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Sample records for alu repeats increase

  1. Comparative Analysis of Alu Repeats in Primate Genomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Alu repeats are SINEs (Short intersperse repetitive elements) which enjoy a successful application in genome evolution, population biology, phylogenetics and forensics. Human Alu consensus sequences were widely used as surrogates in nonhuman primate studies with an assumption that all p...

  2. Alu repeats as markers for forensic DNA analyses

    SciTech Connect

    Batzer, M.A.; Alegria-Hartman, M.; Kass, D.H.

    1994-01-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 98.9% nucleotide identity with the HS subfamily consensus sequence, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 inch and 3 inch unique flanking DNA sequences from each HS Alu that allow the locus to be assayed for the presence or absence of the Alu repeat. The dimorphic HS Alu sequences probably inserted in the human genome after the radiation of modem humans (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project. HS Alu family member insertions differ from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) in that polymorphisms due to Alu insertions arise as a result of a unique event which has occurred only one time in the human population and spread through the population from that point. Therefore, individuals that share HS Alu repeats inherited these elements from a common ancestor. Most VNTR and RFLP polymorphisms may arise multiple times in parallel within a population.

  3. Alu repeats as markers for human population genetics

    SciTech Connect

    Batzer, M.A.; Alegria-Hartman, M.; Bazan, H.

    1993-09-01

    The Human-Specific (HS) subfamily of Alu sequences is comprised of a group of 500 nearly identical members which are almost exclusively restricted to the human genome. Individual subfamily members share an average of 97.9% nucleotide identity with each other and an average of 98.9% nucleotide identity with the HS subfamily consensus sequence. HS Alu family members are thought to be derived from a single source ``master`` gene, and have an average age of 2.8 million years. We have developed a Polymerase Chain Reaction (PCR) based assay using primers complementary to the 5 in. and 3 in. unique flanking DNA sequences from each HS Alu that allows the locus to be assayed for the presence or absence of an Alu repeat. Individual HS Alu sequences were found to be either monomorphic or dimorphic for the presence or absence of each repeat. The monomorphic HS Alu family members inserted in the human genome after the human/great ape divergence (which is thought to have occurred 4--6 million years ago), but before the radiation of modem man. The dimorphic HS Alu sequences inserted in the human genome after the radiation of modem man (within the last 200,000-one million years) and represent a unique source of information for human population genetics and forensic DNA analyses. These sites can be developed into Dimorphic Alu Sequence Tagged Sites (DASTS) for the Human Genome Project as well. HS Alu family member insertion dimorphism differs from other types of polymorphism (e.g. Variable Number of Tandem Repeat [VNTR] or Restriction Fragment Length Polymorphism [RFLP]) because individuals share HS Alu family member insertions based upon identity by descent from a common ancestor as a result of a single event which occurred one time within the human population. The VNTR and RFLP polymorphisms may arise multiple times within a population and are identical by state only.

  4. Nonlinear analysis of correlations in Alu repeat sequences in DNA

    NASA Astrophysics Data System (ADS)

    Xiao, Yi; Huang, Yanzhao; Li, Mingfeng; Xu, Ruizhen; Xiao, Saifeng

    2003-12-01

    We report on a nonlinear analysis of deterministic structures in Alu repeats, one of the richest repetitive DNA sequences in the human genome. Alu repeats contain the recognition sites for the restriction endonuclease AluI, which is what gives them their name. Using the nonlinear prediction method developed in chaos theory, we find that all Alu repeats have novel deterministic structures and show strong nonlinear correlations that are absent from exon and intron sequences. Furthermore, the deterministic structures of Alus of younger subfamilies show panlike shapes. As young Alus can be seen as mutation free copies from the “master genes,” it may be suggested that the deterministic structures of the older subfamilies are results of an evolution from a “panlike” structure to a more diffuse correlation pattern due to mutation.

  5. [Conformational polymorphysm of G-rich fragments of DNA ALU-repeats. I. Potential noncanonical structures].

    PubMed

    Sekridova, A V; Varizhuk, A M; Tatarinova, O N; Severov, V V; Barinov, N A; Smirnov, I P; Lazarev, V N; Klinov, D V; Pozmogova, G E

    2016-07-01

    In this paper, we report results of systematic studies of conformational polymorphism of G-rich DNA fragments from Alu repeats. Alu retrotransposones are primate-specific short interspersed elements. Using the Alu sequence from the prooncogen bcl2 intron and the consensus AluSx sequence as representative examples, we determined characteristic Alu sites that are capable of adopting G-quadruplex (GQ) conformations (i.e., potential quadruplex sites - PQSAlu), and demonstrated by bioinformatics methods that those sites are Alu-specific in the human genome. Genomic frequencies of PQSAlu were assessed (~1/10000 b.p.). The sites were found to be characteristic of young (active) Alu families (Alu-Y). A recombinant DNA sequence bearing the Alu element from the human bcl2 gene (304 b.p.) and its PQS-mutant (Alu-PQS) were constructed. The formation of noncanonical structures in Alubcl2 dsDNA and the absence of such structures in the case of Alu-PQS were shown using DMS-footprinting and AFM microscopy. Expression vectors bearing wild-type and mutant Alu insertions in the promoter regions were obtained, and the effects of these insertions on the expression of the reporter gene in НЕК293 and HeLa cell lines were compared. Our findings on the spatial organization of Alu repeats may provide insight into the mechanisms of genomic rearrangements which underlie many oncological and neurodegenerative diseases.

  6. Whole-genome analysis of Alu repeat elements reveals complex evolutionary history.

    PubMed

    Price, Alkes L; Eskin, Eleazar; Pevzner, Pavel A

    2004-11-01

    Alu repeats are the most abundant family of repeats in the human genome, with over 1 million copies comprising 10% of the genome. They have been implicated in human genetic disease and in the enrichment of gene-rich segmental duplications in the human genome, and they form a rich fossil record of primate and human history. Alu repeat elements are believed to have arisen from the replication of a small number of source elements, whose evolution over time gives rise to the 31 Alu subfamilies currently reported in Repbase Update. We apply a novel method to identify and statistically validate 213 Alu subfamilies. We build an evolutionary tree of these subfamilies and conclude that the history of Alu evolution is more complex than previous studies had indicated.

  7. High-throughput sequence-based epigenomic analysis of Alu repeats in human cerebellum.

    PubMed

    Xie, Hehuang; Wang, Min; Bonaldo, Maria de F; Smith, Christina; Rajaram, Veena; Goldman, Stewart; Tomita, Tadanori; Soares, Marcelo B

    2009-07-01

    DNA methylation, the only known covalent modification of mammalian DNA, occurs primarily in CpG dinucleotides. 51% of CpGs in the human genome reside within repeats, and 25% within Alu elements. Despite that, no method has been reported for large-scale ascertainment of CpG methylation in repeats. Here we describe a sequencing-based strategy for parallel determination of the CpG-methylation status of thousands of Alu repeats, and a computation algorithm to design primers that enable their specific amplification from bisulfite converted genomic DNA. Using a single primer pair, we generated amplicons of high sequence complexity, and derived CpG-methylation data from 31 178 Alu elements and their 5' flanking sequences, altogether representing over 4 Mb of a human cerebellum epigenome. The analysis of the Alu methylome revealed that the methylation level of Alu elements is high in the intronic and intergenic regions, but low in the regions close to transcription start sites. Several hypomethylated Alu elements were identified and their hypomethylated status verified by pyrosequencing. Interestingly, some Alu elements exhibited a strikingly tissue-specific pattern of methylation. We anticipate the amplicons herein described to prove invaluable as epigenome representations, to monitor epigenomic alterations during normal development, in aging and in diseases such as cancer.

  8. Ruminant globin gene structures suggest an evolutionary role for Alu-type repeats.

    PubMed Central

    Schimenti, J C; Duncan, C H

    1984-01-01

    Bovine fetal and adult globin genes were cloned and subjected to DNA sequence analysis. Both of these genes contained insertions of Alu-type repetitive DNA within their introns. Comparison of cow and goat beta-type globin genes indicates that intragenic DNA insertions played a role in their evolution. These data support the theory that Alu-type repeats maintain genetic diversity by inhibiting gene conversion. PMID:6322113

  9. A second major class of Alu family repeated DNA sequences in a primate genome.

    PubMed Central

    Daniels, G R; Deininger, P L

    1983-01-01

    We have analyzed repetitive DNA sequences in a prosimian, Galago crassicaudatus, and found that there are two distinct, highly repetitive families of sequences related to the human Alu family. The Type I family is closely analogous to the human Alu Family. The Type II family of repeats, which appears to be present in higher copy number, has a right half that is almost identical to the Type I family. However, the left half of the Type II sequence shows only limited homology to the galago Type I or human Alu families. A comparison of homologous sequences in the left half indicated that they are centered in regions of the Alu family which function as RNA polymerase III promoters. We have also observed at least one example of a Type II left half that was integrated into the genome independent of the Alu family right half sequence. The Type II family appears to be of much more recent evolutionary origin than the Type I and may have arisen by the independent integration of a RNA polymerase III promoter adjacent to the right half of a Type I Alu family sequence. PMID:6647032

  10. Alu repeats as transcriptional regulatory platforms in macrophage responses to M. tuberculosis infection

    PubMed Central

    Bouttier, Manuella; Laperriere, David; Memari, Babak; Mangiapane, Joseph; Fiore, Amanda; Mitchell, Eric; Verway, Mark; Behr, Marcel A.; Sladek, Robert; Barreiro, Luis B.; Mader, Sylvie; White, John H.

    2016-01-01

    To understand the epigenetic regulation of transcriptional response of macrophages during early-stage M. tuberculosis (Mtb) infection, we performed ChIPseq analysis of H3K4 monomethylation (H3K4me1), a marker of poised or active enhancers. De novo H3K4me1 peaks in infected cells were associated with genes implicated in host defenses and apoptosis. Our analysis revealed that 40% of de novo regions contained human/primate-specific Alu transposable elements, enriched in the AluJ and S subtypes. These contained several transcription factor binding sites, including those for members of the MEF2 and ATF families, and LXR and RAR nuclear receptors, all of which have been implicated in macrophage differentiation, survival, and responses to stress and infection. Combining bioinformatics, molecular genetics, and biochemical approaches, we linked genes adjacent to H3K4me1-associated Alu repeats to macrophage metabolic responses against Mtb infection. In particular, we show that LXRα signaling, which reduced Mtb viability 18-fold by altering cholesterol metabolism and enhancing macrophage apoptosis, can be initiated at response elements present in Alu repeats. These studies decipher the mechanism of early macrophage transcriptional responses to Mtb, highlighting the role of Alu element transposition in shaping human transcription programs during innate immunity. PMID:27604870

  11. Analysis of western lowland gorilla (Gorilla gorilla gorilla) specific Alu repeats

    PubMed Central

    2013-01-01

    Background Research into great ape genomes has revealed widely divergent activity levels over time for Alu elements. However, the diversity of this mobile element family in the genome of the western lowland gorilla has previously been uncharacterized. Alu elements are primate-specific short interspersed elements that have been used as phylogenetic and population genetic markers for more than two decades. Alu elements are present at high copy number in the genomes of all primates surveyed thus far. The AluY subfamily and its derivatives have been recognized as the evolutionarily youngest Alu subfamily in the Old World primate lineage. Results Here we use a combination of computational and wet-bench laboratory methods to assess and catalog AluY subfamily activity level and composition in the western lowland gorilla genome (gorGor3.1). A total of 1,075 independent AluY insertions were identified and computationally divided into 10 subfamilies, with the largest number of gorilla-specific elements assigned to the canonical AluY subfamily. Conclusions The retrotransposition activity level appears to be significantly lower than that seen in the human and chimpanzee lineages, while higher than that seen in orangutan genomes, indicative of differential Alu amplification in the western lowland gorilla lineage as compared to other Homininae. PMID:24262036

  12. Genome-wide target site triplication of Alu elements in the human genome.

    PubMed

    Lee, Wooseok; Mun, Seyoung; Kang, Keunsoo; Hennighausen, Lothar; Han, Kyudong

    2015-05-01

    Alu elements are the most successful short interspersed elements in primate genomes and their retrotransposition is a major source of genomic expansion. Alu elements integrate into genomic regions through target-site primed reverse transcription, which generates target site duplications (TSDs). Unexpectedly, we have identified target site triplications (TSTs) at some loci, where two Alu elements in tandem share one direct repeat. Thus, the three copies of the repeat are present. We located 212 TST loci in the human genome and examined 25 putative human-specific TST loci using PCR validation. As a result, 12 human-specific TST loci were identified. These findings suggest that unequal homologous recombination between TSDs can lead to TST. Through this mechanism, the copy number of Alu elements could have increased in primate genomes without new Alu retrotransposition events. This study provides new insight into the augmentation of Alu elements in the primate genome.

  13. [Conformational polymorphysm of G-rich fragments of DNA Alu-repeats. II. the putative role of G-quadruplex structures in genomic rearrangements].

    PubMed

    Varizhuk, A M; Sekridova, A V; Tankevich, M V; Podgorsky, V S; Smirnov, I P; Pozmogova, G E

    2016-11-01

    Three evolutionary conserved sites of Alu repeats (PQS2, PQS3 and PQS4) were shown to form stable inter- and intramolecular G-quadruplexes (GQs) in vitro. Structures and topologies of these GQs were elucidated using spectral methods. Self-association of G-rich Alu fragments was studied. Dimeric GQ formation from two distal identical or different putative quadruplex sites - (PQS2)2, (PQS3)2 or PQS2-PQS3 - within one lengthy DNA strand was demonstrated by a FRET-based method. Oligomer PQS4 (folded into a parallel intramolecular GQ) was shown to form stacks of quadruplexes that are stabilized by stacking interactions of external G-tetrads (this was confirmed by DOSY NMR, AFM microscopy and differential CD spectroscopy). Comparative analysis of the properties of various GQs allowed us to put forward a hypothesis of two general mechanisms of intermolecular GQ-dependant genomic rearrangements: 1) formation of a dimeric GQs; 2) association of pre-folded intramolecular parallel GQs from different strands into GQ-stacks. Thus, the observed co-localization of G-rich motifs of Alu elements with double-strand break hotspots and rearrangement hotspots may be accounted for by the specific secondary structure of these motifs. At the same time, this is likely primarily due to high abundance of such G-rich Alu fragments in the genome.

  14. Construction and expression in vivo of an internally deleted mouse alpha-fetoprotein gene: presence of a transcribed Alu-like repeat within the first intervening sequence.

    PubMed Central

    Young, P R; Scott, R W; Hamer, D H; Tilghman, S M

    1982-01-01

    An alpha-fetoprotein (AFP) 'minigene' was constructed by joining the first two exons along with 0.9 kilobases of 5' flanking sequence of the mouse AFP gene to its last exon and 0.4 kilobases of 3' flanking sequence. This 'minigene' was tested for activity by inserting it into an SV40 vector and infecting African green monkey kidney cells. Correct initiation, termination, polyadenylation and splicing were observed. Furthermore a 220 nucleotide transcript was detected and mapped to a mouse Alu-like or B1 repeat on the opposite strand to that encoding the AFP gene in the first intervening sequence. Images PMID:6179043

  15. DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome.

    PubMed

    Aktaş, Tuğçe; Avşar Ilık, İbrahim; Maticzka, Daniel; Bhardwaj, Vivek; Pessoa Rodrigues, Cecilia; Mittler, Gerhard; Manke, Thomas; Backofen, Rolf; Akhtar, Asifa

    2017-04-06

    Transposable elements are viewed as 'selfish genetic elements', yet they contribute to gene regulation and genome evolution in diverse ways. More than half of the human genome consists of transposable elements. Alu elements belong to the short interspersed nuclear element (SINE) family of repetitive elements, and with over 1 million insertions they make up more than 10% of the human genome. Despite their abundance and the potential evolutionary advantages they confer, Alu elements can be mutagenic to the host as they can act as splice acceptors, inhibit translation of mRNAs and cause genomic instability. Alu elements are the main targets of the RNA-editing enzyme ADAR and the formation of Alu exons is suppressed by the nuclear ribonucleoprotein HNRNPC, but the broad effect of massive secondary structures formed by inverted-repeat Alu elements on RNA processing in the nucleus remains unknown. Here we show that DHX9, an abundant nuclear RNA helicase, binds specifically to inverted-repeat Alu elements that are transcribed as parts of genes. Loss of DHX9 leads to an increase in the number of circular-RNA-producing genes and amount of circular RNAs, translational repression of reporters containing inverted-repeat Alu elements, and transcriptional rewiring (the creation of mostly nonsensical novel connections between exons) of susceptible loci. Biochemical purifications of DHX9 identify the interferon-inducible isoform of ADAR (p150), but not the constitutively expressed ADAR isoform (p110), as an RNA-independent interaction partner. Co-depletion of ADAR and DHX9 augments the double-stranded RNA accumulation defects, leading to increased circular RNA production, revealing a functional link between these two enzymes. Our work uncovers an evolutionarily conserved function of DHX9. We propose that it acts as a nuclear RNA resolvase that neutralizes the immediate threat posed by transposon insertions and allows these elements to evolve as tools for the post

  16. Alu monomer revisited: recent generation of Alu monomers.

    PubMed

    Kojima, Kenji K

    2011-01-01

    Alu is a predominant short interspersed element (SINE) family in the human genome and consists of two monomer units connected by an A-rich linker. At present, dimeric Alu elements are active in humans, but Alu monomers are present as fossilized sequences. A comparative genome analysis of human and chimpanzee genomes revealed eight recent insertions of Alu monomers. One of them was a retroposed product of another Alu monomer with 3' transduction. Further analysis of 1,404 loci of the Alu monomer in the human genome revealed that some Alu monomers were recently generated by recombination between the internal and 3' A-rich tracts inside of dimeric Alu elements. The data show that Alu monomers were generated by 1) retroposition of other Alu monomers and 2) recombination between two A-rich tracts.

  17. Novel Role of 3'UTR-Embedded Alu Elements as Facilitators of Processed Pseudogene Genesis and Host Gene Capture by Viral Genomes.

    PubMed

    Farré, Domènec; Engel, Pablo; Angulo, Ana

    2016-01-01

    Since the discovery of the high abundance of Alu elements in the human genome, the interest for the functional significance of these retrotransposons has been increasing. Primate Alu and rodent Alu-like elements are retrotransposed by a mechanism driven by the LINE1 (L1) encoded proteins, the same machinery that generates the L1 repeats, the processed pseudogenes (PPs), and other retroelements. Apart from free Alu RNAs, Alus are also transcribed and retrotranscribed as part of cellular gene transcripts, generally embedded inside 3' untranslated regions (UTRs). Despite different proposed hypotheses, the functional implication of the presence of Alus inside 3'UTRs remains elusive. In this study we hypothesized that Alu elements in 3'UTRs could be involved in the genesis of PPs. By analyzing human genome data we discovered that the existence of 3'UTR-embedded Alu elements is overrepresented in genes source of PPs. In contrast, the presence of other retrotransposable elements in 3'UTRs does not show this PP linked overrepresentation. This research was extended to mouse and rat genomes and the results accordingly reveal overrepresentation of 3'UTR-embedded B1 (Alu-like) elements in PP parent genes. Interestingly, we also demonstrated that the overrepresentation of 3'UTR-embedded Alus is particularly significant in PP parent genes with low germline gene expression level. Finally, we provide data that support the hypothesis that the L1 machinery is also the system that herpesviruses, and possibly other large DNA viruses, use to capture host genes expressed in germline or somatic cells. Altogether our results suggest a novel role for Alu or Alu-like elements inside 3'UTRs as facilitators of the genesis of PPs, particularly in lowly expressed genes. Moreover, we propose that this L1-driven mechanism, aided by the presence of 3'UTR-embedded Alus, may also be exploited by DNA viruses to incorporate host genes to their viral genomes.

  18. The Contribution of Alu Elements to Mutagenic DNA Double-Strand Break Repair

    PubMed Central

    Streva, Vincent A.; DeFreece, Cecily B.; Hedges, Dale J.; Deininger, Prescott L.

    2015-01-01

    Alu elements make up the largest family of human mobile elements, numbering 1.1 million copies and comprising 11% of the human genome. As a consequence of evolution and genetic drift, Alu elements of various sequence divergence exist throughout the human genome. Alu/Alu recombination has been shown to cause approximately 0.5% of new human genetic diseases and contribute to extensive genomic structural variation. To begin understanding the molecular mechanisms leading to these rearrangements in mammalian cells, we constructed Alu/Alu recombination reporter cell lines containing Alu elements ranging in sequence divergence from 0%-30% that allow detection of both Alu/Alu recombination and large non-homologous end joining (NHEJ) deletions that range from 1.0 to 1.9 kb in size. Introduction of as little as 0.7% sequence divergence between Alu elements resulted in a significant reduction in recombination, which indicates even small degrees of sequence divergence reduce the efficiency of homology-directed DNA double-strand break (DSB) repair. Further reduction in recombination was observed in a sequence divergence-dependent manner for diverged Alu/Alu recombination constructs with up to 10% sequence divergence. With greater levels of sequence divergence (15%-30%), we observed a significant increase in DSB repair due to a shift from Alu/Alu recombination to variable-length NHEJ which removes sequence between the two Alu elements. This increase in NHEJ deletions depends on the presence of Alu sequence homeology (similar but not identical sequences). Analysis of recombination products revealed that Alu/Alu recombination junctions occur more frequently in the first 100 bp of the Alu element within our reporter assay, just as they do in genomic Alu/Alu recombination events. This is the first extensive study characterizing the influence of Alu element sequence divergence on DNA repair, which will inform predictions regarding the effect of Alu element sequence divergence on both

  19. Proposed roles for DNA methylation in Alu transcriptional repression and mutational inactivation.

    PubMed Central

    Liu, W M; Schmid, C W

    1993-01-01

    Methylation at CpG dinucleotides to produce 5 methyl cytosine (5me-C) has been proposed to regulate the transcriptional expression of human Alu repeats. Similarly, methylation has been proposed to indirectly favor the transpositional activity of young Alu repeats by transcriptionally inactivating older Alu's through the very rapid transition of 5me-C to T. Both hypotheses are examined here by RNA polymerase III (Pol III) in vitro transcription of Alu templates using HeLa cell extracts. A limiting factor represses the template activity of methylated Alu repeats. Competition by methylated prokaryotic vector DNA's relieves repression, showing that the factor is not sequence specific. This competitor has no effect on the activity of unmethylated templates showing that the repressor is highly specific toward methylated DNA. While methylation of a single pair of CpG dinucleotides in the A box of the Poll III promoter is sufficient to cause repression, methylation elsewhere within the template also causes repression. The repressor causing these effects on the Pol III directed transcription of Alu repeats is thought to be a previously reported, repressor for Pol II directed templates. Young Alu repeats are transcriptionally more active templates than a representative older Alu subfamily member. Also, younger Alu's form stable transcriptional complexes faster, potentially giving them an additional advantage. The mutation of three CpG's to CpA's within and near the A box drastically decreases both the template activity and rate of stable complex formation by a young Alu member. The sensitivity of Alu template activity to CpG transitions within the A box partially explains the selective transpositional advantage enjoyed by young Alu members. Images PMID:8464725

  20. Quantification of Unmethylated Alu (QUAlu): a tool to assess global hypomethylation in routine clinical samples

    PubMed Central

    Buj, Raquel; Mallona, Izaskun; Díez-Villanueva, Anna; Barrera, Víctor; Mauricio, Dídac; Puig-Domingo, Manel; Reverter, Jordi L.; Matias-Guiu, Xavier; Azuara, Daniel; Ramírez, Jose L.; Alonso, Sergio; Rosell, Rafael; Capellà, Gabriel; Perucho, Manuel; Robledo, Mercedes; Peinado, Miguel A.; Jordà, Mireia

    2016-01-01

    Hypomethylation of DNA is a hallmark of cancer and its analysis as tumor biomarker has been proposed, but its determination in clinical settings is hampered by lack of standardized methodologies. Here, we present QUAlu (Quantification of Unmethylated Alu), a new technique to estimate the Percentage of UnMethylated Alu (PUMA) as a surrogate for global hypomethylation. QUAlu consists in the measurement by qPCR of Alu repeats after digestion of genomic DNA with isoschizomers with differential sensitivity to DNA methylation. QUAlu performance has been evaluated for reproducibility, trueness and specificity, and validated by deep sequencing. As a proof of use, QUAlu has been applied to a broad variety of pathological examination specimens covering five cancer types. Major findings of the preliminary application of QUAlu to clinical samples include: (1) all normal tissues displayed similar PUMA; (2) tumors showed variable PUMA with the highest levels in lung and colon and the lowest in thyroid cancer; (3) stools from colon cancer patients presented higher PUMA than those from control individuals; (4) lung squamous cell carcinomas showed higher PUMA than lung adenocarcinomas, and an increasing hypomethylation trend associated with smoking habits. In conclusion, QUAlu is a simple and robust method to determine Alu hypomethylation in human biospecimens and may be easily implemented in research and clinical settings. PMID:26859682

  1. Differential alu mobilization and polymorphism among the human and chimpanzee lineages.

    PubMed

    Hedges, Dale J; Callinan, Pauline A; Cordaux, Richard; Xing, Jinchuan; Barnes, Erin; Batzer, Mark A

    2004-06-01

    Alu elements are primate-specific members of the SINE (short interspersed element) retroposon family, which comprise approximately 10% of the human genome. Here we report the first chromosomal-level comparison examining the Alu retroposition dynamics following the divergence of humans and chimpanzees. We find a twofold increase in Alu insertions in humans in comparison to the common chimpanzee (Pan troglodytes). The genomic diversity (polymorphism for presence or absence of the Alu insertion) associated with these inserts indicates that, analogous to recent nucleotide diversity studies, the level of chimpanzee Alu diversity is approximately 1.7 times higher than that of humans. Evolutionarily recent Alu subfamily structure differs markedly between the human and chimpanzee lineages, with the major human subfamilies remaining largely inactive in the chimpanzee lineage. We propose a population-based model to account for the observed fluctuation in Alu retroposition rates across primate taxa.

  2. MIEN1 is tightly regulated by SINE Alu methylation in its promoter

    PubMed Central

    Van Treuren, Timothy; Klinkebiel, David L.; Vishwanatha, Jamboor K.

    2016-01-01

    Migration and invasion enhancer 1 (MIEN1) is a novel gene involved in prostate cancer progression by enhancing prostate cancer cell migration and invasion. DNA methylation, an important epigenetic regulation, is one of the most widely altered mechanisms in prostate cancer. This phenomenon frames the basis to study the DNA methylation patterns in the promoter region of MIEN1. Bisulfite pyrosequencing demonstrates the MIEN1 promoter contains a short interspersed nuclear Alu element (SINE Alu) repeat sequence. Validation of methylation inhibition on MIEN1 was performed using nucleoside analogs and non-nucleoside inhibitors and resulted in an increase in both MIEN1 RNA and protein in normal cells. MIEN1 mRNA and protein increases upon inhibition of individual DNA methyltransferases using RNA interference technologies. Furthermore, dual luciferase reporter assays, in silico analysis, and chromatin immunoprecipitation assays identified a sequence upstream of the transcription start site that has a site for binding of the USF transcription factors. These results suggest the MIEN1 promoter has a SINE Alu region that is hypermethylated in normal cells leading to repression of the gene. In cancer, the hypomethylation of a part of this repeat, in addition to the binding of USF, results in MIEN1 expression. PMID:27589566

  3. Repeated administration of adenosine increases its cardiovascular effects in rats.

    PubMed

    Vidrio, H; García-Márquez, F; Magos, G A

    1987-01-20

    Hypotensive and negative chronotropic responses to adenosine in anesthetized rats increased after previous administration of the nucleoside. Bradycardia after adenosine in the isolated perfused rat heart was also potentiated after repeated administration at short intervals. This self-potentiation could be due to extracellular accumulation of adenosine and persistent stimulation of receptors caused by saturation or inhibition of cellular uptake of adenosine.

  4. The Chinese hamster Alu-equivalent sequence: a conserved highly repetitious, interspersed deoxyribonucleic acid sequence in mammals has a structure suggestive of a transposable element.

    PubMed Central

    Haynes, S R; Toomey, T P; Leinwand, L; Jelinek, W R

    1981-01-01

    A consensus sequence has been determined for a major interspersed deoxyribonucleic acid repeat in the genome of Chinese hamster ovary cells (CHO cells). This sequence is extensively homologous to (i) the human Alu sequence (P. L. Deininger et al., J. Mol. Biol., in press), (ii) the mouse B1 interspersed repetitious sequence (Krayev et al., Nucleic Acids Res. 8:1201-1215, 1980) (iii) an interspersed repetitious sequence from African green monkey deoxyribonucleic acid (Dhruva et al., Proc. Natl. Acad. Sci. U.S.A. 77:4514-4518, 1980) and (iv) the CHO and mouse 4.5S ribonucleic acid (this report; F. Harada and N. Kato, Nucleic Acids Res. 8:1273-1285, 1980). Because the CHO consensus sequence shows significant homology to the human Alu sequence it is termed the CHO Alu-equivalent sequence. A conserved structure surrounding CHO Alu-equivalent family members can be recognized. It is similar to that surrounding the human Alu and the mouse B1 sequences, and is represented as follows: direct repeat-CHO-Alu-A-rich sequence-direct repeat. A composite interspersed repetitious sequence has been identified. Its structure is represented as follows: direct repeat-residue 47 to 107 of CHO-Alu-non-Alu repetitious sequence-A-rich sequence-direct repeat. Because the Alu flanking sequences resemble those that flank known transposable elements, we think it likely that the Alu sequence dispersed throughout the mammalian genome by transposition. Images PMID:9279371

  5. Novel Role of 3’UTR-Embedded Alu Elements as Facilitators of Processed Pseudogene Genesis and Host Gene Capture by Viral Genomes

    PubMed Central

    Engel, Pablo; Angulo, Ana

    2016-01-01

    Since the discovery of the high abundance of Alu elements in the human genome, the interest for the functional significance of these retrotransposons has been increasing. Primate Alu and rodent Alu-like elements are retrotransposed by a mechanism driven by the LINE1 (L1) encoded proteins, the same machinery that generates the L1 repeats, the processed pseudogenes (PPs), and other retroelements. Apart from free Alu RNAs, Alus are also transcribed and retrotranscribed as part of cellular gene transcripts, generally embedded inside 3’ untranslated regions (UTRs). Despite different proposed hypotheses, the functional implication of the presence of Alus inside 3’UTRs remains elusive. In this study we hypothesized that Alu elements in 3’UTRs could be involved in the genesis of PPs. By analyzing human genome data we discovered that the existence of 3’UTR-embedded Alu elements is overrepresented in genes source of PPs. In contrast, the presence of other retrotransposable elements in 3’UTRs does not show this PP linked overrepresentation. This research was extended to mouse and rat genomes and the results accordingly reveal overrepresentation of 3’UTR-embedded B1 (Alu-like) elements in PP parent genes. Interestingly, we also demonstrated that the overrepresentation of 3’UTR-embedded Alus is particularly significant in PP parent genes with low germline gene expression level. Finally, we provide data that support the hypothesis that the L1 machinery is also the system that herpesviruses, and possibly other large DNA viruses, use to capture host genes expressed in germline or somatic cells. Altogether our results suggest a novel role for Alu or Alu-like elements inside 3’UTRs as facilitators of the genesis of PPs, particularly in lowly expressed genes. Moreover, we propose that this L1-driven mechanism, aided by the presence of 3’UTR-embedded Alus, may also be exploited by DNA viruses to incorporate host genes to their viral genomes. PMID:28033411

  6. Alu elements and hominid phylogenetics.

    PubMed

    Salem, Abdel-Halim; Ray, David A; Xing, Jinchuan; Callinan, Pauline A; Myers, Jeremy S; Hedges, Dale J; Garber, Randall K; Witherspoon, David J; Jorde, Lynn B; Batzer, Mark A

    2003-10-28

    Alu elements have inserted in primate genomes throughout the evolution of the order. One particular Alu lineage (Ye) began amplifying relatively early in hominid evolution and continued propagating at a low level as many of its members are found in a variety of hominid genomes. This study represents the first conclusive application of short interspersed elements, which are considered nearly homoplasy-free, to elucidate the phylogeny of hominids. Phylogenetic analysis of Alu Ye5 elements and elements from several other subfamilies reveals high levels of support for monophyly of Hominidae, tribe Hominini and subtribe Hominina. Here we present the strongest evidence reported to date for a sister relationship between humans and chimpanzees while clearly distinguishing the chimpanzee and human lineages.

  7. Repeated Binge Drinking Increases Perineuronal Nets in the Insular Cortex

    PubMed Central

    Chen, Hu; He, Donghong; Lasek, Amy W.

    2015-01-01

    Background Alcohol exposure leads to changes in the extracellular matrix (ECM) in the brain, which profoundly impacts neuronal plasticity. Perineuronal nets (PNs) are specialized ECM structures that enclose subpopulations of neurons in the cortex. Adolescent exposure to alcohol induces long-lasting increases in the expression of PN components in the cortex in adult mice. However, it has not been determined whether binge alcohol exposure in young adults alters PNs. Here, we examined PNs and their core components in the insula and primary motor cortex after repeated binge-like ethanol consumption in adult mice. Methods The 4 day drinking in the dark (DID) procedure was performed in mice for 1 or 6 weeks to model binge alcohol consumption. The impact of ethanol drinking on PNs was examined by fluorescent staining of brain sections using a marker for PNs, Wisteria floribunda agglutinin (WFA). In another set of experiments, cortex was dissected and Western blots and quantitative real-time PCR (qPCR) were performed to evaluate the expression of the PN proteins aggrecan, brevican, and phosphacan. Results Binge-like ethanol drinking for 6 weeks caused a significant increase in PNs in the insula, as measured by WFA binding. Aggrecan, brevican and phosphacan protein expression, and aggrecan mRNA expression, were also elevated in the insula after 6 weeks of ethanol drinking. In contrast, expression of PN components did not change after 1 week of DID. The increase in PNs appears to be specific to the insula, since alterations were not observed in the primary motor cortex. Conclusions Our results provide the first evidence that insular PNs increase after long-term binge drinking. The insula mediates compulsive alcohol use. Since PNs influence neuronal firing and plasticity, increased PNs in the insula after multiple binge cycles may contribute to restricted neuronal plasticity and lead to the development of compulsive alcohol use. PMID:26332441

  8. Aberrant methylation and associated transcriptional mobilization of Alu elements contributes to genomic instability in hypoxia.

    PubMed

    Pal, Arnab; Srivastava, Tapasya; Sharma, Manish K; Mehndiratta, Mohit; Das, Prerna; Sinha, Subrata; Chattopadhyay, Parthaprasad

    2010-11-01

    Hypoxia is an integral part of tumorigenesis and contributes extensively to the neoplastic phenotype including drug resistance and genomic instability. It has also been reported that hypoxia results in global demethylation. Because a majority of the cytosine-phosphate-guanine (CpG) islands are found within the repeat elements of DNA, and are usually methylated under normoxic conditions, we suggested that retrotransposable Alu or short interspersed nuclear elements (SINEs) which show altered methylation and associated changes of gene expression during hypoxia, could be associated with genomic instability. U87MG glioblastoma cells were cultured in 0.1% O₂ for 6 weeks and compared with cells cultured in 21% O₂ for the same duration. Real-time PCR analysis showed a significant increase in SINE and reverse transcriptase coding long interspersed nuclear element (LINE) transcripts during hypoxia. Sequencing of bisulphite treated DNA as well as the Combined Bisulfite Restriction Analysis (COBRA) assay showed that the SINE loci studied underwent significant hypomethylation though there was patchy hypermethylation at a few sites. The inter-alu PCR profile of DNA from cells cultured under 6-week hypoxia, its 4-week revert back to normoxia and 6-week normoxia showed several changes in the band pattern indicating increased alu mediated genomic alteration. Our results show that aberrant methylation leading to increased transcription of SINE and reverse transcriptase associated LINE elements could lead to increased genomic instability in hypoxia. This might be a cause of genetic heterogeneity in tumours especially in variegated hypoxic environment and lead to a development of foci of more aggressive tumour cells.

  9. Resisting sarcolemmal rupture: dystrophin repeats increase membrane-actin stiffness.

    PubMed

    Sarkis, Joe; Vié, Véronique; Winder, Steve J; Renault, Anne; Le Rumeur, Elisabeth; Hubert, Jean-François

    2013-01-01

    Dystrophin is an essential part of a membrane protein complex that provides flexible support to muscle fiber membranes. Loss of dystrophin function leads to membrane fragility and muscle-wasting disease. Given the importance of cytoskeletal interactions in strengthening the sarcolemma, we have focused on actin-binding domain 2 of human dystrophin, constituted by repeats 11 to 15 of the central domain (DYS R11-15). We previously showed that DYS R11-15 also interacts with membrane lipids. We investigated the shear elastic constant (μ) and the surface viscosity (η(s)) of Langmuir phospholipid monolayers mimicking the inner leaflet of the sarcolemma in the presence of DYS R11-15 and actin. The initial interaction of 100 nM DYS R11-15 with the monolayers slightly modifies their rheological properties. Injection of 0.125 μM filamentous actin leads to a strong increase of μ and η(s,) from 0 to 5.5 mN/m and 2.4 × 10(-4) N · s/m, respectively. These effects are specific to DYS R11-15, require filamentous actin, and depend on phospholipid nature and lateral surface pressure. These findings suggest that the central domain of dystrophin contributes significantly to the stiffness and the stability of the sarcolemma through its simultaneous interactions with the cytoskeleton and lipid membrane. This mechanical link is likely to be a major contributing factor to the shock absorber function of dystrophin and muscle sarcolemmal integrity on mechanical stress.

  10. Age-Associated ALU Element Instability in White Blood Cells Is Linked to Lower Survival in Elderly Adults: A Preliminary Cohort Study

    PubMed Central

    Venturelli, Massimo; Gross, Cole; Tarperi, Cantor; Schena, Federico; Reggiani, Carlo; Naro, Fabio; Pedrinolla, Anna; Monaco, Lucia; Richardson, Russell S.; Donato, Anthony J.

    2017-01-01

    Background ALU element instability could contribute to gene function variance in aging, and may partly explain variation in human lifespan. Objective To assess the role of ALU element instability in human aging and the potential efficacy of ALU element content as a marker of biological aging and survival. Design Preliminary cohort study. Methods We measured two high frequency ALU element subfamilies, ALU-J and ALU-Sx, by a single qPCR assay and compared ALU-J/Sx content in white blood cell (WBCs) and skeletal muscle cell (SMCs) biopsies from twenty-three elderly adults with sixteen healthy sex-balanced young adults; all-cause survival rates of elderly adults predicted by ALU-J/Sx content in both tissues; and cardiovascular disease (CVD)- and cancer-specific survival rates of elderly adults predicted by ALU-J/Sx content in both tissues, as planned subgroup analyses. Results We found greater ALU-J/Sx content variance in WBCs from elderly adults than young adults (P < 0.001) with no difference in SMCs (P = 0.94). Elderly adults with low WBC ALU-J/Sx content had worse four-year all-cause and CVD-associated survival than those with high ALU-J/Sx content (both P = 0.03 and hazard ratios (HR) ≥ 3.40), while WBC ALU-J/Sx content had no influence on cancer-associated survival (P = 0.42 and HR = 0.74). SMC ALU-J/Sx content had no influence on all-cause, CVD- or cancer -associated survival (all P ≥ 0.26; HR ≤ 2.07). Conclusions These initial findings demonstrate that ALU element instability occurs with advanced age in WBCs, but not SMCs, and imparts greater risk of all-cause mortality that is likely driven by an increased risk for CVD and not cancer. PMID:28060910

  11. Epigenetic nucleosomes: Alu sequences and CG as nucleosome positioning element.

    PubMed

    Salih, F; Salih, B; Kogan, S; Trifonov, E N

    2008-08-01

    Alu sequences carry periodical pattern with CG dinucleotides (CpG) repeating every 31-32 bases. Similar distances are observed in distribution of DNA curvature in crystallized nucleosomes, at positions +/-1.5 and +/-4.5 periods of DNA from nucleosome DNA dyad. Since CG elements are also found to impart to nucleosomes higher stability when positioned at +/-1.5 sites, it suggests that CG dinucleotides may play a role in modulation of the nucleosome strength when the CG elements are methylated. Thus, Alu sequences may harbor special epigenetic nucleosomes with methylation-dependent regulatory functions. Nucleosome DNA sequence probe is suggested to detect locations of such regulatory nucleosomes in the sequences.

  12. Identification of Alternative Variants and Insertion of the Novel Polymorphic AluYl17 in TSEN54 Gene during Primate Evolution

    PubMed Central

    Kim, Young-Hyun; Choe, Se-Hee; Cho, Hyeon-Mu; Lee, Sang-Rae; Kim, Ji-Su; Song, Bong-Seok; Jeong, Kang-Jin; Jin, Yeung Bae; Kang, Philyong

    2016-01-01

    TSEN54 encodes a subunit of the tRNA-splicing endonuclease complex, which catalyzes the identification and cleavage of introns from precursor tRNAs. Previously, we identified an AluSx-derived alternative transcript in TSEN54 of cynomolgus monkey. Reverse transcription-polymerase chain reaction (RT-PCR) amplification and TSEN54 sequence analysis of primate and human samples identified five novel alternative transcripts, including the AluSx exonized transcript. Additionally, we performed comparative expression analysis via RT-qPCR in various cynomolgus, rhesus monkey, and human tissues. RT-qPCR amplification revealed differential expression patterns. Furthermore, genomic PCR amplification and sequencing of primate and human DNA samples revealed that AluSx elements were integrated in human and all of the primate samples tested. Intriguingly, in langur genomic DNA, an additional AluY element was inserted into AluSx of intron eight of TSEN54. The new AluY element showed polymorphic insertion. Using standardized nomenclature for Alu repeats, the polymorphic AluY of the langur TSEN54 was designated as being of the AluYl17 subfamily. Our results suggest that integration of the AluSx element in TSEN54 contributed to diversity in transcripts and induced lineage- or species-specific evolutionary events such as alternative splicing and polymorphic insertion during primate evolution. PMID:28083540

  13. Evidence for large diversity in the human transcriptome created by Alu RNA editing.

    PubMed

    Barak, Michal; Levanon, Erez Y; Eisenberg, Eli; Paz, Nurit; Rechavi, Gideon; Church, George M; Mehr, Ramit

    2009-11-01

    Adenosine-to-inosine (A-to-I) RNA editing alters the original genomic content of the human transcriptome and is essential for maintenance of normal life in mammals. A-to-I editing in Alu repeats is abundant in the human genome, with many thousands of expressed Alu sequences undergoing editing. Little is known so far about the contribution of Alu editing to transcriptome complexity. Transcripts derived from a single edited Alu sequence can be edited in multiple sites, and thus could theoretically generate a large number of different transcripts. Here we explored whether the combinatorial potential nature of edited Alu sequences is actually fulfilled in the human transcriptome. We analyzed datasets of editing sites and performed an analysis of a detailed transcript set of one edited Alu sequence. We found that editing appears at many more sites than detected by earlier genomic screens. To a large extent, editing of different sites within the same transcript is only weakly correlated. Thus, rather than finding a few versions of each transcript, a large number of edited variants arise, resulting in immense transcript diversity that eclipses alternative splicing as mechanism of transcriptome diversity, although with less impact on the proteome.

  14. Alu-mediated diverse and complex pathogenic copy-number variants within human chromosome 17 at p13.3.

    PubMed

    Gu, Shen; Yuan, Bo; Campbell, Ian M; Beck, Christine R; Carvalho, Claudia M B; Nagamani, Sandesh C S; Erez, Ayelet; Patel, Ankita; Bacino, Carlos A; Shaw, Chad A; Stankiewicz, Paweł; Cheung, Sau Wai; Bi, Weimin; Lupski, James R

    2015-07-15

    Alu repetitive elements are known to be major contributors to genome instability by generating Alu-mediated copy-number variants (CNVs). Most of the reported Alu-mediated CNVs are simple deletions and duplications, and the mechanism underlying Alu-Alu-mediated rearrangement has been attributed to non-allelic homologous recombination (NAHR). Chromosome 17 at the p13.3 genomic region lacks extensive low-copy repeat architecture; however, it is highly enriched for Alu repetitive elements, with a fraction of 30% of total sequence annotated in the human reference genome, compared with the 10% genome-wide and 18% on chromosome 17. We conducted mechanistic studies of the 17p13.3 CNVs by performing high-density oligonucleotide array comparative genomic hybridization, specifically interrogating the 17p13.3 region with ∼150 bp per probe density; CNV breakpoint junctions were mapped to nucleotide resolution by polymerase chain reaction and Sanger sequencing. Studied rearrangements include 5 interstitial deletions, 14 tandem duplications, 7 terminal deletions and 13 complex genomic rearrangements (CGRs). Within the 17p13.3 region, Alu-Alu-mediated rearrangements were identified in 80% of the interstitial deletions, 46% of the tandem duplications and 50% of the CGRs, indicating that this mechanism was a major contributor for formation of breakpoint junctions. Our studies suggest that Alu repetitive elements facilitate formation of non-recurrent CNVs, CGRs and other structural aberrations of chromosome 17 at p13.3. The common observation of Alu-mediated rearrangement in CGRs and breakpoint junction sequences analysis further demonstrates that this type of mechanism is unlikely attributed to NAHR, but rather may be due to a recombination-coupled DNA replicative repair process.

  15. Model-based adhesive shrinkage compensation for increased bonding repeatability

    NASA Astrophysics Data System (ADS)

    Müller, Tobias; Schlette, Christian; Lakshmanan, Shunmuganathan; Haag, Sebastian; Zontar, Daniel; Sauer, Sebastian; Wenzel, Christian; Brecher, Christian; Roβmann, Jürgen

    2016-03-01

    The assembly process of optical components consists of two phases - the alignment and the bonding phase. Precision - or better process repeatability - is limited by the latter one. The limitation of the alignment precision is given by the measurement equipment and the manipulation technology applied. Today's micromanipulators in combination with beam imaging setups allow for an alignment in the range of far below 100nm. However, once precisely aligned optics need to be fixed in their position. State o f the art in optics bonding for laser systems is adhesive bonding with UV-curing adhesives. Adhesive bonding is a multi-factorial process and thus subject to statistical process deviations. As a matter of fact, UV-curing adhesives inherit shrinkage effects during their curing process, making offsets for shrinkage compensation mandatory. Enhancing the process control of the adhesive bonding process is the major goal of the activities described in this paper. To improve the precision of shrinkage compensation a dynamic shrinkage prediction is envisioned by Fraunhofer IPT. Intense research activities are being practiced to gather a deeper understanding of the parameters influencing adhesive shrinkage behavior. These effects are of different nature - obviously being the raw adhesive material itself as well as its condition, the bonding geometry, environmental parameters like surrounding temperature and of course process parameters such as curing properties. Understanding the major parameters and linking them in a model-based shrinkage-prediction environment is the basis for improved process control. Results are being deployed by Fraunhofer in prototyping, as well as volume production solutions for laser systems.

  16. Assembly and characterization of novel Alu inserts detected from next-generation sequencing data

    PubMed Central

    Mustafa, Harun; David, Matei; Brudno, Michael

    2014-01-01

    Repetitive elements generally, and Alu inserts specifically are a large contributor to the recent evolution of the human genome. By assembling the sequences of novel Alu inserts using their respective subfamily consensus sequences as references, we found an exponential decay in the Alu subfamily call enrichment with increased number of sequence variants (Pearson correlation r=−0.68, p<0.0039). By mapping the sequences of these inserts to a human reference genome, we infer the reference Alu sources of a subset of the novel Alus, of which 85% were previously shown to be active. We also evaluate relationships between the loci of the novel inserts and their inferred sources. PMID:26442170

  17. Growth signals employ CGGBP1 to suppress transcription of Alu-SINEs

    PubMed Central

    Agarwal, Prasoon; Enroth, Stefan; Teichmann, Martin; Jernberg Wiklund, Helena; Smit, Arian; Westermark, Bengt; Singh, Umashankar

    2016-01-01

    ABSTRACT CGGBP1 (CGG triplet repeat-binding protein 1) regulates cell proliferation, stress response, cytokinesis, telomeric integrity and transcription. It could affect these processes by modulating target gene expression under different conditions. Identification of CGGBP1-target genes and their regulation could reveal how a transcription regulator affects such diverse cellular processes. Here we describe the mechanisms of differential gene expression regulation by CGGBP1 in quiescent or growing cells. By studying global gene expression patterns and genome-wide DNA-binding patterns of CGGBP1, we show that a possible mechanism through which it affects the expression of RNA Pol II-transcribed genes in trans depends on Alu RNA. We also show that it regulates Alu transcription in cis by binding to Alu promoter. Our results also indicate that potential phosphorylation of CGGBP1 upon growth stimulation facilitates its nuclear retention, Alu-binding and dislodging of RNA Pol III therefrom. These findings provide insights into how Alu transcription is regulated in response to growth signals. PMID:25483050

  18. Repeating a Monologue under Increasing Time Pressure: Effects on Fluency, Complexity, and Accuracy

    ERIC Educational Resources Information Center

    Thai, Chau; Boers, Frank

    2016-01-01

    Studies have shown that learners' task performance improves when they have the opportunity to repeat the task. Conditions for task repetition vary, however. In the 4/3/2 activity, learners repeat a monologue under increasing time pressure. The purpose is to foster fluency, but it has been suggested in the literature that it also benefits other…

  19. Alu-mediated diverse and complex pathogenic copy-number variants within human chromosome 17 at p13.3

    PubMed Central

    Gu, Shen; Yuan, Bo; Campbell, Ian M.; Beck, Christine R.; Carvalho, Claudia M.B.; Nagamani, Sandesh C.S.; Erez, Ayelet; Patel, Ankita; Bacino, Carlos A.; Shaw, Chad A.; Stankiewicz, Paweł; Cheung, Sau Wai; Bi, Weimin; Lupski, James R.

    2015-01-01

    Alu repetitive elements are known to be major contributors to genome instability by generating Alu-mediated copy-number variants (CNVs). Most of the reported Alu-mediated CNVs are simple deletions and duplications, and the mechanism underlying Alu–Alu-mediated rearrangement has been attributed to non-allelic homologous recombination (NAHR). Chromosome 17 at the p13.3 genomic region lacks extensive low-copy repeat architecture; however, it is highly enriched for Alu repetitive elements, with a fraction of 30% of total sequence annotated in the human reference genome, compared with the 10% genome-wide and 18% on chromosome 17. We conducted mechanistic studies of the 17p13.3 CNVs by performing high-density oligonucleotide array comparative genomic hybridization, specifically interrogating the 17p13.3 region with ∼150 bp per probe density; CNV breakpoint junctions were mapped to nucleotide resolution by polymerase chain reaction and Sanger sequencing. Studied rearrangements include 5 interstitial deletions, 14 tandem duplications, 7 terminal deletions and 13 complex genomic rearrangements (CGRs). Within the 17p13.3 region, Alu–Alu-mediated rearrangements were identified in 80% of the interstitial deletions, 46% of the tandem duplications and 50% of the CGRs, indicating that this mechanism was a major contributor for formation of breakpoint junctions. Our studies suggest that Alu repetitive elements facilitate formation of non-recurrent CNVs, CGRs and other structural aberrations of chromosome 17 at p13.3. The common observation of Alu-mediated rearrangement in CGRs and breakpoint junction sequences analysis further demonstrates that this type of mechanism is unlikely attributed to NAHR, but rather may be due to a recombination-coupled DNA replicative repair process. PMID:25908615

  20. Genome-wide chromatin remodeling modulates the Alu heat shock response.

    PubMed

    Kim, C; Rubin, C M; Schmid, C W

    2001-10-03

    During heat shock recovery in Hela cells, the level of Alu RNA transiently increases with kinetics that approximately parallel the transient expression of heat shock protein mRNAs. Coincidentally, there is a transient increase in the accessibility of Alu chromatin to restriction enzyme cleavage suggesting that an opening and re-closing of chromatin regulates the Alu stress response. Similar changes occur in alpha satellite and LINE1 chromatin showing that heat shock induces a genome-wide remodeling of chromatin structure which is independent of transcription. The increased accessibility of restriction sites within these repetitive sequences is inconsistent with a simple lengthening of the nucleosome linker region but instead suggests a scrambling of nucleosome positions. Chromatin structure and its dynamics account for many of the principal features of SINE transcriptional regulation potentially providing a functional rationale for the dispersion and high copy number of SINEs.

  1. Structural Variation of Alu Element and Human Disease

    PubMed Central

    Kim, Songmi; Cho, Chun-Sung; Han, Kyudong

    2016-01-01

    Transposable elements are one of major sources to cause genomic instability through various mechanisms including de novo insertion, insertion-mediated genomic deletion, and recombination-associated genomic deletion. Among them is Alu element which is the most abundant element, composing ~10% of the human genome. The element emerged in the primate genome 65 million years ago and has since propagated successfully in the human and non-human primate genomes. Alu element is a non-autonomous retrotransposon and therefore retrotransposed using L1-enzyme machinery. The 'master gene' model has been generally accepted to explain Alu element amplification in primate genomes. According to the model, different subfamilies of Alu elements are created by mutations on the master gene and most Alu elements are amplified from the hyperactive master genes. Alu element is frequently involved in genomic rearrangements in the human genome due to its abundance and sequence identity between them. The genomic rearrangements caused by Alu elements could lead to genetic disorders such as hereditary disease, blood disorder, and neurological disorder. In fact, Alu elements are associated with approximately 0.1% of human genetic disorders. The first part of this review discusses mechanisms of Alu amplification and diversity among different Alu subfamilies. The second part discusses the particular role of Alu elements in generating genomic rearrangements as well as human genetic disorders. PMID:27729835

  2. Repeated exposure to noise increases tolerance in a coral reef fish.

    PubMed

    Nedelec, Sophie L; Mills, Suzanne C; Lecchini, David; Nedelec, Brendan; Simpson, Stephen D; Radford, Andrew N

    2016-09-01

    Some anthropogenic noise is now considered pollution, with evidence building that noise from human activities such as transportation, construction and exploration can impact behaviour and physiology in a broad range of taxa. However, relatively little research has considered the effects of repeated or chronic noise; extended exposures may result in habituation or sensitisation, and thus changes in response. We conducted a field-based experiment at Moorea Island to investigate how repeated exposure to playback of motorboat noise affected a coral reef fish (Dascyllus trimaculatus). We found that juvenile D. trimaculatus increased hiding behaviour during motorboat noise after two days of repeated exposure, but no longer did so after one and two weeks of exposure. We also found that naïve individuals responded to playback of motorboat noise with elevated ventilation rates, but that this response was diminished after one and two weeks of repeated exposure. We found no strong evidence that baseline blood cortisol levels, growth or body condition were affected by three weeks of repeated motorboat-noise playback. Our study reveals the importance of considering how tolerance levels may change over time, rather than simply extrapolating from results of short-term studies, if we are to make decisions about regulation and mitigation.

  3. An Alu-based phylogeny of gibbons (hylobatidae).

    PubMed

    Meyer, Thomas J; McLain, Adam T; Oldenburg, J Michael; Faulk, Christopher; Bourgeois, Matthew G; Conlin, Erin M; Mootnick, Alan R; de Jong, Pieter J; Roos, Christian; Carbone, Lucia; Batzer, Mark A

    2012-11-01

    Gibbons (Hylobatidae) are small, arboreal apes indigenous to Southeast Asia that diverged from other apes ∼15-18 Ma. Extant lineages radiated rapidly 6-10 Ma and are organized into four genera (Hylobates, Hoolock, Symphalangus, and Nomascus) consisting of 12-19 species. The use of short interspersed elements (SINEs) as phylogenetic markers has seen recent popularity due to several desirable characteristics: the ancestral state of a locus is known to be the absence of an element, rare potentially homoplasious events are relatively easy to resolve, and samples can be quickly and inexpensively genotyped. During radiation of primates, one particular family of SINEs, the Alu family, has proliferated in primate genomes. Nomascus leucogenys (northern white-cheeked gibbon) sequences were analyzed for repetitive content with RepeatMasker using a custom library. The sequences containing Alu elements identified as members of a gibbon-specific subfamily were then compared with orthologous positions in other primate genomes. A primate phylogenetic panel consisting of 18 primate species, including 13 gibbon species representing all four extant genera, was assayed for all loci, and a total of 125 gibbon-specific Alu insertions were identified. The resulting amplification patterns were used to generate a phylogenetic tree. We demonstrate significant support for Symphalangus as the most basal lineage within the family. Our findings also place Nomascus as a derived lineage, sister to Hoolock, with the Nomascus-Hoolock clade sister to Hylobates. Further, our analysis groups N. leucogenys and Nomascus siki as sister taxa to the exclusion of the other Nomascus species assayed. This study represents the first use of SINEs to determine the genus level phylogenetic relationships within the family Hylobatidae. These relationships have been resolved with robust support at most internal nodes, demonstrating the utility of SINE-based phylogenetic analysis. We postulate that hybridization

  4. Sequence Analysis and Characterization of Active Human Alu Subfamilies Based on the 1000 Genomes Pilot Project.

    PubMed

    Konkel, Miriam K; Walker, Jerilyn A; Hotard, Ashley B; Ranck, Megan C; Fontenot, Catherine C; Storer, Jessica; Stewart, Chip; Marth, Gabor T; Batzer, Mark A

    2015-08-29

    The goal of the 1000 Genomes Consortium is to characterize human genome structural variation (SV), including forms of copy number variations such as deletions, duplications, and insertions. Mobile element insertions, particularly Alu elements, are major contributors to genomic SV among humans. During the pilot phase of the project we experimentally validated 645 (611 intergenic and 34 exon targeted) polymorphic "young" Alu insertion events, absent from the human reference genome. Here, we report high resolution sequencing of 343 (322 unique) recent Alu insertion events, along with their respective target site duplications, precise genomic breakpoint coordinates, subfamily assignment, percent divergence, and estimated A-rich tail lengths. All the sequenced Alu loci were derived from the AluY lineage with no evidence of retrotransposition activity involving older Alu families (e.g., AluJ and AluS). AluYa5 is currently the most active Alu subfamily in the human lineage, followed by AluYb8, and many others including three newly identified subfamilies we have termed AluYb7a3, AluYb8b1, and AluYa4a1. This report provides the structural details of 322 unique Alu variants from individual human genomes collectively adding about 100 kb of genomic variation. Many Alu subfamilies are currently active in human populations, including a surprising level of AluY retrotransposition. Human Alu subfamilies exhibit continuous evolution with potential drivers sprouting new Alu lineages.

  5. Sequence Analysis and Characterization of Active Human Alu Subfamilies Based on the 1000 Genomes Pilot Project

    PubMed Central

    Konkel, Miriam K.; Walker, Jerilyn A.; Hotard, Ashley B.; Ranck, Megan C.; Fontenot, Catherine C.; Storer, Jessica; Stewart, Chip; Marth, Gabor T.; Batzer, Mark A.

    2015-01-01

    The goal of the 1000 Genomes Consortium is to characterize human genome structural variation (SV), including forms of copy number variations such as deletions, duplications, and insertions. Mobile element insertions, particularly Alu elements, are major contributors to genomic SV among humans. During the pilot phase of the project we experimentally validated 645 (611 intergenic and 34 exon targeted) polymorphic “young” Alu insertion events, absent from the human reference genome. Here, we report high resolution sequencing of 343 (322 unique) recent Alu insertion events, along with their respective target site duplications, precise genomic breakpoint coordinates, subfamily assignment, percent divergence, and estimated A-rich tail lengths. All the sequenced Alu loci were derived from the AluY lineage with no evidence of retrotransposition activity involving older Alu families (e.g., AluJ and AluS). AluYa5 is currently the most active Alu subfamily in the human lineage, followed by AluYb8, and many others including three newly identified subfamilies we have termed AluYb7a3, AluYb8b1, and AluYa4a1. This report provides the structural details of 322 unique Alu variants from individual human genomes collectively adding about 100 kb of genomic variation. Many Alu subfamilies are currently active in human populations, including a surprising level of AluY retrotransposition. Human Alu subfamilies exhibit continuous evolution with potential drivers sprouting new Alu lineages. PMID:26319576

  6. Alu elements and DNA double-strand break repair.

    PubMed

    White, Travis B; Morales, Maria E; Deininger, Prescott L

    2015-01-01

    Alu elements represent one of the most common sources of homology and homeology in the human genome. Homeologous recombination between Alu elements represents a major form of genetic instability leading to deletions and duplications. Although these types of events have been studied extensively through genomic sequencing to assess the impact of Alu elements on disease mutations and genome evolution, the overall abundance of Alu elements in the genome often makes it difficult to assess the relevance of the Alu elements to specific recombination events. We recently reported a powerful new reporter gene system that allows the assessment of various cis and trans factors on the contribution of Alu elements to various forms of genetic instability. This allowed a quantitative measurement of the influence of mismatches on Alu elements and instability. It also confirmed that homeologous Alu elements are able to stimulate non-homologous end joining events in their vicinity. This appears to be dependent on portions of the mismatch repair pathway. We are now in a position to begin to unravel the complex influences of Alu density, mismatch and location with alterations of DNA repair processes in various tissues and tumors.

  7. Repeating firing fields of CA1 neurons shift forward in response to increasing angular velocity.

    PubMed

    Cowen, Stephen L; Nitz, Douglas A

    2014-01-01

    Self-motion information influences spatially-specific firing patterns exhibited by hippocampal neurons. Moreover, these firing patterns can repeat across similar subsegments of an environment, provided that there is similarity of path shape and head orientations across subsegments. The influence of self-motion variables on repeating fields remains to be determined. To investigate the role of path shape and angular rotation on hippocampal activity, we recorded the activity of CA1 neurons from rats trained to run on spiral-shaped tracks. During inbound traversals of circular-spiral tracks, angular velocity increases continuously. Under this condition, most neurons (74%) exhibited repeating fields across at least three adjacent loops. Of these neurons, 86% exhibited forward shifts in the angles of field centers relative to centers on preceding loops. Shifts were absent on squared-spiral tracks, minimal and less reliable on concentric-circle tracks, and absent on outward-bound runs on circular-spiral tracks. However, outward-bound runs on the circular-spiral track in the dark were associated with backward shifts. Together, the most parsimonious interpretation of the results is that continuous increases or decreases in angular velocity are particularly effective at shifting the center of mass of repeating fields, although it is also possible that a nonlinear integration of step counts contributes to the shift. Furthermore, the unexpected absence of field shifts during outward journeys in light (but not darkness) suggests visual cues around the goal location anchored the map of space to an allocentric reference frame.

  8. Alu Elements as Novel Regulators of Gene Expression in Type 1 Diabetes Susceptibility Genes?

    PubMed

    Kaur, Simranjeet; Pociot, Flemming

    2015-07-13

    Despite numerous studies implicating Alu repeat elements in various diseases, there is sparse information available with respect to the potential functional and biological roles of the repeat elements in Type 1 diabetes (T1D). Therefore, we performed a genome-wide sequence analysis of T1D candidate genes to identify embedded Alu elements within these genes. We observed significant enrichment of Alu elements within the T1D genes (p-value < 10e-16), which highlights their importance in T1D. Functional annotation of T1D genes harboring Alus revealed significant enrichment for immune-mediated processes (p-value < 10e-6). We also identified eight T1D genes harboring inverted Alus (IRAlus) within their 3' untranslated regions (UTRs) that are known to regulate the expression of host mRNAs by generating double stranded RNA duplexes. Our in silico analysis predicted the formation of duplex structures by IRAlus within the 3'UTRs of T1D genes. We propose that IRAlus might be involved in regulating the expression levels of the host T1D genes.

  9. Can the Palatability of Healthy, Satiety-Promoting Foods Increase with Repeated Exposure during Weight Loss?

    PubMed

    Anguah, Katherene O-B; Lovejoy, Jennifer C; Craig, Bruce A; Gehrke, Malinda M; Palmer, Philip A; Eichelsdoerfer, Petra E; McCrory, Megan A

    2017-02-22

    Repeated exposure to sugary, fatty, and salty foods often enhances their appeal. However, it is unknown if exposure influences learned palatability of foods typically promoted as part of a healthy diet. We tested whether the palatability of pulse containing foods provided during a weight loss intervention which were particularly high in fiber and low in energy density would increase with repeated exposure. At weeks 0, 3, and 6, participants (n = 42; body mass index (BMI) 31.2 ± 4.3 kg/m²) were given a test battery of 28 foods, approximately half which had been provided as part of the intervention, while the remaining half were not foods provided as part of the intervention. In addition, about half of each of the foods (provided as part or not provided as part of the intervention) contained pulses. Participants rated the taste, appearance, odor, and texture pleasantness of each food, and an overall flavor pleasantness score was calculated as the mean of these four scores. Linear mixed model analyses showed an exposure type by week interaction effect for taste, texture and overall flavor pleasantness indicating statistically significant increases in ratings of provided foods in taste and texture from weeks 0 to 3 and 0 to 6, and overall flavor from weeks 0 to 6. Repeated exposure to these foods, whether they contained pulses or not, resulted in a ~4% increase in pleasantness ratings. The long-term clinical relevance of this small increase requires further study.

  10. Can the Palatability of Healthy, Satiety-Promoting Foods Increase with Repeated Exposure during Weight Loss?

    PubMed Central

    Anguah, Katherene O.-B.; Lovejoy, Jennifer C.; Craig, Bruce A.; Gehrke, Malinda M.; Palmer, Philip A.; Eichelsdoerfer, Petra E.; McCrory, Megan A.

    2017-01-01

    Repeated exposure to sugary, fatty, and salty foods often enhances their appeal. However, it is unknown if exposure influences learned palatability of foods typically promoted as part of a healthy diet. We tested whether the palatability of pulse containing foods provided during a weight loss intervention which were particularly high in fiber and low in energy density would increase with repeated exposure. At weeks 0, 3, and 6, participants (n = 42; body mass index (BMI) 31.2 ± 4.3 kg/m2) were given a test battery of 28 foods, approximately half which had been provided as part of the intervention, while the remaining half were not foods provided as part of the intervention. In addition, about half of each of the foods (provided as part or not provided as part of the intervention) contained pulses. Participants rated the taste, appearance, odor, and texture pleasantness of each food, and an overall flavor pleasantness score was calculated as the mean of these four scores. Linear mixed model analyses showed an exposure type by week interaction effect for taste, texture and overall flavor pleasantness indicating statistically significant increases in ratings of provided foods in taste and texture from weeks 0 to 3 and 0 to 6, and overall flavor from weeks 0 to 6. Repeated exposure to these foods, whether they contained pulses or not, resulted in a ~4% increase in pleasantness ratings. The long-term clinical relevance of this small increase requires further study. PMID:28231094

  11. Repeated stress increases catalytic TrkB mRNA in rat hippocampus.

    PubMed

    Nibuya, M; Takahashi, M; Russell, D S; Duman, R S

    1999-05-28

    Northern blot analysis was utilized to distinguish between catalytic and truncated TrkB mRNA on the basis of transcript size. Repeated (10 days), but not acute, immobilization stress significantly increased levels of catalytic TrkB mRNA, but did not influence expression of truncated TrkB transcripts in rat hippocampus. Exposure to another paradigm, a combination of different, unpredictable stressors, also increased levels of catalytic, but not truncated, TrkB mRNA. In situ hybridization analysis demonstrated that chronic stress up-regulated TrkB mRNA in CA1 and CA3 pyramidal and dentate gyrus granule cells layers of hippocampus. As previously reported, both acute and chronic immobilization stress decreased expression of BDNF mRNA, suggesting that up-regulation of catalytic TrkB mRNA may be a compensatory adaptation to repeated stress.

  12. AluY-mediated germline deletion, duplication and somatic stem cell reversion in UBE2T defines a new subtype of Fanconi anemia.

    PubMed

    Virts, Elizabeth L; Jankowska, Anna; Mackay, Craig; Glaas, Marcel F; Wiek, Constanze; Kelich, Stephanie L; Lottmann, Nadine; Kennedy, Felicia M; Marchal, Christophe; Lehnert, Erik; Scharf, Rüdiger E; Dufour, Carlo; Lanciotti, Marina; Farruggia, Piero; Santoro, Alessandra; Savasan, Süreyya; Scheckenbach, Kathrin; Schipper, Jörg; Wagenmann, Martin; Lewis, Todd; Leffak, Michael; Farlow, Janice L; Foroud, Tatiana M; Honisch, Ellen; Niederacher, Dieter; Chakraborty, Sujata C; Vance, Gail H; Pruss, Dmitry; Timms, Kirsten M; Lanchbury, Jerry S; Alpi, Arno F; Hanenberg, Helmut

    2015-09-15

    Fanconi anemia (FA) is a rare inherited disorder clinically characterized by congenital malformations, progressive bone marrow failure and cancer susceptibility. At the cellular level, FA is associated with hypersensitivity to DNA-crosslinking genotoxins. Eight of 17 known FA genes assemble the FA E3 ligase complex, which catalyzes monoubiquitination of FANCD2 and is essential for replicative DNA crosslink repair. Here, we identify the first FA patient with biallelic germline mutations in the ubiquitin E2 conjugase UBE2T. Both mutations were aluY-mediated: a paternal deletion and maternal duplication of exons 2-6. These loss-of-function mutations in UBE2T induced a cellular phenotype similar to biallelic defects in early FA genes with the absence of FANCD2 monoubiquitination. The maternal duplication produced a mutant mRNA that could encode a functional protein but was degraded by nonsense-mediated mRNA decay. In the patient's hematopoietic stem cells, the maternal allele with the duplication of exons 2-6 spontaneously reverted to a wild-type allele by monoallelic recombination at the duplicated aluY repeat, thereby preventing bone marrow failure. Analysis of germline DNA of 814 normal individuals and 850 breast cancer patients for deletion or duplication of UBE2T exons 2-6 identified the deletion in only two controls, suggesting aluY-mediated recombinations within the UBE2T locus are rare and not associated with an increased breast cancer risk. Finally, a loss-of-function germline mutation in UBE2T was detected in a high-risk breast cancer patient with wild-type BRCA1/2. Cumulatively, we identified UBE2T as a bona fide FA gene (FANCT) that also may be a rare cancer susceptibility gene.

  13. Newly arisen DNA repeats in primate phylogeny.

    PubMed

    Ryan, S C; Dugaiczyk, A

    1989-12-01

    We discovered the presence of an Alu and an Xba repetitive DNA element within introns 4 and 7, respectively, of the human alpha-fetoprotein (AFP) gene; these elements are absent from the same gene in the gorilla. The Alu element is flanked by 12-base-pair direct repeats, AGGATGTTGTGG ... (Alu) ... AGGATGTTGTGG, which presumably arose by way of duplication of the intronic target site AGGATGTTGTGG at the time of the Alu insertion. In the gorilla, only a single copy of the unoccupied target site is present, which is identical to the terminal repeat flanking the human Alu element. There are two copies of an Xba repeat in the human AFP gene, apparently the only two in the genome. Xba1 and Xba2, located within introns 8 and 7, respectively, differ from each other at 3 of 303 positions. Xba1 is referred to as the old (ancestral) repeat because it lacks direct repeats. The new (derived) Xba2 is flanked by direct repeats, TTTCTTTTT ... (Xba) ... TTTCTTCTT, and is thought to have arisen as a result of transposition of Xba1. The ancestral Xba1 and a single copy of the Xba2 target site are present at orthologous positions in the gorilla, but the new Xba2 is absent. We conclude that the Alu and Xba DNA repeats emerged in the human genome at a time postdating the human-gorilla divergence and became established as genetic novelties in the human lineage. We submit that the chronology of divergence of primate lines of evolution can be correlated with the timing of insertion of new DNA repeats into the genomes of those primates.

  14. Repeated taste exposure increases liking for vegetables by low-income elementary school children.

    PubMed

    Lakkakula, Anantha; Geaghan, James; Zanovec, Michael; Pierce, Sarah; Tuuri, Georgianna

    2010-10-01

    Children's food preferences play a major role in their food choices and consumption. The objective of the present study was to examine if repeated tastings of selected vegetables in a school setting increased children's liking of these items. A total of 360 fourth- and fifth-grade students attending four low-income, public elementary schools in southeastern Louisiana volunteered to participate. During the spring of 2008, children were offered a taste of carrots, peas, tomatoes, and bell peppers once a week for 10 weeks. At each tasting session children recorded whether they swallowed each of the vegetables, spit it into the napkin, or did not put it in their mouth and indicated their liking for each vegetable using a Likert-type response scale. Approximately one-half of the children tasted eight of ten times during the program (46.5% for those who began disliking and 68.5% for those who began liking the vegetables). Proc Glimmix analyses indicated that for children who began the program disliking the vegetables, repeated tasting improved liking scores for carrots, peas, and tomatoes; liking for bell peppers did not change. The number of children who reported liking or liking a lot for previously disliked vegetables was greater after eight or nine taste exposures. Repeated tasting of less-liked vegetables by children in a cafeteria-based setting is a strategy to promote liking of these items and is effective in approximately half of the participants.

  15. The current source of human Alu retroposons is a conserved gene shared with Old World monkey

    SciTech Connect

    Britten, R.J.; Stout, D.B.; Davidson, E.H. )

    1989-05-01

    A significant fraction of human Alu repeated sequences are members of the precise, recently inserted class. A cloned member of this class has been used as a probe for interspecies hybridization and thermal stability determination. The probe was reassociated with human, mandrill, and spider monkey DNA under conditions such that only almost perfectly matching duplexes could form. Equally precise hybrids were formed with human and mandrill DNA (Old World monkey) but not with spider monkey DNA (New World). These measurements as well as reassociation kinetics show the presence in mandrill DNA of many precise class Alu sequences that are very similar or identical in quantity and sequence to those in human DNA. Human and mandrill are moderately distant species with a single-copy DNA divergence of about 6%. Nevertheless, their recently inserted Alu sequences arise by retroposition of transcripts of source genes with nearly identical sequences. Apparently a gene present in our common ancestor at the time of branching was inherited and highly conserved in sequence in both the lineage of Old World monkeys and the lineage of apes and man.

