of variations. MATERIALS & Methods: The study was conducted on 50 adult brain specimens. Each brain was removed in one piece by dissection and the circle of Willis was observed for its formation, pattern and variations. Results: Among the 50 specimens studied, 28 cases (56% had a normal pattern of circle of Willis and variations were observed in the remaining 22 cases (44%. More number of variations was observed on the right side than on the left side. The most common variation observed was hypoplastic posterior communicating artery (7 cases, 31.8%. Posterior communicating artery was found to be the most variable vessel while middle cerebral artery was the least variable vessel. Interpretation and Conclusion: The results with respect to the circle of Willis and all its component arteries were consistent with the results in the available literature. The only exception was the increased incidence of absence of both the anterior and posterior communicating arteries. This finding is of clinical significance to neurologists and neurosurgeons in this geographical location of north Karnataka. A higher incidence of variations in the communicating arteries is likely to manifest as a higher incidence in disorders like migraine, schizophrenia and cerebrovascular disorders due to compromised collateral circulation and poor redistribution of blood.

  14. The Effect of Quality Circles on Nurses Job Satisfaction Working Emergency Medical Service

    Directory of Open Access Journals (Sweden)

    Reza Hossein abadi

    2012-12-01

    Full Text Available Introduction: Quality circle are considered an important approach to improving behavior, increasing motivation, and reducing stress. The aim of this study was to determining the effect of training and applying quality control circles on the nurses’ level of occupation satisfaction.Material and Methods: This research is a two-group quasi-experimental study that after selection of two EMS stations, by simple randomization method 25 nurses worked in central station of Hamden emergency medical service were chosen as the quality circle group and 16 nurses of central station of Malayer emergency medical service formed the control group. The tools was used in this research was the occupation satisfaction questionnaire that was made on Herzburg Two factor theory. After training and performing of quality circle in trial group the occupation satisfaction test was carried out on both groups to get the change taken place in their level of job satisfactions. Then statistical analysis was performed using SPSS.Results: The analysis of data showed that before and after intervention there was significant differences in scores of health (P<0.001 and motivation factors (P<0.001 and also in global scores of occupation satisfaction in quality circle group (P<0.001, but there was no significant differences before and after intervention in scores of health (P=0.069 and motivation factors (P=0.094 and also in global scores of occupation satisfaction in control group (P=0.495. After intervention, the analysis of data showed significant differences in scores motivation factors (P=0.001 and global scores of occupation satisfaction (P=0.003 whereas there was no significant differences in scores of health factors between two groups (P=0.089.Conclusion: This study confirmed the effectiveness of training and applying quality circle in improving EMS nurses job satisfaction and offered as management method for use by EMS managers.

  15. "Socratic Circles are a Luxury": Exploring the Conceptualization of a Dialogic Tool in Three Science Classrooms

    Science.gov (United States)

    Copelin, Michelle Renee

    Research has shown that dialogic instruction promotes learning in students. Secondary science has traditionally been taught from an authoritative stance, reinforced in recent years by testing policies requiring coverage. Socratic Circles are a framework for student-led dialogic discourse, which have been successfully used in English language arts and social studies classrooms. The purpose of this research was to explore the implementation process of Socratic Circles in secondary science classes where they have been perceived to be more difficult. Focusing on two physical science classes and one chemistry class, this study described the nature and characteristics of Socratic Circles, teachers' dispositions toward dialogic instruction, the nature and characteristics of student discussion, and student motivation. Socratic Circles were found to be a dialogic support that influenced classroom climate, social skills, content connections, and student participation. Teachers experienced conflict between using traditional test driven scripted teaching, and exploring innovation through dialogic instruction. Students experienced opportunities for peer interaction, participation, and deeper discussions in a framework designed to improve dialogic skills. Students in two of the classrooms showed evidence of motivation for engaging in peer-led discussion, and students in one class did not. The class that did not show evidence of motivation had not been given the same scaffolding as the other two classes. Two physical science teachers and one chemistry teacher found that Socratic Circles required more scaffolding than was indicated by their peers in other disciplines such as English and social studies. The teachers felt that student's general lack of background knowledge for any given topic in physical science or chemistry necessitated the building of a knowledge platform before work on a discussion could begin. All three of the teachers indicated that Socratic Circles were a

  16. Circular RNA (circRNA) was an important bridge in the switch from the RNA world to the DNA world.

    Science.gov (United States)

