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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. Discovery and characterization of Alu repeat sequences via precise local read assembly

    PubMed Central

    Wildschutte, Julia H.; Baron, Alayna; Diroff, Nicolette M.; Kidd, Jeffrey M.

    2015-01-01

    Alu insertions have contributed to >11% of the human genome and ∼30–35 Alu subfamilies remain actively mobile, yet the characterization of polymorphic Alu insertions from short-read data remains a challenge. We build on existing computational methods to combine Alu detection and de novo assembly of WGS data as a means to reconstruct the full sequence of insertion events from Illumina paired end reads. Comparison with published calls obtained using PacBio long-reads indicates a false discovery rate below 5%, at the cost of reduced sensitivity due to the colocation of reference and non-reference repeats. We generate a highly accurate call set of 1614 completely assembled Alu variants from 53 samples from the Human Genome Diversity Project (HGDP) panel. We utilize the reconstructed alternative insertion haplotypes to genotype 1010 fully assembled insertions, obtaining >99% agreement with genotypes obtained by PCR. In our assembled sequences, we find evidence of premature insertion mechanisms and observe 5′ truncation in 16% of AluYa5 and AluYb8 insertions. The sites of truncation coincide with stem-loop structures and SRP9/14 binding sites in the Alu RNA, implicating L1 ORF2p pausing in the generation of 5′ truncations. Additionally, we identified variable AluJ and AluS elements that likely arose due to non-retrotransposition mechanisms. PMID:26503250

  6. Recombinations between Alu repeat sequences that result in partial deletions within the C1 inhibitor gene.

    PubMed

    Ariga, T; Carter, P E; Davis, A E

    1990-12-01

    Genomic DNA sequence analysis was used to define the extent of deletions within the C1 inhibitor gene in two families with type I hereditary angioneurotic edema. Southern blot analysis initially indicated the presence of the partial deletions. One deletion was approximately 2 kb and included exon VII, whereas the other was approximately 8.5 kb and included exons IV-VI. Genomic libraries from an affected member of each family were constructed and clones containing the deletions were analyzed. Sequence analysis of the deletion joints of the mutants and corresponding regions of the normal gene in the two families demonstrated that both deletion joints resulted from recombination of two Alu repetitive DNA elements. Alu repeat sequences from introns VI and VII combined to make a novel Alu in family A, and Alu sequences in introns III and VI were spliced to make a new Alu in family B. The splice sites in the Alu sequences of both mutants were located in the left arm of the Alu element, and both recombination joints overlapped one of the RNA polymerase III promoter sequences. Because the involved Alu sequences, in both instances, were oriented in the same direction, unequal crossingover is the most likely mechanism to account for these mutations. PMID:2276734

  7. Circular RNAs are abundant, conserved, and associated with ALU repeats

    PubMed Central

    Jeck, William R.; Sorrentino, Jessica A.; Wang, Kai; Slevin, Michael K.; Burd, Christin E.; Liu, Jinze; Marzluff, William F.; Sharpless, Norman E.

    2013-01-01

    Circular RNAs composed of exonic sequence have been described in a small number of genes. Thought to result from splicing errors, circular RNA species possess no known function. To delineate the universe of endogenous circular RNAs, we performed high-throughput sequencing (RNA-seq) of libraries prepared from ribosome-depleted RNA with or without digestion with the RNA exonuclease, RNase R. We identified >25,000 distinct RNA species in human fibroblasts that contained non-colinear exons (a “backsplice”) and were reproducibly enriched by exonuclease degradation of linear RNA. These RNAs were validated as circular RNA (ecircRNA), rather than linear RNA, and were more stable than associated linear mRNAs in vivo. In some cases, the abundance of circular molecules exceeded that of associated linear mRNA by >10-fold. By conservative estimate, we identified ecircRNAs from 14.4% of actively transcribed genes in human fibroblasts. Application of this method to murine testis RNA identified 69 ecircRNAs in precisely orthologous locations to human circular RNAs. Of note, paralogous kinases HIPK2 and HIPK3 produce abundant ecircRNA from their second exon in both humans and mice. Though HIPK3 circular RNAs contain an AUG translation start, it and other ecircRNAs were not bound to ribosomes. Circular RNAs could be degraded by siRNAs and, therefore, may act as competing endogenous RNAs. Bioinformatic analysis revealed shared features of circularized exons, including long bordering introns that contained complementary ALU repeats. These data show that ecircRNAs are abundant, stable, conserved and nonrandom products of RNA splicing that could be involved in control of gene expression. PMID:23249747

  8. Effective Alu Repeat Based RT-Qpcr Normalization in Cancer Cell Perturbation Experiments

    PubMed Central

    Rihani, Ali; Van Maerken, Tom; Pattyn, Filip; Van Peer, Gert; Beckers, Anneleen; De Brouwer, Sara; Kumps, Candy; Mets, Evelien; Van der Meulen, Joni; Rondou, Pieter; Leonelli, Carina; Mestdagh, Pieter; Speleman, Frank; Vandesompele, Jo

    2013-01-01

    Background Measuring messenger RNA (mRNA) levels using the reverse transcription quantitative polymerase chain reaction (RT-qPCR) is common practice in many laboratories. A specific set of mRNAs as internal control reference genes is considered as the preferred strategy to normalize RT-qPCR data. Proper selection of reference genes is a critical issue, especially in cancer cells that are subjected to different in vitro manipulations. These manipulations may result in dramatic alterations in gene expression levels, even of assumed reference genes. In this study, we evaluated the expression levels of 11 commonly used reference genes as internal controls for normalization of 19 experiments that include neuroblastoma, T-ALL, melanoma, breast cancer, non small cell lung cancer (NSCL), acute myeloid leukemia (AML), prostate cancer, colorectal cancer, and cervical cancer cell lines subjected to various perturbations. Results The geNorm algorithm in the software package qbase+ was used to rank the candidate reference genes according to their expression stability. We observed that the stability of most of the candidate reference genes varies greatly in perturbation experiments. Expressed Alu repeats show relatively stable expression regardless of experimental condition. These Alu repeats are ranked among the best reference assays in all perturbation experiments and display acceptable average expression stability values (M<0.5). Conclusions We propose the use of Alu repeats as a reference assay when performing cancer cell perturbation experiments. PMID:23977142

  9. Novel SLC7A7 large rearrangements in lysinuric protein intolerance patients involving the same AluY repeat

    PubMed Central

    Font-Llitjós, Mariona; Rodríguez-Santiago, Benjamín; Espino, Meritxell; Sillué, Ruth; Mañas, Sandra; Gómez, Laia; Pérez-Jurado, Luis A; Palacín, Manuel; Nunes, Virginia

    2009-01-01

    Lysinuric protein intolerance (LPI) is a rare autosomal inherited disease caused by defective cationic aminoacid transport 4F2hc/y+LAT-1 at the basolateral membrane of epithelial cells in the intestine and kidney. LPI is a multisystemic disease with a variety of clinical symptoms such as hepatosplenomegaly, osteoporosis, hypotonia, developmental delay, pulmonary insufficiency or end-stage renal disease. The SLC7A7 gene, which encodes the y+LAT-1 protein, is mutated in LPI patients. Mutation analysis of the promoter localized in intron 1 and all exons of the SLC7A7 gene was performed in 11 patients from 9 unrelated LPI families. Point mutation screening was performed by exon direct sequencing and a new multiplex ligation probe amplification (MLPA) assay was set up for large rearrangement analysis. Eleven SLC7A7-specific mutations were identified, seven of them were novel: p.L124P, p.C425R, p.R468X, p.Y274fsX21, c.625+1G>C, DelE4-E11 and DelE6-E11. The novel large deletions originated by the recombination of Alu repeats at introns 3 and 5, respectively, with the same AluY sequence localized at the SLC7A7 3′ region. The novel MLPA assay is robust and valuable for LPI molecular diagnosis. Our results suggest that genomic rearrangements of SLC7A7 play a more important role in LPI than has been reported, increasing the detection rate from 5.1 to 21.4%. Moreover, the 3′ region AluY repeat could be a recombination hot spot as it is involved in 38% of all SLC7A7 rearranged chromosomes described so far. PMID:18716612

  10. Analysis of genomic rearrangements associated with EGRFvIII expression suggests involvement of Alu repeat elements.

    PubMed Central

    Frederick, L.; Eley, G.; Wang, X. Y.; James, C. D.

    2000-01-01

    We have developed a polymerase chain reaction (PCR)-based strategy for the synthesis and analysis of rearranged epidermal growth factor receptor (EGFR) fragments associated with the vIII mutant receptor expressed in glioblastomas with EGFR amplification. The sequencing of aberrant tumor fragments showed that intragenic deletion rearrangements consistently involve an approximately 600-bp region in intron 7 of EGFR and several rearrangement sites interspersed throughout the large (>100 kb) first intron of this gene. Examination of the intron 7 breakpoint region revealed an Alu repeat element, and all intron 7 rearrangement sites were located within or downstream of this repeat sequence. Analysis of intron 1 for similar sequences resulted in the identification of 11 sites containing >80% homology with parts of the Alu element in intron 7. Reverse transcriptase-PCR and/or Western analysis of the tumors showed the presence of EGFRvIII cDNAs and/or proteins, respectively, in all cases for which a rearranged genomic fragment was generated by long-range PCR. Collectively, these data suggest that EGFR rearrangements, associated with the synthesis of the most common EGFR mutant, are mediated by a specific sequence element. PMID:11302336

  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. The human gene (CSNK2A1) coding for the casein kinase II subunit [alpha] is located on chromosome 20 and contains tandemly arranged Alu repeats

    SciTech Connect

    Wirkner, U.; Lichter, P.; Pyerin, W. ); Voss, H.; Ansorge, W. )

    1994-01-15

    The authors have isolated and characterized an 18.9-kb genomic clone representing a central portion of the human casein kinase II (CKII) subunit [alpha] gene (CSNK2A1). Using the whole clone as a probe, the gene was localized on chromosome 20p13. The clone contains eight exons whose sequences comprise bases 102 to 824 of the coding region of the human CKII[alpha]. The exon/intron splice junctions conform to the gt/ag rule. Three of the nine introns are located at positions corresponding to those in the CKII[alpha] gene of the nematode Caenorhabditis elegans. The introns contain eight complete and eight incomplete Alu repeats. Some of the Alu sequences are arranged in tandems of two or three, which seem to originate from insertions of younger Alu sequences into the poly(A) region of previously integrated Alu sequences, as indicated by flanking direct repeats. 50 refs., 5 figs., 1 tab.

  13. Mapping of 28 (CA)[sub n] microsatellite repeats and 13 Alu markers on human chromosome 11 using a panel of somatic cell hybrids

    SciTech Connect

    Iizuka, Masayoshi; Sekiya, Takao ); Jones, C. ); Hayashi, Kenshi )

    1994-02-01

    The authors report the mapping of 28 (CA)[sub n] microsatellite repeats and 13 Alu repeats. Most are highly polymorphic and map in 24 intervals on chromosome 11 by PCR amplification from DNAs of a panel of somatic hybrids. 10 refs., 1 fig., 1 tab.

  14. Identification of an Alu-repeat-mediated deletion of OPTN upstream region in a patient with a complex ocular phenotype.