  16. Breakpoint Associated with a novel 2.3 Mb deletion in the VCFS region of 22q11 and the role of Alu (SINE) in recurring microdeletions

    PubMed Central

    Uddin, Raihan K; Zhang, Yang; Siu, Victoria Mok; Fan, Yao-Shan; O'Reilly, Richard L; Rao, Jay; Singh, Shiva M

    2006-01-01

    Background Chromosome 22q11.2 region is highly susceptible to rearrangement, specifically deletions that give rise to a variety of genomic disorders including velocardiofacial or DiGeorge syndrome. Individuals with this 22q11 microdeletion syndrome are at a greatly increased risk to develop schizophrenia. Methods Genotype analysis was carried out on the DNA from a patient with the 22q11 microdeletion using genetic markers and custom primer sets to define the deletion. Bioinformatic analysis was performed for molecular characterization of the deletion breakpoint sequences in this patient. Results This 22q11 deletion patient was established to have a novel 2.3 Mb deletion with a proximal breakpoint located between genetic markers RH48663 and RH48348 and a distal breakpoint between markers D22S1138 and SHGC-145314. Molecular characterization of the sequences at the breakpoints revealed a 270 bp shared sequence of the breakpoint regions (SSBR) common to both ends that share >90% sequence similarity to each other and also to short interspersed nuclear elements/Alu elements. Conclusion This Alu sequence like SSBR is commonly in the proximity of all known deletion breakpoints of 22q11 region and also in the low copy repeat regions (LCRs). This sequence may represent a preferred sequence in the breakpoint regions or LCRs for intra-chromosomal homologous recombination mechanisms resulting in common 22q11 deletion. PMID:16512914

  17. Differential regional development of tolerance to increase in dopamine turnover upon repeated neuroleptic administration.

    PubMed

    Scatton, B

    1977-12-15

    Repeated treatment with haloperidol and sulpiride induced tolerance to the increases in homovanillic and dihydroxyphenyl acetic acids in the striatum, nucleus accumbens, tuberculum olfactorium and frontal cortex of the rat. The threshold dose inducing this effect appeared to be lower in the striatum than in the limbic regions. Similar results were found in the frontal cortex by measuring dopamine utilization. Moreover, tolerance developed earlier in the striatum than in the limbic areas. The possible reasons are discussed for the differential development of tolerance in the various DA areas investigated.

  18. Increased Impulsivity and Disrupted Attention Induced by Repeated Phencyclidine are not Attenuated by Chronic Quetiapine Treatment

    PubMed Central

    Amitai, Nurith; Markou, Athina

    2009-01-01

    Atypical antipsychotic medications differ in how effectively they attenuate cognitive and other deficits in schizophrenia. The present study aimed to explore whether quetiapine, an atypical antipsychotic medication, would reverse disruptions of performance in the 5-choice serial reaction time task (5-CSRTT), a test of attention and impulsivity, induced by repeated administration of the psychotomimetic phencyclidine (PCP). In confirmation of previous findings, repeated PCP administration (2 mg/kg, s.c., 30 min before behavioral testing, for two consecutive days, followed by a 2-week PCP-free period and then five consecutive days of PCP treatment) increased premature responding (impulsivity), decreased accuracy (attention), and increased response latencies (processing speed) and timeout responding (impulsivity/cognitive inflexibility). Chronic quetiapine (5 or 10 mg/kg/day, s.c.) did not attenuate these PCP-induced disruptions in performance, while at the highest dose used, quetiapine disrupted 5-CSRTT performance in the absence of PCP treatment and tended to exacerbate the PCP-induced increase in premature responding. Considering that clozapine, another atypical antipsychotic, was shown previously to reverse PCP-induced deficits in the same task (Amitai et al. 2007), the present findings demonstrate differences between clozapine and quetiapine in their effectiveness on schizophrenia-like cognitive deficits and impulsivity that may be attributable to their different receptor affinity profiles. PMID:18809428

  19. Repeated exposure to moderate doses of ethanol augments hippocampal glutamate neurotransmission by increasing release

    PubMed Central

    Chefer, Vladimir; Meis, Jennifer; Wang, Grace; Kuzmin, Alexander; Bakalkin, Georgy; Shippenberg, Toni

    2013-01-01

    The present study used conventional and quantitative microdialysis to assess glutamatergic and GABAergic neurotransmission in the hippocampal CA3 area of the rat following a moderate-dose ethanol treatment regimen. Male Wistar rats received 3.4 g/kg of ethanol or water for 6 days via gastric gavage. Microdialysis experiments commenced 2 days later. Basal and depolarization-induced glutamate overflow were significantly elevated in ethanol-treated animals. Basal and depolarization-induced gamma-aminobutyric acid (GABA) overflow were unaltered. Quantitative no-net-flux microdialysis was used to determine if changes in dialysate glutamate levels following ethanol administration are due to an increase in release or a decrease in uptake.To confirm the validity of this method for quantifying basal glutamate dynamics, extracellular concentrations of glutamate and the extraction fraction, which reflects changes in analyte clearance, were quantified in response to retro-dialysis of the glutamate uptake blocker trans-pyrrolidine-2,4-dicarboxylic acid (tPDC). tPDC significantly decreased the extraction fraction for glutamate, resulting in augmented extracellular glutamate concentrations. Repeated ethanol administration did not alter the glutamate extraction fraction. However, extracellular glutamate concentrations were significantly elevated, indicating that glutamate release is increased as a consequence of repeated ethanol administration. These data demonstrate that repeated bouts of moderate ethanol consumption alter basal glutamate dynamics in the CA3 region of the dorsal hippocampus. Basal glutamate release is augmented, whereas glutamate uptake is unchanged. Furthermore, they suggest that dysregulation of glutamate transmission in this region may contribute to the previously documented deficits in cognitive function associated with moderate dose ethanol use. PMID:21182572

  20. Repeated bonding of fixed retainer increases the risk of enamel fracture.

    PubMed

    Chinvipas, Netrporn; Hasegawa, Yuh; Terada, Kazuto

    2014-01-01

    The aim of this study was to investigate the influences of repeated bonding, using 2 different orthodontic adhesive systems, on the shear bond strength (SBS) and the enamel surface morphology. Sixty premolars were divided into 2 groups (n = 30), and either Transbond XT (T group) or Fuji Ortho LC (F group) adhesives were used. SBS was measured 24 h after bonding, using a universal testing machine. Then, the enamel surfaces were investigated and the mode of failure was described using adhesive remnant index (ARI) scores. After each debonding, 10 teeth from each group were examined by scanning electron microscopy to determine the penetration of adhesives, the length of resin tags, and the state of the enamel surface. The other teeth were subjected to two more bonding/debonding procedures. In T group, the second debonding sequences had significantly higher bond strengths than the other sequences. The length of resin tags was greatest in the second debonding sequence, although there was no significant difference. In F group, the SBS increased with further rebonding and the failure mode tended towards cohesive failure. In both groups, the ARI scores increased with rebonding. Enamel loss could have occurred with both adhesives, although the surfaces appeared unchanged to the naked eye. From this study, we suggest that enamel damage caused by repeated bonding is of concern. To prevent bond failure, we should pay attention to the adhesion method used for bondable retainers.

  1. Effects of a Randomized Controlled Trial to Increase Repeat Mammography Screening in Iranian Women

    PubMed Central

    Taymoori, Parvaneh; Molina, Yamile; Roshani, Daem

    2014-01-01

    Background Although mammography use has increased in developed countries, regular screening in developing countries including Iran remains low. Multiple frameworks, including the Health Belief Model (HBM) and the Theory of Planned Behavior (TPB), have been used to understand screening practices among Iranians. The HBM includes intrapersonal constructs such as perceptions of breast cancer and mammography. The TPB includes interpersonal and environmental constructs, such as perceived control and subjective norms. Objectives The current study had 2 objectives: (1) to examine changes in the HBM and TPB constructs and repeat mammography screening in women receiving either intervention and women in the control group and (2) to compare changes in the HBM and TPB constructs and repeat mammography screening across the 2 interventions. Methods One hundred eight-four women from 3 randomly selected health centers in Sanandaj, Iran, participated. Eligibility criteria were being 50 years or older, having received a mammogram in the past 2 to 3 years, and no intention to obtain a mammogram within the next year. Results The TPB and HBM participants exhibited greater changes in the HBM and TPB constructs and were more likely to have a mammogram relative to control participants. The TPB and HBM participants exhibited comparable changes in constructs and repeat mammography. Conclusion Findings suggest both interventions equally improved mammography screening. Additional studies are furthermore warranted to address nonadherent Iranian women’s needs in line with these conceptual models. Implications for Practice Use of the HBM and TPB constructs in clinical practice may be helpful to promote continued screening among this population. PMID:25122130

  2. Exposing Students to Repeat Photography: Increasing Cultural Understanding on a Short-Term Study Abroad

    ERIC Educational Resources Information Center

    Lemmons, Kelly K.; Brannstrom, Christian; Hurd, Danielle

    2014-01-01

    Traditionally, repeat photography has been used to analyze land cover change. This paper describes how repeat photography may be used as a tool to enhance the short-term study abroad experience by facilitating cultural interaction and understanding. We present evidence from two cases and suggest a five-step repeat photography method for educators…

  3. Polymorphic Alu insertions among Mayan populations.

    PubMed

    Herrera, R J; Rojas, D P; Terreros, M C

    2007-01-01

    The Mayan homeland within Mesoamerica spans five countries: Belize, El Salvador, Guatemala, Honduras and Mexico. There are indications that the people we call the Maya migrated from the north to the highlands of Guatemala as early as 4000 B.C. Their existence was village-based and agricultural. The culture of these Preclassic Mayans owes much to the earlier Olmec civilization, which flourished in the southern portion of North America. In this study, four different Mayan groups were examined to assess their genetic variability. Ten polymorphic Alu insertion (PAI) loci were employed to ascertain the genetic affinities among these Mayan groups. North American, African, European and Asian populations were also examined as reference populations. Our results suggest that the Mayan groups examined in this study are not genetically homogeneous.

  4. Alu Sb2 subfamily is present in all higher primates but was most succesfully amplified in humans

    SciTech Connect

    Richer, C.; Zietkiewicz, E.; Labuda, D.

    1994-09-01

    Alu repeats can be classified into subfamilies which amplified in primate genomes at different evolutionary time periods. A young Alu subfamily, Sb2, with a characteristic 7-nucleotide duplication at position 256, has been described in seven human loci. An Sb2 insertion found near the HD gene was unique to two HD families, indicating that Sb2 was still retropositionally active. Here, we have shown that the Sb2 insertion in the CHOL locus was similarly rare, being absent in 120 individuals of Caucasian, Oriental and Black origin. In contrast, Sb2 inserts in five other loci were found fixed (non-polymorphic), based on measurements in the same population sample, but absent from orthologous positions in higher apes. This suggest that Sb2 repeats spread relatively early in the human lineage following divergence from other primates and that these elements may be human-specific. By quantitative PCR, we investigated the presence of Sb2 sequences in different primate DNA, using one PCR primer anchored at the 5{prime} Alu-end and the other complementary to the duplicated Sb2-specific segment. With an Sb2-containing plasmid as a standard, we estimated the number of Sb2 repeats at 1500-1800 copies per human haploid equivalent; corresponding numbers in chimpanzee and gorilla were almost two orders of magnitude lower, while the signal observed in orangutan and gibbon DNAs was consistent with the presence of a single copy. The analysis of 22 human, 11 chimpanzee and 10 gorilla sequences indicates that the Alu Sb2 dispersed independently in these three primate lineages; gorilla consensus differs from the human Sb2 sequence by one position, while all chimpanzee repeats have their linker expanded by up to eight A-residues. Should they be thus considered as separate subfamilies? It is possible that sequence modifications with respect to the human consensus are responsible for poor retroposition of Sb2 in apes.

  5. Analysis of the regions flanking the human insulin gene and sequence of an Alu family member.

    PubMed Central

    Bell, G I; Pictet, R; Rutter, W J

    1980-01-01

    The regions around the human insulin gene have been studied by heteroduplex, hybridization and sequence analysis. These studies indicated that there is a region of heterogeneous length located approximately 700 bp before the 5' end of the gene; and that the 19 kb of cloned DNA which includes the 1430 bp insulin gene as well as 5650 bp before and 11,500 bp after the gene is single copy sequence except for 500 bp located 6000 bp from the 3' end of the gene. This 500 bp segment contains a member of the Alu family of dispersed middle repetitive sequences as well as another less highly repeated homopolymeric segment. The sequence of this region was determined. This Alu repeat is bordered by 19 bp direct repeats and also contains an 83 bp sequence which is present twice. The regions flanking the human and rat I insulin genes were compared by heteroduplex analysis to localize homologous sequences in the flanking regions which could be involved in the regulation of insulin biosynthesis. The homology between the two genes is restricted to the region encoding preproinsulin and a short region of approximately 60 bp flanking the 5' side of the genes. Images PMID:6253909

  6. Repeated dexamphetamine treatment alters the dopaminergic system and increases the phMRI response to methylphenidate

    PubMed Central

    Schrantee, Anouk; Tremoleda, Jordi L.; Wylezinska-Arridge, Marzena; Bouet, Valentine; Hesseling, Peter; Meerhoff, Gideon F.; de Bruin, Kora M.; Koeleman, Jan; Freret, Thomas; Boulouard, Michel; Desfosses, Emilie; Galineau, Laurent; Gozzi, Alessandro; Dauphin, François; Gsell, Willy; Booij, Jan; Lucassen, Paul J.; Reneman, Liesbeth

    2017-01-01

    Dexamphetamine (AMPH) is a psychostimulant drug that is used both recreationally and as medication for attention deficit hyperactivity disorder. Preclinical studies have demonstrated that repeated exposure to AMPH can induce damage to nerve terminals of dopamine (DA) neurons. We here assessed the underlying neurobiological changes in the DA system following repeated AMPH exposure and pre-treated rats with AMPH or saline (4 times 5 mg/kg s.c., 2 hours apart), followed by a 1-week washout period. We then used pharmacological MRI (phMRI) with a methylphenidate (MPH) challenge, as a sensitive and non-invasive in-vivo measure of DAergic function. We subsequently validated the DA-ergic changes post-mortem, using a.o. high-performance liquid chromatography (HPLC) and autoradiography. In the AMPH pre-treated group, we observed a significantly larger BOLD response to the MPH challenge, particularly in DA-ergic brain areas and their downstream projections. Subsequent autoradiography studies showed that AMPH pre-treatment significantly reduced DA transporter (DAT) density in the caudate-putamen (CPu) and nucleus accumbens, whereas HPLC analysis revealed increases in the DA metabolite homovanillic acid in the CPu. Our results suggest that AMPH pre-treatment alters DAergic responsivity, a change that can be detected with phMRI in rats. These phMRI changes likely reflect increased DA release together with reduced DAT binding. The ability to assess subtle synaptic changes using phMRI is promising for both preclinical studies of drug discovery, and for clinical studies where phMRI can be a useful tool to non-invasively investigate DA abnormalities, e.g. in neuropsychiatric disorders. PMID:28241065

  7. The use of dimorphic Alu insertions in human DNA fingerprinting

    SciTech Connect

    Novick, G.E.; Gonzalez, T.; Garrison, J.; Novick, C.C.; Herrera, R.J.; Batzer, M.A.; Deininger, P.L.

    1992-12-04

    We have characterized certain Human Specific Alu Insertions as either dimorphic (TPA25, PV92, APO), sightly dimorphic (C2N4 and C4N4) or monomorphic (C3N1, C4N6, C4N2, C4N5, C4N8), based on studies of Caucasian, Asian, American Black and African Black populations. Our approach is based upon: (1) PCR amplification using primers directed to the sequences that flank the site of insertion of the different Alu elements studied; (2) gel electrophoresis and scoring according to the presence or absence of an Alu insertion in one or both homologous chromosomes; (3) allelic frequencies calculated and compared according to Hardy-Weinberg equilibrium. Our DNA fingerprinting procedure using PCR amplification of dimorphic Human Specific Alu insertions, is stable enough to be used not only as a tool for genetic mapping but also to characterize populations, study migrational patterns and track the inheritance of human genetic disorders.

  8. Repeated cocaine exposure increases fast-spiking interneuron excitability in the rat medial prefrontal cortex.

    PubMed

    Campanac, Emilie; Hoffman, Dax A

    2013-06-01

    The medial prefrontal cortex plays a key role in cocaine addiction. However, how chronic cocaine exposure affects cortical networks remains unclear. Most studies have focused on layer 5 pyramidal neurons (the circuit output), while the response of local GABAergic interneurons to cocaine remains poorly understood. Here, we recorded from fast-spiking interneurons (FS-IN) after repeated cocaine exposure and found altered membrane excitability. After cocaine withdrawal, FS-IN showed an increase in the number of spikes evoked by positive current injection, increased input resistance, and decreased hyperpolarization-activated current. We also observed a reduction in miniature excitatory postsynaptic currents, whereas miniature inhibitory postsynaptic current activity was unaffected. We show that, in animals with cocaine history, dopamine receptor D(2) activation is less effective in increasing FS-IN intrinsic excitability. Interestingly, these alterations are only observed 1 wk or more after the last cocaine exposure. This suggests that the dampening of D(2)-receptor-mediated response may be a compensatory mechanism to rein down the excitability of FS-IN.

  9. Repeated cocaine exposure increases fast-spiking interneuron excitability in the rat medial prefrontal cortex

    PubMed Central

    Hoffman, Dax A.

    2013-01-01

    The medial prefrontal cortex plays a key role in cocaine addiction. However, how chronic cocaine exposure affects cortical networks remains unclear. Most studies have focused on layer 5 pyramidal neurons (the circuit output), while the response of local GABAergic interneurons to cocaine remains poorly understood. Here, we recorded from fast-spiking interneurons (FS-IN) after repeated cocaine exposure and found altered membrane excitability. After cocaine withdrawal, FS-IN showed an increase in the number of spikes evoked by positive current injection, increased input resistance, and decreased hyperpolarization-activated current. We also observed a reduction in miniature excitatory postsynaptic currents, whereas miniature inhibitory postsynaptic current activity was unaffected. We show that, in animals with cocaine history, dopamine receptor D2 activation is less effective in increasing FS-IN intrinsic excitability. Interestingly, these alterations are only observed 1 wk or more after the last cocaine exposure. This suggests that the dampening of D2-receptor-mediated response may be a compensatory mechanism to rein down the excitability of FS-IN. PMID:23486201

  10. Increased impulsivity in rats as a result of repeated cycles of alcohol intoxication and abstinence

    PubMed Central

    Irimia, Cristina; Wiskerke, Joost; Natividad, Luis A.; Polis, Ilham Y.; de Vries, Taco J.; Pattij, Tommy; Parsons, Loren H.

    2014-01-01

    Impulsivity is a risk factor for alcoholism and long-term alcohol exposure may further impair impulse control in a manner that propels problematic alcohol use. The present study employed the rat 5-Choice Serial Reaction Time Task (5-CSRTT) to measure behavioral inhibition and attentional capacity during abstinence from repeated 5d cycles of alcohol liquid diet consumption. Task performance was not disrupted following the first cycle of alcohol exposure, however, evidence of impaired behavioral inhibition emerged following the third cycle of alcohol exposure. In comparison with controls, alcohol rats exhibited deficits in inhibitory control during cognitively challenging 5-CSRTT tests employing variable inter-trial intervals (varITI). This behavioral disruption was not present during early abstinence (3d) but was evident by 7d abstinence and persisted for at least 34d. Interestingly, renewed alcohol consumption ameliorated these disruptions in impulse control, though deficient behavioral inhibition re-emerged during subsequent abstinence. Indices of increased impulsivity were no longer present in tests conducted after 49 days of abstinence. Alcohol-related impairments in impulse control were not evident in sessions employing highly familiar task parameters regardless of abstinence period and control experiments confirmed that performance deficits during the challenge sessions were unlikely to result from alcohol-related disruption in the adaptation to repeated varITI testing. Together, the current findings demonstrate that chronic intermittent alcohol consumption results in decreased behavioral inhibition in rats that is temporally similar to clinical observations of disrupted impulsive control in abstinent alcoholics performing tasks of behavioral inhibition. PMID:24341858

  11. Increased impulsivity in rats as a result of repeated cycles of alcohol intoxication and abstinence.

    PubMed

    Irimia, Cristina; Wiskerke, Joost; Natividad, Luis A; Polis, Ilham Y; de Vries, Taco J; Pattij, Tommy; Parsons, Loren H

    2015-03-01

    Impulsivity is a risk factor for alcoholism, and long-term alcohol exposure may further impair impulse control in a manner that propels problematic alcohol use. The present study employed the rat 5-choice serial reaction time task (5-CSRTT) to measure behavioral inhibition and attentional capacity during abstinence from repeated 5-day cycles of alcohol liquid diet consumption. Task performance was not disrupted following the first cycle of alcohol exposure; however, evidence of impaired behavioral inhibition emerged following the third cycle of alcohol exposure. In comparison with controls, alcoholic rats exhibited deficits in inhibitory control during cognitively challenging 5-CSRTT tests employing variable intertrial interval (varITI). This behavioral disruption was not present during early abstinence (3 days) but was evident by 7 days of abstinence and persisted for at least 34 days. Interestingly, renewed alcohol consumption ameliorated these disruptions in impulse control, although deficient behavioral inhibition re-emerged during subsequent abstinence. Indices of increased impulsivity were no longer present in tests conducted after 49 days of abstinence. Alcohol-related impairments in impulse control were not evident in sessions employing highly familiar task parameters regardless of the abstinence period, and control experiments confirmed that performance deficits during the challenge sessions were unlikely to result from alcohol-related disruption in the adaptation to repeated varITI testing. Together, the current findings demonstrate that chronic intermittent alcohol consumption results in decreased behavioral inhibition in rats that is temporally similar to clinical observations of disrupted impulsive control in abstinent alcoholics performing tasks of behavioral inhibition.

  12. The tandemly repeated domains of a β-propeller phytase act synergistically to increase catalytic efficiency.

    PubMed

    Li, Zhongyuan; Huang, Huoqing; Yang, Peilong; Yuan, Tiezheng; Shi, Pengjun; Zhao, Junqi; Meng, Kun; Yao, Bin

    2011-09-01

    β-Propeller phytases (BPPs) with tandemly repeated domains are abundant in nature. Previous studies have shown that the intact domain is responsible for phytate hydrolysis, but the function of the other domain is relatively unknown. In this study, a new dual-domain BPP (PhyH) from Bacillus sp. HJB17 was identified to contain an incomplete N-terminal BPP domain (PhyH-DI, residues 41-318) and a typical BPP domain (PhyH-DII, residues 319-644) at the C-terminus. Purified recombinant PhyH and PhyH-DII required Ca(2+) for phytase activity, showed activity at low temperatures (0-35 °C) and pH 6.0-8.0, and remained active (at 37 °C) after incubation at 60 °C and pH 6.0-12.0. Compared with PhyH-DII, PhyH is catalytically more active against phytate (catalytic constant 27.72 versus 4.17 s(-1)), which indicates the importance of PhyH-DI in phytate degradation. PhyH-DI was found to hydrolyze phytate intermediate D-Ins(1,4,5,6) P(4), and to act synergistically (a 1.2-2.5-fold increase in phosphate release) with PhyH-DII, other BPPs (PhyP and 168PhyA) and a histidine acid phosphatase. Furthermore, fusion of PhyH-DI with PhyP or 168PhyA significantly enhanced their catalytic efficiencies. This is the first report to elucidate the substrate specificity of the incomplete domain and the functional relationship of tandemly repeated domains in BPPs. We conjecture that dual-domain BPPs have succeeded evolutionarily because they can increase the amount of available phosphate by interacting together. Additionally, fusing PhyH-DI to a single-domain phytase appears to be an efficient way to improve the activity of the latter.

  13. Exposure to repeated immobilization stress inhibits cocaine-induced increase in dopamine extracellular levels in the rat ventral tegmental area.

    PubMed

    Sotomayor-Zárate, Ramón; Abarca, Jorge; Araya, Katherine A; Renard, Georgina M; Andrés, María E; Gysling, Katia

    2015-11-01

    A higher vulnerability to drug abuse has been observed in human studies of individuals exposed to chronic or persistent stress, as well as in animal models of drug abuse. Here, we explored the effect of repeated immobilization stress on cocaine-induced increase in dopamine extracellular levels in VTA and its regulation by corticotropin-releasing factor (CRF) and GABA systems. Cocaine (10mg/Kg i.p.) induced an increase of VTA DA extracellular levels in control rats. However, this effect was not observed in repeated stress rats. Considering the evidence relating stress with CRF, we decided to perfuse CRF and CP-154526 (selective antagonist of CRF1 receptor) in the VTA of control and repeated stress rats, respectively. We observed that perfusion of 20μM CRF inhibited the increase of VTA DA extracellular levels induced by cocaine in control rats. Interestingly, we observed that in the presence of 10μM CP-154526, cocaine induced a significant increase of VTA DA extracellular levels in repeated stress rats. Regarding the role of VTA GABA neurotransmission, cocaine administration induced a significant increase in VTA GABA extracellular levels only in repeated stress rats. Consistently, cocaine was able to increase VTA DA extracellular levels in repeated stress rats when 100μM bicuculline, an antagonist of GABAA receptor, was perfused intra VTA. Thus, both CRF and GABA systems are involved in the lack of response to cocaine in the VTA of repeated stress rats. It is tempting to suggest that the loss of response in VTA dopaminergic neurons to cocaine, after repeated stress, is due to an interaction between CRF and GABA systems.

  14. Serine-Aspartate Repeat Protein D Increases Staphylococcus aureus Virulence and Survival in Blood

    PubMed Central

    Uchiyama, Satoshi; Valderrama, J. Andrés; Ajayi, Clement; Sollid, Johanna U. E.; van Sorge, Nina M.; Nizet, Victor; van Strijp, Jos A. G.

    2016-01-01

    ABSTRACT Staphylococcus aureus expresses a panel of cell wall-anchored adhesins, including proteins belonging to the microbial surface components recognizing adhesive matrix molecule (MSCRAMM) family, exemplified by the serine-aspartate repeat protein D (SdrD), which serve key roles in colonization and infection. Deletion of sdrD from S. aureus subsp. aureus strain NCTC8325-4 attenuated bacterial survival in human whole blood ex vivo, which was associated with increased killing by human neutrophils. Remarkably, SdrD was able to inhibit innate immune-mediated bacterial killing independently of other S. aureus proteins, since addition of recombinant SdrD protein and heterologous expression of SdrD in Lactococcus lactis promoted bacterial survival in human blood. SdrD contributes to bacterial virulence in vivo, since fewer S. aureus subsp. aureus NCTC8325-4 ΔsdrD bacteria than bacteria of the parent strain were recovered from blood and several organs using a murine intravenous infection model. Collectively, our findings reveal a new property of SdrD as an important key contributor to S. aureus survival and the ability to escape the innate immune system in blood. PMID:27795358

  15. [Utility of chromosome banding with ALU I enzyme for identifying methylated areas in breast cancer].

    PubMed

    Rojas-Atencio, Alicia; Yamarte, Leonard; Urdaneta, Karelis; Soto-Alvarez, Marisol; Alvarez Nava, Francisco; Cañizalez, Jenny; Quintero, Maribel; Atencio, Raquel; González, Richard

    2012-12-01

    Cancer is a group of disorders characterized by uncontrolled cell growth which is produced by two successive events: increased cell proliferation (tumor or neoplasia) and the invasive capacity of these cells (metastasis). DNA methylation is an epigenetic process which has been involved as an important pathogenic factor of cancer. DNA methylation participates in the regulation of gene expression, directly, by preventing the union of transcription factors, and indirectly, by promoting the "closed" structure of the chromatine. The objectives of this study were to identify hypermethyled chromosomal regions through the use of restriction Alu I endonuclease, and to relate cytogenetically these regions with tumor suppressive gene loci. Sixty peripheral blood samples of females with breast cancer were analyzed. Cell cultures were performed and cytogenetic spreads, previously digested with Alu I enzyme, were stained with Giemsa. Chromosomal centromeric and not centromeric regions were stained in 37% of cases. About 96% of stained hypermethyled chromosomal regions (1q, 2q, 6q) were linked with methylated genes associated with breast cancer. In addition, centromeric regions in chromosomes 3, 4, 8, 13, 14, 15 and 17, usually unstained, were found positive to digestion with Alu I enzime and Giemsa staining. We suggest the importance of this technique for the global visualization of the genome which can find methylated genes related to breast cancer, and thus lead to a specific therapy, and therefore a better therapeutic response.

  16. Threshold frequency of an electrically induced cramp increases following a repeated, localized fatiguing exercise.

    PubMed

    Stone, Marcus B; Edwards, Jeffrey E; Huxel, Kellie C; Cordova, Mitchell L; Ingersoll, Christopher D; Babington, J Patrick

    2010-02-01

    Though clinical observations and laboratory data provide some support for the neuromuscular imbalance theory of the genesis of exercise-associated muscle cramps, no direct evidence has been published. The purpose of this study was to determine the effect of local muscle fatigue on the threshold frequency of an electrically induced muscle cramp. To determine baseline threshold frequency, a cramp was electrically induced in the flexor hallucis brevis of 16 apparently healthy participants (7 males, 9 females; age 25.1 +/- 4.8 years). The testing order of control and fatigue conditions was counterbalanced. In the control condition, participants rested in a supine position for 30 min followed by another cramp induction to determine post-threshold frequency. In the fatigue condition, participants performed five bouts of great toe curls at 60% one-repetition maximum to failure with 1 min rest between bouts followed immediately by a post-threshold frequency measurement. Repeated-measures analysis of variance and simple main effects testing showed post-fatigue threshold frequency (32.9 +/- 11.7 Hz) was greater (P < 0.001) than pre-fatigue threshold frequency (20.0 +/- 7.7 Hz). An increase in threshold frequency seems to demonstrate a decrease in one's propensity to cramp following the fatigue exercise regimen used. These results contradict the proposed theory that suggests cramp propensity should increase following fatigue. However, differences in laboratory versus clinical fatiguing exercise and contributions from other sources, as well as the notion of a graded response to fatiguing exercise, on exercise-associated muscle cramp and electrically induced muscle cramp should be considered.

  17. Repeated Social Stress Increases Reward Salience and Impairs Encoding of Prediction by Rat Locus Coeruleus Neurons

    PubMed Central

    Chaijale, Nayla N; Snyder, Kevin; Arner, Jay; Curtis, Andre L; Valentino, Rita J

    2015-01-01

    Stress is implicated in psychopathology characterized by cognitive dysfunction. Cognitive responses to stress are regulated by the locus coeruleus–norepinephrine (LC–NE) system. As social stress is a prevalent human stressor, this study determined the impact of repeated social stress on the relationship between LC neuronal activity and behavior during the performance of cognitive tasks. Social stress-exposed rats performed better at intradimensional set shifting (IDS) and made fewer perseverative errors during reversal learning (REV). LC neurons of control rats were task responsive, being activated after the choice and before reward. Social stress shifted LC neuronal activity from being task responsive to being reward responsive during IDS and REV. LC neurons of stressed rats were activated by reward and tonically inhibited by reward omission with incorrect choices. In contrast, LC neurons of stress-naive rats were only tonically inhibited by reward omission. Reward-related LC activation in stressed rats was unrelated to predictability because it did not habituate as learning progressed. The findings suggest that social stress history increases reward salience and impairs processes that compute predictability for LC neurons. These effects of social stress on LC neuronal activity could facilitate learning as indicated by improved performance in stressed rats. However, the ability of social stress history to enhance responses to behavioral outcomes may have a role in the association between stress and addictive behaviors. In addition, magnified fluctuations in LC activity in response to opposing behavioral consequences may underlie volatile changes in emotional arousal that characterize post-traumatic stress disorder. PMID:25109891

  18. Repeated social stress increases reward salience and impairs encoding of prediction by rat locus coeruleus neurons.

    PubMed

    Chaijale, Nayla N; Snyder, Kevin; Arner, Jay; Curtis, Andre L; Valentino, Rita J

    2015-01-01

    Stress is implicated in psychopathology characterized by cognitive dysfunction. Cognitive responses to stress are regulated by the locus coeruleus-norepinephrine (LC-NE) system. As social stress is a prevalent human stressor, this study determined the impact of repeated social stress on the relationship between LC neuronal activity and behavior during the performance of cognitive tasks. Social stress-exposed rats performed better at intradimensional set shifting (IDS) and made fewer perseverative errors during reversal learning (REV). LC neurons of control rats were task responsive, being activated after the choice and before reward. Social stress shifted LC neuronal activity from being task responsive to being reward responsive during IDS and REV. LC neurons of stressed rats were activated by reward and tonically inhibited by reward omission with incorrect choices. In contrast, LC neurons of stress-naive rats were only tonically inhibited by reward omission. Reward-related LC activation in stressed rats was unrelated to predictability because it did not habituate as learning progressed. The findings suggest that social stress history increases reward salience and impairs processes that compute predictability for LC neurons. These effects of social stress on LC neuronal activity could facilitate learning as indicated by improved performance in stressed rats. However, the ability of social stress history to enhance responses to behavioral outcomes may have a role in the association between stress and addictive behaviors. In addition, magnified fluctuations in LC activity in response to opposing behavioral consequences may underlie volatile changes in emotional arousal that characterize post-traumatic stress disorder.

  19. Cellular inhibitors of long interspersed element 1 and Alu retrotransposition.

    PubMed

    Bogerd, Hal P; Wiegand, Heather L; Hulme, Amy E; Garcia-Perez, José L; O'Shea, K Sue; Moran, John V; Cullen, Bryan R

    2006-06-06

    Long interspersed element (LINE) 1 retrotransposons are major genomic parasites that represent approximately 17% of the human genome. The LINE-1 ORF2 protein is also responsible for the mobility of Alu elements, which constitute a further approximately 11% of genomic DNA. Representative members of each element class remain mobile, and deleterious retrotransposition events can induce spontaneous genetic diseases. Here, we demonstrate that APOBEC3A and APOBEC3B, two members of the APOBEC3 family of human innate antiretroviral resistance factors, can enter the nucleus, where LINE-1 and Alu reverse transcription occurs, and specifically inhibit both LINE-1 and Alu retrotransposition. These data suggest that the APOBEC3 protein family may have evolved, at least in part, to defend the integrity of the human genome against endogenous retrotransposons.

  20. Alu sequences in undifferentiated human embryonic stem cells display high levels of A-to-I RNA editing.

    PubMed

    Osenberg, Sivan; Paz Yaacov, Nurit; Safran, Michal; Moshkovitz, Sharon; Shtrichman, Ronit; Sherf, Ofra; Jacob-Hirsch, Jasmine; Keshet, Gilmor; Amariglio, Ninette; Itskovitz-Eldor, Joseph; Rechavi, Gideon

    2010-06-21

    Adenosine to Inosine (A-to-I) RNA editing is a site-specific modification of RNA transcripts, catalyzed by members of the ADAR (Adenosine Deaminase Acting on RNA) protein family. RNA editing occurs in human RNA in thousands of different sites. Some of the sites are located in protein-coding regions but the majority is found in non-coding regions, such as 3'UTRs, 5'UTRs and introns - mainly in Alu elements. While editing is found in all tissues, the highest levels of editing are found in the brain. It was shown that editing levels within protein-coding regions are increased during embryogenesis and after birth and that RNA editing is crucial for organism viability as well as for normal development. In this study we characterized the A-to-I RNA editing phenomenon during neuronal and spontaneous differentiation of human embryonic stem cells (hESCs). We identified high editing levels of Alu repetitive elements in hESCs and demonstrated a global decrease in editing levels of non-coding Alu sites when hESCs are differentiating, particularly into the neural lineage. Using RNA interference, we showed that the elevated editing levels of Alu elements in undifferentiated hESCs are highly dependent on ADAR1. DNA microarray analysis showed that ADAR1 knockdown has a global effect on gene expression in hESCs and leads to a significant increase in RNA expression levels of genes involved in differentiation and development processes, including neurogenesis. Taken together, we speculate that A-to-I editing of Alu sequences plays a role in the regulation of hESC early differentiation decisions.

  1. An Alu-derived intronic splicing enhancer facilitates intronic processing and modulates aberrant splicing in ATM.

    PubMed

    Pastor, Tibor; Talotti, Gabriele; Lewandowska, Marzena Anna; Pagani, Franco

    2009-11-01

    We have previously reported a natural GTAA deletion within an intronic splicing processing element (ISPE) of the ataxia telangiectasia mutated (ATM) gene that disrupts a non-canonical U1 snRNP interaction and activates the excision of the upstream portion of the intron. The resulting pre-mRNA splicing intermediate is then processed to a cryptic exon, whose aberrant inclusion in the final mRNA is responsible for ataxia telangiectasia. We show here that the last 40 bases of a downstream intronic antisense Alu repeat are required for the activation of the cryptic exon by the ISPE deletion. Evaluation of the pre-mRNA splicing intermediate by a hybrid minigene assay indicates that the identified intronic splicing enhancer represents a novel class of enhancers that facilitates processing of splicing intermediates possibly by recruiting U1 snRNP to defective donor sites. In the absence of this element, the splicing intermediate accumulates and is not further processed to generate the cryptic exon. Our results indicate that Alu-derived sequences can provide intronic splicing regulatory elements that facilitate pre-mRNA processing and potentially affect the severity of disease-causing splicing mutations.

  2. A novel PCR technique using Alu-specific primers to identify unknown flanking sequences from the human genome

    SciTech Connect

    Minami, M.; Poussin, K.; Brechot, C.; Paterlini, P.

    1995-09-20

    The rapid and reproducible identification of new cellular DNA sequences is difficult to achieve with the currently available procedures. Here we describe a novel approach based on the polymerase chain reaction (PCR) using a primer specific to the known sequence and another directed to a human Alu repeat. To avoid undesirable amplifications between Alu sequences, primers are constructed with dUTPs and destroyed by uracil DNA glycosylase treatment after 10 initial cycles of amplification. Only desirable fragments are then further amplified with specific primers to the known region and to a tag sequence introduced in the Alu-specific primer. Using this protocol, we have successfully indentified cellular sequences flanking integrated hepatitis B virus DNA from the human genome of three hepatoma tissues. The method enables a direct specific amplification without any ligation or nonspecific annealing steps as required by previous PCR-based protocols. This rapid and straightforward approach will be a powerful tool for the study of viral integration sites, but is also widely applicable to other studies of the human genome. 39 refs., 4 figs.

  3. Association of AluYb8 insertion/deletion polymorphism in the MUTYH gene with mtDNA maintain in the type 2 diabetes mellitus patients.

    PubMed

    Guo, Wenwen; Zheng, Bixia; Guo, Dong; Cai, Zhenming; Wang, Yaping

    2015-07-05

    A common AluYb8-element insertion/deletion polymorphism of the MUTYH gene (AluYb8MUTYH) is a novel genetic risk factor for type 2 diabetes mellitus (T2DM). In the present study, mtDNA sequencing analysis indicated that the mtDNA sequence heteroplasmy was not associated with AluYb8MUTYH polymorphism. To better understand the genetic risk for T2DM, we investigated the association of this polymorphism with mtDNA content, mtDNA breakage and mtDNA transcription in the leukocytes of T2DM patients. The mtDNA content and unbroken mtDNA were significantly increased in the mutant patients than in the wild-type patients (P <0.05, respectively). However, no association between mtDNA transcription and AluYb8MUTYH variant was observed. The results suggested that the AluYb8MUTYH variant was associated with an altered mtDNA maintain in T2DM patients. The high level of mtDNA content observed in the mutant patients may have resulted from inefficient base excision repair of mitochondrial MUTYH and a compensatory mechanism that is triggered by elevated oxidative stress.

  4. DNA sequences of Alu elements indicate a recent replacement of the human autosomal genetic complement

    SciTech Connect

    Knight, A.; Deininger, P.L.; Batzer, M.A.

    1996-04-30

    DNA sequences of neutral nuclear autosomal loci, compared across diverse human populations, provide a previously untapped perspective into the mode and tempo of the emergence of modern humans and a critical comparison with published clonally inherited mitochondrial DNA and Y chromosome measurements of human diversity. We obtained over 55 kilobases of sequence from three autosomal loci encompassing Alu repeats for representatives of diverse human populations as well as orthologous sequences for other hominoid species at one of these loci. Nucleotide diversity was exceedingly low. Most individuals and populations were identical. Only a single nucleotide difference distinguished presumed ancestral alleles from descendants. These results differ from those expected if alleles from divergent archaic populations were maintained through multiregional continuity. The observed virtual lack of sequence polymorphism is the signature of a recent single origin for modern humans, with general replacement of archaic populations. 47 refs., 2 figs., 1 tab.

  5. Repeated ischaemic isometric exercise increases muscle fibre conduction velocity in humans: involvement of Na+-K+-ATPase

    PubMed Central

    Rongen, G A; van Dijk, J P; van Ginneken, E E; Stegeman, D F; Smits, P; Zwarts, M J

    2002-01-01

    This study was performed to test two hypotheses: (1) ischaemic preconditioning (development of tolerance to ischaemia) influences muscle fibre conduction velocity (MFCV) during repeated ischaemic isometric exercise and (2) the increase in MFCV to supranormal levels during recovery from ischaemic exercise is caused by activation of Na+−K+-ATPase. For this purpose, MFCV was measured with surface electromyography (sEMG) during repeated ischaemic isometric exercise of the brachioradial muscle (2 min at 30 % of maximal voluntary contraction). The involvement of ischaemic preconditioning was tested by changing the duration of ischaemia and by intra-arterial infusion of adenosine (brachial artery, 50 μg min−1 dl−1). The role of Na+−K+-ATPase was explored using ouabain (0.2 μg min−1 dl−1). During the exercise, MFCV decreased from 4.4 ± 0.2 m s−1 to 3.7 ± 0.2 m s−1 (P < 0.01, n = 13). Similar reductions in MFCV were observed during repeated exercise, irrespective of the reperfusion time (10 min vs. 18 min) or duration of the ischaemia (2 vs. 10 min). However, initial MFCV gradually increased for each subsequent contraction when contractions were repeated at 10 min intervals (4.4 ± 0.2 m s−1vs. 4.9 ± 0.2 m s−1 for the first and fourth contraction respectively; P < 0.01; n = 13). This increase was not observed when contractions were performed at 18 min intervals, nor when additional ischaemia was applied. Intra-arterial adenosine did not affect MFCV. Intra-arterial ouabain did not affect the reduction in MFCV during exercise but completely prevented the increase in MFCV during recovery: from 4.7 ± 0.2 m s−1 to 5.2 ± 0.2 m s−1vs. 4.5 ± 0.1 m s−1 to 4.5 ± 0.1 m s−1 in the absence and presence of ouabain respectively (P < 0.05 for ouabain effect; n = 6). In conclusion, ischaemic preconditioning is not involved in changes in MFCV during repeated ischaemic isometric exercise. The increase in MFCV during recovery from repeated ischaemic

  6. Increases in fruit intakes in older low consumers of fruit following two community-based repeated exposure interventions.

    PubMed

    Appleton, K M

    2013-03-14

    The present study investigated the value of two repeated exposure interventions for increasing intakes of fruit in older people. A total of ninety-five participants (aged 65 years and over) were randomised to receive either one (E1), five (E5) or five plus (E5+) exposures to fruit over a 5-week period. Fruit exposures occurred in community-based church and social groups, through fruit-tasting sessions involving familiar fruits and novel fruit products and dishes (E1, E5, E5+), and through fruit provision (E5+). Daily intakes of fruit and vegetables were assessed before and after all interventions. Liking for all fruits was also measured during repeated exposure (E5, E5+). In low consumers of fruit (one portion/d or less), fruit intakes increased significantly in the repeated exposure groups (E5, E5+) (t(30) = 5·79, P< 0·01), but did not change in the E1 group (t(16) = 0·29, P= 0·78). No differences were found between E5 and E5+ groups (F(3,87) = 1·22, P= 0·31). Similar effects were also found in fruit and vegetable intakes. No effects were found in other participants. Also, no changes in liking were found. These findings suggest that compared to single exposure, repeated exposure to fruit via fruit-tasting sessions once per week for 5 weeks in a community setting significantly improved fruit intakes, and fruit and vegetable intakes in older low consumers of fruit, although no benefits of additional fruit provision were found. Repeated exposure was also easy to implement, of low cost and enjoyable.

  7. Methylation status of individual CpG sites within Alu elements in the human genome and Alu hypomethylation in gastric carcinomas

    PubMed Central

    2010-01-01

    Background Alu methylation is correlated with the overall level of DNA methylation and recombination activity of the genome. However, the maintenance and methylation status of each CpG site within Alu elements (Alu) and its methylation status have not well characterized. This information is useful for understanding natural status of Alu in the genome and helpful for developing an optimal assay to quantify Alu hypomethylation. Methods Bisulfite clone sequencing was carried out in 14 human gastric samples initially. A Cac8I COBRA-DHPLC assay was developed to detect methylated-Alu proportion in cell lines and 48 paired gastric carcinomas and 55 gastritis samples. DHPLC data were statistically interpreted using SPSS version 16.0. Results From the results of 427 Alu bisulfite clone sequences, we found that only 27.2% of CpG sites within Alu elements were preserved (4.6 of 17 analyzed CpGs, A ~ Q) and that 86.6% of remaining-CpGs were methylated. Deamination was the main reason for low preservation of methylation targets. A high correlation coefficient of methylation was observed between Alu clones and CpG site J (0.963), A (0.950), H (0.946), D (0.945). Comethylation of the sites H and J were used as an indicator of the proportion of methylated-Alu in a Cac8I COBRA-DHPLC assay. Validation studies showed that hypermethylation or hypomethylation of Alu elements in human cell lines could be detected sensitively by the assay after treatment with 5-aza-dC and M.SssI, respectively. The proportion of methylated-Alu copies in gastric carcinomas (3.01%) was significantly lower than that in the corresponding normal samples (3.19%) and gastritis biopsies (3.23%). Conclusions Most Alu CpG sites are deaminated in the genome. 27% of Alu CpG sites represented in our amplification products. 87% of the remaining CpG sites are methylated. Alu hypomethylation in primary gastric carcinomas could be detected with the Cac8I COBRA-DHPLC assay quantitatively. PMID:20163738

  8. Markedly reduced activity of mutant calcium-sensing receptor with an inserted Alu element from a kindred with familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism.

    PubMed Central

    Bai, M; Janicic, N; Trivedi, S; Quinn, S J; Cole, D E; Brown, E M; Hendy, G N

    1997-01-01

    Missense mutations have been identified in the coding region of the extracellular calcium-sensing receptor (CASR) gene and cause human autosomal dominant hypo- and hypercalcemic disorders. The functional effects of several of these mutations have been characterized in either Xenopus laevis oocytes or in human embryonic kidney (HEK293) cells. All of the mutations that have been examined to date, however, cause single putative amino acid substitutions. In this report, we studied a mutant CASR with an Alu-repetitive element inserted at codon 876, which was identified in affected members of families with the hypercalcemic disorders, familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), to understand how this insertion affects CASR function. After cloning of the Alu-repetitive element into the wild-type CASR cDNA, we transiently expressed the mutant receptor in HEK293 cells. Expression of mutant and wild-type receptors was assessed by Western analysis, and the effects of the mutation on extracellular calcium (Ca2+(o)) and gadolinium (Gd3+(o)) elicited increases in the cytosolic calcium concentration (Ca2+(i)) were examined in fura-2-loaded cells using dual wavelength fluorimetry. The insertion resulted in truncated receptor species that had molecular masses some 30 kD less than that of the wild-type CASR and exhibited no Ca2+(i) responses to either Ca2+(o) or Gd3+(o). A similar result was observed with a mutated CASR truncated at residue 876. However, the Alu mutant receptor had no impact on the function of the coexpressed wild-type receptor. Interestingly, the Alu mutant receptor demonstrated decreased cell surface expression relative to the wild-type receptor, whereas the CASR (A877stop) mutant exhibited increased cell surface expression. Thus, like the missense mutations that have been characterized to date in families with FHH, the Alu insertion in this family is a loss-of-function mutation that produces hypercalcemia by

  9. Does a Repeated Guided-Instruction Approach with Multiple Assessments Increase Student Learning of Science?

    ERIC Educational Resources Information Center

    Smith, Robert; Peethambaran, Bela; Pontiggia, Laura; Blumberg, Phyllis

    2013-01-01

    Guided instruction is an approach that fully explains the concepts and procedures that students are required to learn. It seems intuitive that this approach should increase student learning; however, there is evidence in the literature that this may not always be the case. We wanted to assess the effectiveness of our own repeated…

  10. Repeated burning of eastern tallgrass prairie increases richness and diversity, stabilizing late successional vegetation.

    PubMed

    Bowles, Marlin L; Jones, Michael D

    2013-03-01

    Understanding temporal effects of fire frequency on plant species diversity and vegetation structure is critical for managing tallgrass prairie (TGP), which occupies a mid-continental longitudinal precipitation and productivity gradient. Eastern TGP has contributed little information toward understanding whether vegetation-fire interactions are uniform or change across this biome. We resampled 34 fire-managed mid- and late-successional ungrazed TGP remnants occurring across a dry to wet-mesic moisture gradient in the Chicago region of Illinois, USA. We compared hypotheses that burning acts either as a stabilizing force or causes change in diversity and structure, depending upon fire frequency and successional stage. Based on western TGP, we expected a unimodal species richness distribution across a cover-productivity gradient, variable functional group responses to fire frequency, and a negative relationship between fire frequency and species richness. Species diversity was unimodal across the cover gradient and was more strongly humpbacked in stands with greater fire frequency. In support of a stabilizing hypothesis, temporal similarity of late-successional vegetation had a logarithmic relationship with increasing fire frequency, while richness and evenness remained stable. Temporal similarity within mid-successional stands was not correlated with fire frequency, while richness increased and evenness decreased over time. Functional group responses to fire frequency were variable. Summer forb richness increased under high fire frequency, while C4 grasses, spring forbs, and nitrogen-fixing species decreased with fire exclusion. On mesic and wet-mesic sites, vegetation structure measured by the ratio of woody to graminoid species was negatively correlated with abundance of forbs and with fire frequency. Our findings that species richness responds unimodally to an environmental-productivity gradient, and that fire exclusion increases woody vegetation and leads to loss

  11. Detecting Alu insertions from high-throughput sequencing data

    PubMed Central

    David, Matei; Mustafa, Harun; Brudno, Michael

    2013-01-01

    High-throughput sequencing technologies have allowed for the cataloguing of variation in personal human genomes. In this manuscript, we present alu-detect, a tool that combines read-pair and split-read information to detect novel Alus and their precise breakpoints directly from either whole-genome or whole-exome sequencing data while also identifying insertions directly in the vicinity of existing Alus. To set the parameters of our method, we use simulation of a faux reference, which allows us to compute the precision and recall of various parameter settings using real sequencing data. Applying our method to 100 bp paired Illumina data from seven individuals, including two trios, we detected on average 1519 novel Alus per sample. Based on the faux-reference simulation, we estimate that our method has 97% precision and 85% recall. We identify 808 novel Alus not previously described in other studies. We also demonstrate the use of alu-detect to study the local sequence and global location preferences for novel Alu insertions. PMID:23921633

  12. Repeat work bouts increase thermal strain for Australian firefighters working in the heat

    PubMed Central

    Walker, Anthony; Argus, Christos; Driller, Matthew; Rattray, Ben

    2015-01-01

    Background: Firefighters regularly re-enter fire scenes during long duration emergency events with limited rest between work bouts. It is unclear whether this practice is impacting on the safety of firefighters. Objectives:To evaluate the effects of multiple work bouts on firefighter physiology, strength, and cognitive performance when working in the heat. Methods: Seventy-seven urban firefighters completed two 20-minute simulated search and rescue tasks in a heat chamber (105 ± 5°C), separated by a 10-minute passive recovery. Core and skin temperature, rate of perceived exertion (RPE), thermal sensation (TS), grip strength, and cognitive changes between simulations were evaluated. Results: Significant increases in core temperature and perceptual responses along with declines in strength were observed following the second simulation. No differences for other measures were observed. Conclusions: A significant increase in thermal strain was observed when firefighters re-entered a hot working environment. We recommend that longer recovery periods or active cooling methods be employed prior to re-entry. PMID:25849044

  13. Fentanyl, clonidine, and repeated increases in desflurane concentration, but not nitrous oxide or esmolol, block the transient mydriasis caused by rapid increases in desflurane concentration.

    PubMed

    Daniel, M; Larson, M D; Eger, E I; Noorani, M; Weiskopf, R B

    1995-08-01

    Initial, but not subsequent, inhalation of 8% desflurane produces transient sympathetic stimulation. We hypothesized that initial but not subsequent increases should produce pupil dilation, and that N2O, fentanyl, and clonidine, but not esmolol, should blunt the response. In 10 volunteers, we maintained anesthesia with 4% end-tidal desflurane in oxygen for 32 min, then increased the concentration to 8% for 10 min. In nine of the volunteers, we twice repeated the increase to 8%, separating each increase by a 32-min period at 4%. On separate days, five volunteers received 4%-8% desflurane in 60% N2O; five received fentanyl 1.5 micrograms/kg or 4.5 micrograms/kg intravenously 5 min before 4%-8% desflurane; four received clonidine 4.3 micrograms/kg, orally, 90 min before 4% to 8%; and four received esmolol 0.75 mg/kg, intravenously, 1.5 min before 4%-8%. Without other drugs present, 4%-8% desflurane transiently increased pupil diameter to 5.4 +/- 0.5 mm (mean +/- SD), with subsequent 4%-8% increases producing attenuated responses (2.9 +/- 1.5 and 3.2 +/- 1.8 mm). N2O produced a higher peak (6.2 +/- 0.7 mm). Fentanyl 1.5 micrograms/kg and 4.5 micrograms/kg decreased peak diameter (2.3 +/- 0.9 and 1.6 +/- 0.3 mm), as did clonidine (2.3 +/- 1.7 mm) but not esmolol. We conclude that, concurrent with sympathetic stimulation, an initial rapid increase in desflurane concentration transiently increases pupil diameter, whereas repeated increases produce attenuated responses. N2O augments, fentanyl and clonidine attenuate, and esmolol does not affect the response.

  14. Increased Length of Long Terminal Repeats Inhibits Ty1 Transposition and Leads to the Formation of Tandem Multimers

    PubMed Central

    Lauermann, V.; Hermankova, M.; Boeke, J. D.

    1997-01-01

    The Ty1 retrotransposon of Saccharomyces cerevisiae is bounded by long-terminal repeats (LTRs). We have constructed a variety of Ty1 elements in which the LTR length has been increased from the normal length of 334 bp to >2 kb. Although small insertions in the LTR have minimal effects on transposition frequency, larger insertions dramatically reduce it. Nevertheless, elements with long LTRs are incorporated into the genome at a low frequency. Most of these rare insertion events represent Ty1 tandem (head to tail) multimers. PMID:9093846

  15. Genetic change in the polynesian population of Easter Island: evidence from Alu insertion polymorphisms.

    PubMed

    González-Pérez, E; Esteban, E; Via, M; García-Moro, C; Hernández, M; Moral, P

    2006-11-01

    The origin of Pacific islanders is still an open issue in human population genetics. To address this topic we analyzed a set of 18 Alu insertion polymorphisms in a total of 176 chromosomes from native Easter Island inhabitants (Rapanui). Available genealogical records allowed us to subdivide the total island sample into two groups, representative of the native population living in the island around 1900, and another formed by individuals with some ancestors of non-Rapanui origin. Significant genetic differentiation was found between these groups, allowing us to make some biodemographic and historical inferences about the origin and evolution of this geographically isolated island population. Our data are consistent with equivalent and recent contributions from Amerindian and European migrants to the 1900s Rapanui population, with an accelerated increase in the European gene flow during the 20(th) century, especially since the 1960s. Comparative analysis of our results with other available Alu variation data on neighbouring populations supports the "Voyaging Corridor" model of Polynesian human settlement, which indicates that pre-Polynesians are mainly derived from Southeast Asian and Wallacean populations rather than from Taiwan or the Philippines. This study underlines the importance of sampling and taking into account historical information in genetic studies to unravel the recent evolution of human populations.

  16. Iron toxicity in the retina requires Alu RNA and the NLRP3 inflammasome

    PubMed Central

    Gelfand, Bradley D.; Wright, Charles B.; Kim, Younghee; Yasuma, Tetsuhiro; Yasuma, Reo; Li, Shengjian; Fowler, Benjamin J.; Bastos-Carvalho, Ana; Kerur, Nagaraj; Uittenbogaard, Annette; Han, Youn Seon; Lou, Dingyuan; Kleinman, Mark E.; McDonald, W. Hayes; Núñez, Gabriel; Georgel, Philippe; Dunaief, Joshua L.; Ambati, Jayakrishna

    2015-01-01

    Excess iron induces tissue damage and is implicated in age-related macular degeneration (AMD). Iron toxicity is widely attributed to hydroxyl radical formation through Fenton's reaction. We report that excess iron, but not other Fenton catalytic metals, induces activation of the NLRP3 inflammasome, a pathway also implicated in AMD. Additionally, iron-induced degeneration of the retinal pigmented epithelium (RPE) is suppressed in mice lacking inflammasome components Caspase-1/11 or Nlrp3 or by inhibition of Caspase-1. Iron overload increases abundance of RNAs transcribed from short interspersed nuclear elements (SINEs): Alu RNAs and the rodent equivalent B1 and B2 RNAs, which are inflammasome agonists. Targeting Alu or B2 RNA prevents iron-induced inflammasome activation and RPE degeneration. Iron-induced SINE RNA accumulation is due to suppression of DICER1 via sequestration of the co-factor poly(C)-binding protein 2 (PCBP2). These findings reveal an unexpected mechanism of iron toxicity, with implications for AMD and neurodegenerative diseases associated with excess iron. PMID:26074074

  17. Increased 5-HT Levels Following Repeated Administration of Nigella sativa L. (Black Seed) Oil Produce Antidepressant Effects in Rats

    PubMed Central

    Perveen, Tahira; Haider, Saida; Zuberi, Nudrat Anwar; Saleem, Sadia; Sadaf, Sana; Batool, Zehra

    2014-01-01

    The seeds of Nigella sativa L., commonly known as black seed or black cumin, and its extracts are used in folk medicine in the Middle East and in Asian countries for the promotion of good health and as a remedy for many ailments. These seeds have many acclaimed medicinal properties such as broncho-dilatory, immunopotentiating, analgesic, anti-inflammatory, and hypotensive. In the present study, the antidepressant activity following the repeated administration of Nigella sativa L. oil has been monitored using the forced swim test. Rats treated with Nigella sativa L. oil exhibited a significant increase in struggling time after oral administration of Nigella sativa L. oil (0.1 ml/kg/day) for four weeks. Nigella sativa L. oil increased brain 5-HT levels and decreased 5-HT turnover (5-HT/5-HIAA ratio). Levels of tryptophan increased significantly in the brain and plasma following the repeated administration of Nigella sativa L. oil. Nigella sativa L. oil showed a potential antidepressant-like effect. PMID:24634848

  18. Threshold concentration of ozone causing an increase in bronchial reactivity in humans and adaptation with repeated exposures

    SciTech Connect

    Dimeo, M.J.; Glenn, M.G.; Holtzman, M.J.; Sheller, J.R.; Nadel, J.A.; Boushey, H.A.

    1981-09-01

    To determine the lowest concentration of ozone that causes an increase in bronchial reactivity to histamine and to determine whether adaptation to this effect of ozone develops with repeated exposures, we studied 19 healthy adult subjects. Bronchial reactivity was assessed by measuring the rise in specific airway resistance (delta SRaw) produced by inhalation of 10 breaths of histamine aerosol (1.6% solution). Results indicate that the threshold concentration of ozone causing an increase in bronchial reactivity in healthy human subjects is between 0.2 and 0.4 ppm, and that adaptation to this effect of ozone develops with repeated exposures. The threshold concentration of ozone identified in other studies as causing changes in symptoms, lung volumes, or airway resistance was also between 0.2 and 0.4 ppm, and the time course of the development of tolerance to ozone in these other studies was similar to hat observed in our study. We propose that the appearance of symptoms, changes in pulmonary function, and the increase in bronchial reactivity may be caused by a change in the activity of afferent nerve endings in the airway epithelium.

  19. Repeat traumatic brain injury in the juvenile rat is associated with increased axonal injury and cognitive impairments.

    PubMed

    Prins, M L; Hales, A; Reger, M; Giza, C C; Hovda, D A

    2010-01-01

    Among the enormous population of head-injured children and young adults are a growing subpopulation who experience repeat traumatic brain injury (RTBI). The most common cause of RTBI in this age group is sports-related concussions, and athletes who have experienced a head injury are at greater risk for subsequent TBI, with consequent long-term cognitive dysfunction. While several animal models have been proposed to study RTBI, they have been shown to either produce injuries too severe, were conducted in adults, involved craniotomy, or failed to show behavioral deficits. A closed head injury model for postnatal day 35 rats was established, and single and repeat TBI (1-day interval) were examined histologically for axonal injury and behaviorally by the novel object recognition (NOR) task. The results from the current study demonstrate that an experimental closed head injury in the rodent with low mortality rates and absence of gross pathology can produce measurable cognitive deficits in a juvenile age group. The introduction of a second injury 24 h after the first impact resulted in increased axonal injury, astrocytic reactivity and increased memory impairment in the NOR task. The histological evidence demonstrates the potential usefulness of this RTBI model for studying the impact and time course of RTBI as it relates to the pediatric and young adult population. This study marks the first critical step in experimentally addressing the consequences of concussions and the cumulative effects of RTBI in the developing brain.

  20. Repeated Administration of Korea Red Ginseng Extract Increases Non-Rapid Eye Movement Sleep via GABAAergic Systems.

    PubMed

    Lee, Chung-Il; Kim, Chung-Soo; Han, Jin-Yi; Oh, Eun-Hye; Oh, Ki-Wan; Eun, Jae Soon

    2012-10-01

    The current inquiry was conducted to assess the change in sleep architecture after long periods of administration to determine whether ginseng can be used in the therapy of sleeplessness. Following post-surgical recovery, red ginseng extract (RGE, 200 mg/ kg) was orally administrated to rats for 9 d. Data were gathered on the 1st, 5th, and 9th day, and an electroencephalogram was recorded 24 h after RGE administration. Polygraphic signs of unobstructed sleep-wake activities were simultaneously recorded with sleep-wake recording electrodes from 11:00 a.m. to 5:00 p.m. for 6 h. Rodents were generally tamed to freely moving polygraphic recording conditions. Although the 1st and 5th day of RGE treatment showed no effect on power densities in non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, the 9th day of RGE administration showed augmented α-wave (8.0 to 13.0 Hz) power densities in NREM and REM sleep. RGE increased total sleep and NREM sleep. The total percentage of wakefulness was only decreased on the 9th day, and the number of sleep-wake cycles was reduced after the repeated administration of RGE. Thus, the repeated administration of RGE increased NREM sleep in rats. The α-wave activities in the cortical electroencephalograms were increased in sleep architecture by RGE. Moreover, the levels of both α- and β-subunits of the γ-aminobutyric acid (GABA)A receptor were reduced in the hypothalamus of the RGE-treated groups. The level of glutamic acid decarboxylase was over-expressed in the hypothalamus. These results demonstrate that RGE increases NREM sleep via GABAAergic systems.

  1. Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium.

    PubMed

    Sobajima, Mitsuo; Nozawa, Takashi; Shida, Takuya; Ohori, Takashi; Suzuki, Takayuki; Matsuki, Akira; Inoue, Hiroshi

    2011-08-01

    Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P < 0.01) and end-systolic (8.6 ± 0.5 vs. 9.6 ± 0.6 mm, P < 0.01) dimensions and attenuated MI-induced increases in LV end-diastolic pressure. Cross-sectional areas of cardiomyocytes were smaller in ST rats and associated with a significant reduction in myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.

  2. Risk of Anterior Cruciate Ligament Fatigue Failure Is Increased by Limited Internal Femoral Rotation During In Vitro Repeated Pivot Landings

    PubMed Central

    Beaulieu, Mélanie L.; Wojtys, Edward M.; Ashton-Miller, James A.

    2015-01-01

    Background A reduced range of hip internal rotation is associated with increased peak anterior cruciate ligament (ACL) strain and risk for injury. It is unknown, however, whether limiting the available range of internal femoral rotation increases the susceptibility of the ACL to fatigue failure. Hypothesis Risk of ACL failure is significantly greater in female knee specimens with a limited range of internal femoral rotation, smaller femoral-ACL attachment angle, and smaller tibial eminence volume during repeated in vitro simulated single-leg pivot landings. Study Design Controlled laboratory study. Methods A custom-built testing apparatus was used to simulate repeated single-leg pivot landings with a 4×-body weight impulsive load that induces knee compression, knee flexion, and internal tibial torque in 32 paired human knee specimens from 8 male and 8 female donors. These test loads were applied to each pair of specimens, in one knee with limited internal femoral rotation and in the contralateral knee with femoral rotation resisted by 2 springs to simulate the active hip rotator muscles’ resistance to stretch. The landings were repeated until ACL failure occurred or until a minimum of 100 trials were executed. The angle at which the ACL originates from the femur and the tibial eminence volume were measured on magnetic resonance images. Results The final Cox regression model (P = .024) revealed that range of internal femoral rotation and sex of donor were significant factors in determining risk of ACL fatigue failure. The specimens with limited range of internal femoral rotation had a failure risk 17.1 times higher than did the specimens with free rotation (P = .016). The female knee specimens had a risk of ACL failure 26.9 times higher than the male specimens (P = .055). Conclusion Limiting the range of internal femoral rotation during repetitive pivot landings increases the risk of an ACL fatigue failure in comparison with free rotation in a cadaveric model

  3. DNA methylation of LINE-1 and Alu repetitive elements in relation to sex hormones and pubertal timing in Mexican-American children

    PubMed Central

    Huen, Karen; Harley, Kim; Kogut, Katherine; Rauch, Stephen; Eskenazi, Brenda; Holland, Nina

    2015-01-01

    Background The molecular mechanisms linking environmental exposures to earlier pubertal development are not well characterized. Epigenetics may play an important role, but data on the relationship between epigenetic marks and puberty, particularly in humans, is limited. Methods We used pyrosequencing to measure Alu and long interspersed nucleotide elements (LINE-1) methylation in DNA isolated from whole blood samples collected from newborns and 9-year-old children (n=266). Tanner staging was completed six times between ages 9 and 12 years to determine pubertal status, and hormone levels were measured in 12-year-old boys. Results Among girls, we observed a suggestive trend of increased odds of breast and pubic hair development with higher Alu and LINE-1 methylation in 9-year-old blood, respectively. The strongest association identified was an inverse association of LINE-1 methylation in 9-year-old girls with odds of experiencing menarche by age 12 (OR(95%CI): 0.63(0.46,0.87); p=0.005). We observed a consistent inverse relationship for Alu and LINE-1 methylation at 9 years with luteinizing hormone (LH), testosterone and follicle stimulating hormone levels in boys but it was only significant between LINE-1 and LH. Conclusion DNA methylation of Alu and LINE-1 may be involved in puberty initiation and development. This relationship should be confirmed in future studies. PMID:26882368

  4. Alu Insertions and Genetic Diversity: A Preliminary Investigation by an Undergraduate Bioinformatics Class

    ERIC Educational Resources Information Center

    Elwess, Nancy L.; Duprey, Stephen L.; Harney, Lindesay A.; Langman, Jessie E.; Marino, Tara C.; Martinez, Carolina; McKeon, Lauren L.; Moss, Chantel I. E.; Myrie, Sasha S.; Taylor, Luke Ryan

    2008-01-01

    "Alu"-insertion polymorphisms were used by an undergraduate Bioinformatics class to study how these insertion sites could be the basis for an investigation in human population genetics. Based on the students' investigation, both allele and genotype "Alu" frequencies were determined for African-American and Japanese populations as well as a…

  5. Terrestrial Sediment and Nutrient Fluxes to the Faga'alu Reefs in American Samoa

    NASA Astrophysics Data System (ADS)

    Messina, A. T.

    2013-12-01

    Land-based sources of pollution including increased sediment and nutrient fluxes to coastal waters have been identified and linked to degraded coral health in reef ecosystems adjacent to impacted streams such as Faga'alu in American Samoa. Monthly monitoring since 2002 has shown that Faga'alu stream has the highest turbidity of monitored streams on Tutuila, where degraded water quality is linked to lower reef health and fish biomass. To guide local and federal managers in mitigating land-based sources of pollution from agricultural, mining, urban, and residential areas, fluxes of sediment and nutrients were measured upstream and downstream of disturbed areas to identify and quantify significant pollution sources and guide mitigation efforts. Sediment flux from disturbed areas, mainly an open-pit aggregate quarry, contributed over 75% of the sediment loading to the bay. Faga'alu stream is characterized by flashy response to rainfall events and the total observed sediment yield was contributed by a small number of large storm events. Event-total sediment yield was more closely correlated with event-total discharge than event-total precipitation. It is hypothesized that the intensity of rainfall controls sediment yield for small events where sheetwash erosion from the quarry is more important. For larger events where easily available sediment is washed away in the first part of the storm it is hypothesized that increased sediment yield is due to streambank erosion and gullying from both disturbed and undisturbed areas. Based on sediment yield measurements and modeled sediment loading to the bay, recommendations for mitigation of land-based sources of pollution are focused on sediment mitigation at the quarry and runoff from the large impervious areas associated with the hospital. Measurements of sediment accumulation on the coral reef itself show sedimentation is controlled by sediment loading from the watershed and sediment scouring by increased wave and wind

  6. Characterization of Alu and recombination-associated motifs mediating a large homozygous SPG7 gene rearrangement causing hereditary spastic paraplegia.

    PubMed

    López, Eva; Casasnovas, Carlos; Giménez, Javier; Matilla-Dueñas, Antoni; Sánchez, Ivelisse; Volpini, Víctor

    2015-04-01

    Spastic paraplegia type 7 (SPG7) is one of the most common forms of autosomal recessive hereditary spastic paraplegia (AR-HSP). Although over 77 different mutations have been identified in SPG7 patients, only 9 gross deletions have been reported with only a few of them being fully characterized. Here, we present a detailed description of a large homozygous intragenic SPG7 gene rearrangement involving a 5144-base pair (bp) genomic loss (c. 1450-446_1779 + 746 delinsAAAGTGCT) encompassing exons 11 to 13, identified in a Spanish AR-HSP family. Analysis of the deletion junction sequences revealed that the 5' breakpoint of this SPG7 gene deletion was located within highly homologous Alu sequences where the 3' breakpoint appears to be flanked by the core crossover hotspot instigator (chi)-like sequence (GCTGG). Furthermore, an 8-bp (AAAGTTGCT) conserved sequence at the breakpoint junction was identified, suggesting that the most likely mechanism for the occurrence of this rearrangement is by Alu microhomology and chi-like recombination-associated motif-mediated multiple exon deletion. Our results are consistent with non-allelic homologous recombination and non-homologous end joining in deletion mutagenesis for the generation of rearrangements. This study provides more evidence associating repeated elements as a genetic mechanism underlying neurodegenerative disorders, highlighting their importance in human diseases.

  7. Repeated Listening Increases the Liking for Music Regardless of Its Complexity: Implications for the Appreciation and Aesthetics of Music

    PubMed Central

    Madison, Guy; Schiölde, Gunilla

    2017-01-01

    Psychological and aesthetic theories predict that music is appreciated at optimal, peak levels of familiarity and complexity, and that appreciation of music exhibits an inverted U-shaped relationship with familiarity as well as complexity. Because increased familiarity conceivably leads to improved processing and less perceived complexity, we test whether there is an interaction between familiarity and complexity. Specifically, increased familiarity should render the music subjectively less complex, and therefore move the apex of the U curve toward greater complexity. A naturalistic listening experiment was conducted, featuring 40 music examples (ME) divided by experts into 4 levels of complexity prior to the main experiment. The MEs were presented 28 times each across a period of approximately 4 weeks, and individual ratings were assessed throughout the experiment. Ratings of liking increased monotonically with repeated listening at all levels of complexity; both the simplest and the most complex MEs were liked more as a function of listening time, without any indication of a U-shaped relation. Although the MEs were previously unknown to the participants, the strongest predictor of liking was familiarity in terms of having listened to similar music before, i.e., familiarity with musical style. We conclude that familiarity is the single most important variable for explaining differences in liking among music, regardless of the complexity of the music.

  8. MORF9 increases the RNA-binding activity of PLS-type pentatricopeptide repeat protein in plastid RNA editing.

    PubMed

    Yan, Junjie; Zhang, Qunxia; Guan, Zeyuan; Wang, Qiang; Li, Li; Ruan, Fengying; Lin, Rongcheng; Zou, Tingting; Yin, Ping

    2017-04-10

    RNA editing is a post-transcriptional process that modifies the genetic information on RNA molecules. In flowering plants, RNA editing usually alters cytidine to uridine in plastids and mitochondria. The PLS-type pentatricopeptide repeat (PPR) protein and the multiple organellar RNA editing factor (MORF, also known as RNA editing factor interacting protein (RIP)) are two types of key trans-acting factors involved in this process. However, how they cooperate with one another remains unclear. Here, we have characterized the interactions between a designer PLS-type PPR protein (PLS)3PPR and MORF9, and found that RNA-binding activity of (PLS)3PPR is drastically increased on MORF9 binding. We also determined the crystal structures of (PLS)3PPR, MORF9 and the (PLS)3PPR-MORF9 complex. MORF9 binding induces significant compressed conformational changes of (PLS)3PPR, revealing the molecular mechanisms by which MORF9-bound (PLS)3PPR has increased RNA-binding activity. Similarly, increased RNA-binding activity is observed for the natural PLS-type PPR protein, LPA66, in the presence of MORF9. These findings significantly expand our understanding of MORF function in plant organellar RNA editing.

  9. Altering a gene involved in nuclear distribution increases the repeat-induced point mutation process in the fungus Podospora anserina.