    Soslau, Gerald

    2018-06-14

    osmolarity. Circular RNA, circRNA, is proposed as a critical stable RNA molecule that served as the genetic precursor for the switch to DNA and the replication of circRNA by a rolling circle mechanism gave rise to the RNA complexity required for the genetic functions of the cell. The replicating ribocyte would have required protein synthesis as well as RNA replication and a model for non-coded and primordial coded protein synthesis is proposed. Finally, the switch from the RNA to the DNA world would have involved the synthesis of an RNA:DNA hybrid prior to the formation of dsDNA. If the hybrid was a circular molecule that ultimately yielded a circular dsDNA molecule, it could predict that the primordial DNA cell would evolve into a bacterial cell with a single circular chromosome. One would hope that continued speculation of the origin of life will spur new directions of research that may never fully answer the questions of the past but add to our ability to regulate potentially harmful biological events in the present and in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. High SINE RNA Expression Correlates with Post-Transcriptional Downregulation of BRCA1

    Directory of Open Access Journals (Sweden)

    Giovanni Bosco

    2013-04-01

    Full Text Available Short Interspersed Nuclear Elements (SINEs are non-autonomous retrotransposons that comprise a large fraction of the human genome. SINEs are demethylated in human disease, but whether SINEs become transcriptionally induced and how the resulting transcripts may affect the expression of protein coding genes is unknown. Here, we show that downregulation of the mRNA of the tumor suppressor gene BRCA1 is associated with increased transcription of SINEs and production of sense and antisense SINE small RNAs. We find that BRCA1 mRNA is post-transcriptionally down-regulated in a Dicer and Drosha dependent manner and that expression of a SINE inverted repeat with sequence identity to a BRCA1 intron is sufficient for downregulation of BRCA1 mRNA. These observations suggest that transcriptional activation of SINEs could contribute to a novel mechanism of RNA mediated post-transcriptional silencing of human genes.

  18. The quantum harmonic oscillator on a circle and a deformed quantum field theory

    International Nuclear Information System (INIS)

    Rego-Monteiro, M.A.

    2001-05-01

    We construct a deformed free quantum field theory with an standard Hilbert space based on a deformed Heisenberg algebra. This deformed algebra is a Heisenberg-type algebra describing the first levels of the quantum harmonic oscillator on a circle of large length L. The successive energy levels of this quantum harmonic oscillator on a circle of large length L are interpreted, similarly to the standard quantum one-dimensional harmonic oscillator on an infinite line, as being obtained by the creation of a quantum particle of frequency w at very high energies. (author)

  19. From the Weyl quantization of a particle on the circle to number–phase Wigner functions

    International Nuclear Information System (INIS)

    Przanowski, Maciej; Brzykcy, Przemysław; Tosiek, Jaromir

    2014-01-01

    A generalized Weyl quantization formalism for a particle on the circle is shown to supply an effective method for defining the number–phase Wigner function in quantum optics. A Wigner function for the state ϱ ^ and the kernel K for a particle on the circle is defined and its properties are analysed. Then it is shown how this Wigner function can be easily modified to give the number–phase Wigner function in quantum optics. Some examples of such number–phase Wigner functions are considered

  20. Sensitive Blu-ray detection of clustered rolling circle products for molecular Diagnostics

    DEFF Research Database (Denmark)

    Ahlford, Annika; Donolato, Marco; Antunes, Paula Soares Martins

    2014-01-01

    In this paper we present a method for low cost and rapid sensing of nucleic acids (NA) for infectious diagnostics, where isothermal rolling circle amplification (RCA) products, specifically generated by the presence of the human pathogen Pseudomonas aeruginosa (PA), are bound to magnetic nanopart......In this paper we present a method for low cost and rapid sensing of nucleic acids (NA) for infectious diagnostics, where isothermal rolling circle amplification (RCA) products, specifically generated by the presence of the human pathogen Pseudomonas aeruginosa (PA), are bound to magnetic...