    PubMed

    Schilter, Kala F; Reis, Linda M; Sorokina, Elena A; Semina, Elena V

    2015-11-01

    Genetic causes of ocular conditions remain largely unknown. To reveal the molecular basis for a congenital ocular phenotype associated with glaucoma we performed whole-exome sequencing (WES) and whole-genome copy number analyses of patient DNA. WES did not identify a causative variant. Copy number variation analysis identified a deletion of 10p13 in the patient and his unaffected father; the deletion breakpoint contained a single 37-bp sequence that is normally present in two distinct Alu repeats separated by ~181 kb. The deletion removed part of the upstream region of optineurin (OPTN) as well as the upstream sequence and two coding exons of coiled-coil domain containing 3 (CCDC3); analysis of the patient's second allele showed normal OPTN and CCDC3 sequences. Studies of zebrafish orthologs identified expression in the developing eye for both genes. OPTN is a known factor in dominant adult-onset glaucoma and Amyotrophic Lateral Sclerosis (ALS). The deletion eliminates 98 kb of the OPTN upstream sequence leaving only ~1 kb of the proximal promoter region. Comparison of transcriptional activation capability of the 3 kb normal and the rearranged del(10)(p13) OPTN promoter sequences demonstrated a statistically significant decrease for the deleted allele; sequence analysis of the entire deleted region identified multiple conserved elements with possible cis-regulatory activity. Additional screening of CCDC3 indicated that heterozygous loss-of-function alleles are unlikely to cause congenital ocular disease. In summary, we report the first regulatory region deletion involving OPTN, caused by Alu-mediated nonallelic homologous recombination and possibly contributing to the patient's ocular phenotype. In addition, our data indicate that Alu-mediated rearrangements of the OPTN upstream region may represent a new source of affected alleles in human conditions. Evaluation of the upstream OPTN sequences in additional ocular and ALS patients may help to determine the role

  15. Alu elements: know the SINEs

    PubMed Central

    2011-01-01

    Alu elements are primate-specific repeats and comprise 11% of the human genome. They have wide-ranging influences on gene expression. Their contribution to genome evolution, gene regulation and disease is reviewed. PMID:22204421

  16. Three RFLPs defining a haplotype associated with the common mutation in a human medium-chain acyl-CoA dehydrogenase (MCAD) deficiency occur in Alu repeats

    SciTech Connect

    Zhifang Zhang; Yeqing Zhou; Kelly, D.P.; Strauss, A.W. St. Louis Children's Hospital, MO ); Kolvraa, S.; Gregersen, N. )

    1993-06-01

    Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a common inborn error of fatty-acid oxidation and may cause sudden infant death. Previous studies revealed that (i) homozygosity for an A-to-G mutation at nucleotide 985 of the mRNA coding region (A985G) is an extremely common cause of MCAD deficiency and (ii) MCAD deficiency is strongly associated with a particular haplotype for RFLPs for BanII, PstI, and TaqI. TaqI allele 2 is always associated with the A985G mutation in human MCAD deficiency. In this study, the authors have delineated the molecular basis of the RFLPs for PstI, BamHI, and TaqI in the human MCAD gene. Their results prove that the three RFLPs are caused by point mutations in the 8 kb of DNA encompassing exons 8--10 of the human MCAD gene. The TaqI polymorphism is caused by a C-to-A substitution 392 bp upstream of the exon 8, and the PstI and BamHI polymorphisms are due to T-to-C and G-to-A substitutions, respectively, which are 727 and 931 bp downstream of exon 10, respectively. All three RFLPs lie within Alu repetitive sequences. Comparison of intronic sequences immediately following exon 10 from two normal individuals with different haplotypes showed that this region contains densely packed Alu repeats and is highly polymorphic. The results are consistent both with a founder effect as the cause of the high prevalence of a single (A985G) mutation in MCAD deficiency and with its association with a particular haplotype for these intragenic RFLPs. 27 refs., 6 figs., 1 tab.

  17. ALU repeats in promoters are position-dependent co-response elements (coRE) that enhance or repress transcription by dimeric and monomeric progesterone receptors.

    PubMed

    Jacobsen, Britta M; Jambal, Purevsuren; Schittone, Stephanie A; Horwitz, Kathryn B

    2009-07-01

    We have conducted an in silico analysis of progesterone response elements (PRE) in progesterone receptor (PR) up-regulated promoters. Imperfect inverted repeats, direct repeats, and half-site PRE are widespread, not only in PR-regulated, but also in non-PR-regulated and random promoters. Few resemble the commonly used palindromic PRE with three nucleotide (nt) spacers. We speculated that PRE may be necessary but insufficient to control endogenous PR-dependent transcription. A search for PRE partners identified a highly conserved 234-nt sequence invariably located within 1-2 kb of transcription start sites. It resembles ALU repeats and contains binding sites for 11 transcription factors. The 234-nt sequence of the PR-regulated 8-oxoguanine DNA glycosylase promoter was cloned in the forward or reverse orientation in front of zero, one, or two inverted repeat PRE, and one or tandem PRE half-sites, driving luciferase. Under these conditions the 234-nt sequence functions as a co-response element (coRE). From the PRE or tandem half-sites, the reverse coRE is a strong activator of PR and glucocorticoid receptor-dependent transcription. The forward coRE is a powerful repressor. The prevalence of PRE half-sites in natural promoters suggested that PR monomers regulate transcription. Indeed, dimerization-domain mutant PR monomers were stronger transactivators than wild-type PR on PRE or tandem half-sites. This was repressed by the forward coRE. We propose that in natural promoters the coRE functions as a composite response element with imperfect PRE and half-sites to present variable, orientation-dependent transcription factors for interaction with nearby PR. PMID:19372234

  18. Patterns of Ancestral Human Diversity: An Analysis of Alu-Insertion and Restriction-Site Polymorphisms

    PubMed Central

    Watkins, W. S.; Ricker, C. E.; Bamshad, M. J.; Carroll, M. L.; Nguyen, S. V.; Batzer, M. A.; Harpending, H. C.; Rogers, A. R.; Jorde, L. B.

    2001-01-01

    We have analyzed 35 widely distributed, polymorphic Alu loci in 715 individuals from 31 world populations. The average frequency of Alu insertions (the derived state) is lowest in Africa (.42) but is higher and similar in India (.55), Europe (.56), and Asia (.57). A comparison with 30 restriction-site polymorphisms (RSPs) for which the ancestral state has been determined shows that the frequency of derived RSP alleles is also lower in Africa (.35) than it is in Asia (.45) and in Europe (.46). Neighbor-joining networks based on Alu insertions or RSPs are rooted in Africa and show African populations as separate from other populations, with high statistical support. Correlations between genetic distances based on Alu and nuclear RSPs, short tandem-repeat polymorphisms, and mtDNA, in the same individuals, are high and significant. For the 35 loci, Alu gene diversity and the diversity attributable to population subdivision is highest in Africa but is lower and similar in Europe and Asia. The distribution of ancestral alleles is consistent with an origin of early modern human populations in sub-Saharan Africa, the isolation and preservation of ancestral alleles within Africa, and an expansion out of Africa into Eurasia. This expansion is characterized by increasing frequencies of Alu inserts and by derived RSP alleles with reduced genetic diversity in non-African populations. PMID:11179020

  19. Adenovirus type 2 preferentially stimulates polymerase III transcription of Alu elements by relieving repression: a potential role for chromatin.

    PubMed Central

    Russanova, V R; Driscoll, C T; Howard, B H

    1995-01-01

    The number of Alu transcripts that accumulate in HeLa and other human cells is normally very low; however, infection with adenovirus type 5 increases the expression of Alu elements dramatically, indicating that the potential for polymerase III (pol III)-dependent Alu transcription in vivo is far greater than generally observed (B. Panning and J.R. Smiley, Mol. Cell. Biol. 13:3231-3244, 1993). In this study, we employed nuclear run-on in combination with a novel RNase H-based assay to investigate transcription from uninfected and adenovirus type 2-infected nuclei, as well as genomic DNAs from uninfected and infected cells. When performed in the presence of excess uninfected nuclear extract, such assays revealed that (i) the vast majority of transcriptionally competent Alu elements in nuclei are masked from the pol III transcriptional machinery and (ii) the induction of Alu expression upon adenovirus infection can be largely accounted for by an increased availability of these elements to the pol III transcription machinery. We also investigated the role of H1 histone for silencing of Alu genes and, in comparison, mouse B2 repetitive elements. Depletion of H1 led to an approximately 17-fold activation of B2 repetitive elements but did not change Alu transcription relative to that of constitutively expressed 5S rRNA genes. These results are consistent with the view that Alu repeats are efficiently sequestered by chromatin proteins, that such masking cannot be accounted for by nonspecific H1-dependent repression, and that adenovirus infection at least partially overrides the repressive mechanism(s). PMID:7623822

  20. 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

  1. 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

  2. African origin of human-specific polymorphic Alu insertions

    SciTech Connect

    Batzer, M.A.; Alegria-Hartman, M. ); Stoneking, M. ); Bazan, H.; Kass, D.H.; Shaikh, T.H.; Scheer, W.D. ); Novick, G.E.; Herrera, R.J. ); Ioannou, P.A. )

    1994-12-06

    Alu elements are a family of interspersed repeats that have mobilized throughout primate genomes by retroposition from a few [open quotes]master[close quotes] genes. Among the 500,000 Alu elements in the human genome are members of the human-specific subfamily that are not fixed in the human species. Four such polymorphic human-specific Alu insertions were analyzed by a rapid, PCR-based assay. These four polymorphic Alu insertions were shown to be absent from the genomes of a number of nonhuman primates, consistent with their arising as human genetic polymorphisms sometime after the human/African ape divergence. Analysis of 664 unrelated individuals from 16 population groups from around the world revealed substantial levels of variation within population groups and significant genetic differentiation among groups. No significant associations were found among the four loci, consistent with their location on different chromosomes. A maximum-likelihood tree of population relationships showed four major groupings consisting of Africa, Europe, Asia/Americas, and Australia/New Guinea, which is concordant with similar trees based on other loci. A particularly useful feature of the polymorphic Alu insertions is that the ancestral state is known to be the absence of the Alu element, and the presence of the Alu element at a particular chromosomal site reflects a single, unique event in human evolution. A hypothetical ancestral group can then be included in the tree analysis, with the frequency of each insertion set to zero. The ancestral group connected to the maximum-likelihood tree within the African branch, which suggests an African origin of these polymorphic Alu insertions. These data are concordant with other diverse data sets, which lends further support to the recent African origin hypothesis for modern humans. Polymorphic Alu insertions represent a source of genetic variation for studying human population structure and evolution. 45 refs., 2 figs., 1 tab.

  3. A knowledgebase of the human Alu repetitive elements.

    PubMed

    Mallona, Izaskun; Jordà, Mireia; Peinado, Miguel A

    2016-04-01

    Alu elements are the most abundant retrotransposons in the human genome with more than one million copies. Alu repeats have been reported to participate in multiple processes related with genome regulation and compartmentalization. Moreover, they have been involved in the facilitation of pathological mutations in many diseases, including cancer. The contribution of Alus and other repeats in genomic regulation is often overlooked because their study poses technical and analytical challenges hardly attainable with conventional strategies. Here we propose the integration of ontology-based semantic methods to query a knowledgebase for the human Alus. The knowledgebase for the human Alus leverages Sequence (SO) and Gene Ontologies (GO) and is devoted to address functional and genetic information in the genomic context of the Alus. For each Alu element, the closest gene and transcript are stored, as well their functional annotation according to GO, the state of the chromatin and the transcription factors binding sites inside the Alu. The model uses Web Ontology Language (OWL) and Semantic Web Rule Language (SWRL). As a case of use and to illustrate the utility of the tool, we have evaluated the epigenetic states of Alu repeats associated with gene promoters according to their transcriptional activity. The ontology is easily extendable, offering a scaffold for the inclusion of new experimental data. The RDF/XML formalization is freely available at http://aluontology.sourceforge.net/. PMID:26827622

  4. Alu element-containing RNAs maintain nucleolar structure and function.

    PubMed

    Caudron-Herger, Maïwen; Pankert, Teresa; Seiler, Jeanette; Németh, Attila; Voit, Renate; Grummt, Ingrid; Rippe, Karsten

    2015-11-12

    Non-coding RNAs play a key role in organizing the nucleus into functional subcompartments. By combining fluorescence microscopy and RNA deep-sequencing-based analysis, we found that RNA polymerase II transcripts originating from intronic Alu elements (aluRNAs) were enriched in the nucleolus. Antisense-oligo-mediated depletion of aluRNAs or drug-induced inhibition of RNA polymerase II activity disrupted nucleolar structure and impaired RNA polymerase I-dependent transcription of rRNA genes. In contrast, overexpression of a prototypic aluRNA sequence increased both nucleolus size and levels of pre-rRNA, suggesting a functional link between aluRNA, nucleolus integrity and pre-rRNA synthesis. Furthermore, we show that aluRNAs interact with nucleolin and target ectopic genomic loci to the nucleolus. Our study suggests an aluRNA-based mechanism that links RNA polymerase I and II activities and modulates nucleolar structure and rRNA production. PMID:26464461

  5. Increasing Positive Perceptions of Counseling: The Importance of Repeated Exposures

    ERIC Educational Resources Information Center

    Kaplan, Scott A.; Vogel, David L.; Gentile, Douglas A.; Wade, Nathaniel G.