    PubMed Central

    Bouhouche, Khaled; Zickler, Denise; Debuchy, Robert; Arnaise, Sylvie

    2004-01-01

    Repeat-induced point mutation (RIP) is a homology-dependent gene-silencing mechanism that introduces C:G-to-T:A transitions in duplicated DNA segments. Cis-duplicated sequences can also be affected by another mechanism called premeiotic recombination (PR). Both are active over the sexual cycle of some filamentous fungi, e.g., Neurospora crassa and Podospora anserina. During the sexual cycle, several developmental steps require precise nuclear movement and positioning, but connections between RIP, PR, and nuclear distributions have not yet been established. Previous work has led to the isolation of ami1, the P. anserina ortholog of the Aspergillus nidulans apsA gene, which is required for nuclear positioning. We show here that ami1 is involved in nuclear distribution during the sexual cycle and that alteration of ami1 delays the fruiting-body development. We also demonstrate that ami1 alteration affects loss of transgene functions during the sexual cycle. Genetically linked multiple copies of transgenes are affected by RIP and PR much more frequently in an ami1 mutant cross than in a wild-type cross. Our results suggest that the developmental slowdown of the ami1 mutant during the period of RIP and PR increases time exposure to the duplication detection system and thus increases the frequency of RIP and PR. PMID:15166143

  10. Adeno-associated virus inverted terminal repeats stimulate gene editing.

    PubMed

    Hirsch, M L

    2015-02-01

    Advancements in genome editing have relied on technologies to specifically damage DNA which, in turn, stimulates DNA repair including homologous recombination (HR). As off-target concerns complicate the therapeutic translation of site-specific DNA endonucleases, an alternative strategy to stimulate gene editing based on fragile DNA was investigated. To do this, an episomal gene-editing reporter was generated by a disruptive insertion of the adeno-associated virus (AAV) inverted terminal repeat (ITR) into the egfp gene. Compared with a non-structured DNA control sequence, the ITR induced DNA damage as evidenced by increased gamma-H2AX and Mre11 foci formation. As local DNA damage stimulates HR, ITR-mediated gene editing was investigated using DNA oligonucleotides as repair substrates. The AAV ITR stimulated gene editing >1000-fold in a replication-independent manner and was not biased by the polarity of the repair oligonucleotide. Analysis of additional human DNA sequences demonstrated stimulation of gene editing to varying degrees. In particular, inverted yet not direct, Alu repeats induced gene editing, suggesting a role for DNA structure in the repair event. Collectively, the results demonstrate that inverted DNA repeats stimulate gene editing via double-strand break repair in an episomal context and allude to efficient gene editing of the human chromosome using fragile DNA sequences.

  11. Alu polymorphic insertions reveal genetic structure of north Indian populations.

    PubMed

    Tripathi, Manorama; Tripathi, Piyush; Chauhan, Ugam Kumari; Herrera, Rene J; Agrawal, Suraksha

    2008-10-01

    The Indian subcontinent is characterized by the ancestral and cultural diversity of its people. Genetic input from several unique source populations and from the unique social architecture provided by the caste system has shaped the current genetic landscape of India. In the present study 200 individuals each from three upper-caste and four middle-caste Hindu groups and from two Muslim populations in North India were examined for 10 polymorphic Alu insertions (PAIs). The investigated PAIs exhibit high levels of polymorphism and average heterozygosity. Limited interpopulation variance and genetic flow in the present study suggest admixture. The results of this study demonstrate that, contrary to common belief, the caste system has not provided an impermeable barrier to genetic exchange among Indian groups.

  12. Identification of RNA polymerase III-transcribed Alu loci by computational screening of RNA-Seq data.

    PubMed

    Conti, Anastasia; Carnevali, Davide; Bollati, Valentina; Fustinoni, Silvia; Pellegrini, Matteo; Dieci, Giorgio

    2015-01-01

    Of the ∼ 1.3 million Alu elements in the human genome, only a tiny number are estimated to be active in transcription by RNA polymerase (Pol) III. Tracing the individual loci from which Alu transcripts originate is complicated by their highly repetitive nature. By exploiting RNA-Seq data sets and unique Alu DNA sequences, we devised a bioinformatic pipeline allowing us to identify Pol III-dependent transcripts of individual Alu elements. When applied to ENCODE transcriptomes of seven human cell lines, this search strategy identified ∼ 1300 Alu loci corresponding to detectable transcripts, with ∼ 120 of them expressed in at least three cell lines. In vitro transcription of selected Alus did not reflect their in vivo expression properties, and required the native 5'-flanking region in addition to internal promoter. We also identified a cluster of expressed AluYa5-derived transcription units, juxtaposed to snaR genes on chromosome 19, formed by a promoter-containing left monomer fused to an Alu-unrelated downstream moiety. Autonomous Pol III transcription was also revealed for Alus nested within Pol II-transcribed genes. The ability to investigate Alu transcriptomes at single-locus resolution will facilitate both the identification of novel biologically relevant Alu RNAs and the assessment of Alu expression alteration under pathological conditions.

  13. Identification of RNA polymerase III-transcribed Alu loci by computational screening of RNA-Seq data

    PubMed Central

    Conti, Anastasia; Carnevali, Davide; Bollati, Valentina; Fustinoni, Silvia; Pellegrini, Matteo; Dieci, Giorgio

    2015-01-01

    Of the ∼1.3 million Alu elements in the human genome, only a tiny number are estimated to be active in transcription by RNA polymerase (Pol) III. Tracing the individual loci from which Alu transcripts originate is complicated by their highly repetitive nature. By exploiting RNA-Seq data sets and unique Alu DNA sequences, we devised a bioinformatic pipeline allowing us to identify Pol III-dependent transcripts of individual Alu elements. When applied to ENCODE transcriptomes of seven human cell lines, this search strategy identified ∼1300 Alu loci corresponding to detectable transcripts, with ∼120 of them expressed in at least three cell lines. In vitro transcription of selected Alus did not reflect their in vivo expression properties, and required the native 5′-flanking region in addition to internal promoter. We also identified a cluster of expressed AluYa5-derived transcription units, juxtaposed to snaR genes on chromosome 19, formed by a promoter-containing left monomer fused to an Alu-unrelated downstream moiety. Autonomous Pol III transcription was also revealed for Alus nested within Pol II-transcribed genes. The ability to investigate Alu transcriptomes at single-locus resolution will facilitate both the identification of novel biologically relevant Alu RNAs and the assessment of Alu expression alteration under pathological conditions. PMID:25550429

  14. High Altitude Increases Alteration in Maximal Torque but Not in Rapid Torque Development in Knee Extensors after Repeated Treadmill Sprinting

    PubMed Central

    Girard, Olivier; Brocherie, Franck; Millet, Grégoire P.

    2016-01-01

    . Additionally, the EMG rise for VL muscle was similar (P > 0.05), whereas it increased (P < 0.05) for RF muscle during all epochs post-exercise, independently of the conditions. In summary, alteration in repeated-sprint ability and post-exercise MVC decrease were greater at high altitude than in normoxia or at low altitude. However, the post-exercise alterations in RTD were similar between normoxia and low-to-high hypoxia. PMID:27014095

  15. Design of CNTFET-based 2-bit ternary ALU for nanoelectronics

    NASA Astrophysics Data System (ADS)

    Lata Murotiya, Sneh; Gupta, Anu

    2014-09-01

    This article presents a hardware-efficient design of 2-bit ternary arithmetic logic unit (ALU) using carbon nanotube field-effect transistors (CNTFETs) for nanoelectronics. The proposed structure introduces a ternary adder-subtractor functional module to optimise ALU architecture. The full adder-subtractor (FAS) cell uses nearly 72% less transistors than conventional architecture, which contains separate ternary cells for addition as well as subtraction. The presented ALU also minimises ternary function expressions with utilisation of binary gates for optimisation at the circuit level, thus attaining a simple design. Hspice simulations results demonstrate that the ALU ternary circuits achieve great improvement in terms of power delay product with respect to their CMOS counterpart at 32 nm.

  16. Alu-Derived Alternative Splicing Events Specific to Macaca Lineages in CTSF Gene

    PubMed Central

    Lee, Ja-Rang; Park, Sang-Je; Kim, Young-Hyun; Choe, Se-Hee; Cho, Hyeon-Mu; Lee, Sang-Rae; Kim, Sun-Uk; Kim, Ji-Su; Sim, Bo-Woong; Song, Bong-Seok; Jeong, Kang-Jin; Lee, Youngjeon; Jin, Yeung Bae; Kang, Philyong; Huh, Jae-Won; Chang, Kyu-Tae

    2017-01-01

    Cathepsin F, which is encoded by CTSF, is a cysteine proteinase ubiquitously expressed in several tissues. In a previous study, novel transcripts of the CTSF gene were identified in the crab-eating monkey deriving from the integration of an Alu element–AluYRa1. The occurrence of AluYRa1-derived alternative transcripts and the mechanism of exonization events in the CTSF gene of human, rhesus monkey, and crab-eating monkey were investigated using PCR and reverse transcription PCR on the genomic DNA and cDNA isolated from several tissues. Results demonstrated that AluYRa1 was only integrated into the genome of Macaca species and this lineage-specific integration led to exonization events by producing a conserved 3′ splice site. Six transcript variants (V1–V6) were generated by alternative splicing (AS) events, including intron retention and alternative 5′ splice sites in the 5′ and 3′ flanking regions of CTSF_AluYRa1. Among them, V3–V5 transcripts were ubiquitously expressed in all tissues of rhesus monkey and crab-eating monkey, whereas AluYRa1-exonized V1 was dominantly expressed in the testis of the crab-eating monkey, and V2 was only expressed in the testis of the two monkeys. These five transcript variants also had different amino acid sequences in the C-terminal region of CTSF, as compared to reference sequences. Thus, species-specific Alu-derived exonization by lineage-specific integration of Alu elements and AS events seems to have played an important role during primate evolution by producing transcript variants and gene diversification. PMID:28196413

  17. Higher Alu Methylation Levels in Catch-Up Growth in Twenty-Year-Old Offsprings

    PubMed Central

    Rerkasem, Kittipan; Rattanatanyong, Prakasit; Rerkasem, Amaraporn; Wongthanee, Antika; Rungruengthanakit, Kittipong; Mangklabruks, Ampica; Mutirangura, Apiwat

    2015-01-01

    Alu elements and long interspersed element-1 (LINE-1 or L1) are two major human intersperse repetitive sequences. Lower Alu methylation, but not LINE-1, has been observed in blood cells of people in old age, and in menopausal women having lower bone mass and osteoporosis. Nevertheless, Alu methylation levels also vary among young individuals. Here, we explored phenotypes at birth that are associated with Alu methylation levels in young people. In 2010, 249 twenty-years-old volunteers whose mothers had participated in a study association between birth weight (BW) and nutrition during pregnancy in 1990, were invited to take part in our present study. In this study, the LINE-1 and Alu methylation levels and patterns were measured in peripheral mononuclear cells and correlated with various nutritional parameters during intrauterine and postnatal period of offspring. This included the amount of maternal intake during pregnancy, the mother’s weight gain during pregnancy, birth weight, birth length, and the rate of weight gain in the first year of life. Catch-up growth (CUG) was defined when weight during the first year was >0.67 of the standard score, according to WHO data. No association with LINE-1 methylation was identified. The mean level of Alu methylation in the CUG group was significantly higher than those non-CUG (39.61% and 33.66 % respectively, P < 0.0001). The positive correlation between the history of CUG in the first year and higher Alu methylation indicates the role of Alu methylation, not only in aging cells, but also in the human growth process. Moreover, here is the first study that demonstrated the association between a phenotype during the newborn period and intersperse repetitive sequences methylation during young adulthood. PMID:25807557

  18. Splicing repression allows the gradual emergence of new Alu-exons in primate evolution

    PubMed Central

    Attig, Jan; Ruiz de los Mozos, Igor; Haberman, Nejc; Wang, Zhen; Emmett, Warren; Zarnack, Kathi; König, Julian; Ule, Jernej

    2016-01-01

    Alu elements are retrotransposons that frequently form new exons during primate evolution. Here, we assess the interplay of splicing repression by hnRNPC and nonsense-mediated mRNA decay (NMD) in the quality control and evolution of new Alu-exons. We identify 3100 new Alu-exons and show that NMD more efficiently recognises transcripts with Alu-exons compared to other exons with premature termination codons. However, some Alu-exons escape NMD, especially when an adjacent intron is retained, highlighting the importance of concerted repression by splicing and NMD. We show that evolutionary progression of 3' splice sites is coupled with longer repressive uridine tracts. Once the 3' splice site at ancient Alu-exons reaches a stable phase, splicing repression by hnRNPC decreases, but the exons generally remain sensitive to NMD. We conclude that repressive motifs are strongest next to cryptic exons and that gradual weakening of these motifs contributes to the evolutionary emergence of new alternative exons. DOI: http://dx.doi.org/10.7554/eLife.19545.001 PMID:27861119

  19. Amphiphysin I but not dynamin I nor synaptojanin mRNA expression increased after repeated methamphetamine administration in the rat cerebrum and cerebellum.

    PubMed

    Hamamura, Mitsuko; Okouchi, Jiro; Ozawa, Hidetoshi; Kimuro, Yoshihiko; Iwaki, Akiko; Fukumaki, Yasuyuki

    2013-07-01

    Dopamine increases/decreases synaptic vesicle recycling and in schizophrenia the proteins/mRNA is decreased. We isolated cDNA clone, similar to amphiphysin 1 (vesicle protein) mRNA from the neocortex of rats injected repeatedly with methamphetamine using polymerase chain reaction (PCR) differential display. This clone is highly homologous to the 3' region of the human amphiphysin gene. PCR extension study using a primer specific for the rat amphiphysin 1 gene and a primer located within the clone revealed that it is the 3' UTR region of the rat amphiphysin 1 gene. Furthermore, in situ hybridization revealed that amphiphysin 1 mRNA is expressed in the cerebrum, medial thalamus, hippocampus and cerebellum. In the cerebellum, amphiphysin mRNA expression was confined to upper granule cell layer. Repeated methamphetamine administration increased amphiphysin I mRNA expression in both anterior part of the cerebrum, and the cerebellum. However, the repeated administration did not alter mRNA expression of the other vesicle proteins, synaptotagmin I, synapsin I, synaptojanin and dynamin I, we conclude that the repeated administration selectively increased amphiphysin 1 mRNA expression. Thus, amphiphysin 1 does not work as synaptic recycling, but it is suggested, as a part of pathogenesis of brain tissue injury (under Ca²⁺ and Mg²⁺ devoid environment) in repeated methamphetamine-injected states, the gene regulate actin-asssembly, learning, cell stress signaling and cell polarity.

  20. The 2-repeat allele of the MAOA gene confers an increased risk for shooting and stabbing behaviors.

    PubMed

    Beaver, Kevin M; Barnes, J C; Boutwell, Brian B

    2014-09-01

    There has been a great deal of research examining the link between a polymorphism in the promoter region of the MAOA gene and antisocial phenotypes. The results of these studies have consistently revealed that low activity MAOA alleles are related to antisocial behaviors for males who were maltreated as children. Recently, though, some evidence has emerged indicating that a rare allele of the MAOA gene-that is, the 2-repeat allele-may have effects on violence that are independent of the environment. The current study builds on this research and examines the association between the 2-repeat allele and shooting and stabbing behaviors in a sample of males drawn from the National Longitudinal Study of Adolescent Health. Analyses revealed that African-American males who carry the 2-repeat allele are significantly more likely than all other genotypes to engage in shooting and stabbing behaviors and to report having multiple shooting and stabbing victims. The limitations of the study are discussed and suggestions for future research are offered.

  1. Social Stories: Mechanisms of Effectiveness in Increasing Game Play Skills in Children Diagnosed with Autism Spectrum Disorder Using a Pretest Posttest Repeated Measures Randomized Control Group Design

    ERIC Educational Resources Information Center

    Quirmbach, Linda M.; Lincoln, Alan J.; Feinberg-Gizzo, Monica J.; Ingersoll, Brooke R.; Andrews, Siri M.

    2009-01-01

    An increasing body of literature has indicated that social stories are an effective way to teach individuals diagnosed with autism appropriate social behavior. This study compared two formats of a social story targeting the improvement of social skills during game play using a pretest posttest repeated measures randomized control group design. A…

  2. Increasing the reliability of the shutdown of 500 - 750-kV overhead lines equipped with shunt reactors in an unsuccessful three-phase automatic repeated closure cycle

    SciTech Connect

    Kuz'micheva, K. I.; Merzlyakov, A. S.; Fokin, G. G.

    2013-05-15

    The reasons for circuit-breaker failures during repeated disconnection of 500 - 750 kV overhead lines with shunt reactors in a cycle of unsuccessful three-phase automatic reconnection (TARC) are analyzed. Recommendations are made for increasing the operating reliability of power transmission lines with shunt reactors when there is unsuccessful reconnection.

  3. Repeated immobilization stress increases the binding of c-Fos-like proteins to a rat dopamine beta-hydroxylase promoter enhancer sequence.

    PubMed

    Nankova, B; Devlin, D; Kvetnanský, R; Kopin, I J; Sabban, E L

    1993-08-01

    Repeated immobilization stress elicits a large elevation in adrenal dopamine beta-hydroxylase (DBH) mRNA levels. This study attempts to analyze the molecular mechanism of increased DBH gene expression in stress. Adrenomedullary nuclear proteins were prepared from controls and rats exposed to various intervals of immobilization stress. Electrophoretic mobility shift assays showed that repeated stress led to increased binding of adrenomedullary nuclear factors to a cis-acting regulatory element in the rat DBH promoter (DBH-1). One of the partners in the DNA-protein complex is c-Fos or a Fos-related protein. There was a correlation between promoter binding activity and elevated steady-state levels of DBH mRNA. Our data indicate that this cis regulatory element in the rat DBH promoter is functional in vivo, and increased binding of AP1-like transcription factors to this motif is induced by immobilization stress.

  4. Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor

    PubMed Central

    Morales-Hernández, Antonio; González-Rico, Francisco J.; Román, Angel C.; Rico-Leo, Eva; Alvarez-Barrientos, Alberto; Sánchez, Laura; Macia, Ángela; Heras, Sara R.; García-Pérez, José L.; Merino, Jaime M.; Fernández-Salguero, Pedro M.

    2016-01-01

    Cell differentiation is a central process in development and in cancer growth and dissemination. OCT4 (POU5F1) and NANOG are essential for cell stemness and pluripotency; yet, the mechanisms that regulate their expression remain largely unknown. Repetitive elements account for almost half of the Human Genome; still, their role in gene regulation is poorly understood. Here, we show that the dioxin receptor (AHR) leads to differentiation of human carcinoma cells through the transcriptional upregulation of Alu retrotransposons, whose RNA transcripts can repress pluripotency genes. Despite the genome-wide presence of Alu elements, we provide evidences that those located at the NANOG and OCT4 promoters bind AHR, are transcribed by RNA polymerase-III and repress NANOG and OCT4 in differentiated cells. OCT4 and NANOG repression likely involves processing of Alu-derived transcripts through the miRNA machinery involving the Microprocessor and RISC. Consistently, stable AHR knockdown led to basal undifferentiation, impaired Alus transcription and blockade of OCT4 and NANOG repression. We suggest that transcripts produced from AHR-regulated Alu retrotransposons may control the expression of stemness genes OCT4 and NANOG during differentiation of carcinoma cells. The control of discrete Alu elements by specific transcription factors may have a dynamic role in genome regulation under physiological and diseased conditions. PMID:26883630

  5. Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor.

    PubMed

    Morales-Hernández, Antonio; González-Rico, Francisco J; Román, Angel C; Rico-Leo, Eva; Alvarez-Barrientos, Alberto; Sánchez, Laura; Macia, Ángela; Heras, Sara R; García-Pérez, José L; Merino, Jaime M; Fernández-Salguero, Pedro M

    2016-06-02

    Cell differentiation is a central process in development and in cancer growth and dissemination. OCT4 (POU5F1) and NANOG are essential for cell stemness and pluripotency; yet, the mechanisms that regulate their expression remain largely unknown. Repetitive elements account for almost half of the Human Genome; still, their role in gene regulation is poorly understood. Here, we show that the dioxin receptor (AHR) leads to differentiation of human carcinoma cells through the transcriptional upregulation of Alu retrotransposons, whose RNA transcripts can repress pluripotency genes. Despite the genome-wide presence of Alu elements, we provide evidences that those located at the NANOG and OCT4 promoters bind AHR, are transcribed by RNA polymerase-III and repress NANOG and OCT4 in differentiated cells. OCT4 and NANOG repression likely involves processing of Alu-derived transcripts through the miRNA machinery involving the Microprocessor and RISC. Consistently, stable AHR knockdown led to basal undifferentiation, impaired Alus transcription and blockade of OCT4 and NANOG repression. We suggest that transcripts produced from AHR-regulated Alu retrotransposons may control the expression of stemness genes OCT4 and NANOG during differentiation of carcinoma cells. The control of discrete Alu elements by specific transcription factors may have a dynamic role in genome regulation under physiological and diseased conditions.

  6. Methylation Status of Alu and LINE-1 Interspersed Repetitive Sequences in Behcet's Disease Patients.

    PubMed

    Yüksel, Şahru; Kucukazman, Selma Ozbek; Karataş, Gülten Sungur; Ozturk, Mehmet Akif; Prombhul, Sasiprapa; Hirankarn, Nattiya

    2016-01-01

    Behcet's Disease (BD) is a multisystem chronic inflammatory disease. The pathology is believed to involve both genetic susceptibility and environmental factors. Hypomethylation leading to activation of interspersed repetitive sequences (IRSs) such as LINE-1 and Alu contributes to the pathologies of autoimmune diseases and cancer. Herein, the epigenetic changes of IRSs in BD were evaluated using combined bisulfite restriction analysis-interspersed repetitive sequences (COBRA-IRS). DNA from neutrophils and peripheral blood mononuclear cells (PBMCs) of BD patients with ocular involvement that were in active or inactive states and healthy controls were used to analyze LINE-1 and Alu methylation levels. For Alu sequences, significant differences were observed in the frequency of (u)C(u)C alleles between PBMCs of patients and controls (p = 0.03), and between inactive patients and controls (p = 0.03). For neutrophils, the frequency of (u)C(u)C was significantly higher between patients and controls (p = 0.006) and between inactive patients and controls (p = 0.002). The partial methylation ((u)C(m)C + (m)C(u)C) frequencies of Alu between inactive patients and control samples also differed (p = 0.02). No statistically significant differences for LINE-1 were detected. Thus, changes in the methylation level of IRS elements might contribute to the pathogenesis of BD. The role of Alu transcripts in BD should be investigated further.

  7. A novel composite retrotransposon derived from or generated independently of the SVA (SINE/VNTR/Alu) transposon has undergone proliferation in gibbon genomes.

    PubMed

    Hara, Toru; Hirai, Yuriko; Baicharoen, Sudarath; Hayakawa, Takashi; Hirai, Hirohisa; Koga, Akihiko

    2012-01-01

    The superfamily Hominoidea (hominoids) comprises two families: Hominidae (hominids) and Hylobatidae (gibbons, also called small apes). The SVA transposon is a composite retrotransposon that occurs widely in hominoids and is considered to have been generated by stepwise fusions of three genetic elements: SINE-R, a variable number of tandem repeat (VNTR) sequence, and Alu. We identified a novel transposon whose basic structure is the same as that of SVA, with one prominent difference being the presence of part of prostaglandin reductase 2 (PTGR2) in place of SINE-R. We designate this composite transposon as PVA and propose two possible mechanisms regarding its generation. One is the derivation of PVA from SVA: the SINE-R region of SVA was replaced with a PTGR2 fragment by template switching. The other is the formation of PVA independently of SVA: a PTGR2 fragment was fused to an evolutionary intermediate comprising the VNTR and Alu regions. The nucleotide sequence of the junction between the VNTR and PTGR2 regions supports the second hypothesis. We identified PVA in the white-cheeked gibbon Nomascus leucogenys by analysis of genome sequence databases, and subsequent experimental analysis revealed its presence in all four gibbon genera. The white-cheeked gibbon harbors at least 93 PVA copies in its haploid genome. Another SVA-like composite transposon carrying parts of the LINE1 and Alu transposons in place of SINE-R, designated as LAVA, has recently been reported. The significance of the discovery of PVA is that its substituted fragment originates not from a transposon but from a single-copy gene. PVA should provide additional insights into the transposition mechanism of this type of composite transposon; the transposition activity is conferred even if the substituted fragment is not related to a transposon.

  8. Polymorphic Alu insertions in six Brazilian African-derived populations.

    PubMed

    Cotrim, Nelson Henderson; Auricchio, Maria Teresa B M; Vicente, João Pedro; Otto, Paulo A; Mingroni-Netto, Regina Célia

    2004-01-01

    At least 25 African-derived populations (quilombo remnants) are believed to exist in the Ribeira River Valley, located in the southern part of São Paulo State, Brazil. We studied four Alu polymorphic loci (APO, ACE, TPA25, and FXIIIB) in individuals belonging to six quilombo remnants in addition to individuals sampled from the city of São Paulo. The allelic frequencies observed in the quilombo remnants were similar to those previously observed in African-derived populations from Central and North America. Genetic variability indexes (Fst and Gst values) in our quilombos were higher than the reported values for the majority of other populations analyzed for the same kind of markers, but lower than the variability usually observed in Amerindian groups. The observed high degree of genetic differentiation may be due to genetic drift, especially the founder effect. Our results suggest that these populations behave genetically as semi-isolates. The degree of genetic variability within populations was larger than among them, a finding described in other studies. In the neighbor-joining tree, some of the Brazilian quilombos clustered with the African and African-derived populations (São Pedro and Galvão), others with the Europeans (Pilões, Maria Rosa, and Abobral). Pedro Cubas was placed in an isolated branch. Principal component analysis was also performed and confirmed the trends observed in the neighbor-joining tree. Overall, the quilombos showed a higher degree of gene flow than average when compared to other worldwide populations, but similar to other African-derived populations.

  9. Transfer of genetic therapy across human populations: molecular targets for increasing patient coverage in repeat expansion diseases.

    PubMed

    Varela, Miguel A; Curtis, Helen J; Douglas, Andrew G L; Hammond, Suzan M; O'Loughlin, Aisling J; Sobrido, Maria J; Scholefield, Janine; Wood, Matthew J A

    2016-02-01

    Allele-specific gene therapy aims to silence expression of mutant alleles through targeting of disease-linked single-nucleotide polymorphisms (SNPs). However, SNP linkage to disease varies between populations, making such molecular therapies applicable only to a subset of patients. Moreover, not all SNPs have the molecular features necessary for potent gene silencing. Here we provide knowledge to allow the maximisation of patient coverage by building a comprehensive understanding of SNPs ranked according to their predicted suitability toward allele-specific silencing in 14 repeat expansion diseases: amyotrophic lateral sclerosis and frontotemporal dementia, dentatorubral-pallidoluysian atrophy, myotonic dystrophy 1, myotonic dystrophy 2, Huntington's disease and several spinocerebellar ataxias. Our systematic analysis of DNA sequence variation shows that most annotated SNPs are not suitable for potent allele-specific silencing across populations because of suboptimal sequence features and low variability (>97% in HD). We suggest maximising patient coverage by selecting SNPs with high heterozygosity across populations, and preferentially targeting SNPs that lead to purine:purine mismatches in wild-type alleles to obtain potent allele-specific silencing. We therefore provide fundamental knowledge on strategies for optimising patient coverage of therapeutics for microsatellite expansion disorders by linking analysis of population genetic variation to the selection of molecular targets.

  10. Loss of the mu opioid receptor on different genetic backgrounds leads to increased bromodeoxyuridine labeling in the dentate gyrus only after repeated injection.

    PubMed

    Cominski, T P; Turchin, C E; Hsu, M S; Ansonoff, M A; Pintar, J E

    2012-03-29

    The endogenous opioid system is involved in various physiological processes, including neurogenesis in the dentate gyrus (DG) of the hippocampus. In the current study, we investigated the role of the mu opioid receptor (MOR-1) on DG neurogenesis and measured glucocorticoid levels following several injection paradigms to supplement the neurogenesis experiments. MOR-1 knockout (KO) mice on C57BL/6 and 129S6 backgrounds were injected with bromodeoxyuridine (BrdU) using either a single injection or two different repeated injection protocols and then sacrificed at different time points. The total number of BrdU and proliferating cell nuclear antigen (PCNA) positive cells in the DG is significantly increased in MOR-1 KO mice compared with wild type (WT) on both strains after repeated injection, but not after a single injection. Plasma corticosterone (CORT) levels increased similarly in MOR-1 KO and WT mice following both single and repeated injection, indicating that the stress response is activated following any injection protocol, but that the mechanism responsible for the increase in BrdU labeling in MOR-1 KO mice is CORT-level independent. Finally, WT 129S6 mice, independent of genotype, showed higher levels of plasma CORT compared with WT C57BL/6 mice in both noninjected controls and following injection at two separate time points; these levels were inversely correlated with low numbers of BrdU cells in the DG in 129S6 mice compared with C57BL/6 mice. In summary, these data demonstrate that loss of MOR-1 increases BrdU labeling in the DG independent of CORT levels, but only following a repeated injection, illustrating the capability of injection paradigms to influence cell-proliferative responses in a genotype-dependent manner.

  11. Repeated administration of aripiprazole produces a sensitization effect in the suppression of avoidance responding and phencyclidine-induced hyperlocomotion and increases D2 receptor-mediated behavioral function

    PubMed Central

    Gao, Jun; Qin, Rongyin; Li, Ming

    2016-01-01

    The present study investigated how repeated administration of aripiprazole (a novel antipsychotic drug) alters its behavioral effects in two behavioral tests of antipsychotic activity and whether this alteration is correlated with an increase in dopamine D2 receptor function. Male adult Sprague-Dawley rats were first repeatedly tested with aripiprazole (3, 10 and 30 mg/kg, subcutaneously (sc)) or vehicle in a conditioned avoidance response (CAR) test or a phencyclidine (PCP) (3.20 mg/kg, sc)-induced hyperlocomotion test daily for five consecutive days. After 2–3 days of drug-free retraining or resting, all rats were then challenged with aripiprazole (1.5 or 3.0 mg/kg, sc). Repeated administration of aripiprazole progressively increased its inhibition of avoidance responding and PCP-induced hyperlocomotion. More importantly, rats previously treated with aripiprazole showed significantly lower avoidance response and lower PCP-induced hyperlocomotion than those previously treated with vehicle in the challenge tests. An increased sensitivity to quinpirole (a selective D2/3 agonist) in prior aripiprazole-treated rats was also found in the quinpirole-induced hyperlocomotion test, suggesting an enhanced D2/3-mediated function. These findings suggest that aripiprazole, despite its distinct receptor mechanisms of action, induces a sensitization effect similar to those induced by other antipsychotic drugs and this effect may be partially mediated by brain plasticity involving D2/3 receptor systems. PMID:25586399

  12. Repeated administration of aripiprazole produces a sensitization effect in the suppression of avoidance responding and phencyclidine-induced hyperlocomotion and increases D2 receptor-mediated behavioral function.

    PubMed

    Gao, Jun; Qin, Rongyin; Li, Ming

    2015-04-01

    The present study investigated how repeated administration of aripiprazole (a novel antipsychotic drug) alters its behavioral effects in two behavioral tests of antipsychotic activity and whether this alteration is correlated with an increase in dopamine D2 receptor function. Male adult Sprague-Dawley rats were first repeatedly tested with aripiprazole (3, 10 and 30 mg/kg, subcutaneously (sc)) or vehicle in a conditioned avoidance response (CAR) test or a phencyclidine (PCP) (3.20 mg/kg, sc)-induced hyperlocomotion test daily for five consecutive days. After 2-3 days of drug-free retraining or resting, all rats were then challenged with aripiprazole (1.5 or 3.0 mg/kg, sc). Repeated administration of aripiprazole progressively increased its inhibition of avoidance responding and PCP-induced hyperlocomotion. More importantly, rats previously treated with aripiprazole showed significantly lower avoidance response and lower PCP-induced hyperlocomotion than those previously treated with vehicle in the challenge tests. An increased sensitivity to quinpirole (a selective D2/3 agonist) in prior aripiprazole-treated rats was also found in the quinpirole-induced hyperlocomotion test, suggesting an enhanced D2/3-mediated function. These findings suggest that aripiprazole, despite its distinct receptor mechanisms of action, induces a sensitization effect similar to those induced by other antipsychotic drugs and this effect may be partially mediated by brain plasticity involving D2/3 receptor systems.

  13. Alu insertions in the Iberian Peninsula and north west Africa--genetic boundaries or melting pot?

    PubMed

    González-Pérez, Emili; Via, Marc; Esteban, Esther; López-Alomar, Antoni; Mazieres, Stéphane; Harich, Nourdin; Kandil, Mostafa; Dugoujon, Jean-Michel; Moral, Pedro

    2003-12-01

    The Western Mediterranean Basin joins a set of ethnically different populations as Iberians and Basques in the North shore and Berbers and Arab-speakers in the South one. In spite of this differentiation, they have maintained historical contacts since ancient times. The existence of a possible common genetic background (specially for Berbers and Iberians) together with the genetic impact of the Islamic occupation of the Iberian Peninsula during 7 centuries are some of the intriguing anthropological questions that have been studied in this area using several classical and DNA markers. The aim of this work is to present the results on a survey of polymorphic Alu elements in 10 human populations of the Western Mediterranean. Recent Alu subfamilies include a significant number of polymorphic Alu insertions in humans. The polymorphic Alu elements are neutral genetic markers of identical descent with known ancestral states. This fact turns Alu insertions into useful markers for the study of human population genetics. A total number of 14 Alu insertions were analyzed in 5 Iberian populations, 3 Berber groups from North-Western Africa, an Arab-speaker population from Morocco and a sub-Saharan ethnic group from Ivory Coast. The results of this study allow the genetic characterization of Berber populations, which show a certain degree of differentiation from Arab-speaking groups of the same geographic area. Furthermore, a closer genetic distance between South Spain and Moroccan Berbers as compared with other Spanish samples supports a major genetic influx consistent with some (but not all) previous genetic studies on populations from the two shores of the Gibraltar Straits.

  14. Repeated exposure of the posterior ventral tegmental area to nicotine increases the sensitivity of local dopamine neurons to the stimulating effects of ethanol.

    PubMed

    Ding, Zheng-Ming; Katner, Simon N; Rodd, Zachary A; Truitt, William; Hauser, Sheketha R; Deehan, Gerald A; Engleman, Eric A; McBride, William J

    2012-05-01

    Clinical evidence indicates a frequent co-morbidity of nicotine and alcohol abuse and dependence. The posterior ventral tegmental area (pVTA) appears to support the reinforcing and dopamine-stimulating effects of both drugs. The current study tested the hypothesis that repeated exposure of the pVTA to one drug would increase the sensitivity of local dopamine neurons to the stimulating effects of the other drug. Female Wistar rats received repeated daily microinjections of either 100 μM nicotine or vehicle directly into the pVTA for 7 days. On the 8th day, rats received microinjections of either vehicle or ethanol (100 or 200 mg%) into the pVTA while extracellular dopamine samples were collected from the ipsilateral nucleus accumbens shell (NACsh) with microdialysis. Another experiment tested the effects of challenge microinjections of 200 μM nicotine in the pVTA on extracellular dopamine levels in the NACsh following 7 daily pretreatments with 200 mg% ethanol in the pVTA. Nicotine pretreatments increased the dopamine-stimulating effects of ethanol in the pVTA (100 mg% ethanol: 115% vs 160% of baseline in the vehicle and nicotine groups, respectively, p < 0.05; 200 mg% ethanol: 145% vs 190% of baseline in the vehicle and nicotine groups, respectively, p < 0.05). In contrast, ethanol pretreatments did not alter the stimulating effects of nicotine in the pVTA. The results suggest that repeated exposure of the pVTA to nicotine increased the response of local dopamine neurons to the stimulating effects of ethanol, whereas repeated exposure of the pVTA to ethanol did not alter the responses of pVTA dopamine neurons to nicotine.

  15. Rewarding effects of electrical stimulation of the insular cortex: decayed effectiveness after repeated tests and subsequent increase in vertical behavioral activity and conditioned place aversion after naloxone administration.

    PubMed

    García, Raquel; Zafra, Maria A; Puerto, Amadeo

    2015-02-01

    The insular cortex has been associated with various aversive and rewarding sensory, regulatory, and learning processes. The objective of this study was to examine the characteristics of the reinforcement induced by electrical stimulation of this brain area in rats. Results obtained confirm that electrical stimulation of the insular cortex may induce conditioned place and flavor preferences but the learning acquired is not transferred in a reversal test. Unexpectedly, they also demonstrate that this rewarding effect diminishes after repeated tests. In follow-up experiments, locomotor activity tests revealed an increased number of rearings (a sensitization index) in stimulated animals. Furthermore, in these same animals, administration of low doses of naloxone, an opiate antagonist, developed place aversion toward the maze compartment for which the animals had previously shown preference. These results are interpreted in relation to the effects induced by the repeated administration of natural and artificial rewarding stimuli.

  16. The SRP9/14 subunit of the signal recognition particle (SRP) is present in more than 20-fold excess over SRP in primate cells and exists primarily free but also in complex with small cytoplasmic Alu RNAs.

    PubMed Central

    Bovia, F; Fornallaz, M; Leffers, H; Strub, K

    1995-01-01

    The heterodimeric protein SRP9/14 bound to the Alu sequences of SRP RNA is essential for the translational control function of the signal recognition particle (SRP). The Alu RNAs of primate cells are believed to be derived from SRP RNA and have been shown to bind to an SRP14-related protein in vitro. We have used antibodies to characterize SRP9/14 and examine its association with small RNAs in vivo. Although SRP9 proteins are the same size in both rodent and primate cells, SRP14 subunits are generally larger in primate cells. An additional alanine-rich domain at the C-terminus accounts for the larger size of one human isoform. Although the other four SRP proteins are largely assembled into SRP in both rodent and primate cells, we found that the heterodimer SRP9/14 is present in 20-fold excess over SRP in primate cells. An increased synthesis rate of both proteins may contribute to their accumulation. The majority of the excess SRP9/14 is cytoplasmic and does not appear to be bound to any small RNAs; however, a significant fraction of a small cytoplasmic Alu RNA is complexed with SRP9/14 in a 8.5 S particle. Our findings that there is a large excess of SRP9/14 in primate cells and that Alu RNAs are bound to SRP9/14 in vivo suggest that this heterodimeric protein may play additional roles in the translational control of gene expression and/or Alu transcript metabolism. Images PMID:7542942

  17. β-Adrenergic receptor mediated increases in activation and function of natural killer cells following repeated social disruption.

    PubMed

    Tarr, Andrew J; Powell, Nicole D; Reader, Brenda F; Bhave, Neela S; Roloson, Amanda L; Carson, William E; Sheridan, John F

    2012-11-01

    Natural killer (NK) cells are specialized innate lymphocytes important in the early defense against tumor and virus bearing cells. Many factors influence the immune system's effectiveness against pathogens, including stress. Social disruption (SDR) "primes" macrophages/monocytes and dendritic cells thereby enhancing their anti-microbial function. What remains unclear is whether similar responses are evident in NK cells. Current studies investigated the cellular distribution and activation/inhibitory phenotypes of NK cells in the spleen, lung, and blood of C57BL/6 male mice following SDR. Furthermore, cytolytic activity and anti-viral cytokine production of splenic NK cells were determined. Lastly, β-adrenergic receptor (β-AR) signaling was investigated to determine possible mechanisms behind the SDR-induced NK cell alterations. Results indicated NK cells from SDR mice have increased expression of CD16 and CD69 and reduced NKG2a and Ly49a expression on splenic CD3-/DX5+ NK cells indicative of an activated phenotype, both immediately and 14h post-SDR. Administration of propranolol (10mg/kg; non-selective β-adrenergic receptor antagonist) was shown to block these "priming" effects at the 14h time-point. In the lung, SDR had similar effects on activation and inhibitory receptors 14h post-SDR, however no alterations were evident in the blood besides increased NK cells directly after SDR. Additionally, splenic NK cells from SDR mice had increased CD107a surface expression, cytolytic activity, and IFN-γ production was increased upon costimulation with IgG and IL-2 ex vivo. Collectively, these data suggest that social stress "primes" NK cells in the spleen and lung to be more proficient in their cytolytic and anti-viral/tumor effecter functions through β-adrenergic receptor dependent signaling.

  18. Repeated social defeat increases reactive emotional coping behavior and alters functional responses in serotonergic neurons in the rat dorsal raphe nucleus.

    PubMed

    Paul, Evan D; Hale, Matthew W; Lukkes, Jodi L; Valentine, McKenzie J; Sarchet, Derek M; Lowry, Christopher A

    2011-08-03

    Chronic stress is a vulnerability factor for a number of psychiatric disorders, including anxiety and affective disorders. Social defeat in rats has proven to be a useful paradigm to investigate the neural mechanisms underlying physiologic and behavioral adaptation to acute and chronic stress. Previous studies suggest that serotonergic systems may contribute to the physiologic and behavioral adaptation to chronic stress, including social defeat in rodent models. In order to test the hypothesis that repeated social defeat alters the emotional behavior and the excitability of brainstem serotonergic systems implicated in control of emotional behavior, we exposed adult male rats either to home cage control conditions, acute social defeat, or social defeat followed 24h later by a second social defeat encounter. We then assessed behavioral responses during social defeat as well as the excitability of serotonergic neurons within the dorsal raphe nucleus using immunohistochemical staining of tryptophan hydroxylase, a marker of serotonergic neurons, and the protein product of the immediate-early gene, c-fos. Repeated social defeat resulted in a shift away from proactive emotional coping behaviors, such as rearing (explorative escape behavior), and toward reactive emotional coping behaviors such as freezing. Both acute and repeated defeat led to widespread increases in c-Fos expression in serotonergic neurons in the dorsal raphe nucleus. Changes in behavior following a second exposure to social defeat, relative to acute defeat, were associated with decreased c-Fos expression in serotonergic neurons within the dorsal and ventral parts of the mid-rostrocaudal dorsal raphe nucleus, regions that have been implicated in 1) serotonergic modulation of fear- and anxiety-related behavior and 2) defensive behavior in conspecific aggressive encounters, respectively. These data support the hypothesis that serotonergic systems play a role in physiologic and behavioral responses to both

  19. Lithium chloride administration prevents spatial learning and memory impairment in repeated cerebral ischemia-reperfusion mice by depressing apoptosis and increasing BDNF expression in hippocampus.

    PubMed

    Fan, Mingyue; Jin, Wei; Zhao, Haifeng; Xiao, Yining; Jia, Yanqiu; Yin, Yu; Jiang, Xin; Xu, Jing; Meng, Nan; Lv, Peiyuan

    2015-09-15

    Lithium has been reported to have neuroprotective effects, but the preventive and treated role on cognition impairment and the underlying mechanisms have not been determined. In the present study, C57Bl/6 mice were subjected to repeated bilateral common carotid artery occlusion to induce the learning and memory deficits. 2 mmol/kg or 5 mmol/kg of lithium chloride (LiCl) was injected intraperitoneally per day before (for 7 days) or post (for 28 days) the operation. This repeated cerebral ischemia-reperfusion (IR) induced dynamic overexpression of ratio of Bcl-2/Bax and BDNF in hippocampus of mice. LiCl pretreatment and treatment significantly decreased the escape latency and increased the percentage of time that the mice spent in the target quadrant in Morris water maze. 2 mmol/kg LiCl evidently reversed the morphologic changes, up-regulated the survival neuron count and increased the BDNF gene and protein expression. 5 mmol/kg pre-LiCl significantly increased IR-stimulated reduce of Bcl-2/Bax and p-CREB/CREB. These results described suggest that pre-Li and Li treatment may induce a pronounced prevention on cognitive impairment. These effects may relay on the inhibition of apoptosis and increasing BDNF and p-CREB expression.

  20. Genetic variation among world populations: inferences from 100 Alu insertion polymorphisms.

    PubMed

    Watkins, W Scott; Rogers, Alan R; Ostler, Christopher T; Wooding, Steve; Bamshad, Michael J; Brassington, Anna-Marie E; Carroll, Marion L; Nguyen, Son V; Walker, Jerilyn A; Prasad, B V Ravi; Reddy, P Govinda; Das, Pradipta K; Batzer, Mark A; Jorde, Lynn B

    2003-07-01

    We examine the distribution and structure of human genetic diversity for 710 individuals representing 31 populations from Africa, East Asia, Europe, and India using 100 Alu insertion polymorphisms from all 22 autosomes. Alu diversity is highest in Africans (0.349) and lowest in Europeans (0.297). Alu insertion frequency is lowest in Africans (0.463) and higher in Indians (0.544), E. Asians (0.557), and Europeans (0.559). Large genetic distances are observed among African populations and between African and non-African populations. The root of a neighbor-joining network is located closest to the African populations. These findings are consistent with an African origin of modern humans and with a bottleneck effect in the human populations that left Africa to colonize the rest of the world. Genetic distances among all pairs of populations show a significant product-moment correlation with geographic distances (r = 0.69, P < 0.00001). F(ST), the proportion of genetic diversity attributable to population subdivision is 0.141 for Africans/E. Asians/Europeans, 0.047 for E. Asians/Indians/Europeans, and 0.090 for all 31 populations. Resampling analyses show that approximately 50 Alu polymorphisms are sufficient to obtain accurate and reliable genetic distance estimates. These analyses also demonstrate that markers with higher F(ST) values have greater resolving power and produce more consistent genetic distance estimates.

  1. Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome.

    PubMed

    Gu, Zhuoya; Jin, Ke; Crabbe, M James C; Zhang, Yang; Liu, Xiaolin; Huang, Yanyan; Hua, Mengyi; Nan, Peng; Zhang, Zhaolei; Zhong, Yang

    2016-04-01

    Transposable elements (TEs) have no longer been totally considered as "junk DNA" for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C (chromosome conformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r = 0.9, P < 2.2 × 10(16); IMR90 fibroblasts: r = 0.94, P < 2.2 × 10(16)) and also have a significant positive correlation with some remote functional DNA elements like enhancers and promoters (Enhancer: hESC: r = 0.997, P = 2.3 × 10(-4); IMR90: r = 0.934, P = 2 × 10(-2); Promoter: hESC: r = 0.995, P = 3.8 × 10(-4); IMR90: r = 0.996, P = 3.2 × 10(-4)). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes.

  2. Repeated exposure to corticosterone increases depression-like behavior in two different versions of the forced swim test without altering nonspecific locomotor activity or muscle strength.

    PubMed

    Marks, Wendie; Fournier, Neil M; Kalynchuk, Lisa E

    2009-08-04

    We have recently shown that repeated high dose injections of corticosterone (CORT) reliably increase depression-like behavior on a modified one-day version of the forced swim test. The main purpose of this experiment was to compare the effect of these CORT injections on our one-day version of the forced swim test and the more traditional two-day version of the test. A second purpose was to determine whether altered behavior in the forced swim test could be due to nonspecific changes in locomotor activity or muscle strength. Separate groups of rats received a high dose CORT injection (40 mg/kg) or a vehicle injection once per day for 21 consecutive days. Then, half the rats from each group were exposed to the traditional two-day forced swim test and the other half were exposed to our one-day forced swim test. After the forced swim testing, all the rats were tested in an open field and in a wire suspension grip strength test. The CORT injections significantly increased the time spent immobile and decreased the time spent swimming in both versions of the forced swim test. However, they had no significant effect on activity in the open field or grip strength in the wire suspension test. These results show that repeated CORT injections increase depression-like behavior regardless of the specific parameters of forced swim testing, and that these effects are independent of changes in locomotor activity or muscle strength.

  3. Alu elements in primates are preferentially lost from areas of high GC content

    PubMed Central

    Brookfield, John FY

    2013-01-01

    The currently-accepted dogma when analysing human Alu transposable elements is that ‘young’ Alu elements are found in low GC regions and ‘old’ Alus in high GC regions. The correlation between high GC regions and high gene frequency regions make this observation particularly difficult to explain. Although a number of studies have tackled the problem, no analysis has definitively explained the reason for this trend. These observations have been made by relying on the subfamily as a proxy for age of an element. In this study, we suggest that this is a misleading assumption and instead analyse the relationship between the taxonomic distribution of an individual element and its surrounding GC environment. An analysis of 103906 Alu elements across 6 human chromosomes was carried out, using the presence of orthologous Alu elements in other primate species as a proxy for age. We show that the previously-reported effect of GC content correlating with subfamily age is not reflected by the ages of the individual elements. Instead, elements are preferentially lost from areas of high GC content over time. The correlation between GC content and subfamily may be due to a change in insertion bias in the young subfamilies. The link between Alu subfamily age and GC region was made due to an over-simplification of the data and is incorrect. We suggest that use of subfamilies as a proxy for age is inappropriate and that the analysis of ortholog presence in other primate species provides a deeper insight into the data. PMID:23717800

  4. Saccharomyces SRP RNA secondary structures: a conserved S-domain and extended Alu-domain.

    PubMed

    Van Nues, Rob W; Brown, Jeremy D

    2004-01-01

    The contribution made by the RNA component of signal recognition particle (SRP) to its function in protein targeting is poorly understood. We have generated a complete secondary structure for Saccharomyces cerevisiae SRP RNA, scR1. The structure conforms to that of other eukaryotic SRP RNAs. It is rod-shaped with, at opposite ends, binding sites for proteins required for the SRP functions of signal sequence recognition (S-domain) and translational elongation arrest (Alu-domain). Micrococcal nuclease digestion of purified S. cerevisiae SRP separated the S-domain of the RNA from the Alu-domain as a discrete fragment. The Alu-domain resolved into several stable fragments indicating a compact structure. Comparison of scR1 with SRP RNAs of five yeast species related to S. cerevisiae revealed the S-domain to be the most conserved region of the RNA. Extending data from nuclease digestion with phylogenetic comparison, we built the secondary structure model for scR1. The Alu-domain contains large extensions, including a sequence with hallmarks of an expansion segment. Evolutionarily conserved bases are placed in the Alu- and S-domains as in other SRP RNAs, the exception being an unusual GU(4)A loop closing the helix onto which the signal sequence binding Srp54p assembles (domain IV). Surprisingly, several mutations within the predicted Srp54p binding site failed to disrupt SRP function in vivo. However, the strength of the Srp54p-scR1 and, to a lesser extent, Sec65p-scR1 interaction was decreased in these mutant particles. The availability of a secondary structure for scR1 will facilitate interpretation of data from genetic analysis of the RNA.

  5. Pharmacokinetics of Repeated Sodium Salicylate Administration to Laying Hens: Evidence for Time Dependent Increase in Drug Elimination from Plasma and Eggs

    PubMed Central

    Poźniak, Błażej; Grabowski, Tomasz; Motykiewicz-Pers, Karolina; Bobrek, Kamila; Rak, Lech; Bobusia, Katarzyna; Gaweł, Andrzej; Świtała, Marcin

    2015-01-01

    Salicylates were the first non-steroid anti-inflammatory drugs (NSAIDs) to be used in any species and are still widely used in humans and livestock. However, the data on their pharmacokinetics in animals is limited, especially after repeated administration. Evidence exist that in chickens (Gallus gallus) salicylate (SA) may induce its own elimination. The aim of this study was to investigate salicylate pharmacokinetics and egg residues during repeated administration of sodium salicylate (SS) to laying hens. Pharmacokinetics of SA was assessed during 14 d oral administration of SS at daily doses of 50 mg/kg and 200 mg/kg body weight to laying hens. On the 1st, 7th and 14th d a 24 h-long pharmacokinetic study was carried out, whereas eggs were collected daily. Salicylate concentrations in plasma and eggs were determined using high-performance liquid chromatography with ultraviolet detection and pharmacokinetic variables were calculated using a non-compartmental model. Mean residence time (MRT), minimal plasma concentration (Cmin, C16h) and elimination half-life (T1/2el) of SA showed gradual decrease in layers administered with a lower dose. Total body clearance (ClB) increased. Layers administered with the higher dose showed a decrease only in the T1/2el. In the low dose group, SA was found only in the egg white and was low throughout the experiment. Egg whites from the higher dose group showed initially high SA levels which significantly decreased during the experiment. Yolk SA levels were lower and showed longer periods of accumulation and elimination. Repeated administration of SS induces SA elimination, although this effect may differ depending on the dose and production type of a chicken. Decreased plasma drug concentration may have clinical implications during prolonged SS treatment. PMID:25893240

  6. Sensitization of depressive-like behavior during repeated maternal separation is associated with more-rapid increase in core body temperature and reduced plasma cortisol levels.

    PubMed

    Yusko, Brittany; Hawk, Kiel; Schiml, Patricia A; Deak, Terrence; Hennessy, Michael B

    2012-02-01

    Infant guinea pigs exhibit a 2-stage response to maternal separation: an initial active stage, characterized by vocalizing, and a second passive stage marked by depressive-like behavior (hunched posture, prolonged eye-closure, extensive piloerection) that appears to be mediated by proinflammatory activity. Recently we found that pups showed an enhanced (i.e., sensitized) depressive-like behavioral response during repeated separation. Further, core body temperature was higher during the beginning of a second separation compared to the first, suggesting a more-rapid stress-induced febrile response to separation the second day, though the possibility that temperature was already elevated prior to the second separation could not be ruled out. Therefore, the present study examined temperature prior to, and during, 2 daily separations. We also examined the temperature response to a third separation conducted 3 days after the second, and assessed the effect of repeated separation on plasma cortisol levels. Core temperature did not differ just prior to the separations, but showed a more-rapid increase and then decline during both a second and third separation than during a first. Temperature responses were not associated with changes in motor activity. Depressive-like behavior was greater during the second and third separations. Pups separated a first time showed a larger plasma cortisol response at the conclusion of separation than did animals of the same age separated a third time. In all, the results indicate that the sensitization of depressive-like behavior during repeated separations over several days is accompanied by a more-rapid febrile response that may be related to a reduction of glucocorticoid suppression.

  7. Development and validation of InnoQuant™, a sensitive human DNA quantitation and degradation assessment method for forensic samples using high copy number mobile elements Alu and SVA.

    PubMed

    Pineda, Gina M; Montgomery, Anne H; Thompson, Robyn; Indest, Brooke; Carroll, Marion; Sinha, Sudhir K

    2014-11-01

    There is a constant need in forensic casework laboratories for an improved way to increase the first-pass success rate of forensic samples. The recent advances in mini STR analysis, SNP, and Alu marker systems have now made it possible to analyze highly compromised samples, yet few tools are available that can simultaneously provide an assessment of quantity, inhibition, and degradation in a sample prior to genotyping. Currently there are several different approaches used for fluorescence-based quantification assays which provide a measure of quantity and inhibition. However, a system which can also assess the extent of degradation in a forensic sample will be a useful tool for DNA analysts. Possessing this information prior to genotyping will allow an analyst to more informatively make downstream decisions for the successful typing of a forensic sample without unnecessarily consuming DNA extract. Real-time PCR provides a reliable method for determining the amount and quality of amplifiable DNA in a biological sample. Alu are Short Interspersed Elements (SINE), approximately 300bp insertions which are distributed throughout the human genome in large copy number. The use of an internal primer to amplify a segment of an Alu element allows for human specificity as well as high sensitivity when compared to a single copy target. The advantage of an Alu system is the presence of a large number (>1000) of fixed insertions in every human genome, which minimizes the individual specific variation possible when using a multi-copy target quantification system. This study utilizes two independent retrotransposon genomic targets to obtain quantification of an 80bp "short" DNA fragment and a 207bp "long" DNA fragment in a degraded DNA sample in the multiplex system InnoQuant™. The ratio of the two quantitation values provides a "Degradation Index", or a qualitative measure of a sample's extent of degradation. The Degradation Index was found to be predictive of the observed loss

  8. Expansion of GA Dinucleotide Repeats Increases the Density of CLAMP Binding Sites on the X-Chromosome to Promote Drosophila Dosage Compensation

    PubMed Central

    Chery, Jessica; Siggers, Trevor; Boor, Sonia; Bliss, Jacob; Liu, Wei; Jogl, Gerwald; Rohs, Remo; Singh, Nadia D.; Bulyk, Martha L.; Tolstorukov, Michael Y.; Larschan, Erica

    2016-01-01

    Dosage compensation is an essential process that equalizes transcript levels of X-linked genes between sexes by forming a domain of coordinated gene expression. Throughout the evolution of Diptera, many different X-chromosomes acquired the ability to be dosage compensated. Once each newly evolved X-chromosome is targeted for dosage compensation in XY males, its active genes are upregulated two-fold to equalize gene expression with XX females. In Drosophila melanogaster, the CLAMP zinc finger protein links the dosage compensation complex to the X-chromosome. However, the mechanism for X-chromosome identification has remained unknown. Here, we combine biochemical, genomic and evolutionary approaches to reveal that expansion of GA-dinucleotide repeats likely accumulated on the X-chromosome over evolutionary time to increase the density of CLAMP binding sites, thereby driving the evolution of dosage compensation. Overall, we present new insight into how subtle changes in genomic architecture, such as expansions of a simple sequence repeat, promote the evolution of coordinated gene expression. PMID:27414415

  9. Repeated nightmares

    MedlinePlus

    ... different from night terrors . Alternative Names Nightmares - repeated; Dream anxiety disorder References American Academy of Family Physicians. Information from your family doctor. Nightmares and night terrors in children. ...

  10. Social stories: mechanisms of effectiveness in increasing game play skills in children diagnosed with autism spectrum disorder using a pretest posttest repeated measures randomized control group design.

    PubMed

    Quirmbach, Linda M; Lincoln, Alan J; Feinberg-Gizzo, Monica J; Ingersoll, Brooke R; Andrews, Siri M

    2009-02-01

    An increasing body of literature has indicated that social stories are an effective way to teach individuals diagnosed with autism appropriate social behavior. This study compared two formats of a social story targeting the improvement of social skills during game play using a pretest posttest repeated measures randomized control group design. A total of 45 children diagnosed with Autism Spectrum Disorder (ASD) ages 7-14 were randomly assigned to standard, directive, or control story conditions. Results demonstrated that the standard and directive story formats were equally as effective in eliciting, generalizing and maintaining the targeted social skills in participants who had prior game play experience and Verbal Comprehension Index (VCI) scores from the WISC-IV intelligence test in the borderline range or above.

  11. Replacement of histone H1 by H5 in vivo does not change the nucleosome repeat length of chromatin but increases its stability.

    PubMed Central

    Sun, J M; Ali, Z; Lurz, R; Ruiz-Carrillo, A

    1990-01-01

    In vivo competition between histones H1 and H5 for chromatin has been studied in rat sarcoma XC10 cells transfected with a glucocorticoid responsive MMTV-H5 gene. Activation of H5 expression results in accumulation of H5 in the nuclei where it partially replaces H1. H5 displaces H1 from its primary binding sites presumably during chromatin replication and also binds with high affinity to secondary chromatin sites normally not occupied by H1. Replacement of H1 by H5 to levels similar to those of mature chicken erythrocytes does not alter the nucleosome repeat length of chromatin. This indicates that H5 is not solely responsible for the increase in nucleosome spacing of maturing erythroid cells. Exchange of H1 by H5 in vivo or in vitro results in a higher compaction/stability of chromatin. Images Fig. 1. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. PMID:2328730

  12. Development of two highly sensitive forensic sex determination assays based on human DYZ1 and Alu repetitive DNA elements.

    PubMed

    Fazi, Amanda; Gobeski, Brianne; Foran, David

    2014-11-01

    Sex determination is a critical component of forensic identification, the standard genetic method for which is detection of the single copy amelogenin gene that has differing homologues on the X and Y chromosomes. However, this assay may not be sensitive enough when DNA samples are minute or highly compromised, thus other strategies for sex determination are needed. In the current research, two ultrasensitive sexing assays, based on real-time PCR and pyrosequencing, were developed targeting the highly repetitive elements DYZ1 on the Y chromosome and Alu on the autosomes. The DYZ1/Alu strategy was compared to amelogenin for overall sensitivity based on high molecular weight and degraded DNA, followed by assaying the sex of 34 touch DNA samples and DNA from 30 hair shafts. The real-time DYZ1/Alu assay proved to be approximately 1500 times more sensitive than its amelogenin counterpart based on high molecular weight DNA, and even more sensitive when sexing degraded DNA. The pyrosequencing DYZ1/Alu assay correctly sexed 26 of the touch DNAs, compared to six using amelogenin. Hair shaft DNAs showed equally improved sexing results using the DYZ1/Alu assays. Overall, both DYZ1/Alu assays were far more sensitive and accurate than was the amelogenin assay, and thus show great utility for sexing poor quality and low quantity DNA evidence.

  13. Alu-mediated large deletion of the CDSN gene as a cause of peeling skin disease.

    PubMed

    Wada, T; Matsuda, Y; Muraoka, M; Toma, T; Takehara, K; Fujimoto, M; Yachie, A

    2014-10-01

    Peeling skin disease (PSD) is an autosomal recessive skin disorder caused by mutations in CDSN and is characterized by superficial peeling of the upper epidermis. Corneodesmosin (CDSN) is a major component of corneodesmosomes that plays an important role in maintaining epidermis integrity. Herein, we report a patient with PSD caused by a novel homozygous large deletion in the 6p21.3 region encompassing the CDSN gene, which abrogates CDSN expression. Several genes including C6orf15, PSORS1C1, PSORS1C2, CCHCR1, and TCF19 were also deleted, however, the patient showed only clinical features typical of PSD. The deletion size was 59.1 kb. Analysis of the sequence surrounding the breakpoint showed that both telomeric and centromeric breakpoints existed within Alu-S sequences that were oriented in opposite directions. These results suggest an Alu-mediated recombination event as the mechanism underlying the deletion in our patient.

  14. Polymorphic Alu Insertion/Deletion in Different Caste and Tribal Populations from South India

    PubMed Central

    Chinniah, Rathika; Vijayan, Murali; Thirunavukkarasu, Manikandan; Mani, Dhivakar; Raju, Kamaraj; Ravi, Padma Malini; Sivanadham, Ramgopal; C, Kandeepan; N, Mahalakshmi; Karuppiah, Balakrishnan

    2016-01-01

    Seven human-specific Alu markers were studied in 574 unrelated individuals from 10 endogamous groups and 2 hill tribes of Tamil Nadu and Kerala states. DNA was isolated, amplified by PCR-SSP, and subjected to agarose gel electrophoresis, and genotypes were assigned for various Alu loci. Average heterozygosity among caste populations was in the range of 0.292–0.468. Among tribes, the average heterozygosity was higher for Paliyan (0.3759) than for Kani (0.2915). Frequency differences were prominent in all loci studied except Alu CD4. For Alu CD4, the frequency was 0.0363 in Yadavas, a traditional pastoral and herd maintaining population, and 0.2439 in Narikuravars, a nomadic gypsy population. The overall genetic difference (Gst) of 12 populations (castes and tribes) studied was 3.6%, which corresponds to the Gst values of 3.6% recorded earlier for Western Asian populations. Thus, our study confirms the genetic similarities between West Asian populations and South Indian castes and tribes and supported the large scale coastal migrations from Africa into India through West Asia. However, the average genetic difference (Gst) of Kani and Paliyan tribes with other South Indian tribes studied earlier was 8.3%. The average Gst of combined South and North Indian Tribes (CSNIT) was 9.5%. Neighbor joining tree constructed showed close proximity of Kani and Paliyan tribal groups to the other two South Indian tribes, Toda and Irula of Nilgiri hills studied earlier. Further, the analysis revealed the affinities among populations and confirmed the presence of North and South India specific lineages. Our findings have documented the highly diverse (micro differentiated) nature of South Indian tribes, predominantly due to isolation, than the endogamous population groups of South India. Thus, our study firmly established the genetic relationship of South Indian castes and tribes and supported the proposed large scale ancestral migrations from Africa, particularly into South India

  15. TRIzol and Alu qPCR-based quantification of metastatic seeding within the skeleton.

    PubMed

    Preston Campbell, J; Mulcrone, P; Masood, S K; Karolak, M; Merkel, A; Hebron, K; Zijlstra, A; Sterling, J; Elefteriou, F

    2015-08-14

    Current methods for detecting disseminated tumor cells in the skeleton are limited by expense and technical complexity. We describe a simple and inexpensive method to quantify, with single cell sensitivity, human metastatic cancer in the mouse skeleton, concurrently with host gene expression, using TRIzol-based DNA/RNA extraction and Alu sequence qPCR amplification. This approach enables precise quantification of tumor cells and corresponding host gene expression during metastatic colonization in xenograft models.

  16. Design and implementation of low power clock gated 64-bit ALU on ultra scale FPGA

    NASA Astrophysics Data System (ADS)

    Gupta, Ashutosh; Murgai, Shruti; Gulati, Anmol; Kumar, Pradeep

    2016-03-01

    64-bit energy efficient Arithmetic and Logic Unit using negative latch based clock gating technique is designed in this paper. The 64-bit ALU is designed using multiplexer based full adder cell. We have designed a 64-bit ALU with a gated clock. We have used negative latch based circuit for generating gated clock. This gated clock is used to control the multiplexer based 64-bit ALU. The circuit has been synthesized on kintex FPGA through Xilinx ISE Design Suite 14.7 using 28 nm technology in Verilog HDL. The circuit has been simulated on Modelsim 10.3c. The design is verified using System Verilog on QuestaSim in UVM environment. We have achieved 74.07%, 92. 93% and 95.53% reduction in total clock power, 89.73%, 91.35% and 92.85% reduction in I/Os power, 67.14%, 62.84% and 74.34% reduction in dynamic power and 25.47%, 29.05% and 46.13% reduction in total supply power at 20 MHz, 200 MHz and 2 GHz frequency respectively. The power has been calculated using XPower Analyzer tool of Xilinx ISE Design Suite 14.3.

  17. Repeated anabolic-androgenic steroid treatment during adolescence increases vasopressin V(1A) receptor binding in Syrian hamsters: correlation with offensive aggression.

    PubMed

    DeLeon, Katrina R; Grimes, Jill M; Melloni, Richard H

    2002-09-01

    Repeated anabolic-androgenic steroid treatment during adolescence increases hypothalamic vasopressin and facilitates offensive aggression in male Syrian hamsters (Mesocricetus auratus). The current study investigated whether anabolic-androgenic steroid exposure during this developmental period influenced vasopressin V(1A) receptor binding activity in the hypothalamus and several other brain areas implicated in aggressive behavior in hamsters. To test this, adolescent male hamsters were administered anabolic steroids or sesame oil throughout adolescence, tested for offensive aggression, and examined for differences in vasopressin V(1A) receptor binding using in situ autoradiography. When compared with control animals, aggressive, adolescent anabolic steroid-treated hamsters showed significant increases (20-200%) in the intensity of vasopressin V(1A) receptor labeling in several aggression areas, including the ventrolateral hypothalamus, bed nucleus of the stria terminalis, and lateral septum. However, no significant differences in vasopressin V(1A) receptor labeling were found in other brain regions implicated in aggressive responding, most notably the lateral zone from the medial preoptic area to anterior hypothalamus and the corticomedial amygdala. These data suggest that adolescent anabolic steroid exposure may facilitate offensive aggression by increasing vasopressin V(1A) receptor binding in several key areas of the hamster brain.

  18. Repeated social defeat causes increased anxiety-like behavior and alters splenocyte function in C57BL/6 and CD-1 mice.

    PubMed

    Kinsey, Steven G; Bailey, Michael T; Sheridan, John F; Padgett, David A; Avitsur, Ronit

    2007-05-01

    The experimental model, social disruption (SDR), is a model of social stress in which mice are repeatedly attacked and defeated in their home cage by an aggressive conspecific. In terms of the impact of this stressor on the immune response, SDR has been reported to cause hyperinflammation and glucocorticoid insensitivity. To this point however, the behavioral consequences of SDR have not been thoroughly characterized. Because social defeat has been reported to cause anxiety- and depressive-like behaviors, the current study was designed to assess whether SDR also causes anxiety- and depressive-like behaviors. Using the light/dark preference test and the open field test as tools to measure behaviors characteristic of anxiety, the data showed that C57BL/6 and CD-1 male mice subjected to SDR displayed increased anxiety-like behavior. The increase in anxiety-like behaviors persisted for at least 1 week after the cessation of the stressor. In contrast, depressive-like behaviors were not elicited by SDR as assessed by the forced swim test or the tail suspension test. These data indicate that social disruption stress causes an increase in anxiety-like behaviors, but not depressive-like behaviors.

  19. Repeated Social Defeat Causes Increased Anxiety-Like Behavior and Alters Splenocyte Function in C57BL/6 and CD-1 Mice

    PubMed Central

    Kinsey, Steven G.; Bailey, Michael T.; Sheridan, John F.; Padgett, David A.; Avitsur, Ronit

    2007-01-01

    The experimental model, social disruption (SDR), is a model of social stress in which mice are repeatedly attacked and defeated in their home cage by an aggressive conspecific. In terms of the impact of this stressor on the immune response, SDR has been reported to cause hyperinflammation and glucocorticoid insensitivity. To this point however, the behavioral consequences of SDR have not been thoroughly characterized. Because social defeat has been reported to cause anxiety- and depressive-like behaviors, the current study was designed to assess whether SDR also causes anxiety- and depressive-like behaviors. Using the light/dark preference test and the open field test as tools to measure behaviors characteristic of anxiety, the data showed that C57BL/6 and CD-1 male mice subjected to SDR displayed increased anxiety-like behavior. The increase in anxiety-like behaviors persisted for at least one week after the cessation of the stressor. In contrast, depressive-like behaviors were not elicited by SDR as assessed by the forced swim test or the tail suspension test. These data indicate that social disruption stress causes an increase in anxiety-like behaviors, but not depressive-like behaviors. PMID:17178210

  20. Human intron-encoded AluACA RNAs and telomerase RNA share a common element promoting RNA accumulation

    PubMed Central

    Ketele, Amandine; Kiss, Tamás; Jády, Beáta E.

    2016-01-01

    ABSTRACT Mammalian cells express hundreds of intron-encoded box H/ACA RNAs which fold into a common hairpin-hinge-hairpin-tail structure, interact with 4 evolutionarily conserved proteins, dyskerin, Nop10, Nhp2 and Gar1, and function mainly in RNA pseudouridylation. The human telomerase H/ACA RNA (hTR) directs telomeric DNA synthesis and it carries a 5′-terminal domain encompassing the telomeric template sequence. The primary hTR transcript is synthesized from an independent gene by RNA polymerase II and undergoes 3′ end processing controlled by the 3′-terminal H/ACA domain. The apical stem-loop of the 3′ hairpin of hTR carries a unique biogenesis-promoting element, the BIO motif that promotes hTR processing and RNP assembly. AluACA RNAs represent a distinct class of human H/ACA RNAs; they are processed from intronic Alu repetitive sequences. As compared to canonical H/ACA RNAs, the AluACA RNAs carry unusually short or long 5′ hairpins and generally, they accumulate at low levels. Here, we demonstrate that the suboptimal 5′ hairpins are responsible for the weak expression of AluACA RNAs. We also show that AluACA RNAs frequently carry a processing/stabilization element that is structurally and functionally indistinguishable from the hTR BIO motif. Both hTR and AluACA biogenesis-promoting elements are located in the terminal stem-loop of the 3′-terminal H/ACA hairpin, they show perfect structural conservation and are functionally interchangeable in in vivo RNA processing reactions. Our results demonstrate that the BIO motif, instead of being confined to hTR, is a more general H/ACA RNP biogenesis-facilitating element that can also promote processing/assembly of intron-encoded AluACA RNPs. PMID:27726486

  1. Alu-miRNA interactions modulate transcript isoform diversity in stress response and reveal signatures of positive selection

    NASA Astrophysics Data System (ADS)

    Pandey, Rajesh; Bhattacharya, Aniket; Bhardwaj, Vivek; Jha, Vineet; Mandal, Amit K.; Mukerji, Mitali

    2016-09-01

    Primate-specific Alus harbor different regulatory features, including miRNA targets. In this study, we provide evidence for miRNA-mediated modulation of transcript isoform levels during heat-shock response through exaptation of Alu-miRNA sites in mature mRNA. We performed genome-wide expression profiling coupled with functional validation of miRNA target sites within exonized Alus, and analyzed conservation of these targets across primates. We observed that two miRNAs (miR-15a-3p and miR-302d-3p) elevated in stress response, target RAD1, GTSE1, NR2C1, FKBP9 and UBE2I exclusively within Alu. These genes map onto the p53 regulatory network. Ectopic overexpression of miR-15a-3p downregulates GTSE1 and RAD1 at the protein level and enhances cell survival. This Alu-mediated fine-tuning seems to be unique to humans as evident from the absence of orthologous sites in other primate lineages. We further analyzed signatures of selection on Alu-miRNA targets in the genome, using 1000 Genomes Phase-I data. We found that 198 out of 3177 Alu-exonized genes exhibit signatures of selection within Alu-miRNA sites, with 60 of them containing SNPs supported by multiple evidences (global-FST > 0.3, pair-wise-FST > 0.5, Fay-Wu’s H < ‑20, iHS > 2.0, high ΔDAF) and implicated in p53 network. We propose that by affecting multiple genes, Alu-miRNA interactions have the potential to facilitate population-level adaptations in response to environmental challenges.

  2. Alu-miRNA interactions modulate transcript isoform diversity in stress response and reveal signatures of positive selection

    PubMed Central

    Pandey, Rajesh; Bhattacharya, Aniket; Bhardwaj, Vivek; Jha, Vineet; Mandal, Amit K.; Mukerji, Mitali

    2016-01-01

    Primate-specific Alus harbor different regulatory features, including miRNA targets. In this study, we provide evidence for miRNA-mediated modulation of transcript isoform levels during heat-shock response through exaptation of Alu-miRNA sites in mature mRNA. We performed genome-wide expression profiling coupled with functional validation of miRNA target sites within exonized Alus, and analyzed conservation of these targets across primates. We observed that two miRNAs (miR-15a-3p and miR-302d-3p) elevated in stress response, target RAD1, GTSE1, NR2C1, FKBP9 and UBE2I exclusively within Alu. These genes map onto the p53 regulatory network. Ectopic overexpression of miR-15a-3p downregulates GTSE1 and RAD1 at the protein level and enhances cell survival. This Alu-mediated fine-tuning seems to be unique to humans as evident from the absence of orthologous sites in other primate lineages. We further analyzed signatures of selection on Alu-miRNA targets in the genome, using 1000 Genomes Phase-I data. We found that 198 out of 3177 Alu-exonized genes exhibit signatures of selection within Alu-miRNA sites, with 60 of them containing SNPs supported by multiple evidences (global-FST > 0.3, pair-wise-FST > 0.5, Fay-Wu’s H < −20, iHS > 2.0, high ΔDAF) and implicated in p53 network. We propose that by affecting multiple genes, Alu-miRNA interactions have the potential to facilitate population-level adaptations in response to environmental challenges. PMID:27586304

  3. Repeated adolescent MDMA ("Ecstasy") exposure in rats increases behavioral and neuroendocrine responses to a 5-HT2A/2C agonist.