  1. CircleBoard-Pro: Concrete manipulative-based learning cycle unit for learning geometry

    Science.gov (United States)

    Jamhari, Wongkia, Wararat

    2018-01-01

    Currently, a manipulative is commonly used in mathematics education as a supported tool for teaching and learning. With engaging natural interaction of a concrete manipulative and advantages of a learning cycle approach, we proposed the concrete manipulative-based learning cycle unit to promote mathematics learning. Our main objectives are to observe possibilities on the use of a concrete manipulative in learning geometry, and to assess students' understanding of a specific topic, angle properties in a circle, of secondary level students. To meet the first objective, the concrete manipulative, called CricleBoard-Pro, was designed. CircleBoard-Pro is built for easy to writing on or deleting from, accurate angle measurement, and flexible movement. Besides, learning activities and worksheets were created for helping students to learn angle properties in a circle. Twenty eighth graders on a lower secondary school in Indonesia were voluntarily involved to learn mathematics using CircleBoard-Pro with the designed learning activities and worksheets. We informally observed students' performance by focusing on criteria of using manipulative tools in learning mathematics while the learning activities were also observed in terms of whether they work and which step of activities need to be improved. The results of this part showed that CircleBoard-Pro complied the criteria of the use of the manipulative in learning mathematics. Nevertheless, parts of learning activities and worksheets need to be improved. Based on the results of the observation, CircleBoard-Pro, learning activities, and worksheets were merged together and became the CircleBoardPro embedded on 5E (Engage - Explore - Explain - Elaborate - Evaluate) learning cycle unit. Then, students understanding were assessed to reach the second objective. Six ninth graders from an Indonesian school in Thailand were recruited to participate in this study. Conceptual tests for both pre-and post-test, and semi

  2. Collective motions of globally coupled oscillators and some probability distributions on circle

    Energy Technology Data Exchange (ETDEWEB)

    Jaćimović, Vladimir [Faculty of Natural Sciences and Mathematics, University of Montenegro, Cetinjski put, bb., 81000 Podgorica (Montenegro); Crnkić, Aladin, E-mail: aladin.crnkic@hotmail.com [Faculty of Technical Engineering, University of Bihać, Ljubijankićeva, bb., 77000 Bihać, Bosnia and Herzegovina (Bosnia and Herzegovina)

    2017-06-28

    In 2010 Kato and Jones described a new family of probability distributions on circle, obtained as Möbius transformation of von Mises distribution. We present the model demonstrating that these distributions appear naturally in study of populations of coupled oscillators. We use this opportunity to point out certain relations between Directional Statistics and collective motion of coupled oscillators. - Highlights: • We specify probability distributions on circle that arise in Kuramoto model. • We study how the mean-field coupling affects the shape of distribution of phases. • We discuss potential applications in some experiments on cell cycle. • We apply Directional Statistics to study collective dynamics of coupled oscillators.

  3. From Death to Life – The Hydrological Circle of Cosmos and Copulation

    Directory of Open Access Journals (Sweden)

    Terje Oestigaard

    2008-10-01

    Full Text Available When a person dies, how is the soul transferred from the dead body to an infant in a mother's womb? In Hinduism this process in understood and explained metaphorically by the hydrological circle and the interrelatedness of fire and water. The cosmological circle of reincarnation is a life-giving process which includes the life-giving waters; the essence of life. Based on mythology and the sacred scriptures, this process is investigated.Key Words: Hindu Mythology, eroticism, funeral practice, sexualityDOI = 10.3126/dsaj.v2i0.1360Dhaulagiri Journal of Sociology and Anthropology Vol.2 pp.121-144

  4. Shielded transient self-interaction of a bunch entering a circle from a straight path

    International Nuclear Information System (INIS)

    Li, R.; Bohn, C.L.; Bisognano, J.J.

    1997-01-01

    When a short (mm-length) bunch with high (nC-regime) charge is transported through a magnetic bending system, self-interaction via coherent synchrotron radiation (CSR) and space charge may alter the bunch dynamics significantly. The authors consider a Gaussian rigid-line-charge bunch following a straight-path trajectory into a circle, with the trajectory centered between two infinite, parallel, perfectly conducting plates. Transients associated with CSR and space charge generated from source particles both on the straight path and the circle are calculated, and their net effect on the radiated power is contrasted with that of shielded steady-state CSR

  5. Vicious circles of punishment: a reading of Melanie Klein's Envy and gratitude.

    Science.gov (United States)

    Smith, Henry F

    2008-01-01

    Staged as a moral drama, Melanie Klein's Envy and Gratitude (1957) straddles two eras: one reflecting a simpler more concrete, historical method, and the other an approach of greater complexity, focused on the transferential moment. Embedded within the transference are the vicious circles of envy and punishment that are the hallmark of Klein's text. Punishment itself which is always punishment of both self and other, creates its own vicious circle, set in motion by a single act. In the sadomasochistic enactments that result, the moral force of Klein's categories fuels the countertransference. A detailed clinical hour is presented.