    2012-01-01

    This study assesses the effectiveness of repeated exposures to a video intervention based on the Elaboration Likelihood Model. The video was designed to increase help-seeking attitudes and perceptions of peer norms and to decrease the stigma associated with seeking counseling. Participants were 290 undergraduates who were randomly assigned to a…

  6. 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

  7. Can nursing students' confidence levels increase with repeated simulation activities?

    PubMed

    Cummings, Cynthia L; Connelly, Linda K

    2016-01-01

    In 2014, nursing faculty conducted a study with undergraduate nursing students on their satisfaction, confidence, and educational practice levels, as it related to simulation activities throughout the curriculum. The study was a voluntary survey conducted on junior and senior year nursing students. It consisted of 30 items based on the Student Satisfaction and Self-Confidence in Learning and the Educational Practices Questionnaire (Jeffries, 2012). Mean averages were obtained for each of the 30 items from both groups and were compared using T scores for unpaired means. The results showed that 8 of the items had a 95% confidence level and when combined the items were significant for p <.001. The items identified were those related to self-confidence and active learning. Based on these findings, it can be assumed that repeated simulation experiences can lead to an increase in student confidence and active learning. PMID:26599594

  8. Reduced hnRNPA3 increases C9orf72 repeat RNA levels and dipeptide-repeat protein deposition.

    PubMed

    Mori, Kohji; Nihei, Yoshihiro; Arzberger, Thomas; Zhou, Qihui; Mackenzie, Ian R; Hermann, Andreas; Hanisch, Frank; Kamp, Frits; Nuscher, Brigitte; Orozco, Denise; Edbauer, Dieter; Haass, Christian

    2016-09-01

    Intronic hexanucleotide (G4C2) repeat expansions in C9orf72 are genetically associated with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). The repeat RNA accumulates within RNA foci but is also translated into disease characterizing dipeptide repeat proteins (DPR). Repeat-dependent toxicity may affect nuclear import. hnRNPA3 is a heterogeneous nuclear ribonucleoprotein, which specifically binds to the G4C2 repeat RNA We now report that a reduction of nuclear hnRNPA3 leads to an increase of the repeat RNA as well as DPR production and deposition in primary neurons and a novel tissue culture model that reproduces features of the C9orf72 pathology. In fibroblasts derived from patients carrying extended C9orf72 repeats, nuclear RNA foci accumulated upon reduction of hnRNPA3. Neurons in the hippocampus of C9orf72 patients are frequently devoid of hnRNPA3. Reduced nuclear hnRNPA3 in the hippocampus of patients with extended C9orf72 repeats correlates with increased DPR deposition. Thus, reduced hnRNPA3 expression in C9orf72 cases leads to increased levels of the repeat RNA as well as enhanced production and deposition of DPR proteins and RNA foci. PMID:27461252

  9. 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. PMID:19740767

  10. Alu Evolution in Human Populations: Using the Coalescent to Estimate Effective Population Size

    PubMed Central

    Sherry, S. T.; Harpending, H. C.; Batzer, M. A.; Stoneking, M.

    1997-01-01

    There are estimated to be ~1000 members of the Ya5 Alu subfamily of retroposons in humans. This subfamily has a distribution restricted to humans, with a few copies in gorillas and chimpanzees. Fifty-seven Ya5 elements were previously cloned from a HeLa-derived randomly sheared total genomic library, sequenced, and screened for polymorphism in a panel of 120 unrelated humans. Forty-four of the 57 cloned Alu repeats were monomorphic in the sample and 13 Alu repeats were dimorphic for insertion presence/absence. The observed distribution of sample frequencies of the 13 dimorphic elements is consistent with the theoretical expectation for elements ascertained in a single diploid cell line. Coalescence theory is used to compute expected total pedigree branch lengths for monomorphic and dimorphic elements, leading to an estimate of human effective population size of ~18,000 during the last one to two million years. PMID:9409852

  11. Alu elements shape the primate transcriptome by cis-regulation of RNA editing

    PubMed Central

    2014-01-01

    Background RNA editing by adenosine to inosine deamination is a widespread phenomenon, particularly frequent in the human transcriptome, largely due to the presence of inverted Alu repeats and their ability to form double-stranded structures – a requisite for ADAR editing. While several hundred thousand editing sites have been identified within these primate-specific repeats, the function of Alu-editing has yet to be elucidated. Results We show that inverted Alu repeats, expressed in the primate brain, can induce site-selective editing in cis on sites located several hundred nucleotides from the Alu elements. Furthermore, a computational analysis, based on available RNA-seq data, finds that site-selective editing occurs significantly closer to edited Alu elements than expected. These targets are poorly edited upon deletion of the editing inducers, as well as in homologous transcripts from organisms lacking Alus. Sequences surrounding sites near edited Alus in UTRs, have been subjected to a lesser extent of evolutionary selection than those far from edited Alus, indicating that their editing generally depends on cis-acting Alus. Interestingly, we find an enrichment of primate-specific editing within encoded sequence or the UTRs of zinc finger-containing transcription factors. Conclusions We propose a model whereby primate-specific editing is induced by adjacent Alu elements that function as recruitment elements for the ADAR editing enzymes. The enrichment of site-selective editing with potentially functional consequences on the expression of transcription factors indicates that editing contributes more profoundly to the transcriptomic regulation and repertoire in primates than previously thought. PMID:24485196

  12. Repeated Training with Augmentative Vibrotactile Feedback Increases Object Manipulation Performance

    PubMed Central

    Stepp, Cara E.; An, Qi; Matsuoka, Yoky

    2012-01-01

    Most users of prosthetic hands must rely on visual feedback alone, which requires visual attention and cognitive resources. Providing haptic feedback of variables relevant to manipulation, such as contact force, may thus improve the usability of prosthetic hands for tasks of daily living. Vibrotactile stimulation was explored as a feedback modality in ten unimpaired participants across eight sessions in a two-week period. Participants used their right index finger to perform a virtual object manipulation task with both visual and augmentative vibrotactile feedback related to force. Through repeated training, participants were able to learn to use the vibrotactile feedback to significantly improve object manipulation. Removal of vibrotactile feedback in session 8 significantly reduced task performance. These results suggest that vibrotactile feedback paired with training may enhance the manipulation ability of prosthetic hand users without the need for more invasive strategies. PMID:22384283

  13. 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

  14. 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.

  15. The Basques according to polymorphic Alu insertions.

    PubMed

    de Pancorbo, M M; López-Martínez, M; Martínez-Bouzas, C; Castro, A; Fernández-Fernández, I; de Mayolo, G A; de Mayolo, A A; de Mayolo, P A; Rowold, D J; Herrera, R J

    2001-08-01

    Polymorphic Alu insertions provide a set of DNA markers of interest in human population genetics. Approximately 1000-2000 of these insertions have not reached fixation within the human genome. Each one of these polymorphic loci most probably resulted from a unique insertional event, and therefore all individuals possessing the insertion are related by descent not just state. In addition, the direction of mutational change is toward the gain of the Alu element at a particular locus. Therefore, the improved knowledge of both the ancestral state and the direction of mutational change greatly facilitates the analysis of population relationships. As a result, Alu insertion polymorphisms represent a significant tool for population genetic studies. In this study, polymorphic Alu insertions have been employed to ascertain phylogenetic relationships among Basque groups and worldwide populations. The Basques are considered to be a geographic isolate with a unique language and customs. They may be direct descendants of Cro-Magnon enclaves from the upper Paleolithic (38,000 to 10,000 years). The Basques are distributed among narrow valleys in northeastern Spain with little migration between them until recently. This characteristic may have had an effect on allelic frequency distributions. With the aim of studying this possible effect, we have analyzed six autosomal polymorphic Alu loci from four different sites within the Spanish Basque region in order to ascertain any genetic heterogeneity among the Basques. The results are consistent with a lack of homogeneity among these four autochthonous Basque groups. PMID:11511929

  16. Urinary 3-methylhistidine excretion increases with repeated weight training exercise.

    PubMed

    Pivarnik, J M; Hickson, J F; Wolinsky, I

    1989-06-01

    This investigation examines the effect of progressive resistance weight training exercise on urinary 3-methylhistidine (3-MH) excretions in untrained subjects. For 19 consecutive days, 11 males were fed a weight maintenance, lactovegetarian diet which contained the Recommended Dietary Allowance (0.8g.kg-1.d-1) for protein. No exercise was performed for the first 7 d of the study. Subjects were strength tested on day 8 and performed upper and lower body weight training exercises from days 9-19. Complete, 24-h urine collections were obtained from each subject on a daily basis. Samples were assayed for creatinine and 3-MH. Stable baseline 3-MH values were present during the pre-exercise control period. Significant increases in 3-MH occurred by study day 11, which was the third day of weight training exercise. This was true regardless of whether the data were expressed by daily excretions (microM.d-1; P less than 0.01), per unit of body weight (microM.kg-1.d-1; P less than 0.005), or per unit of creatinine excretion (microM.g Creat-1.d-1; P less than 0.001). Since urinary 3-MH is an index of actin and myosin catabolism, these data support the hypothesis that the rate of skeletal muscle degradation is increased during strength building exercises. PMID:2733577

  17. Decreased Rate of Evolution in Y Chromosome STR Loci of Increased Size of the Repeat Unit

    PubMed Central

    Järve, Mari; Zhivotovsky, Lev A.; Rootsi, Siiri; Help, Hela; Rogaev, Evgeny I.; Khusnutdinova, Elza K.; Kivisild, Toomas; Sanchez, Juan J.

    2009-01-01

    Background Polymorphic Y chromosome short tandem repeats (STRs) have been widely used in population genetic and evolutionary studies. Compared to di-, tri-, and tetranucleotide repeats, STRs with longer repeat units occur more rarely and are far less commonly used. Principal Findings In order to study the evolutionary dynamics of STRs according to repeat unit size, we analysed variation at 24 Y chromosome repeat loci: 1 tri-, 14 tetra-, 7 penta-, and 2 hexanucleotide loci. According to our results, penta- and hexanucleotide repeats have approximately two times lower repeat variance and diversity than tri- and tetranucleotide repeats, indicating that their mutation rate is about half of that of tri- and tetranucleotide repeats. Thus, STR markers with longer repeat units are more robust in distinguishing Y chromosome haplogroups and, in some cases, phylogenetic splits within established haplogroups. Conclusions Our findings suggest that Y chromosome STRs of increased repeat unit size have a lower rate of evolution, which has significant relevance in population genetic and evolutionary studies. PMID:19789645

  18. 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

  19. 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…

  20. Repeated seizures induce long-term increase in hippocampal benzodiazepine receptors.

    PubMed Central

    McNamara, J O; Peper, A M; Patrone, V

    1980-01-01

    Repeated seizures, whether induced by kindling or electroshock, caused a long-lasting (at least 24 hr) increase of [3H]diazepam binding in hippocampal membranes of Sprague-Dawley rats. Scatchard analyses demonstrated that increased numbers of binding sites accounted for the increase. Neither repeated hypoxia nor repeated administration of electrical current without inducing seizures caused an increase of [3H]diazepam binding. Regardless of the method used for seizure induction, the response was graded in that large numbers of seizures were required to induce significant increases, whereas fewer seizures induced only slight increases. We suggest that the receptor increases imply a heightened response to benzodiazepines and more powerful hippocampal recurrent inhibition. PMID:6930682

  1. Maternal phthalate exposure during pregnancy is associated with DNA methylation of LINE-1 and Alu repetitive elements in Mexican-American children.

    PubMed

    Huen, Karen; Calafat, Antonia M; Bradman, Asa; Yousefi, Paul; Eskenazi, Brenda; Holland, Nina

    2016-07-01

    Phthalates are frequently used in personal care products and plasticizers and phthalate exposure is ubiquitous in the US population. Exposure to phthalates during critical periods in utero has been associated with a variety of adverse health outcomes but the biological mechanisms linking these exposures with disease are not well characterized. In this study, we examined the relationship of in utero phthalate exposure with repetitive element DNA methylation, an epigenetic marker of genome instability, in children from the longitudinal birth cohort CHAMACOS. Methylation of Alu and long interspersed nucleotide elements (LINE-1) was determined using pyrosequencing of bisulfite-treated DNA isolated from whole blood samples collected from newborns and 9 year old children (n=355). Concentrations of eleven phthalate metabolites were measured in urine collected from pregnant mothers at 13 and 26 weeks gestation. We found a consistent inverse association between prenatal concentrations of monoethyl phthalate, the most frequently detected urinary metabolite, with cord blood methylation of Alu repeats (β(95%CI): -0.14 (-0.28,0.00) and -0.16 (-0.31, -0.02)) for early and late pregnancy, respectively, and a similar but weaker association with LINE-1 methylation. Additionally, increases in urinary concentrations of di-(2-ethylhexyl) phthalate metabolites during late pregnancy were associated with lower levels of methylation of Alu repeats in 9 year old blood (significant p-values ranged from 0.003 to 0.03). Our findings suggest that prenatal exposure to some phthalates may influence differences in repetitive element methylation, highlighting epigenetics as a plausible biological mechanism through which phthalates may affect health. PMID:27019040

  2. An Alu-Based Phylogeny of Gibbons (Hylobatidae)

    PubMed Central

    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.