    PubMed

    Biezonski, Dominik K; Courtemanche, Andrea B; Hong, Sang B; Piper, Brian J; Meyer, Jerrold S

    2009-02-03

    MDMA (3,4-methylenedioxymethamphetamine) is a popular recreational drug among adolescents. The present study aimed to determine the effects of repeated intermittent administration of 10 mg/kg MDMA during adolescence on behavioral (Experiment 1) and neuroendocrine (Experiment 2) responses of rats to the 5-HT(2A/2C) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and on [(3)H]ketanserin binding to 5-HT(2A) receptors. In the first experiment, MDMA pretreatment increased the frequency of head twitches and back muscle contractions, but not wet-dog shakes, to a high-dose DOI challenge. In the second experiment, both the prolactin and corticosterone responses to DOI were potentiated in MDMA-pretreated animals. No changes were found in 5-HT(2A) receptor binding in the hypothalamus or other forebrain areas that were examined. These results indicate that intermittent adolescent MDMA exposure enhances sensitivity of 5-HT(2A/2C) receptors in the CNS, possibly through changes in downstream signaling mechanisms.

  4. Repeated 6-Hz Corneal Stimulation Progressively Increases FosB/ΔFosB Levels in the Lateral Amygdala and Induces Seizure Generalization to the Hippocampus

    PubMed Central

    Giordano, Carmela; Vinet, Jonathan; Curia, Giulia; Biagini, Giuseppe

    2015-01-01

    Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session, most likely due to activity of principal cells. These findings indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs. PMID:26555229

  5. Repeated 6-Hz Corneal Stimulation Progressively Increases FosB/ΔFosB Levels in the Lateral Amygdala and Induces Seizure Generalization to the Hippocampus.

    PubMed

    Giordano, Carmela; Vinet, Jonathan; Curia, Giulia; Biagini, Giuseppe

    2015-01-01

    Exposure to repetitive seizures is known to promote convulsions which depend on specific patterns of network activity. We aimed at evaluating the changes in seizure phenotype and neuronal network activation caused by a modified 6-Hz corneal stimulation model of psychomotor seizures. Mice received up to 4 sessions of 6-Hz corneal stimulation with fixed current amplitude of 32 mA and inter-stimulation interval of 72 h. Video-electroencephalography showed that evoked seizures were characterized by a motor component and a non-motor component. Seizures always appeared in frontal cortex, but only at the fourth stimulation they involved the hippocampus, suggesting the establishment of an epileptogenic process. Duration of seizure non-motor component progressively decreased after the second session, whereas convulsive seizures remained unchanged. In addition, a more severe seizure phenotype, consisting of tonic-clonic generalized convulsions, was predominant after the second session. Immunohistochemistry and double immunofluorescence experiments revealed a significant increase in neuronal activity occurring in the lateral amygdala after the fourth session, most likely due to activity of principal cells. These findings indicate a predominant role of amygdala in promoting progressively more severe convulsions as well as the late recruitment of the hippocampus in the seizure spread. We propose that the repeated 6-Hz corneal stimulation model may be used to investigate some mechanisms of epileptogenesis and to test putative antiepileptogenic drugs.

  6. Hoffmann reflex is increased after 14 days of daily repeated Achilles tendon vibration for the soleus but not for the gastrocnemii muscles.

    PubMed

    Lapole, Thomas; Pérot, Chantal

    2012-02-01

    In a previous study, Achilles tendon vibrations were enough to improve the triceps surae (TS) activation capacities and also to slightly increase TS Hoffmann reflex (H-reflex) obtained by summing up soleus (Sol) and gastrocnemii (GM and GL) EMGs. The purpose of the present study was to analyze separately Sol and GM or GL reflexes to account for different effects of the vibrations on the reflex excitability of the slow soleus and of the gastrocnemii muscles. A control group (n = 13) and a vibration group (n = 16) were tested in pre-test and post-test conditions. The Achilles tendon vibration program consisted of 1 h of daily vibration (frequency: 50 Hz) applied during 14 days. Maximal Sol, GM and GL H-reflexes, and M-waves were recorded, and their H(max)/M(max) ratios gave the index of reflex excitability. After the vibration protocol, only Sol H(max)/M(max) was enhanced (p < 0.001). The enhanced Sol reflex excitability after vibration is in favor of a decrease in the pre-synaptic inhibition due to the repeated vibrations and the high solicitation of the reflex pathway. Those results of a short period of vibration applied at rest may be limited to the soleus because of its high density in muscle spindles and slow motor units, both structures being very sensitive to vibrations.

  7. Pediatric Brain: Repeated Exposure to Linear Gadolinium-based Contrast Material Is Associated with Increased Signal Intensity at Unenhanced T1-weighted MR Imaging.

    PubMed

    Flood, Thomas F; Stence, Nicholas V; Maloney, John A; Mirsky, David M

    2017-01-01

    Purpose To determine whether repeated exposure of the pediatric brain to a linear gadolinium-based contrast agent (GBCA) is associated with an increase in signal intensity (SI) relative to that in GBCA-naive control subjects at unenhanced T1-weighted magnetic resonance (MR) imaging. Materials and Methods This single-center, retrospective study was approved by the institutional review board and compliant with HIPAA. The authors evaluated 46 pediatric patients who had undergone at least three GBCA-enhanced MR examinations (30 patients for two-group analysis and 16 for pre- and post-GBCA exposure comparisons) and 57 age-matched GBCA-naive control subjects. The SI in the globus pallidus, thalamus, dentate nucleus, and pons was measured at unenhanced T1-weighted MR imaging. Globus pallidus-thalamus and dentate nucleus-pons SI ratios were calculated and compared between groups and relative to total cumulative gadolinium dose, age, sex, and number of and mean time between GBCA-enhanced examinations. Analysis included the Wilcoxon signed rank test, Wilcoxon rank sum test, and Spearman correlation coefficient. Results Patients who underwent multiple GBCA-enhanced examinations had increased SI ratios within the dentate nucleus (mean SI ratio ± standard error of the mean for two-group comparison: 1.007 ± 0.0058 for GBCA-naive group and 1.046 ± 0.0060 for GBCA-exposed group [P < .001]; mean SI ratio for pre- and post-GBCA comparison: 0.995 ± 0.0062 for pre-GBCA group and 1.035 ± 0.0063 for post-GBCA group [P < .001]) but not the globus pallidus (mean SI ratio for two-group comparison: 1.131 ± 0.0070 for GBCA-naive group and 1.014 ± 0.0091 for GBCA-exposed group [P = .21]; mean SI ratio for pre- and post-GBCA comparison: 1.068 ± 0.0094 for pre-GBCA group and 1.093 ± 0.0134 for post-GBCA group [P = .12]). There was a significant correlation between dentate nucleus SI and total cumulative gadolinium dose (r = 0.4; 95% confidence interval [CI]: 0.03, 0.67; P = .03), but

  8. Atomic interaction of the MEAM type for the study of intermetallics in the Al-U alloy

    NASA Astrophysics Data System (ADS)

    Pascuet, M. I.; Fernández, J. R.

    2015-12-01

    Interaction for both pure Al and Al-U alloys of the MEAM type are developed. The obtained Al interatomic potential assures its compatibility with the details of the framework presently adopted. The Al-U interaction fits various properties of the Al2U, Al3U and Al4U intermetallics. The potential verifies the stability of the intermetallic structures in a temperature range compatible with that observed in the phase diagram, and also takes into account the greater stability of these structures relative to others that are competitive in energy. The intermetallics are characterized by calculating elastic and thermal properties and point defect parameters. Molecular dynamics simulations show a growth of the Al3U intermetallic in the Al/U interface in agreement with experimental evidence.

  9. Development of an Alu-based, QSY 7-labeled primer PCR method for quantitation of human DNA in forensic samples.

    PubMed

    Nicklas, Janice A; Buel, Eric

    2003-03-01

    Determining the amount of human DNA extracted from a crime scene sample is an important step in DNA profiling. The forensic community relies almost entirely upon a technique (slot blot) to quantitate human DNA that is imprecise, time consuming, and labor intensive. This paper describes the development of a new technique based on PCR amplification of a repetitive Alu sequence. Specific primers were used to amplify a 124-bp fragment of Alu sequence; amplification was detected by SYBR Green I staining in a fluorescent plate reader. To reduce background in the plate reader assay, QSY-7 labeled primers were utilized. The assay was tested on animal DNAs, human blood spots, mock crime samples, and degraded DNA in comparison with the slot blot technique. The QSY Alu assay has a dynamic range of 10 ng to 10 pg, and is sensitive, specific, fast, quantitative, and comparable in cost to the slot blot assay.

  10. Distribution of a marker of germline methylation differs between major families of transposon-derived repeats in the human genome

    PubMed Central

    Sigurdsson, Martin I.; Smith, Albert V.; Bjornsson, Hans T.; Jonsson, Jon J.

    2012-01-01

    A potential relationship between transposon-derived repeats (TDR) and human germline methylation is of biological importance since many genes are flanked by TDR and methylation could affect the expression of nearby genes. Furthermore, DNA methylation has been suggested as a global defense mechanism against genome instability threatened by TDR. We studied the correlation between the density of HapMap methyl-associated SNPs (mSNPs), a marker of germline methylation, and proportion of TDR. After correcting for confounding variables, we found a negative correlation between proportion of Alu repeats and mSNP density for 125–1000 kb windows. Similar results were found for the most active subgroup of repeats. In contrast, a negative correlation between proportion of L1 repeats and mSNP density was found only in the larger 1000 kb windows. Using methylation data on germ cells (sperm) from the Human Epigenome Project, we found a lower proportion of Alu repeats adjacent (3–15 kb) to hypermethylated amplicons. On the contrary, there was a higher proportion of L1 repeats in the 3–5 kb of sequence flanking hypermethylated amplicons but not in the 10–15 kb flanks. Our data indicate a differential response to the major repeat families and that DNA methylation is unlikely to be a uniform global defense system against all TDR. It appears to play a role for the L1 subgroup, with sequences adjacent to L1 repeats methylated in response to their proximity. In contrast, sequences adjacent to Alu repeats appear to be hypomethylated, arguing against a role of methylation in germline defense against those elements. PMID:22093876

  11. Reprogramming triggers endogenous L1 and Alu retrotransposition in human induced pluripotent stem cells.

    PubMed

    Klawitter, Sabine; Fuchs, Nina V; Upton, Kyle R; Muñoz-Lopez, Martin; Shukla, Ruchi; Wang, Jichang; Garcia-Cañadas, Marta; Lopez-Ruiz, Cesar; Gerhardt, Daniel J; Sebe, Attila; Grabundzija, Ivana; Merkert, Sylvia; Gerdes, Patricia; Pulgarin, J Andres; Bock, Anja; Held, Ulrike; Witthuhn, Anett; Haase, Alexandra; Sarkadi, Balázs; Löwer, Johannes; Wolvetang, Ernst J; Martin, Ulrich; Ivics, Zoltán; Izsvák, Zsuzsanna; Garcia-Perez, Jose L; Faulkner, Geoffrey J; Schumann, Gerald G

    2016-01-08

    Human induced pluripotent stem cells (hiPSCs) are capable of unlimited proliferation and can differentiate in vitro to generate derivatives of the three primary germ layers. Genetic and epigenetic abnormalities have been reported by Wissing and colleagues to occur during hiPSC derivation, including mobilization of engineered LINE-1 (L1) retrotransposons. However, incidence and functional impact of endogenous retrotransposition in hiPSCs are yet to be established. Here we apply retrotransposon capture sequencing to eight hiPSC lines and three human embryonic stem cell (hESC) lines, revealing endogenous L1, Alu and SINE-VNTR-Alu (SVA) mobilization during reprogramming and pluripotent stem cell cultivation. Surprisingly, 4/7 de novo L1 insertions are full length and 6/11 retrotransposition events occurred in protein-coding genes expressed in pluripotent stem cells. We further demonstrate that an intronic L1 insertion in the CADPS2 gene is acquired during hiPSC cultivation and disrupts CADPS2 expression. These experiments elucidate endogenous retrotransposition, and its potential consequences, in hiPSCs and hESCs.

  12. Signal Increase on Unenhanced T1-Weighted Images in the Rat Brain After Repeated, Extended Doses of Gadolinium-Based Contrast Agents

    PubMed Central

    Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin Andrew; Lohrke, Jessica; Frenzel, Thomas; Pietsch, Hubertus

    2016-01-01

    Objectives In this prospective preclinical study, we evaluated T1-weighted signal intensity in the deep cerebellar nuclei (CN) and globus pallidus (GP) up to 24 days after repeated administration of linear and macrocyclic gadolinium-based contrast agents (GBCAs) using homologous imaging and evaluation methods as in the recently published retrospective clinical studies. In a second part of the study, cerebrospinal fluid (CSF) spaces were evaluated for contrast enhancement by fluid-attenuated magnetic resonance imaging (MRI). Materials and Methods Sixty adult male Wistar-Han rats were randomly divided into a control and 5 GBCA groups (n = 10 per group). The administered GBCAs were gadodiamide, gadopentetate dimeglumine, and gadobenate dimeglumine (linear GBCAs) as well as gadobutrol and gadoterate meglumine (macrocyclic GBCAs) and saline (control). Over a period of 2 weeks, the animals received 10 intravenous injections at a dose of 2.5 mmol Gd/kg body weight, each on 5 consecutive days per week. Before GBCA administration, as well as 3 and 24 days after the last injection, a whole-brain MRI was performed using a standard T1-weighted 3-dimensional turbo spin echo sequence on a clinical 1.5 T scanner. The ratios of signal intensities in deep CN to pons (CN/Po) and GP to thalamus (GP/Th) were determined. For the evaluation of the CSF spaces, 18 additional rats were randomly divided into 6 groups (n = 3 per group) that received the same GBCAs as in the first part of the study. After MR cisternography for anatomical reference, a fluid-attenuated inversion recovery sequence was performed before and 1 minute after intravenous injection of a dose of 1 mmol Gd/kg body weight GBCA or saline. Results A significantly increased signal intensity ratio of CN/Po was observed 3 and 24 days after the last injection of gadodiamide and gadobenate dimeglumine. No significant changes were observed between the 2 time points. Gadopentetate dimeglumine injection led to a moderately elevated

  13. Increased prevalence of the seven-repeat variant of the dopamine D4 receptor gene in patients with obsessive-compulsive disorder with tics.

    PubMed

    Cruz, C; Camarena, B; King, N; Páez, F; Sidenberg, D; de la Fuente, J R; Nicolini, H

    1997-08-01

    The polymorphism characterized by a varying number of 48 bp repeats (VNTR) in the dopamine D4 receptor (DRD4) gene was examined in 61 obsessive-compulsive disorder (OCD) probands with and without tics. Most of the OCD patients with tics showed at least one copy of the 7-fold variant compared to those affected subjects without tics (91 vs. 48%, respectively, Yates corrected chi2 = 5.54, P = 0.018). Similarly, a higher number of copies of this common variant were detected in the group of probands displaying tics compared to those OCD's without tics (Yates corrected chi2 = 4.66, P = 0.03). Our study suggests that the seven-repeat allele of the DRD4 gene could be a factor in the phenotypic variance of tics among OCD individuals.

  14. A spontaneously arising mutation in connexin32 with repeated passage of FRTL-5 cells coincides with increased growth rate and reduced thyroxine release

    NASA Technical Reports Server (NTRS)

    Green, L. M.; Murray, D. K.; Tran, D. T.; Nelson, G. A.; Shah, M. M.; Luben, R. A.

    2001-01-01

    regions of the Cx32 molecule contain the sequences and epitopes to which probes and antibodies are directed, and as such alterations of these regions with repeated passage explains reports by others that FRTL-5 cells do not express Cx32, and implies that cultures used for these assessments were passed more than 15 times. To determine if genetic or epigenetic abnormalities existed in FRTL-5 cells we performed chromosome spreads from various passage cultures. FRTL-5 cells have been reported to be diploid and more recently non-diploid; however, we found them to be fully tetraploid. This tetraploidy appears to be unstable in that later passes are tetraploid plus two or three extra chromosomes. There were no obvious translocations, breaks or large-scale interstitial deletions of any chromosomes in the FRTL-5 cultures tested. As FRTL-5 cells were repeatedly passed their morphology changed. Monolayer areas spread from beneath the follicles, and the follicles became flattened in appearance. These physical changes were coincident with dramatically increased growth rates. Early cultures (passed 3-12 times) divided on average every 49+/-1 h, whereas later passes (passes 20-25) divided every 28+/-3 h. To correlate these changes with a measure of thyroid function we assayed T(4) output. Early passage follicular cultures incubated for 6 h with sodium iodide, released on average 5.27+/- 0.33 ng/ml of T(4)/100 follicles. Later passes, or early passes treated with heptanol to down-regulate Cx32, released an average of 3.84+/-0.50 ng/ml of T(4)/100 follicles. There was a 27% difference in T(4) release between early follicular cultures, that were coupled by Cx32, and late or down-regulated early follicular cultures, that were uncoupled (P<0.0001). Collectively, the physical changes documented in this study were coincident with the loss of functional Cx32. This implies a relationship between the loss of intercellular communication and changes in morphogenic appearance, growth rate and

  15. A spontaneously arising mutation in connexin32 with repeated passage of FRTL-5 cells coincides with increased growth rate and reduced thyroxine release

    NASA Technical Reports Server (NTRS)

    Green, L. M.; Murray, D. K.; Tran, D. T.; Nelson, G. A.; Shah, M. M.; Luben, R. A.

    2001-01-01

    regions of the Cx32 molecule contain the sequences and epitopes to which probes and antibodies are directed, and as such alterations of these regions with repeated passage explains reports by others that FRTL-5 cells do not express Cx32, and implies that cultures used for these assessments were passed more than 15 times. To determine if genetic or epigenetic abnormalities existed in FRTL-5 cells we performed chromosome spreads from various passage cultures. FRTL-5 cells have been reported to be diploid and more recently non-diploid; however, we found them to be fully tetraploid. This tetraploidy appears to be unstable in that later passes are tetraploid plus two or three extra chromosomes. There were no obvious translocations, breaks or large-scale interstitial deletions of any chromosomes in the FRTL-5 cultures tested. As FRTL-5 cells were repeatedly passed their morphology changed. Monolayer areas spread from beneath the follicles, and the follicles became flattened in appearance. These physical changes were coincident with dramatically increased growth rates. Early cultures (passed 3-12 times) divided on average every 49+/-1 h, whereas later passes (passes 20-25) divided every 28+/-3 h. To correlate these changes with a measure of thyroid function we assayed T(4) output. Early passage follicular cultures incubated for 6 h with sodium iodide, released on average 5.27+/- 0.33 ng/ml of T(4)/100 follicles. Later passes, or early passes treated with heptanol to down-regulate Cx32, released an average of 3.84+/-0.50 ng/ml of T(4)/100 follicles. There was a 27% difference in T(4) release between early follicular cultures, that were coupled by Cx32, and late or down-regulated early follicular cultures, that were uncoupled (P<0.0001). Collectively, the physical changes documented in this study were coincident with the loss of functional Cx32. This implies a relationship between the loss of intercellular communication and changes in morphogenic appearance, growth rate and

  16. Gain of a New Exon by a Lineage-Specific Alu Element-Integration Event in the BCS1L Gene during Primate Evolution

    PubMed Central

    Park, Sang-Je; Kim, Young-Hyun; Lee, Sang-Rae; Choe, Se-Hee; Kim, Myung-Jin; Kim, Sun-Uk; Kim, Ji-Su; Sim, Bo-Woong; Song, Bong-Seok; Jeong, Kang-Jin; Jin, Yeung-Bae; Lee, Youngjeon; Park, Young-Ho; Park, Young Il; Huh, Jae-Won; Chang, Kyu-Tae

    2015-01-01

    BCS1L gene encodes mitochondrial protein and is a member of conserved AAA protein family. This gene is involved in the incorporation of Rieske FeS and Qcr10p into complex III of respiratory chain. In our previous study, AluYRa2-derived alternative transcript in rhesus monkey genome was identified. However, this transcript has not been reported in human genome. In present study, we conducted evolutionary analysis of AluYRa2-exonized transcript with various primate genomic DNAs and cDNAs from humans, rhesus monkeys, and crab-eating monkeys. Remarkably, our results show that AluYRa2 element has only been integrated into genomes of Macaca species. This Macaca lineage-specific integration of AluYRa2 element led to exonization event in the first intron region of BCS1L gene by producing a conserved 3′ splice site. Intriguingly, in rhesus and crab-eating monkeys, more diverse transcript variants by alternative splicing (AS) events, including exon skipping and different 5′ splice sites from humans, were identified. Alignment of amino acid sequences revealed that AluYRa2-exonized transcript has short N-terminal peptides. Therefore, AS events play a major role in the generation of various transcripts and proteins during primate evolution. In particular, lineage-specific integration of Alu elements and species-specific Alu-derived exonization events could be important sources of gene diversification in primates. PMID:26537194

  17. Gene flow and genetic structure in the Galician population (NW Spain) according to Alu insertions

    PubMed Central

    Varela, Tito A; Fariña, José; Diéguez, Lois Pérez; Lodeiro, Rosa

    2008-01-01

    Background The most recent Alu insertions reveal different degrees of polymorphism in human populations, and a series of characteristics that make them particularly suitable genetic markers for Human Biology studies. This has led these polymorphisms to be used to analyse the origin and phylogenetic relationships between contemporary human groups. This study analyses twelve Alu sequences in a sample of 216 individuals from the autochthonous population of Galicia (NW Spain), with the aim of studying their genetic structure and phylogenetic position with respect to the populations of Western and Central Europe and North Africa, research that is of special interest in revealing European population dynamics, given the peculiarities of the Galician population due to its geographical situation in western Europe, and its historical vicissitudes. Results The insertion frequencies of eleven of the Alu elements analysed were within the variability range of European populations, while Yb8NBC125 proved to be the lowest so far recorded to date in Europe. Taking the twelve polymorphisms into account, the GD value for the Galician population was 0.268. The comparative analyses carried out using the MDS, NJ and AMOVA methods reveal the existence of spatial heterogeneity, and identify three population groups that correspond to the geographic areas of Western-Central Europe, Eastern Mediterranean Europe and North Africa. Galicia is shown to be included in the Western-Central European cluster, together with other Spanish populations. When only considering populations from Mediterranean Europe, the Galician population revealed a degree of genetic flow similar to that of the majority of the populations from this geographic area. Conclusion The results of this study reveal that the Galician population, despite its geographic situation in the western edge of the European continent, occupies an intermediate position in relation to other European populations in general, and Iberian

  18. Association of the Alu insertion polymorphism in the progesterone receptor gene with breast cancer in a Mexican population

    PubMed Central

    Figuera, Luis E.; Flores-Ramos, Liliana Gómez; Puebla-Pérez, Ana María; Zúñiga-González, Guillermo Moisés

    2015-01-01

    Introduction The progesterone receptor (PR) gene plays an important role in reproduction-related events. Data on polymorphisms in the PR gene have revealed associations with cancer, particularly for the Alu insertion polymorphism, which has been suggested to affect progesterone receptor function and contribute to tumor promotion in the mammary gland. Material and methods We examined the role of the Alu insertion polymorphism in the PR gene by comparing the genotypes of 209 healthy Mexican women with those of 481 Mexican women with breast cancer (BC). Results The genotype frequencies observed in the controls and BC patients were 0% and 4% for T2/T2 (Alu insertion), 16% and 21% for T1/T2, and 84% and 75% for T1/T1 (Alu deletion), respectively. The obtained odds ratio (OR) was 1.7, with a 95% confidence interval (95% CI) of 1.1–2.6, p = 0.009, for the T1/T2–T2/T2 genotypes. The association was also evident when the distributions of the T1/T2–T2/T2 genotypes in patients in the following categories were compared: obesity grade II (OR = 1.81, 95% CI: 1.03–3.18, p = 0.039) and the chemotherapy response (OR = 1.91, 95% CI: 1.27–3.067, p = 0.002). Conclusions The T1/T2–T2/T2 genotypes of the Alu insertion polymorphism in the PR gene are associated with BC susceptibility in the analyzed Mexican population. PMID:26170848

  19. Does RNA editing compensate for Alu invasion of the primate genome?

    PubMed

    Levanon, Erez Y; Eisenberg, Eli

    2015-02-01

    One of the distinctive features of the primate genome is the Alu element, a repetitive short interspersed element, over a million highly similar copies of which account for >10% of the genome. A direct consequence of this feature is that primates' transcriptome is highly enriched in long stable dsRNA structures, the preferred target of adenosine deaminases acting on RNAs (ADARs), which are the enzymes catalyzing A-to-I RNA editing. Indeed, A-to-I editing by ADARs is extremely abundant in primates: over a hundred million editing sites exist in their genomes. However, there are few essential editing sites conserved across mammals that have maintained their editing level despite the radical change in ADAR target landscape. Here, we review and discuss the cost of having an unusual amount of dsRNA and editing in the transcriptome, as well as the opportunities it presents, which might have contributed to the accelerated evolution of the primates.

  20. Alu sequence involvement in transcriptional insulation of the keratin 18 gene in transgenic mice.

    PubMed Central

    Thorey, I S; Ceceña, G; Reynolds, W; Oshima, R G

    1993-01-01

    The human keratin 18 (K18) gene is expressed in a variety of adult simple epithelial tissues, including liver, intestine, lung, and kidney, but is not normally found in skin, muscle, heart, spleen, or most of the brain. Transgenic animals derived from the cloned K18 gene express the transgene in appropriate tissues at levels directly proportional to the copy number and independently of the sites of integration. We have investigated in transgenic mice the dependence of K18 gene expression on the distal 5' and 3' flanking sequences and upon the RNA polymerase III promoter of an Alu repetitive DNA transcription unit immediately upstream of the K18 promoter. Integration site-independent expression of tandemly duplicated K18 transgenes requires the presence of either an 825-bp fragment of the 5' flanking sequence or the 3.5-kb 3' flanking sequence. Mutation of the RNA polymerase III promoter of the Alu element within the 825-bp fragment abolishes copy number-dependent expression in kidney but does not abolish integration site-independent expression when assayed in the absence of the 3' flanking sequence of the K18 gene. The characteristics of integration site-independent expression and copy number-dependent expression are separable. In addition, the formation of the chromatin state of the K18 gene, which likely restricts the tissue-specific expression of this gene, is not dependent upon the distal flanking sequences of the 10-kb K18 gene but rather may depend on internal regulatory regions of the gene. Images PMID:7692231

  1. microRNAs and Alu elements in the p53-Mdm2-Mdm4 regulatory network.

    PubMed

    Hoffman, Yonit; Pilpel, Yitzhak; Oren, Moshe

    2014-06-01

    p53 is a transcription factor that governs numerous stress response pathways within the cell. Maintaining the right levels of p53 is crucial for cell survival and proper cellular homeostasis. The tight regulation of p53 involves many cellular components, most notably its major negative regulators Mdm2 and Mdm4, which maintain p53 protein amount and activity in tight check. microRNAs (miRNAs) are small non-coding RNAs that target specific mRNAs to translational arrest and degradation. miRNAs are also key components of the normal p53 pathway, joining forces with Mdm2 and Mdm4 to maintain proper p53 activity. Here we review the current knowledge of miRNAs targeting Mdm2 and Mdm4, and their importance in different tissues and in pathological states such as cancer. In addition, we address the role of Alu sequences-highly abundant retroelements spread throughout the human genome, and their impact on gene regulation via the miRNA machinery. Alus occupy a significant portion of genes' 3'UTR, and as such they have the potential to impact mRNA regulation. Since Alus are primate-specific, they introduce a new regulatory layer into primate genomes. Alus can influence and alter gene regulation, creating primate-specific cancer-preventive regulatory mechanisms to sustain the transition to longer life span in primates. We review the possible influence of Alu sequences on miRNA functionality in general and specifically within the p53 network.

  2. Effects of Short-term Exposure to Inhalable Particulate Matter on DNA Methylation of Tandem Repeats

    PubMed Central

    Guo, Liqiong; Byun, Hyang-Min; Zhong, Jia; Motta, Valeria; Barupal, Jitendra; Zheng, Yinan; Dou, Chang; Zhang, Feiruo; McCracken, John P.; Diaz, Anaité; Marco, Sanchez-Guerra; Colicino, Silvia; Schwartz, Joel; Wang, Sheng; Hou, Lifang; Baccarelli, Andrea A.

    2015-01-01

    There is compelling evidence that particulate matter (PM) increases lung cancer risk by triggering systemic inflammation, and leukocyte DNA hypomethylation. However, previous investigations focused on repeated element sequences from LINE-1 and Alu families. Tandem repeats, which display a greater propensity to mutate, and are often hypomethylated in cancer patients, have never been investigated in individuals exposed to PM. We measured methylation of three tandem repeats (SATα, NBL2, D4Z4) by polymerase chain reaction–pyrosequencing on blood samples from truck drivers and office workers (60 per group) in Beijing, China. We used lightweight monitors to measure personal PM2.5 (PM with aerodynamic diameter ≤2.5 µm) and elemental carbon (EC, a tracer of PM from vehicular traffic). Ambient PM10 data were obtained from air quality measuring stations. Overall, an interquartile increase in personal PM2.5 and ambient PM10 levels was associated with a significant covariate-adjusted decrease in SATα methylation (−1.35% 5-methyl cytosine [5mC], P = 0.01; and −1.33%5mC; P = 0.01, respectively). Effects from personal PM2.5 and ambient PM10 on SATα methylation were stronger in truck drivers (−2.34%5mC, P = 0.02; −1.44%5mC, P = 0.06) than office workers (−0.95%5mC, P = 0.26; −1.25%5mC, P = 0.12, respectively). Ambient PM10 was negatively correlated with NBL2 methylation in truck drivers (−1.38%5mC, P = 0.03) but not in office workers (1.04%5mC, P = 0.13). Our result suggests that PM exposure is associated with hypomethylation of selected tandem repeats. Measuring tandem-repeat hypomethylation in easy-to-obtain blood specimens might identify individuals with biological effects and potential cancer risk from PM exposure. PMID:24436168

  3. Repeated 3-minute stair climbing-descending exercise after a meal over 2 weeks increases serum 1,5-anhydroglucitol levels in people with type 2 diabetes

    PubMed Central

    Honda, Hiroto; Igaki, Makoto; Hatanaka, Yuki; Komatsu, Motoaki; Tanaka, Shin-Ichiro; Miki, Tetsuo; Matsuki, Yumika; Takaishi, Tetsuo; Hayashi, Tatsuya

    2017-01-01

    [Purpose] The purpose of this study was to examine the hypoglycemic effect of a postprandial exercise program using brief stair climbing-descending exercise in people with type 2 diabetes. [Subjects and Methods] Seven males with uncomplicated type 2 diabetes (age 68.0 ± 3.7 years) performed two sets of stair climbing-descending exercise 60 and 120 min after each meal for the first 2 weeks but not for the following 2 weeks. Each set of exercise comprised 3-min of continuous repetition of climbing briskly to the second floor followed by slow waking down to the first floor in their home. A rest period of 1–2 min was allowed between each set. [Results] Serum 1,5-anhydroglucitol level was significantly higher by 11.5% at the end of the 2-week exercise period than at the baseline. By contrast, the 1,5-anhydroglucitol level at the end of the following 2-week period did not differ from the baseline value. Fasting blood glucose level and insulin resistance index at the end of the exercise period did not differ from the baseline value. [Conclusion] Repeated 3-min bouts of stair climbing-descending exercise after a meal may be a promising method for improving postprandial glycemic control in people with type 2 diabetes. PMID:28210043

  4. Opposing Control by Transcription Factors MYB61 and MYB3 Increases Freezing Tolerance by Relieving C-Repeat Binding Factor Suppression1[OPEN

    PubMed Central

    Zhang, Yunqin; Miao, Zhenyan; Xie, Can; Meng, Xiangzhao; Deng, Jie; Mysore, Kirankumar S.; Frugier, Florian; Wang, Tao

    2016-01-01

    Cold acclimation is an important process by which plants respond to low temperature and enhance their winter hardiness. C-REPEAT BINDING FACTOR1 (CBF1), CBF2, and CBF3 genes were shown previously to participate in cold acclimation in Medicago truncatula. In addition, MtCBF4 is transcriptionally induced by salt, drought, and cold stresses. We show here that MtCBF4, shown previously to enhance drought and salt tolerance, also positively regulates cold acclimation and freezing tolerance. To identify molecular factors acting upstream and downstream of the MtCBF4 transcription factor (TF) in cold responses, we first identified genes that are differentially regulated upon MtCBF4 overexpression using RNAseq Digital Gene Expression Profiling. Among these, we showed that MtCBF4 directly activates the transcription of the COLD ACCLIMATION SPECIFIC15 (MtCAS15) gene. To gain insights into how MtCBF4 is transcriptionally regulated in response to cold, an R2R3-MYB TF, MtMYB3, was identified based on a yeast one-hybrid screen as binding directly to MYB cis-elements in the MtCBF4 promoter, leading to the inhibition of MtCBF4 expression. In addition, another MYB TF, MtMYB61, identified as an interactor of MtMYB3, can relieve the inhibitory effect of MtMYB3 on MtCBF4 transcription. This study, therefore, supports a model describing how MtCBF4 is regulated by antagonistic MtMYB3/MtMYB61 TFs, leading to the up-regulation of downstream targets such as MtCAS15 acting in cold acclimation in M. truncatula. PMID:27578551

  5. The Infertility of Repeat-Breeder Cows During Summer Is Associated with Decreased Mitochondrial DNA and Increased Expression of Mitochondrial and Apoptotic Genes in Oocytes.

    PubMed

    Ferreira, Roberta Machado; Chiaratti, Marcos Roberto; Macabelli, Carolina Habermann; Rodrigues, Carlos Alberto; Ferraz, Márcio Leão; Watanabe, Yeda Fumie; Smith, Lawrence Charles; Meirelles, Flávio Vieira; Baruselli, Pietro Sampaio

    2016-03-01

    Oocyte quality is known to be a major cause of infertility in repeat-breeder (RB) and heat-stressed dairy cows. However, the mechanisms by which RB oocytes become less capable of supporting embryo development remain largely unknown. Thus, the aim of this study was to investigate whether the decreased oocyte competence of RB cows (RBs) during summer is associated with an altered gene expression profile and a decrease in mitochondrial DNA (mtDNA) copy number. Therefore, oocytes collected from heifers, non-RBs in peak lactation (PLs), and RBs were used to evaluate mtDNA amounts as well as the expression levels of genes associated with the mitochondria (MT-CO1, NRF1, POLG, POLG2, PPARGC1A, and TFAM), apoptosis (BAX, BCL2, and ITM2B), and oocyte maturation (BMP15, FGF8, FGF10, FGF16, FGF17, and GDF9). The oocytes retrieved from RBs during winter contained over eight times more mtDNA than those retrieved from RBs during summer. They also contained significantly less mtDNA than oocytes retrieved from heifers and PLs during summer. Moreover, the expression of mitochondria- (NRF1, POLG, POLG2, PPARGC1A, and TFAM) and apoptosis-related (BAX and ITM2B) genes, as well as of GDF9, in RB oocytes collected during summer was significantly greater than that in oocytes collected from heifers and PLs during the same season. In oocytes from heifers and PLs, the expression levels of these genes were lower in those collected during summer compared with winter, but this difference was not observed in oocytes collected from RBs. Altogether, these data provide evidence of altered gene expression and reduced mtDNA copy number in the oocytes collected from RBs during summer. This indicates a loss of fertility in RBs during summer, which might be caused by a possible mitochondrial dysfunction associated with a greater chance of oocytes to undergo apoptosis.

  6. An Alu-based, MGB Eclipse real-time PCR method for quantitation of human DNA in forensic samples.

    PubMed

    Nicklas, Janice A; Buel, Eric

    2005-09-01

    The forensic community needs quick, reliable methods to quantitate human DNA in crime scene samples to replace the laborious and imprecise slot blot method. A real-time PCR based method has the possibility of allowing development of a faster and more quantitative assay. Alu sequences are primate-specific and are found in many copies in the human genome, making these sequences an excellent target or marker for human DNA. This paper describes the development of a real-time Alu sequence-based assay using MGB Eclipse primers and probes. The advantages of this assay are simplicity, speed, less hands-on-time and automated quantitation, as well as a large dynamic range (128 ng/microL to 0.5 pg/microL).

  7. Inhibition of LINE-1 and Alu retrotransposition by exosomes encapsidating APOBEC3G and APOBEC3F.

    PubMed

    Khatua, Atanu K; Taylor, Harry E; Hildreth, James E K; Popik, Waldemar

    2010-04-25

    Human cytidine deaminases, including APOBEC3G (A3G) and A3F, are part of a cellular defense system against retroviruses and retroelements including non-LTR retrotransposons LINE-1 (L1) and Alu. Expression of cellular A3 proteins is sufficient for inhibition of L1 and Alu retrotransposition, but the effect of A3 proteins transferred in exosomes on retroelement mobilization is unknown. Here, we demonstrate for the first time that exosomes secreted by CD4(+)H9 T cells and mature monocyte-derived dendritic cells encapsidate A3G and A3F and inhibit L1 and Alu retrotransposition. A3G is the major contributor to the inhibitory activity of exosomes, however, the contribution of A3F in H9 exosomes cannot be excluded. Additionally, we show that exosomes encapsidate mRNAs coding for A3 proteins. A3G mRNA, and less so A3F, was enriched in exosomes secreted by H9 cells. Exosomal A3G mRNA was functional in vitro. Whether exosomes inhibit retrotransposons in vivo requires further investigation.

  8. The Y Alu polymorphism in southern African populations and its relationship to other Y-specific polymorphisms

    SciTech Connect

    Spurdle, A.B.; Jenkins, T. ); Hammer, M.F. )

    1994-02-01

    Y-linked polymorphisms were studied in a number of African populations. The frequency of the alleles of a Y-specific Alu insertion polymorphism, termed the [open quotes]Y Alu polymorphism,[close quotes] was determined in 889 individuals from 23 different African population groups. A trend in frequency was observed, with the insert largely absent in Caucasoid populations, at intermediate frequency in the Khoisan, and at high frequency in Negroids. The insert predates diversification of Homo sapiens, since it occurs in all groups. The Alu insertion is believed to result from a unique mutation event, and comparisons between this and several other Y-linked polymorphisms were carried out in an attempt to validate their usefulness in population and evolutionary studies. The p21A1/Taql and pDP31/EcoRI polymorphisms and 49a/TaqI alleles were all shown to have arisen on more than one occasion, and evidence exists for a preraciation crossover event between the Y-linked pseudoautosomal XY275 locus and the Y chromosome pseudoautosomal boundary. 33 refs., 4 figs., 5 tabs.

  9. Are the surgeon's movements repeatable? An analysis of the feasibility and expediency of implementing support procedures guiding the surgical tools and increasing motion accuracy during the performance of stereotypical movements by the surgeon.

    PubMed

    Podsędkowski, Leszek Robert; Moll, Jacek; Moll, Maciej; Frącczak, Łukasz

    2014-03-01

    The developments in surgical robotics suggest that it will be possible to entrust surgical robots with a wider range of tasks. So far, it has not been possible to automate the surgery procedures related to soft tissue. Thus, the objective of the conducted studies was to confirm the hypothesis that the surgery telemanipulator can be equipped with certain routines supporting the surgeon in leading the surgical tools and increasing motion accuracy during stereotypical movements. As the first step in facilitating the surgery, an algorithm will be developed which will concurrently provide automation and allow the surgeon to maintain full control over the slave robot. The algorithm will assist the surgeon in performing typical movement sequences. This kind of support must, however, be preceded by determining the reference points for accurately defining the position of the stitched tissue. It is in relation to these points that the tool's trajectory will be created, along which the master manipulator will guide the surgeon's hand. The paper presents the first stage, concerning the selection of movements for which the support algorithm will be used. The work also contains an analysis of surgical movement repeatability. The suturing movement was investigated in detail by experimental research in order to determine motion repeatability and verify the position of the stitched tissue. Tool trajectory was determined by a motion capture stereovision system. The study has demonstrated that the suturing movement could be considered as repeatable; however, the trajectories performed by different surgeons exhibit some individual characteristics.

  10. Alu insertion polymorphisms in the Balkans and the origins of the Aromuns.

    PubMed

    Comas, D; Schmid, H; Braeuer, S; Flaiz, C; Busquets, A; Calafell, F; Bertranpetit, J; Scheil, H-G; Huckenbeck, W; Efremovska, L; Schmidt, H

    2004-03-01

    We have analysed 11 human-specific Alu insertion polymorphisms in the Balkans to elucidate the origins of the Aromuns, a linguistic isolate inhabiting scattered areas in the Balkan Peninsula. Four Aromun samples (two from the Republic of Macedonia, one from Albania, and one from Romania) and five neighbouring populations (Macedonians, Albanians, Romanians, Greeks, and Turks) were analysed by means of genetic distances, principal components and analyses of the molecular variance (AMOVA). Three hypotheses were tested: Aromuns are Romanophonic Greeks; the result of a Romanian southward migration; or local descendants of the Thracians. The analyses show that the Aromuns do not constitute a homogeneous group separated from the rest of the Balkan populations. Grouping by language or geography does not explain the genetic differences observed in the region, suggesting a lack of genetic structure in the area. Aromuns do not seem to be particularly related to Greeks, Romanians, or to other Romance speakers. The Aromuns might have their origin to the south of the Danube river, with extensive gene flow with the neighbouring populations. The present results suggest a common ancestry of all Balkan populations, including Aromuns, with a lack of correlation between genetic differentiation and language or ethnicity, stressing that no major migration barriers have existed in the making of the complex Balkan human puzzle.

  11. Questioning the "melting pot": analysis of Alu inserts in three population samples from Uruguay.

    PubMed

    Hidalgo, Pedro C; Mut, Patricia; Ackermann, Elizabeth; Figueiro, Gonzalo; Sans, Monica

    2014-01-01

    The way that immigrants integrate into recipient societies has been discussed for decades, mainly from the perspective of the social sciences. Uruguay, as other American countries, received diffferent waves of European immigrants, although the details of the process of assimilation, when it did occur, are unclear. In this study we used genetic markers to understand the process experienced by the Basques, one of the major migration waves that populated Uruguay, and their relation to other immigrants, as well as to Native American and African descendants. For this purpose, we analyzed the allele frequencies of 10 ALU loci (A25, ACE, APOA1, B65, D1, F13B, PV92, TPA25, HS2.43, and HS4.65) in three samples from Uruguay (two of Basque descendants, one of non-Basque descendants) from two locations: Montevideo and Trinidad. No departure from Hardy-Weinberg expectations was observed, with the exceptions of the APOA1 and D1 loci in the non-Basque descendants' samples. Our data show that the major genetic contribution in the three samples comes from Europe (78-88%), with minor African (10-15%) and Native American (0-10%) contributions. Genetic distances reveal that Basque descendants from Trinidad cluster with Europeans, whereas both Montevideo samples cluster together and are separate from other populations, showing two diffferent types of integration, related to the general characteristics of each regional population.

  12. Phylogenetic information in polymorphic L1 and Alu insertions from East Asians and Native American populations.

    PubMed

    Mateus Pereira, L H; Socorro, A; Fernandez, I; Masleh, M; Vidal, D; Bianchi, N O; Bonatto, S L; Salzano, F M; Herrera, R J

    2005-09-01

    This study attempts to ascertain genetic affinities between Native American and East Asian populations by analyzing four polymorphic Alu insertions (PAIs) and three L1 polymorphic loci. These two genetic systems demonstrated strong congruence when levels of diversity and genetic distances were considered. Overall, genetic relatedness within Native American groups does not correlate with geographical and linguistic structure, although strong grouping for Native Americans with East Asians was demonstrated, with clear discrimination from African and European groups. Most of the variation was assigned to differences occurring within groups, but the interpopulation variation found for South Amerindians was recognizably higher in comparison to the other sampled groups of populations. Our data suggest that bottleneck events followed by strong influence of genetic drift in the process of the peopling of the Americas may have been determinant factors in delineating the genetic background of present-day South Amerindians. Since no clear subgroups were detected within Native Americans and East Asians, there is no indication of multiple waves in the early colonization of the New World.

  13. Increasing Belief in the Effectiveness of HIV Treatment as Prevention: Results of Repeated, National Surveys of Australian Gay and Bisexual Men, 2013-15.

    PubMed

    Holt, Martin; Lea, Toby; Schmidt, Heather-Marie; Murphy, Dean; Rosengarten, Marsha; Crawford, David; Ellard, Jeanne; Kolstee, Johann; de Wit, John

    2016-07-01

    We surveyed Australian gay and bisexual men, assessing belief in HIV treatment as prevention (TasP) and support for early treatment. We identified the characteristics of participants who believed in TasP and supported early treatment using multivariate logistic regression. In 2013, 1316 men participated; 1251 participated in 2015. Belief in TasP increased from 2.6 % in 2013 to 13.1 % in 2015 (p < 0.001). The increase was most noticeable among HIV-positive men (from 9.7 % to 46.2 %). Support for early treatment increased from 71.8 % to 75.3 % (p = 0.02). Belief in TasP was associated with being HIV-positive, having a tertiary education, having recent condomless anal intercourse with casual male partners, and ever having taken post-exposure prophylaxis. Support for early HIV treatment was associated with being younger, living in New South Wales and being in paid employment. We recommend continued monitoring of the growing gap in belief about TasP between HIV-positive men and HIV-negative/untested men.

  14. Progressive Seizure Aggravation in the Repeated 6-Hz Corneal Stimulation Model Is Accompanied by Marked Increase in Hippocampal p-ERK1/2 Immunoreactivity in Neurons

    PubMed Central

    Giordano, Carmela; Costa, Anna M.; Lucchi, Chiara; Leo, Giuseppina; Brunel, Luc; Fehrentz, Jean-Alain; Martinez, Jean; Torsello, Antonio; Biagini, Giuseppe

    2016-01-01

    The 6-Hz corneal stimulation test is used to screen novel antiepileptic molecules to overcome the problem of drug refractoriness. Although recognized as a standard test, it has been evaluated only recently in the attempt to characterize the putative neuronal networks involved in seizures caused by corneal stimulation. In particular, by recording from the CA1 region we previously established that the hippocampus participates to propagation of seizure activity. However, these findings were not corroborated by using markers of neuronal activation such as FosB/ΔFosB antigens. In view of this discrepancy, we performed new experiments to characterize the changes in levels of phosphorylated extracellular signal-regulated kinases1/2 (p-ERK1/2), which are also used as markers of neuronal activation. To this aim, mice underwent corneal stimulation up to three different times, in three sessions separated by an interval of 3 days. To characterize a group in which seizures could be prevented by pharmacological treatment, we also considered pretreatment with the ghrelin receptor antagonist EP-80317 (330 μg/kg). Control mice were sham-treated. Video electrocorticographic (ECoG) recordings were obtained from mice belonging to each group of treatment. Animals were finally used to characterize the immunoreactivity for FosB/ΔFosB and p-ERK1/2 in the hippocampus. As previously shown, FosB/ΔFosB levels were highly increased throughout the hippocampus by the first induced seizure but, in spite of the progressively increased seizure severity, they were restored to control levels after the third stimulation. At variance, corneal stimulation caused a progressive increase in p-ERK1/2 immunoreactivity all over the hippocampus, especially in CA1, peaking in the third session. Predictably, EP-80317 administration reduced both duration and severity of seizures, prevented the increase in FosB/ΔFosB levels in the first session, and partially counteracted the increase in p-ERK1/2 levels in

  15. The reinforcement enhancing effects of nicotine depend on the incentive value of non-drug reinforcers and increase with repeated drug injections.

    PubMed

    Palmatier, Matthew I; Matteson, Gina L; Black, Jessica J; Liu, Xiu; Caggiula, Anthony R; Craven, Laure; Donny, Eric C; Sved, Alan F

    2007-06-15

    We have hypothesized that nicotine has two effects on reinforcement; it increases the probability of responses resulting in nicotine delivery (primary reinforcement) and enhances the apparent reward value of non-nicotine reinforcers (reinforcement enhancing effect). The present studies investigated two predictions generated by this hypothesis: (1) that the reinforcement enhancing effect will depend on apparent stimulus reward value and (2) that the temporal profile of this effect would depend on the pharmacological profile of nicotine. In Experiment 1, rats were trained to lever press for one of two audio-visual stimuli that differed in their intrinsic reinforcing value and then the effect of pre-session nicotine (0.4 mg/kg base) or saline injections was tested. The stimulus that supported very low rates of operant responding displayed smaller increases in responding after pre-session injections of nicotine. In Experiment 2 the effect of nicotine injected 5 min before the session was compared to the effect of nicotine injected 1h after the session using the more reinforcing stimulus condition from the first experiment. A control group received only vehicle injections. In contrast to nicotine injected just prior to the session, post-session injections of nicotine had no detectable effect on responding for the more reinforcing stimulus. These results indicate that the reinforcement enhancing action of nicotine depends on the intensity of the primary reinforcer and that enhanced reinforcement by nicotine depends on coincident access to a stimulus with reinforcing properties.

  16. A Repeated Measures Experiment of School Playing Environment to Increase Physical Activity and Enhance Self-Esteem in UK School Children

    PubMed Central

    Wood, Carly; Gladwell, Valerie; Barton, Jo

    2014-01-01

    School playtime provides daily opportunities for children to be active outdoors, but only makes small contributions to physical activity (PA) requirements. Natural environments facilitate unstructured PA and children report a preference for play in nature. Thus, play on the school field might encourage children to be more active during playtime. The primary aim of this study was to examine the impact of the school playing environment on children's PA. Descriptive data and fitness were assessed in 25 children aged 8–9 years from a single primary school. Over two consecutive weeks participants were allocated to either play on the school field or playground during playtime. The order of play in the two areas was randomised and counterbalanced. Moderate to vigorous PA (MVPA) was assessed during playtime on the last two days of each week using accelerometers. There was a significant interaction of environment and sex on MVPA during morning play (F(1,22) = 6.27; P<0.05; np2 = 0.222), but not during lunch (P>0.05; np2 = 0.060) or all of playtime combined (P>0.05; np2 = 0.140). During morning play boys were significantly more active than girls on the playground (t(23) = 1.32; P<0.01; n2 = 0.291), but not on the field (P>0.05; n2 = 0.071). For lunch (F(1,22) = 24,11; P<0.001; np2 = 0.523) and all of playtime combined (F(1,22) = 33.67; P<0.001; np2 = 0.616) there was a significant effect of environment. There was also a significant main effect of sex during lunch (F(1,22) = 11.56; P<0.01; np2 = 0.344) and all of playtime combined (F(1,22) = 12.37; P<0.01; np2 = 0.371). MVPA was higher on the field and boys were more active than girls. Play on the field leads to increases in MVPA, particularly in girls. The promising trend for the effect of the natural environment on MVPA indicates that interventions aimed at increasing MVPA should use the natural environment and that schools should encourage greater use of their

  17. School-based intervention with children. Peer-modeling, reward and repeated exposure reduce food neophobia and increase liking of fruits and vegetables.

    PubMed

    Laureati, Monica; Bergamaschi, Valentina; Pagliarini, Ella

    2014-12-01

    This study investigated the effectiveness of the 'Food Dudes' school-based intervention consisting of rewards, peer-modeling and food exposure on food neophobia and the liking of fruits and vegetables (FV) in a large cohort of children. Five-hundred sixty children recruited from three schools were assigned to the experimental or control group. For 16 days, children in the experimental group watched motivational videos, were read letters to encourage them to eat FV and received a small reward for eating one portion of both a fruit and a vegetable. The control group was only provided with FV for the same time period. Food neophobia and liking were measured in both groups of children before and after the intervention, and a follow-up measurement was carried out 6 months later. The intervention was effective in reducing food neophobia and, most importantly, a persistent effect was observed 6 months after the intervention as children of the experimental group showed significantly lower neophobia scores than the control group. Additionally, the program was effective in increasing liking for both FV; however, this effect was maintained only for fruit after 6 months.

  18. Repeating LP events and increases in high-frequency seismic energy preceding the December 1999 eruption of the quiescently active Telica Volcano, Nicaragua

    NASA Astrophysics Data System (ADS)

    Rodgers, M.; Roman, D. C.; Geirsson, H.; Lafemina, P.; Muñoz, A.; Guzman, C.; Tenorio, V.

    2010-12-01

    Telica volcano, Nicaragua, is a ‘quiescently active’ basaltic andesite stratovolcano located in the Central American volcanic front. A high rate of long-period (LP) seismicity has been recorded at Telica since the installation of a single vertical-component 1 Hz seismic sensor (TELN) near its summit in 1993 by the Instituto Nicaragüense de Estudios Territoriales (INETER). Due to the continuously high rate of LPs at Telica, traditional methods of forecasting volcanic activity may not be applicable; therefore an understanding of the nature of precursory changes in Telica’s seismicity is necessary to accurately forecast future volcanic activity. A VEI 2 eruption of Telica occurred on the 29th December 1999, preceded by a series of small explosions between the 3rd-15th October 1999. Here we analyse an eight-month period of seismicity bracketing this activity, in an attempt to identify precursory changes with respect to background seismicity. Between August 1999 and March 2000 over 18,000 seismic events were recorded on TELN. We first calculated the dominant frequencies (i.e. frequency with dominant spectral energy) for all events recorded during this period. A time series of the dominant event frequencies between August 1999 and March 2000 shows a significant increase in the number of high frequency (> 5 Hz) events and, in LP events, a shift in the two dominant spectral energy peaks from 2 Hz and 4 Hz to 2 Hz and 3 Hz in the month before the October 1999 explosions. Next, we selected six representative eight-day periods, three from before the explosions and three from after, for multiplet analysis using waveform cross-correlation. Multiplet analysis of the six selected time periods reveal significant changes in behaviour. In period 1 (more than one month before the explosions) events are poorly correlated. In periods 2 and 3 (less than one month before the explosions) we identified several unique families of LP events, each having high cross-correlation values

  19. N-Terminal Ile-Orn- and Trp-Orn-Motif Repeats Enhance Membrane Interaction and Increase the Antimicrobial Activity of Apidaecins against Pseudomonas aeruginosa

    PubMed Central

    Bluhm, Martina E. C.; Schneider, Viktoria A. F.; Schäfer, Ingo; Piantavigna, Stefania; Goldbach, Tina; Knappe, Daniel; Seibel, Peter; Martin, Lisandra L.; Veldhuizen, Edwin J. A.; Hoffmann, Ralf

    2016-01-01

    The Gram-negative bacterium Pseudomonas aeruginosa is a life-threatening nosocomial pathogen due to its generally low susceptibility toward antibiotics. Furthermore, many strains have acquired resistance mechanisms requiring new antimicrobials with novel mechanisms to enhance treatment options. Proline-rich antimicrobial peptides, such as the apidaecin analog Api137, are highly efficient against various Enterobacteriaceae infections in mice, but less active against P. aeruginosa in vitro. Here, we extended our recent work by optimizing lead peptides Api755 (gu-OIORPVYOPRPRPPHPRL-OH; gu = N,N,N′,N′-tetramethylguanidino, O = L-ornithine) and Api760 (gu-OWORPVYOPRPRPPHPRL-OH) by incorporation of Ile-Orn- and Trp-Orn-motifs, respectively. Api795 (gu-O(IO)2RPVYOPRPRPPHPRL-OH) and Api794 (gu-O(WO)3RPVYOPRPRPPHPRL-OH) were highly active against P. aeruginosa with minimal inhibitory concentrations of 8–16 and 8–32 μg/mL against Escherichia coli and Klebsiella pneumoniae. Assessed using a quartz crystal microbalance, these peptides inserted into a membrane layer and the surface activity increased gradually from Api137, over Api795, to Api794. This mode of action was confirmed by transmission electron microscopy indicating some membrane damage only at the high peptide concentrations. Api794 and Api795 were highly stable against serum proteases (half-life times >5 h) and non-hemolytic to human erythrocytes at peptide concentrations of 0.6 g/L. At this concentration, Api795 reduced the cell viability of HeLa cells only slightly, whereas the IC50 of Api794 was 0.23 ± 0.09 g/L. Confocal fluorescence microscopy revealed no colocalization of 5(6)-carboxyfluorescein-labeled Api794 or Api795 with the mitochondria, excluding interactions with the mitochondrial membrane. Interestingly, Api795 was localized in endosomes, whereas Api794 was present in endosomes and the cytosol. This was verified using flow cytometry showing a 50% higher uptake of Api794 in HeLa cells compared

  20. Alu and L1 sequence distributions in Xq24-q28 and their comparative utility in YAC contig assembly and verification

    SciTech Connect

    Porta, G.; Zucchi, I.; Schlessinger, D.; Hillier, L.; Green, P.; Nowotny, V.; D`Urso, M.

    1993-05-01

    The contents of Alu- and L1-containing TaqI restriction fragments were assessed by Southern blot analyses across YAC contigs already assembled by other means and localized within Xq24-q28. Fingerprinting patterns of YACs in contigs were concordant. Using software based on that of M. V. Olson et al. to analyze digitized data on fragment sizes, fingerprinting itself could establish matches among about 40% of a test group of 435 YACs. At 100-kb resolution, both repetitive elements were found throughout the region, with no apparent enrichment of Alu or L1 in DNA of G compared to that found in R bands. However, consistent with a random overall distribution, delimited regions of up to 100 kb contained clusters of repetitive elements. The local concentrations may help to account for the reported differential hybridization of Alu and L1 probes to segments of metaphase chromosomes. 40 refs., 6 figs., 2 tabs.

  1. Emulsifying and Foaming Properties of Different Protein Fractions Obtained from a Novel Lupin Variety AluProt-CGNA(®) (Lupinus luteus).

    PubMed

    Burgos-Díaz, César; Piornos, José A; Wandersleben, Traudy; Ogura, Takahiro; Hernández, Xaviera; Rubilar, Mónica

    2016-07-01

    The use of vegetable proteins as food ingredient is becoming increasingly important due to their high versatility and environmental acceptability. This work describes a chemical characterization and techno-functional properties (emulsifying and foaming properties) of 3 protein fractions obtained from a protein-rich novel lupin variety, AluProt-CGNA(®) . This nongenetically modified variety have a great protein content in dehulled seeds (60.6 g protein/100 g, dry matter), which is higher than soybean and other lupin varieties. A simple procedure was utilized to obtain 3 different fractions by using alkali solubilization and isoelectric precipitation. Fractions 1 and 3 were mainly composed of protein and polysaccharides (NNE), whereas fraction 2 was mainly composed by protein (97%, w/w). Fraction 3 presented interesting and potential foaming properties in comparison to the other fractions evaluated in the study. Besides, its solubility, foaming and emulsifying capacity were practically not affected by pH variations. The 3 fractions also presented good emulsion stability, reaching values above a 95%. SDS-PAGE showed that fractions 1 and 2 contained mainly conglutin α, β, and δ, but in different ratios, whereas fraction 3 contained mainly conglutin γ and albumins. The results of this work will provide better understanding for the utilization of each protein fractions as potential ingredients in food industry.

  2. Repeated Reading. What Works Clearinghouse Intervention Report

    ERIC Educational Resources Information Center

    What Works Clearinghouse, 2014

    2014-01-01

    "Repeated reading" is an academic practice that aims to increase oral reading fluency. "Repeated reading" can be used with students who have developed initial word reading skills but demonstrate inadequate reading fluency for their grade level. During "repeated reading," a student sits in a quiet location with a…

  3. Development of an Alu-based, real-time PCR method for quantitation of human DNA in forensic samples.

    PubMed

    Nicklas, Janice A; Buel, Eric

    2003-09-01

    Determining the amount of human DNA extracted from a crime scene sample is an important step in DNA profiling. The forensic community relies almost entirely upon a technique (slot blot) to quantitate human DNA that is imprecise, time consuming, and labor intensive. We have previously described a method for quantitation of human DNA based on PCR amplification of a repetitive Alu sequence that uses a fluorescence plate reader. This manuscript describes and validates a variation of this assay using real-time PCR and SYBR Green I for quantitation. The advantages of the real-time assay over the plate reader assay are: reduced hands-on time, lower assay cost, and a greater dynamic range. The main disadvantage is the cost of the real-time instrument. However, for those forensic laboratories with access to a real-time instrument, this Alu-based assay has a dynamic range of 16 ng to 1 pg, is sensitive, specific, fast, quantitative, and uses only 2 microL of sample.

  4. Direct Competition between hnRNP C and U2AF65 Protects the Transcriptome from the Exonization of Alu Elements

    PubMed Central

    Zarnack, Kathi; König, Julian; Tajnik, Mojca; Martincorena, Iñigo; Eustermann, Sebastian; Stévant, Isabelle; Reyes, Alejandro; Anders, Simon; Luscombe, Nicholas M.; Ule, Jernej

    2013-01-01

    Summary There are ∼650,000 Alu elements in transcribed regions of the human genome. These elements contain cryptic splice sites, so they are in constant danger of aberrant incorporation into mature transcripts. Despite posing a major threat to transcriptome integrity, little is known about the molecular mechanisms preventing their inclusion. Here, we present a mechanism for protecting the human transcriptome from the aberrant exonization of transposable elements. Quantitative iCLIP data show that the RNA-binding protein hnRNP C competes with the splicing factor U2AF65 at many genuine and cryptic splice sites. Loss of hnRNP C leads to formation of previously suppressed Alu exons, which severely disrupt transcript function. Minigene experiments explain disease-associated mutations in Alu elements that hamper hnRNP C binding. Thus, by preventing U2AF65 binding to Alu elements, hnRNP C plays a critical role as a genome-wide sentinel protecting the transcriptome. The findings have important implications for human evolution and disease. PMID:23374342

  5. Noninvasive pulsed focused ultrasound allows spatiotemporal control of targeted homing for multiple stem cell types in murine skeletal muscle and the magnitude of cell homing can be increased through repeated applications

    PubMed Central

    Burks, Scott R.; Ziadloo, Ali; Kim, Saejeong J.; Nguyen, Ben A.; Frank, Joseph A.

    2013-01-01

    Stem cells are promising therapeutics for cardiovascular diseases and intravenous injection is the most desirable route of administration clinically. Subsequent homing of exogenous stem cells to pathological loci is frequently required for therapeutic efficacy and is mediated by chemo attractants (cell adhesion molecules, cytokines, and growth factors). Homing processes are inefficient and depend on short-lived pathological inflammation that limits the window of opportunity for cell injections. Noninvasive pulsed focused ultrasound (plus), which emphasizes mechanical ultrasound-tissue interactions, can be precisely targeted in the body and is a promising approach to target and maximize stem cell delivery by stimulating chemo attractant expression in plus-treated tissue prior to cell infusions. We demonstrate that plus is nondestructive to marine skeletal muscle tissue (no necrosis, hemorrhage, or muscle stem cell activation) and initiates a largely M2-type macrophage response. We also demonstrate local up regulation of chemo attractants in plus-treated skeletal muscle leads to enhance homing, permeability, and retention of human mesenchymal stem cells (MSC) and human endothelial precursor cells (EPC). Furthermore, the magnitude of MSC or EPC homing was increased when plus treatments and cell infusions were repeated daily. This study demonstrates that plus defines transient “molecular zip codes” of elevated chemo attractants in targeted muscle tissue, which effectively provides spatiotemporal control and tenability of the homing process for multiple stem cell types. plus is a clinically-translatable modality that may ultimately improve homing efficiency and flexibility of cell therapies for cardiovascular diseases. PMID:23922277

  6. The Role of the Y-Chromosome in the Establishment of Murine Hybrid Dysgenesis and in the Analysis of the Nucleotide Sequence Organization, Genetic Transmission and Evolution of Repeated Sequences.

    NASA Astrophysics Data System (ADS)

    Nallaseth, Ferez Soli

    The Y-chromosome presents a unique cytogenetic framework for the evolution of nucleotide sequences. Alignment of nine Y-chromosomal fragments in their increasing Y-specific/non Y-specific (male/female) sequence divergence ratios was directly and inversely related to their interspersion on these two respective genomic fractions. Sequence analysis confirmed a direct relationship between divergence ratios and the Alu, LINE-1, Satellite and their derivative oligonucleotide contents. Thus their relocation on the Y-chromosome is followed by sequence divergence rather than the well documented concerted evolution of these non-coding progenitor repeated sequences. Five of the nine Y-chromosomal fragments are non-pseudoautosomal and transcribed into heterogeneous PolyA^+ RNA and thus can be retrotransposed. Evolutionary and computer analysis identified homologous oligonucleotide tracts in several human loci suggesting common and random mechanistic origins. Dysgenic genomes represent the accelerated evolution driving sequence divergence (McClintock, 1984). Sex reversal and sterility characterizing dysgenesis occurs in C57BL/6JY ^{rm Pos} but not in 129/SvY^{rm Pos} derivative strains. High frequency, random, multi-locus deletion products of the feral Y^{ rm Pos}-chromosome are generated in the germlines of F1(C57BL/6J X 129/SvY^{ rm Pos})(male) and C57BL/6JY ^{rm Pos}(male) but not in 129/SvY^{rm Pos}(male). Equal, 10^{-1}, 10^ {-2}, and 0 copies (relative to males) of Y^{rm Pos}-specific deletion products respectively characterize C57BL/6JY ^{rm Pos} (HC), (LC), (T) and (F) females. The testes determining loci of inactive Y^{rm Pos}-chromosomes in C57BL/6JY^{rm Pos} HC females are the preferentially deleted/rearranged Y ^{rm Pos}-sequences. Disruption of regulation of plasma testosterone and hepatic MUP-A mRNA levels, TRD of a 4.7 Kbp EcoR1 fragment suggest disruption of autosomal/X-chromosomal sequences. These data and the highly repeated progenitor (Alu, GATA, LINE-1

  7. Unfolding a linker between helical repeats.

    PubMed

    Ortiz, Vanessa; Nielsen, Steven O; Klein, Michael L; Discher, Dennis E

    2005-06-10

    In many multi-repeat proteins, linkers between repeats have little secondary structure and place few constraints on folding or unfolding. However, the large family of spectrin-like proteins, including alpha-actinin, spectrin, and dystrophin, share three-helix bundle, spectrin repeats that appear in crystal structures to be linked by long helices. All of these proteins are regularly subjected to mechanical stress. Recent single molecule atomic force microscopy (AFM) experiments demonstrate not only forced unfolding but also simultaneous unfolding of tandem repeats at finite frequency, which suggests that the contiguous helix between spectrin repeats can propagate a cooperative helix-to-coil transition. Here, we address what happens atomistically to the linker under stress by steered molecular dynamics simulations of tandem spectrin repeats in explicit water. The results for alpha-actinin repeats reveal rate-dependent pathways, with one pathway showing that the linker between repeats unfolds, which may explain the single-repeat unfolding pathway observed in AFM experiments. A second pathway preserves the structural integrity of the linker, which explains the tandem-repeat unfolding event. Unfolding of the linker begins with a splay distortion of proximal loops away from hydrophobic contacts with the linker. This is followed by linker destabilization and unwinding with increased hydration of the backbone. The end result is an unfolded helix that mechanically decouples tandem repeats. Molecularly detailed insights obtained here aid in understanding the mechanical coupling of domain stability in spectrin family proteins.

  8. Benthic habitat map of U.S. Coral Reef Task Force Faga‘alu Bay priority study area, Tutuila, American Samoa

    USGS Publications Warehouse

    Cochran, Susan A.; Gibbs, Ann E.; D'Antonio, Nicole L.; Storlazzi, Curt D.

    2016-05-18

    The coral reef in Faga‘alu Bay, Tutuila, American Samoa, has suffered numerous natural and anthropogenic stresses. Areas once dominated by live coral are now mostly rubble surfaces covered with turf or macroalgae. In an effort to improve the health and resilience of the coral reef system, the U.S. Coral Reef Task Force selected Faga‘alu Bay as a priority study area. To support these efforts, the U.S. Geological Survey mapped nearly 1 km2 of seafloor to depths of about 60 m. Unconsolidated sediment (predominantly sand) constitutes slightly greater than 50 percent of the seafloor in the mapped area; reef and other hardbottom potentially available for coral recruitment constitute nearly 50 percent of the mapped area. Of this potentially available hardbottom, only slightly greater than 37 percent is covered with at least 10 percent coral, which is fairly evenly distributed between the reef flat, fore reef, and offshore bank/shelf. 

  9. High Degree of Plasmodium vivax Diversity in the Peruvian Amazon Demonstrated by Tandem Repeat Polymorphism Analysis

    PubMed Central

    Kosek, Margaret; Yori, Pablo P.; Gilman, Robert H.; Calderon, Maritza; Zimic, Mirko; Chuquiyauri, Raul; Jeri, Cesar; Pinedo-Cancino, Viviana; Matthias, Michael A.; Llanos-Cuentas, Alejandro; Vinetz, Joseph M.

    2012-01-01

    Molecular tools to distinguish strains of Plasmodium vivax are important for studying the epidemiology of malaria transmission. Two sets of markers—tandem repeat (TR) polymorphisms and MSP3α—were used to study Plasmodium vivax in patients in the Peruvian Amazon region of Iquitos. Of 110 patients, 90 distinct haplotypes were distinguished using 9 TR markers. An MSP3α polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using HhaI and AluI revealed 8 and 9 profiles, respectively, and 36 profiles when analyzed in combination. Combining TR and PCR-RFLP markers, 101 distinct molecular profiles were distinguished among these 110 patients. Nine TR markers arrayed along a 100 kB stretch of a P. vivax chromosome containing the gene for circumsporozoite protein showed non-linear linkage disequilibrium (ISA = 0.03, P = 0.001). These findings demonstrate the potential use of TR markers for molecular epidemiology studies. PMID:22492139

  10. Identification of region-specific yeast artificial chromosomes using pools of Alu element-mediated polymerase chain reaction probes labeled via linear amplification.

    PubMed

    Cole, C G; Patel, K; Shipley, J; Sheer, D; Bobrow, M; Bentley, D R; Dunham, I

    1992-12-01

    The ability to identify large numbers of yeast artificial chromosomes (YACs) specific to any given genomic region rapidly and efficiently enhances both the construction of clone maps and the isolation of region-specific landmarks (e.g., polymorphic markers). We describe a method of preparing region-specific single-stranded hybridization probes from Alu element-mediated polymerase chain reaction (Alu-PCR) products of somatic cell hybrids for YAC library screening. Pools of up to 50 cloned Alu-PCR products from an irradiation-reduced hybrid containing 22q11.2-q13.1 were labeled to high specific activity by linear amplification using a single vector primer. The resulting single-stranded probes were extensively competed to remove repetitive sequences, while retaining the full complexity of the probe. Extensive coverage of the region by YACs using multiple probe pools was demonstrated as many YACs were detected more than once. In situ analysis using chosen YACs confirmed that the clones were specific for the region. Thus, this pooled probe approach constitutes a rapid method to identify large numbers of YACs relevant to a large chromosomal region.

  11. Sill emplacement and corresponding ground deformation processes at the Alu-Dalafilla volcanic centre in the Danakil Depression, Ethiopia

    NASA Astrophysics Data System (ADS)

    Magee, Craig; Bastow, Ian; Hetherington, Rachel; van Wyk de Vries, Ben; Jackson, Christopher

    2016-04-01

    A consensus has emerged from a variety of disciplines over the past 15 years that Quaternary magmatism in Ethiopia is almost entirely dominated by dike intrusion. Focused dike intrusion within 60 km long, 20 km wide, rift zones is considered to mark the present day locus of extension in Ethiopia, and represent the proto-ridge axis location of an incipient ocean spreading centre. However, it has been suggested on the strength of Moho depths and Quaternary eruptive volumes in northernmost Ethiopia, that the final transition from continental rifting to incipient oceanic spreading may instead be characterised by an abrupt, rheologically driven, late-phase of crustal thinning. Development of a sedimentary basin and mantle decompression melting occurring in the Danakil Depression, driven by this late-phase crustal thinning, should result in a markedly different style of magmatism in the upper crust: i.e. field observations, high-resolution seismic reflection studies, and experimental modelling suggest that interconnected networks of sill intrusions dominate in sedimentary basins. Here, we present the first evidence from the Danakil Depression that links surficial structures, observed at the Alu-Dalafilla volcanic centre, to the ongoing emplacement of an underlying sill. In particular, we use satellite imagery to examine a dome-shaped fold, associated fracture patterns, and surrounding lava flows, which we suggest likely formed in response to roof uplift above and extrusion from a saucer-shaped sill; i.e. a sub-horizontal inner sill encircled by an inward-dipping, transgressive inclined rim. InSAR observations by Pagli et al. (2012) of ground uplift and deflation occurring during the eruption of basaltic lava at Alu-Dalafilla in 2008 capture what we believe to be the first real-time evidence for intrusion-induced forced folding dynamics above a saucer-shaped sill. InSAR data further suggest that intrusion occurred at a depth of ~1 km, likely placing the sill within an

  12. Repeating the Past

    NASA Astrophysics Data System (ADS)

    Moore, John W.

    1998-05-01

    As part of the celebration of the Journal 's 75th year, we are scanning each Journal issue from 25, 50, and 74 years ago. Many of the ideas and practices described are so similar to present-day "innovations" that George Santayana's adage (1) "Those who cannot remember the past are condemned to repeat it" comes to mind. But perhaps "condemned" is too strong - sometimes it may be valuable to repeat something that was done long ago. One example comes from the earliest days of the Division of Chemical Education and of the Journal.

  13. Prenatal Air Pollution Exposures, DNA Methyl Transferase Genotypes, and Associations with Newborn LINE1 and Alu Methylation and Childhood Blood Pressure and Carotid Intima-Media Thickness in the Children’s Health Study

    PubMed Central

    Breton, Carrie V.; Yao, Jin; Millstein, Josh; Gao, Lu; Siegmund, Kimberly D.; Mack, Wendy; Whitfield-Maxwell, Lora; Lurmann, Fred; Hodis, Howard; Avol, Ed; Gilliland, Frank D.