  6. Circle of Willis variation in a complex stroke presentation: a case report

    Directory of Open Access Journals (Sweden)

    Young Carolyn A

    2006-03-01

    Full Text Available Abstract Background The impact of circle of Willis anatomical variation upon the presentation of stroke is probably underrecognised. Case presentation A 63-year-old right-handed woman developed a left hemiparesis and right leg weakness sequentially following a road traffic accident (RTA. Despite initial concern about the possibility of cervical spinal cord injury, the final diagnosis was bilateral artery-to-artery embolic cerebral infarction with dominant right internal carotid artery. Conclusion The case illustrates the complex presentation of stroke as a pseudo-cervical cord lesion and the impact of circle of Willis anatomical variation upon the expression of large vessel cerebrovascular disease.

  7. Extreme heterogeneity of polyadenylation sites in mRNAs encoding chloroplast RNA-binding proteins in Nicotiana plumbaginifolia.

    Science.gov (United States)

    Klahre, U; Hemmings-Mieszczak, M; Filipowicz, W

    1995-06-01

    We have previously characterized nuclear cDNA clones encoding two RNA binding proteins, CP-RBP30 and CP-RBP-31, which are targeted to chloroplasts in Nicotiana plumbaginifolia. In this report we describe the analysis of the 3'-untranslated regions (3'-UTRs) in 22 CP-RBP30 and 8 CP-RBP31 clones which reveals that mRNAs encoding both proteins have a very complex polyadenylation pattern. Fourteen distinct poly(A) sites were identified among CP-RBP30 clones and four sites among the CP-RBP31 clones. The authenticity of the sites was confirmed by RNase A/T1 mapping of N. plumbaginifolia RNA. CP-RBP30 provides an extreme example of the heterogeneity known to be a feature of mRNA polyadenylation in higher plants. Using PCR we have demonstrated that CP-RBP genes in N. plumbaginifolia and N. sylvestris, in addition to the previously described introns interrupting the coding region, contain an intron located in the 3' non-coding part of the gene. In the case of the CP-RBP31, we have identified one polyadenylation event occurring in this intron.

  8. Development of ent-kaurene Oxidase-Based Conserved Intron Spanning Primers for Species Identification in the Genus Poa (Poaceae; Bluegrass)

    OpenAIRE

    Jonathan M. LaMantia; Ambika Chandra; David R. Huff

    2018-01-01

    Interspecific hybridization has been attempted to combine the heat and drought of Poa arachnifera Torr. with the turf quality characteristics of several Poa species. Confirmation of an F1 hybrid through morphological analysis of vegetative and flowering characteristics is often time consuming and ambiguous. Ent-kaurene oxidase (KO) has been sequenced in rice, barley, and wheat. In rice, each of the five copies of KO gene has unique lengths for the first intron. Conserved intron spanning prime...

  9. [Reconstruction of the phylogenetic position of larch (Larix sukaczewii Dylis) by sequencing data for the trnK intron of chloroplast DNA].

    Science.gov (United States)

    Bashalkhanov, S I; Konstantinov, Iu M; Verbitskiĭ, D S; Kobzev, V F

    2003-10-01

    To reconstruct the systematic relationships of larch Larix sukaczewii, we used the chloroplast trnK intron sequences of L. decidua, L. sukaczewii, L. sibirica, L. czekanovskii, and L. gmelinii. Analysis of phylogenetic trees constructed using the maximum parsimony and maximum likelihood methods showed a clear divergence of the trnK intron sequences between L. sukaczewii and L. sibirica. This divergence reaches intraspecific level, which supports a previously published hypothesis on the taxonomic isolation of L. sukaczewii.