    2012-01-01

    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

  3. 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

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

    PubMed Central

    Kaur, Simranjeet; Pociot, Flemming

    2015-01-01

    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. PMID:26184322

  5. A Novel Protein Isoform of the Multicopy Human NAIP Gene Derives from Intragenic Alu SINE Promoters

    PubMed Central

    Romanish, Mark T.; Nakamura, Hisae; Lai, C. Benjamin; Wang, Yuzhuo; Mager, Dixie L.

    2009-01-01

    The human neuronal apoptosis inhibitory protein (NAIP) gene is no longer principally considered a member of the Inhibitor of Apoptosis Protein (IAP) family, as its domain structure and functions in innate immunity also warrant inclusion in the Nod-Like Receptor (NLR) superfamily. NAIP is located in a region of copy number variation, with one full length and four partly deleted copies in the reference human genome. We demonstrate that several of the NAIP paralogues are expressed, and that novel transcripts arise from both internal and upstream transcription start sites. Remarkably, two internal start sites initiate within Alu short interspersed element (SINE) retrotransposons, and a third novel transcription start site exists within the final intron of the GUSBP1 gene, upstream of only two NAIP copies. One Alu functions alone as a promoter in transient assays, while the other likely combines with upstream L1 sequences to form a composite promoter. The novel transcripts encode shortened open reading frames and we show that corresponding proteins are translated in a number of cell lines and primary tissues, in some cases above the level of full length NAIP. Interestingly, some NAIP isoforms lack their caspase-sequestering motifs, suggesting that they have novel functions. Moreover, given that human and mouse NAIP have previously been shown to employ endogenous retroviral long terminal repeats as promoters, exaptation of Alu repeats as additional promoters provides a fascinating illustration of regulatory innovations adopted by a single gene. PMID:19488400

  6. Transcription in vivo of an Alu family member upstream from the human epsilon-globin gene.

    PubMed Central

    Allan, M; Paul, J

    1984-01-01

    The more distal Alu repeat flanking the epsilon-globin gene is transcribed in K562 cells to generate transcripts 350-400 nucleotides in length. Initiation occurs at the start of the repeat, upstream of a putative PolIII control signal. These transcripts originate from the strand which does not code epsilon-globin and are oriented in the opposite direction from the gene. They are non-polyadenylated, nucleus-confined and are only detectable in association with expression of the epsilon-globin gene. Images PMID:6320117

  7. Increasing Reading Fluency in Elementary Students with Low Vision through Repeated Readings.

    ERIC Educational Resources Information Center

    Koenig, A. J.; Layton, C. A.

    1998-01-01

    Evaluation of the use of repeated readings to increase the reading fluency of four elementary students with low vision found the intervention was effective in improving all four students' reading fluency without adversely affecting error rates or comprehension. Students' improved reading rates also generalized to classroom reading. (DB)

  8. 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. PMID:27325546

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26085575

  10. 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. PMID:26085575

  11. Deletion of internal structured repeats increases the stability of a leucine-rich repeat protein, YopM

    PubMed Central

    Barrick, Doug

    2011-01-01

    Mapping the stability distributions of proteins in their native folded states provides a critical link between structure, thermodynamics, and function. Linear repeat proteins have proven more amenable to this kind of mapping than globular proteins. C-terminal deletion studies of YopM, a large, linear leucine-rich repeat (LRR) protein, show that stability is distributed quite heterogeneously, yet a high level of cooperativity is maintained [1]. Key components of this distribution are three interfaces that strongly stabilize adjacent sequences, thereby maintaining structural integrity and promoting cooperativity. To better understand the distribution of interaction energy around these critical interfaces, we studied internal (rather than terminal) deletions of three LRRs in this region, including one of these stabilizing interfaces. Contrary to our expectation that deletion of structured repeats should be destabilizing, we find that internal deletion of folded repeats can actually stabilize the native state, suggesting that these repeats are destabilizing, although paradoxically, they are folded in the native state. We identified two residues within this destabilizing segment that deviate from the consensus sequence at a position that normally forms a stacked leucine ladder in the hydrophobic core. Replacement of these nonconsensus residues with leucine is stabilizing. This stability enhancement can be reproduced in the context of nonnative interfaces, but it requires an extended hydrophobic core. Our results demonstrate that different LRRs vary widely in their contribution to stability, and that this variation is context-dependent. These two factors are likely to determine the types of rearrangements that lead to folded, functional proteins, and in turn, are likely to restrict the pathways available for the evolution of linear repeat proteins. PMID:21764506

  12. Alu insertion loci and platyrrhine primate phylogeny.

    PubMed

    Ray, David A; Xing, Jinchuan; Hedges, Dale J; Hall, Michael A; Laborde, Meredith E; Anders, Bridget A; White, Brittany R; Stoilova, Nadica; Fowlkes, Justin D; Landry, Kate E; Chemnick, Leona G; Ryder, Oliver A; Batzer, Mark A

    2005-04-01

    Short INterspersed Elements (SINEs) make very useful phylogenetic markers because the integration of a particular element at a location in the genome is irreversible and of known polarity. These attributes make analysis of SINEs as phylogenetic characters an essentially homoplasy-free affair. Alu elements are primate-specific SINEs that make up a large portion of the human genome and are also widespread in other primates. Using a combination wet-bench and computational approach we recovered 190 Alu insertions, 183 of which are specific to the genomes of nine New World primates. We used these loci to investigate branching order and have produced a cladogram that supports a sister relationship between Atelidae (spider, woolly, and howler monkeys) and Cebidae (marmosets, tamarins, and owl monkeys) and then the joining of this two family clade to Pitheciidae (titi and saki monkeys). The data support these relationships with a homoplasy index of 0.00. In this study, we report one of the largest applications of SINE elements to phylogenetic analysis to date, and the results provide a robust molecular phylogeny for platyrrhine primates. PMID:15737586

  13. Effect of alcohol consumption on peripheral blood Alu methylation in Korean men.

    PubMed

    Kim, Dong-Sun; Kim, Young Hun; Lee, Won Kee; Na, Yeon Kyung; Hong, Hae Sook

    2016-05-01

    Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create a substantial public health problem worldwide. To date, no therapeutic can effectively solve these problems. They are complex diseases characterized by both genetic and environmental factors. DNA methylation can act as a downstream effector of environmental signals and account for multi-factorial nature of the disease. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Alu elements host one-quarter of CpG dinucelotides in the genome to function as proxies for global DNA methylation. In this study, we evaluated the Alu methylation in the peripheral blood DNA of healthy volunteers and AUD patients using the pyrosequencing technology. The Alu methylation level is significantly higher in AUD compared to healthy controls (23.4 ± 1.6 versus 22.1 ± 1.0, t = 7.83, p < 0.0001). Moreover, significant correlation was found between Alu methylation and alcohol use disorders identification test score (r = 0.250, p < 0.0001), alcohol problem (r = 0.294, p < 0.0001), and life position (r = -0.205, p = 0.0005). Overall, these novel findings indicate that alcohol-related increase in Alu methylation might play a complex role in the etiology and pathogenesis of AUD. Further studies are required to elucidate the mechanisms underlying this relationship. PMID:26846433

  14. 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.

  15. 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

  16. 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. PMID:24381284

  17. 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. PMID:20541572

  18. 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.

  19. 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.

  20. 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

  1. Structure of the complete bacterial SRP Alu domain

    PubMed Central

    Kempf, Georg; Wild, Klemens; Sinning, Irmgard

    2014-01-01

    The Alu domain of the signal recognition particle (SRP) arrests protein biosynthesis by competition with elongation factor binding on the ribosome. The mammalian Alu domain is a protein–RNA complex, while prokaryotic Alu domains are protein-free with significant extensions of the RNA. Here we report the crystal structure of the complete Alu domain of Bacillus subtilis SRP RNA at 2.5 Å resolution. The bacterial Alu RNA reveals a compact fold, which is stabilized by prokaryote-specific extensions and interactions. In this ‘closed’ conformation, the 5′ and 3′ regions are clamped together by the additional helix 1, the connecting 3-way junction and a novel minor groove interaction, which we term the ‘minor-saddle motif’ (MSM). The 5′ region includes an extended loop–loop pseudoknot made of five consecutive Watson–Crick base pairs. Homology modeling with the human Alu domain in context of the ribosome shows that an additional lobe in the pseudoknot approaches the large subunit, while the absence of protein results in the detachment from the small subunit. Our findings provide the structural basis for purely RNA-driven elongation arrest in prokaryotes, and give insights into the structural adaption of SRP RNA during evolution. PMID:25270875

  2. 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. PMID:23239387

  3. 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

  4. 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…

  5. Mutations in Haemophilus influenzae mismatch repair genes increase mutation rates of dinucleotide repeat tracts but not dinucleotide repeat-driven pilin phase variation rates.

    PubMed

    Bayliss, Christopher D; Sweetman, Wendy A; Moxon, E Richard

    2004-05-01

    High-frequency, reversible switches in expression of surface antigens, referred to as phase variation (PV), are characteristic of Haemophilus influenzae. PV enables this bacterial species, an obligate commensal and pathogen of the human upper respiratory tract, to adapt to changes in the host environment. Phase-variable hemagglutinating pili are expressed by many H. influenzae isolates. PV involves alterations in the number of 5' TA repeats located between the -10 and -35 promoter elements of the overlapping, divergently orientated promoters of hifA and hifBCDE, whose products mediate biosynthesis and assembly of pili. Dinucleotide repeat tracts are destabilized by mismatch repair (MMR) mutations in Escherichia coli. The influence of mutations in MMR genes of H. influenzae strain Rd on dinucleotide repeat-mediated PV rates was investigated by using reporter constructs containing 20 5' AT repeats. Mutations in mutS, mutL, and mutH elevated rates approximately 30-fold, while rates in dam and uvrD mutants were increased 14- and 3-fold, respectively. PV rates of constructs containing 10 to 12 5' AT repeats were significantly elevated in mutS mutants of H. influenzae strains Rd and Eagan. An intact hif locus was found in 14 and 12% of representative nontypeable H. influenzae isolates associated with either otitis media or carriage, respectively. Nine or more tandem 5' TA repeats were present in the promoter region. Surprisingly, inactivation of mutS in two serotype b H. influenzae strains did not alter pilin PV rates. Thus, although functionally analogous to the E. coli MMR pathway and active on dinucleotide repeat tracts, defects in H. influenzae MMR do not affect 5' TA-mediated pilin PV. PMID:15126452

  6. Mitochondrial Complex 1 Inhibition Increases 4-Repeat Isoform Tau by SRSF2 Upregulation

    PubMed Central

    De Andrade, Anderson; Höglinger, Günter

    2014-01-01

    Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterised by intracellular aggregation of the microtubule-associated protein tau. The tau protein exists in 6 predominant isoforms. Depending on alternative splicing of exon 10, three of these isoforms have four microtubule-binding repeat domains (4R), whilst the others only have three (3R). In PSP there is an excess of the 4R tau isoforms, which are thought to contribute significantly to the pathological process. The cause of this 4R increase is so far unknown. Several lines of evidence link mitochondrial complex I inhibition to the pathogenesis of PSP. We demonstrate here for the first time that annonacin and MPP+, two prototypical mitochondrial complex I inhibitors, increase the 4R isoforms of tau in human neurons. We show that the splicing factor SRSF2 is necessary to increase 4R tau with complex I inhibition. We also found SRSF2, as well as another tau splicing factor, TRA2B, to be increased in brains of PSP patients. Thereby, we provide new evidence that mitochondrial complex I inhibition may contribute as an upstream event to the pathogenesis of PSP and suggest that splicing factors may represent an attractive therapeutic target to intervene in the disease process. PMID:25402454

  7. Alu-associated enhancement of single nucleotide polymorphisms in the human genome.

    PubMed

    Ng, Siu-Kin; Xue, Hong

    2006-03-01

    Identifying features shaping the architecture of sequence variations is important for understanding genome evolution and mapping disease loci. In this study, high-resolution scanning of Alu-centered alignments of the human genome sequences has revealed a striking elevation of the frequency of single nucleotide polymorphisms (SNP) in the body and tail of Alu sequences compared to flanking regions. This enhancement in SNP density is evident for all twenty-four chromosomes, and in both the Alu-body and Alu-tail, which together may be referred to as the Alu-SNPs. Reduced levels of Alu-SNPs in the sex chromosomes, especially in the non-recombining NRY region of the Y chromosome, are consistent with recombination events playing an important role in the enhancement. The Alu elements are unstable recombination-mutation hotspots in the human genome, and it is suggested that the Alu-SNPs represent a key manifestation of this instability. Variations in Alu-SNPs among the HapMap populations of northern and western European ancestry (CEU), Han Chinese from Beijing (CHB), Japanese from Tokyo (JPT), and Yoruba from Ibadan, Nigeria (YRI) indicate that the Alu-SNPs provide useful sequence markers, in addition to the Alu-insertion polymorphisms themselves, for the delineation of human genome evolution. That Alu-SNP levels are highest in the youngest Alu-Y, intermediate in the Alu-S of intermediate age, and lowest in the oldest Alu-J is consistent with the occurrence of not only genetic drift but also natural selection on the Alu-SNPs. Such evolutionary selection in turn suggests that Alu-SNPs might include potential sites of disease association, and therefore deserve detailed investigation. PMID:16380220

  8. 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. PMID:26318765

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

    PubMed Central

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

    2009-01-01

    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. PMID:19773425

  10. 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.