    2016-01-01

    Background: Although exposure to ambient air pollutants increases cardiovascular disease risk in adults little is known about the effects of prenatal exposure. Genetic variation and epigenetic alterations are two mechanisms that may influence the effects of early-life exposures on cardiovascular phenotypes. Objectives: We investigated whether genetic and epigenetic variation modify associations between prenatal air pollution on markers of cardiovascular risk in childhood. Methods: We used linear regression analysis to investigate the associations between prenatal pollutants (PM2.5, PM10, NO2, O3), long interspersed nuclear elements (LINE1) and AluYb8 DNA methylation levels measured in newborn blood spot tests, and carotid intima-media thickness (CIMT) and blood pressure (BP) in 459 participants as part of the Children’s Health Study. Interaction terms were also included to test for effect modification of these associations by genetic variation in methylation reprogramming genes. Results: Prenatal exposure to NO2 in the third trimester of pregnancy was associated with higher systolic BP in 11-year-old children. Prenatal exposure to multiple air pollutants in the first trimester was associated with lower DNA methylation in LINE1, whereas later exposure to O3 was associated with higher LINE1 methylation levels in newborn blood spots. The magnitude of associations with prenatal air pollution varied according to genotype for 11 SNPs within DNA methyltransferase 1 (DNMT1), DNA methyltransferase 3 Beta (DNMT3B), Tet methylcytosine dioxygenase 2 (TET2), and Thymine DNA glycosylase (TDG) genes. Although first-trimester O3 exposure was not associated with CIMT and systolic BP overall, associations within strata of DNMT1 or DNMT3B were observed, and the magnitude and the direction of these associations depended on DNMT1 genotypes. Conclusions: Genetic and epigenetic variation in DNA methylation reprogramming genes and in LINE1 retrotransposons may play important roles in

  14. Increase Return on Investment of Software Development Life Cycle by Managing the Risk - A Case Study

    DTIC Science & Technology

    2015-04-01

    Image designed by Diane Fleischer INCREASE RETURN on Investment of Software Development Life Cycle by Managing the Risk —A Case Study...for increasing the return on investment during the Software Development Life Cycle (SDLC) through selected quantitative analyses employing both the...defect rate, return on investment (ROI), software development life cycle (SDLC) DE FE N SE A C Q U IS IT IO N UN IVERSITY ALU M N I A SSO C IATIO N R

  15. Alu insertion polymorphisms and an assessment of the genetic contribution of Central Asia to Anatolia with respect to the Balkans.

    PubMed

    Berkman, Ceren Caner; Dinc, Havva; Sekeryapan, Ceran; Togan, Inci

    2008-05-01

    In the evolutionary history of modern humans, Anatolia acted as a bridge between the Caucasus, the Near East, and Europe. Because of its geographical location, Anatolia was subject to migrations from multiple different regions throughout time. The last, well-known migration was the movement of Turkic speaking, nomadic groups from Central Asia. They invaded Anatolia and then the language of the region was gradually replaced by the Turkic language. In the present study, insertion frequencies of 10 Alu loci (A25 = 0.07, APO = 0.96, TPA25 = 0.44, ACE = 0.37, B65 = 0.57, PV92 = 0.18, FXIIIB = 0.52, D1 = 0.40, HS4.32 = 0.66, and HS4.69 = 0.30) have been determined in the Anatolian population. Together with the data compiled from other databases, the similarity of the Anatolian population to that of the Balkans and Central Asia has been visualized by multidimensional scaling method. Analysis suggested that, genetically, Anatolia is more closely related with the Balkan populations than to the Central Asian populations. Central Asian contribution to Anatolia with respect to the Balkans was quantified with an admixture analysis. Furthermore, the association between the Central Asian contribution and the language replacement episode was examined by comparative analysis of the Central Asian contribution to Anatolia, Azerbaijan (another Turkic speaking country) and their neighbors. In the present study, the Central Asian contribution to Anatolia was estimated as 13%. This was the lowest value among the populations analyzed. This observation may be explained by Anatolia having the lowest migrant/resident ratio at the time of migrations.

  16. Duct Leakage Repeatability Testing

    SciTech Connect

    Walker, Iain; Sherman, Max

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  17. Accumulate repeat accumulate codes

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative channel coding scheme called 'Accumulate Repeat Accumulate codes' (ARA). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes, thus belief propagation can be used for iterative decoding of ARA codes on a graph. The structure of encoder for this class can be viewed as precoded Repeat Accumulate (RA) code or as precoded Irregular Repeat Accumulate (IRA) code, where simply an accumulator is chosen as a precoder. Thus ARA codes have simple, and very fast encoder structure when they representing LDPC codes. Based on density evolution for LDPC codes through some examples for ARA codes, we show that for maximum variable node degree 5 a minimum bit SNR as low as 0.08 dB from channel capacity for rate 1/2 can be achieved as the block size goes to infinity. Thus based on fixed low maximum variable node degree, its threshold outperforms not only the RA and IRA codes but also the best known LDPC codes with the dame maximum node degree. Furthermore by puncturing the accumulators any desired high rate codes close to code rate 1 can be obtained with thresholds that stay close to the channel capacity thresholds uniformly. Iterative decoding simulation results are provided. The ARA codes also have projected graph or protograph representation that allows for high speed decoder implementation.

  18. Erroneous Memories Arising from Repeated Attempts to Remember

    ERIC Educational Resources Information Center

    Henkel, Linda A.

    2004-01-01

    The impact of repeated and prolonged attempts at remembering on false memory rates was assessed in three experiments. Participants saw and imagined pictures and then made repeated recall attempts before taking a source memory test. Although the number of items recalled increased with repeated tests, the net gains were associated with more source…

  19. Digital repeat analysis; setup and operation.

    PubMed

    Nol, J; Isouard, G; Mirecki, J

    2006-06-01

    Since the emergence of digital imaging, there have been questions about the necessity of continuing reject analysis programs in imaging departments to evaluate performance and quality. As a marketing strategy, most suppliers of digital technology focus on the supremacy of the technology and its ability to reduce the number of repeats, resulting in less radiation doses given to patients and increased productivity in the department. On the other hand, quality assurance radiographers and radiologists believe that repeats are mainly related to positioning skills, and repeat analysis is the main tool to plan training needs to up-skill radiographers. A comparative study between conventional and digital imaging was undertaken to compare outcomes and evaluate the need for reject analysis. However, digital technology still being at its early development stages, setting a credible reject analysis program became the major task of the study. It took the department, with the help of the suppliers of the computed radiography reader and the picture archiving and communication system, over 2 years of software enhancement to build a reliable digital repeat analysis system. The results were supportive of both philosophies; the number of repeats as a result of exposure factors was reduced dramatically; however, the percentage of repeats as a result of positioning skills was slightly on the increase for the simple reason that some rejects in the conventional system qualifying for both exposure and positioning errors were classified as exposure error. The ability of digitally adjusting dark or light images reclassified some of those images as positioning errors.

  20. Duct Leakage Repeatability Testing

    SciTech Connect

    Walker, Iain; Sherman, Max

    2014-08-01

    The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques for duct leakage using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards. The three duct leak measurement methods assessed in this report are the two duct pressurization methods that are commonly used by many practitioners and the DeltaQ technique. These are methods B, C and A, respectively of the ASTM E1554 standard. Although it would be useful to evaluate other duct leak test methods, this study focused on those test methods that are commonly used and are required in various test standards, such as BPI (2010), RESNET (2014), ASHRAE 62.2 (2013), California Title 24 (CEC 2012), DOE Weatherization and many other energy efficiency programs.

  1. Identification of human chromosome region 3p14. 2-21. 3-specific YAC clones using Alu-PCR products from a radiation hybrid

    SciTech Connect

    Siden, T.S.; Drumheller, T.; Smith, S.E.; Smith, D.I. ); Kumlien, J.; Lehrach, H. ); Roehme, D. )

    1994-03-01

    Deletion of DNA sequences from at least three different regions on the short arm of human chromosome 3 (3p13-14, 3p21 and 3p25) are frequently observed during the development of many solid tumors, including lung cancers and renal cell carcinomas. In order to physically characterize the 3p21 region, the authors previously identified a radiation fusion hybrid that contained about 20 megabases of DNA from chromosome region 3p14.2p21.3. In this study total Alu-PCR products from this hybrid were used as a probe to isolate 86 yeast artificial chromosome (YAC) clones from a 620-kb average insert YAC library (ICRF). Sixty-nine Alu-PCR markers, generated from the YACs, and seven PCR primers were used to screen for overlaps between individual clones. Seven contigs were identified encompassing 32 YAC clones. Based on previous information about localization of the PCR primers, the three largest contigs could be assigned to smaller subregions between 3p14.2 and 3p21.3. By this work a large proportion of the 3p14.21.3 region is covered with large-insert YAC clones.

  2. Repeat Customer Success in Extension

    ERIC Educational Resources Information Center

    Bess, Melissa M.; Traub, Sarah M.

    2013-01-01

    Four multi-session research-based programs were offered by two Extension specialist in one rural Missouri county. Eleven participants who came to multiple Extension programs could be called "repeat customers." Based on the total number of participants for all four programs, 25% could be deemed as repeat customers. Repeat customers had…

  3. 78 FR 65594 - Vehicular Repeaters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-01

    ... changes, and on whether current mobile repeater filter technologies can support reduced frequency... feasibility of adapting SAW filters, or other filter technology, for mobile repeater use. We particularly... mobile repeaters by public safety licensees on certain frequencies in the VHF band. DATES:...

  4. RepeatsDB: a database of tandem repeat protein structures

    PubMed Central

    Di Domenico, Tomás; Potenza, Emilio; Walsh, Ian; Gonzalo Parra, R.; Giollo, Manuel; Minervini, Giovanni; Piovesan, Damiano; Ihsan, Awais; Ferrari, Carlo; Kajava, Andrey V.; Tosatto, Silvio C.E.

    2014-01-01

    RepeatsDB (http://repeatsdb.bio.unipd.it/) is a database of annotated tandem repeat protein structures. Tandem repeats pose a difficult problem for the analysis of protein structures, as the underlying sequence can be highly degenerate. Several repeat types haven been studied over the years, but their annotation was done in a case-by-case basis, thus making large-scale analysis difficult. We developed RepeatsDB to fill this gap. Using state-of-the-art repeat detection methods and manual curation, we systematically annotated the Protein Data Bank, predicting 10 745 repeat structures. In all, 2797 structures were classified according to a recently proposed classification schema, which was expanded to accommodate new findings. In addition, detailed annotations were performed in a subset of 321 proteins. These annotations feature information on start and end positions for the repeat regions and units. RepeatsDB is an ongoing effort to systematically classify and annotate structural protein repeats in a consistent way. It provides users with the possibility to access and download high-quality datasets either interactively or programmatically through web services. PMID:24311564

  5. Increasing health inequalities between women in and out of work - the impact of recession or policy change? A repeated cross-sectional study in Stockholm county, 2006 and 2010

    PubMed Central

    2014-01-01

    Introduction The social insurance system in Sweden underwent extensive change between 2006 and 2010, with the overall aim of making people enter the labour market. At the same time, economic recession hit Sweden. Previous studies suggest that the economic recession particularly affected women. In light of these changes, the aim of this study is to investigate whether health inequalities between employed women and groups outside the labour market changed between 2006 and 2010. A second aim is to examine the explanatory weight of socio-demographic factors vs social and economic conditions. Methods Data consists of the Stockholm Public Health Surveys (SPHS) for 2006 and 2010. Women aged 18–64 were studied. Through logistic regression, levels of mental distress and limiting longstanding illness (LLI), were compared between four labour market groups; employed and unemployed, sickness absentees and disability pension recipients, at the two time points. Results Mental distress increased among women in all four labour market groups between 2006 and 2010. Differences in mental distress between those employed and groups outside the labour market also increased. These were explained primarily by social and economic conditions. Levels of LLI were unchanged except among the unemployed. The difference in LLI between the unemployed and the employed was mostly explained by social and economic conditions. In the other groups socio-demographic factors were more salient. For both health outcomes, the weight of social and economic conditions had increased in 2010 compared to 2006. Conclusions Results indicate that levels of mental distress increased in all groups, but more so among groups outside the labour market, possibly due to stricter eligibility criteria and lower benefit levels, which particularly affected their social and economic conditions. PMID:25063363

  6. To Repeat or Not to Repeat a Course

    ERIC Educational Resources Information Center

    Armstrong, Michael J.; Biktimirov, Ernest N.

    2013-01-01

    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  7. Role of memory errors in quantum repeaters

    NASA Astrophysics Data System (ADS)

    Hartmann, L.; Kraus, B.; Briegel, H.-J.; Dür, W.

    2007-03-01

    We investigate the influence of memory errors in the quantum repeater scheme for long-range quantum communication. We show that the communication distance is limited in standard operation mode due to memory errors resulting from unavoidable waiting times for classical signals. We show how to overcome these limitations by (i) improving local memory and (ii) introducing two operational modes of the quantum repeater. In both operational modes, the repeater is run blindly, i.e., without waiting for classical signals to arrive. In the first scheme, entanglement purification protocols based on one-way classical communication are used allowing to communicate over arbitrary distances. However, the error thresholds for noise in local control operations are very stringent. The second scheme makes use of entanglement purification protocols with two-way classical communication and inherits the favorable error thresholds of the repeater run in standard mode. One can increase the possible communication distance by an order of magnitude with reasonable overhead in physical resources. We outline the architecture of a quantum repeater that can possibly ensure intercontinental quantum communication.

  8. ATXN2 trinucleotide repeat length correlates with risk of ALS.

    PubMed

    Sproviero, William; Shatunov, Aleksey; Stahl, Daniel; Shoai, Maryam; van Rheenen, Wouter; Jones, Ashley R; Al-Sarraj, Safa; Andersen, Peter M; Bonini, Nancy M; Conforti, Francesca L; Van Damme, Philip; Daoud, Hussein; Del Mar Amador, Maria; Fogh, Isabella; Forzan, Monica; Gaastra, Ben; Gellera, Cinzia; Gitler, Aaron D; Hardy, John; Fratta, Pietro; La Bella, Vincenzo; Le Ber, Isabelle; Van Langenhove, Tim; Lattante, Serena; Lee, Yi-Chung; Malaspina, Andrea; Meininger, Vincent; Millecamps, Stéphanie; Orrell, Richard; Rademakers, Rosa; Robberecht, Wim; Rouleau, Guy; Ross, Owen A; Salachas, Francois; Sidle, Katie; Smith, Bradley N; Soong, Bing-Wen; Sorarù, Gianni; Stevanin, Giovanni; Kabashi, Edor; Troakes, Claire; van Broeckhoven, Christine; Veldink, Jan H; van den Berg, Leonard H; Shaw, Christopher E; Powell, John F; Al-Chalabi, Ammar

    2017-03-01

    We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10(-18)), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R(2) = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk.

  9. Fusion of Epstein-Barr virus nuclear antigen-1-derived glycine-alanine repeat to trans-dominant HIV-1 Gag increases inhibitory activities and survival of transduced cells in vivo.

    PubMed

    Hammer, Diana; Wild, Jens; Ludwig, Christine; Asbach, Benedikt; Notka, Frank; Wagner, Ralf

    2008-06-01

    Trans-dominant human immunodeficiency virus type 1 (HIV-1) Gag derivatives have been shown to efficiently inhibit late steps of HIV-1 replication in vitro by interfering with Gag precursor assembly, thus ranking among the interesting candidates for gene therapy approaches. However, efficient antiviral activities of corresponding transgenes are likely to be counteracted in particular by cell-mediated host immune responses toward the transgene-expressing cells. To decrease this potential immunogenicity, a 24-amino acid Gly-Ala (GA) stretch derived from Epstein-Barr virus nuclear antigen-1 (EBNA1) and known to overcome proteasomal degradation was fused to a trans-dominant Gag variant (sgD1). To determine the capacity of this fusion polypeptide to repress viral replication, PM-1 cells were transduced with sgD1 and GAsgD1 transgenes, using retroviral gene transfer. Challenge of stably transfected permissive cell lines with various viral strains indicated that N-terminal GA fusion even enhanced the inhibitory properties of sgD1. Further studies revealed that the GA stretch increased protein stability by blocking proteasomal degradation of Gag proteins. Immunization of BALB/c mice with a DNA vaccine vector expressing sgD1 induced substantial Gag-specific immune responses that were, however, clearly diminished in the presence of GA. Furthermore, recognition of cells expressing the GA-fused transgene by CD8(+) T cells was drastically reduced, both in vitro and in vivo, resulting in prolonged survival of the transduced cells in recipient mice.

  10. Nifty Nines and Repeating Decimals

    ERIC Educational Resources Information Center

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  11. All-photonic quantum repeaters

    NASA Astrophysics Data System (ADS)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-04-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories.

  12. A Semiparametric Bayesian Model for Repeatedly Repeated Binary Outcomes

    PubMed Central

    Quintana, Fernando A.; Müller, Peter; Rosner, Gary L.; Relling, Mary V.

    2009-01-01

    Summary We discuss the analysis of data from single nucleotide polymorphism (SNP) arrays comparing tumor and normal tissues. The data consist of sequences of indicators for loss of heterozygosity (LOH) and involve three nested levels of repetition: chromosomes for a given patient, regions within chromosomes, and SNPs nested within regions. We propose to analyze these data using a semiparametric model for multi-level repeated binary data. At the top level of the hierarchy we assume a sampling model for the observed binary LOH sequences that arises from a partial exchangeability argument. This implies a mixture of Markov chains model. The mixture is defined with respect to the Markov transition probabilities. We assume a nonparametric prior for the random mixing measure. The resulting model takes the form of a semiparametric random effects model with the matrix of transition probabilities being the random effects. The model includes appropriate dependence assumptions for the two remaining levels of the hierarchy, i.e., for regions within chromosomes and for chromosomes within patient. We use the model to identify regions of increased LOH in a dataset coming from a study of treatment-related leukemia in children with an initial cancer diagnostic. The model successfully identifies the desired regions and performs well compared to other available alternatives. PMID:19746193

  13. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    SciTech Connect

    Aubuchon, Adam C.; Chan, Michael D.; Lovato, James F.; Balamucki, Christopher J.; Ellis, Thomas L.; Tatter, Stephen B.; McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G.

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  14. An Expanded CAG Repeat in Huntingtin Causes +1 Frameshifting.

    PubMed

    Saffert, Paul; Adamla, Frauke; Schieweck, Rico; Atkins, John F; Ignatova, Zoya

    2016-08-26

    Maintenance of triplet decoding is crucial for the expression of functional protein because deviations either into the -1 or +1 reading frames are often non-functional. We report here that expression of huntingtin (Htt) exon 1 with expanded CAG repeats, implicated in Huntington pathology, undergoes a sporadic +1 frameshift to generate from the CAG repeat a trans-frame AGC repeat-encoded product. This +1 recoding is exclusively detected in pathological Htt variants, i.e. those with expanded repeats with more than 35 consecutive CAG codons. An atypical +1 shift site, UUC C at the 5' end of CAG repeats, which has some resemblance to the influenza A virus shift site, triggers the +1 frameshifting and is enhanced by the increased propensity of the expanded CAG repeats to form a stem-loop structure. The +1 trans-frame-encoded product can directly influence the aggregation of the parental Htt exon 1.

  15. Survey of simple sequence repeats in woodland strawberry (Fragaria vesca).

    PubMed

    Guan, L; Huang, J F; Feng, G Q; Wang, X W; Wang, Y; Chen, B Y; Qiao, Y S

    2013-07-30

    The use of simple sequence repeats (SSRs), or microsatellites, as genetic markers has become popular due to their abundance and variation in length among individuals. In this study, we investigated linkage groups (LGs) in the woodland strawberry (Fragaria vesca) and demonstrated variation in the abundances, densities, and relative densities of mononucleotide, dinucleotide, and trinucleotide repeats. Mononucleotide, dinucleotide, and trinucleotide repeats were more common than longer repeats in all LGs examined. Perfect SSRs were the predominant SSR type found and their abundance was extremely stable among LGs and chloroplasts. Abundances of mononucleotide, dinucleotide, and trinucleotide repeats were positively correlated with LG size, whereas those of tetranucleotide and hexanucleotide SSRs were not. Generally, in each LG, the abundance, relative abundance, relative density, and the proportion of each unique SSR all declined rapidly as the repeated unit increased. Furthermore, the lengths and frequencies of SSRs varied among different LGs.

  16. Repeated-sprint and effort ability in rugby league players.

    PubMed

    Johnston, Rich D; Gabbett, Tim J

    2011-10-01

    The aim of this study was to (a) investigate the influence of tackling on repeated-sprint performance; (b) determine whether repeated-sprint ability (RSA) and repeated-effort ability (REA) are 2 distinct qualities; and (c) assess the test-retest reliability of repeated-sprint and repeated-effort tests in rugby league. Twelve rugby league players performed a repeated-sprint (12 × 20-m sprints performed on a 20-second cycle) and a repeated-effort (12 × 20-m sprints with intermittent tackling, performed on a 20-second cycle) test 7 days apart. The test-retest reliability of these tests was also established. Heart rate and rating of perceived exertion were recorded throughout the tests. There was a significantly greater (p ≤ 0.05) and large effect size (ES) differences for total sprint time (ES = 1.19), average heart rate (ES = 1.64), peak heart rate (ES = 1.35), and perceived exertion (ES = 3.39) for the repeated-effort test compared with the repeated-sprint test. A large difference (ES = 1.02, p = 0.06) was detected for percentage decrement between the 2 tests. No significant relationship was found between the repeated-sprint and repeated-effort tests for any of the dependent variables. Both tests proved reliable, with total sprint time being the most reliable method of assessing performance. This study demonstrates that the addition of tackling significantly increases the physiological response to repeated-sprint exercise and reduces repeated-sprint performance in rugby league players. Furthermore, RSA and REA appear to be 2 distinct qualities that can be reliably assessed with total time being the most reliable measure of performance.

  17. Quantum repeaters: fundamental and future

    NASA Astrophysics Data System (ADS)

    Li, Yue; Hua, Sha; Liu, Yu; Ye, Jun; Zhou, Quan

    2007-04-01

    An overview of the Quantum Repeater techniques based on Entanglement Distillation and Swapping is provided. Beginning with a brief history and the basic concepts of the quantum repeaters, the article primarily focuses on the communication model based on the quantum repeater techniques, which mainly consists of two fundamental modules --- the Entanglement Distillation module and the Swapping module. The realizations of Entanglement Distillation are discussed, including the Bernstein's Procrustean method, the Entanglement Concentration and the CNOT-purification method, etc. The schemes of implementing Swapping, which include the Swapping based on Bell-state measurement and the Swapping in Cavity QED, are also introduced. Then a comparison between these realizations and evaluations on them are presented. At last, the article discusses the experimental schemes of quantum repeaters at present, documents some remaining problems and emerging trends in this field.

  18. Repeatability in redundant manipulator systems

    NASA Astrophysics Data System (ADS)

    Mukherjee, Ranjan

    1994-02-01

    Terrestrial manipulators with more DOF than the dimension of the workspace and space manipulators with as many manipulator DOF as the dimension of the workspace are both redundant systems. An interesting problem of such redundant systems has been the repeatability problem due to the presence of nonholonomic constraints. We show, contrary to the existing belief, that integrability of the nonholonomic constraints is not a necessary condition for the repeatability of the configuration variables. There exist certain trajectories in the independent configuration variable space that are like 'holonomic loops' along which the redundant manipulators exhibit repeatable motion. We present a simple method based on optimization techniques for designing repeatable trajectories for free-flying space manipulators and terrestrial manipulators under pseudoinverse control.

  19. Protein Repeats from First Principles.

    PubMed

    Turjanski, Pablo; Parra, R Gonzalo; Espada, Rocío; Becher, Verónica; Ferreiro, Diego U

    2016-04-05

    Some natural proteins display recurrent structural patterns. Despite being highly similar at the tertiary structure level, repeating patterns within a single repeat protein can be extremely variable at the sequence level. We use a mathematical definition of a repetition and investigate the occurrences of these in sequences of different protein families. We found that long stretches of perfect repetitions are infrequent in individual natural proteins, even for those which are known to fold into structures of recurrent structural motifs. We found that natural repeat proteins are indeed repetitive in their families, exhibiting abundant stretches of 6 amino acids or longer that are perfect repetitions in the reference family. We provide a systematic quantification for this repetitiveness. We show that this form of repetitiveness is not exclusive of repeat proteins, but also occurs in globular domains. A by-product of this work is a fast quantification of the likelihood of a protein to belong to a family.

  20. Protein Repeats from First Principles

    PubMed Central

    Turjanski, Pablo; Parra, R. Gonzalo; Espada, Rocío; Becher, Verónica; Ferreiro, Diego U.

    2016-01-01

    Some natural proteins display recurrent structural patterns. Despite being highly similar at the tertiary structure level, repeating patterns within a single repeat protein can be extremely variable at the sequence level. We use a mathematical definition of a repetition and investigate the occurrences of these in sequences of different protein families. We found that long stretches of perfect repetitions are infrequent in individual natural proteins, even for those which are known to fold into structures of recurrent structural motifs. We found that natural repeat proteins are indeed repetitive in their families, exhibiting abundant stretches of 6 amino acids or longer that are perfect repetitions in the reference family. We provide a systematic quantification for this repetitiveness. We show that this form of repetitiveness is not exclusive of repeat proteins, but also occurs in globular domains. A by-product of this work is a fast quantification of the likelihood of a protein to belong to a family. PMID:27044676

  1. Nanospring behaviour of ankyrin repeats.

    PubMed

    Lee, Gwangrog; Abdi, Khadar; Jiang, Yong; Michaely, Peter; Bennett, Vann; Marszalek, Piotr E

    2006-03-09

    Ankyrin repeats are an amino-acid motif believed to function in protein recognition; they are present in tandem copies in diverse proteins in nearly all phyla. Ankyrin repeats contain antiparallel alpha-helices that can stack to form a superhelical spiral. Visual inspection of the extrapolated structure of 24 ankyrin-R repeats indicates the possibility of spring-like behaviour of the putative superhelix. Moreover, stacks of 17-29 ankyrin repeats in the cytoplasmic domains of transient receptor potential (TRP) channels have been identified as candidates for a spring that gates mechanoreceptors in hair cells as well as in Drosophila bristles. Here we report that tandem ankyrin repeats exhibit tertiary-structure-based elasticity and behave as a linear and fully reversible spring in single-molecule measurements by atomic force microscopy. We also observe an unexpected ability of unfolded repeats to generate force during refolding, and report the first direct measurement of the refolding force of a protein domain. Thus, we show that one of the most common amino-acid motifs has spring properties that could be important in mechanotransduction and in the design of nanodevices.

  2. Chlorinated hydrocarbons in women with repeated miscarriages.

    PubMed Central

    Gerhard, I; Daniel, V; Link, S; Monga, B; Runnebaum, B

    1998-01-01

    This study was conducted to investigate a possible etiological role of chlorinated hydrocarbons in the pathogenesis of repeated miscarriages. The blood levels of chlorinated hydrocarbons [CHCs: pentachlorophenol, hexachlorocyclohexane, hexachlorobenzene, the dichlorodiphenyltrichloroethane (DDT) group, polychlorinated biphenyls] were determined in 89 women with repeated miscarriages, who were referred to the University Hospital of Obstetrics and Gynecology of Heidelberg for investigations between 1989 and 1993, and compared to a previously investigated reference population. In more than 20% of the women, at least one of the CHC levels exceeded the reference range. CHC levels did not differ significantly between women with primary or secondary and early or late miscarriages; neither did they differ between women with hormonal or immunological disorders as causes of repeated miscarriages or women with idiopathic repeated miscarriages. No significant associations were detected between CHC levels and further conceptions or the outcome of further pregnancies. As significant associations were found between increasing CHC blood concentrations and immunological and hormonal changes, CHCs may have an impact on the pregnancy course in certain cases. PMID:9755145

  3. Repeated suicide attempts.

    PubMed

    Mynatt, S

    2000-12-01

    Attempted suicide is an act associated with childhood sexual abuse, depression, bipolar illness, substance abuse, and other diagnoses, as documented in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) (American Psychiatric Association [APA], 1994). Three women, who attended a group to decrease their depression and increase their self-esteem and who had histories of multiple suicide attempts, agreed to participate in interviews designed to determine the common factors associated with their suicide attempts and to examine the assertion that their suicide attempts were an addiction, similar to their addictions to alcohol and drugs. The common factors found were depression, substance use disorders with early abuse and risky behaviors, history of sexual abuse, faulty relationships, alteration of mood with a suicide plan, and distorted and illogical thinking and motivation. The similarities to addiction also were described. Based on the complexity of factors that emerged and the addictive nature of the suicide attempts, treatment for similar patients needs to be multidimensional and ongoing to allow sufficient time to monitor progress and address the numerous factors involved.

  4. Repeated sprint training in normobaric hypoxia.

    PubMed

    Galvin, Harvey M; Cooke, Karl; Sumners, David P; Mileva, Katya N; Bowtell, Joanna L

    2013-12-01

    Repeated sprint ability (RSA) is a critical success factor for intermittent sport performance. Repeated sprint training has been shown to improve RSA, we hypothesised that hypoxia would augment these training adaptations. Thirty male well-trained academy rugby union and rugby league players (18.4 ± 1.5 years, 1.83 ± 0.07 m, 88.1 ± 8.9 kg) participated in this single-blind repeated sprint training study. Participants completed 12 sessions of repeated sprint training (10 × 6 s, 30 s recovery) over 4 weeks in either hypoxia (13% FiO₂) or normoxia (21% FiO₂). Pretraining and post-training, participants completed sports specific endurance and sprint field tests and a 10 × 6 s RSA test on a non-motorised treadmill while measuring speed, heart rate, capillary blood lactate, muscle and cerebral deoxygenation and respiratory measures. Yo-Yo Intermittent Recovery Level 1 test performance improved after RS training in both groups, but gains were significantly greater in the hypoxic (33 ± 12%) than the normoxic group (14 ± 10%, p<0.05). During the 10 × 6 s RS test there was a tendency for greater increases in oxygen consumption in the hypoxic group (hypoxic 6.9 ± 9%, normoxic (-0.3 ± 8.8%, p=0.06) and reductions in cerebral deoxygenation (% changes for both groups, p=0.09) after hypoxic than normoxic training. Twelve RS training sessions in hypoxia resulted in twofold greater improvements in capacity to perform repeated aerobic high intensity workout than an equivalent normoxic training. Performance gains are evident in the short term (4 weeks), a period similar to a preseason training block.

  5. Repeated sprint training in normobaric hypoxia

    PubMed Central

    Galvin, Harvey M; Cooke, Karl; Sumners, David P; Mileva, Katya N; Bowtell, Joanna L

    2013-01-01

    Repeated sprint ability (RSA) is a critical success factor for intermittent sport performance. Repeated sprint training has been shown to improve RSA, we hypothesised that hypoxia would augment these training adaptations. Thirty male well-trained academy rugby union and rugby league players (18.4±1.5 years, 1.83±0.07 m, 88.1±8.9 kg) participated in this single-blind repeated sprint training study. Participants completed 12 sessions of repeated sprint training (10×6 s, 30 s recovery) over 4 weeks in either hypoxia (13% FiO2) or normoxia (21% FiO2). Pretraining and post-training, participants completed sports specific endurance and sprint field tests and a 10×6 s RSA test on a non-motorised treadmill while measuring speed, heart rate, capillary blood lactate, muscle and cerebral deoxygenation and respiratory measures. Yo-Yo Intermittent Recovery Level 1 test performance improved after RS training in both groups, but gains were significantly greater in the hypoxic (33±12%) than the normoxic group (14±10%, p<0.05). During the 10×6 s RS test there was a tendency for greater increases in oxygen consumption in the hypoxic group (hypoxic 6.9±9%, normoxic (−0.3±8.8%, p=0.06) and reductions in cerebral deoxygenation (% changes for both groups, p=0.09) after hypoxic than normoxic training. Twelve RS training sessions in hypoxia resulted in twofold greater improvements in capacity to perform repeated aerobic high intensity workout than an equivalent normoxic training. Performance gains are evident in the short term (4 weeks), a period similar to a preseason training block. PMID:24282212

  6. Repeat Lumbar Punctures in Infants with Meningitis in the Neonatal Intensive Care Unit

    PubMed Central

    Greenberg, Rachel G.; Benjamin, Daniel K.; Cohen-Wolkowiez, Michael; Clark, Reese H.; Cotten, C. Michael; Laughon, Matthew; Smith, P. Brian

    2010-01-01

    Objective The purpose of this study is to examine the results of repeat lumbar puncture in infants with initial positive cerebrospinal fluid (CSF) cultures in order to determine the clinical characteristics and outcomes of infants with repeat positive cultures. Study Design Cohort study of infants with an initial positive CSF culture undergoing repeat lumbar puncture between 1997 and 2004 at 150 neonatal intensive care units managed by the Pediatrix Medical group. We compared the clinical outcomes of infants with repeat positive cultures and infants with repeat negative cultures. Result We identified 118 infants with repeat CSF cultures. Of these, 26 infants had repeat positive cultures. A higher proportion with repeat positive cultures died compared to those with repeat negative cultures, 6/23 (26%) vs. 6/81 (7%), respectively (p=0.02). Conclusion Among infants with a positive CSF culture, a repeat positive CSF culture is common. The presence of a second positive culture is associated with increased mortality. PMID:21164430

  7. Limitations on quantum key repeaters.

    PubMed

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  8. Magnetars as soft gamma repeaters

    NASA Astrophysics Data System (ADS)

    O'Meara, Karen

    1999-05-01

    The source of non-periodic, repeating, gamma-ray bursts located within our galaxy and near supernova remnants has been a mystery. A new theory by Christopher Thompson and Robert Duncan, postulating the existence of young neutron stars with intense magnetic fields (1E14 Gauss or more) offers an explanation. The intense magnetic fields of these "magnetars" suffice to create the phenomena detected from soft gamma-ray repeaters. The poles of a magnetar are hot enough to emit steady, low level x-ray emissions. Stresses on the star's crust due to the drifting of the magnetic field through the superfluid core create seismic activity and "starquakes," which release enormous bursts of energy. Data collected from recent soft gamma-ray repeater bursts appear to be strong evidence in support of this exciting new theory.

  9. Limitations on quantum key repeaters

    NASA Astrophysics Data System (ADS)

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-01

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  10. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    NASA Astrophysics Data System (ADS)

    Provenzano, Virgil; Della Torre, Edward; Bennett, Lawrence H.; ElBidweihy, Hatem

    2014-02-01

    The Gd5Ge2Si2 alloy and the off-stoichiometric Ni50Mn35In15 Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd5Ge2Si2 and Ni50Mn35In15 alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

  11. Stability of dental waxes following repeated heatings.

    PubMed

    Kotsiomiti, E; McCabe, J F

    1995-02-01

    The flow and strength properties of dental waxes were examined following excessive and repeated heatings of the materials. For one product, the flow at 40 +/- 0.5 degrees C was reduced by 25.3% following heating above 200 degrees C. A decrease of the elastic modulus at 20 +/- 1 degree C by approximately 66% was observed in some cases after the heating temperature had been increased to 300 degrees C. Property variations were related to compositional changes, which were investigated by infrared spectoscopy and thermal analysis. Exposure of dental waxes to temperatures higher than 200 degrees C, particularly if it is repeated, may affect the composition and properties, resulting in inferior materials.

  12. Validation of a quantitative polymerase chain reaction method for human Alu gene detection in microchimeric pigs used as donors for xenotransplantation.

    PubMed

    Abellaneda, J M; Martínez-Alarcón, L; Quereda, J J; Herrero-Medrano, J M; Mendonça, L; Mrowiec, A; García-Nicolás, O; Pallarés, F J; Ríos, A; Muñoz, A; Ramírez, P; Ramis, G

    2015-01-01

    This work was undertaken to evaluate whether a real-time quantitative polymerase chain reaction (qPCR) is as an adequate method for detection and quantification of human-specific DNA elements (Alu gene) in tissues and blood samples of pigs in which human stem cells were engrafted. Real-time qPCR quantification was performed with the use of previously described primers. The human DNA was mixed with different quantities of porcine DNA. The primer concentration and specificity, the qPCR efficiency, the quantification variations due to different porcine DNA concentrations, and the dissociation curve produced by the assay were evaluated. The qPCR proved to be specific, robust, with a reproducible and specific bimodal melting curve. High porcine DNA concentration produced subquantification, especially with low human DNA quantity. However, the assay proved to be useful for the detection of chimeric piglets produced by human cells injected in utero, because the effect caused by the porcine DNA interference was corrected in quantification of human DNA from piglets.

  13. Do Twelfths Terminate or Repeat?

    ERIC Educational Resources Information Center

    Ambrose, Rebecca; Burnison, Erica

    2015-01-01

    When finding the decimal equivalent of a fraction with 12 in the denominator, will it terminate or repeat? This question came from a seventh grader in author Erica Burnison's class as the student was pondering a poster generated by one of her classmates. Not only was the question intriguing, but it also affirmed the belief in the power of…

  14. Mechanical Anisotropy of Ankyrin Repeats

    PubMed Central

    Lee, Whasil; Zeng, Xiancheng; Rotolo, Kristina; Yang, Ming; Schofield, Christopher J.; Bennett, Vann; Yang, Weitao; Marszalek, Piotr E.

    2012-01-01

    Red blood cells are frequently deformed and their cytoskeletal proteins such as spectrin and ankyrin-R are repeatedly subjected to mechanical forces. While the mechanics of spectrin was thoroughly investigated in vitro and in vivo, little is known about the mechanical behavior of ankyrin-R. In this study, we combine coarse-grained steered molecular dynamics simulations and atomic force spectroscopy to examine the mechanical response of ankyrin repeats (ARs) in a model synthetic AR protein NI6C, and in the D34 fragment of native ankyrin-R when these proteins are subjected to various stretching geometry conditions. Our steered molecular dynamics results, supported by AFM measurements, reveal an unusual mechanical anisotropy of ARs: their mechanical stability is greater when their unfolding is forced to propagate from the N-terminus toward the C-terminus (repeats unfold at ∼60 pN), as compared to the unfolding in the opposite direction (unfolding force ∼ 30 pN). This anisotropy is also reflected in the complex refolding behavior of ARs. The origin of this unfolding and refolding anisotropy is in the various numbers of native contacts that are broken and formed at the interfaces between neighboring repeats depending on the unfolding/refolding propagation directions. Finally, we discuss how these complex mechanical properties of ARs in D34 may affect its behavior in vivo. PMID:22404934

  15. Pentapeptide Repeat Proteins and Cyanobacteria

    SciTech Connect

    Buchko, Garry W.

    2009-10-16

    Cyanobacteria are unique in many ways and one unusual feature is the presence of a suite of proteins that contain at least one domain with a minimum of eight tandem repeated five-residues (Rfr) of the general consensus sequence A[N/D]LXX. The function of such pentapeptide repeat proteins (PRPs) are still unknown, however, their prevalence in cyanobacteria suggests that they may play some role in the unique biological activities of cyanobacteria. As part of an inter-disciplinary Membrane Biology Grand Challenge at the Environmental Molecular Sciences Laboratory (Pacific Northwest National Laboratory) and Washington University in St. Louis, the genome of Cyanothece 51142 was sequenced and its molecular biology studied with relation to circadian rhythms. The genome of Cyanothece encodes for 35 proteins that contain at least one PRP domain. These proteins range in size from 105 (Cce_3102) to 930 (Cce_2929) kDa with the PRP domains ranging in predicted size from 12 (Cce_1545) to 62 (cce_3979) tandem pentapeptide repeats. Transcriptomic studies with 29 out of the 35 genes showed that at least three of the PRPs in Cyanothece 51142 (cce_0029, cce_3083, and cce_3272) oscillated with repeated periods of light and dark, further supporting a biological function for PRPs. Using X-ray diffraction crystallography, the structure for two pentapeptide repeat proteins from Cyanothece 51142 were determined, cce_1272 (aka Rfr32) and cce_4529 (aka Rfr23). Analysis of their molecular structures suggests that all PRP may share the same structural motif, a novel type of right-handed quadrilateral β-helix, or Rfr-fold, reminiscent of a square tower with four distinct faces. Each pentapeptide repeat occupies one face of the Rfr-fold with four consecutive pentapeptide repeats completing a coil that, in turn, stack upon each other to form “protein skyscrapers”. Details of the structural features of the Rfr-fold are reviewed here together with a discussion for the possible role of end

  16. Evolution of Repeated Sequence Arrays in the D-Loop Region of Bat Mitochondrial DNA

    PubMed Central

    Wilkinson, G. S.; Mayer, F.; Kerth, G.; Petri, B.

    1997-01-01

    Analysis of mitochondrial DNA control region sequences from 41 species of bats representing 11 families revealed that repeated sequence arrays near the tRNA-Pro gene are present in all vespertilionine bats. Across 18 species tandem repeats varied in size from 78 to 85 bp and contained two to nine repeats. Heteroplasmy ranged from 15% to 63%. Fewer repeats among heteroplasmic than homoplasmic individuals in a species with up to nine repeats indicates selection may act against long arrays. A lower limit of two repeats and more repeats among heteroplasmic than homoplasmic individuals in two species with few repeats suggests length mutations are biased. Significant regressions of heteroplasmy, θ and π, on repeat number further suggest that repeat duplication rate increases with repeat number. Comparison of vespertilionine bat consensus repeats to mammal control region sequences revealed that tandem repeats of similar size, sequence and number also occur in shrews, cats and bighorn sheep. The presence of two conserved protein-binding sequences in all repeat units indicates that convergent evolution has occurred by duplication of functional units. We speculate that D-loop region tandem repeats may provide signal redundancy and a primitive repair mechanism in the event of somatic mutations to these binding sites. PMID:9215906

  17. Agreement and repeatability of an infrared thermometer.

    PubMed

    Kelechi, Teresa J; Good, Angela; Mueller, Martina

    2011-01-01

    Recently, manufacturers have devised thermometers for home use by patients, such as the TempTouch Infrared Thermometer (TTIR; Diabetica Solutions, San Antonio, TX), which is designed with a long handle that can be used for self-monitoring localized skin temperature of the feet and legs. This study assessed the level of agreement and repeatability of the TTIR compared to a thermistor-type thermometer (TT; PeriFlux, 5020 Temperature Unit, Perimed, Stockholm, Sweden), the reference standard. In 17 healthy subjects, localized skin temperature was measured 8 cm above the right medial malleolus at baseline (Time 1), after a 10-minute rest period (Time 2), and after 10 minutes of cold provocation (Time 3) with a cryotherapy gel wrap placed around the lower legs using the TTIR and TT for temperature measurement. Scatter plots and correlation coefficients showed strong positive relationships between the two measurement methods at all three time points (Time 1: r = 0.95; Time 2: r = 0.97; and, Time 3: r = 0.87). Results showed a reasonable level of agreement between the two methods at Times 1 and 2 but not after cold provocation. Agreement between the methods appears to be better than repeatability within each method. Results for repeatability from both the TT and TTIR were very similar suggesting that there was a systematic bias with increasing temperatures between Time 1 and Time 2.

  18. Monocytes from patients with rheumatoid arthritis and type 2 diabetes mellitus display an increased production of interleukin (IL)-1β via the nucleotide-binding domain and leucine-rich repeat containing family pyrin 3(NLRP3)-inflammasome activation: a possible implication for therapeutic decision in these patients.

    PubMed

    Ruscitti, P; Cipriani, P; Di Benedetto, P; Liakouli, V; Berardicurti, O; Carubbi, F; Ciccia, F; Alvaro, S; Triolo, G; Giacomelli, R

    2015-10-01

    A better understanding about the mechanisms involved in the pathogenesis of type 2 diabetes mellitus (T2D) showed that inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin (IL)-1β play a pivotal role, mirroring data largely reported in rheumatoid arthritis (RA). IL-1β is produced mainly by monocytes (MO), and hyperglycaemia may be able to modulate, in the cytoplasm of these cells, the assembly of a nucleotide-binding domain and leucine-rich repeat containing family pyrin (NLRP3)-inflammosome, a cytosolic multi-protein platform where the inactive pro-IL-1β is cleaved into active form, via caspase-1 activity. In this paper, we evaluated the production of IL-1 β and TNF, in peripheral blood MO of patients affected by RA or T2D or both diseases, in order to understand if an alteration of the glucose metabolism may influence their proinflammatory status. Our data showed, after 24 h of incubation with different glucose concentrations, a significantly increased production of IL-1β and TNF in all evaluated groups when compared with healthy controls. However, a significant increase of IL-1β secretion by T2D/RA was observed when compared with other groups. The analysis of relative mRNA expression confirmed these data. After 24 h of incubation with different concentrations of glucose, our results showed a significant increase in NLRP3 expression. In this work, an increased production of IL-1β by MO obtained from patients affected by both RA and T2D via NLRP3-inflammasome activation may suggest a potential IL-1β targeted therapy in these patients.

  19. Dominant short repeated sequences in bacterial genomes.

    PubMed

    Avershina, Ekaterina; Rudi, Knut

    2015-03-01

    We use a novel multidimensional searching approach to present the first exhaustive search for all possible repeated sequences in 166 genomes selected to cover the bacterial domain. We found an overrepresentation of repeated sequences in all but one of the genomes. The most prevalent repeats by far were related to interspaced short palindromic repeats (CRISPRs)—conferring bacterial adaptive immunity. We identified a deep branching clade of thermophilic Firmicutes containing the highest number of CRISPR repeats. We also identified a high prevalence of tandem repeated heptamers. In addition, we identified GC-rich repeats that could potentially be involved in recombination events. Finally, we identified repeats in a 16322 amino acid mega protein (involved in biofilm formation) and inverted repeats flanking miniature transposable elements (MITEs). In conclusion, the exhaustive search for repeated sequences identified new elements and distribution of these, which has implications for understanding both the ecology and evolution of bacteria.

  20. Environmental stress induces trinucleotide repeat mutagenesis in human cells

    PubMed Central

    Chatterjee, Nimrat; Lin, Yunfu; Santillan, Beatriz A.; Yotnda, Patricia; Wilson, John H.

    2015-01-01

    The dynamic mutability of microsatellite repeats is implicated in the modification of gene function and disease phenotype. Studies of the enhanced instability of long trinucleotide repeats (TNRs)—the cause of multiple human diseases—have revealed a remarkable complexity of mutagenic mechanisms. Here, we show that cold, heat, hypoxic, and oxidative stresses induce mutagenesis of a long CAG repeat tract in human cells. We show that stress-response factors mediate the stress-induced mutagenesis (SIM) of CAG repeats. We show further that SIM of CAG repeats does not involve mismatch repair, nucleotide excision repair, or transcription, processes that are known to promote TNR mutagenesis in other pathways of instability. Instead, we find that these stresses stimulate DNA rereplication, increasing the proportion of cells with >4 C-value (C) DNA content. Knockdown of the replication origin-licensing factor CDT1 eliminates both stress-induced rereplication and CAG repeat mutagenesis. In addition, direct induction of rereplication in the absence of stress also increases the proportion of cells with >4C DNA content and promotes repeat mutagenesis. Thus, environmental stress triggers a unique pathway for TNR mutagenesis that likely is mediated by DNA rereplication. This pathway may impact normal cells as they encounter stresses in their environment or during development or abnormal cells as they evolve metastatic potential. PMID:25775519

  1. Observations of Soft Gamma Repeaters

    NASA Technical Reports Server (NTRS)

    Kouveliotou, Chryssa

    2004-01-01

    Magnetars (Soft Gamma Repeaters and Anomalous X-ray Pulsars) are a subclass of neutron stars characterized by their recurrent X-ray bursts. While in an active (bursting) state (lasting anywhere between days and years), they are emit&ng hundreds of predominantly soft (kT=30 kev), short (0.1-100 ms long) events. Their quiescent source x-ray light ewes exhibit puhlions rotational period rate changes (spin-down) indicate that their magnetic fields are extremely high, of the order of 10^14- 10^l5 G. Such high B-field objects, dubbed "magnetars", had been predicted to exist in 1992, but the first concrete observational evidence were obtained in 1998 for two of these sources. I will discuss here the history of Soft Gamma Repeaters, and their spectral, timing and flux characteristics both in the persistent and their burst emission.

  2. Disease-associated repeat instability and mismatch repair.

    PubMed

    Schmidt, Monika H M; Pearson, Christopher E

    2016-02-01

    Expanded tandem repeat sequences in DNA are associated with at least 40 human genetic neurological, neurodegenerative, and neuromuscular diseases. Repeat expansion can occur during parent-to-offspring transmission, and arise at variable rates in specific tissues throughout the life of an affected individual. Since the ongoing somatic repeat expansions can affect disease age-of-onset, severity, and progression, targeting somatic expansion holds potential as a therapeutic target. Thus, understanding the factors that regulate this mutation is crucial. DNA repair, in particular mismatch repair (MMR), is the major driving force of disease-associated repeat expansions. In contrast to its anti-mutagenic roles, mammalian MMR curiously drives the expansion mutations of disease-associated (CAG)·(CTG) repeats. Recent advances have broadened our knowledge of both the MMR proteins involved in disease repeat expansions, including: MSH2, MSH3, MSH6, MLH1, PMS2, and MLH3, as well as the types of repeats affected by MMR, now including: (CAG)·(CTG), (CGG)·(CCG), and (GAA)·(TTC) repeats. Mutagenic slipped-DNA structures have been detected in patient tissues, and the size of the slip-out and their junction conformation can determine the involvement of MMR. Furthermore, the formation of other unusual DNA and R-loop structures is proposed to play a key role in MMR-mediated instability. A complex correlation is emerging between tissues showing varying amounts of repeat instability and MMR expression levels. Notably, naturally occurring polymorphic variants of DNA repair genes can have dramatic effects upon the levels of repeat instability, which may explain the variation in disease age-of-onset, progression and severity. An increasing grasp of these factors holds prognostic and therapeutic potential.

  3. A repeating fast radio burst

    NASA Astrophysics Data System (ADS)

    Spitler, L. G.; Scholz, P.; Hessels, J. W. T.; Bogdanov, S.; Brazier, A.; Camilo, F.; Chatterjee, S.; Cordes, J. M.; Crawford, F.; Deneva, J.; Ferdman, R. D.; Freire, P. C. C.; Kaspi, V. M.; Lazarus, P.; Lynch, R.; Madsen, E. C.; McLaughlin, M. A.; Patel, C.; Ransom, S. M.; Seymour, A.; Stairs, I. H.; Stappers, B. W.; van Leeuwen, J.; Zhu, W. W.

    2016-03-01

    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  4. A repeating fast radio burst.

    PubMed

    Spitler, L G; Scholz, P; Hessels, J W T; Bogdanov, S; Brazier, A; Camilo, F; Chatterjee, S; Cordes, J M; Crawford, F; Deneva, J; Ferdman, R D; Freire, P C C; Kaspi, V M; Lazarus, P; Lynch, R; Madsen, E C; McLaughlin, M A; Patel, C; Ransom, S M; Seymour, A; Stairs, I H; Stappers, B W; van Leeuwen, J; Zhu, W W

    2016-03-10

    Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

  5. Tracking the processing of damaged DNA double-strand break ends by ligation-mediated PCR: increased persistence of 3'-phosphoglycolate termini in SCAN1 cells.

    PubMed

    Akopiants, Konstantin; Mohapatra, Susovan; Menon, Vijay; Zhou, Tong; Valerie, Kristoffer; Povirk, Lawrence F

    2014-03-01

    To track the processing of damaged DNA double-strand break (DSB) ends in vivo, a method was devised for quantitative measurement of 3'-phosphoglycolate (PG) termini on DSBs induced by the non-protein chromophore of neocarzinostatin (NCS-C) in the human Alu repeat. Following exposure of cells to NCS-C, DNA was isolated, and labile lesions were chemically stabilized. All 3'-phosphate and 3'-hydroxyl ends were enzymatically capped with dideoxy termini, whereas 3'-PG ends were rendered ligatable, linked to an anchor, and quantified by real-time Taqman polymerase chain reaction. Using this assay and variations thereof, 3'-PG and 3'-phosphate termini on 1-base 3' overhangs of NCS-C-induced DSBs were readily detected in DNA from the treated lymphoblastoid cells, and both were largely eliminated from cellular DNA within 1 h. However, the 3'-PG termini were processed more slowly than 3'-phosphate termini, and were more persistent in tyrosyl-DNA phosphodiesterase 1-mutant SCAN1 than in normal cells, suggesting a significant role for tyrosyl-DNA phosphodiesterase 1 in removing 3'-PG blocking groups for DSB repair. DSBs with 3'-hydroxyl termini, which are not directly induced by NCS-C, were formed rapidly in cells, and largely eliminated by further processing within 1 h, both in Alu repeats and in heterochromatic α-satellite DNA. Moreover, absence of DNA-PK in M059J cells appeared to accelerate resolution of 3'-PG ends.

  6. Genomic diversity and affinities in population groups of North West India: an analysis of Alu insertion and a single nucleotide polymorphism.

    PubMed

    Saini, J S; Kumar, A; Matharoo, K; Sokhi, J; Badaruddoza; Bhanwer, A J S

    2012-12-15

    The North West region of India is extremely important to understand the peopling of India, as it acted as a corridor to the foreign invaders from Eurasia and Central Asia. A series of these invasions along with multiple migrations led to intermixture of variable populations, strongly contributing to genetic variations. The present investigation was designed to explore the genetic diversities and affinities among the five major ethnic groups from North West India; Brahmin, Jat Sikh, Bania, Rajput and Gujjar. A total of 327 individuals of the abovementioned ethnic groups were analyzed for 4 Alu insertion marker loci (ACE, PV92, APO and D1) and a Single Nucleotide Polymorphism (SNP) rs2234693 in the intronic region of the ESR1 gene. Statistical analysis was performed to interpret the genetic structure and diversity of the population groups. Genotypes for ACE, APO, ESR1 and PV92 loci were found to be in Hardy-Weinberg equilibrium in all the ethnic groups, while significant departures were observed at the D1 locus in every investigated population after Bonferroni's correction. The average heterozygosity for all the loci in these ethnic groups was fairly substantial ranging from 0.3927 ± 0.1877 to 0.4333 ± 0.1416. Inbreeding coefficient indicated an overall 10% decrease in heterozygosity in these North West Indian populations. The gene differentiation among the populations was observed to be of the order of 0.013. Genetic distance estimates revealed that Gujjars were close to Banias and Jat Sikhs were close to Rajputs. Overall the study favored the recent division of the populations of North West India into largely endogamous groups. It was observed that the populations of North West India represent a more or less homogenous genetic entity, owing to their common ancestral history as well as geographical proximity.

  7. Accumulate Repeat Accumulate Coded Modulation

    NASA Technical Reports Server (NTRS)

    Abbasfar, Aliazam; Divsalar, Dariush; Yao, Kung

    2004-01-01

    In this paper we propose an innovative coded modulation scheme called 'Accumulate Repeat Accumulate Coded Modulation' (ARA coded modulation). This class of codes can be viewed as serial turbo-like codes, or as a subclass of Low Density Parity Check (LDPC) codes that are combined with high level modulation. Thus at the decoder belief propagation can be used for iterative decoding of ARA coded modulation on a graph, provided a demapper transforms the received in-phase and quadrature samples to reliability of the bits.

  8. Crowding by a repeating pattern

    PubMed Central

    Rosen, Sarah; Pelli, Denis G.

    2015-01-01

    Theinability to recognize a peripheral target among flankers is called crowding. For a foveal target, crowding can be distinguished from overlap masking by its sparing of detection, linear scaling with eccentricity, and invariance with target size.Crowding depends on the proximity and similarity of the flankers to the target. Flankers that are far from or dissimilar to the target do not crowd it. On a gray page, text whose neighboring letters have different colors, alternately black and white, has enough dissimilarity that it might escape crowding. Since reading speed is normally limited by crowding, escape from crowding should allow faster reading. Yet reading speed is unchanged (Chung & Mansfield, 2009). Why? A recent vernier study found that using alternating-color flankers produces strong crowding (Manassi, Sayim, & Herzog, 2012). Might that effect occur with letters and reading? Critical spacing is the minimum center-to-center target–flanker spacing needed to correctly identify the target. We measure it for a target letter surrounded by several equidistant flanker letters of the same polarity, opposite polarity, or mixed polarity: alternately white and black. We find strong crowding in the alternating condition, even though each flanker letter is beyond its own critical spacing (as measured in a separate condition). Thus a periodic repeating pattern can produce crowding even when the individual elements do not. Further, in all conditions we find that, once a periodic pattern repeats (two cycles), further repetition does not affect critical spacing of the innermost flanker. PMID:26024457

  9. Crowding by a repeating pattern.

    PubMed

    Rosen, Sarah; Pelli, Denis G

    2015-01-01

    Theinability to recognize a peripheral target among flankers is called crowding. For a foveal target, crowding can be distinguished from overlap masking by its sparing of detection, linear scaling with eccentricity, and invariance with target size.Crowding depends on the proximity and similarity of the flankers to the target. Flankers that are far from or dissimilar to the target do not crowd it. On a gray page, text whose neighboring letters have different colors, alternately black and white, has enough dissimilarity that it might escape crowding. Since reading speed is normally limited by crowding, escape from crowding should allow faster reading. Yet reading speed is unchanged (Chung & Mansfield, 2009). Why? A recent vernier study found that using alternating-color flankers produces strong crowding (Manassi, Sayim, & Herzog, 2012). Might that effect occur with letters and reading? Critical spacing is the minimum center-to-center target-flanker spacing needed to correctly identify the target. We measure it for a target letter surrounded by several equidistant flanker letters of the same polarity, opposite polarity, or mixed polarity: alternately white and black. We find strong crowding in the alternating condition, even though each flanker letter is beyond its own critical spacing (as measured in a separate condition). Thus a periodic repeating pattern can produce crowding even when the individual elements do not. Further, in all conditions we find that, once a periodic pattern repeats (two cycles), further repetition does not affect critical spacing of the innermost flanker.

  10. Evolution of Protein Domain Repeats in Metazoa

    PubMed Central

    Schüler, Andreas; Bornberg-Bauer, Erich

    2016-01-01

    Repeats are ubiquitous elements of proteins and they play important roles for cellular function and during evolution. Repeats are, however, also notoriously difficult to capture computationally and large scale studies so far had difficulties in linking genetic causes, structural properties and evolutionary trajectories of protein repeats. Here we apply recently developed methods for repeat detection and analysis to a large dataset comprising over hundred metazoan genomes. We find that repeats in larger protein families experience generally very few insertions or deletions (indels) of repeat units but there is also a significant fraction of noteworthy volatile outliers with very high indel rates. Analysis of structural data indicates that repeats with an open structure and independently folding units are more volatile and more likely to be intrinsically disordered. Such disordered repeats are also significantly enriched in sites with a high functional potential such as linear motifs. Furthermore, the most volatile repeats have a high sequence similarity between their units. Since many volatile repeats also show signs of recombination, we conclude they are often shaped by concerted evolution. Intriguingly, many of these conserved yet volatile repeats are involved in host-pathogen interactions where they might foster fast but subtle adaptation in biological arms races. Key Words: protein evolution, domain rearrangements, protein repeats, concerted evolution. PMID:27671125

  11. Repeatable assessment protocol for electromagnetic trackers

    NASA Astrophysics Data System (ADS)

    Haidegger, Tamas; Sirokai, Beáta; Fenyvesi, Gábor; Kovács, Levente; Benyó, Balázs; Benyó, Zoltán

    2012-02-01

    In the past decades, many new trends appeared in interventional medicine. One of the most groundbreaking ones is Image-Guided Surgery (IGS). The main benefit of IGS procedures is the reduction of the patient's pain and collateral damage through improved accuracy and targeting. Electromagnetic Tracking (EMT) has been introduced to medical applications as an effective tool for navigation. However, magnetic fields can be severely distorted by ferromagnetic materials and electronic equipment, which is a major barrier towards their wider application. The focus of the study is to determine and compensate the inherent errors of the different types of EMTs, in order to improve their accuracy. Our aim is to develop a standardized, simple and repeatable assessment protocol; to determine tracking errors with sub-millimeter accuracy, hence increasing the measurement precision and reliability. For initial experiments, the NDI Aurora and the Ascension medSAFE systems were used in a standard laboratory environment. We aim to advance to the state-of-the art by describing and disseminating an easily reproducible calibration method, publishing the CAD files of the accuracy phantom and the source of the evaluation data. This should allow the wider spread of the technique, and eventually lead to the repeatable and comparable assessment of EMT systems.

  12. Chromosome-specific DNA Repeat Probes

    SciTech Connect

    Baumgartner, Adolf; Weier, Jingly Fung; Weier, Heinz-Ulrich G.

    2006-03-16

    In research as well as in clinical applications, fluorescence in situ hybridization (FISH) has gained increasing popularity as a highly sensitive technique to study cytogenetic changes. Today, hundreds of commercially available DNA probes serve the basic needs of the biomedical research community. Widespread applications, however, are often limited by the lack of appropriately labeled, specific nucleic acid probes. We describe two approaches for an expeditious preparation of chromosome-specific DNAs and the subsequent probe labeling with reporter molecules of choice. The described techniques allow the preparation of highly specific DNA repeat probes suitable for enumeration of chromosomes in interphase cell nuclei or tissue sections. In addition, there is no need for chromosome enrichment by flow cytometry and sorting or molecular cloning. Our PCR-based method uses either bacterial artificial chromosomes or human genomic DNA as templates with {alpha}-satellite-specific primers. Here we demonstrate the production of fluorochrome-labeled DNA repeat probes specific for human chromosomes 17 and 18 in just a few days without the need for highly specialized equipment and without the limitation to only a few fluorochrome labels.

  13. Two-dimensional quantum repeaters

    NASA Astrophysics Data System (ADS)

    Wallnöfer, J.; Zwerger, M.; Muschik, C.; Sangouard, N.; Dür, W.

    2016-11-01

    The endeavor to develop quantum networks gave rise to a rapidly developing field with far-reaching applications such as secure communication and the realization of distributed computing tasks. This ultimately calls for the creation of flexible multiuser structures that allow for quantum communication between arbitrary pairs of parties in the network and facilitate also multiuser applications. To address this challenge, we propose a two-dimensional quantum repeater architecture to establish long-distance entanglement shared between multiple communication partners in the presence of channel noise and imperfect local control operations. The scheme is based on the creation of self-similar multiqubit entanglement structures at growing scale, where variants of entanglement swapping and multiparty entanglement purification are combined to create high-fidelity entangled states. We show how such networks can be implemented using trapped ions in cavities.

  14. Linear Synchronous Motor Repeatability Tests

    SciTech Connect

    Ward, C.R.

    2002-10-18

    A cart system using linear synchronous motors was being considered for the Plutonium Immobilization Plant (PIP). One of the applications in the PIP was the movement of a stack of furnace trays, filled with the waste form (pucks) from a stacking/unstacking station to several bottom loaded furnaces. A system was ordered to perform this function in the PIP Ceramic Prototype Test Facility (CPTF). This system was installed and started up in SRTC prior to being installed in the CPTF. The PIP was suspended and then canceled after the linear synchronous motor system was started up. This system was used to determine repeatability of a linear synchronous motor cart system for the Modern Pit Facility.

  15. Structure and expression of the human Lysyl hydroxylase gene (PLOD): Introns 9 and 16 contain Alu sequences at the sites of recombination in Ehlers-Danlos syndrome type VI patients

    SciTech Connect

    Heikkinen, J.; Hautala, T.; Kivirikko, K.I.

    1994-12-01

    Lysyl hydroxylase (EC 1.14.11.4) catalyzes the formation of hydroxylysine in collagens by the hydroxylation of lysine residues in peptide linkages. This enzyme activity is known to be reduced in patients with the type VI variant of the Ehlers-Danlos syndrome, and the first mutations in the lysyl hydroxylase gene (PLOD) have recently been identified. We have now isolated genomic clones for human lysyl hydroxylase and determined the complete structure of the gene, which contains 19 exons and a 5{prime} flanking region with characteristics shared by housekeeping genes. The constitutive expression of the gene in different tissues further suggests that lysyl hydroxylase has an essential function. We have sequenced the introns of the gene in the region where many mutations and rearrangements analyzed to date are concentrated. Intron 9 and intron 16 show extensive homology resulting from the many Alu sequences found in these introns. Intron 9 contains five and intron 16 eight Alu sequences. The high homology and many short identical or complementary sequences in these introns generate many potential recombination sites with the gene. The delineation of the structure of the lysyl hydroxylase gene contributes significantly to our understanding of the rearrangements in the genome of Ehlers-Danlos type VI patients. 21 refs., 2 figs., 2 tabs.

  16. Repeat instability: mechanisms of dynamic mutations.

    PubMed

    Pearson, Christopher E; Nichol Edamura, Kerrie; Cleary, John D

    2005-10-01

    Disease-causing repeat instability is an important and unique form of mutation that is linked to more than 40 neurological, neurodegenerative and neuromuscular disorders. DNA repeat expansion mutations are dynamic and ongoing within tissues and across generations. The patterns of inherited and tissue-specific instability are determined by both gene-specific cis-elements and trans-acting DNA metabolic proteins. Repeat instability probably involves the formation of unusual DNA structures during DNA replication, repair and recombination. Experimental advances towards explaining the mechanisms of repeat instability have broadened our understanding of this mutational process. They have revealed surprising ways in which metabolic pathways can drive or protect from repeat instability.

  17. SRS2 and SGS1 prevent chromosomal breaks and stabilize triplet repeats by restraining recombination.

    PubMed

    Kerrest, Alix; Anand, Ranjith P; Sundararajan, Rangapriya; Bermejo, Rodrigo; Liberi, Giordano; Dujon, Bernard; Freudenreich, Catherine H; Richard, Guy-Franck

    2009-02-01

    Several molecular mechanisms have been proposed to explain trinucleotide repeat expansions. Here we show that in yeast srs2Delta cells, CTG repeats undergo both expansions and contractions, and they show increased chromosomal fragility. Deletion of RAD52 or RAD51 suppresses these phenotypes, suggesting that recombination triggers trinucleotide repeat instability in srs2Delta cells. In sgs1Delta cells, CTG repeats undergo contractions and increased fragility by a mechanism partially dependent on RAD52 and RAD51. Analysis of replication intermediates revealed abundant joint molecules at the CTG repeats during S phase. These molecules migrate similarly to reversed replication forks, and their presence is dependent on SRS2 and SGS1 but not RAD51. Our results suggest that Srs2 promotes fork reversal in repetitive sequences, preventing repeat instability and fragility. In the absence of Srs2 or Sgs1, DNA damage accumulates and is processed by homologous recombination, triggering repeat rearrangements.

  18. Ising Model Reprogramming of a Repeat Protein's Equilibrium Unfolding Pathway.

    PubMed

    Millership, C; Phillips, J J; Main, E R G

    2016-05-08

    Repeat proteins are formed from units of 20-40 aa that stack together into quasi one-dimensional non-globular structures. This modular repetitive construction means that, unlike globular proteins, a repeat protein's equilibrium folding and thus thermodynamic stability can be analysed using linear Ising models. Typically, homozipper Ising models have been used. These treat the repeat protein as a series of identical interacting subunits (the repeated motifs) that couple together to form the folded protein. However, they cannot describe subunits of differing stabilities. Here we show that a more sophisticated heteropolymer Ising model can be constructed and fitted to two new helix deletion series of consensus tetratricopeptide repeat proteins (CTPRs). This analysis, showing an asymmetric spread of stability between helices within CTPR ensembles, coupled with the Ising model's predictive qualities was then used to guide reprogramming of the unfolding pathway of a variant CTPR protein. The designed behaviour was engineered by introducing destabilising mutations that increased the thermodynamic asymmetry within a CTPR ensemble. The asymmetry caused the terminal α-helix to thermodynamically uncouple from the rest of the protein and preferentially unfold. This produced a specific, highly populated stable intermediate with a putative dimerisation interface. As such it is the first step in designing repeat proteins with function regulated by a conformational switch.

  19. Impact of Repeated Exposures on Information Spreading in Social Networks.

    PubMed

    Zhou, Cangqi; Zhao, Qianchuan; Lu, Wenbo

    2015-01-01

    Clustered structure of social networks provides the chances of repeated exposures to carriers with similar information. It is commonly believed that the impact of repeated exposures on the spreading of information is nontrivial. Does this effect increase the probability that an individual forwards a message in social networks? If so, to what extent does this effect influence people's decisions on whether or not to spread information? Based on a large-scale microblogging data set, which logs the message spreading processes and users' forwarding activities, we conduct a data-driven analysis to explore the answer to the above questions. The results show that an overwhelming majority of message samples are more probable to be forwarded under repeated exposures, compared to those under only a single exposure. For those message samples that cover various topics, we observe a relatively fixed, topic-independent multiplier of the willingness of spreading when repeated exposures occur, regardless of the differences in network structure. We believe that this finding reflects average people's intrinsic psychological gain under repeated stimuli. Hence, it makes sense that the gain is associated with personal response behavior, rather than network structure. Moreover, we find that the gain is robust against the change of message popularity. This finding supports that there exists a relatively fixed gain brought by repeated exposures. Based on the above findings, we propose a parsimonious model to predict the saturated numbers of forwarding activities of messages. Our work could contribute to better understandings of behavioral psychology and social media analytics.

  20. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    SciTech Connect

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-06-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  1. Repeated recall and PKMζ maintain fear memories in juvenile rats.

    PubMed

    Oliver, Chicora F; Kabitzke, Patricia; Serrano, Peter; Egan, Laura J; Barr, Gordon A; Shair, Harry N; Wiedenmayer, Christoph

    2016-12-01

    We examined the neural substrates of fear memory formation and maintenance when repeated recall was used to prevent forgetting in young animals. In contrast to adult rats, juveniles failed to show contextual fear responses at 4 d post-fear conditioning. Reconsolidation sessions 3 and 6 d after conditioning restored contextual fear responses in juveniles 7 d after initial training. In juveniles that received reconsolidation sessions, protein kinase M zeta (PKMζ) increased in the amygdala, but not in the hippocampus. These data suggest that repeated reminders and increased PKMζ maintain fear responses in juvenile animals that otherwise would not exhibit this behavior.

  2. Regeneration of Human Liver After Hepatic Lobectomy Studied by Repeated Liver Scanning and Repeated Needle Biopsy

    PubMed Central

    Lin, Tien-Yu; Lee, Chue-Shue; Chen, Chiou-Chiang; Liau, Kuong-Yi; Lin, Wen-Shih-Jen

    1979-01-01

    Regeneration of the residual lobe of the liver after hepatic lobectomy in humans was studied by repeated liver scanning in seven noncirrhotic and three cirrhotic patients. Each patient was studied for several months during the study which lasted from 1-12 years. Regeneration was apparent in noncirrhotic liver remnants following hepatic lobectomy. In the case of a long standing, space occupying lesions such as benign giant cysts, the liver remnant would complete its regeneration process rather early, usually within a few months of hepatic lobectomy. In hepatoma cases, however, regeneration of the residual lobe after hepatic resection usually took five or six months for completion. On the contrary, no definite increase in the size of the liver remnant was seen on repeated liver scanning in cirrhotic patients. Histologic study of the residual lobe was repeated on needle biopsy specimens in two noncirrhotic and four cirrhotic patients. Regenerative hyperplasia of liver cells with large hyperchromatic, or double nuclei never seen in the preresection liver appeared in the liver remnant five, 11, and 27 days after hepatic lobectomy in noncirrhotic patients. In cirrhotics, however, there were no histologic changes between the preresection liver and the postresection remnant studied three, five, 15, 40 days or even two years and 8 months after hepatic lobectomy. ImagesFig. 1.Fig. 2.Fig. 3.Fig. 4.Fig. 5.Fig. 6. PMID:464678

  3. Association between Age and Striatal Volume Stratified by CAG Repeat Length in Prodromal Huntington Disease

    PubMed Central

    Aylward, Elizabeth; Mills, James; Liu, Dawei; Nopoulos, Peggy; Ross, Christopher A.; Pierson, Ronald; Paulsen, Jane S.

    2011-01-01

    Background: Longer CAG repeat length is associated with faster clinical progression in Huntington disease, although the effect of higher repeat length on brain atrophy is not well documented. Method: Striatal volumes were obtained from MRI scans of 720 individuals with prodromal Huntington disease. Striatal volume was plotted against age separately for groups with CAG repeat lengths of 38–39, 40, 41, 42, 43, 44, 45, 46, and 47–54. Results: Slopes representing the association between age and striatal volume were significantly steeper as CAG repeat length increased. Discussion: Although cross-sectional, these data suggest that striatal atrophy, like clinical progression, may occur faster with higher CAG repeat lengths. PMID:21593963

  4. Quantum repeaters using continuous-variable teleportation

    NASA Astrophysics Data System (ADS)

    Dias, Josephine; Ralph, T. C.

    2017-02-01

    Quantum optical states are fragile and can become corrupted when passed through a lossy communication channel. Unlike for classical signals, optical amplifiers cannot be used to recover quantum signals. Quantum repeaters have been proposed as a way of reducing errors and hence increasing the range of quantum communications. Current protocols target specific discrete encodings, for example quantum bits encoded on the polarization of single photons. We introduce a more general approach that can reduce the effect of loss on any quantum optical encoding, including those based on continuous variables such as the field amplitudes. We show that in principle the protocol incurs a resource cost that scales polynomially with distance. We analyze the simplest implementation and find that while its range is limited it can still achieve useful improvements in the distance over which quantum entanglement of field amplitudes can be distributed.

  5. Discrepancy variation of dinucleotide microsatellite repeats in eukaryotic genomes.

    PubMed

    Gao, Huan; Cai, Shengli; Yan, Binlun; Chen, Baiyao; Yu, Fei

    2009-01-01

    To address whether there are differences of variation among repeat motif types and among taxonomic groups, we present here an analysis of variation and correlation of dinucleotide microsatellite repeats in eukaryotic genomes. Ten taxonomic groups were compared, those being primates, mammalia (excluding primates and rodentia), rodentia, birds, fish, amphibians and reptiles, insects, molluscs, plants and fungi, respectively. The data used in the analysis is from the literature published in the Journal of Molecular Ecology Notes. Analysis of variation reveals that there are no significant differences between AC and AG repeat motif types. Moreover, the number of alleles correlates positively with the copy number in both AG and AC repeats. Similar conclusions can be obtained from each taxonomic group. These results strongly suggest that the increase of SSR variation is almost linear with the increase of the copy number of each repeat motif. As well, the results suggest that the variability of SSR in the genomes of low-ranking species seem to be more than that of high-ranking species, excluding primates and fungi.