  10. Molecular characterization of a novel HEXA mutation at the +3 position of intron 8 in a Tay-Sachs disease patient

    Energy Technology Data Exchange (ETDEWEB)

    Richard, M.; Triggs-Raine, B. [Univ. of Manitoba, Winnipeg (Canada); Natowicz, M. [E.K. Shriver Center, Waltham, MA (United States)

    1994-09-01

    Tay-Sachs disease is an autosomal recessive lysosomal storage disorder resulting from mutations in the HEXA gene that cause a deficiency in the activity of that enzyme {beta}-hexosaminidase A (Hex A). This deficiency leads to the build-up of G{sub M2} ganglioside, resulting in neurodegeneration and death. Biochemical analysis of a non-Jewish patient with a late-infantile form of Tay-Sachs disease revealed a substantial level of Hex A activity (38.4%) when 4-MUG was used as the substrate. However, when a substrate (4-MUGS) specific for the {alpha}-subunit of Hex A ({alpha}{beta}) was used, almost no activity was detected in the HEXA gene of the patient using SSCP analysis followed by sequencing. The first mutation, a G533A substitution in exon 5, is previously described and associated with the B1 form of Tay-Sachs disease. The second mutation is a novel a-to-g base change at the +3 position of intron 8. This was confirmed using the AIRS method, whereby a MaeIII site was created in the presence of the mutation. Normal and patient mRNA was reverse transcribed and exons 7 to 9 were PCR-amplified from the cDNA. An abnormally sized amplification product detected only in the patient cDNA was sequenced; exon 8 had been deleted and exons 7 and 9 were spliced together. A substantial level of normally-sized PCR product was also detected in the patient`s cDNA. Experiments are in progress to determine if this is produced from the allele harboring the G533A mutation. Given that previous mutations of this type have been associated with 97-100% abnormal splicing, this mutation is likely to be the cause, together with the G533A mutation, of Tay-Sachs disease in this patient.

  11. Migraine with aura is associated with an incomplete circle of willis: results of a prospective observational study.

    Directory of Open Access Journals (Sweden)

    Brett Cucchiara

    Full Text Available To compare the prevalence of an incomplete circle of Willis in patients with migraine with aura, migraine without aura, and control subjects, and correlate circle of Willis variations with alterations in cerebral perfusion.Migraine with aura, migraine without aura, and control subjects were prospectively enrolled in a 1∶1∶1 ratio. Magnetic resonance angiography was performed to examine circle of Willis anatomy and arterial spin labeled perfusion magnetic resonance imaging to measure cerebral blood flow. A standardized template rating system was used to categorize circle of Willis variants. The primary pre-specified outcome measure was the frequency of an incomplete circle of Willis. The association between circle of Willis variations and cerebral blood flow was also analyzed.170 subjects were enrolled (56 migraine with aura, 61 migraine without aura, 53 controls. An incomplete circle of Willis was significantly more common in the migraine with aura compared to control group (73% vs. 51%, p = 0.02, with a similar trend for the migraine without aura group (67% vs. 51%, p = 0.08. Using a quantitative score of the burden of circle of Willis variants, migraine with aura subjects had a higher burden of variants than controls (p = 0.02. Compared to those with a complete circle, subjects with an incomplete circle had greater asymmetry in hemispheric cerebral blood flow (p = 0.05. Specific posterior cerebral artery variants were associated with greater asymmetries of blood flow in the posterior cerebral artery territory.An incomplete circle of Willis is more common in migraine with aura subjects than controls, and is associated with alterations in cerebral blood flow.

  12. ULYSSES comes full circle, before revisiting the Sun's poles

    Science.gov (United States)

    1998-04-01

    From its unique perspective, Ulysses has provided scientists with the very first all-round map of the heliosphere, the huge bubble in space filled by the Sun's wind. The Earth swims deep inside the heliosphere, and gusts and shocks in the solar wind can harm satellites, power supplies and ommunications. They may also affect our planet's weather. A better grasp of the solar weather in the heliosphere is therefore one of the major aims of ESA's science programme. In a project of international cooperation between ESA and NASA, Ulysses was launched towards Jupiter in October 1990 by the US space shuttle Discovery. Arriving in February 1992, Ulysses stole energy from the giant planet in a slingshot manoeuvre and was propelled back towards the Sun in an elongated orbit almost at right angles to the ecliptic plane, where the Earth and other planets circle the Sun. "This month Ulysses returns to the point in space where its out-of-ecliptic journey began, but Jupiter isn't there," explains Richard Marsden, ESA's project scientist for Ulysses. "Following its own inexorable path around the Sun, Jupiter is far away on the opposite side of the Solar System. So Ulysses' course will not be changed a second time. The spacecraft is now in effect a man-made comet, forever bound into a 6-year polar orbit around the Sun." Ulysses now starts its second orbit. It will travel over the poles of the Sun in 2000-2001 just as the count of dark sunspots is expected to reach a maximum. With its operational life extended for the Ulysses Solar Maximum Mission, the spacecraft will find the heliosphere much stormier than during its first orbit. Discoveries so far Like its mythical namesake, Ulysses has already had an eventful voyage of discovery. Its unique trajectory has provided the scientific teams with a new perspective, from far out in space and especially in the previously unknown regions of the heliosphere over the Sun's poles. Passing within 9.8 degrees of the polar axis, the highly