  11. Reciprocal Peer Tutoring and Repeated Reading: Increasing Practicality Using Student Groups

    ERIC Educational Resources Information Center

    Oddo, Maria; Barnett, David W.; Hawkins, Renee O.; Musti-Rao, Shobana

    2010-01-01

    Previous research has investigated the efficacy of peer-mediated repeated reading (RR) interventions carried out by student dyads. This research extends the existing research by investigating the impact of RR on oral reading fluency and comprehension when carried out by a teacher in small groups of fourth-grade students. Outcomes were analyzed…

  12. Repeated Exposure to Conditioned Fear Stress Increases Anxiety and Delays Sleep Recovery Following Exposure to an Acute Traumatic Stressor

    PubMed Central

    Greenwood, Benjamin N.; Thompson, Robert S.; Opp, Mark R.; Fleshner, Monika

    2014-01-01

    Repeated stressor exposure can sensitize physiological responses to novel stressors and facilitate the development of stress-related psychiatric disorders including anxiety. Disruptions in diurnal rhythms of sleep–wake behavior accompany stress-related psychiatric disorders and could contribute to their development. Complex stressors that include fear-eliciting stimuli can be a component of repeated stress experienced by human beings, but whether exposure to repeated fear can prime the development of anxiety and sleep disturbances is unknown. In the current study, adult male F344 rats were exposed to either control conditions or repeated contextual fear conditioning for 22 days followed by exposure to no, mild (10), or severe (100) acute uncontrollable tail shock stress. Exposure to acute stress produced anxiety-like behavior as measured by a reduction in juvenile social exploration and exaggerated shock-elicited freezing in a novel context. Prior exposure to repeated fear enhanced anxiety-like behavior as measured by shock-elicited freezing, but did not alter social exploratory behavior. The potentiation of anxiety produced by prior repeated fear was temporary; exaggerated fear was present 1 day but not 4 days following acute stress. Interestingly, exposure to acute stress reduced rapid eye movement (REM) and non-REM (NREM) sleep during the hours immediately following acute stress. This initial reduction in sleep was followed by robust REM rebound and diurnal rhythm flattening of sleep/wake behavior. Prior repeated fear extended the acute stress-induced REM and NREM sleep loss, impaired REM rebound, and prolonged the flattening of the diurnal rhythm of NREM sleep following acute stressor exposure. These data suggest that impaired recovery of sleep/wake behavior following acute stress could contribute to the mechanisms by which a history of prior repeated stress increases vulnerability to subsequent novel stressors and stress-related disorders. PMID

  13. Identification of human-specific AluS elements through comparative genomics.

    PubMed

    Lee, Jae; Kim, Yun-Ji; Mun, Seyoung; Kim, Heui-Soo; Han, Kyudong

    2015-01-25

    Mobile elements are responsible for ~45% of the human genome. Among them is the Alu element, accounting for 10% of the human genome (>1.1million copies). Several studies of Alu elements have reported that they are frequently involved in human genetic diseases and genomic rearrangements. In this study, we investigated the AluS subfamily, which is a relatively old Alu subfamily and has the highest copy number in primate genomes. Previously, a set of 263 human-specific AluS insertions was identified in the human genome. To validate these, we compared each of the human-specific AluS loci with its pre-insertion site in other primate genomes, including chimpanzee, gorilla, and orangutan. We obtained 24 putative human-specific AluS candidates via the in silico analysis and manual inspection, and then tried to verify them using PCR amplification and DNA sequencing. Through the PCR product sequencing, we were able to detect two instances of near-parallel Alu insertions in nearby sites that led to computational false negatives. Finally, we computationally and experimentally verified 23 human-specific AluS elements. We reported three alternative Alu insertion events, which are accompanied by filler DNA and/or Alu retrotransposition mediated-deletion. Bisulfite sequencing was carried out to examine DNA methylation levels of human-specific AluS elements. The results showed that fixed AluS elements are hypermethylated compared with polymorphic elements, indicating a possible relation between DNA methylation and Alu fixation in the human genome. PMID:25447892

  14. 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.

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

    PubMed Central

    Knight, A; Batzer, M A; Stoneking, M; Tiwari, H K; Scheer, W D; Herrera, R J; Deininger, P L

    1996-01-01

    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. PMID:8633071

  16. Effect of repeated insertions of curved sequences in DNA plasmids: a light-scattering study

    NASA Astrophysics Data System (ADS)

    Beretta, Stefano; Chirico, Giuseppe; Baldini, Giancarlo; Kapp, U.; Badaracco, G.

    1993-06-01

    The effect of the insertion of different amounts (from 0 to 6) of the curved sequence AluI in pUC18m plasmid (2686 base pairs, bp) is studied by dynamic light scattering. This sequence is a highly repeated 113 base pairs long sequence from Artemia Franciscana shrimp. A 30% compaction of the plasmids containing 2 and 6 adjacent AluI sequences compared to pUC8 plasmid (2717 bp) is observed. Furthermore the behavior of the translational diffusion coefficient Dt versus the number of adjacent AluI insertion is not monotonic.

  17. Repeated cocaine administration increases B-cell leukemia/lymphoma 2 phosphorylation in the rat dorsal striatum.

    PubMed

    Ahn, Sung Min; Jang, Dong Hye; Choe, Eun Sang

    2010-01-01

    Protein phosphorylation caused by drug administration is a critical step in the regulation of behavioral alterations. This study was conducted to determine how repeated exposure to cocaine phosphorylates B-cell leukemia/lymphoma 2 (Bcl2), which may be responsible for the regulation of behavioral alterations in the rat dorsal striatum. The results revealed that repeated systemic injections of cocaine (20 mg/kg) once a day for 7 consecutive days increased the phosphorylation of Bcl2 at serine 70 (Bcl2-S70). However, this increase was reduced by the blockade of dopamine D1 receptors, group I metabotropic glutamate receptors (mGluRs), and N-methyl-D-aspartate (NMDA) receptors. In addition, elevation of behavioral locomotor activity after repeated exposure to cocaine was partially reduced by the inhibition of Bcl2. These data suggest that stimulation of dopamine D1 receptors, group I mGluRs, and NMDA receptors following repeated cocaine administration is necessary for the induction of Bcl2-S70 phosphorylation, which contributes to the expression of behavioral sensitization. PMID:19879923

  18. An Alu-Based Phylogeny of Lemurs (Infraorder: Lemuriformes)

    PubMed Central

    McLain, Adam T.; Meyer, Thomas J.; Faulk, Christopher; Herke, Scott W.; Oldenburg, J. Michael; Bourgeois, Matthew G.; Abshire, Camille F.

    2012-01-01

    Lemurs (infraorder: Lemuriformes) are a radiation of strepsirrhine primates endemic to the island of Madagascar. As of 2012, 101 lemur species, divided among five families, have been described. Genetic and morphological evidence indicates all species are descended from a common ancestor that arrived in Madagascar ∼55–60 million years ago (mya). Phylogenetic relationships in this species-rich infraorder have been the subject of debate. Here we use Alu elements, a family of primate-specific Short INterspersed Elements (SINEs), to construct a phylogeny of infraorder Lemuriformes. Alu elements are particularly useful SINEs for the purpose of phylogeny reconstruction because they are identical by descent and confounding events between loci are easily resolved by sequencing. The genome of the grey mouse lemur (Microcebus murinus) was computationally assayed for synapomorphic Alu elements. Those that were identified as Lemuriformes-specific were analyzed against other available primate genomes for orthologous sequence in which to design primers for PCR (polymerase chain reaction) verification. A primate phylogenetic panel of 24 species, including 22 lemur species from all five families, was examined for the presence/absence of 138 Alu elements via PCR to establish relationships among species. Of these, 111 were phylogenetically informative. A phylogenetic tree was generated based on the results of this analysis. We demonstrate strong support for the monophyly of Lemuriformes to the exclusion of other primates, with Daubentoniidae, the aye-aye, as the basal lineage within the infraorder. Our results also suggest Lepilemuridae as a sister lineage to Cheirogaleidae, and Indriidae as sister to Lemuridae. Among the Cheirogaleidae, we show strong support for Microcebus and Mirza as sister genera, with Cheirogaleus the sister lineage to both. Our results also support the monophyly of the Lemuridae. Within Lemuridae we place Lemur and Hapalemur together to the exclusion of

  19. An alu-based phylogeny of lemurs (infraorder: Lemuriformes).

    PubMed

    McLain, Adam T; Meyer, Thomas J; Faulk, Christopher; Herke, Scott W; Oldenburg, J Michael; Bourgeois, Matthew G; Abshire, Camille F; Roos, Christian; Batzer, Mark A

    2012-01-01

    LEMURS (INFRAORDER: Lemuriformes) are a radiation of strepsirrhine primates endemic to the island of Madagascar. As of 2012, 101 lemur species, divided among five families, have been described. Genetic and morphological evidence indicates all species are descended from a common ancestor that arrived in Madagascar ∼55-60 million years ago (mya). Phylogenetic relationships in this species-rich infraorder have been the subject of debate. Here we use Alu elements, a family of primate-specific Short INterspersed Elements (SINEs), to construct a phylogeny of infraorder Lemuriformes. Alu elements are particularly useful SINEs for the purpose of phylogeny reconstruction because they are identical by descent and confounding events between loci are easily resolved by sequencing. The genome of the grey mouse lemur (Microcebus murinus) was computationally assayed for synapomorphic Alu elements. Those that were identified as Lemuriformes-specific were analyzed against other available primate genomes for orthologous sequence in which to design primers for PCR (polymerase chain reaction) verification. A primate phylogenetic panel of 24 species, including 22 lemur species from all five families, was examined for the presence/absence of 138 Alu elements via PCR to establish relationships among species. Of these, 111 were phylogenetically informative. A phylogenetic tree was generated based on the results of this analysis. We demonstrate strong support for the monophyly of Lemuriformes to the exclusion of other primates, with Daubentoniidae, the aye-aye, as the basal lineage within the infraorder. Our results also suggest Lepilemuridae as a sister lineage to Cheirogaleidae, and Indriidae as sister to Lemuridae. Among the Cheirogaleidae, we show strong support for Microcebus and Mirza as sister genera, with Cheirogaleus the sister lineage to both. Our results also support the monophyly of the Lemuridae. Within Lemuridae we place Lemur and Hapalemur together to the exclusion of

  20. Viral vector-induced amygdala NPY overexpression reverses increased alcohol intake caused by repeated deprivations in Wistar rats

    PubMed Central

    Thorsell, Annika; Repunte-Canonigo, Vez; O'Dell, Laura E.; Chen, Scott A.; King, Alvin R.; Lekic, Dusan; Koob, George F.; Sanna, Pietro Paolo