  6. Modeling Repeatedly Flaring δ Sunspots

    NASA Astrophysics Data System (ADS)

    Chatterjee, Piyali; Hansteen, Viggo; Carlsson, Mats

    2016-03-01

    Active regions (ARs) appearing on the surface of the Sun are classified into α , β , γ , and δ by the rules of the Mount Wilson Observatory, California on the basis of their topological complexity. Amongst these, the δ sunspots are known to be superactive and produce the most x-ray flares. Here, we present results from a simulation of the Sun by mimicking the upper layers and the corona, but starting at a more primitive stage than any earlier treatment. We find that this initial state consisting of only a thin subphotospheric magnetic sheet breaks into multiple flux tubes which evolve into a colliding-merging system of spots of opposite polarity upon surface emergence, similar to those often seen on the Sun. The simulation goes on to produce many exotic δ sunspot associated phenomena: repeated flaring in the range of typical solar flare energy release and ejective helical flux ropes with embedded cool-dense plasma filaments resembling solar coronal mass ejections.

  7. Modeling Repeatedly Flaring δ Sunspots.

    PubMed

    Chatterjee, Piyali; Hansteen, Viggo; Carlsson, Mats

    2016-03-11

    Active regions (ARs) appearing on the surface of the Sun are classified into α, β, γ, and δ by the rules of the Mount Wilson Observatory, California on the basis of their topological complexity. Amongst these, the δ sunspots are known to be superactive and produce the most x-ray flares. Here, we present results from a simulation of the Sun by mimicking the upper layers and the corona, but starting at a more primitive stage than any earlier treatment. We find that this initial state consisting of only a thin subphotospheric magnetic sheet breaks into multiple flux tubes which evolve into a colliding-merging system of spots of opposite polarity upon surface emergence, similar to those often seen on the Sun. The simulation goes on to produce many exotic δ sunspot associated phenomena: repeated flaring in the range of typical solar flare energy release and ejective helical flux ropes with embedded cool-dense plasma filaments resembling solar coronal mass ejections.

  8. Trinucleotide Repeats: A Structural Perspective

    PubMed Central

    Almeida, Bruno; Fernandes, Sara; Abreu, Isabel A.; Macedo-Ribeiro, Sandra

    2013-01-01

    Trinucleotide repeat (TNR) expansions are present in a wide range of genes involved in several neurological disorders, being directly involved in the molecular mechanisms underlying pathogenesis through modulation of gene expression and/or the function of the RNA or protein it encodes. Structural and functional information on the role of TNR sequences in RNA and protein is crucial to understand the effect of TNR expansions in neurodegeneration. Therefore, this review intends to provide to the reader a structural and functional view of TNR and encoded homopeptide expansions, with a particular emphasis on polyQ expansions and its role at inducing the self-assembly, aggregation and functional alterations of the carrier protein, which culminates in neuronal toxicity and cell death. Detail will be given to the Machado-Joseph Disease-causative and polyQ-containing protein, ataxin-3, providing clues for the impact of polyQ expansion and its flanking regions in the modulation of ataxin-3 molecular interactions, function, and aggregation. PMID:23801983

  9. TRDB—The Tandem Repeats Database

    PubMed Central

    Gelfand, Yevgeniy; Rodriguez, Alfredo; Benson, Gary

    2007-01-01

    Tandem repeats in DNA have been under intensive study for many years, first, as a consequence of their usefulness as genomic markers and DNA fingerprints and more recently as their role in human disease and regulatory processes has become apparent. The Tandem Repeats Database (TRDB) is a public repository of information on tandem repeats in genomic DNA. It contains a variety of tools for repeat analysis, including the Tandem Repeats Finder program, query and filtering capabilities, repeat clustering, polymorphism prediction, PCR primer selection, data visualization and data download in a variety of formats. In addition, TRDB serves as a centralized research workbench. It provides user storage space and permits collaborators to privately share their data and analysis. TRDB is available at . PMID:17175540

  10. Hypoxic Repeat Sprint Training Improves Rugby Player's Repeated Sprint but Not Endurance Performance.

    PubMed

    Hamlin, Michael J; Olsen, Peter D; Marshall, Helen C; Lizamore, Catherine A; Elliot, Catherine A

    2017-01-01

    hypoxia for six sessions increases repeat sprint ability but not YYIR1 performance in well-trained rugby players.

  11. Hypoxic Repeat Sprint Training Improves Rugby Player's Repeated Sprint but Not Endurance Performance

    PubMed Central

    Hamlin, Michael J.; Olsen, Peter D.; Marshall, Helen C.; Lizamore, Catherine A.; Elliot, Catherine A.

    2017-01-01

    group. Repeat-sprint training in hypoxia for six sessions increases repeat sprint ability but not YYIR1 performance in well-trained rugby players. PMID:28223938

  12. Visual Scan Adaptation During Repeated Visual Search

    DTIC Science & Technology

    2010-01-01

    repeated distractor –target configurations both require environmental stability. For stable distractor – target configurations, Chun and Jiang (1998) have...demon- strated search time savings from repeating distractor –target configurations, and Song and Jiang (2005) demonstrated that as little as 25% of the...search environment (i.e., two distractor locations and the target location out of 12 total locations per trial) repeated from trial to trial resulted

  13. Short Tandem Repeat DNA Internet Database

    National Institute of Standards and Technology Data Gateway

    SRD 130 Short Tandem Repeat DNA Internet Database (Web, free access)   Short Tandem Repeat DNA Internet Database is intended to benefit research and application of short tandem repeat DNA markers for human identity testing. Facts and sequence information on each STR system, population data, commonly used multiplex STR systems, PCR primers and conditions, and a review of various technologies for analysis of STR alleles have been included.

  14. Lambda Exonuclease Digestion of CGG Trinucleotide Repeats

    PubMed Central

    Conroy, R.S.; Koretsky, A.P.; Moreland, J.

    2011-01-01

    Fragile X syndrome and other triplet repeat diseases are characterized by an elongation of a repeating DNA triplet. The ensemble-averaged lambda exonuclease digestion rate of different substrates, including one with an elongated FMR1 gene containing 120 CGG repeats, was measured using absorption and fluorescence spectroscopy. Using magnetic tweezers sequence-dependent digestion rates and pausing was measured for individual lambda exonucleases. Within the triplet repeats a lower average and narrower distribution of rates and a higher frequency of pausing was observed. PMID:19562332

  15. The Repeat Expansion Diseases: the dark side of DNA repair?

    PubMed Central

    Zhao, Xiao-Nan; Usdin, Karen

    2015-01-01

    DNA repair normally protects the genome against mutations that threaten genome integrity and thus cell viability. However, growing evidence suggests that in the case of the Repeat Expansion Diseases, disorders that result from an increase in the size of a disease-specific microsatellite, the disease-causing mutation is actually the result of aberrant DNA repair. A variety of proteins from different DNA repair pathways have thus far been implicated in this process. This review will summarize recent findings from patients and from mouse models of these diseases that shed light on how these pathways may interact to cause repeat expansion. PMID:26002199

  16. Potential Role of the Last Half Repeat in TAL Effectors Revealed by a Molecular Simulation Study

    PubMed Central

    Wan, Hua; Chang, Shan; Hu, Jian-ping; Tian, Xu-hong

    2016-01-01

    TAL effectors (TALEs) contain a modular DNA-binding domain that is composed of tandem repeats. In all naturally occurring TALEs, the end of tandem repeats is invariantly a truncated half repeat. To investigate the potential role of the last half repeat in TALEs, we performed comparative molecular dynamics simulations for the crystal structure of DNA-bound TALE AvrBs3 lacking the last half repeat and its modeled structure having the last half repeat. The structural stability analysis indicates that the modeled system is more stable than the nonmodeled system. Based on the principle component analysis, it is found that the AvrBs3 increases its structural compactness in the presence of the last half repeat. The comparison of DNA groove parameters of the two systems implies that the last half repeat also causes the change of DNA major groove binding efficiency. The following calculation of hydrogen bond reveals that, by stabilizing the phosphate binding with DNA at the C-terminus, the last half repeat helps to adopt a compact conformation at the protein-DNA interface. It further mediates more contacts between TAL repeats and DNA nucleotide bases. Finally, we suggest that the last half repeat is required for the high-efficient recognition of DNA by TALE. PMID:27803930

  17. Systematic exchanges between nucleotides: Genomic swinger repeats and swinger transcription in human mitochondria.

    PubMed

    Seligmann, Hervé

    2015-11-07

    Chargaff׳s second parity rule, quasi-equal single strand frequencies for complementary nucleotides, presumably results from insertion of repeats and inverted repeats during sequence genesis. Vertebrate mitogenomes escape this rule because repeats are counterselected: their hybridization produces loop bulges whose deletion is deleterious. Some DNA/RNA sequences match mitogenomes only after assuming one among 23 systematic nucleotide exchanges (swinger DNA/RNA: nine symmetric, e.g. A ↔ C; and 14 asymmetric, e.g. A → C → G → A). Swinger-transformed repeats do not hybridize, escaping selection against deletions due to bulge formation. Blast analyses of the human mitogenome detect swinger repeats for all 23 swinger types, more than in randomized sequences with identical length and nucleotide contents. Mean genomic swinger repeat lengths increase with observed human swinger RNA frequencies: swinger repeat and swinger RNA productions appear linked, perhaps by swinger RNA retrotranscription. Mean swinger repeat lengths are proportional to reading frame retrievability, post-swinger transformation, by the natural circular code. Genomic swinger repeats confirm at genomic level, independently of swinger RNA detection, occurrence of swinger polymerizations. They suggest that repeats, and swinger repeats in particular, contribute to genome genesis.

  18. Polymorphism of CAG repeats in androgen receptor of carnivores.

    PubMed

    Wang, Qin; Zhang, Xiuyue; Wang, Xiaofang; Zeng, Bo; Jia, Xiaodong; Hou, Rong; Yue, Bisong

    2012-03-01

    Androgen effect is mediated by the androgen receptor (AR). The polymorphism of CAG triplet repeat (polyCAG), in the N-terminal transactivation domain of the AR protein, has been involved either in endocrine or neurological disorders in human. We obtained partial sequence of AR exon 1 in 10 carnivore species. In most carnivore species, polyglutamine length polymorphism presented in all three CAG repeat regions of AR, in contrast, only CAG-I site polymorphism presented in primate species, and CAG-I and CAG-III sites polymorphism presented in Canidae. Therefore, studies focusing on disease-associated polymorphism of poly(CAG) in carnivore species AR should investigate all three CAG repeats sites, and should not only consider CAG-I sites as the human disease studies. The trinucleotide repeat length in carnivore AR exon 1 had undergone from expansions to contractions during carnivores evolution, unlike a linear increase in primate species. Furthermore, the polymorphisms of the triplet-repeats in the same tissue (somatic mosaicism) were demonstrated in Moutain weasel, Eurasian lynx, Clouded leopard, Chinese tiger, Black leopard and Leopard AR. And, the abnormal stop codon was found in the exon 1 of three carnivore species AR (Moutain weasel, Eurasian lynx and Black leopard). It seemed to have a high frequency presence of tissue-specific somatic in carnivores AR genes. Thus the in vivo mechanism leading to such highly variable phenotypes of the described mutations, and their impact on these animals, are worthwhile to be further elucidated.

  19. Implementation of bipartite or remote unitary gates with repeater nodes

    NASA Astrophysics Data System (ADS)

    Yu, Li; Nemoto, Kae

    2016-08-01

    We propose some protocols to implement various classes of bipartite unitary operations on two remote parties with the help of repeater nodes in-between. We also present a protocol to implement a single-qubit unitary with parameters determined by a remote party with the help of up to three repeater nodes. It is assumed that the neighboring nodes are connected by noisy photonic channels, and the local gates can be performed quite accurately, while the decoherence of memories is significant. A unitary is often a part of a larger computation or communication task in a quantum network, and to reduce the amount of decoherence in other systems of the network, we focus on the goal of saving the total time for implementing a unitary including the time for entanglement preparation. We review some previously studied protocols that implement bipartite unitaries using local operations and classical communication and prior shared entanglement, and apply them to the situation with repeater nodes without prior entanglement. We find that the protocols using piecewise entanglement between neighboring nodes often require less total time compared to preparing entanglement between the two end nodes first and then performing the previously known protocols. For a generic bipartite unitary, as the number of repeater nodes increases, the total time could approach the time cost for direct signal transfer from one end node to the other. We also prove some lower bounds of the total time when there are a small number of repeater nodes. The application to position-based cryptography is discussed.

  20. All repeats are not equal: a module-based approach to guide repeat protein design.

    PubMed

    Sawyer, Nicholas; Chen, Jieming; Regan, Lynne

    2013-05-27

    Repeat proteins composed of tandem arrays of a short structural motif often mediate protein-protein interactions. Past efforts to design repeat protein-based molecular recognition tools have focused on the creation of templates from the consensus of individual repeats, regardless of their natural context. Such an approach assumes that all repeats are essentially equivalent. In this study, we present the results of a "module-based" approach in which modules composed of tandem repeats are aligned to identify repeat-specific features. Using this approach to analyze tetratricopeptide repeat modules that contain three tandem repeats (3TPRs), we identify two classes of 3TPR modules with distinct structural signatures that are correlated with different sets of functional residues. Our analyses also reveal a high degree of correlation between positions across the entire ligand-binding surface, indicative of a coordinated, coevolving binding surface. Extension of our analyses to different repeat protein modules reveals more examples of repeat-specific features, especially in armadillo repeat modules. In summary, the module-based analyses that we present effectively capture key repeat-specific features that will be important to include in future repeat protein design templates.

  1. Evolution Analysis of Simple Sequence Repeats in Plant Genome.

    PubMed

    Qin, Zhen; Wang, Yanping; Wang, Qingmei; Li, Aixian; Hou, Fuyun; Zhang, Liming

    2015-01-01

    Simple sequence repeats (SSRs) are widespread units on genome sequences, and play many important roles in plants. In order to reveal the evolution of plant genomes, we investigated the evolutionary regularities of SSRs during the evolution of plant species and the plant kingdom by analysis of twelve sequenced plant genome sequences. First, in the twelve studied plant genomes, the main SSRs were those which contain repeats of 1-3 nucleotides combination. Second, in mononucleotide SSRs, the A/T percentage gradually increased along with the evolution of plants (except for P. patens). With the increase of SSRs repeat number the percentage of A/T in C. reinhardtii had no significant change, while the percentage of A/T in terrestrial plants species gradually declined. Third, in dinucleotide SSRs, the percentage of AT/TA increased along with the evolution of plant kingdom and the repeat number increased in terrestrial plants species. This trend was more obvious in dicotyledon than monocotyledon. The percentage of CG/GC showed the opposite pattern to the AT/TA. Forth, in trinucleotide SSRs, the percentages of combinations including two or three A/T were in a rising trend along with the evolution of plant kingdom; meanwhile with the increase of SSRs repeat number in plants species, different species chose different combinations as dominant SSRs. SSRs in C. reinhardtii, P. patens, Z. mays and A. thaliana showed their specific patterns related to evolutionary position or specific changes of genome sequences. The results showed that, SSRs not only had the general pattern in the evolution of plant kingdom, but also were associated with the evolution of the specific genome sequence. The study of the evolutionary regularities of SSRs provided new insights for the analysis of the plant genome evolution.

  2. Hydrological Modeling and Repeatability with Brokering

    NASA Astrophysics Data System (ADS)

    Easton, Z. M.; Collick, A.; Srinivasan, R.; Braeckel, A.; Nativi, S.; McAlister, C.; Wright, D. J.; Khalsa, S. J. S.; Fuka, D.

    2014-12-01

    Data brokering aims to provide those in the hydrological sciences with access to relevant data to represent physical, biological, and chemical characteristics researchers need to accelerate discovery in their domain. Environmental models are useful tools to understand the behavior of hydrological systems. Unfortunately, parameterization of these models requires many different data sources from different disciplines (e.g., atmospheric, geoscience, ecology). In hydrological modeling, the traditional procedure for model initialization starts with obtaining elevation models, land-use characterizations, soils maps, and weather data. It is often the researcher's past experience with these datasets that determines which datasets will be used in a study, and often newer, more suitable data products exist. An added complexity is that various science communities have differing data formats, storage protocols and manipulation methods, which makes use by a non domain scientist difficult and time consuming. We propose data brokering as a means to address several of these challenges. We present two test case scenarios in which researchers attempt to reproduce hydrological model results using 1) general internet based data gathering techniques, and 2) a scientific data brokering interface. We show that data brokering increases the efficiency with which data are collected, models are initialized, and results are analyzed. As an added benefit, it appears brokering significantly increases the repeatability of a study.

  3. Types of DNA methylation status of the interspersed repetitive sequences for LINE-1, Alu, HERV-E and HERV-K in the neutrophils from systemic lupus erythematosus patients and healthy controls.

    PubMed

    Sukapan, Patadon; Promnarate, Paramate; Avihingsanon, Yingyos; Mutirangura, Apiwat; Hirankarn, Nattiya

    2014-04-01

    Changes of the DNA methylation at the interspersed repetitive sequences can occur in various conditions including cancer as well as autoimmune diseases. We previously reported the hypomethylation of LINE-1 and HERV-E in the lymphocytes of systemic lupus erythematosus (SLE) patients. As neutrophils are another important cell type contributing to SLE pathogenesis, in this study, we evaluated the methylation levels and patterns for LINE-1, ALU, HERV-E and HERV-K in the neutrophils from SLE patients compared with the healthy controls. We observed that the methylation levels, especially for LINE-1, in the neutrophils from SLE patients were significantly lower than the healthy controls (P-value < 0.0001). Interestingly, this hypomethylation was not correlated with the activity of the disease. Furthermore, the methylation levels and patterns for Alu, HERV-E and HERV-K in the neutrophils from the SLE patients were not significantly different from the healthy controls. In addition, we further investigated whether there were any correlations between the intragenic LINE-1 and differential expressions of the neutrophils from the SLE patients using public arrays data. The upregulated genes in the neutrophils from the SLE patients were significantly associated with the genes containing LINE-1s compared with the healthy controls (P-value GSE27427 = 7.74 × 10(-3); odds ratio (OR) = 1.28). Interestingly, this association was mainly found among genes with antisense LINE-1s (P-value GSE27427 = 6.22 × 10(-3); OR = 1.38). Bioinformatics data suggest that LINE-1 hypomethylation may affect expression of the genes that may contribute to the pathogenesis of SLE. However, additional functional studies of these proposed genes are warranted to prove this hypothesis.

  4. A Comparison of DWI Repeaters and Non-repeaters Who Attended a Level I Rehabilitation Program.

    ERIC Educational Resources Information Center

    Landrum, James W.; Windham, Gerald O.

    1981-01-01

    Compares behavioral and demographic characteristics of drunk drivers with repeated arrests and drivers not having repeated arrests, after attending an alcohol education program. Previous public drunkeness and previous drunk driving arrests were strong predictors of repeat arrests and were judged useful in screening offenders for rehabilitation…

  5. Repeated Testing Produces Superior Transfer of Learning Relative to Repeated Studying

    ERIC Educational Resources Information Center

    Butler, Andrew C.

    2010-01-01

    The present research investigated whether test-enhanced learning can be used to promote transfer. More specifically, 4 experiments examined how repeated testing and repeated studying affected retention and transfer of facts and concepts. Subjects studied prose passages and then either repeatedly restudied or took tests on the material. One week…

  6. Experimentally Induced Repeated Anhydrobiosis in the Eutardigrade Richtersius coronifer

    PubMed Central

    2016-01-01

    Tardigrades represent one of the main animal groups with anhydrobiotic capacity at any stage of their life cycle. The ability of tardigrades to survive repeated cycles of anhydrobiosis has rarely been studied but is of interest to understand the factors constraining anhydrobiotic survival. The main objective of this study was to investigate the patterns of survival of the eutardigrade Richtersius coronifer under repeated cycles of desiccation, and the potential effect of repeated desiccation on size, shape and number of storage cells. We also analyzed potential change in body size, gut content and frequency of mitotic storage cells. Specimens were kept under non-cultured conditions and desiccated under controlled relative humidity. After each desiccation cycle 10 specimens were selected for analysis of morphometric characteristics and mitosis. The study demonstrates that tardigrades may survive up to 6 repeated desiccations, with declining survival rates with increased number of desiccations. We found a significantly higher proportion of animals that were unable to contract properly into a tun stage during the desiccation process at the 5th and 6th desiccations. Also total number of storage cells declined at the 5th and 6th desiccations, while no effect on storage cell size was observed. The frequency of mitotic storage cells tended to decline with higher number of desiccation cycles. Our study shows that the number of consecutive cycles of anhydrobiosis that R. coronifer may undergo is limited, with increased inability for tun formation and energetic constraints as possible causal factors. PMID:27828978

  7. Validity of repeated initial rise thermoluminescence kinetic parameter determinations

    SciTech Connect

    Kierstead, J.A.; Levy, P.W.

    1990-01-01

    The validity of thermoluminescence (TL) analysis by repeated initial rise measurements has been studied by computer simulation. Thermoluminescence described by 1st Order, 2nd Order, General One Trap and Interactive TL Kinetics was investigated. In the simulation each of the repeated temperature increase and decrease cycles contains a linear temperature increase followed by a decrease appropriate for radiative cooling, i.e. the latter is approximated by a decreasing exponential. The activation energies computed from the simulated emission are readily compared with those used to compute the TL emission. In all cases studied, the repeated initial rise technique provides reliable results only for single peak glow curves or for glow curves containing peaks that do not overlap and, if sufficiently separated, the lowest temperature peak in multipeak curves. Also the temperatures, or temperature cycles corresponding to correct activation energies occur on the low temperature side of the normal glow curve, often well below the peak temperature. A variety of misleading and/or incorrect results an be obtained when the repeated initial rise technique is applied to TL systems that produce overlapping peaks in the usual glow curve. 6 refs., 10 figs.

  8. Impact of Repeated Exposures on Information Spreading in Social Networks

    PubMed Central

    Zhou, Cangqi; Zhao, Qianchuan; Lu, Wenbo

    2015-01-01

    Clustered structure of social networks provides the chances of repeated exposures to carriers with similar information. It is commonly believed that the impact of repeated exposures on the spreading of information is nontrivial. Does this effect increase the probability that an individual forwards a message in social networks? If so, to what extent does this effect influence people’s decisions on whether or not to spread information? Based on a large-scale microblogging data set, which logs the message spreading processes and users’ forwarding activities, we conduct a data-driven analysis to explore the answer to the above questions. The results show that an overwhelming majority of message samples are more probable to be forwarded under repeated exposures, compared to those under only a single exposure. For those message samples that cover various topics, we observe a relatively fixed, topic-independent multiplier of the willingness of spreading when repeated exposures occur, regardless of the differences in network structure. We believe that this finding reflects average people’s intrinsic psychological gain under repeated stimuli. Hence, it makes sense that the gain is associated with personal response behavior, rather than network structure. Moreover, we find that the gain is robust against the change of message popularity. This finding supports that there exists a relatively fixed gain brought by repeated exposures. Based on the above findings, we propose a parsimonious model to predict the saturated numbers of forwarding activities of messages. Our work could contribute to better understandings of behavioral psychology and social media analytics. PMID:26465749

  9. Repeatability of locomotor performance and morphology-locomotor performance relationships.

    PubMed

    Conradsen, Cara; Walker, Jeffrey A; Perna, Catherine; McGuigan, Katrina

    2016-09-15

    There is good evidence that natural selection drives the evolution of locomotor performance, but the processes that generate the among-individual variation for selection to act on are relatively poorly understood. We measured prolonged swimming performance, Ucrit, and morphology in a large cohort (n=461) of wild-type zebrafish (Danio rerio) at ∼6 months and again at ∼9 months. Using mixed-model analyses to estimate repeatability as the intraclass correlation coefficient, we determined that Ucrit was significantly repeatable (r=0.55; 95% CI: 0.45-0.64). Performance differences between the sexes (males 12% faster than females) and changes with age (decreasing 0.07% per day) both contributed to variation in Ucrit and, therefore, the repeatability estimate. Accounting for mean differences between sexes within the model decreased the estimate of Ucrit repeatability to 21% below the naïve estimate, while fitting age in the models increased the estimate to 14% above the naïve estimate. Greater consideration of factors such as age and sex is therefore necessary for the interpretation of performance repeatability in wild populations. Body shape significantly predicted Ucrit in both sexes in both assays, with the morphology-performance relationship significantly repeatable at the population level. However, morphology was more strongly predicative of performance in older fish, suggesting a change in the contribution of morphology relative to other factors such as physiology and behaviour. The morphology-performance relationship changed with age to a greater extent in males than females.

  10. Context dependency of trait repeatability and its relevance for management and conservation of fish populations

    PubMed Central

    Killen, S. S.; Adriaenssens, B.; Marras, S.; Claireaux, G.; Cooke, S. J.

    2016-01-01

    Repeatability of behavioural and physiological traits is increasingly a focus for animal researchers, for which fish have become important models. Almost all of this work has been done in the context of evolutionary ecology, with few explicit attempts to apply repeatability and context dependency of trait variation toward understanding conservation-related issues. Here, we review work examining the degree to which repeatability of traits (such as boldness, swimming performance, metabolic rate and stress responsiveness) is context dependent. We review methods for quantifying repeatability (distinguishing between within-context and across-context repeatability) and confounding factors that may be especially problematic when attempting to measure repeatability in wild fish. Environmental factors such temperature, food availability, oxygen availability, hypercapnia, flow regime and pollutants all appear to alter trait repeatability in fishes. This suggests that anthropogenic environmental change could alter evolutionary trajectories by changing which individuals achieve the greatest fitness in a given set of conditions. Gaining a greater understanding of these effects will be crucial for our ability to forecast the effects of gradual environmental change, such as climate change and ocean acidification, the study of which is currently limited by our ability to examine trait changes over relatively short time scales. Also discussed are situations in which recent advances in technologies associated with electronic tags (biotelemetry and biologging) and respirometry will help to facilitate increased quantification of repeatability for physiological and integrative traits, which so far lag behind measures of repeatability of behavioural traits. PMID:27382470

  11. Epigenetics and Triplet-Repeat Neurological Diseases.

    PubMed

    Nageshwaran, Sathiji; Festenstein, Richard

    2015-01-01

    The term "junk DNA" has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterochromatinized resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions frequently exist as dinucleotide, trinucleotide, and tetranucleotide repeats. The association between repetitive regions and disease was emphasized following the discovery of abnormal trinucleotide repeats underlying spinal and bulbar muscular atrophy (Kennedy's disease) and fragile X syndrome of mental retardation (FRAXA) in 1991. In this review, we provide a brief overview of epigenetic mechanisms and then focus on several diseases caused by DNA triplet-repeat expansions, which exhibit diverse epigenetic effects. It is clear that the emerging field of epigenetics is already generating novel potential therapeutic avenues for this group of largely incurable diseases.

  12. DNA Triplet Repeat Expansion and Mismatch Repair

    PubMed Central

    Iyer, Ravi R.; Pluciennik, Anna; Napierala, Marek; Wells, Robert D.

    2016-01-01

    DNA mismatch repair is a conserved antimutagenic pathway that maintains genomic stability through rectification of DNA replication errors and attenuation of chromosomal rearrangements. Paradoxically, mutagenic action of mismatch repair has been implicated as a cause of triplet repeat expansions that cause neurological diseases such as Huntington disease and myotonic dystrophy. This mutagenic process requires the mismatch recognition factor MutSβ and the MutLα (and/or possibly MutLγ) endonuclease, and is thought to be triggered by the transient formation of unusual DNA structures within the expanded triplet repeat element. This review summarizes the current knowledge of DNA mismatch repair involvement in triplet repeat expansion, which encompasses in vitro biochemical findings, cellular studies, and various in vivo transgenic animal model experiments. We present current mechanistic hypotheses regarding mismatch repair protein function in mediating triplet repeat expansions and discuss potential therapeutic approaches targeting the mismatch repair pathway. PMID:25580529

  13. Investigation of a Quadruplex-Forming Repeat Sequence Highly Enriched in Xanthomonas and Nostoc sp.

    PubMed Central

    Rehm, Charlotte; Wurmthaler, Lena A.; Li, Yuanhao; Frickey, Tancred; Hartig, Jörg S.

    2015-01-01

    In prokaryotes simple sequence repeats (SSRs) with unit sizes of 1–5 nucleotides (nt) are causative for phase and antigenic variation. Although an increased abundance of heptameric repeats was noticed in bacteria, reports about SSRs of 6–9 nt are rare. In particular G-rich repeat sequences with the propensity to fold into G-quadruplex (G4) structures have received little attention. In silico analysis of prokaryotic genomes show putative G4 forming sequences to be abundant. This report focuses on a surprisingly enriched G-rich repeat of the type GGGNATC in Xanthomonas and cyanobacteria such as Nostoc. We studied in detail the genomes of Xanthomonas campestris pv. campestris ATCC 33913 (Xcc), Xanthomonas axonopodis pv. citri str. 306 (Xac), and Nostoc sp. strain PCC7120 (Ana). In all three organisms repeats are spread all over the genome with an over-representation in non-coding regions. Extensive variation of the number of repetitive units was observed with repeat numbers ranging from two up to 26 units. However a clear preference for four units was detected. The strong bias for four units coincides with the requirement of four consecutive G-tracts for G4 formation. Evidence for G4 formation of the consensus repeat sequences was found in biophysical studies utilizing CD spectroscopy. The G-rich repeats are preferably located between aligned open reading frames (ORFs) and are under-represented in coding regions or between divergent ORFs. The G-rich repeats are preferentially located within a distance of 50 bp upstream of an ORF on the anti-sense strand or within 50 bp from the stop codon on the sense strand. Analysis of whole transcriptome sequence data showed that the majority of repeat sequences are transcribed. The genetic loci in the vicinity of repeat regions show increased genomic stability. In conclusion, we introduce and characterize a special class of highly abundant and wide-spread quadruplex-forming repeat sequences in bacteria. PMID:26695179

  14. Investigation of a Quadruplex-Forming Repeat Sequence Highly Enriched in Xanthomonas and Nostoc sp.

    PubMed

    Rehm, Charlotte; Wurmthaler, Lena A; Li, Yuanhao; Frickey, Tancred; Hartig, Jörg S

    2015-01-01

    In prokaryotes simple sequence repeats (SSRs) with unit sizes of 1-5 nucleotides (nt) are causative for phase and antigenic variation. Although an increased abundance of heptameric repeats was noticed in bacteria, reports about SSRs of 6-9 nt are rare. In particular G-rich repeat sequences with the propensity to fold into G-quadruplex (G4) structures have received little attention. In silico analysis of prokaryotic genomes show putative G4 forming sequences to be abundant. This report focuses on a surprisingly enriched G-rich repeat of the type GGGNATC in Xanthomonas and cyanobacteria such as Nostoc. We studied in detail the genomes of Xanthomonas campestris pv. campestris ATCC 33913 (Xcc), Xanthomonas axonopodis pv. citri str. 306 (Xac), and Nostoc sp. strain PCC7120 (Ana). In all three organisms repeats are spread all over the genome with an over-representation in non-coding regions. Extensive variation of the number of repetitive units was observed with repeat numbers ranging from two up to 26 units. However a clear preference for four units was detected. The strong bias for four units coincides with the requirement of four consecutive G-tracts for G4 formation. Evidence for G4 formation of the consensus repeat sequences was found in biophysical studies utilizing CD spectroscopy. The G-rich repeats are preferably located between aligned open reading frames (ORFs) and are under-represented in coding regions or between divergent ORFs. The G-rich repeats are preferentially located within a distance of 50 bp upstream of an ORF on the anti-sense strand or within 50 bp from the stop codon on the sense strand. Analysis of whole transcriptome sequence data showed that the majority of repeat sequences are transcribed. The genetic loci in the vicinity of repeat regions show increased genomic stability. In conclusion, we introduce and characterize a special class of highly abundant and wide-spread quadruplex-forming repeat sequences in bacteria.

  15. Cumulative Effect of Repeated Brief Cerebral Ischemia

    DTIC Science & Technology

    1993-05-31

    KL, Pohost GM and Conger KA, Correlating EEG and Lactate Kinetics During Repeated Brief Cerebral Ischemia, Proceedings of the American Heart Association 1993...Cornelating EEG and Lactate Kinetics During Repeated Brief Cerebral Ischemia, Proceedings of the American Heart Association 1993. 4) HP Hetherington...thes Bernhard Foundation. ass- 134 󈧑&.1 n5. 9# American Heart Association 026085 66th Scientific Sessions Abstract Form Medical Research Nursing

  16. Repeat radiosurgery for cerebral arteriovenous malformations

    PubMed Central

    Stapleton, Christopher J.; Ding, Dale; Leed, Cheng-Chia; Loeffler, Jay S.

    2015-01-01

    We perform a systematic review of repeated radiosurgery for cerebral arteriovenous malformations (AVM) with an emphasis on lesion obliteration rates and complications. Radiosurgery is an accepted treatment modality for AVM located in eloquent cortex or deep brain structures. For residual or persistent lesions, repeated radiosurgery can be considered if sufficient time has passed to allow for a full appreciation of treatment effects, usually at least 3 years. A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. References for this review were identified by searches of MEDLINE, Web of Science and Google Scholar databases. A total of 14 studies comprising 733 patients met the review criteria and were included. For series that reported target dose at both first and repeat treatments, the weighted means were 19.42 Gy and 19.06 Gy, respectively. The mean and median obliteration rate for the repeat radiosurgery treatments were 61% (95% confidence interval 51.9–71.7%) and 61.5%, respectively. The median follow up following radiosurgery ranged from 19.5 to 80 months. Time to complete obliteration after the repeat treatment ranged from 21 to 40.8 months. The most common complications of repeated radiosurgery for AVM included hemorrhage (7.6%) and radiation-induced changes (7.4%). Repeat radiosurgery can be used to treat incompletely obliterated AVM with an obliteration rate of 61%. Complications are related to treatment effect latency (hemorrhage risk) as well as radiation-induced changes. Repeat radiosurgery can be performed at three years following the initial treatment, allowing for full realization of effects from the initial treatment prior to commencing therapy. PMID:25913746

  17. Dynamic combinatorial libraries of artificial repeat proteins.

    PubMed

    Eisenberg, Margarita; Shumacher, Inbal; Cohen-Luria, Rivka; Ashkenasy, Gonen

    2013-06-15

    Repeat proteins are found in almost all cellular systems, where they are involved in diverse molecular recognition processes. Recent studies have suggested that de novo designed repeat proteins may serve as universal binders, and might potentially be used as practical alternative to antibodies. We describe here a novel chemical methodology for producing small libraries of repeat proteins, and screening in parallel the ligand binding of library members. The first stage of this research involved the total synthesis of a consensus-based three-repeat tetratricopeptide (TPR) protein (~14 kDa), via sequential attachment of the respective peptides. Despite the effectiveness of the synthesis and ligation steps, this method was found to be too demanding for the production of proteins containing variable number of repeats. Additionally, the analysis of binding of the individual proteins was time consuming. Therefore, we designed and prepared novel dynamic combinatorial libraries (DCLs), and show that their equilibration can facilitate the formation of TPR proteins containing up to eight repeating units. Interestingly, equilibration of the library building blocks in the presence of the biologically relevant ligands, Hsp90 and Hsp70, induced their oligomerization into forming more of the proteins with large recognition surfaces. We suggest that this work presents a novel simple and rapid tool for the simultaneous screening of protein mixtures with variable binding surfaces, and for identifying new binders for ligands of interest.

  18. Proliferating cell nuclear antigen prevents trinucleotide repeat expansions by promoting repeat deletion and hairpin removal

    PubMed Central

    Beaver, Jill M.; Lai, Yanhao; Rolle, Shantell J.; Liu, Yuan

    2017-01-01

    DNA base lesions and base excision repair (BER) within trinucleotide repeat (TNR) tracts modulate repeat instability through the coordination among the key BER enzymes DNA polymerase β, flap endonuclease 1 (FEN1) and DNA ligase I (LIG I). However, it remains unknown whether BER cofactors can also alter TNR stability. In this study, we discovered that proliferating cell nuclear antigen (PCNA), a cofactor of BER, promoted CAG repeat deletion and removal of a CAG repeat hairpin during BER in a duplex CAG repeat tract and CAG hairpin loop, respectively. We showed that PCNA stimulated LIG I activity on a nick across a small template loop during BER in a duplex (CAG)20 repeat tract promoting small repeat deletions. Surprisingly, we found that during BER in a hairpin loop, PCNA promoted reannealing of the upstream flap of a double-flap intermediate, thereby facilitating the formation of a downstream flap and stimulating FEN1 cleavage activity and hairpin removal. Our results indicate that PCNA plays a critical role in preventing CAG repeat expansions by modulating the structures of dynamic DNA via cooperation with BER enzymes. We provide the first evidence that PCNA prevents CAG repeat expansions during BER by promoting CAG repeat deletion and removal of a TNR hairpin. PMID:27793507

  19. The development of ingroup favoritism in repeated social dilemmas

    PubMed Central

    Dorrough, Angela R.; Glöckner, Andreas; Hellmann, Dshamilja M.; Ebert, Irena

    2015-01-01

    In two comprehensive and fully incentivized studies, we investigate the development of ingroup favoritism as one of two aspects of parochial altruism in repeated social dilemmas. Specifically, we test whether ingroup favoritism is a fixed phenomenon that can be observed from the very beginning and remains stable over time, or whether it develops (increases vs. decreases) during repeated contact. Ingroup favoritism is assessed through cooperation behavior in a repeated continuous prisoner's dilemma where participants sequentially interact with 10 members of the ingroup (own city and university) and subsequently with 10 members of the outgroup (other city and university), or vice versa. In none of the experiments do we observe initial differences in cooperation behavior for interaction partners from the ingroup, as compared to outgroup, and we only observe small differences in expectations regarding the interaction partners' cooperation behavior. After repeated interaction, however, including a change of groups, clear ingroup favoritism can be observed. Instead of being due to gradual and potentially biased updating of expectations, we found that these emerging differences were mainly driven by the change of interaction partners' group membership that occurred after round 10. This indicates that in social dilemma settings ingroup favoritism is to some degree dynamic in that it is enhanced and sometimes only observable if group membership is activated by thinking about both the interaction with the ingroup and the outgroup. PMID:25972821

  20. Activating frataxin expression by repeat-targeted nucleic acids

    PubMed Central

    Li, Liande; Matsui, Masayuki; Corey, David R.

    2016-01-01

    Friedreich's ataxia is an incurable genetic disorder caused by a mutant expansion of the trinucleotide GAA within an intronic FXN RNA. This expansion leads to reduced expression of frataxin (FXN) protein and evidence suggests that transcriptional repression is caused by an R-loop that forms between the expanded repeat RNA and complementary genomic DNA. Synthetic agents that increase levels of FXN protein might alleviate the disease. We demonstrate that introducing anti-GAA duplex RNAs or single-stranded locked nucleic acids into patient-derived cells increases FXN protein expression to levels similar to analogous wild-type cells. Our data are significant because synthetic nucleic acids that target GAA repeats can be lead compounds for restoring curative FXN levels. More broadly, our results demonstrate that interfering with R-loop formation can trigger gene activation and reveal a new strategy for upregulating gene expression. PMID:26842135

  1. Microevolution of pandemic Vibrio parahaemolyticus assessed by the number of repeat units in short sequence tandem repeat regions.

    PubMed

    García, Katherine; Gavilán, Ronnie G; Höfle, Manfred G; Martínez-Urtaza, Jaime; Espejo, Romilio T

    2012-01-01

    The emergence of the pandemic strain Vibrio parahaemolyticus O3:K6 in 1996 caused a large increase of diarrhea outbreaks related to seafood consumption in Southeast Asia, and later worldwide. Isolates of this strain constitutes a clonal complex, and their effectual differentiation is possible by comparison of their variable number tandem repeats (VNTRs). The differentiation of the isolates by the differences in VNTRs will allow inferring the population dynamics and microevolution of this strain but this requires knowing the rate and mechanism of VNTRs' variation. Our study of mutants obtained after serial cultivation of clones showed that mutation rates of the six VNTRs examined are on the order of 10(-4) mutant per generation and that difference increases by stepwise addition of single mutations. The single stepwise mutation (SSM) was deduced because mutants with 1, 2, 3, or more repeat unit deletions or insertions follow a geometric distribution. Plausible phylogenetic trees are obtained when, according to SSM, the genetic distance between clusters with different number of repeats is assessed by the absolute differences in repeats. Using this approach, mutants originated from different isolates of pandemic V. parahaemolyticus after serial cultivation are clustered with their parental isolates. Additionally, isolates of pandemic V. parahaemolyticus from Southeast Asia, Tokyo, and northern and southern Chile are clustered according their geographical origin. The deepest split in these four populations is observed between the Tokyo and southern Chile populations. We conclude that proper phylogenetic relations and successful tracing of pandemic V. parahaemolyticus requires measuring the differences between isolates by the absolute number of repeats in the VNTRs considered.

  2. Factors Associated with Repeat Blood Donation at the Northern Zone Blood Transfusion Centre in Tanzania.

    PubMed

    Mauka, Wilhellmuss I; Mahande, Michael J; Msuya, Sia E; Philemon, Rune N

    2015-01-01

    Background and Objective. The aim of this study was to determine factors associated with repeat blood donation. Methods. This was a cross-sectional study carried out among blood donors aged 18-65 years in northern Tanzania. The questionnaire was administered among 454 participants through the phone. Results. Of the 454 participants, the proportion of repeat donation was 63.9%. In the backward logistic regression analysis, the significant predictors were living in Arusha which had lower odds of repeat donation compared to those living in Kilimanjaro. Knowledge of time interval between donations increased odds of repeating donations. High intention increased odds of repeat donation compared to low intention. Altruistic score had minor effect on increasing odds of repeating donation. Conclusion. Repeat blood donation is affected by proximity of donating site, awareness of the blood donation interval, intention to donate, and experience on previous donation. We recommend continuous education concerning blood donors and donation among health workers and society as a whole; this will create awareness on motivational factors for repeat donations.

  3. Automated genotyping of dinucleotide repeat markers

    SciTech Connect

    Perlin, M.W.; Hoffman, E.P. |

    1994-09-01

    The dinucleotide repeats (i.e., microsatellites) such as CA-repeats are a highly polymorphic, highly abundant class of PCR-amplifiable markers that have greatly streamlined genetic mapping experimentation. It is expected that over 30,000 such markers (including tri- and tetranucleotide repeats) will be characterized for routine use in the next few years. Since only size determination, and not sequencing, is required to determine alleles, in principle, dinucleotide repeat genotyping is easily performed on electrophoretic gels, and can be automated using DNA sequencers. Unfortunately, PCR stuttering with these markers generates not one band for each allele, but a pattern of bands. Since closely spaced alleles must be disambiguated by human scoring, this poses a key obstacle to full automation. We have developed methods that overcome this obstacle. Our model is that the observed data is generated by arithmetic superposition (i.e., convolution) of multiple allele patterns. By quantitatively measuring the size of each component band, and exploiting the unique stutter pattern associated with each marker, closely spaced alleles can be deconvolved; this unambiguously reconstructs the {open_quotes}true{close_quotes} allele bands, with stutter artifact removed. We used this approach in a system for automated diagnosis of (X-linked) Duchenne muscular dystrophy; four multiplexed CA-repeats within the dystrophin gene were assayed on a DNA sequencer. Our method accurately detected small variations in gel migration that shifted the allele size estimate. In 167 nonmutated alleles, 89% (149/167) showed no size variation, 9% (15/167) showed 1 bp variation, and 2% (3/167) showed 2 bp variation. We are currently developing a library of dinucleotide repeat patterns; together with our deconvolution methods, this library will enable fully automated genotyping of dinucleotide repeats from sizing data.

  4. Novel triplet repeat containing genes in human brain: Cloning, expression, and length polymorphisms

    SciTech Connect

    Li, Shi Hua; Margolis, R.L.; Ross, C.A.; McInnis, M.G.; Antonarakis, S.E. )

    1993-06-01

    Human genes containing triplet repeats may markedly expand in length and cause neuropsychiatric disease, explaining the phenomenon of anticipation (increasing severity or earlier age of onset in successive generations in a pedigree). To identify novel genes with triplet repeats, the authors screened a human brain cDNA library with oligonucleotide probes containing CTG or CCG triplet repeats. Fourteen of 40 clones encoded novel human genes, and 8 of these inserts have been sequenced on both strands. All contain repeats, and 5 of the 8 have 9 or more consecutive perfect repeats. All are expressed in brain. Chromosomal assignments reveal a distribution of these genes on multiple autosomes and the X-chromosome. Further, the repeat length in two of the genes is highly polymorphic, making them valuable index linkage markers. The authors predict that many triplet repeat-containing genes exist; screening with the CTG probe suggests approximately 50-100 genes containing this type of repeat are expressed in the human brain. Since additional disorders, such as Huntington's disease, bipolar affective disorder, and possibly others, show features of anticipation, they suggest that these novel human genes with triplet repeats are candidates for causing neuropsychiatric diseases.

  5. A Comparison of Pairs Figure Skaters in Repeated Jumps

    PubMed Central

    Sands, William A.; Kimmel, Wendy L.; McNeal, Jeni R.; Murray, Steven Ross; Stone, Michael H.

    2012-01-01

    Trends in pairs figure skating have shown that increasingly difficult jumps have become an essential aspect of high-level performance, especially in the latter part of a competitive program. We compared a repeated jump power index in a 60 s repeated jump test to determine the relationship of repeated jump test to competitive rank and to measure 2D hip, knee, and ankle angles and angular velocities at 0, 20, 40, and 60 s. Eighteen National Team Pairs Figure Skaters performed a 60 s repeated jump test on a large switch-mat with timing of flight and ground durations and digital video recording. Each 60-s period was divided into 6, 10-s intervals, with power indexes (W/kg) calculated for each 10-s interval. Power index by 10-s interval repeated measures ANOVAs (RMANOVA) showed that males exceeded females at all intervals, and the highest power index interval was during 10 to 20 s for both sexes. RMANOVAs of angles and angular velocities showed main effects for time only. Power index and jumping techniques among figure skaters showed rapid and steady declines over the test duration. Power index can predict approximately 50% of competitive rank variance, and sex differences in jumping technique were rare. Key pointsThe repeated jumps test can account for about 50% of the variance in pairs ranks.Changes in technique are largely due to fatigue, but the athletes were able to maintain a maximum flexion knee angle very close to the desired 90 degrees. Changes in angular velocity and jump heights occurred as expected, again probably due to fatigue.As expected from metabolic information, the athletes' power indexes peak around 20s and decline thereafter. Coaches should be aware of this time as a boundary beyond which fatigue becomes more manifest, and use careful choreographic choices to provide rest periods that are disguised as less demanding skating elements to afford recovery.The repeated jumps test may be a helpful off-ice test of power-endurance for figure skaters. PMID

  6. A comparison of pairs figure skaters in repeated jumps.

    PubMed

    Sands, William A; Kimmel, Wendy L; McNeal, Jeni R; Murray, Steven Ross; Stone, Michael H

    2012-01-01

    Trends in pairs figure skating have shown that increasingly difficult jumps have become an essential aspect of high-level performance, especially in the latter part of a competitive program. We compared a repeated jump power index in a 60 s repeated jump test to determine the relationship of repeated jump test to competitive rank and to measure 2D hip, knee, and ankle angles and angular velocities at 0, 20, 40, and 60 s. Eighteen National Team Pairs Figure Skaters performed a 60 s repeated jump test on a large switch-mat with timing of flight and ground durations and digital video recording. Each 60-s period was divided into 6, 10-s intervals, with power indexes (W/kg) calculated for each 10-s interval. Power index by 10-s interval repeated measures ANOVAs (RMANOVA) showed that males exceeded females at all intervals, and the highest power index interval was during 10 to 20 s for both sexes. RMANOVAs of angles and angular velocities showed main effects for time only. Power index and jumping techniques among figure skaters showed rapid and steady declines over the test duration. Power index can predict approximately 50% of competitive rank variance, and sex differences in jumping technique were rare. Key pointsThe repeated jumps test can account for about 50% of the variance in pairs ranks.Changes in technique are largely due to fatigue, but the athletes were able to maintain a maximum flexion knee angle very close to the desired 90 degrees. Changes in angular velocity and jump heights occurred as expected, again probably due to fatigue.As expected from metabolic information, the athletes' power indexes peak around 20s and decline thereafter. Coaches should be aware of this time as a boundary beyond which fatigue becomes more manifest, and use careful choreographic choices to provide rest periods that are disguised as less demanding skating elements to afford recovery.The repeated jumps test may be a helpful off-ice test of power-endurance for figure skaters.

  7. Effects of repeated Valsalva maneuver straining on cardiac and vasoconstrictive baroreflex responses

    NASA Technical Reports Server (NTRS)

    Convertino, Victor A.; Ratliff, Duane A.; Doerr, Donald F.; Ludwig, David A.; Muniz, Gary W.; Benedetti, Erik; Chavarria, Jose; Koreen, Susan; Nguyen, Claude; Wang, Jeff

    2003-01-01

    INTRODUCTION: We hypothesized that repeated respiratory straining maneuvers (repeated SM) designed to elevate arterial BPs (arterial baroreceptor loading) would acutely increase baroreflex responses. METHODS: We tested this hypothesis by measuring cardiac baroreflex responses to carotid baroreceptor stimulation (neck pressures), and changes in heart rate and diastolic BP after reductions in BP induced by a 15-s Valsalva maneuver in 10 female and 10 male subjects at 1, 3, 6, and 24 h after performing repeated SM. Baroreflex responses were also measured in each subject at 1, 3, 6, and 24 h at the same time on a separate day without repeated SM (control) in a randomized, counter-balanced cross-over experimental design. RESULTS: There was no statistical difference in carotid-cardiac and peripheral vascular baroreflex responses measured across time following repeated SM compared with the control condition. Integrated cardiac baroreflex response (deltaHR/ deltaSBP) measured during performance of a Valsalva maneuver was increased by approximately 50% to 1.1 +/- 0.2 bpm x mm Hg(-1) at 1 h and 1.0 +/- 0.1 bpm x mm Hg(-1) at 3 h following repeated SM compared with the control condition (0.7 +/- 0.1 bpm x mm Hg(-1) at both 1 and 3 h, respectively). However, integrated cardiac baroreflex response after repeated SM returned to control levels at 6 and 24 h after training. These responses did not differ between men and women. CONCLUSIONS: Our results are consistent with the notion that arterial baroreceptor loading induced by repeated SM increased aortic, but not carotid, cardiac baroreflex responses for as long as 3 h after repeated SM. We conclude that repeated SM increases cardiac baroreflex responsiveness which may provide patients, astronauts, and high-performance aircraft pilots with protection from development of orthostatic hypotension.

  8. Characterization of conservative somatic instability of the CAG repeat region in Huntington`s disease

    SciTech Connect

    Schaefer, F.V.; Calikoglu, A.S.; Whetsell, L.H.

    1994-09-01

    Instability and enlargement of a CAG repeat region at the beginning of the huntingtin gene (IT-15) has been linked with Huntington`s disease. The CAG repeat size shows a highly significant correlation with age-of-onset of clinicial features in individuals with 40 or more repeats who have Huntington disease. The clinical status of nonsymptomatic individuals with 30 to 39 CAG repeats is considered ambiguous. In order to define more carefully the nature of the HD expansion instability, we examined patients in our HD population using a discriminating fluorescence-based PCR approach. The degree of somatic mutation increases with both earlier age of onset and the size of the inherited allele. A single prominent band one repeat larger than the index peak was typical in individuals with 40-41 CAG repeats. Three to four larger bands are typically discerned in individuals with 50 or more repeats. In an extreme example, an individual with approximately 95 repeats had at least 8 prominent bands. Plotting the degree of somatic mutation relative to the size of the HD allele shows somatic mutation activity increases with size. By this approach 40-60% of the alleles in a 40-41 CAG repeat HD loci is represented in the primary allele. In contrast, the primary allele represents a relatively minor proportion of the total alleles for expansions greater than 50 CAG repeats (10-20%). The limited range of somatic mutation suggest that the instability is restricted to very early stages of embryogenesis before tissue development diverges or that persistent somatic instability occurs at a slow rate. Therefore, the properties of somatic instability in Huntington`s disease have aspects that are both in common but also different from that found in other trinucleotide repeat expanding diseases such as myotonic muscular dystrophy and fragile X syndrome.

  9. Spectrin repeat proteins in the nucleus.

    PubMed

    Young, Kevin G; Kothary, Rashmi

    2005-02-01

    Spectrin repeat sequences are among the more common repeat elements identified in proteins, typically occurring in large structural proteins. Examples of spectrin repeat-containing proteins include dystrophin, alpha-actinin and spectrin itself--all proteins with well-demonstrated roles of establishing and maintaining cell structure. Over the past decade, it has become clear that, although these proteins display a cytoplasmic and plasma membrane distribution, several are also found both at the nuclear envelope, and within the intranuclear space. In this review, we provide an overview of recent work regarding various spectrin repeat-containing structural proteins in the nucleus. As well, we hypothesize about the regulation of their nuclear localization and possible nuclear functions based on domain architecture, known interacting proteins and evolutionary relationships. Given their large size, and their potential for interacting with multiple proteins and with chromatin, spectrin repeat-containing proteins represent strong candidates for important organizational proteins within the nucleus. Supplementary material for this article can be found on the BioEssays website (http://www.interscience.wiley.com/jpages/0265-9247/suppmat/index.html).

  10. Unusual Structures Are Present in DNA Fragments Containing Super-Long Huntingtin CAG Repeats

    PubMed Central

    Duzdevich, Daniel; Li, Jinliang; Whang, Jhoon; Takahashi, Hirohide; Takeyasu, Kunio; Dryden, David T. F.; Morton, A. Jennifer; Edwardson, J. Michael

    2011-01-01

    Background In the R6/2 mouse model of Huntington's disease (HD), expansion of the CAG trinucleotide repeat length beyond about 300 repeats induces a novel phenotype associated with a reduction in transcription of the transgene. Methodology/Principal Findings We analysed the structure of polymerase chain reaction (PCR)-generated DNA containing up to 585 CAG repeats using atomic force microscopy (AFM). As the number of CAG repeats increased, an increasing proportion of the DNA molecules exhibited unusual structural features, including convolutions and multiple protrusions. At least some of these features are hairpin loops, as judged by cross-sectional analysis and sensitivity to cleavage by mung bean nuclease. Single-molecule force measurements showed that the convoluted DNA was very resistant to untangling. In vitro replication by PCR was markedly reduced, and TseI restriction enzyme digestion was also hindered by the abnormal DNA structures. However, significantly, the DNA gained sensitivity to cleavage by the Type III restriction-modification enzyme, EcoP15I. Conclusions/Significance “Super-long” CAG repeats are found in a number of neurological diseases and may also appear through CAG repeat instability. We suggest that unusual DNA structures associated with super-long CAG repeats decrease transcriptional efficiency in vitro. We also raise the possibility that if these structures occur in vivo, they may play a role in the aetiology of CAG repeat diseases such as HD. PMID:21347256

  11. Rate analysis for a hybrid quantum repeater

    SciTech Connect

    Bernardes, Nadja K.; Loock, Peter van

    2011-01-15

    We present a detailed rate analysis for a hybrid quantum repeater assuming perfect memories and using optimal probabilistic entanglement generation and deterministic swapping routines. The hybrid quantum repeater protocol is based on atomic qubit-entanglement distribution through optical coherent-state communication. An exact, analytical formula for the rates of entanglement generation in quantum repeaters is derived, including a study on the impacts of entanglement purification and multiplexing strategies. More specifically, we consider scenarios with as little purification as possible and we show that for sufficiently low local losses, such purifications are still more powerful than multiplexing. In a possible experimental scenario, our hybrid system can create near-maximally entangled (F=0.98) pairs over a distance of 1280 km at rates of the order of 100 Hz.

  12. Hematuria home screening: repeat testing results.

    PubMed

    Messing, E M; Young, T B; Hunt, V B; Newton, M A; Bram, L L; Vaillancourt, A; Hisgen, W J; Greenberg, E B; Kuglitsch, M E; Wegenke, J D

    1995-07-01

    To determine at what interval screening should be repeated to detect bladder cancer before it becomes muscle invasive 856 men who had 14 negative daily home tests for hematuria with a chemical reagent strip 9 months previously performed repeat tests. Of these men 50 (5.8%) had at least 1 positive test during the second 14-day screening period and 38 were evaluated, 15 of whom (39.5%) had significant urological pathological conditions, including 8 with malignancies. Bladder cancer was noted in 7 men, with no tumor invading the muscularis propria. The finding of 7 bladder cancers in 856 men (0.82%) who had a negative test 9 months previously indicates that bladder cancer has a brief preclinical duration and that testing must be repeated at least annually for screening to detect bladder cancer consistently before invasion occurs.

  13. Some characteristics of repeated sickness absence

    PubMed Central

    Ferguson, David

    1972-01-01

    Ferguson, D. (1972).Brit. J. industr. Med.,29, 420-431. Some characteristics of repeated sickness absence. Several studies have shown that frequency of absence attributed to sickness is not distributed randomly but tends to follow the negative binomial distribution, and this has been taken to support the concept of `proneness' to such absence. Thus, the distribution of sickness absence resembles that of minor injury at work demonstrated over 50 years ago. Because the investigation of proneness to absence does not appear to have been reported by others in Australia, the opportunity was taken, during a wider study of health among telegraphists in a large communications undertaking, to analyse some characteristics of repeated sickness absence. The records of medically certified and uncertified sickness absence of all 769 telegraphists continuously employed in all State capitals over a two-and-a-half-year period were compared with those of 411 clerks and 415 mechanics and, in Sydney, 380 mail sorters and 80 of their supervisors. All telegraphists in Sydney, Melbourne, and Brisbane, and all mail sorters in Sydney, who were available and willing were later medically examined. From their absence pattern repeaters (employees who had had eight or more certified absences in two and a half years) were separated into three types based on a presumptive origin in chance, recurrent disease and symptomatic non-specific disorder. The observed distribution of individual frequency of certified absence over the full two-and-a-half-year period of study followed that expected from the univariate negative binomial, using maximum likelihood estimators, rather than the poisson distribution, in three of the four occupational groups in Sydney. Limited correlational and bivariate analysis supported the interpretation of proneness ascribed to the univariate fit. In the two groups studied, frequency of uncertified absence could not be fitted by the negative binomial, although the numbers of

  14. Do gamma-ray burst sources repeat?

    NASA Technical Reports Server (NTRS)

    Meegan, Charles A.; Hartmann, Dieter H.; Brainerd, J. J.; Briggs, Michael S.; Paciesas, William S.; Pendleton, Geoffrey; Kouveliotou, Chryssa; Fishman, Gerald; Blumenthal, George; Brock, Martin

    1995-01-01

    The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports (Quashnock and Lamb, 1993; Wang and Lingenfelter, 1993) of evidence for repetition in the first BATSE burst catalog have generated renewed interest in this issue. Here, we analyze the angular distribution of 585 bursts of the second BATSE catalog (Meegan et al., 1994). We search for evidence of burst recurrence using the nearest and farthest neighbor statistic and the two-point angular correlation function. We find the data to be consistent with the hypothesis that burst sources do not repeat; however, a repeater fraction of up to about 20% of the observed bursts cannot be excluded.

  15. Formation of the Arabidopsis pentatricopeptide repeat family.

    PubMed

    Rivals, Eric; Bruyère, Clémence; Toffano-Nioche, Claire; Lecharny, Alain

    2006-07-01

    In Arabidopsis (Arabidopsis thaliana) the 466 pentatricopeptide repeat (PPR) proteins are putative RNA-binding proteins with essential roles in organelles. Roughly half of the PPR proteins form the plant combinatorial and modular protein (PCMP) subfamily, which is land-plant specific. PCMPs exhibit a large and variable tandem repeat of a standard pattern of three PPR variant motifs. The association or not of this repeat with three non-PPR motifs at their C terminus defines four distinct classes of PCMPs. The highly structured arrangement of these motifs and the similar repartition of these arrangements in the four classes suggest precise relationships between motif organization and substrate specificity. This study is an attempt to reconstruct an evolutionary scenario of the PCMP family. We developed an innovative approach based on comparisons of the proteins at two levels: namely the succession of motifs along the protein and the amino acid sequence of the motifs. It enabled us to infer evolutionary relationships between proteins as well as between the inter- and intraprotein repeats. First, we observed a polarized elongation of the repeat from the C terminus toward the N-terminal region, suggesting local recombinations of motifs. Second, the most N-terminal PPR triple motif proved to evolve under different constraints than the remaining repeat. Altogether, the evidence indicates different evolution for the PPR region and the C-terminal one in PCMPs, which points to distinct functions for these regions. Moreover, local sequence homogeneity observed across PCMP classes may be due to interclass shuffling of motifs, or to deletions/insertions of non-PPR motifs at the C terminus.

  16. The puzzle of the triple repeats

    SciTech Connect

    Morell, V.

    1993-06-04

    Two years ago, when researchers discovered the gene that causes a hereditary form of mental retardation known as fragile-X syndrome, they also turned up a mutation so unexpected geneticists are still scratching their heads over it. The defect, which makes genes balloon in size by adding extra copies of a three base-pair repeated sequence of DNA, was the first of its kind. Despite decades of study, nothing like it had ever been seen in any of the species that laid the foundations for modern genetics: bacteria, the fruit fly Drosophila melanogaster, and the mouse. The mutations caused by these expanding trinucleotide repeats turned out be common causes of human disease. In the past 2 years, they have been fingered as the culprits in three hereditary disorders besides fragile-X syndrome: myotronic dystrophy, spinobullar muscular atrophy (also known as Kennedy's disease), and just this March-Huntington's disease. The FMR-1 gene, which is the one at fault in fragile-X syndrome, shows just how much the trinucleotide repeats can expand. The normal gene carries at most 50 copies of the CGG trinucleotide. But in children who inherit the gene from these carriers and actually develop mental retardation and the other fragile-X symptoms, the FMR-1 gene may have hundreds to thousands of CGG repeats. Huge expansions of another trinucleotide repeat (CTG) can also occur from one generation to the next in the gene that causes myotonic dystrophy (DM), while smaller, although no less devastating, expansions in the CAG trinucleotide repeat lead to Huntington's and Kennedy's diseases.

  17. Safety of Repeated Yttrium-90 Radioembolization

    SciTech Connect

    Lam, Marnix G. E. H.; Louie, John D.; Iagaru, Andrei H.; Goris, Michael L.; Sze, Daniel Y.

    2013-10-15

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

  18. Hippocampal ER stress and learning deficits following repeated pyrethroid exposure.

    PubMed

    Hossain, Muhammad M; DiCicco-Bloom, Emanuel; Richardson, Jason R

    2015-01-01

    Endoplasmic reticulum (ER) stress is implicated as a significant contributor to neurodegeneration and cognitive dysfunction. Previously, we reported that the widely used pyrethroid pesticide deltamethrin causes ER stress-mediated apoptosis in SK-N-AS neuroblastoma cells. Whether or not this occurs in vivo remains unknown. Here, we demonstrate that repeated deltamethrin exposure (3 mg/kg every 3 days for 60 days) causes hippocampal ER stress and learning deficits in adult mice. Repeated exposure to deltamethrin caused ER stress in the hippocampus as indicated by increased levels of C/EBP-homologous protein (131%) and glucose-regulated protein 78 (96%). This was accompanied by increased levels of caspase-12 (110%) and activated caspase-3 (50%). To determine whether these effects resulted in learning deficits, hippocampal-dependent learning was evaluated using the Morris water maze. Deltamethrin-treated animals exhibited profound deficits in the acquisition of learning. We also found that deltamethrin exposure resulted in decreased BrdU-positive cells (37%) in the dentate gyrus of the hippocampus, suggesting potential impairment of hippocampal neurogenesis. Collectively, these results demonstrate that repeated deltamethrin exposure leads to ER stress, apoptotic cell death in the hippocampus, and deficits in hippocampal precursor proliferation, which is associated with learning deficits.

  19. CAG repeat expansions in bipolar and unipolar disorders

    SciTech Connect

    Oruc, L.; Verheyen, G.R.; Raeymaekers, P.; Van Broeckhoven, C.

    1997-03-01

    Family, twin, and adoption studies consistently have indicated that the familial aggregation of bipolar (BP) disorder and unipolar recurrent major depression (UPR) is accounted for largely by genetic factors. However, the mode of inheritance is complex. One of the possible explanations could be that a gene with variable penetrance and variable expression is involved. Recently there have been reports on a new class of genetic diseases caused by an abnormal trinucleotide-repeat expansion (TRE). In a number of genetic disorders, these dynamic mutations were proved to be the biological basis for the clinically observed phenomenon of anticipation. DNA consisting of repeated triplets of nucleotides becomes unstable and increases in size over generations within families, giving rise to an increased severity and/or an earlier onset of the disorder. It has been recognized for a long time that anticipation occurs in multiplex families transmitting mental illness. More recent studies also suggest that both BP disorder and UPR show features that are compatible with anticipation. Although the findings of anticipation in BP disorders and in UPR must be interpreted with caution because of the possible presence of numerous ascertainment biases, they support the hypothesis that pathological TREs are implicated in the transmission of these disorders. TRE combined with variable penetrance of expression could explain the complex transmission pattern observed in BP disorder. In view of this, the recent reports of an association between CAG-repeat length and BP disorder in a Belgian, Swedish, and British population are promising. 14 refs., 1 fig., 1 tab.

  20. Repeat-containing protein effectors of plant-associated organisms

    PubMed Central

    Mesarich, Carl H.; Bowen, Joanna K.; Hamiaux, Cyril; Templeton, Matthew D.

    2015-01-01

    Many plant-associated organisms, including microbes, nematodes, and insects, deliver effector proteins into the apoplast, vascular tissue, or cell cytoplasm of their prospective hosts. These effectors function to promote colonization, typically by altering host physiology or by modulating host immune responses. The same effectors however, can also trigger host immunity in the presence of cognate host immune receptor proteins, and thus prevent colonization. To circumvent effector-triggered immunity, or to further enhance host colonization, plant-associated organisms often rely on adaptive effector evolution. In recent years, it has become increasingly apparent that several effectors of plant-associated organisms are repeat-containing proteins (RCPs) that carry tandem or non-tandem arrays of an amino acid sequence or structural motif. In this review, we highlight the diverse roles that these repeat domains play in RCP effector function. We also draw attention to the potential role of these repeat domains in adaptive evolution with regards to RCP effector function and the evasion of effector-triggered immunity. The aim of this review is to increase the profile of RCP effectors from plant-associated organisms. PMID:26557126

  1. Therapeutics development for triplet repeat expansion diseases.

    PubMed

    Di Prospero, Nicholas A; Fischbeck, Kenneth H

    2005-10-01

    The underlying genetic mutations for many inherited neurodegenerative disorders have been identified in recent years. One frequent type of mutation is trinucleotide repeat expansion. Depending on the location of the repeat expansion, the mutation might result in a loss of function of the disease gene, a toxic gain of function or both. Disease gene identification has led to the development of model systems for investigating disease mechanisms and evaluating treatments. Examination of experimental findings reveals similarities in disease mechanisms as well as possibilities for treatment.

  2. A low-magnetic-field soft gamma repeater.

    PubMed

    Rea, N; Esposito, P; Turolla, R; Israel, G L; Zane, S; Stella, L; Mereghetti, S; Tiengo, A; Götz, D; Göğüş, E; Kouveliotou, C

    2010-11-12

    Soft gamma repeaters (SGRs) and anomalous x-ray pulsars form a rapidly increasing group of x-ray sources exhibiting sporadic emission of short bursts. They are believed to be magnetars, that is, neutron stars powered by extreme magnetic fields, B ~ 10(14) to 10(15) gauss. We report on a soft gamma repeater with low magnetic field, SGR 0418+5729, recently detected after it emitted bursts similar to those of magnetars. X-ray observations show that its dipolar magnetic field cannot be greater than 7.5 × 10(12) gauss, well in the range of ordinary radio pulsars, implying that a high surface dipolar magnetic field is not necessarily required for magnetar-like activity. The magnetar population may thus include objects with a wider range of B-field strengths, ages, and evolutionary stages than observed so far.

  3. Repeated Witnessing of Conspecifics in Pain: Effects on Emotional Contagion

    PubMed Central

    Bruls, Rune; Han, Yingying; Heinemans, Mirjam; Pruis, Ilanah; Gazzola, Valeria; Keysers, Christian

    2015-01-01

    Witnessing of conspecifics in pain has been shown to elicit socially triggered freezing in rodents. It is unknown how robust this response is to repeated exposure to a cage-mate experiencing painful stimulation. To address this question, shock-experienced Observer rats repeatedly witnessed familiar Demonstrators receive painful footshocks (six sessions). Results confirm that Observers freeze during the first testing session. The occurrence of this behaviour however gradually diminished as the experimental sessions progressed, reaching minimal freezing levels by the end of the experiments. In contrast, the appearance and continuous increase in the frequency of yawning, a behavior that was inhibited by metyrapone (i.e,. a glucocorticoid synthesis blocker), might represent an alternative coping strategy, suggesting that the observer’s reduced freezing does not necessarily indicate a disappearance in the affective response to the Demonstrator’s distress. PMID:26356506

  4. Effect of Repeated Evaluation and Repeated Exposure on Acceptability Ratings of Sentences

    ERIC Educational Resources Information Center

    Zervakis, Jennifer; Mazuka, Reiko

    2013-01-01

    This study investigated the effect of repeated evaluation and repeated exposure on grammatical acceptability ratings for both acceptable and unacceptable sentence types. In Experiment 1, subjects in the Experimental group rated multiple examples of two ungrammatical sentence types (ungrammatical binding and double object with dative-only verb),…

  5. Hepcidin level predicts hemoglobin concentration in individuals undergoing repeated phlebotomy.

    PubMed

    Mast, Alan E; Schlumpf, Karen S; Wright, David J; Johnson, Bryce; Glynn, Simone A; Busch, Michael P; Olbina, Gordana; Westerman, Mark; Nemeth, Elizabeta; Ganz, Tomas

    2013-08-01

    Dietary iron absorption is regulated by hepcidin, an iron regulatory protein produced by the liver. Hepcidin production is regulated by iron stores, erythropoiesis and inflammation, but its physiology when repeated blood loss occurs has not been characterized. Hepcidin was assayed in plasma samples obtained from 114 first-time/reactivated (no blood donations in preceding 2 years) female donors and 34 frequent (≥3 red blood cell donations in preceding 12 months) male donors as they were phlebotomized ≥4 times over 18-24 months. Hepcidin levels were compared to ferritin and hemoglobin levels using multivariable repeated measures regression models. Hepcidin, ferritin and hemoglobin levels declined with increasing frequency of donation in the first-time/reactivated females. Hepcidin and ferritin levels correlated well with each other (Spearman's correlation of 0.74), but on average hepcidin varied more between donations for a given donor relative to ferritin. In a multivariable repeated measures regression model the predicted inter-donation decline in hemoglobin varied as a function of hepcidin and ferritin; hemoglobin was 0.51 g/dL lower for subjects with low (>45.7 ng/mL) or decreasing hepcidin and low ferritin (>26 ng/mL), and was essentially zero for other subjects including those with high (>45.7 ng/mL) or increasing hepcidin and low ferritin (>26 ng/mL) levels (P<0.001). In conclusion, hepcidin levels change rapidly in response to dietary iron needed for erythropoiesis. The dynamic regulation of hepcidin in the presence of a low levels of ferritin suggests that plasma hepcidin concentration may provide clinically useful information about an individual's iron status (and hence capacity to tolerate repeated blood donations) beyond that of ferritin alone. Clinicaltrials.gov identifier: NCT00097006.

  6. AGG interspersions within the FMR1 CGG repeat: Mechanisms and models of triplet repeat instability

    SciTech Connect

    Eichler, E.E.; Nelson, D.L.

    1994-09-01

    Fragile X syndrome CGG repeat alleles are typically classified as normal, premutation, or full mutation based on the length of the repeat in the 5{prime} UTR of the FMR1 gene. The distinction between high-end normals and low-end premutation alleles, however, is not always clear since repeats of similar size differ markedly in their intergenerational stability. This fact suggest that differences in sequence content may play a key role in determining an allele`s predisposition to instability. It has been postulated that the loss of AGG interruptions within the CGG tract may trigger this instability. To test this model, we have developed a simple indirect method to determine the presence or absence of internal AGGs within the FMR1 CGG repeat tract. Analysis of 84 human X chromosomes for the presence of interrupting AGG trinucleotides revealed that most alleles possess two interspersed AGGs at a periodicity of 9 or 10 CGGs. The longest tract of uninterrupted CGG repeats is usually found at the 3{prime} end indicating that variation in the length of the repeat is polar. Alleles containing between 34 and 55 repeats, with documented unstable transmissions, were shown to have lost one or both AGG interruptions when compared to stable alleles of similar length. These comparisons define an instability threshold between 34 and 38 uninterrupted CGG repeats. Analysis of premutation alleles in fragile X syndrome carriers reveals that 70% of these alleles contain a single AGG interruption. Population studies confirm that such highly punctuated FMR1 CGG repeats are virtually static in terms of length variation. These data suggest that the loss of an AGG is an important mutational event in the generation of unstable alleles predisposed to the fragile X syndrome. Loss of AGG trinucleotides and polarized variability support Okazaki fragment slippage as a model for CGG repeat instability and hyperexpansion.

  7. Structures of designed armadillo-repeat proteins show propagation of inter-repeat interface effects

    PubMed Central

    Reichen, Christian; Madhurantakam, Chaithanya; Hansen, Simon; Grütter, Markus G.; Plückthun, Andreas; Mittl, Peer R. E.