  13. Genome-wide profiling of the PIWI-interacting RNA-mRNA regulatory networks in epithelial ovarian cancers.

    Science.gov (United States)

    Singh, Garima; Roy, Jyoti; Rout, Pratiti; Mallick, Bibekanand

    2018-01-01

    PIWI-interacting (piRNAs), ~23-36 nucleotide-long small non-coding RNAs (sncRNAs), earlier believed to be germline-specific, have now been identified in somatic cells, including cancer cells. These sncRNAs impact critical biological processes by fine-tuning gene expression at post-transcriptional and epigenetic levels. The expression of piRNAs in ovarian cancer, the most lethal gynecologic cancer is largely uncharted. In this study, we investigated the expression of PIWILs by qRT-PCR and western blotting and then identified piRNA transcriptomes in tissues of normal ovary and two most prevalent epithelial ovarian cancer subtypes, serous and endometrioid by small RNA sequencing. We detected 219, 256 and 234 piRNAs in normal ovary, endometrioid and serous ovarian cancer samples respectively. We observed piRNAs are encoded from various genomic regions, among which introns harbor the majority of them. Surprisingly, piRNAs originated from different genomic contexts showed the varied level of conservations across vertebrates. The functional analysis of predicted targets of differentially expressed piRNAs revealed these could modulate key processes and pathways involved in ovarian oncogenesis. Our study provides the first comprehensive piRNA landscape in these samples and a useful resource for further functional studies to decipher new mechanistic views of piRNA-mediated gene regulatory networks affecting ovarian oncogenesis. The RNA-seq data is submitted to GEO database (GSE83794).

  14. Binding interactions between yeast tRNA ligase and a precursor transfer ribonucleic acid containing two photoreactive uridine analogues

    International Nuclear Information System (INIS)

    Tanner, N.K.; Hanna, M.M.; Abelson, J.

    1988-01-01

    Yeast tRNA ligase, from Saccharomyces cerevisiae, is one of the protein components that is involved in the splicing reaction of intron-containing yeast precursor tRNAs. It is an unusual protein because it has three distinct catalytic activities. It functions as a polynucleotide kinase, as a cyclic phosphodiesterase, and as an RNA ligase. We have studied the binding interactions between ligase and precursor tRNAs containing two photoreactive uridine analogues, 4-thiouridine and 5-bromouridine. When irradiated with long ultraviolet light, RNA containing these analogues can form specific covalent bonds with associated proteins. In this paper, we show that 4-thiouridine triphosphate and 5-bromouridine triphosphate were readily incorporated into a precursor tRNA(Phe) that was synthesized, in vitro, with bacteriophage T7 RNA polymerase. The analogue-containing precursor tRNAs were authentic substrates for the two splicing enzymes that were tested (endonuclease and ligase), and they formed specific covalent bonds with ligase when they were irradiated with long-wavelength ultraviolet light. We have determined the position of three major cross-links and one minor cross-link on precursor tRNA(Phe) that were located within the intron and near the 3' splice site. On the basis of these data, we present a model for the in vivo splicing reaction of yeast precursor tRNAs

  15. An essential role for trimethylguanosine RNA caps in Saccharomyces cerevisiae meiosis and their requirement for splicing of SAE3 and PCH2 meiotic pre-mRNAs.

    Science.gov (United States)