    2009-01-01

    Acute administration of neuropeptide Y (NPY) modulates alcohol intake in genetic and chemical models of high intake, while leaving intake unaffected during ‘normal’ or baseline conditions. In non-selected, normal rat lines, alcohol consumption can be increased by prolonged exposure to alcohol, and it is unclear what effect a constitutive increase in NPY function will have on alcohol intake. The purpose of the present study was to examine the effects on alcohol intake of an inducible, constitutive overexpression of NPY, one of the most abundant neuropeptides in the central nervous system. A liquid diet was used in combination with repeated alcohol deprivation sessions to increase alcohol intake in normal Wistar rats. We then examined the effect of NPY overexpression in the amygdala on excessive alcohol intake produced by prolonged exposure to alcohol and alcohol deprivation. Repeated withdrawal increased alcohol consumption in a 24-h continuous access two-bottle choice model. Both the number of withdrawals as well as the length of the withdrawal periods affected alcohol consumption with an increased intake resulting from multiple withdrawals and the alcohol deprivation effect being enhanced by longer periods of abstinence. The increase in intake following repeated abstinence was blunted by intra-amygdala administration of a Sindbis viral vector containing NPY cDNA. Amygdala NPY overexpression also was demonstrated to be anxiolytic in the open field test. Repeated withdrawal in combination with a history of alcohol consumption significantly elevated alcohol intake, and the amygdala may mediate the transition to high-drinking states in this model. PMID:17405766

  1. Repeated oral administration of capsaicin increases anxiety-like behaviours with prolonged stress-response in rats.

    PubMed

    Choi, Y-J; Kim, J Y; Yoo, S B; Lee, J-H; Jahng, J W

    2013-09-01

    This study was conducted to examine the psycho-emotional effects of repeated oral exposure to capsaicin, the principal active component of chili peppers. Each rat received 1 mL of 0.02 percent capsaicin into its oral cavity daily, and was subjected to behavioural tests following 10 daily administrations of capsaicin. Stereotypy counts and rostral grooming were significantly increased, and caudal grooming decreased, in capsaicin-treated rats during the ambulatory activity test. In elevated plus maze test, not only the time spent in open arms but also the percent arm entry into open arms was reduced in capsaicin-treated rats compared with control rats. In forced swim test, although swimming duration was decreased, struggling increased in the capsaicin group, immobility duration did not differ between the groups. Repeated oral capsaicin did not affect the basal levels of plasma corticosterone; however, the stress-induced elevation of plasma corticosterone was prolonged in capsaicin treated rats. Oral capsaicin exposure significantly increased c-Fos expression not only in the nucleus tractus of solitarius but also in the paraventricular nucleus. Results suggest that repeated oral exposure to capsaicin increases anxiety-like behaviours in rats, and dysfunction of the hypothalamic-pituitary-adrenal axis may play a role in its pathophysiology. PMID:23938388

  2. Intergenic Alu exonisation facilitates the evolution of tissue-specific transcript ends.

    PubMed

    Tajnik, Mojca; Vigilante, Alessandra; Braun, Simon; Hänel, Heike; Luscombe, Nicholas M; Ule, Jernej; Zarnack, Kathi; König, Julian

    2015-12-01

    The 3' untranslated regions (3' UTRs) of transcripts serve as important hubs for posttranscriptional gene expression regulation. Here, we find that the exonisation of intergenic Alu elements introduced new terminal exons and polyadenylation sites during human genome evolution. While Alu exonisation from introns has been described previously, we shed light on a novel mechanism to create alternative 3' UTRs, thereby opening opportunities for differential posttranscriptional regulation. On the mechanistic level, we show that intergenic Alu exonisation can compete both with alternative splicing and polyadenylation in the upstream gene. Notably, the Alu-derived isoforms are often expressed in a tissue-specific manner, and the Alu-derived 3' UTRs can alter mRNA stability. In summary, we demonstrate that intergenic elements can affect processing of preceding genes, and elucidate how intergenic Alu exonisation can contribute to tissue-specific posttranscriptional regulation by expanding the repertoire of 3' UTRs. PMID:26400176

  3. Activation of RNA polymerase III transcription of human Alu repetitive elements by adenovirus type 5: Requirement for the E1b 58-Kilodalton protein and the products of E4 open reading frames 3 and 6

    SciTech Connect

    Panning, B.; Smiley, J.R. )

    1993-06-01

    Alu elements are the single most abundant class of dispersed repeated sequences in the human genome, comprising 5-10% of the mass of human DNA. This report demonstrates that Ad5 infection strongly stimulates Pol III transcription of human Alu elements in HeLa and 293 cells. In contrast to the cases of Ad5-induced Pol III transcriptional activation, this process requires the E1b 58-kDa protein and the products of E4 open reading frames (ORFs) 3 and 6 in addition to the E1a 289-residue product. These findings suggest novel regulatory properties of the Ad5 E1b and E4 proteins and raise the possibility that analogous cellular trans-acting factors serve to modulate Alu expression in vivo.

  4. The Zinc-Finger Antiviral Protein ZAP Inhibits LINE and Alu Retrotransposition

    PubMed Central

    Moldovan, John B.; Moran, John V.

    2015-01-01

    Long INterspersed Element-1 (LINE-1 or L1) is the only active autonomous retrotransposon in the human genome. To investigate the interplay between the L1 retrotransposition machinery and the host cell, we used co-immunoprecipitation in conjunction with liquid chromatography and tandem mass spectrometry to identify cellular proteins that interact with the L1 first open reading frame-encoded protein, ORF1p. We identified 39 ORF1p-interacting candidate proteins including the zinc-finger antiviral protein (ZAP or ZC3HAV1). Here we show that the interaction between ZAP and ORF1p requires RNA and that ZAP overexpression in HeLa cells inhibits the retrotransposition of engineered human L1 and Alu elements, an engineered mouse L1, and an engineered zebrafish LINE-2 element. Consistently, siRNA-mediated depletion of endogenous ZAP in HeLa cells led to a ~2-fold increase in human L1 retrotransposition. Fluorescence microscopy in cultured human cells demonstrated that ZAP co-localizes with L1 RNA, ORF1p, and stress granule associated proteins in cytoplasmic foci. Finally, molecular genetic and biochemical analyses indicate that ZAP reduces the accumulation of full-length L1 RNA and the L1-encoded proteins, yielding mechanistic insight about how ZAP may inhibit L1 retrotransposition. Together, these data suggest that ZAP inhibits the retrotransposition of LINE and Alu elements. PMID:25951186

  5. Repeated Isoflurane Exposures Impair Long-Term Potentiation and Increase Basal GABAergic Activity in the Basolateral Amygdala

    PubMed Central

    Long II, Robert P.; Aroniadou-Anderjaska, Vassiliki; Prager, Eric M.; Pidoplichko, Volodymyr I.; Figueiredo, Taiza H.; Braga, Maria F. M.

    2016-01-01

    After surgery requiring general anesthesia, patients often experience emotional disturbances, but it is unclear if this is due to anesthetic exposure. In the present study, we examined whether isoflurane anesthesia produces long-term pathophysiological alterations in the basolateral amygdala (BLA), a brain region that plays a central role in emotional behavior. Ten-week-old, male rats were administered either a single, 1 h long isoflurane (1.5%) anesthesia or three, 1 h long isoflurane exposures, separated by 48 h. Long-term potentiation (LTP) and spontaneous GABAergic activity in the BLA were studied 1 day, 1 week, and 1 month later. Single isoflurane anesthesia had no significant effect on the magnitude of LTP. In contrast, after repeated isoflurane exposures, LTP was dramatically impaired at both 1 day and 1 week after the last exposure but was restored by 1 month after the exposures. Spontaneous GABAA receptor-mediated IPSCs were increased at 1 day and 1 week after repeated exposures but had returned to control levels by 1 month after exposure. Thus, repeated exposures to isoflurane cause a long-lasting—but not permanent—impairment of synaptic plasticity in the BLA, which could be due to increased basal GABAergic activity. These pathophysiological alterations may produce emotional disturbances and impaired fear-related learning. PMID:27313904

  6. 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…

  7. 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

  8. Computational analysis reveals increased blood deposition following repeated mild traumatic brain injury☆

    PubMed Central

    Donovan, Virginia; Bianchi, Anthony; Hartman, Richard; Bhanu, Bir; Carson, Monica J.; Obenaus, Andre

    2012-01-01

    Mild traumatic brain injury (mTBI) has become an increasing public health concern as subsequent injuries can exacerbate existing neuropathology and result in neurological deficits. This study investigated the temporal development of cortical lesions using magnetic resonance imaging (MRI) to assess two mTBIs delivered to opposite cortical hemispheres. The controlled cortical impact model was used to produce an initial mTBI on the right cortex followed by a second injury induced on the left cortex at 3 (rmTBI 3d) or 7 (rmTBI 7d) days later. Histogram analysis was combined with a novel semi-automated computational approach to perform a voxel-wise examination of extravascular blood and edema volumes within the lesion. Examination of lesion volume 1d post last injury revealed increased tissue abnormalities within rmTBI 7d animals compared to other groups, particularly at the site of the second impact. Histogram analysis of lesion T2 values suggested increased edematous tissue within the rmTBI 3d group and elevated blood deposition in the rm TBI 7d animals. Further quantification of lesion composition for blood and edema containing voxels supported our histogram findings, with increased edema at the site of second impact in rmTBI 3d animals and elevated blood deposition in the rmTBI 7d group at the site of the first injury. Histological measurements revealed spatial overlap of regions containing blood deposition and microglial activation within the cortices of all animals. In conclusion, our findings suggest that there is a window of tissue vulnerability where a second distant mTBI, induced 7d after an initial injury, exacerbates tissue abnormalities consistent with hemorrhagic progression. PMID:24179733

  9. Assessment of Azorean ancestry by Alu insertion polymorphisms.

    PubMed

    Branco, Claudia C; Palla, Raquel; Lino, Sílvia; Pacheco, Paula R; Cabral, Rita; De Fez, Laura; Peixoto, Bernardo R; Mota-Vieira, Luisa

    2006-01-01

    Knowledge of population ancestry from genetic markers is essential, for example, to understand the history of human migration and to carry out admixture and association studies. Here we assess the genome ancestry of the Azorean population through analysis of six Alu polymorphic sites (TPA-25, ACE, APO, B65, PV92, and D1) in 65 Azoreans and 30 Portuguese unrelated blood donors and compare data for the Y-chromosome and mtDNA. Allele frequencies were calculated by direct counting. Statistical analysis was performed using Arlequin 2.0. Nei's genetic distance was calculated with DISPAN software, and trees were constructed by neighbor joining (NJ) using PHYLIP 3.63. The results show that all Alu insertions were polymorphic. APO is the closest to fixation. The less frequent insertions are PV92 and D1 in the Azores and Portugal, respectively. ACE and TPA-25 show the highest values of heterozygosity in both populations. Allele frequencies are very similar to those obtained in European populations. These results are validated by the Y-chromosome and mtDNA data, where the majority of the maternal and paternal lineages are European. Overall, these data are reflected in the phylogenetic tree, in which the Azoreans and the Portuguese branch with Catalans, Andalusians, Moroccans, and Algerians. We conclude that the population of the Azores shows no significant genetic differences from that of mainland Portugal and that it is an outbred population. Moreover, the data validate the use of Alu insertion polymorphisms to assess the origin and history of human populations. PMID:16493635

  10. Increasing viscosity and yields of bacterial exopolysaccharides by repeatedly exposing strains to ampicillin.

    PubMed

    Li, Ou; Liu, Ao; Lu, Cui; Zheng, Dao-qiong; Qian, Chao-dong; Wang, Pin-Mei; Jiang, Xin-Hang; Wu, Xue-Chang

    2014-09-22

    A universal method to enhance productivity and viscosity of bacterial exopolysaccharides was developed. The technique was based on the principle that ampicillin can inhibit the biosynthesis of peptidoglycan, which shares a common synthetic pathway with that of bacterial exopolysaccharides. Serial passages of three typical representatives of bacterial EPS-producing strains, namely Sphingomonas elodea, Xanthomonas campestris, and Paenibacillus elgii, were subjected to ampicillin, which was used as a stressor and a mutagen. These mutant strains are advantageous over other strains because of two major factors. First, all of the resulting strains were almost mutants with increase in EPS productivity and viscosity. Second, isolated serial strains showed different levels of increase in EPS production and viscosity to satisfy the different requirements of practical applications. No differences were observed in the monosaccharide composition produced by the mutant and parent strains; however, high-viscosity mutant strains exhibited higher molecular weights. The results confirmed that the developed method is a controlled universal one that can improve exopolysaccharides productivity and viscosity. PMID:24906747

  11. 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

  12. 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…

  13. Repeated Glacial-Lake Outburst Floods in Patagonia: An Increasing Hazard?

    NASA Astrophysics Data System (ADS)

    Dussaillant, A.; Benito, G.; Buytaert, W.; Carling, P.; Gonzalez, F.; Link, O.; Meier, C.