    2016-01-01

    The armadillo repeat serves as a scaffold for the development of modular peptide-recognition modules. In order to develop such a system, three crystal structures of designed armadillo-repeat proteins with third-generation N-caps (YIII-type), four or five internal repeats (M-type) and second-generation C-caps (AII-type) were determined at 1.8 Å (His-YIIIM4AII), 2.0 Å (His-YIIIM5AII) and 1.95 Å (YIIIM5AII) resolution and compared with those of variants with third-generation C-caps. All constructs are full consensus designs in which the internal repeats have exactly the same sequence, and hence identical conformations of the internal repeats are expected. The N-cap and internal repeats M1 to M3 are indeed extremely similar, but the comparison reveals structural differences in internal repeats M4 and M5 and the C-cap. These differences are caused by long-range effects of the C-cap, contacting molecules in the crystal, and the intrinsic design of the repeat. Unfortunately, the rigid-body movement of the C-terminal part impairs the regular arrangement of internal repeats that forms the putative peptide-binding site. The second-generation C-cap improves the packing of buried residues and thereby the stability of the protein. These considerations are useful for future improvements of an armadillo-repeat-based peptide-recognition system. PMID:26894544

  8. A method for fast database search for all k-nucleotide repeats.

    PubMed Central

    Benson, G; Waterman, M S

    1994-01-01

    A significant portion of DNA consists of repeating patterns of various sizes, from very small (one, two and three nucleotides) to very large (over 300 nucleotides). Although the functions of these repeating regions are not well understood, they appear important for understanding the expression, regulation and evolution of DNA. For example, increases in the number of trinucleotide repeats have been associated with human genetic disease, including Fragile-X mental retardation and Huntington's disease. Repeats are also useful as a tool in mapping and identifying DNA; the number of copies of a particular pattern at a site is often variable among individuals (polymorphic) and is therefore helpful in locating genes via linkage studies and also in providing DNA fingerprints of individuals. The number of repeating regions is unknown as is the distribution of pattern sizes. It would be useful to search for such regions in the DNA database in order that they may be studied more fully. The DNA database currently consists of approximately 150 million basepairs and is growing exponentially. Therefore, any program to look for repeats must be efficient and fast. In this paper, we present some new techniques that are useful in recognizing repeating patterns and describe a new program for rapidly detecting repeat regions in the DNA database where the basic unit of the repeat has size up to 32 nucleotides. It is our hope that the examples in this paper will illustrate the unrealized diversity of repeats in DNA and that the program we have developed will be a useful tool for locating new and interesting repeats. PMID:7984436

  9. A Prospective Study of Psychiatric Comorbidity and Recidivism Among Repeat DUI Offenders.

    PubMed

    Nelson, Sarah E; Belkin, Katerina; LaPlante, Debi A; Bosworth, Leslie; Shaffer, Howard J

    2015-04-13

    Psychiatric comorbidity has emerged as a key element distinguishing DUI offenders from others, and, in some cases, distinguishing repeat offenders from first-time offenders. This paper utilizes a prospective design to determine whether the comorbid disorders identified among repeat DUI offenders can predict recidivism. Seven hundred forty-three repeat DUI offenders were recruited from a two-week inpatient treatment program at which they received a standardized mental health assessment and followed across five years post-treatment to track DUI offense, motor vehicle-related offenses, and general criminal offenses. Psychiatric comorbidity, though it did not predict DUI recidivism specifically, predicted criminal re-offense more generally. In addition, there was a specific relationship between lifetime attention deficit disorder and repeated motor vehicle-related offenses. These findings suggest that for many repeat offenders, DUI is one outlet in a constellation of criminal behavior, and that psychiatric comorbidity increases vulnerability for criminal re-offense.

  10. Effect of trinucleotide repeat length and parental sex on phenotypic variation in spinocerebellar ataxia I

    SciTech Connect

    Jodice, C.; Malaspina, P.; Persichetti, F.; Novelletto, A.; Terrenato, L. ); Spadaro, M.; Morocutti, C. ); Giunti, P. Institute of Neurology, London ); Harding, A.E. ); Frontali, M. )

    1994-06-01

    Trinucleotide repeat expansion has been found in 64 subjects from 19 families: 57 patients with SCA1 and 7 subjects predicted, by haplotype analysis, to carry the mutation. Comparison with a large set of normal chromosomes shows two distinct distributions, with a much wider variation among expanded chromosomes. The sex of transmitting parent plays a major role in the size distribution of expanded alleles, those with >54 repeats being transmitted by affected fathers exclusively. The data suggest that alleles with >54 repeats have a reduced chance of survival; these appear to be replaced in each generation by further expansion of alleles in the low- to medium-expanded repeat range, preferentially in male transmission. Detailed clinical follow-up of a subset of patients demonstrates significant relationships between increasing repeat number on expanded chromosomes and earlier age at onset, faster progression of the disease, and earlier age at death.

  11. Multiple-locus variable number tandem repeats analysis for genetic fingerprinting of pathogenic bacteria.

    PubMed

    Lindstedt, Bjørn-Arne

    2005-06-01

    DNA fingerprinting has attracted considerable interest as means for identifying, tracing and preventing the dissemination of infectious agents. Various methods have been developed for typing of pathogenic bacteria, which differ in discriminative power, reproducibility and ease of interpretation. During recent years a typing method, which uses the information provided by whole genome sequencing of bacterial species, has gained increased attention. Short sequence repeat (SSR) motifs are known to undergo frequent variation in the number of repeated units through cellular mechanisms most commonly active during chromosome replication. A class of SSRs, named variable number of tandem repeats (VNTRs), has proven to be a suitable target for assessing genetic polymorphisms within bacterial species. This review attempts to give an overview of bacterial agents where VNTR-based typing, or multiple-locus variant-repeat analysis (MLVA) has been developed for typing purposes, together with addressing advantages and drawbacks associated with the use of tandem repeated DNA motifs as targets for bacterial typing and identification.

  12. Parturition date for a given female is highly repeatable within five roe deer populations.

    PubMed

    Plard, Floriane; Gaillard, Jean-Michel; Bonenfant, Christophe; Hewison, A J Mark; Delorme, Daniel; Cargnelutti, Bruno; Kjellander, Petter; Nilsen, Erlend B; Coulson, Tim

    2013-02-23

    Births are highly synchronized among females in many mammal populations in temperate areas. Although laying date for a given female is also repeatable within populations of birds, limited evidence suggests low repeatability of parturition date for individual females in mammals, and between-population variability in repeatability has never, to our knowledge, been assessed. We quantified the repeatability of parturition date for individual females in five populations of roe deer, which we found to vary between 0.54 and 0.93. Each year, some females gave birth consistently earlier in the year, whereas others gave birth consistently later. In addition, all females followed the same lifetime trajectory for parturition date, giving birth progressively earlier as they aged. Giving birth early should allow mothers to increase offspring survival, although few females managed to do so. The marked repeatability of parturition date in roe deer females is the highest ever reported for a mammal, suggesting low phenotypic plasticity in this trait.

  13. Maximum cell productivity by repeated fed-batch culture for constant yield case

    SciTech Connect

    Weigand, W.A.

    1981-02-01

    Optimal operation of repeatedly fed-batch fermentation was determined by the continuous maximum principle for the constant yield case. The objective of maximum cell productivity for a fixed final cell concentration was achieved by finding the substrate feeding policy that minimized the processing time. Analytical criteria for the optimal filling policy show that an exponential policy is optimum when the specific growth rate has a maximum, and also that operation in the simple repeated batch model is optimum when the specific growth rate is optimum when the specific growth rate is monotonic increasing. Comparisons between optimal repeated fed-batch culture and other modes of operation were made for the case of substrate-inhibited growth. Cell productivity by repeated fed-batch exceeds both repeated batch and continuous operation for the case of low residual substrate concentration.

  14. A Prospective Study of Psychiatric Comorbidity and Recidivism Among Repeat DUI Offenders

    PubMed Central

    Nelson, Sarah E.; Belkin, Katerina; LaPlante, Debi A.; Bosworth, Leslie; Shaffer, Howard J.

    2015-01-01

    Psychiatric comorbidity has emerged as a key element distinguishing DUI offenders from others, and, in some cases, distinguishing repeat offenders from first-time offenders. This paper utilizes a prospective design to determine whether the comorbid disorders identified among repeat DUI offenders can predict recidivism. Seven hundred forty-three repeat DUI offenders were recruited from a two-week inpatient treatment program at which they received a standardized mental health assessment and followed across five years post-treatment to track DUI offense, motor vehicle-related offenses, and general criminal offenses. Psychiatric comorbidity, though it did not predict DUI recidivism specifically, predicted criminal re-offense more generally. In addition, there was a specific relationship between lifetime attention deficit disorder and repeated motor vehicle-related offenses. These findings suggest that for many repeat offenders, DUI is one outlet in a constellation of criminal behavior, and that psychiatric comorbidity increases vulnerability for criminal re-offense. PMID:26539339

  15. Triggering of repeating earthquakes in central California

    USGS Publications Warehouse

    Wu, Chunquan; Gomberg, Joan; Ben-Naim, Eli; Johnson, Paul

    2014-01-01

    Dynamic stresses carried by transient seismic waves have been found capable of triggering earthquakes instantly in various tectonic settings. Delayed triggering may be even more common, but the mechanisms are not well understood. Catalogs of repeating earthquakes, earthquakes that recur repeatedly at the same location, provide ideal data sets to test the effects of transient dynamic perturbations on the timing of earthquake occurrence. Here we employ a catalog of 165 families containing ~2500 total repeating earthquakes to test whether dynamic perturbations from local, regional, and teleseismic earthquakes change recurrence intervals. The distance to the earthquake generating the perturbing waves is a proxy for the relative potential contributions of static and dynamic deformations, because static deformations decay more rapidly with distance. Clear changes followed the nearby 2004 Mw6 Parkfield earthquake, so we study only repeaters prior to its origin time. We apply a Monte Carlo approach to compare the observed number of shortened recurrence intervals following dynamic perturbations with the distribution of this number estimated for randomized perturbation times. We examine the comparison for a series of dynamic stress peak amplitude and distance thresholds. The results suggest a weak correlation between dynamic perturbations in excess of ~20 kPa and shortened recurrence intervals, for both nearby and remote perturbations.

  16. Is Retrieval Mediated after Repeated Testing?

    ERIC Educational Resources Information Center

    Kole, James A.; Healy, Alice F.

    2013-01-01

    In 2 main experiments, the mediated priming effect was used to determine whether retrieval continues to be mediated after repeated testing. In each experiment, participants used the keyword method to learn French vocabulary, then completed a modified lexical decision task in which they first translated a French word, and then made a lexical…

  17. Repeater For A Digital-Communication Bus

    NASA Technical Reports Server (NTRS)

    Torres-Guzman, Esteban; Olson, Stephen; Heaps, Tim

    1993-01-01

    Digital repeater circuit designed to extend range of communication on MIL-STD-1553 bus beyond original maximum allowable length of 300 ft. Circuit provides two-way communication, one way at time, and conforms to specifications of MIL-STD-1553. Crosstalk and instability eliminated.

  18. Rectourethral fistula after repeat transrectal prostate biopsy.

    PubMed

    Loran, Oleg B; Veliev, Evgeny I; Sokolov, Egor A; Dadashev, Elmar O; Guspanov, Renat I

    2013-09-01

    Transrectal prostate biopsy is considered a relatively safe procedure, with a quite small number of complications. We report a patient with a rectourethral fistula after a repeat transrectal prostate biopsy. To our knowledge, this is the first incident in the published literature.

  19. Repeated Random Sampling in Year 5

    ERIC Educational Resources Information Center

    Watson, Jane M.; English, Lyn D.

    2016-01-01

    As an extension to an activity introducing Year 5 students to the practice of statistics, the software "TinkerPlots" made it possible to collect repeated random samples from a finite population to informally explore students' capacity to begin reasoning with a distribution of sample statistics. This article provides background for the…

  20. [Preventive maintenance of repeated ischemic insults].

    PubMed

    Gavrilenko, A V; Kuklin, A V; Kravchenko, A A; Agafonov, I N

    2008-01-01

    In the review we offer analysis of the effectiveness of carotid endarterectomy in treatment of post-functional apoplexy or stroke patients. Published results of the researches specify possible efficiency of carotid endarterectomy in preventive maintenance against repeated apoplectic attack or strokes. Yet the criteria of usage and execution of the carotid endarterectomy are still to be discussed.

  1. Epigenetics and Triplet-Repeat Neurological Diseases

    PubMed Central

    Nageshwaran, Sathiji; Festenstein, Richard

    2015-01-01

    The term “junk DNA” has been reconsidered following the delineation of the functional significance of repetitive DNA regions. Typically associated with centromeres and telomeres, DNA repeats are found in nearly all organisms throughout their genomes. Repetitive regions are frequently heterochromatinized resulting in silencing of intrinsic and nearby genes. However, this is not a uniform rule, with several genes known to require such an environment to permit transcription. Repetitive regions frequently exist as dinucleotide, trinucleotide, and tetranucleotide repeats. The association between repetitive regions and disease was emphasized following the discovery of abnormal trinucleotide repeats underlying spinal and bulbar muscular atrophy (Kennedy’s disease) and fragile X syndrome of mental retardation (FRAXA) in 1991. In this review, we provide a brief overview of epigenetic mechanisms and then focus on several diseases caused by DNA triplet-repeat expansions, which exhibit diverse epigenetic effects. It is clear that the emerging field of epigenetics is already generating novel potential therapeutic avenues for this group of largely incurable diseases. PMID:26733936

  2. Testing Multiple Outcomes in Repeated Measures Designs

    ERIC Educational Resources Information Center

    Lix, Lisa M.; Sajobi, Tolulope

    2010-01-01

    This study investigates procedures for controlling the familywise error rate (FWR) when testing hypotheses about multiple, correlated outcome variables in repeated measures (RM) designs. A content analysis of RM research articles published in 4 psychology journals revealed that 3 quarters of studies tested hypotheses about 2 or more outcome…

  3. Y Se Repite = And It Repeats Itself

    ERIC Educational Resources Information Center

    Katzew, Adriana

    2010-01-01

    In this article, the author discusses Y Se Repite [And It Repeats Itself], a project she conceptualized due to the growing number of Latino/a Mexican migrant workers in dairy farms in the state of Vermont. In 2006, approximately 2,000 Latinos/as--most of them undocumented Mexican migrant workers--worked throughout the state's dairy farms, yet…

  4. Longer-baseline telescopes using quantum repeaters.

    PubMed

    Gottesman, Daniel; Jennewein, Thomas; Croke, Sarah

    2012-08-17

    We present an approach to building interferometric telescopes using ideas of quantum information. Current optical interferometers have limited baseline lengths, and thus limited resolution, because of noise and loss of signal due to the transmission of photons between the telescopes. The technology of quantum repeaters has the potential to eliminate this limit, allowing in principle interferometers with arbitrarily long baselines.

  5. The Effect of Repeaters on Equating

    ERIC Educational Resources Information Center

    Kim, HeeKyoung; Kolen, Michael J.

    2010-01-01

    Test equating might be affected by including in the equating analyses examinees who have taken the test previously. This study evaluated the effect of including such repeaters on Medical College Admission Test (MCAT) equating using a population invariance approach. Three-parameter logistic (3-PL) item response theory (IRT) true score and…

  6. Independent movement, dimerization and stability of tandem repeats of chicken brain alpha-spectrin

    SciTech Connect

    Kusunoki, H.; Minasov, G.; Macdonald, R.I.; Mondragon, A.

    2010-03-08

    Previous X-ray crystal structures have shown that linkers of five amino acid residues connecting pairs of chicken brain {alpha}-spectrin and human erythroid {beta}-spectrin repeats can undergo bending without losing their {alpha}-helical structure. To test whether bending at one linker can influence bending at an adjacent linker, the structures of two and three repeat fragments of chicken brain {alpha}-spectrin have been determined by X-ray crystallography. The structure of the three-repeat fragment clearly shows that bending at one linker can occur independently of bending at an adjacent linker. This observation increases the possible trajectories of modeled chains of spectrin repeats. Furthermore, the three-repeat molecule crystallized as an antiparallel dimer with a significantly smaller buried interfacial area than that of {alpha}-actinin, a spectrin-related molecule, but large enough and of a type indicating biological specificity. Comparison of the structures of the spectrin and {alpha}-actinin dimers supports weak association of the former, which could not be detected by analytical ultracentrifugation, versus strong association of the latter, which has been observed by others. To correlate features of the structure with solution properties and to test a previous model of stable spectrin and dystrophin repeats, the number of inter-helical interactions in each repeat of several spectrin structures were counted and compared to their thermal stabilities. Inter-helical interactions, but not all interactions, increased in parallel with measured thermal stabilities of each repeat and in agreement with the thermal stabilities of two and three repeats and also partial repeats of spectrin.

  7. The evidence for increased L1 activity in the site of human adult brain neurogenesis.

    PubMed

    Kurnosov, Alexey A; Ustyugova, Svetlana V; Nazarov, Vadim I; Minervina, Anastasia A; Komkov, Alexander Yu; Shugay, Mikhail; Pogorelyy, Mikhail V; Khodosevich, Konstantin V; Mamedov, Ilgar Z; Lebedev, Yuri B

    2015-01-01

    Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus-the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.

  8. Browsing repeats in genomes: Pygram and an application to non-coding region analysis

    PubMed Central

    Durand, Patrick; Mahé, Frédéric; Valin, Anne-Sophie; Nicolas, Jacques

    2006-01-01

    Background A large number of studies on genome sequences have revealed the major role played by repeated sequences in the structure, function, dynamics and evolution of genomes. In-depth repeat analysis requires specialized methods, including visualization techniques, to achieve optimum exploratory power. Results This article presents Pygram, a new visualization application for investigating the organization of repeated sequences in complete genome sequences. The application projects data from a repeat index file on the analysed sequences, and by combining this principle with a query system, is capable of locating repeated sequences with specific properties. In short, Pygram provides an efficient, graphical browser for studying repeats. Implementation of the complete configuration is illustrated in an analysis of CRISPR structures in Archaea genomes and the detection of horizontal transfer between Archaea and Viruses. Conclusion By proposing a new visualization environment to analyse repeated sequences, this application aims to increase the efficiency of laboratories involved in investigating repeat organization in single genomes or across several genomes. PMID:17067389

  9. Effects of Velocity on Electromyographic, Mechanomyographic, and Torque Responses to Repeated Eccentric Muscle Actions.

    PubMed

    Hill, Ethan C; Housh, Terry J; Camic, Clayton L; Smith, Cory M; Cochrane, Kristen C; Jenkins, Nathaniel D M; Cramer, Joel T; Schmidt, Richard J; Johnson, Glen O

    2016-06-01

    The purposes of this study were to examine the effects of the velocity of repeated eccentric muscle actions on the torque and neuromuscular responses during maximal isometric and eccentric muscle actions. Twelve resistance-trained men performed 30 repeated, maximal, eccentric, isokinetic muscle actions at randomly ordered velocities of 60, 120, or 180°·s on separate days. Maximal voluntary isometric contractions (MVICs) were performed before (pretest) and after (posttest) the repeated eccentric muscle actions on each day. Eccentric isokinetic peak torque (EIPT) values were the averages of the first 3 and last 3 repetitions of the 30 repeated eccentric muscle actions. During the EIPT and MVIC muscle actions, electromyographic (EMG) and mechanomyographic (MMG) amplitude (EMG AMP and MMG AMP) and mean power frequency (EMG MPF and MMG MPF) values were assessed. These results indicated that the repeated eccentric muscle actions had no effects on EIPT, or the EMG AMP, EMG MPF, or MMG MPF values assessed during the EIPT muscle actions, but decreased MMG AMP. The repeated eccentric muscle actions, however, decreased MVIC torque, and also the EMG AMP and MMG MPF values assessed during the MVIC muscle actions, but increased MMG AMP. The results indicated that the velocity of the repeated eccentric muscle actions affected the MVIC torque responses, but not EIPT or any of the neuromuscular parameters. Furthermore, there are differences in the torque and neuromuscular responses for isometric vs. eccentric muscle actions after repeated eccentric muscle actions.

  10. Genetic Contributors to Intergenerational CAG Repeat Instability in Huntington’s Disease Knock-In Mice

    PubMed Central

    Neto, João Luís; Lee, Jong-Min; Afridi, Ali; Gillis, Tammy; Guide, Jolene R.; Dempsey, Stephani; Lager, Brenda; Alonso, Isabel; Wheeler, Vanessa C.; Pinto, Ricardo Mouro

    2017-01-01

    Huntington’s disease (HD) is a neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in exon 1 of the HTT gene. Longer repeat sizes are associated with increased disease penetrance and earlier ages of onset. Intergenerationally unstable transmissions are common in HD families, partly underlying the genetic anticipation seen in this disorder. HD CAG knock-in mouse models also exhibit a propensity for intergenerational repeat size changes. In this work, we examine intergenerational instability of the CAG repeat in over 20,000 transmissions in the largest HD knock-in mouse model breeding datasets reported to date. We confirmed previous observations that parental sex drives the relative ratio of expansions and contractions. The large datasets further allowed us to distinguish effects of paternal CAG repeat length on the magnitude and frequency of expansions and contractions, as well as the identification of large repeat size jumps in the knock-in models. Distinct degrees of intergenerational instability were observed between knock-in mice of six background strains, indicating the occurrence of trans-acting genetic modifiers. We also found that lines harboring a neomycin resistance cassette upstream of Htt showed reduced expansion frequency, indicative of a contributing role for sequences in cis, with the expanded repeat as modifiers of intergenerational instability. These results provide a basis for further understanding of the mechanisms underlying intergenerational repeat instability. PMID:27913616

  11. Genetic Contributors to Intergenerational CAG Repeat Instability in Huntington's Disease Knock-In Mice.

    PubMed

    Neto, João Luís; Lee, Jong-Min; Afridi, Ali; Gillis, Tammy; Guide, Jolene R; Dempsey, Stephani; Lager, Brenda; Alonso, Isabel; Wheeler, Vanessa C; Pinto, Ricardo Mouro

    2017-02-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in exon 1 of the HTT gene. Longer repeat sizes are associated with increased disease penetrance and earlier ages of onset. Intergenerationally unstable transmissions are common in HD families, partly underlying the genetic anticipation seen in this disorder. HD CAG knock-in mouse models also exhibit a propensity for intergenerational repeat size changes. In this work, we examine intergenerational instability of the CAG repeat in over 20,000 transmissions in the largest HD knock-in mouse model breeding datasets reported to date. We confirmed previous observations that parental sex drives the relative ratio of expansions and contractions. The large datasets further allowed us to distinguish effects of paternal CAG repeat length on the magnitude and frequency of expansions and contractions, as well as the identification of large repeat size jumps in the knock-in models. Distinct degrees of intergenerational instability were observed between knock-in mice of six background strains, indicating the occurrence of trans-acting genetic modifiers. We also found that lines harboring a neomycin resistance cassette upstream of Htt showed reduced expansion frequency, indicative of a contributing role for sequences in cis, with the expanded repeat as modifiers of intergenerational instability. These results provide a basis for further understanding of the mechanisms underlying intergenerational repeat instability.

  12. RepeatsDB 2.0: improved annotation, classification, search and visualization of repeat protein structures

    PubMed Central

    Paladin, Lisanna; Hirsh, Layla; Piovesan, Damiano; Andrade-Navarro, Miguel A.; Kajava, Andrey V.; Tosatto, Silvio C.E.

    2017-01-01

    RepeatsDB 2.0 (URL: http://repeatsdb.bio.unipd.it/) is an update of the database of annotated tandem repeat protein structures. Repeat proteins are a widespread class of non-globular proteins carrying heterogeneous functions involved in several diseases. Here we provide a new version of RepeatsDB with an improved classification schema including high quality annotations for ∼5400 protein structures. RepeatsDB 2.0 features information on start and end positions for the repeat regions and units for all entries. The extensive growth of repeat unit characterization was possible by applying the novel ReUPred annotation method over the entire Protein Data Bank, with data quality is guaranteed by an extensive manual validation for >60% of the entries. The updated web interface includes a new search engine for complex queries and a fully re-designed entry page for a better overview of structural data. It is now possible to compare unit positions, together with secondary structure, fold information and Pfam domains. Moreover, a new classification level has been introduced on top of the existing scheme as an independent layer for sequence similarity relationships at 40%, 60% and 90% identity. PMID:27899671

  13. Unusually large telomeric repeats in the yeast Candida albicans.

    PubMed Central

    McEachern, M J; Hicks, J B

    1993-01-01

    We have identified sequences at the telomeres of the yeast Candida albicans and have found that they are composed of tandem copies of a 23-bp sequence. Through the cloning of native telomeric ends and the characterization and cloning of a "healed" end, we demonstrate that these repeated sequences are sufficient to function as a telomere. All copies of the 23-bp repeat that have been sequenced from a number of C. albicans strains are identical. In contrast, adjacent subtelomeric sequences are variable both between strains and within the WO-1 strain. In the WO-1 strain, the lengths of the telomeres are dependent upon growth temperature and are substantially longer at higher temperatures. Telomere growth is accompanied by increases in the number of the 23-bp repeats present on the telomeric fragments. These results suggest that either telomerase-maintained telomeres can be more complex in structure than was previously imagined or that Candida telomeres are maintained via a telomerase-independent mechanism. Images PMID:8417351

  14. Evolution of Determinant Factors of Repeated Sprint Ability.

    PubMed

    Pareja-Blanco, Fernando; Suarez-Arrones, Luis; Rodríguez-Rosell, David; López-Segovia, Manuel; Jiménez-Reyes, Pedro; Bachero-Mena, Beatriz; González-Badillo, Juan José

    2016-12-01

    The aim of this study was to investigate the changes in the relationships between repeated sprint ability (RSA) and anthropometric measures as well as fitness qualities in soccer players. Twenty-one professional soccer players performed several anthropometric and physical tests including countermovement vertical jumps (CMJs), a straight-line 30 m sprint (T30), an RSA test (6 x 20 + 20 m with 20 s recovery), a progressive isoinertial loading test in a full squat, a Yo-Yo Intermittent Recovery Test Level-1 (YYIRT-1) and a 20 m shuttle run test (20mSRT). The mean (RSAmean), the fastest (RSAbest), each single sprint time, and the percentage in a sprint decrease (%Dec) in the RSA test were calculated. RSAbest correlated significantly with RSAmean (r = .82) and with all single sprints (p < 0.05), showing a downward trend as the number of sprints performed increased. No significant relationship was observed between the %Dec and RSA performance. CMJs and the T30 also showed a correlation with RSA performance, whereas lower limb strength did not show any relationship with RSA performance. RSAmean showed significant (p < 0.05) relationships with body mass (r = .44), adiposity (r = .59) and the YYIRT-1 (r = -.62), increasing as the number of repeated sprints increased. The 20mSRT showed minimal relationships with RSA performance. In conclusion, maximal sprint capacity seems to be relevant for the RSA performance, mainly in the first sprints. However, high intermittent endurance capacity and low adiposity might help enhance the RSA performance when increasing the number of repeated sprints.

  15. Evolution of Determinant Factors of Repeated Sprint Ability

    PubMed Central

    Suarez-Arrones, Luis; Rodríguez-Rosell, David; López-Segovia, Manuel; Jiménez-Reyes, Pedro; Bachero-Mena, Beatriz; González-Badillo, Juan José

    2016-01-01

    Abstract The aim of this study was to investigate the changes in the relationships between repeated sprint ability (RSA) and anthropometric measures as well as fitness qualities in soccer players. Twenty-one professional soccer players performed several anthropometric and physical tests including countermovement vertical jumps (CMJs), a straight-line 30 m sprint (T30), an RSA test (6 x 20 + 20 m with 20 s recovery), a progressive isoinertial loading test in a full squat, a Yo-Yo Intermittent Recovery Test Level-1 (YYIRT-1) and a 20 m shuttle run test (20mSRT). The mean (RSAmean), the fastest (RSAbest), each single sprint time, and the percentage in a sprint decrease (%Dec) in the RSA test were calculated. RSAbest correlated significantly with RSAmean (r = .82) and with all single sprints (p < 0.05), showing a downward trend as the number of sprints performed increased. No significant relationship was observed between the %Dec and RSA performance. CMJs and the T30 also showed a correlation with RSA performance, whereas lower limb strength did not show any relationship with RSA performance. RSAmean showed significant (p < 0.05) relationships with body mass (r = .44), adiposity (r = .59) and the YYIRT-1 (r = -.62), increasing as the number of repeated sprints increased. The 20mSRT showed minimal relationships with RSA performance. In conclusion, maximal sprint capacity seems to be relevant for the RSA performance, mainly in the first sprints. However, high intermittent endurance capacity and low adiposity might help enhance the RSA performance when increasing the number of repeated sprints. PMID:28031763

  16. Vectorette PCR isolation of microsatellite repeat sequences using anchored dinucleotide repeat primers.

    PubMed Central

    Lench, N J; Norris, A; Bailey, A; Booth, A; Markham, A F

    1996-01-01

    We have developed a vectorette PCR approach to provide an improved method for isolation of microsatellite repeats. The modified procedure relies on PCR amplification using a vectorette-specific primer in combination with one of a panel of anchored dinucleotide repeat primers. The target DNA to be screened for microsatellite sequences can be from YAC, P1, cosmid, bacteriophage or plasmid clones. We have used this technique to isolate novel, polymorphic microsatellite repeats from clones containing the amelogenin gene (AMGX) located on human chromosome Xp22.3. PMID:8668553

  17. Short-Sequence DNA Repeats in Prokaryotic Genomes

    PubMed Central

    van Belkum, Alex; Scherer, Stewart; van Alphen, Loek; Verbrugh, Henri

    1998-01-01

    Short-sequence DNA repeat (SSR) loci can be identified in all eukaryotic and many prokaryotic genomes. These loci harbor short or long stretches of repeated nucleotide sequence motifs. DNA sequence motifs in a single locus can be identical and/or heterogeneous. SSRs are encountered in many different branches of the prokaryote kingdom. They are found in genes encoding products as diverse as microbial surface components recognizing adhesive matrix molecules and specific bacterial virulence factors such as lipopolysaccharide-modifying enzymes or adhesins. SSRs enable genetic and consequently phenotypic flexibility. SSRs function at various levels of gene expression regulation. Variations in the number of repeat units per locus or changes in the nature of the individual repeat sequences may result from recombination processes or polymerase inadequacy such as slipped-strand mispairing (SSM), either alone or in combination with DNA repair deficiencies. These rather complex phenomena can occur with relative ease, with SSM approaching a frequency of 10−4 per bacterial cell division and allowing high-frequency genetic switching. Bacteria use this random strategy to adapt their genetic repertoire in response to selective environmental pressure. SSR-mediated variation has important implications for bacterial pathogenesis and evolutionary fitness. Molecular analysis of changes in SSRs allows epidemiological studies on the spread of pathogenic bacteria. The occurrence, evolution and function of SSRs, and the molecular methods used to analyze them are discussed in the context of responsiveness to environmental factors, bacterial pathogenicity, epidemiology, and the availability of full-genome sequences for increasing numbers of microorganisms, especially those that are medically relevant. PMID:9618442

  18. Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation.

    PubMed

    Tinckam, Kathryn J; Rose, Caren; Hariharan, Sundaram; Gill, John

    2016-09-01

    Kidney retransplantation is a risk factor for decreased allograft survival. Repeated mismatched HLA antigens between first and second transplant may be a stimulus for immune memory responses and increased risk of alloimmune damage to the second allograft. Historical data identified a role of repeated HLA mismatches in allograft loss. However, evolution of HLA testing methods and a modern transplant era necessitate re-examination of this role to more accurately risk-stratify recipients. We conducted a contemporary registry analysis of data from 13,789 patients who received a second kidney transplant from 1995 to 2011, of which 3868 had one or more repeated mismatches. Multivariable Cox proportional hazards modeling revealed no effect of repeated mismatches on all-cause or death-censored graft loss. Analysis of predefined subgroups, however, showed that any class 2 repeated mismatch increased the hazard of death-censored graft loss, particularly in patients with detectable panel-reactive antibody before second transplant (hazard ratio [HR], 1.15; 95% confidence interval [95% CI], 1.02 to 1.29). Furthermore, in those who had nephrectomy of the first allograft, class 2 repeated mismatches specifically associated with all-cause (HR, 1.30; 95% CI, 1.07 to 1.58) and death-censored graft loss (HR, 1.41; 95% CI, 1.12 to 1.78). These updated data redefine the effect of repeated mismatches in retransplantation and challenge the paradigm that repeated mismatches in isolation confer increased immunologic risk. We also defined clear recipient categories for which repeated mismatches may be of greater concern in a contemporary cohort. Additional studies are needed to determine appropriate interventions for these recipients.

  19. Appetite - increased

    MedlinePlus

    ... Have you noticed any other symptoms such as anxiety, palpitations , increased thirst , vomiting , frequent urination , or unintentional weight gain? Tests that may be done include: Blood tests, ...

  20. Overcoming fixation with repeated memory suppression.

    PubMed

    Angello, Genna; Storm, Benjamin C; Smith, Steven M

    2015-01-01

    Fixation (blocks to memories or ideas) can be alleviated not only by encouraging productive work towards a solution, but, as the present experiments show, by reducing counterproductive work. Two experiments examined relief from fixation in a word-fragment completion task. Blockers, orthographically similar negative primes (e.g., ANALOGY), blocked solutions to word fragments (e.g., A_L_ _GY) in both experiments. After priming, but before the fragment completion test, participants repeatedly suppressed half of the blockers using the Think/No-Think paradigm, which results in memory inhibition. Inhibiting blockers did not alleviate fixation in Experiment 1 when conscious recollection of negative primes was not encouraged on the fragment completion test. In Experiment 2, however, when participants were encouraged to remember negative primes at fragment completion, relief from fixation was observed. Repeated suppression may nullify fixation effects, and promote creative thinking, particularly when fixation is caused by conscious recollection of counterproductive information.

  1. Mutagenic inverted repeat assisted genome engineering (MIRAGE).

    PubMed

    Nair, Nikhil U; Zhao, Huimin

    2009-01-01

    Here we describe a one-step method to create precise modifications in the genome of Saccharomyces cerevisiae as a tool for synthetic biology, metabolic engineering, systems biology and genetic studies. Through homologous recombination, a mutagenesis cassette containing an inverted repeat of selection marker(s) is integrated into the genome. Due to its inherent instability in genomic DNA, the inverted repeat catalyzes spontaneous self-excision, resulting in precise genome modification. Since this excision occurs at very high frequencies, selection for the integration event can be followed immediately by counterselection, without the need for growth in permissive conditions. This is the first time a truly one-step method has been described for genome modification in any organism.

  2. Accumulate-Repeat-Accumulate-Accumulate Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Dolinar, Samuel; Thorpe, Jeremy

    2007-01-01

    Accumulate-repeat-accumulate-accumulate (ARAA) codes have been proposed, inspired by the recently proposed accumulate-repeat-accumulate (ARA) codes. These are error-correcting codes suitable for use in a variety of wireless data-communication systems that include noisy channels. ARAA codes can be regarded as serial turbolike codes or as a subclass of low-density parity-check (LDPC) codes, and, like ARA codes they have projected graph or protograph representations; these characteristics make it possible to design high-speed iterative decoders that utilize belief-propagation algorithms. The objective in proposing ARAA codes as a subclass of ARA codes was to enhance the error-floor performance of ARA codes while maintaining simple encoding structures and low maximum variable node degree.

  3. Repeat-PPM Super-Symbol Synchronization

    NASA Astrophysics Data System (ADS)

    Connelly, J.

    2016-11-01

    To attain a wider range of data rates in pulse position modulation (PPM) schemes with constrained pulse durations, the sender can repeat a PPM symbol multiple times, forming a super-symbol. In addition to the slot and symbol synchronization typically required for PPM, the receiver must also properly align the noisy super-symbols. We present a low-complexity approximation of the maximum-likelihood method for performing super-symbol synchronization without use of synchronization sequences. We provide simulation results demonstrating performance advantage when PPM symbols are spread by a pseudo-noise sequence, as opposed to simply repeating. Additionally, the results suggest that this super-symbol synchronization technique requires signal levels below those required for reliable communication. This validates that the PPM spreading approach proposed to CCSDS can work properly as part of the overall scheme.

  4. Repeated interactions in open quantum systems

    SciTech Connect

    Bruneau, Laurent; Joye, Alain; Merkli, Marco

    2014-07-15

    Analyzing the dynamics of open quantum systems has a long history in mathematics and physics. Depending on the system at hand, basic physical phenomena that one would like to explain are, for example, convergence to equilibrium, the dynamics of quantum coherences (decoherence) and quantum correlations (entanglement), or the emergence of heat and particle fluxes in non-equilibrium situations. From the mathematical physics perspective, one of the main challenges is to derive the irreversible dynamics of the open system, starting from a unitary dynamics of the system and its environment. The repeated interactions systems considered in these notes are models of non-equilibrium quantum statistical mechanics. They are relevant in quantum optics, and more generally, serve as a relatively well treatable approximation of a more difficult quantum dynamics. In particular, the repeated interaction models allow to determine the large time (stationary) asymptotics of quantum systems out of equilibrium.

  5. DNA Replication Dynamics of the GGGGCC Repeat of the C9orf72 Gene.

    PubMed

    Thys, Ryan Griffin; Wang, Yuh-Hwa

    2015-11-27

    DNA has the ability to form a variety of secondary structures in addition to the normal B-form DNA, including hairpins and quadruplexes. These structures are implicated in a number of neurological diseases and cancer. Expansion of a GGGGCC repeat located at C9orf72 is associated with familial amyotrophic lateral sclerosis and frontotemporal dementia. This repeat expands from two to 24 copies in normal individuals to several hundreds or thousands of repeats in individuals with the disease. Biochemical studies have demonstrated that as little as four repeats have the ability to form a stable DNA secondary structure known as a G-quadruplex. Quadruplex structures have the ability to disrupt normal DNA processes such as DNA replication and transcription. Here we examine the role of GGGGCC repeat length and orientation on DNA replication using an SV40 replication system in human cells. Replication through GGGGCC repeats leads to a decrease in overall replication efficiency and an increase in instability in a length-dependent manner. Both repeat expansions and contractions are observed, and replication orientation is found to influence the propensity for expansions or contractions. The presence of replication stress, such as low-dose aphidicolin, diminishes replication efficiency but has no effect on instability. Two-dimensional gel electrophoresis analysis demonstrates a replication stall with as few as 20 GGGGCC repeats. These results suggest that replication of the GGGGCC repeat at C9orf72 is perturbed by the presence of expanded repeats, which has the potential to result in further expansion, leading to disease.

  6. Nucleosome repeat lengths and columnar chromatin structure.

    PubMed

    Trifonov, Edward N

    2016-06-01

    Thorough quantitative study of nucleosome repeat length (NRL) distributions, conducted in 1992 by J. Widom, resulted in a striking observation that the linker lengths between the nucleosomes are quantized. Comparison of the NRL average values with the MNase cut distances predicted from the hypothetical columnar structure of chromatin (this work) shows a close correspondence between the two. This strongly suggests that the NRL distribution, actually, reflects the dominant role of columnar chromatin structure common for all eukaryotes.

  7. Identical repeated backbone of the human genome

    PubMed Central

    2010-01-01

    Background Identical sequences with a minimal length of about 300 base pairs (bp) have been involved in the generation of various meiotic/mitotic genomic rearrangements through non-allelic homologous recombination (NAHR) events. Genomic disorders and structural variation, together with gene remodelling processes have been associated with many of these rearrangements. Based on these observations, we identified and integrated all the 100% identical repeats of at least 300 bp in the NCBI version 36.2 human genome reference assembly into non-overlapping regions, thus defining the Identical Repeated Backbone (IRB) of the reference human genome. Results The IRB sequences are distributed all over the genome in 66,600 regions, which correspond to ~2% of the total NCBI human genome reference assembly. Important structural and functional elements such as common repeats, segmental duplications, and genes are contained in the IRB. About 80% of the IRB bp overlap with known copy-number variants (CNVs). By analyzing the genes embedded in the IRB, we were able to detect some identical genes not previously included in the Ensembl release 50 annotation of human genes. In addition, we found evidence of IRB gene copy-number polymorphisms in raw sequence reads of two diploid sequenced genomes. Conclusions In general, the IRB offers new insight into the complex organization of the identical repeated sequences of the human genome. It provides an accurate map of potential NAHR sites which could be used in targeting the study of novel CNVs, predicting DNA copy-number variation in newly sequenced genomes, and improve genome annotation. PMID:20096123

  8. Repeatability of Response to Asthma Medications

    PubMed Central

    Wu, Ann; Tantisira, Kelan; Li, Lingling; Schuemann, Brooke; Weiss, Scott

    2010-01-01

    Background Pharmacogenetic studies of drug response in asthma assume that patients respond consistently to a treatment but that treatment response varies across patients, however, no formal studies have demonstrated this. Objective To determine the repeatability of commonly used outcomes for treatment response to asthma medications: bronchodilator response, forced expiratory volume in 1 second (FEV1), and provocative concentration of methacholine producing a 20% decline in FEV1 (PC20). Methods The Childhood Asthma Management Program (CAMP) was a multi-center clinical trial of children randomized to receiving budesonide, nedocromil, or placebo. We determined the intraclass correlation coefficient (ICC) for each outcome over repeated visits over four years in CAMP using mixed effects regression models. We adjusted for the covariates: age, race/ethnicity, height, family income, parental education, and symptom score. We incorporated each outcome for each child as repeated outcome measurements and stratified by treatment group. Results The ICC for bronchodilator response was 0.31 in the budesonide group, 0.35 in the nedocromil group, and 0.40 in the placebo group, after adjusting for covariates. The ICC for FEV1 was 0.71 in the budesonide group, 0.60 in the nedocromil group, and 0.69 in the placebo group, after adjusting for covariates. The ICC for PC20 was 0.67 in the budesonide and placebo groups and 0.73 in the nedocromil group, after adjusting for covariates. Conclusion The within treatment group repeatability of FEV1 and PC20 are high; thus these phenotypes are heritable. FEV1 and PC20 may be better phenotypes than bronchodilator response for studies of treatment response in asthma. PMID:19064281

  9. 2D Metals by Repeated Size Reduction.

    PubMed

    Liu, Hanwen; Tang, Hao; Fang, Minghao; Si, Wenjie; Zhang, Qinghua; Huang, Zhaohui; Gu, Lin; Pan, Wei; Yao, Jie; Nan, Cewen; Wu, Hui

    2016-10-01

    A general and convenient strategy for manufacturing freestanding metal nanolayers is developed on large scale. By the simple process of repeatedly folding and calendering stacked metal sheets followed by chemical etching, free-standing 2D metal (e.g., Ag, Au, Fe, Cu, and Ni) nanosheets are obtained with thicknesses as small as 1 nm and with sizes of the order of several micrometers.

  10. Automatic-repeat-request error control schemes

    NASA Technical Reports Server (NTRS)

    Lin, S.; Costello, D. J., Jr.; Miller, M. J.

    1983-01-01

    Error detection incorporated with automatic-repeat-request (ARQ) is widely used for error control in data communication systems. This method of error control is simple and provides high system reliability. If a properly chosen code is used for error detection, virtually error-free data transmission can be attained. Various types of ARQ and hybrid ARQ schemes, and error detection using linear block codes are surveyed.

  11. Chromosome breakage in Prader-Willi and Angelman syndrome deletions may involve recombination between a repeat at the proximal and distal breakpoints

    SciTech Connect

    Amos-Landgraf J.; Nicholls, R.D.; Gottlieb, W.

    1994-09-01

    Prader-Willi (PWS) and Angelman (AS) syndromes most commonly arise from large deletions of 15q11-q13. Deletions in PWS are paternal in origin, while those in AS are maternal in origin, clearly demonstrating genomic imprinting in these clinically distinct neurobehavioural disorders. In at least 90% of PWS and AS deletion patients, the same 4 Mb region within 15q11-q13 is deleted with breakpoints clustering in single YAC clones at the proximal and distal ends. To study the mechanism of chromosome breakage in PWS and AS, we have previously isolated 25 independent clones from these three YACs using Alu-vector PCR. Four clones were selected that appear to detect a low copy repeat that is located in the proximal and distal breakpoint regions of chromosome 15q11-q13. Three clones detect the same 4 HindIII bands in genomic DNA, all from 15q11-q13, with differing intensities for the probes located at the proximal or distal breakpoints region, respectively. This suggests that these probes detect related members of a low-copy repeat at either location. Moreover, the 254RL2 probe detects a novel HindIII band in two unrelated PWS deletion patients, suggesting that this may represent a breakpoint fragment, with recombination occurring within a similar interval in both patients. A fourth clone, 318RL3 detects 5 bands in HindIII-digested genomic DNA, all from 15q11-q13. This YAC endclone itself is not deleted in PWS and AS deletion patients, as seen by an invariant strong band. Two other strong bands are variably intact or deleted in different PWS or AS deletion patients, suggesting a relationship of this sequence to the breakpoints. Moreover, PCR using 318RL3 primers from the distal 93C9 YAC led to the isolation of a related clone with 96% identity, demonstrating the existence of a low-copy repeat with members close to the proximal and distal breakpoints. Taken together, our data suggest a complex, low-copy repeat with members at both the proximal and distal boundaries.

  12. Genomic Repeat Abundances Contain Phylogenetic Signal

    PubMed Central

    Dodsworth, Steven; Chase, Mark W.; Kelly, Laura J.; Leitch, Ilia J.; Macas, Jiří; Novák, Petr; Piednoël, Mathieu; Weiss-Schneeweiss, Hanna; Leitch, Andrew R.

    2015-01-01

    A large proportion of genomic information, particularly repetitive elements, is usually ignored when researchers are using next-generation sequencing. Here we demonstrate the usefulness of this repetitive fraction in phylogenetic analyses, utilizing comparative graph-based clustering of next-generation sequence reads, which results in abundance estimates of different classes of genomic repeats. Phylogenetic trees are then inferred based on the genome-wide abundance of different repeat types treated as continuously varying characters; such repeats are scattered across chromosomes and in angiosperms can constitute a majority of nuclear genomic DNA. In six diverse examples, five angiosperms and one insect, this method provides generally well-supported relationships at interspecific and intergeneric levels that agree with results from more standard phylogenetic analyses of commonly used markers. We propose that this methodology may prove especially useful in groups where there is little genetic differentiation in standard phylogenetic markers. At the same time as providing data for phylogenetic inference, this method additionally yields a wealth of data for comparative studies of genome evolution. PMID:25261464

  13. Landauer's Principle in Repeated Interaction Systems

    NASA Astrophysics Data System (ADS)

    Hanson, Eric P.; Joye, Alain; Pautrat, Yan; Raquépas, Renaud

    2017-01-01

    We study Landauer's Principle for Repeated Interaction Systems (RIS) consisting of a reference quantum system S in contact with a structured environment E made of a chain of independent quantum probes; S interacts with each probe, for a fixed duration, in sequence. We first adapt Landauer's lower bound, which relates the energy variation of the environment E to a decrease of entropy of the system S during the evolution, to the peculiar discrete time dynamics of RIS. Then we consider RIS with a structured environment E displaying small variations of order {T^{-1}} between the successive probes encountered by S, after {n ˜eq T} interactions, in keeping with adiabatic scaling. We establish a discrete time non-unitary adiabatic theorem to approximate the reduced dynamics of S in this regime, in order to tackle the adiabatic limit of Landauer's bound. We find that saturation of Landauer's bound is related to a detailed balance condition on the repeated interaction system, reflecting the non-equilibrium nature of the repeated interaction system dynamics. This is to be contrasted with the generic saturation of Landauer's bound known to hold for continuous time evolution of an open quantum system interacting with a single thermal reservoir in the adiabatic regime.

  14. Repeated-sprint ability: where are we?

    PubMed

    Dawson, Brian

    2012-09-01

    Repeated-sprint ability (RSA) is now well accepted as an important fitness component in team-sport performance. It is broadly described as the ability to perform repeated short (~3-4 s, 20-30 m) sprints with only brief (~10-30 s) recovery between bouts. Over the past 25 y a plethora of RSA tests have been trialed and reported in the literature. These range from a single set of ~6-10 short sprints, departing every 20-30 s, to team-sport game simulations involving repeating cycles of walk-jog-stride-sprint movements over 45-90 min. Such a wide range of RSA tests has not assisted the synthesis of research findings in this area, and questions remain regarding the optimal methods of training to best improve RSA. In addition, how RSA test scores relate to player "work rate," match performance, or both requires further investigation to improve the application of RSA testing and training to elite team-sport athletes.

  15. Accumulate-Repeat-Accumulate-Accumulate-Codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Dolinar, Sam; Thorpe, Jeremy

    2004-01-01

    Inspired by recently proposed Accumulate-Repeat-Accumulate (ARA) codes [15], in this paper we propose a channel coding scheme called Accumulate-Repeat-Accumulate-Accumulate (ARAA) codes. These codes can be seen as serial turbo-like codes or as a subclass of Low Density Parity Check (LDPC) codes, and they have a projected graph or protograph representation; this allows for a high-speed iterative decoder implementation using belief propagation. An ARAA code can be viewed as a precoded Repeat-and-Accumulate (RA) code with puncturing in concatenation with another accumulator, where simply an accumulator is chosen as the precoder; thus ARAA codes have a very fast encoder structure. Using density evolution on their associated protographs, we find examples of rate-lJ2 ARAA codes with maximum variable node degree 4 for which a minimum bit-SNR as low as 0.21 dB from the channel capacity limit can be achieved as the block size goes to infinity. Such a low threshold cannot be achieved by RA or Irregular RA (IRA) or unstructured irregular LDPC codes with the same constraint on the maximum variable node degree. Furthermore by puncturing the accumulators we can construct families of higher rate ARAA codes with thresholds that stay close to their respective channel capacity thresholds uniformly. Iterative decoding simulation results show comparable performance with the best-known LDPC codes but with very low error floor even at moderate block sizes.

  16. Orthologous repeats and mammalian phylogenetic inference

    PubMed Central

    Bashir, Ali; Ye, Chun; Price, Alkes L.; Bafna, Vineet

    2005-01-01

    Determining phylogenetic relationships between species is a difficult problem, and many phylogenetic relationships remain unresolved, even among eutherian mammals. Repetitive elements provide excellent markers for phylogenetic analysis, because their mode of evolution is predominantly homoplasy-free and unidirectional. Historically, phylogenetic studies using repetitive elements have relied on biological methods such as PCR analysis, and computational inference is limited to a few isolated repeats. Here, we present a novel computational method for inferring phylogenetic relationships from partial sequence data using orthologous repeats. We apply our method to reconstructing the phylogeny of 28 mammals, using more than 1000 orthologous repeats obtained from sequence data available from the NISC Comparative Sequencing Program. The resulting phylogeny has robust bootstrap numbers, and broadly matches results from previous studies which were obtained using entirely different data and methods. In addition, we shed light on some of the debatable aspects of the phylogeny. With rapid expansion of available partial sequence data, computational analysis of repetitive elements holds great promise for the future of phylogenetic inference. PMID:15998912

  17. Repeat Stereotactic Radiosurgery for Acoustic Neuromas

    SciTech Connect

    Kano, Hideyuki; Kondziolka, Douglas; Niranjan, Ajay M.Ch.; Flannery, Thomas J.; Flickinger, John C.; Lunsford, L. Dade

    2010-02-01

    Purpose: To evaluate the outcome of repeat stereotactic radiosurgery (SRS) for acoustic neuromas, we assessed tumor control, clinical outcomes, and the risk of adverse radiation effects in patients whose tumors progressed after initial management. Methods and Materials: During a 21-year experience at our center, 1,352 patients underwent SRS as management for their acoustic neuromas. We retrospectively identified 6 patients who underwent SRS twice for the same tumor. The median patient age was 47 years (range, 35-71 years). All patients had imaging evidence of tumor progression despite initial SRS. One patient also had incomplete surgical resection after initial SRS. All patients were deaf at the time of the second SRS. The median radiosurgery target volume at the time of the initial SRS was 0.5 cc and was 2.1 cc at the time of the second SRS. The median margin dose at the time of the initial SRS was 13 Gy and was 11 Gy at the time of the second SRS. The median interval between initial SRS and repeat SRS was 63 months (range, 25-169 months). Results: At a median follow-up of 29 months after the second SRS (range, 13-71 months), tumor control or regression was achieved in all 6 patients. No patient developed symptomatic adverse radiation effects or new neurological symptoms after the second SRS. Conclusions: With this limited experience, we found that repeat SRS for a persistently enlarging acoustic neuroma can be performed safely and effectively.

  18. Wide-field optical coherence tomography angiography enabled by two repeated measurements of B-scans.

    PubMed

    Wang, Ruikang K; Zhang, Anqi; Choi, Woo June; Zhang, Qinqin; Chen, Chieh-Li; Miller, Andrew; Gregori, Giovanni; Rosenfeld, Philip J

    2016-05-15

    Optical coherence tomography angiography (OCTA) has increasingly become clinically important, particularly in ophthalmology. However, the field of view (FOV) for current OCTA imaging is severely limited due to A-scan rates that can be afforded by current clinical systems and, more importantly, the requirement of a repeated scanning protocol. This Letter evaluates the possibility of using only two repeated B-scans for OCTA for the purpose of an increased FOV. The effect of repeated numbers on the OCTA result is discussed through experiments on an animal model in vivo and evaluated using quantitative metrics for image quality. Demonstrated through in vivo imaging of a pathological human eye, we show that optical microangiography-based OCTA with two repeated B-scans can provide wide-field angiography up to 12×12  mm with clinically acceptable image quality.

  19. Timing of Elective Repeat Cesarean Delivery at Term and Neonatal Outcomes: A Cost Analysis

    PubMed Central

    ROBINSON, Christopher J.; VILLERS, Margaret S.; JOHNSON, Donna D.; SIMPSON, Kit N.

    2011-01-01

    Objective The purpose of this investigation was to examine the economic impact of performing elective repeat cesarean during the 37th or 38th week of gestation relative to the ACOG recommendation of 39 week delivery. Methods Decision analysis modeling was used to estimate economic outcomes for a hypothetical cohort of neonates using data from the NICHD/MFMU study entitled “Timing of elective repeat cesarean delivery at term and neonatal outcomes.” Costs and charges were estimated using the Florida Healthcare Cost and Utilization Project. Results 82,541 deliveries occurring between 37–39 complete weeks gestation were analyzed for the incidence of adverse outcomes and their hospital costs and charges. The model demonstrated increased costs through increasing adverse outcomes among elective repeat cesarean deliveries performed prior to 39 weeks gestation. Conclusion Our findings suggest that there are benefits to waiting until 39 weeks of gestation to perform an elective repeat cesarean delivery. PMID:20435284

  20. A Unified Model for Repeating and Non-repeating Fast Radio Bursts

    NASA Astrophysics Data System (ADS)

    Bagchi, Manjari

    2017-04-01

    The model that fast radio bursts (FRBs) are caused by plunges of asteroids onto neutron stars can explain both repeating and non-repeating bursts. If a neutron star passes through an asteroid belt around another star, there would be a series of bursts caused by a series of asteroid impacts. Moreover, the neutron star would cross the same belt repetitively if it were in a binary with the star hosting the asteroid belt, leading to a repeated series of bursts. I explore the properties of neutron star binaries that could lead to the only known repeating FRB so far (FRB121102). In this model, the next two epochs of bursts are expected around 2017 February 27 and 2017 December 18. On the other hand, if the asteroid belt is located around the neutron star itself, then a chance fall of an asteroid from that belt onto the neutron star would lead to a non-repeating burst. Even a neutron star grazing an asteroid belt can lead to a non-repeating burst caused by just one asteroid plunge during the grazing. This is possible even when the neutron star is in a binary with the asteroid-hosting star, if the belt and the neutron star orbit are non-coplanar.

  1. Analysis of Short Tandem Repeats by Parallel DNA Threading

    PubMed Central

    Zajac, Pawel; Öberg, Christine; Ahmadian, Afshin

    2009-01-01

    The majority of studies employing short tandem repeats (STRs) require investigation of several of these genetic markers. As such, we demonstrate the feasibility of the trinucleotide threading (TnT) approach for scalable analysis of STRs. The TnT method represents a parallel amplification alternative that addresses the obstacles associated with multiplex PCR. In this study, analysis of the STR fragments was performed with capillary gel electrophoresis; however, it should be possible to combine our approach with the massive 454 sequencing platform to considerably increase the number of targeted STRs. PMID:19915680

  2. Approaching infinite temperature upon repeated measurements of a quantum system

    SciTech Connect

    Yi, Juyeon; Talkner, Peter; Ingold, Gert-Ludwig

    2011-09-15

    The influence of repeated projective measurements on the dynamics of the state of a quantum system is studied as a function of the time lag {tau} between successive measurements. In the limit of infinitely many measurements of the occupancy of a single state the total system approaches a uniform state. The asymptotic approach to this state is exponential in the case of finite Hilbert space dimension. The rate characterizing this approach undergoes a sharp transition from a monotonically increasing to an erratically varying function of the time between subsequent measurements.

  3. Repeated mild lateral fluid percussion brain injury in the rat causes cumulative long-term behavioral impairments, neuroinflammation, and cortical loss in an animal model of repeated concussion.

    PubMed

    Shultz, Sandy R; Bao, Feng; Omana, Vanessa; Chiu, Charlotte; Brown, Arthur; Cain, Donald Peter

    2012-01-20

    There is growing evidence that repeated brain concussion can result in cumulative and long-term behavioral symptoms, neuropathological changes, and neurodegeneration. Little is known about the factors and mechanisms that contribute to these effects. The current study addresses the need to investigate and better understand the effects of repeated concussion through the development of an animal model. Male Long-Evans rats received 1, 3, or 5 mild lateral fluid percussion injuries or sham injuries spaced 5 days apart. After the final injury, rats received either a short (24 h) or long (8 weeks) post-injury recovery period, followed by a detailed behavioral analysis consisting of tests for rodent anxiety-like behavior, cognition, social behavior, sensorimotor function, and depression-like behavior. Brains were examined immunohistochemically to assess neuroinflammation and cortical damage. Rats given 1, 3, or 5 mild percussion injuries displayed significant short-term cognitive impairments. Rats given repeated mild percussion injuries displayed significantly worse short- and long-term cognitive impairments. Rats given 5 mild percussion injuries also displayed increased anxiety- and depression-like behaviors. Neuropathological analysis revealed short-term neuroinflammation in 3-injury rats, and both short- and long-term neuroinflammation in 5-injury rats. There was also evidence that repeated injuries induced short- and long-term cortical damage. These cumulative and long-term changes are consistent with findings in human patients suffering repeated brain concussion, provide support for the use of repeated mild lateral fluid percussion injuries to study repeated concussion in the rat, and suggest that neuroinflammation may be important for understanding the cumulative and chronic effects of repeated concussion.

  4. Characteristics of Intergenerational Contractions of the CTG Repeat in Myotonic Dystrophy

    PubMed Central

    Ashizawa, T.; Anvret, M.; Baiget, M.; Barceló, J. M.; Brunner, H.; Cobo, A. M.; Dallapiccola, B.; Fenwick, R. G.; Grandell, U.; Harley, H.; Junien, C.; Koch, M. C.; Korneluk, R. G.; Lavedan, C.; Miki, T.; Mulley, J. C.; de Munain, A. López; Novelli, G.; Roses, A. D.; Seltzer, W. K.; Shaw, D. J.; Smeets, H.; Sutherland, G. R.; Yamagata, H.; Harper, P. S.

    1994-01-01

    In myotonic dystrophy (DM), the size of a CTG repeat in the DM kinase gene generally increases in successive generations with clinical evidence of anticipation. However, there have also been cases with an intergenerational contraction of the repeat. We examined 1,489 DM parent-offspring pairs, of which 95 (6.4%) showed such contractions in peripheral blood leukocytes (PBL). In 56 of the 95 pairs, clinical data allowed an analysis of their anticipation status. It is surprising that anticipation occurred in 27 (48%) of these 56 pairs, while none clearly showed a later onset of DM in the symptomatic offspring. The contraction occurred in 76 (10%) of 753 paternal transmissions and in 19 (3%) of 736 maternal transmissions. Anticipation was observed more frequently in maternal (85%) than in paternal (37%) transmissions (P < .001). The parental repeat size correlated with the size of intergenerational contraction (r2 = .50, P « .001), and the slope of linear regression was steeper in paternal (–.62) than in maternal (–.30) transmissions (P « .001). Sixteen DM parents had multiple DM offspring with the CTG repeat contractions. This frequency was higher than the frequency expected from the probability of the repeat contractions (6.4%) and the size of DM sib population (1.54 DM offspring per DM parent, in 968 DM parents). We conclude that (1) intergenerational contraction of the CTG repeat in leukocyte DNA frequently accompanies apparent anticipation, especially when DM is maternally transmitted, and (2) the paternal origin of the repeat and the presence of the repeat contraction in a sibling increase the probability of the CTG repeat contraction. PMID:8116611

  5. Sensitization of locomotion following repeated ventral tegmental injections of cytisine.

    PubMed

    Museo, E; Wise, R A

    1994-06-01

    Systemic injections of nicotine increase locomotion, and repeating these injections brings about a sensitization of the locomotor response. Ventral tegmental injections of the nicotinic agonist cytisine also increase locomotion. In the present study cytisine was administered repeatedly into the ventral tegmentum to determine whether sensitization of its locomotor-activating effects would develop. Four groups of animals were tested; each group received a total of six injections at a rate of one injection every 48 h. Two of these groups received injections of cytisine (10 nmol/side): one group received injections into the ventral tegmentum, and, to insure the anatomical specificity of the locomotor effect, a second group received injections dorsal to the ventral tegmentum. The remaining two groups received vehicle injections: one group received injections into the ventral tegmentum, and the other received injections into more dorsal sites. The group of animals that received injections of cytisine into the ventral tegmentum locomoted more than any other group. In addition, only with this group was a progressive increase in the locomotor response evident across test days. These findings raise the possibility that a neural substrate in the ventral tegmentum mediates the locomotor-activating and sensitizing effects associated with the systemic administration of nicotine.

  6. Effects of repeated baking on the mechanical and physical properties of metal-ceramic systems.

    PubMed

    Nagasawa, Sakae; Yoshida, Takamitsu; Mizoguchi, Toshihide; Terashima, Nobuyoshi; Kamijyo, Kuni; Ito, Michio; Oshida, Yoshiki

    2004-06-01

    This study evaluates effects of repeated baking processes on the mechanical and physical properties of single and triple applications of opaque, body and enamel porcelains fused to three different metal substrates (precious metal, semi-precious metal and non-precious metal). The vintage halo porcelain system was employed and fused to metals. Fused samples were subjected to three-point bend tests to evaluate bend strength and modulus of elasticity. It was found that, by increasing repeated baking cycles, (1) body and enamel porcelains increased bend strengths but opaque porcelain did not show any changes, (2) all triple-layered porcelains fired to metals increased bend strengths, and (3) all three porcelains and metal substrates did not exhibit changes in thermal expansion percentage. It was concluded that repeating baking procedures up to 10 cycles did not exhibit any adverse effects on the final properties of porcelain-fired to metals, rather it was noticed that mechanical strengths increased by increasing cycles.

  7. Antenatal Corticosteroids for Preterm Premature Rupture of Membranes: Single or Repeat Course?

    PubMed Central

    Brookfield, Kathleen F.; El-Sayed, Yasser Y.; Chao, Lisa; Berger, Victoria; Naqvi, Mariam; Butwick, Alexander J.

    2015-01-01

    Objective The aim of this article is to determine the risk of maternal chorioamnionitis and neonatal morbidity in women with preterm premature rupture of membranes (PPROM) exposed to one corticosteroid course versus a single repeat corticosteroid steroid course. Study Design Secondary analysis of a cohort of women with singleton pregnancies and PPROM. The primary outcome was a clinical diagnosis of maternal chorioamnionitis. Using multivariate logistic regression, we controlled for maternal age, race, body mass index, diabetes, gestational age at membrane rupture, preterm labor, and antibiotic administration. Neonatal morbidities were compared between groups controlling for gestational age at delivery. Results Of 1,652 women with PPROM, 1,507 women received one corticosteroid course and 145 women received a repeat corticosteroid course. The incidence of chorioamnionitis was similar between groups (single course = 12.3% vs. repeat course = 11.0%; p = 0.8). Women receiving a repeat corticosteroid course were not at increased risk of chorioamnionitis (adjusted odds ratio, 1.28; 95% confidence interval, 0.69–2.14). A repeat course of steroids was not associated with an increased risk of any neonatal morbidity. Conclusion Compared with a single steroid course, our findings suggest that the risk of maternal chorioamnionitis or neonatal morbidity may not be increased for women with PPROM receiving a repeat corticosteroid course. PMID:25545441

  8. C9orf72 hypermethylation protects against repeat expansion-associated pathology in ALS/FTD.

    PubMed

    Liu, Elaine Y; Russ, Jenny; Wu, Kathryn; Neal, Donald; Suh, Eunran; McNally, Anna G; Irwin, David J; Van Deerlin, Vivianna M; Lee, Edward B

    2014-10-01

    Hexanucleotide repeat expansions of C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal degeneration. The mutation is associated with reduced C9orf72 expression and the accumulation of potentially toxic RNA and protein aggregates. CpG methylation is known to protect the genome against unstable DNA elements and to stably silence inappropriate gene expression. Using bisulfite cloning and restriction enzyme-based methylation assays on DNA from human brain and peripheral blood, we observed CpG hypermethylation involving the C9orf72 promoter in cis to the repeat expansion mutation in approximately one-third of C9orf72 repeat expansion mutation carriers. Promoter hypermethylation of mutant C9orf72 was associated with transcriptional silencing of C9orf72 in patient-derived lymphoblast cell lines, resulting in reduced accumulation of intronic C9orf72 RNA and reduced numbers of RNA foci. Furthermore, demethylation of mutant C9orf72 with 5-aza-deoxycytidine resulted in increased vulnerability of mutant cells to oxidative and autophagic stress. Promoter hypermethylation of repeat expansion carriers was also associated with reduced accumulation of RNA foci and dipeptide repeat protein aggregates in human brains. These results indicate that C9orf72 promoter hypermethylation prevents downstream molecular aberrations associated with the hexanucleotide repeat expansion, suggesting that epigenetic silencing of the mutant C9orf72 allele may represent a protective counter-regulatory response to hexanucleotide repeat expansion.

  9. Myotonic dystrophy type 1 patient-derived iPSCs for the investigation of CTG repeat instability

    PubMed Central

    Ueki, Junko; Nakamori, Masayuki; Nakamura, Masahiro; Nishikawa, Misato; Yoshida, Yoshinori; Tanaka, Azusa; Morizane, Asuka; Kamon, Masayoshi; Araki, Toshiyuki; Takahashi, Masanori P.; Watanabe, Akira; Inagaki, Nobuya; Sakurai, Hidetoshi

    2017-01-01

    Myotonic dystrophy type 1 (DM1) is an autosomal-dominant multi-system disease caused by expanded CTG repeats in dystrophia myotonica protein kinase (DMPK). The expanded CTG repeats are unstable and can increase the length of the gene with age, which worsens the symptoms. In order to establish a human stem cell system suitable for the investigation of repeat instability, DM1 patient-derived iPSCs were generated and differentiated into three cell types commonly affected in DM1, namely cardiomyocytes, neurons and myocytes. Then we precisely analysed the CTG repeat lengths in these cells. Our DM1-iPSCs showed a gradual lengthening of CTG repeats with unchanged repeat distribution in all cell lines depending on the passage numbers of undifferentiated cells. However, the average CTG repeat length did not change significantly after differentiation into different somatic cell types. We also evaluated the chromatin accessibility in DM1-iPSCs using ATAC-seq. The chromatin status in DM1 cardiomyocytes was closed at the DMPK locus as well as at SIX5 and its promoter region, whereas it was open in control, suggesting that the epigenetic modifications may be related to the CTG repeat expansion in DM1. These findings may help clarify the role of repeat instability in the CTG repeat expansion in DM1. PMID:28211918

  10. Repeat-mediated epigenetic dysregulation of the FMR1 gene in the fragile X-related disorders.

    PubMed

    Usdin, Karen; Kumari, Daman

    2015-01-01

    The fragile X-related disorders are members of the Repeat Expansion Diseases, a group of genetic conditions resulting from an expansion in the size of a tandem repeat tract at a specific genetic locus. The repeat responsible for disease pathology in the fragile X-related disorders is CGG/CCG and the repeat tract is located in the 5' UTR of the FMR1 gene, whose protein product FMRP, is important for the proper translation of dendritic mRNAs in response to synaptic activation. There are two different pathological FMR1 allele classes that are distinguished only by the number of repeats. Premutation alleles have 55-200 repeats and confer risk of fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency. Full mutation alleles on the other hand have >200 repeats and result in fragile X syndrome, a disorder that affects learning and behavior. Different symptoms are seen in carriers of premutation and full mutation alleles because the repeat number has paradoxical effects on gene expression: Epigenetic changes increase transcription from premutation alleles and decrease transcription from full mutation alleles. This review will cover what is currently known about the mechanisms responsible for these changes in FMR1 expression and how they may relate to other Repeat Expansion Diseases that also show repeat-mediated changes in gene expression.

  11. Repeatability of a running heat tolerance test.

    PubMed

    Mee, Jessica A; Doust, Jo; Maxwell, Neil S

    2015-01-01

    At present there is no standardised heat tolerance test (HTT) procedure adopting a running mode of exercise. Current HTTs may misdiagnose a runner's susceptibility to a hyperthermic state due to differences in exercise intensity. The current study aimed to establish the repeatability of a practical running test to evaluate individual's ability to tolerate exercise heat stress. Sixteen (8M, 8F) participants performed the running HTT (RHTT) (30 min, 9 km h(-1), 2% elevation) on two separate occasions in a hot environment (40 °C and 40% relative humidity). There were no differences in peak rectal temperature (RHTT1: 38.82 ± 0.47 °C, RHTT2: 38.86 ± 0.49 °C, Intra-class correlation coefficient (ICC)=0.93, typical error of measure (TEM) = 0.13 °C), peak skin temperature (RHTT1: 38.12 ± 0.45, RHTT2: 38.11 ± 0.45 °C, ICC = 0.79, TEM = 0.30 °C), peak heart rate (RHTT1: 182 ± 15 beats min(-1), RHTT2: 183 ± 15 beats min(-1), ICC = 0.99, TEM = 2 beats min(-1)), nor sweat rate (1721 ± 675 g h(-1), 1716 ± 745 g h(-1), ICC = 0.95, TEM = 162 g h(-1)) between RHTT1 and RHTT2 (p>0.05). Results demonstrate good agreement, strong correlations and small differences between repeated trials, and the TEM values suggest low within-participant variability. The RHTT was effective in differentiating between individuals physiological responses; supporting a heat tolerance continuum. The findings suggest the RHTT is a repeatable measure of physiological strain in the heat and may be used to assess the effectiveness of acute and chronic heat alleviating procedures.

  12. Are all repeats created equal? Understanding DNA repeats at an individual level.

    PubMed

    Yang, Jinpu; Li, Fei

    2017-02-01

    Repetitive DNA sequences, comprising up to 50 % of the genome in all eukaryotes, play important roles in a wide range of cellular functions, such as transcriptional regulation, genome stability, and cellular differentiation. However, due to technical difficulties in differentiating their sequences, DNA repeats remain one of the most mysterious parts of eukaryotic genomes. Key questions, such as how repetitive entities behave at individual level and how the internal architecture of these repeats is organized, are still poorly understood. Recent advances from our group reveal unexpected position-dependent variation within tandem DNA repeats in fission yeast. Despite sharing identical DNA sequences, the peri-centromeric repeats are organized into diverse epigenetic states and chromatin structures. We demonstrate that this position-dependent variation requires key heterochromatin factors and condensin. Our works further suggest that the peri-centromeric repeats are organized into distinct higher order structures that ensure a proper positioning of CENP-A, the centromere-specific histone H3 variant, to centromeres. These most recent developments offer insights into the mechanisms underlying the position effect within tandem DNA arrays, and have broad implications in the field of epigenetics and chromatin biology.

  13. Repeats identification using improved suffix trees.

    PubMed

    Huo, Hongwei; Wang, Xiaowu; Stojkovic, Vojislav

    2009-01-01

    The suffix tree data structure plays an important role in the efficient implementations of some querying algorithms. This paper presents the fast Rep(eats)Seeker algorithm for repeats identification based on the improvements of suffix tree construction. The leaf nodes and the branch nodes are numbered in different ways during the construction of a suffix tree and extra information is added to the branch nodes. The experimental results show that improvements reduce the running time of the RepSeeker algorithm without losing the accuracy. The experimental results coincide with the theoretical expectations.

  14. Distillation by repeated measurements: Continuous spectrum case

    SciTech Connect

    Bellomo, Bruno; Compagno, Giuseppe; Nakazato, Hiromichi; Yuasa, Kazuya

    2010-12-15

    Repeated measurements on one part of a bipartite system strongly affect the other part that is not measured, the dynamics of which is regulated by an effective contracted evolution operator. When the spectrum of this operator is discrete, the nonmeasured system is driven into a pure state, irrespective of the initial state, provided that the spectrum satisfies certain conditions. We show here that, even in the case of continuous spectrum, an effective distillation can occur under rather general conditions. We confirm it by applying our formalism to a simple model.

  15. Platelet peripheral benzodiazepine receptors in repeated stress

    SciTech Connect

    Dar, D.E.; Bidder, M.; Gavish, M. ); Weizman, A.; Karp, L.; Tyano, S. ); Grinshpoon, A.; Bleich, A.

    1991-01-01

    ({sup 3}H)PK 11195 binding to platelet membranes and plasma stress hormones were studied in soldiers at the beginning of a parachute training course, following 6 days of preparatory exercises, and after the fourth actual parachute jump. A slight reduction (15%; NS) in the number of peripheral benzodiazepine receptors (PBR) was detected at the end of the exercise period, prior to the first jump. Reduced density of PBR was observed immediately after the repeated actual jumps. Equilibrium dissociation constants were not affected by the stressful situation. Plasma cortisol and prolactin levels remained unaltered during the entire study period.

  16. Platelet peripheral benzodiazepine receptors in repeated stress.

    PubMed

    Dar, D E; Weizman, A; Karp, L; Grinshpoon, A; Bidder, M; Kotler, M; Tyano, S; Bleich, A; Gavish, M

    1991-01-01

    [3H]PK 11195 binding to platelet membranes and plasma stress hormones were studied in soldiers at the beginning of a parachute training course, following 6 days of preparatory exercises, and after the fourth actual parachute jump. A slight reduction (15%; NS) in the number of peripheral benzodiazepine receptors (PBR) was detected at the end of the exercise period, prior to the first jump. Reduced (26%; P less than 0.05) density of PBR was observed immediately after the repeated actual jumps. Equilibrium dissociation constants were not affected by the stressful situation. Plasma cortisol and prolactin levels remained unaltered during the entire study period.