    Qiu, Zhicheng R; Shuman, Stewart; Schwer, Beate

    2011-07-01

    Tgs1 is the enzyme that converts m(7)G RNA caps to the 2,2,7-trimethylguanosine (TMG) caps characteristic of spliceosomal snRNAs. Fungi grow vegetatively without TMG caps, thereby raising the question of what cellular transactions, if any, are TMG cap-dependent. Here, we report that Saccharomyces cerevisiae Tgs1 methyltransferase activity is essential for meiosis. tgs1Δ cells are specifically defective in splicing PCH2 and SAE3 meiotic pre-mRNAs. The TMG requirement for SAE3 splicing is alleviated by two intron mutations: a UAUUAAC to UACUAAC change that restores a consensus branchpoint and disruption of a stem-loop encompassing the branchpoint. The TMG requirement for PCH2 splicing is alleviated by a CACUAAC to UACUAAC change restoring a consensus branchpoint and by shortening the PCH2 5' exon. Placing the SAE3 and PCH2 introns within a HIS3 reporter confers Tgs1-dependent histidine prototrophy, signifying that the respective introns are portable determinants of TMG-dependent gene expression. Analysis of in vitro splicing in extracts of TGS1 versus tgs1Δ cells showed that SAE3 intron removal was enfeebled without TMG caps, whereas splicing of ACT1 was unaffected. Our findings illuminate a new mode of tunable splicing, a reliance on TMG caps for an essential developmental RNA transaction, and three genetically distinct meiotic splicing regulons in budding yeast.

  16. RNA sequencing of the exercise transcriptome in equine athletes.

    Directory of Open Access Journals (Sweden)

    Stefano Capomaccio

    Full Text Available The horse is an optimal model organism for studying the genomic response to exercise-induced stress, due to its natural aptitude for athletic performance and the relative homogeneity of its genetic and environmental backgrounds. Here, we applied RNA-sequencing analysis through the use of SOLiD technology in an experimental framework centered on exercise-induced stress during endurance races in equine athletes. We monitored the transcriptional landscape by comparing gene expression levels between animals at rest and after competition. Overall, we observed a shift from coding to non-coding regions, suggesting that the stress response involves the differential expression of not annotated regions. Notably, we observed significant post-race increases of reads that correspond to repeats, especially the intergenic and intronic L1 and L2 transposable elements. We also observed increased expression of the antisense strands compared to the sense strands in intronic and regulatory regions (1 kb up- and downstream of the genes, suggesting that antisense transcription could be one of the main mechanisms for transposon regulation in the horse under stress conditions. We identified a large number of transcripts corresponding to intergenic and intronic regions putatively associated with new transcriptional elements. Gene expression and pathway analysis allowed us to identify several biological processes and molecular functions that may be involved with exercise-induced stress. Ontology clustering reflected mechanisms that are already known to be stress activated (e.g., chemokine-type cytokines, Toll-like receptors, and kinases, as well as "nucleic acid binding" and "signal transduction activity" functions. There was also a general and transient decrease in the global rates of protein synthesis, which would be expected after strenuous global stress. In sum, our network analysis points toward the involvement of specific gene clusters in equine exercise

  17. "I am a different man now” Sex offenders in Circles of Support and Accountability : A prospective study

    NARCIS (Netherlands)

    Höing, M.A.; Vogelvang, B.; Bogaerts, S.

    2017-01-01

    In Circles of Support and Accountability (CoSA), a group of trained and supervised volunteers support a sex offender (core member in a circle), with the aim of supporting the core member’s transitions toward full desistance. A prospective, multi-method design was used to explore psychological and

  18. Influence of a Mathematics Teachers' Circle on Elementary Teachers' Use of Problem Solving

    Science.gov (United States)

    Garner, Mary L.; Watson, Virginia; Rogers, Beth; Head, Catherine

    2017-01-01

    Math teachers' circles are a form of professional development that is recommended by the Conference Board of the Mathematical Sciences in their publication Mathematical Education of Teachers II (2012). However, little research has been published on how effective math teachers' circles are in advancing the mathematical knowledge of teachers and…

  19. Studies of G-quadruplexes formed within self-assembled DNA mini-circles.

    Science.gov (United States)

    Klejevskaja, Beata; Pyne, Alice L B; Reynolds, Matthew; Shivalingam, Arun; Thorogate, Richard; Hoogenboom, Bart W; Ying, Liming; Vilar, Ramon

    2016-10-13

    We have developed self-assembled DNA mini-circles that contain a G-quadruplex-forming sequence from the c-Myc oncogene promoter and demonstrate by FRET that the G-quadruplex unfolding kinetics are 10-fold slower than for the simpler 24-mer G-quadruplex that is commonly used for FRET experiments.

  20. A connection between the Uncertainty Principles on the real line and on the circle

    OpenAIRE

    Andersen, Nils Byrial

    2013-01-01

    The purpose of this short note is to exhibit a new connection between the Heisenberg Uncertainty Principle on the line and the Breitenberger Uncertainty Principle on the circle, by considering the commutator of the multiplication and difference operators on Bernstein functions