    2009-04-01

    Patagonian glaciers are recording one of the fastest glacial retreats on Earth, inferred to be a direct response to recorded climate change in South America. The dynamic response of the region's glaciers to climate change was evident when two self-similar glacial-lake outburst floods occurred in April and October 2008, the largest floods from this glacier on record. On each occasion, the lake Cachet 2, in the Northern Patagonia Ice-Field, dammed by the Colonia glacier, released about 200 million m3 water into the Colonia river. The lake is refilling rapidly, such that further outbreak floods can be expected. This paper anticipates future events, by providing an assessment of the hydraulic properties of the 2008 events. Pipeflow calculations of the subglacial tunnel drainage and hydraulic models of the river flood give consistent results, with an estimated peak discharge of between 2500 and 3000 m3s-1. However, geomorphological analysis of the Colonia valley shows evidence of former catastrophic outburst floods, with flood discharges possibly as high as 16,000 m3s-1. Given the impacts of climate change on glacier dynamics in the area, the frequency and high magnitude jökulhlaups may increase future flood risks for infrastructure and population, particularly relevant in view of the current development of hydropower projects in Chilean Patagonia.

  14. 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

  15. Alu-alu recombination results in a duplication of seven exons in the lysyl hydroxylase gene in a patient with the type VI variant of Ethlers-Danlos syndrome

    SciTech Connect

    Pousi, B.; Hautala, T.; Heikkinen, J.; Pajunen, L.; Kivirikko, K.I.; Myllylae, R.

    1994-11-01

    The type VI variant of the Ethlers-Danlos syndrome (EDS) is a recessively inherited connective-tissue disorder. The characteristic features of the variant are muscular hyptonia, kyphoscoliosis, ocular manifestations, joint hypermobility, skin fragility and hyperextensibility, and other signs of connective-tissue involvement. The biochemical defect in most but not all patients is a deficiency in lysyl hydroxylase activity. Lysyl hydroxylase is an enzyme that catalyzes the formation of hydroxylysine in collagens and other proteins with collagen-like amino acid sequences. We have recently reported an apparently homozygous large-duplication rearrangement in the gene for lysyl hydroxylase, leading to the type VI variant of EDS in two siblings. We now report an identical, apparently homozygous large duplication in an unrelated 49-year-old female originally analyzed by Sussman et al. Our simple-sequence-repeat-polymorphism analysis does not support uniparental isodisomy inheritance for either of the two duplications. Furthermore, we indicate in this study that the duplication in the lysyl hydroxylase gene is caused by an Alu-Alu recombination in both families. Cloning of the junction fragment of the duplication has allowed synthesis of appropriate primers for rapid screening for this rearrangement in other families with the type VI variant of EDS. 38 refs., 6 figs.

  16. 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

  17. Increased Mesohippocampal Dopaminergic Activity and Improved Depression-Like Behaviors in Maternally Separated Rats Following Repeated Fasting/Refeeding Cycles

    PubMed Central

    Jahng, Jeong Won; Yoo, Sang Bae; Kim, Jin Young; Kim, Bom-Taeck; Lee, Jong-Ho

    2012-01-01

    We have previously reported that rats that experienced 3 h of daily maternal separation during the first 2 weeks of birth (MS) showed binge-like eating behaviors with increased activity of the hypothalamic-pituitary-adrenal axis when they were subjected to fasting/refeeding cycles repeatedly. In this study, we have examined the psychoemotional behaviors of MS rats on the fasting/refeeding cycles, together with their brain dopamine levels. Fasting/refeeding cycles normalized the ambulatory activity of MS rats, which was decreased by MS experience. Depression-like behaviors, but not anxiety, by MS experience were improved after fasting/refeeding cycles. Fasting/refeeding cycles did not significantly affect the behavioral scores of nonhandled (NH) control rats. Fasting/refeeding cycles increased dopamine levels not only in the hippocampus but also in the midbrain dopaminergic neurons in MS rats, but not in NH controls. Results demonstrate that fasting/refeeding cycles increase the mesohippocampal dopaminergic activity and improve depression-like behaviors in rats that experienced MS. Together with our previous paper, it is suggested that increased dopamine neurotransmission in the hippocampus may be implicated in the underlying mechanisms by which the fasting/refeeding cycles induce binge-like eating and improve depression-like behaviors in MS rats. PMID:22934157

  18. Increased levels of FFA during passive heat loading after a 2-week repeated heat load in Koreans

    NASA Astrophysics Data System (ADS)

    Lee, Jeong Beom; Kim, Tae Wook

    2015-04-01

    The purpose of this study was to determine whether repeated heat load is closely related to circulating levels of free fatty acids (FFA) during repeated passive heat loading (PHL), defined as immersion of the lower body up to an umbilical level in hot water, 42 ± 0.5 °C (three times/week, 30 min/day) for 2 weeks. There were significant correlations between mean body temperature and FFA before and after repeated heat load ( p < 0.001, respectively), and the level of FFA was significantly higher after repeated heat load during PHL ( p < 0.01). The threshold of mean body temperature for lipolysis was lowered by repeated heat load and enhanced lipolysis during PHL. However, caution is needed for diabetic individuals.

  19. 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

  20. Gradual increase in secondary ionization coefficient γ and charge accumulation on a dielectric electrode during DBD with repeated breakdown

    NASA Astrophysics Data System (ADS)

    Suzuki, S.; Itoh, H.

    2015-10-01

    We have investigated the effect of the surface roughness of a dielectric electrode for dielectric barrier discharge (DBD). We prepared three alumina plates made from the same material with different surface roughnesses for use as electrodes. During the repeated breakdown from the first breakdown to the stationary state, we observed gradual increases in the secondary ionization coefficient and the charge accumulated on the alumina electrodes under the application of a sinusoidal voltage in argon up to a pressure of 105 Torr. A strong correlation was also observed between them, similarly to in a previous paper on CaO film electrodes. The results suggest that increasing the surface roughness of an alumina electrode results in a larger secondary ionization coefficient and greater charge accumulation on the electrode. Moreover, it is concluded that the charges that accumulate on the alumina can be liberated from the surface as initial electrons when it acts as a cathode, depending on the polarity of the alternating gap voltage. These electrons induce the formation of an atmospheric-pressure Townsend discharge. Finally, we discuss the effect of the secondary ionization coefficient in DBD.

  1. Homologous recombination among three intragene Alu sequences causes an inversion-deletion resulting in the hereditary bleeding disorder glanzmann thrombasthenia

    SciTech Connect

    Li, L.; Bray, P.F. )

    1993-07-01

    The crucial role of the human platelet fibrinogen receptor in maintaining normal hemostasis is best exemplified by the autosomal recessive bleeding disorder Glanzmann thrombasthenia (GT). The platelet fibrinogen receptor is a heterodimer composed of glycoproteins IIb (GPIIb) and IIIa (GPIIIa). Platelets from patients with GT have a quantitative or qualitative abnormality in GPIIb and GPIIIa and can neither bind fibrinogen nor aggregate. Very few genetic defects have been identified that cause this disorder. The authors describe a kindred with GT in which the affected individuals have a unique inversion-deletion mutation in the gene for GPIIIa. Patient platelets lacked both GPIIIa protein and mRNA. Southern blots of patient genomic DNA probed with an internal 1.0-kb GPIIIa cDNA suggested a large rearrangement of this gene but were normal when probed with small GPIIIa cDNA fragments that were outside the mutation. Cytogenetics and pulsed-field gel analysis of the GPIIIa gene were normal, making a translocation or a very large rearrangement unlikely. Additional Southern analyses suggested that the abnormality was not a small insertion. The authors constructed a patient genomic DNA library and isolated fragments containing the 5' and 3' breakpoints of the mutation. The nucleotide sequence from these genomic clones was determined and revealed that, relative to the normal gene, the mutant allele contained a 1-kb deletion immediately preceding a 15-kb inversion. The DNA breaks occurred in two inverted and one forward Alu sequence within the gene for GPIIIa and in the left, right, and left arms, respectively, of these sequences. There was a 5-bp repeat at the 3 terminus of the inversion. One copy of the repeat remained in the mutant allele breakpoint junction. The alignment and orientation of the different Alu sequences, as well as the position of the breakpoints, suggest that the inversion preceded the deletion in this complex rearrangement. 41 refs., 5 figs.

  2. 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

  3. 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

  4. Naturally Extended CT · AG Repeats Increase H-DNA Structures and Promoter Activity in the Smooth Muscle Myosin Light Chain Kinase Gene▿

    PubMed Central

    Han, Yoo-Jeong; de Lanerolle, Primal

    2008-01-01

    Naturally occurring repeat sequences capable of adopting H-DNA structures are abundant in promoters of disease-related genes. In support of this, we found (CT)22 · (AG)22 repeats in the promoter of smooth muscle myosin light chain kinase (smMLCK), a key regulator of vascular smooth muscle function. We also found an insertion mutation that adds another six pairs of CT · AG repeats and increases smMLCK promoter activity in spontaneously hypertensive rats (SHR). Therefore, we used the smMLCK promoters from normotensive and hypertensive rats as a model system to determine how CT · AG repeats form H-DNA, an intramolecular triplex, and regulate promoter activity. High-resolution mapping with a chemical probe selective for H-DNA showed that the CT · AG repeats adopt H-DNA structures at a neutral pH. Importantly, the SHR promoter forms longer H-DNA structures than the promoter from normotensive rats. Reconstituting nucleosomes on the promoters, in vitro, showed no difference in nucleosome positioning between the two promoters. However, chromatin immunoprecipitation analyses revealed that histone acetylations are greater in the hypertensive promoter. Thus, our findings suggest that the extended CT · AG repeats in the SHR promoter increase H-DNA structures, histone modifications, and promoter activity of the smMLCK, perhaps contributing to vascular disorders in hypertension. PMID:17991897

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

    PubMed

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

    2016-01-01

    (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

  6. 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

  7. 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. PMID:15101052

  8. Retrotransposition and Crystal Structure of an Alu RNP in the Ribosome-Stalling Conformation.

    PubMed

    Ahl, Valentina; Keller, Heiko; Schmidt, Steffen; Weichenrieder, Oliver

    2015-12-01

    The Alu element is the most successful human genomic parasite affecting development and causing disease. It originated as a retrotransposon during early primate evolution of the gene encoding the signal recognition particle (SRP) RNA. We defined a minimal Alu RNA sufficient for effective retrotransposition and determined a high-resolution structure of its complex with the SRP9/14 proteins. The RNA adopts a compact, closed conformation that matches the envelope of the SRP Alu domain in the ribosomal translation elongation factor-binding site. Conserved structural elements in SRP RNAs support an ancient function of the closed conformation that predates SRP9/14. Structure-based mutagenesis shows that retrotransposition requires the closed conformation of the Alu ribonucleoprotein particle and is consistent with the recognition of stalled ribosomes. We propose that ribosome stalling is a common cause for the cis-preference of the mammalian L1 retrotransposon and for the efficiency of the Alu RNA in hijacking nascent L1 reverse transcriptase. PMID:26585389

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

    PubMed Central

    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 uCuC alleles between PBMCs of patients and controls (p = 0.03), and between inactive patients and controls (p = 0.03). For neutrophils, the frequency of uCuC was significantly higher between patients and controls (p = 0.006) and between inactive patients and controls (p = 0.002). The partial methylation (uCmC + mCuC) 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. PMID:27123441

  10. 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

    2016-06-01

    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

  11. 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

  12. 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. PMID:27123441

  13. 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…

  14. 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.

  15. General strategies to increase the repeatability in non-target screening by liquid chromatography-high resolution mass spectrometry.