  17. Relationship of social support and social burden to repeated breast cancer screening in the women's health initiative.

    PubMed

    Messina, Catherine R; Lane, Dorothy S; Glanz, Karen; West, Delia Smith; Taylor, Vicky; Frishman, William; Powell, Lynda

    2004-11-01

    Direct and interactive effects of social support, social burden (caregiving, negative life events, and social strain), education, and income on repeated use of breast cancer screening among a large (N=55,278), national sample of postmenopausal women participating in the Women's Health Initiative observational study were examined. Repeated screening decreased as emotional/informational support and positive social interactions decreased (ps<.01). Repeated mammography decreased with frequent caregiving (p<.01). Less social strain reduced the frequency of repeated breast self-examinations (BSEs; ps<.01), but frequent caregiving and more negative life events increased repeated use of BSE (ps<.01). Interactive effects suggested that emotional/informational but not tangible support is associated with repeated mammography and clinical breast examinations (ps<.01) and may be particularly important among low-income older women, especially those burdened by caregiving.

  18. Brokering as a framework for hydrological model repeatability

    NASA Astrophysics Data System (ADS)

    Fuka, Daniel; Collick, Amy; MacAlister, Charlotte; Braeckel, Aaron; Wright, Dawn; Jodha Khalsa, Siri; Boldrini, Enrico; Easton, Zachary

    2015-04-01

    Data brokering aims to provide those in the the sciences with quick and repeatable access to data that represents physical, biological, and chemical characteristics; specifically to accelerate scientific discovery. Environmental models are useful tools to understand the behavior of hydrological systems. Unfortunately, parameterization of these hydrological models requires many different data, from different sources, and from different disciplines (e.g., atmospheric, geoscience, ecology). In basin scale hydrological modeling, the traditional procedure for model initialization starts with obtaining elevation models, land-use characterizations, soils maps, and weather data. It is often the researcher's past experience with these datasets that determines which datasets will be used in a study, and often newer, or more suitable data products will exist. An added complexity is that various science communities have differing data formats, storage protocols, and manipulation methods, which makes use by a non native user exceedingly difficult and time consuming. We demonstrate data brokering as a means to address several of these challenges. We present two test case scenarios in which researchers attempt to reproduce hydrological model results using 1) general internet based data gathering techniques, and 2) a scientific data brokering interface. We show that data brokering can increase the efficiency with which data are obtained, models are initialized, and results are analyzed. As an added benefit, it appears brokering can significantly increase the repeatability of a given study.

  19. Analysis of the repeatability of time-lapse 3d vsp multicomponent surveys, delhi field

    NASA Astrophysics Data System (ADS)

    Carvalho, Mariana Fernandes de

    Delhi Field is a producing oil field located in northeastern Louisiana. In order to monitor the CO2 sweep efficiency, time-lapse 3D seismic data have been acquired in this area. Time-lapse studies are increasingly used to evaluate changes in the seismic response induced by the production of hydrocarbons or the injection of water, CO2 or steam into a reservoir. A 4D seismic signal is generated by a combination of production and injection effects within the reservoir as well as non-repeatability effects. In order to get reliable results from time-lapse seismic methods, it is important to distinguish the production and injection effects from the non-repeatability effects in the 4D seismic signal. Repeatability of 4D land seismic data is affected by several factors. The most significant of them are: source and receiver geometry inaccuracies, differences in seismic sources signatures, variations in the immediate near surface and ambient non-repeatable noise. In this project, two 3D multicomponent VSP surveys acquired in Delhi Field were used to quantify the relative contribution of each factor that can affect the repeatability in land seismic data. The factors analyzed in this study were: source and receiver geometry inaccura- cies, variations in the immediate near surface and ambient non-repeatable noise. This study showed that all these factors had a significant impact on the repeatability of the successive multicomponent VSP surveys in Delhi Field. This project also shows the advantages and disadvantages in the use of different repeata- bility metrics, normalized-root-mean-square (NRMS) difference and signal-to-distortion ratio (SDR) attribute, to evaluate the level of seismic repeatability between successive time-lapse seismic surveys. It is observed that NRMS difference is greatly influenced by time-shifts and that SDR attribute combined with the time-shift may give more distinct and representative repeatability information than the NRMS difference.

  20. Hybrid de novo tandem repeat detection using short and long reads

    PubMed Central

    2015-01-01

    Background As one of the most studied genome rearrangements, tandem repeats have a considerable impact on genetic backgrounds of inherited diseases. Many methods designed for tandem repeat detection on reference sequences obtain high quality results. However, in the case of a de novo context, where no reference sequence is available, tandem repeat detection remains a difficult problem. The short reads obtained with the second-generation sequencing methods are not long enough to span regions that contain long repeats. This length limitation was tackled by the long reads obtained with the third-generation sequencing platforms such as Pacific Biosciences technologies. Nevertheless, the gain on the read length came with a significant increase of the error rate. The main objective of nowadays studies on long reads is to handle the high error rate up to 16%. Methods In this paper we present MixTaR, the first de novo method for tandem repeat detection that combines the high-quality of short reads and the large length of long reads. Our hybrid algorithm uses the set of short reads for tandem repeat pattern detection based on a de Bruijn graph. These patterns are then validated using the long reads, and the tandem repeat sequences are constructed using local greedy assemblies. Results MixTaR is tested with both simulated and real reads from complex organisms. For a complete analysis of its robustness to errors, we use short and long reads with different error rates. The results are then analysed in terms of number of tandem repeats detected and the length of their patterns. Conclusions Our method shows high precision and sensitivity. With low false positive rates even for highly erroneous reads, MixTaR is able to detect accurate tandem repeats with pattern lengths varying within a significant interval. PMID:26399998

  1. Length-dependent CTG·CAG triplet-repeat expansion in myotonic dystrophy patient-derived induced pluripotent stem cells

    PubMed Central

    Du, Jintang; Campau, Erica; Soragni, Elisabetta; Jespersen, Christine; Gottesfeld, Joel M.

    2013-01-01

    Myotonic dystrophy type 1 (DM1) is an inherited dominant muscular dystrophy caused by expanded CTG·CAG triplet repeats in the 3′ untranslated region of the DMPK1 gene, which produces a toxic gain-of-function CUG RNA. It has been shown that the severity of disease symptoms, age of onset and progression are related to the length of the triplet repeats. However, the mechanism(s) of CTG·CAG triplet-repeat instability is not fully understood. Herein, induced pluripotent stem cells (iPSCs) were generated from DM1 and Huntington's disease patient fibroblasts. We isolated 41 iPSC clones from DM1 fibroblasts, all showing different CTG·CAG repeat lengths, thus demonstrating somatic instability within the initial fibroblast population. During propagation of the iPSCs, the repeats expanded in a manner analogous to the expansion seen in somatic cells from DM1 patients. The correlation between repeat length and expansion rate identified the interval between 57 and 126 repeats as being an important length threshold where expansion rates dramatically increased. Moreover, longer repeats showed faster triplet-repeat expansion. However, the overall tendency of triplet repeats to expand ceased on differentiation into differentiated embryoid body or neurospheres. The mismatch repair components MSH2, MSH3 and MSH6 were highly expressed in iPSCs compared with fibroblasts, and only occupied the DMPK1 gene harboring longer CTG·CAG triplet repeats. In addition, shRNA silencing of MSH2 impeded CTG·CAG triplet-repeat expansion. The information gained from these studies provides new insight into a general mechanism of triplet-repeat expansion in iPSCs. PMID:23933738

  2. An isoform of microtubule-associated protein 2 (MAP2) containing four repeats of the tubulin-binding motif.

    PubMed

    Doll, T; Meichsner, M; Riederer, B M; Honegger, P; Matus, A

    1993-10-01

    Microtubule-associated protein 2 (MAP2) exists in both high- and low-molecular mass isoforms, each of which has a tubulin-binding domain consisting of 3 imperfect tandem repeats of 31 amino acids containing a more highly conserved 18 amino acid 'core' sequence. We describe here a novel form of low molecular mass MAP2 (MAP2c) that contains an additional 4th repeat of this tubulin-binding motif. Like the 3 previously known repeat sequences, this 4th copy is highly conserved between MAP2 and the two other known members of the same gene family, tau and MAP4. In each of these three genes the additional 4th repeat is inserted between the 1st and 2nd repeats of the 3-repeat form of the molecule. Experiments with brain cell cultures, in which the relative proportions of neurons and glia had been manipulated by drug treatment, showed that 4-repeat MAP2c is associated with glial cells whereas 3-repeat MAP2c is expressed in neurons. Whereas 3-repeat MAP2c is expressed early in development and then declines, the level of 4-repeat MAP2c increases later in development, corresponding to the relatively late differentiation of glial cells compared to neurons. When transfected into non-neuronal cells, the 4-repeat version of MAP2c behaved indistinguishably from the 3-repeat form in stabilising and rearranging cellular microtubules. The presence of an additional 4th repeat of the tubulin-binding motif in all three members of the MAP2 gene family suggests that this variant arose prior to their differentiation from an ancestral gene.

  3. Changes in meat quality of ovine longissimus dorsi muscle in response to repeated freeze and thaw.

    PubMed

    Qi, Jun; Li, Chunbao; Chen, Yinji; Gao, Feifei; Xu, Xinglian; Zhou, Guanghong

    2012-12-01

    Changes in eating and technological quality attributes of ovine longissimus dorsi muscle during repeated freeze and thaw were investigated. Shear force value, L* value, a* value and fiber diameter decreased (P<0.05) but lipid oxidation increased (P<0.05) with repeated freeze-thaw cycles. Sarcomere length and pH decreased (P<0.05) within the first 10 freeze-thaw cycles but increased (P<0.05) after 5 further cycles. Total and myofibrillar protein solubility, and intramuscular free fatty acids concentration decreased (P<0.05) after 1 cycle of freeze and thaw but then increased (P<0.05) gradually with further cycles. Hardness, chewiness, cohesiveness and resilience of comminuted lamb products decreased (P<0.05) with increased freeze-thaw cycles. And therefore, repeated freeze and thaw should be minimized in terms of meat color for commercial value and water holding capacity for further processing.

  4. Enhancement of Odor Sensitivity Following Repeated Odor and Visual Fear Conditioning.

    PubMed

    Parma, Valentina; Ferraro, Stefania; Miller, Stacie S; Åhs, Fredrik; Lundström, Johan N

    2015-09-01

    Odor detection sensitivity can be rapidly altered by fear conditioning; whether this effect is augmented over time is not known. The present study aimed to test whether repeated conditioning sessions induce changes in odor detection threshold as well as in conditioned responses and whether olfactory stimuli evoke stronger conditioned responses than visual stimuli. The repeated conditioning group participated in repeated sessions over 2 weeks whereas the single conditioning group participated in 1 conditioning session; both groups were presented with visual and olfactory stimuli, were paired with an electric shock (CS+) and 2 matched control stimuli not paired with shock (CS-) while olfactory detection threshold and skin conductance responses (SCRs) were measured before and after the last session. We found increased sensitivity for the CS+ odor in the repeated but not in the single conditioning group, consistent with changes in olfactory sensitivity following repeated aversive learning and of a similar magnitude to what has previously been demonstrated in the periphery. SCR to the visual and olfactory CS+ were similar between groups, indicating that sensory thresholds can change without corresponding change in conditioned responses. In conclusion, repeated conditioning increases detection sensitivity and reduces conditioned responses, suggesting that segregated processes influence perception and conditioned responses.

  5. Distributed parameter modeling of repeated truss structures

    NASA Technical Reports Server (NTRS)

    Wang, Han-Ching

    1994-01-01

    A new approach to find homogeneous models for beam-like repeated flexible structures is proposed which conceptually involves two steps. The first step involves the approximation of 3-D non-homogeneous model by a 1-D periodic beam model. The structure is modeled as a 3-D non-homogeneous continuum. The displacement field is approximated by Taylor series expansion. Then, the cross sectional mass and stiffness matrices are obtained by energy equivalence using their additive properties. Due to the repeated nature of the flexible bodies, the mass, and stiffness matrices are also periodic. This procedure is systematic and requires less dynamics detail. The first step involves the homogenization from a 1-D periodic beam model to a 1-D homogeneous beam model. The periodic beam model is homogenized into an equivalent homogeneous beam model using the additive property of compliance along the generic axis. The major departure from previous approaches in literature is using compliance instead of stiffness in homogenization. An obvious justification is that the stiffness is additive at each cross section but not along the generic axis. The homogenized model preserves many properties of the original periodic model.

  6. Analysis of a random repeated impact process

    NASA Astrophysics Data System (ADS)

    Wood, L. A.; Byrne, K. P.

    1981-10-01

    A simple random repeated impact process similar to the classical random walk process is analyzed. The process, which consists of a ball bouncing on a randomly vibrating surface, is analogous to loss-of-contact situations which can occur in linkages and vibrating tools. It also has relevance to rolling contact where the rolling element may separate from the surface and sustain repeated impacts. A coefficient of restitution is used to describe impact, and some important assumptions limit the analysis to values of this coefficient greater than 0°8. The Markov nature of the process is demonstrated by its one-step "memory". It may be regarded as a discrete Markov process "imbedded" in continuous time. A difference equation governing the process is developed and analyzed for the case where the vibrating surface has a Gaussian distribution of velocities. With the one-step transition probability density function a linear weighting function is used to account for the weighting effect of the ball's velocity on the distribution of table velocities at impact. The resulting integral equation is solved iteratively to yield the probability density function of ball velocities after impact. This information may then be used to predict the magnitudes of the impacts and the time between them.

  7. Repeated proton beam therapy for hepatocellular carcinoma

    SciTech Connect

    Hashimoto, Takayuki |. E-mail: hashimoto@pmrc.tsukuba.ac.jp; Tokuuye, Koichi |; Fukumitsu, Nobuyoshi |; Igaki, Hiroshi |; Hata, Masaharu |; Kagei, Kenji |; Sugahara, Shinji; Ohara, Kiyoshi; Matsuzaki, Yasushi; Akine, Yasuyuki |

    2006-05-01

    Purpose: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC). Methods and Materials: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively. Results: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure. Conclusions: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A.

  8. Airborne Radar Interferometric Repeat-Pass Processing

    NASA Technical Reports Server (NTRS)

    Hensley, Scott; Michel, Thierry R.; Jones, Cathleen E.; Muellerschoen, Ronald J.; Chapman, Bruce D.; Fore, Alexander; Simard, Marc; Zebker, Howard A.

    2011-01-01

    Earth science research often requires crustal deformation measurements at a variety of time scales, from seconds to decades. Although satellites have been used for repeat-track interferometric (RTI) synthetic-aperture-radar (SAR) mapping for close to 20 years, RTI is much more difficult to implement from an airborne platform owing to the irregular trajectory of the aircraft compared with microwave imaging radar wavelengths. Two basic requirements for robust airborne repeat-pass radar interferometry include the ability to fly the platform to a desired trajectory within a narrow tube and the ability to have the radar beam pointed in a desired direction to a fraction of a beam width. Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) is equipped with a precision auto pilot developed by NASA Dryden that allows the platform, a Gulfstream III, to nominally fly within a 5 m diameter tube and with an electronically scanned antenna to position the radar beam to a fraction of a beam width based on INU (inertial navigation unit) attitude angle measurements.

  9. IMHEX fuel cell repeat component manufacturing continuous improvement accomplishments

    SciTech Connect

    Jakaitis, L.A.; Petraglia, V.J.; Bryson, E.S.

    1996-12-31

    M-C Power is taking a power generation technology that has been proven in the laboratory and is making it a commercially competitive product. There are many areas in which this technology required scale up and refinement to reach the market entry goals for the IMHEX{reg_sign} molten carbonate fuel cell power plant. One of the primary areas that needed to be addressed was the manufacturing of the fuel cell stack. Up to this point, the fuel cell stack and associated components were virtually hand made for each system to be tested. M-C Power has now continuously manufactured the repeat components for three 250 kW stacks. M-C Power`s manufacturing strategy integrated both evolutionary and revolutionary improvements into its comprehensive commercialization effort. M-C Power`s objectives were to analyze and continuously improve stack component manufacturing and assembly techniques consistent with established specifications and commercial scale production requirements. Evolutionary improvements are those which naturally occur as the production rates are increased and experience is gained. Examples of evolutionary (learning curve) improvements included reducing scrap rates and decreasing raw material costs by buying in large quantities. Revolutionary improvements result in significant design and process changes to meet cost and performance requirements of the market entry system. Revolutionary changes often involve identifying new methods and developing designs to accommodate the new process. Based upon our accomplishments, M-C Power was able to reduce the cost of continuously manufactured fuel cell repeat components from the first to third 250 kW stack by 63%. This paper documents the continuous improvement accomplishments realized by M-C Power during IMHEX{reg_sign} fuel cell repeat component manufacturing.

  10. Hyperventilation as a strategy for improved repeated sprint performance.

    PubMed

    Sakamoto, Akihiro; Naito, Hisashi; Chow, Chin-Moi

    2014-04-01

    Repeated high-intensity sprints incur substantial anaerobic metabolic challenges and create an acidic muscle milieu that is unfavorable for subsequent performance. Hyperventilation, resulting in respiratory alkalosis, acts as a compensatory mechanism for metabolic acidosis. This study tested the hypothesis that hyperventilation performed during recovery intervals would attenuate performance decrement in repeated sprint pedaling. Thirteen male university athletes performed 10 sets of 10-second maximal pedaling on a cycle ergometer with a 60-second recovery between sets under control (spontaneous breathing) and hyperventilation conditions in a crossover counter-balanced manner. Pedaling load was set at 0.075 × body mass. Peak and mean power outputs were documented for each set to compare performance decrements for 10 sets between conditions. Hyperventilation (60 breaths per minute and end-tidal partial pressure of CO2 maintained at 20-25 mm Hg) was performed 30 seconds before each sprint set. This intervention successfully increased blood pH by 0.03-0.07 but lowered P(CO2) by 1.2-8.4 mm Hg throughout exercise (p < 0.001). The peak and mean power outputs, and blood [La] accumulation were not significantly different between the conditions. However, a significant condition × time interaction existed for peak power (p = 0.035) and mean power (p = 0.023), demonstrating an attenuation in power decrement in later sprint sets with hyperventilation. In conclusion, hyperventilation implemented during recovery intervals of repeated sprint pedaling attenuated performance decrements in later exercise bouts that was associated with substantial metabolic acidosis. The practical implication is that hyperventilation may have a strategic role for enhancing training effectiveness and may give an edge in performance outcomes.

  11. Transient CNS responses to repeated binge ethanol treatment

    PubMed Central

    Zahr, Natalie M; Rohlfing, Torsten; Mayer, Dirk; Luong, Richard; Sullivan, Edith V; Pfefferbaum, Adolf

    2016-01-01

    Adaptive changes occur in response to repeated exposure to drugs. Although ethanol (EtOH) is known to induce pharmacokinetic tolerance, the effects of EtOH on in vivo, magnetic resonance (MR)-detectable brain measures across repeated exposures have not previously been reported. Of 28 rats weighing 341±22g at baseline, 15 were assigned to the EtOH group and 13 to the control (Ctrl) group. EtOH animals were exposed to 5 cycles of 4-days of EtOH treatment followed by 10 days of recovery. Rats in both groups had structural MR imaging (MRI) scans and whole brain MR spectroscopy (MRS) at baseline, immediately following each binge period, and after each recovery period (total=11 MR scans per rat). Average blood alcohol levels (BALs) across each of the 5, 4-day binge periods were 298, 300, 301, 312, 318 mg/dL. Cerebrospinal fluid (CSF) volumes of the lateral ventricles and cisterns showed enlargement with each binge EtOH exposure but recovery with each abstinence period. Similarly, changes to MRS metabolites were transient: levels of N-acetyl aspartate (NAA) and total creatine (tCr) decreased, while those of choline-containing compounds (Cho) and glutamate/glutamine (Glx) increased with each binge EtOH exposure cycle, but also recovered during each abstinence period. The directionality of changes in response to EtOH were in expected directions based on previous, single-binge EtOH exposure experiments, but the current results do not provide support for accruing pathology with repeated binge EtOH exposure. PMID:26283309

  12. Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation

    SciTech Connect

    Mathew, Sherin T.; Bergström, Petra; Hammarsten, Ola

    2014-05-01

    Most of the cytotoxicity induced by ionizing radiation is mediated by radical-induced DNA double-strand breaks. Cellular protection from free radicals can be stimulated several fold by sulforaphane-mediated activation of the transcription factor Nrf2 that regulates more than 50 genes involved in the detoxification of reactive substances and radicals. Here, we report that repeated sulforaphane treatment increases radioresistance in primary human skin fibroblasts. Cells were either treated with sulforaphane for four hours once or with four-hour treatments repeatedly for three consecutive days prior to radiation exposure. Fibroblasts exposed to repeated-sulforaphane treatment showed a more pronounced dose-dependent induction of Nrf2-regulated mRNA and reduced amount of radiation-induced free radicals compared with cells treated once with sulforaphane. In addition, radiation- induced DNA double-strand breaks measured by gamma-H2AX foci were attenuated following repeated sulforaphane treatment. As a result, cellular protection from ionizing radiation measured by the 5-ethynyl-2′-deoxyuridine (EdU) assay was increased, specifically in cells exposed to repeated sulforaphane treatment. Sulforaphane treatment was unable to protect Nrf2 knockout mouse embryonic fibroblasts, indicating that the sulforaphane-induced radioprotection was Nrf2-dependent. Moreover, radioprotection by repeated sulforaphane treatment was dose-dependent with an optimal effect at 10 uM, whereas both lower and higher concentrations resulted in lower levels of radioprotection. Our data indicate that the Nrf2 system can be trained to provide further protection from radical damage. - Highlights: • Repeated treatment with sulforaphane protects fibroblasts from ionizing radiation • Repeated sulforaphane treatment attenuates radiation induced ROS and DNA damage • Sulforaphane mediated protection is Nrf2 dependent.

  13. COPASAAR – A database for proteomic analysis of single amino acid repeats

    PubMed Central

    Depledge, Daniel P; Dalby, Andrew R

    2005-01-01

    Background Single amino acid repeats make up a significant proportion in all of the proteomes that have currently been determined. They have been shown to be functionally and medically significant, and are associated with cancers and neuro-degenerative diseases such as Huntington's Chorea, where a poly-glutamine repeat is responsible for causing the disease. The COPASAAR database is a new tool to facilitate the rapid analysis of single amino acid repeats at a proteome level. The database aims to simplify the comparison of repeat distributions between proteomes in order to provide a better understanding of their function and evolution. Results A comparative analysis of all proteomes in the database (currently 244) shows that single amino acid repeats account for about 12–14% of the proteome of any given species. They are more common in eukaryotes (14%) than in either archaea or bacteria (both 13%). Individual analyses of proteomes show that long single amino acid repeats (6+ residues) are much more common in the Eukaryotes and that longer repeats are usually made up of hydrophilic amino acids such as glutamine, glutamic acid, asparagine, aspartic acid and serine. Conclusion COPASAAR is a useful tool for comparative proteomics that provides rapid access to amino acid repeat data that can be readily data-mined. The COPASAAR database can be queried at the kingdom, proteome or individual protein level. As the amount of available proteome data increases this will be increasingly important in order to automate proteome comparison. The insights gained from these studies will give a better insight into the evolution of protein sequence and function. PMID:16078990

  14. Analysis of LRRK2 accessory repeat domains: prediction of repeat length, number and sites of Parkinson's disease mutations.

    PubMed

    Mills, Ryan D; Mulhern, Terrence D; Cheng, Heung-Chin; Culvenor, Janetta G

    2012-10-01

    Various investigators have identified the major domain organization of LRRK2 (leucine-rich repeat kinase 2), which includes a GTPase ROC (Ras of complex proteins) domain followed by a COR (C-terminal of ROC) domain and a protein kinase domain. In addition, there are four domains composed of structural repeat motifs likely to be involved in regulation and localization of this complex protein. In the present paper, we report our bioinformatic analyses of the human LRRK2 amino acid sequence to predict the repeat size, number and likely boundaries for the armadillo repeat, ankyrin repeat, the leucine-rich repeat and WD40 repeat regions of LRRK2. Homology modelling using known protein structures with similar domains was used to predict structures, exposed residues and location of mutations for these repeat regions. We predict that the armadillo repeats, ankyrin repeats and leucine-rich repeats together form an extended N-terminal flexible 'solenoid'-like structure composed of tandem repeat modules likely to be important in anchoring to the membrane and cytoskeletal structures as well as binding to other protein ligands. Near the C-terminus of LRRK2, the WD40 repeat region is predicted to form a closed propeller structure that is important for protein complex formation.

  15. Relation of cardiac abnormalities and CTG-repeat size in myotonic dystrophy.

    PubMed

    Finsterer, J; Gharehbaghi-Schnell, E; Stöllberger, C; Fheodoroff, K; Seiser, A

    2001-05-01

    It is unclear if the severity of cardiac involvement in patients with myotonic dystrophy (MD) is related to the size of the CTG-repeat expansion. This open, uncontrolled, observational, prospective study aimed to find out if there is a relation between the severity of cardiac involvement in MD and the CTG-repeat size. In 21 patients with MD, (8 women, 13 men, aged 11-88 years) a detailed cardiologic examination, including history, clinical examination, electrocardiography (ECG), transthoracic echocardiography and ambulatory 24-h ECG, was carried out and cardiac involvement was assessed according to a previously described scoring system. Additionally, the CTG-repeat size was determined from nuclear DNA of blood leukocytes. The correlation between the CTG-repeat size and the mean heart rate, PQ-interval, QTc-interval, fractional shortening, left ventricular enddiastolic diameter, septal thickness, posterior wall thickness, mean heart rate on 24-h ECG and cardiac involvement score was r=0.47, r=0.086, r=0.11, r=-0.27, r=-0.34, r=-0.06, r=-0.12, r=0.16 and r=0.09 (all p>0.05), respectively. In patients 21-30, 31-40 and 41-50 years of age, cardiac involvement increased with increasing CTG-repeat size. In younger patients, the number of CTG-repeats needed to develop a reasonable cardiac involvement was higher than in older patients. Depending on age, cardiac involvement increases with increasing CTG-repeat size obtained from blood leukocytes in patients with MD.

  16. Ex vivo response to histone deacetylase (HDAC) inhibitors of the HIV long terminal repeat (LTR) derived from HIV-infected patients on antiretroviral therapy.

    PubMed

    Lu, Hao K; Gray, Lachlan R; Wightman, Fiona; Ellenberg, Paula; Khoury, Gabriela; Cheng, Wan-Jung; Mota, Talia M; Wesselingh, Steve; Gorry, Paul R; Cameron, Paul U; Churchill, Melissa J; Lewin, Sharon R

    2014-01-01

    Histone deacetylase inhibitors (HDACi) can induce human immunodeficiency virus (HIV) transcription from the HIV long terminal repeat (LTR). However, ex vivo and in vivo responses to HDACi are variable and the activity of HDACi in cells other than T-cells have not been well characterised. Here, we developed a novel assay to determine the activity of HDACi on patient-derived HIV LTRs in different cell types. HIV LTRs from integrated virus were amplified using triple-nested Alu-PCR from total memory CD4+ T-cells (CD45RO+) isolated from HIV-infected patients prior to and following suppressive antiretroviral therapy. NL4-3 or patient-derived HIV LTRs were cloned into the chromatin forming episomal vector pCEP4, and the effect of HDACi investigated in the astrocyte and epithelial cell lines SVG and HeLa, respectively. There were no significant differences in the sequence of the HIV LTRs isolated from CD4+ T-cells prior to and after 18 months of combination antiretroviral therapy (cART). We found that in both cell lines, the HDACi panobinostat, trichostatin A, vorinostat and entinostat activated patient-derived HIV LTRs to similar levels seen with NL4-3 and all patient derived isolates had similar sensitivity to maximum HDACi stimulation. We observed a marked difference in the maximum fold induction of luciferase by HDACi in HeLa and SVG, suggesting that the effect of HDACi may be influenced by the cellular environment. Finally, we observed significant synergy in activation of the LTR with vorinostat and the viral protein Tat. Together, our results suggest that the LTR sequence of integrated virus is not a major determinant of a functional response to an HDACi.

  17. Secular trend in the occurrence of asthma among children and young adults: critical appraisal of repeated cross sectional surveys.

    PubMed Central

    Magnus, P.; Jaakkola, J. J.

    1997-01-01

    OBJECTIVES: To review repeated surveys of the rising prevalence of obstructive lung disease among children and young adults and determine whether systematic biases may explain the observed trends. DESIGN: Review of published reports of repeated cross sectional surveys of asthma and wheezing among children and young adults. The repeated surveys used the same sampling frame, the same definition of outcome variables, and equivalent data collection methods. SETTING: Repeated surveys conducted anywhere in the world. SUBJECTS: All repeated surveys whose last set of results were published in 1983 or later. MAIN OUTCOME MEASURES: Lifetime and current prevalences of asthma and current prevalence of wheezing. The absolute increase (yearly percentage) in the prevalences of asthma and wheezing was calculated and compared between studies. RESULTS: 16 repeated surveys fulfilled the inclusion criteria. 12 reported increases in the current prevalence of asthma (from 0.09% to 0.97% a year) and eight reported increases in the current prevalence of wheezing (from 0.14% to 1.24% a year). Changes in labelling are likely to have occurred for the reporting of asthma, and information biases may have occurred for the reporting of wheezing. Only one study reported an increase in an objective measurement. CONCLUSIONS: The evidence for increased prevalences of asthma and wheezing is weak because the measures used are susceptible to systematic errors. Until repeated surveys incorporating more objective data are available no firm conclusions about increases in obstructive lung disease among children and young adults can be drawn. PMID:9224081

  18. Repeated social defeat stress induces chronic hyperthermia in rats.

    PubMed

    Hayashida, Sota; Oka, Takakazu; Mera, Takashi; Tsuji, Sadatoshi

    2010-08-04

    Psychological stressors are known to increase core body temperature (T(c)) in laboratory animals. Such single stress-induced hyperthermic responses are typically monophasic, as T(c) returns to baseline within several hours. However, studies on the effects of repeated psychological stress on T(c) are limited. Therefore, we measured T(c) changes in male Wistar rats after they were subjected to 4 social defeat periods (each period consisting of 7 daily 1h stress exposures during the light cycle followed by a stress-free day). We also assessed affective-like behavioral changes by elevated plus maze and forced swim tests. In the stressed rats, the first social defeat experience induced a robust increase in T(c) (+1.3 degrees C). However, the T(c) of these rats was not different from control animals during the subsequent dark period. In comparison, after 4 periods of social defeat, stressed rats showed a small but significantly higher (+0.2-0.3 degree C) T(c) versus control rats during both light and dark periods. Stressed rats did not show increased anxiety-like behavior versus control rats as assessed by the elevated plus maze test. However, in the forced swim test, the immobility time of stressed rats was significantly longer versus control rats, suggesting an increase in depression-like behavior. Furthermore, hyperthermia and depression-like behavior were still observed 8 days after cessation of the final social defeat session. These results suggest that repeated social defeat stress induces a chronic hyperthermia in rats that is associated with behavior resembling depression but not anxiety.

  19. The Effects of Repeated Readings on the Development of Lower Identification Skills of FL Readers.

    ERIC Educational Resources Information Center

    Taguchi, Etsuo

    1997-01-01

    Investigates the effects of repeated readings of a passage in a foreign language (English) on the ability of slow beginning readers at a Japanese university to increase their oral and silent reading rates. Results indicate that, for practice passages, silent reading rates increased significantly. This transfer of practice effects to a new passage…

  20. Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2.

    PubMed

    Vinther-Jensen, Tua; Ek, Jakob; Duno, Morten; Skovby, Flemming; Hjermind, Lena E; Nielsen, Jørgen E; Nielsen, Troels Tolstrup

    2013-06-01

    The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective genes leading to pathogenic expansions of polyglutamine stretches in the encoded proteins. In general, unstable CAG repeats have an uninterrupted CAG repeat, whereas stable CAG repeats are either short or interrupted by CAA codons, which - like CAG codons - code for glutamine. Here we report on an infantile SCA2 patient who, due to germ-line CAG repeat instability in her father, inherited an extremely expanded CAG repeat in the SCA2 locus. Surprisingly, the expanded allele of the father was an interrupted CAG repeat sequence. Furthermore, analyses of single spermatozoa showed a high frequency of paternal germ-line repeat sequence instability of the expanded SCA2 locus.

  1. [The repeated biopsy in patients with lupus nephritis].

    PubMed

    Subils, Gisella; Alba, Paula; Gobbi, Carla; Astesana, Pablo; Babini, Alejandra; Albiero, Eduardo

    2014-01-01

    We retrospectively studied patients with SLE according to ACR criteria, with NL who underwent a repeat renal biopsy from 2005 to 2012. We analyzed the main indications of renal biopsies, the histopathological Class and activity and chronicity changes. RESULTS The total number of patients with NL was 120, of which 18 (15%) patients underwent repeat renal biopsy, 18 had 2 renal biopsies and 6 had 3 biopsies. 3 (16.7%) patients were smokers; 1 (5.6%) had a history of previous DBT, 2 (11.1%) had a history of hypertension; and 3 (16.7%) patients had previous obesity. The duration of SLE was 15 ± 96 months; the time between the 1st and the 2nd biopsy was 45 ± 11 months and the time between the 2nd and 3rd biopsy was 56 ± 12 months. Indications for repeat biopsy were proteinuria in 10 biopsies (41.6%); proteinuria with impaired renal function in 2 biopsies (8.3%); proteinuria with pathological urine sediment in 8 (33.3%); . and pathological proteinuria with pathological urine sediment and impaired renal function in 4 biopsies (16.6%) The most frequent histological changes found between first and repeat biopsies were class IV to class III: 2 (8.2%) ; Class IV to Class IV: 8 (33.3%), class IV to class III + V: 2 (8.2%); class IV to class IV + V 3 (12.5%); class IV to class V: 2 (8.2%). Changes in NL biopsies with proliferative activity and chronicity indices (A / C) were: A to A / C: 7 (29.1%), A / C to A / C: 7 (29.1%). The immunosuppressive therapy was increased in 79.1% and 16.6% remained without changes. 20% patients received cyclophosphamide 1 g every 30 days, 26% Cyclophosphamide 500 mg every 15 days, 23% induction therapy with mycophenolate mofetil; 23% with Rituximab; 8% Cyclosporin A. Maintenance therapy with mycophenolate mofetil was performed in 87.5%; azathioprine in 1 case. Hydroxychloroquine was used in all cases.

  2. Chlamydia trachomatis among Youth - Testing Behaviour and Incidence of Repeat Testing in Stockholm County, Sweden 2010-2012

    PubMed Central

    Marrone, Gaetano; De Costa, Ayesha

    2016-01-01

    Background Widespread testing and screening for genital Chlamydia trachomatis is often advocated as an important method to halt the epidemic. Sweden has long tradition of opportunistic screening services. Nevertheless infections rates have continued to rise over the past two decades, despite increased access to testing and treatment services. Methods In this retrospective cohort study we describe the testing behavior for genital Chlamydia trachomatis among youth in Stockholm County, with a focus on repeated testing. Specifically we (a) study positivity rates among single and repeat testers, we (b) estimate the incidence of repeat testing and the rates of infection in repeat testing episodes, and we (c) estimate time to repeat testing and factors associated with repeat testing. All youth (aged ≥12 and <26) that tested for Chlamydia trachomatis in one of 33 Youth Health Clinics in Stockholm County between 1 January 2010 and 31 December 2012 were included in the study. Results The cohort comprised a total of 65,951 individuals who did 119,699 tests during the study period. 42% of youth were repeat testers, the incidence of repeat testing was 35.0/100 person years. The overall baseline prevalence was 7.9%. Positivity rates of baseline tests among repeat testers were nearly twice as high among single testers of either sex. These were 17.1% and 9.8% among male repeat and single testers respectively. The corresponding rates for women were 9.4% and 4.3%. Positivity rates among repeat tests did not decline compared to the overall baseline positivity. Baseline test result and sex significantly influenced the occurrence of repeat testing. Conclusion Among repeat testers we found high rates of Chlamydia trachomatis both at baseline and at repeat tests which suggests the possibility that this group might be continuing to engage in unsafe sexual practices. Given the extent of repeat testing and the high positivity rates on repeat testing, further research among this group is

  3. Who Repeats Algebra, and How Does Initial Performance Relate to Improvement When the Course Is Repeated?

    ERIC Educational Resources Information Center

    Fong, Anthony; Jaquet, Karina; Finkelstein, Neal

    2016-01-01

    The information provided in this report shows how students perform when they repeat algebra I and how the level of improvement varies depending on initial course performance and the academic measure (course grades or CST scores). This information can help inform decisions and policies regarding whether and under what circumstances students should…

  4. Tandemly repeated exons encode 81-base repeats in multiple, developmentally regulated Schistosoma mansoni transcripts.

    PubMed Central

    Davis, R E; Davis, A H; Carroll, S M; Rajkovic, A; Rottman, F M

    1988-01-01

    The adult Schistosoma mansoni cDNA clone 10-3 encodes an antigen that is recognized by sera from infected humans. We characterized multiple developmentally regulated transcripts homologous to the 10-3 cDNA and portions of the complex genomic loci encoding those transcripts. Transcripts of approximately 950, 870, and 780 nucleotides were expressed in adults, whereas only the 780-nucleotide transcript was observed in the larval stage. These transcripts were highly similar, containing variable numbers of identical direct tandem repeats of 81 bases. Although the sequence of the repeating elements and sequences 3' to them were identical in all the transcripts, sequences 5' of the repeating elements exhibited variations, including a 27-base insertion, alternative start sites for transcription, and alternate 5' exon usage. These transcripts appeared to be derived in part by the developmentally controlled alternative splicing of small exons and the use of alternative transcription initiation sites from the one or two complex loci of at least 40 kilobase pairs. Each 81-base repeat in the transcripts was encoded by three dispersed 27-base-pair exons. These 27-base-pair exons were contained within highly conserved, reiterated 3-kilobase-pair genomic tandem arrays. Images PMID:3211127

  5. Repeat Testing Effects on Credentialing Exams: Are Repeaters Misinformed or Uninformed?

    ERIC Educational Resources Information Center

    Feinberg, Richard A.; Raymond, Mark R.; Haist, Steven A.

    2015-01-01

    To mitigate security concerns and unfair score gains, credentialing programs routinely administer new test material to examinees retesting after an initial failing attempt. Counterintuitively, a small but growing body of recent research suggests that repeating the identical form does not create an unfair advantage. This study builds upon and…

  6. Serum cardiac troponin T after repeated endurance exercise events.

    PubMed

    Bonetti, A; Tirelli, F; Albertini, R; Monica, C; Monica, M; Tredici, G

    1996-05-01

    Recently Dr. Rowe made a hypothesis according to which small areas of myocardial necrosis can be caused by microvascular spasm, related to high catecholamine concentrations and other mechanisms, following extraordinary unremitting endurance exercises or due to the cumulative effect of several endurance events. It was this last suggestion which prompted us to investigate 25 top cyclists, taking part in the 77th Giro d'Italia. Blood samples were obtained the day before the start of the competition and once a week thereafter until the end. We measured myoglobin, lactic dehydrogenase, total creatine kinase, creatine kinase isoenzyme MB and serum cardiac troponin T (Tn-T), a highly sensitive and specific method for the detection of myocardial injury. While at measuring time points which followed we found a significant increase in the serum indicators of muscle damage, compared with their values at the beginning of the race, creatine kinase isoenzyme MB did not rise significantly and cardiac Tn-T was found in the serum of only 5 athletes, repeatedly in some cases, but always below the cut off values considered as indicating myocardial ischemia. On the basis of the behaviour of creatine kinase isoenzyme MB and, above all, of cardiac Tn-T, we can conclude that heavy endurance exercises, repeated daily for 22 days, as was the case in our study, do not seem able to produce, in top athletes, permanent heart damage by means of acute myocardial injury.

  7. High teleportation rates using Rydberg-based quantum repeaters

    NASA Astrophysics Data System (ADS)

    Solmeyer, Neal; Quraishi, Qudsia

    2015-05-01

    Quantum networking over long distances may be achieved using repeater protocols to generate entanglement between memory nodes. Typically, long-lived memories have low entanglement generation rates. Neutral atom memories can be long-lived, emit at visible wavelengths and can be collectively excited leading to directionally emitted entangled photons. Here, we propose a simplified Rydberg-based quantum repeater based on recent work, where we reduce the number of ground states used for entanglement generation and use only one ensemble at each node, reducing the required resources. The collective excitation allows for deterministic memory generation that is mapped into a directionally emitted photonic qubit without the use of a high finesse optical cavity. We demonstrate a protocol between multiple memories stored within a single ensemble to implement a two-qubit gate. Additionally, we predict teleportation rates of 1 Hz without the use of a high finesse optical cavity, which could be increased to kHz if efficiencies are improved over the currently realized values. We plan to explore these protocols in ultra-cold ensemble of neutral 87Rb atoms and are currently building this setup.

  8. Novel mutational mechanism in man: Expansion of trinucleotide repeats

    SciTech Connect

    Ilarioshkin, S.N.; Ivanova-Smolenskaya, I.A.; Markova, E.D.

    1995-11-01

    An analysis of a novel, recently discovered class of mutations in man - an expansion, i.e., an increase of the copy number of intragenic unstable trinucleotide repeats - is presented. The expansion of trinucleotide X chromosome syndrome (two separate variants of the disease - FRAXA and FRAXE), myotonic dystrophy, spinal and bulbar Kennedy`s amyotrophy, Huntington`s chorea, type 1 spinocerebellar ataxia, and dentatorubral-pallidolyusian atrophy. The discovery of triplet expansion allows a satisfactory explanation on the molecular level of a series of unusual clinical genetic phenomena, such as anticipation, the {open_quotes}paternal transmission{close_quotes} effect, the {open_quotes}Sherman paradox,{close_quotes} and others. The common properties and the distinctions of unstable trinucleotide mutations in the nosologic forms mentioned above are analyzed comprehensively. These features include the mechanism by which these mutations cause disease, the time of their appearance in ontogenesis, and various clinical genetic correlations. The evolutionary origin of this class of mutations and, in particular, the role of alleles with an {open_quotes}intermediate{close_quotes} triplet number, which are the persistent reservoir of mutations arising de novo in a population, are also discussed. The possible implication of unstable trinucleotide repeats for a series of other hereditary diseases, such as type 2, spinocerebellar ataxia, Machado-Joseph disease, hereditary spastic paraplegia, essential tremor, schizophrenia, and others, is also suggested. 108 refs., 1 tab.

  9. Cybersickness Following Repeated Exposure to DOME and HMD Virtual Environments

    NASA Technical Reports Server (NTRS)

    Taylor, Laura C.; Harm, Deborah L.; Kennedy, Robert S.; Reschke, Millard F.; Loftin, R. Bowen

    2011-01-01

    Virtual environments (VE) offer unique training opportunities, including training astronauts to preadapt them to the novel sensory conditions of microgravity. However, one unresolved issue with VE use is the occurrence of cybersickness during and following exposure to VE systems. Most individuals adapt and become less ill with repeated interaction with VEs. The goal of this investigation was to compare motion sickness symptoms (MSS) produced by dome and head-mounted (HMD) displays and to examine the effects of repeated exposures on MSS. Sixty-one subjects participated in the study. Three experimental sessions were performed each separated by one day. The subjects performed a navigation and pick and place task in either a dome or HMD VE. MSS were measured using a Simulator Sickness Questionnaire before, immediately after, and at 1, 2, 4 and 6 hours following exposure to the VEs. MSS data were normalized by calculating the natural log of each score and an analysis of variance was performed. We observed significant main effects for day and time and a significant day by time interaction for total sickness and for each of the subscales, nausea, oculomotor and disorientation. However, there was no significant main effect for device. In conclusion, subjects reported a large increase in MSS immediately following exposure to both the HMD and dome, followed by a rapid recovery across time. Sickness severity also decreased over days, which suggests that subjects become dual-adapted over time making VE training a viable pre-flight countermeasure for space motion sickness.

  10. Simple sequence repeats in bryophyte mitochondrial genomes.

    PubMed

    Zhao, Chao-Xian; Zhu, Rui-Liang; Liu, Yang

    2016-01-01

    Simple sequence repeats (SSRs) are thought to be common in plant mitochondrial (mt) genomes, but have yet to be fully described for bryophytes. We screened the mt genomes of two liverworts (Marchantia polymorpha and Pleurozia purpurea), two mosses (Physcomitrella patens and Anomodon rugelii) and two hornworts (Phaeoceros laevis and Nothoceros aenigmaticus), and detected 475 SSRs. Some SSRs are found conserved during the evolution, among which except one exists in both liverworts and mosses, all others are shared only by the two liverworts, mosses or hornworts. SSRs are known as DNA tracts having high mutation rates; however, according to our observations, they still can evolve slowly. The conservativeness of these SSRs suggests that they are under strong selection and could play critical roles in maintaining the gene functions.

  11. Design principles for efficient, repeated jumpgliding.

    PubMed

    Desbiens, Alexis Lussier; Pope, Morgan T; Christensen, David L; Hawkes, Elliot W; Cutkosky, Mark R

    2014-06-01

    Combined jumping and gliding locomotion, or 'jumpgliding', can be an efficient way for small robots or animals to travel over cluttered terrain. This paper presents functional requirements and models for a simple jumpglider which formalize the benefits and limitations of using aerodynamic surfaces to augment jumping ability. Analysis of the model gives insight into design choices and control strategies for higher performance and to accommodate special conditions such as a slippery launching surface. The model informs the design of a robotic platform that can perform repeated jumps using a carbon fiber spring and a pivoting wing. Experiments with two different versions of the platform agree with predictions from the model and demonstrate a significantly greater range, and lower cost-of-transport, than a comparable ballistic jumper.

  12. Manipulation of Avoidance Behavior As A Function of Increased or Decreased Demand On Repeated Behavioral Tests

    ERIC Educational Resources Information Center

    Bernstein, Douglas A.

    1974-01-01

    Five groups of 15 female subjects reporting fear of snakes participated in two behavioral avoidance tests employing a snake as the target object. Results are discussed both in terms of implications for psychotherapy outcome research design and possible usefulness of situational variables in the development of more effective anxiety-reduction…

  13. The autolytic activity of the recombinant amidase of Staphylococcus saprophyticus is inhibited by its own recombinant GW repeats.

    PubMed

    Hell, Wolfgang; Reichl, Sylvia; Anders, Agnes; Gatermann, Sören

    2003-10-10

    The Aas (autolysin/adhesin of Staphylococcus saprophyticus) is a multifunctional surface protein containing two enzymatic domains an N-acetyl-muramyl-L-alanine amidase, an endo-beta-N-acetyl-D-glucosaminidase, and two different regions of repetitive sequences, an N-terminal and a C-terminal repetitive domain. The C-terminal repetitive domain is built up by the repeats R1, R2 and R3, which interconnect the putative active centers of the amidase and glucosaminidase. To investigate the influence of the C-terminal repeats and the N-terminal repeats on the amidase activity, the repetitive domains and fragments of them were cloned and expressed in Escherichia coli. The influence of the different fragments on the activity of the recombinant amidase of the Aas, consisting of the active center of the enzyme and repeat R1, was investigated in a turbidimetric microassay. The different fragments derived from the C-terminal repeats inhibited the amidase activity, while the N-terminal repeats did not influence the activity of the enzyme. The inhibiting activity increased with the number of GW repeats the recombinant fragment contained. Thus we conclude, that the C-terminal GW repeats and not the N-terminal repeats are necessary for the cell wall targeting and the autolytic function of the amidase.

  14. Methylation of C9orf72 expansion reduces RNA foci formation and dipeptide-repeat proteins expression in cells.

    PubMed

    Bauer, Peter O

    2016-01-26

    A hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of both frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), together referred to as c9FTD/ALS. It has been suggested that a loss of C9orf72 protein expression, the formation of toxic RNA foci and dipeptide-repeat proteins contribute to C9orf72-related diseases. Interestingly, it has been shown that trimethylation of histones and methylation of CpG islands near the repeat expansion may play a role in the pathogenesis c9FTD/ALS. Recently, methylation of expanded repeat itself has been reported. To further elucidate the mechanisms underlying these diseases, the influence of epigenetic modification in the repeat expansion on its pathogenic effect was assessed. Here, a reduced formation of toxic RNA foci and dipeptide-repeat proteins upon methylation of the GGGGCC repeat in a cellular model of c9FTD/ALS is shown. Additionally, a novel methylcytosine-capture DNA hybridization immunoassay for semi-quantitative detection of the repeat methylation levels is presented, potentially usable for methylation analysis in patients carrying C9orf72 repeat expansion carriers as a diagnostic tool. Presented results suggest that increased level of pathogenic GGGGCC expansion methylation may be sufficient to alleviate the molecular pathology of the C9orf72-related diseases.

  15. A pan-European study of the C9orf72 repeat associated with FTLD: geographic prevalence, genomic instability, and intermediate repeats.

    PubMed

    van der Zee, Julie; Gijselinck, Ilse; Dillen, Lubina; Van Langenhove, Tim; Theuns, Jessie; Engelborghs, Sebastiaan; Philtjens, Stéphanie; Vandenbulcke, Mathieu; Sleegers, Kristel; Sieben, Anne; Bäumer, Veerle; Maes, Githa; Corsmit, Ellen; Borroni, Barbara; Padovani, Alessandro; Archetti, Silvana; Perneczky, Robert; Diehl-Schmid, Janine; de Mendonça, Alexandre; Miltenberger-Miltenyi, Gabriel; Pereira, Sónia; Pimentel, José; Nacmias, Benedetta; Bagnoli, Silvia; Sorbi, Sandro; Graff, Caroline; Chiang, Huei-Hsin; Westerlund, Marie; Sanchez-Valle, Raquel; Llado, Albert; Gelpi, Ellen; Santana, Isabel; Almeida, Maria Rosário; Santiago, Beatriz; Frisoni, Giovanni; Zanetti, Orazio; Bonvicini, Cristian; Synofzik, Matthis; Maetzler, Walter; Vom Hagen, Jennifer Müller; Schöls, Ludger; Heneka, Michael T; Jessen, Frank; Matej, Radoslav; Parobkova, Eva; Kovacs, Gabor G; Ströbel, Thomas; Sarafov, Stayko; Tournev, Ivailo; Jordanova, Albena; Danek, Adrian; Arzberger, Thomas; Fabrizi, Gian Maria; Testi, Silvia; Salmon, Eric; Santens, Patrick; Martin, Jean-Jacques; Cras, Patrick; Vandenberghe, Rik; De Deyn, Peter Paul; Cruts, Marc; Van Broeckhoven, Christine; van der Zee, Julie; Gijselinck, Ilse; Dillen, Lubina; Van Langenhove, Tim; Theuns, Jessie; Philtjens, Stéphanie; Sleegers, Kristel; Bäumer, Veerle; Maes, Githa; Corsmit, Ellen; Cruts, Marc; Van Broeckhoven, Christine; van der Zee, Julie; Gijselinck, Ilse; Dillen, Lubina; Van Langenhove, Tim; Philtjens, Stéphanie; Theuns, Jessie; Sleegers, Kristel; Bäumer, Veerle; Maes, Githa; Cruts, Marc; Van Broeckhoven, Christine; Engelborghs, Sebastiaan; De Deyn, Peter P; Cras, Patrick; Engelborghs, Sebastiaan; De Deyn, Peter P; Vandenbulcke, Mathieu; Vandenbulcke, Mathieu; Borroni, Barbara; Padovani, Alessandro; Archetti, Silvana; Perneczky, Robert; Diehl-Schmid, Janine; Synofzik, Matthis; Maetzler, Walter; Müller Vom Hagen, Jennifer; Schöls, Ludger; Synofzik, Matthis; Maetzler, Walter; Müller Vom Hagen, Jennifer; Schöls, Ludger; Heneka, Michael T; Jessen, Frank; Ramirez, Alfredo; Kurzwelly, Delia; Sachtleben, Carmen; Mairer, Wolfgang; de Mendonça, Alexandre; Miltenberger-Miltenyi, Gabriel; Pereira, Sónia; Firmo, Clara; Pimentel, José; Sanchez-Valle, Raquel; Llado, Albert; Antonell, Anna; Molinuevo, Jose; Gelpi, Ellen; Graff, Caroline; Chiang, Huei-Hsin; Westerlund, Marie; Graff, Caroline; Kinhult Ståhlbom, Anne; Thonberg, Håkan; Nennesmo, Inger; Börjesson-Hanson, Anne; Nacmias, Benedetta; Bagnoli, Silvia; Sorbi, Sandro; Bessi, Valentina; Piaceri, Irene; Santana, Isabel; Santiago, Beatriz; Santana, Isabel; Helena Ribeiro, Maria; Rosário Almeida, Maria; Oliveira, Catarina; Massano, João; Garret, Carolina; Pires, Paula; Frisoni, Giovanni; Zanetti, Orazio; Bonvicini, Cristian; Sarafov, Stayko; Tournev, Ivailo; Jordanova, Albena; Tournev, Ivailo; Kovacs, Gabor G; Ströbel, Thomas; Heneka, Michael T; Jessen, Frank; Ramirez, Alfredo; Kurzwelly, Delia; Sachtleben, Carmen; Mairer, Wolfgang; Jessen, Frank; Matej, Radoslav; Parobkova, Eva; Danel, Adrian; Arzberger, Thomas; Maria Fabrizi, Gian; Testi, Silvia; Ferrari, Sergio; Cavallaro, Tiziana; Salmon, Eric; Santens, Patrick; Cras, Patrick

    2013-02-01

    We assessed the geographical distribution of C9orf72 G(4) C(2) expansions in a pan-European frontotemporal lobar degeneration (FTLD) cohort (n = 1,205), ascertained by the European Early-Onset Dementia (EOD) consortium. Next, we performed a meta-analysis of our data and that of other European studies, together 2,668 patients from 15 Western European countries. The frequency of the C9orf72 expansions in Western Europe was 9.98% in overall FTLD, with 18.52% in familial, and 6.26% in sporadic FTLD patients. Outliers were Finland and Sweden with overall frequencies of respectively 29.33% and 20.73%, but also Spain with 25.49%. In contrast, prevalence in Germany was limited to 4.82%. In addition, we studied the role of intermediate repeats (7-24 repeat units), which are strongly correlated with the risk haplotype, on disease and C9orf72 expression. In vitro reporter gene expression studies demonstrated significantly decreased transcriptional activity of C9orf72 with increasing number of normal repeat units, indicating that intermediate repeats might act as predisposing alleles and in favor of the loss-of-function disease mechanism. Further, we observed a significantly increased frequency of short indels in the GC-rich low complexity sequence adjacent to the G(4) C(2) repeat in C9orf72 expansion carriers (P < 0.001) with the most common indel creating one long contiguous imperfect G(4) C(2) repeat, which is likely more prone to replication slippage and pathological expansion.

  16. Digital Genotyping of Macrosatellites and Multicopy Genes Reveals Novel Biological Functions Associated with Copy Number Variation of Large Tandem Repeats

    PubMed Central

    Quilez, Javier; Hasson, Dan; Borel, Christelle; Warburton, Peter; Sharp, Andrew J.

    2014-01-01

    Tandem repeats are common in eukaryotic genomes, but due to difficulties in assaying them remain poorly studied. Here, we demonstrate the utility of Nanostring technology as a targeted approach to perform accurate measurement of tandem repeats even at extremely high copy number, and apply this technology to genotype 165 HapMap samples from three different populations and five species of non-human primates. We observed extreme variability in copy number of tandemly repeated genes, with many loci showing 5–10 fold variation in copy number among humans. Many of these loci show hallmarks of genome assembly errors, and the true copy number of many large tandem repeats is significantly under-represented even in the high quality ‘finished’ human reference assembly. Importantly, we demonstrate that most large tandem repeat variations are not tagged by nearby SNPs, and are therefore essentially invisible to SNP-based GWAS approaches. Using association analysis we identify many cis correlations of large tandem repeat variants with nearby gene expression and DNA methylation levels, indicating that variations of tandem repeat length are associated with functional effects on the local genomic environment. This includes an example where expansion of a macrosatellite repeat is associated with increased DNA methylation and suppression of nearby gene expression, suggesting a mechanism termed “repeat induced gene silencing”, which has previously been observed only in transgenic organisms. We also observed multiple signatures consistent with altered selective pressures at tandemly repeated loci, suggesting important biological functions. Our studies show that tandemly repeated loci represent a highly variable fraction of the genome that have been systematically ignored by most previous studies, copy number variation of which can exert functionally significant effects. We suggest that future studies of tandem repeat loci will lead to many novel insights into their role in

  17. The expansion of amino-acid repeats is not associated to adaptive evolution in mammalian genes

    PubMed Central

    2009-01-01

    Background The expansion of amino acid repeats is determined by a high mutation rate and can be increased or limited by selection. It has been suggested that recent expansions could be associated with the potential of adaptation to new environments. In this work, we quantify the strength of this association, as well as the contribution of potential confounding factors. Results Mammalian positively selected genes have accumulated more recent amino acid repeats than other mammalian genes. However, we found little support for an accelerated evolutionary rate as the main driver for the expansion of amino acid repeats. The most significant predictors of amino acid repeats are gene function and GC content. There is no correlation with expression level. Conclusions Our analyses show that amino acid repeat expansions are causally independent from protein adaptive evolution in mammalian genomes. Relaxed purifying selection or positive selection do not associate with more or more recent amino acid repeats. Their occurrence is slightly favoured by the sequence context but mainly determined by the molecular function of the gene. PMID:20021652

  18. Geometric Positioning for Satellite Imagery without Ground Control Points by Exploiting Repeated Observation.

    PubMed

    Ma, Zhenling; Wu, Xiaoliang; Yan, Li; Xu, Zhenliang

    2017-01-26

    With the development of space technology and the performance of remote sensors, high-resolution satellites are continuously launched by countries around the world. Due to high efficiency, large coverage and not being limited by the spatial regulation, satellite imagery becomes one of the important means to acquire geospatial information. This paper explores geometric processing using satellite imagery without ground control points (GCPs). The outcome of spatial triangulation is introduced for geo-positioning as repeated observation. Results from combining block adjustment with non-oriented new images indicate the feasibility of geometric positioning with the repeated observation. GCPs are a must when high accuracy is demanded in conventional block adjustment; the accuracy of direct georeferencing with repeated observation without GCPs is superior to conventional forward intersection and even approximate to conventional block adjustment with GCPs. The conclusion is drawn that taking the existing oriented imagery as repeated observation enhances the effective utilization of previous spatial triangulation achievement, which makes the breakthrough for repeated observation to improve accuracy by increasing the base-height ratio and redundant observation. Georeferencing tests using data from multiple sensors and platforms with the repeated observation will be carried out in the follow-up research.

  19. DNA CTG triplet repeats involved in dynamic mutations of neurologically related gene sequences form stable duplexes

    NASA Technical Reports Server (NTRS)

    Smith, G. K.; Jie, J.; Fox, G. E.; Gao, X.

    1995-01-01

    DNA triplet repeats, 5'-d(CTG)n and 5'-d(CAG)n, are present in genes which have been implicated in several neurodegenerative disorders. To investigate possible stable structures formed by these repeating sequences, we have examined d(CTG)n, d(CAG)n and d(CTG).d(CAG)n (n = 2 and 3) using NMR and UV optical spectroscopy. These studies reveal that single stranded (CTG)n (n > 2) forms stable, antiparallel helical duplexes, while the single stranded (CAG)n requires at least three repeating units to form a duplex. NMR and UV melting experiments show that the Tm increases in the order of [(CAG)3]2 < [(CTG)3]2 << (CAG)3.(CTG)3. The (CTG)3 duplex is stable and exhibits similar NMR spectra in solutions containing 0.1-4 M NaCl and at a pH range from 4.6 to 8.8. The (CTG)3 duplex, which contains multiple-T.T mismatches, displays many NMR spectral characteristics similar to those of B-form DNA. However, unique NOE and 1H-31P coupling patterns associated with the repetitive T.T mismatches in the CTG repeats are discerned. These results, in conjunction with recent in vitro studies suggest that longer CTG repeats may form hairpin structures, which can potentially cause interruption in replication, leading to dynamic expansion or deletion of triplet repeats.

  20. DNA CTG triplet repeats involved in dynamic mutations of neurologically related gene sequences form stable duplexes.

    PubMed Central

    Smith, G K; Jie, J; Fox, G E; Gao, X

    1995-01-01

    DNA triplet repeats, 5'-d(CTG)n and 5'-d(CAG)n, are present in genes which have been implicated in several neurodegenerative disorders. To investigate possible stable structures formed by these repeating sequences, we have examined d(CTG)n, d(CAG)n and d(CTG).d(CAG)n (n = 2 and 3) using NMR and UV optical spectroscopy. These studies reveal that single stranded (CTG)n (n > 2) forms stable, antiparallel helical duplexes, while the single stranded (CAG)n requires at least three repeating units to form a duplex. NMR and UV melting experiments show that the Tm increases in the order of [(CAG)3]2 < [(CTG)3]2 << (CAG)3.(CTG)3. The (CTG)3 duplex is stable and exhibits similar NMR spectra in solutions containing 0.1-4 M NaCl and at a pH range from 4.6 to 8.8. The (CTG)3 duplex, which contains multiple-T.T mismatches, displays many NMR spectral characteristics similar to those of B-form DNA. However, unique NOE and 1H-31P coupling patterns associated with the repetitive T.T mismatches in the CTG repeats are discerned. These results, in conjunction with recent in vitro studies suggest that longer CTG repeats may form hairpin structures, which can potentially cause interruption in replication, leading to dynamic expansion or deletion of triplet repeats. PMID:7501450

  1. Interpersonal violence and the prediction of short-term risk of repeat suicide attempt

    PubMed Central

    Haglund, Axel; Lindh, Åsa U.; Lysell, Henrik; Renberg, Ellinor Salander; Jokinen, Jussi; Waern, Margda; Runeson, Bo

    2016-01-01

    In this multi-center cohort study, suicide attempters presenting to hospital (N = 355, 63% women) were interviewed using the Karolinska Interpersonal Violence Scale (KIVS) and followed-up by medical record review. Main outcome was non-fatal or fatal repeat suicide attempt within six months. Also, repeat attempt using a violent method was used as an additional outcome in separate analyses. Data were analyzed for the total group and for men and women separately. Repeat attempts were observed within six months in 78 persons (22%) and 21 (6%) of these used a violent method. KIVS total score of 6 or more was associated with repeat suicide attempt within six months (OR = 1.81, CI 1.08–3.02) and predicted new attempts with a sensitivity of 62% and a specificity of 53%. A three-fold increase in odds ratio was observed for repeat attempt using a violent method (OR = 3.40, CI 1.22–9.49). An association between exposure to violence in adulthood and violent reattempt was seen in women (OR = 1.38, CI 1.06–1.82). The overall conclusions are that information about interpersonal violence may help predict short-term risk for repeat suicide attempt, and that structured assessment of interpersonal violence may be of value in risk assessment after attempted suicide. PMID:27841333

  2. Geometric Positioning for Satellite Imagery without Ground Control Points by Exploiting Repeated Observation

    PubMed Central

    Ma, Zhenling; Wu, Xiaoliang; Yan, Li; Xu, Zhenliang

    2017-01-01

    With the development of space technology and the performance of remote sensors, high-resolution satellites are continuously launched by countries around the world. Due to high efficiency, large coverage and not being limited by the spatial regulation, satellite imagery becomes one of the important means to acquire geospatial information. This paper explores geometric processing using satellite imagery without ground control points (GCPs). The outcome of spatial triangulation is introduced for geo-positioning as repeated observation. Results from combining block adjustment with non-oriented new images indicate the feasibility of geometric positioning with the repeated observation. GCPs are a must when high accuracy is demanded in conventional block adjustment; the accuracy of direct georeferencing with repeated observation without GCPs is superior to conventional forward intersection and even approximate to conventional block adjustment with GCPs. The conclusion is drawn that taking the existing oriented imagery as repeated observation enhances the effective utilization of previous spatial triangulation achievement, which makes the breakthrough for repeated observation to improve accuracy by increasing the base-height ratio and redundant observation. Georeferencing tests using data from multiple sensors and platforms with the repeated observation will be carried out in the follow-up research. PMID:28134779

  3. Tianeptine modulates amygdalar glutamate neurochemistry and synaptic proteins in rats subjected to repeated stress.

    PubMed

    Piroli, Gerardo G; Reznikov, Leah R; Grillo, Claudia A; Hagar, Janel M; Fadel, Jim R; Reagan, Lawrence P

    2013-03-01

    Stress is a common environmental factor associated with depressive illness and the amygdala is thought to be integral for this association. For example, repeated stress impairs amygdalar neuroplasticity in rodents and these defects parallel amygdalar deficits in depressive illness patients. Because the excitatory neurotransmitter glutamate is important in neuroplasticity, we hypothesized that alterations in amygdalar glutamatergic systems may serve as key players in depressive illness. Moreover, restoration of amygdalar glutamatergic systems may serve as important therapeutic targets in the successful management of multiple stress-related mood disorders. To address these hypotheses, we measured glutamate efflux in the basolateral and central amygdalar complexes via in vivo microdialysis, as well as the expression of synaptic proteins that regulate vesicular glutamate packaging and release, in rats subjected to repeated stress and treated daily with saline or the antidepressant tianeptine. Glutamate efflux was significantly reduced in the central amygdalar complex of animals subjected to repeated stress. In addition, repeated stress nearly eliminated amygdalar vGLUT2 expression, thereby proving a potential mechanism through which repeated stress impairs amygdalar glutamate neurochemistry. These stress-induced changes in glutamate efflux and vGLUT2 expression were inhibited by daily tianeptine administration. Moreover, tianeptine administration increased the vesicular localization of SNAP-25, which could account for the ability of tianeptine to modify glutamatergic tone in non-stressed control rats. Collectively, these results demonstrate that repeated stress differentially affects amygdalar glutamate systems and further supports our previous studies indicating that tianeptine's antidepressant efficacy may involve targeting amygdalar glutatamatergic systems.

  4. Novel Y-chromosome Short Tandem Repeat Variants Detected Through the Use of Massively Parallel Sequencing

    PubMed Central

    Warshauer, David H.; Churchill, Jennifer D.; Novroski, Nicole; King, Jonathan L.; Budowle, Bruce

    2015-01-01

    Massively parallel sequencing (MPS) technology is capable of determining the sizes of short tandem repeat (STR) alleles as well as their individual nucleotide sequences. Thus, single nucleotide polymorphisms (SNPs) within the repeat regions of STRs and variations in the pattern of repeat units in a given repeat motif can be used to differentiate alleles of the same length. In this study, MPS was used to sequence 28 forensically-relevant Y-chromosome STRs in a set of 41 DNA samples from the 3 major U.S. population groups (African Americans, Caucasians, and Hispanics). The resulting sequence data, which were analyzed with STRait Razor v2.0, revealed 37 unique allele sequence variants that have not been previously reported. Of these, 19 sequences were variations of documented sequences resulting from the presence of intra-repeat SNPs or alternative repeat unit patterns. Despite a limited sampling, two of the most frequently-observed variants were found only in African American samples. The remaining 18 variants represented allele sequences for which there were no published data with which to compare. These findings illustrate the great potential of MPS with regard to increasing the resolving power of STR typing and emphasize the need for sample population characterization of STR alleles. PMID:26391384

  5. Effect of repeated manipulation on range of motion in patients with stiff total knee arthroplasty.

    PubMed

    Choi, Ho-Rim; Siliski, John M; Malchau, Henrik; Kwon, Young-Min

    2015-03-01

    Although manipulation under anesthesia (MUA) has been considered effective first-line treatment for stiff total knee arthroplasty (TKA), there is no consensus regarding the usefulness of repeated MUA. The purpose of this study was to investigate the usefulness of repeated MUA performed for patients in whom satisfactory range of motion (ROM) was not achieved by MUA. The authors retrospectively reviewed 15 patients who underwent repeated MUA after failure of initial MUA for stiff TKA. Demographic and ROM data were collected. A final ROM of less than 90° was considered a failed manipulation (failure group) and a final ROM of 90° or more was considered a successful manipulation (success group). Average pre-repeated MUA ROM (72.3°±19.5°) immediately improved to 112.3°±9.7° (P<.001) in the operating room, and final ROM was 89.6°±23.9°, an overall gain of 17.3° (P=.04). However, despite this overall ROM increase, a successful final ROM (90° or more) was achieved in approximately half of patients (7 of 13; 54%). There were no significant differences in demographics between the success and failure groups, except that there was significantly less pre-TKA ROM in the failure group (P=.02). There were no complications related to either the first or the repeated MUA procedures. The findings of this study suggest that repeated MUA can improve overall ROM for stiff TKA. The success rate of repeated MUA was less than that of primary MUA; however, it is a useful treatment modality for stiff TKA. Decreased pre-TKA ROM appeared to be associated with poor outcomes after repeated MUA.

  6. A novel GAA-repeat-expansion-based mouse model of Friedreich’s ataxia

    PubMed Central

    Anjomani Virmouni, Sara; Ezzatizadeh, Vahid; Sandi, Chiranjeevi; Sandi, Madhavi; Al-Mahdawi, Sahar; Chutake, Yogesh; Pook, Mark A.

    2015-01-01

    Friedreich’s ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a GAA repeat expansion mutation within intron 1 of the FXN gene, resulting in reduced levels of frataxin protein. We have previously reported the generation of human FXN yeast artificial chromosome (YAC) transgenic FRDA mouse models containing 90–190 GAA repeats, but the presence of multiple GAA repeats within these mice is considered suboptimal. We now describe the cellular, molecular and behavioural characterisation of a newly developed YAC transgenic FRDA mouse model, designated YG8sR, which we have shown by DNA sequencing to contain a single pure GAA repeat expansion. The founder YG8sR mouse contained 120 GAA repeats but, due to intergenerational expansion, we have now established a colony of YG8sR mice that contain ~200 GAA repeats. We show that YG8sR mice have a single copy of the FXN transgene, which is integrated at a single site as confirmed by fluorescence in situ hybridisation (FISH) analysis of metaphase and interphase chromosomes. We have identified significant behavioural deficits, together with a degree of glucose intolerance and insulin hypersensitivity, in YG8sR FRDA mice compared with control Y47R and wild-type (WT) mice. We have also detected increased somatic GAA repeat instability in the brain and cerebellum of YG8sR mice, together with significantly reduced expression of FXN, FAST-1 and frataxin, and reduced aconitase activity, compared with Y47R mice. Furthermore, we have confirmed the presence of pathological vacuoles within neurons of the dorsal root ganglia (DRG) of YG8sR mice. These novel GAA-repeat-expansion-based YAC transgenic FRDA mice, which exhibit progressive FRDA-like pathology, represent an excellent model for the investigation of FRDA disease mechanisms and therapy. PMID:25681319

  7. On the validity of repeated assessments in the UMAT, a high-stakes admissions test.

    PubMed

    Andrich, David; Styles, Irene; Mercer, Annette; Puddey, Ian B

    2017-02-04

    The possibility that the validity of assessment is compromised by repeated sittings of highly competitive and high profile selection tests has been documented and is of concern to stake-holders. An illustrative example is the Undergraduate Medicine and Health Sciences Admission Test (UMAT) used by some medical and dental courses in Australia and New Zealand. The proficiencies of all applicants who sat the UMAT from one to four sittings between 2006 and 2012 were estimated on the same metric using the probabilistic Rasch model. A fit index characterising each profile's degree of conformity to the model was also calculated. Confirming expectations, mean proficiencies increased with repeated sittings on all three UMAT scales with the greatest difference (which was nevertheless relatively small) between the first two sittings. The fit index showed that the increases in proficiency estimates arose from additional easier items being answered correctly on repeated sittings rather than additional more difficult ones, suggesting that improvements are not on the substantive construct of the variable of assessment but in skills in answering the questions. Although strategies for dealing with the increase in proficiency estimates on repeated sittings could be canvassed, these results suggest that the validity of results on repeated sittings was not compromised. Accordingly, it might be concluded that although particular individuals might improve substantially between sittings, any validity is not likely to be compromised with the possibility that for some applicants, the second sitting might be the most valid.

  8. A practical approach to mentoring students with repeated performance deficiencies

    PubMed Central

    2013-01-01

    Background With the increasing use of competency-based evaluations we now have more and better ways to identify performance deficiencies in our learners. Yet the emphasis placed on identifying deficiencies appears to exceed that given to improving these deficiencies. Aims Here we describe the program at the University of Calgary for mentoring students with repeated performance deficiencies. We focus primarily on the key steps of mentoring and remediation, and establishing a program that provides consistency and accountability to this process. Conclusions A small cohort of trainees with persistent performance deficiencies may need intensive remediation to reach the expected level of performance. Ultimately, not all learners will be successful in their remediation, but we feel that it is the responsibility of training programs to provide mentorship and an organized approach to remediation in order to maximize the chances of successful remediation. PMID:23597111

  9. Sequence Analysis of the Direct Repeat Region in Mycobacterium bovis

    PubMed Central

    Caimi, Karina; Romano, Maria I.; Alito, Alicia; Zumarraga, Martin; Bigi, Fabiana; Cataldi, Angel

    2001-01-01

    Spoligotyping is a major tool for molecular typing of Mycobacterium bovis. This technique is based on the polymorphism of spacers that separate direct repeats (DRs) in the M. tuberculosis complex DR region. Numerous M. bovis strains show a lack of several spacers which appears as a gap in the spoligotyping pattern. To determine whether these gaps contain alternative spacers not included in the spoligotyping membrane, PCRs using primers that hybridize to the spacers adjacent to the gaps were performed. Comparing the sizes of products obtained by PCR with those deduced from spoligotyping patterns, fragments were selected and sequenced to look for alternative spacers. Upon analysis of the sequences, five alternative spacers were detected, although deletions of spacers are mainly responsible for the observed gaps. The alternative spacers, which are more frequent in M. bovis than in M. tuberculosis, may contribute to increased M. bovis differentiation. PMID:11230428