    PubMed

    Bader, Tobias; Schulz, Wolfgang; Kümmerer, Klaus; Winzenbacher, Rudi

    2016-09-01

    This article focuses on the data evaluation of non-target high-resolution LC-MS profiles of water samples. Taking into account multiple technical replicates, the difficulties in peak recognition and the related problems of false positive and false negative findings are systematically demonstrated. On the basis of a combinatorial approach, different models involving sophisticated workflows are evaluated, particularly with regard to the repeatability. In addition, the improvement resulting from data processing was systematically taken into consideration where the recovery of spiked standards emphasized that real peaks of interest were barely or not removed by the derived filter criteria. The comprehensive evaluation included different matrix types spiked with up to 263 analytical standards which were analyzed repeatedly leading to a total number of more than 250 injections that were incorporated in the assessment of different models of data processing. It was found that the analysis of multiple replicates is the key factor as, on the one hand, it provides the option of integrating valuable filters in order to minimize the false positive rate and, on the other hand, allows correcting partially false negative findings occurring during the peak recognition. The developed processing strategies including replicates clearly point to an enhanced data quality since both the repeatability as well as the peak recognition could be considerably improved. As proof of concept, four different matrix types, including a wastewater treatment plant (WWTP) effluent, were spiked with 130 isotopically labeled standards at different concentration levels. Despite the stringent filter criteria, at 100 ng L(-1) recovery rates of up to 93% were reached in the positive ionization mode. The proposed model, comprising three technical replicates, filters less than 5% and 2% of the standards recognized at 100 and 500 ng L(-1), respectively and thus indicates the general applicability of the

  16. Repeated methylphenidate administration during lactation reduces maternal behavior, induces maternal tolerance, and increases anxiety-like behavior in pups in adulthood.

    PubMed

    Ponchio, R A; Teodorov, E; Kirsten, T B; Coelho, C P; Oshiro, A; Florio, J C; Bernardi, M M

    2015-01-01

    Methylphenidate (MPD) is a dopamine uptake inhibitor and the most commonly prescribed drug for the treatment of attention-deficit/hyperactivity disorder in children. Several studies have shown that such stimulants as cocaine and amphetamine that are administered during gestation and lactation may disrupt maternal behavior. Also, MPD is used in lactation. Repeated MPD administration can induce either sensitization or tolerance. The aim of the present study was to investigate whether repeated MPD administration alters maternal behavior and promotes tolerance or sensitization in these females. The effects in adult offspring were also examined in models of anxiety. Methylphenidate (5mg/kg) was administered from lactation day 2 to 4, and maternal pup retrieval behavior was assessed. This treatment was continued until lactation day 7. At weaning, the dams received a challenge dose of MPD, and general activity was evaluated in the open field. Striatal monoamine and metabolite levels were also measured to determine whether this treatment promotes behavioral or biochemical plasticity. The long-term behavioral effects of MPD exposure were evaluated in pups in adulthood. The results showed an increase in the latency to retrieve the first, second, and third pups and a decrease in the number of dams that retrieved all pups. After a challenge dose of MPD, the dams exhibited a decrease in locomotion frequency, an increase in immobility duration in the open field, and a decrease in striatal serotonin levels. In pups, anxiety-like behavior increased in the light/dark box test. These results indicate that repeated MPD administration during early lactation impairs maternal behavior, likely by decreasing maternal motivation. Repeated MPD administration induced maternal tolerance at weaning after a challenge dose of MPD, suggesting the development of central nervous system plasticity. In pups, maternal exposure to MPD during early lactation induced long-term effects and increased

  17. Loss of MOR-1 on different genetic backgrounds leads to increased BrdU labeling in the dentate gyrus only after repeated injection

    PubMed Central

    Cominski, Tara P.; Turchin, Carol E.; Hsu, Ming-Sing; Ansonoff, Michael A.

    2012-01-01

    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 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 PCNA positive cells in the DG is significantly increased in MOR-1 KO mice compared to 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 to WT C57BL/6 mice in both non-injected 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 to 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. PMID:22280973

  18. 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. PMID:26861146

  19. Increased Sushi repeat-containing protein X-linked 2 is associated with progression of colorectal cancer.

    PubMed

    Liu, K L; Wu, J; Zhou, Y; Fan, J H

    2015-04-01

    Sushi repeat-containing protein X-linked 2 (SRPX2) is a novel chondroitin sulfate proteoglycan overexpressed in gastrointestinal cancer. Its role in tumor biology remains unknown. The aim of this study was to investigate the expression of SRPX2 in colorectal cancer and its potential association with cancer progression. The expression of SRPX2 and its clinicopathological significance was evaluated using immunohistochemistry in a tissue microarray including 88 colon cancer and pairing normal tissues. The impact of SRPX2 on behavior of colorectal cancer cells and possible mechanism was explored using gene transfection and silencing. Strong staining of SRPX2 was noted in 71 (80.7 %) of 88 colon cancer specimen and 30 (34.1 %) of 88 adjacent normal tissues (P < 0.001). The expression of SRPX2 was significantly correlated with histological differentiation grade (P = 0.003), infiltration depth (P = 0.003), and clinical stage (P = 0.006). The expression of SRPX2 was significantly higher in HCT116 than in HT29 and SW480 cells. Suppression of endogenous SRPX2 expression by small interfering ribonucleic acid (siRNA) in HCT116 cells resulted in significant reduction in the ability of cell proliferation, adhesion, migration, and invasion. Up-regulation of endogenous SRPX2 in SW480 cells significantly promoted the migration and invasion of SW480 cells. In addition, inhibition of SRPX2 by siRNA led to notable down-regulation of β-catenin, matrix metalloproteinase (MMP)-2, and MMP-9. These findings indicate that overexpressed SRPX2 exerts an oncogenic role in colorectal cancer. SRPX2 may promote the invasion of colorectal cancer through MMP-2 and MMP-9 modulated by Wnt/β-catenin pathway. PMID:25737434

  20. Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle

    PubMed Central

    Perry, Christopher G R; Lally, James; Holloway, Graham P; Heigenhauser, George J F; Bonen, Arend; Spriet, Lawrence L

    2010-01-01

    Exercise training induces mitochondrial biogenesis, but the time course of molecular sequelae that accompany repetitive training stimuli remains to be determined in human skeletal muscle. Therefore, throughout a seven-session, high-intensity interval training period that increased (12%), we examined the time course of responses of (a) mitochondrial biogenesis and fusion and fission proteins, and (b) selected transcriptional and mitochondrial mRNAs and proteins in human muscle. Muscle biopsies were obtained 4 and 24 h after the 1st, 3rd, 5th and 7th training session. PGC-1α mRNA was increased >10-fold 4 h after the 1st session and returned to control within 24 h. This ‘saw-tooth’ pattern continued until the 7th bout, with smaller increases after each bout. In contrast, PGC-1α protein was increased 24 h after the 1st bout (23%) and plateaued at +30–40% between the 3rd and 7th bout. Increases in PGC-1β mRNA and protein were more delayed and smaller, and did not persist. Distinct patterns of increases were observed in peroxisome proliferator-activated receptor (PPAR) α and γ protein (1 session), PPAR β/δ mRNA and protein (5 sessions) and nuclear respiratory factor-2 protein (3 sessions) while no changes occurred in mitochondrial transcription factor A protein. Citrate synthase (CS) and β-HAD mRNA were rapidly increased (1 session), followed 2 sessions later (session 3) by increases in CS and β-HAD activities, and mitochondrial DNA. Changes in COX-IV mRNA (session 3) and protein (session 5) were more delayed. Training also increased mitochondrial fission proteins (fission protein-1, >2-fold; dynamin-related protein-1, 47%) and the fusion protein mitofusin-1 (35%) but not mitofusin-2. This study has provided the following novel information: (a) the training-induced increases in transcriptional and mitochondrial proteins appear to result from the cumulative effects of transient bursts in their mRNAs, (b) training-induced mitochondrial biogenesis appears to

  1. Alu sequences transcription in X. laevis oocytes: nuclear-cytoplasmic partitioning and evidence for 3' end processing reactions.

    PubMed Central

    Perlino, E; Paonessa, G; Ciliberto, G

    1985-01-01

    A large Alu-family cluster in the 5' flanking region of a human alpha 1-acid glycoprotein gene has been identified and sequenced. Individual members microinjected into X. laevis oocytes are transcribed only when canonical box A and B components of the split pol III promoter are present. Alu transcripts accumulate in the nucleus. An unusually short Alu transcript, able to assume a stable secondary structure, undergoes a 3' end processing reaction similar to the one required for tRNA 3' end maturation. Images PMID:4080545

  2. Increased Resting-State Perfusion after Repeated Encoding Is Related to Later Retrieval of Declarative Associative Memories

    PubMed Central

    Groen, Georg; Sokolov, Alexander N.; Jonas, Christina; Roebling, Robert; Spitzer, Manfred

    2011-01-01

    Electrophysiological studies in animals have shown coordinated reactivation of neuronal ensembles during a restricted time period of behavioral inactivity that immediately followed active encoding. In the present study we directly investigated off-line processing of associative memory formation in the human brain. Subjects' regional cerebral blood flow (rCBF) as a surrogate marker of neural activity during rest was measured by MR-based perfusion imaging in a sample of 14 healthy male subjects prior to (Pre2) and after (Post) extensive learning of 24 face-name associations within a selective reminding task (SR). Results demonstrated significant Post-Pre2 rCBF increases in hippocampal and temporal lobe regions, while in a control comparison of two perfusion scans with no learning task in-between (Pre2-Pre1) no differences in rCBF emerged. Post perfusion scanning was followed by a surprise cued associative recall task from which two types of correctly retrieved names were obtained: older names already correctly retrieved at least once during one of the SR blocks, and recent names acquired during the last SR block immediately prior to the Post scan. In the anterior hippocampus individual perfusion increases were correlated with both correct retrievals of older and recent names. By contrast, older but not recently learned names showed a significant correlation with perfusion increases in the left lateral temporal cortex known to be associated with long-term memory. Recent, but not older names were correlated with dopaminergic midbrain structures reported to contribute to the persistence of memory traces for novel information. Although the direct investigation of off-line memory processing did not permit concomitant experimental control, neither intentional rehearsal, nor substantial variations in subjects' states of alertness appear to contribute to present results. We suggest that the observed rCBF increases might reflect processes that possibly contribute to the long

  3. Afar unrest: the 2008 Alu eruption in the Erta `Ale volcanic system (Ethiopia)

    NASA Astrophysics Data System (ADS)

    Pagli, C.; Wright, T. J.; Ayele, A.; Barnie, T.

    2009-04-01

    The Alu volcano is located within the Erta ‘Ale volcanic system in northern Afar (Ethiopia), about 30 km to the north of the Erta ‘Ale volcano whose summit caldera hosts a lava lake. Aster, Hotspot and S02 emissions images formed on 3rd November, 2008 showed that a fissural eruption was occurring east of the Alu volcano. Here we present an InSAR study of the area, using data from four tracks of the Envisat satellite both in descending ad ascending orbits, also including data in Wide Swath acquisition mode. The interferograms span different time periods allowing us to separate pre-, co- and post-eruptive deformation. In particular, an acquisition made on 3rd November at 19:20 (the day of the eruption) is used to observe deformation over two different co-eruptive periods. The co-eruptive interferograms show two closely-spaced but distinct concentric deformation patterns, both consistent with deflation, on the Alu volcano and on another unnamed volcano 3 km south of Alu. Most deformation in both volcanoes occurred during the first part of 3rd November (until 19:20) but significant deflation, up to ~ 45 cm, is also observed in the following interferogram from 3rd November at 19:20 to 8th December. Interestingly, no significant pre-eruptive deformation was observed in the area, nor any deformation was observed at the Erta ‘Ale lava lake prior to, during or after the Alu eruption. Preliminary modelling results, using two deflating Mogi sources, suggest that the two shallow magma chambers at ~1-1.5 km depth deflated during the eruption, with a volume change of the sources of ~-0.01 km3. Lack of pre-eruptive deformation suggests that the erupted magma was sitting at shallow depth under the Alu volcanoes. The lava lake in the nearby Erta 'Ale volcano also indicates that shallow magma reservoirs are a common feature in the area. We plan to model the observed deformations using different models, i.e. sill, penny shaped crack and ellipsoidal source and to compare our

  4. Repeat Sequences and Base Correlations in Human Y Chromosome Palindromes

    NASA Astrophysics Data System (ADS)

    Jin, Neng-zhi; Liu, Zi-xian; Qi, Yan-jiao; Qiu, Wen-yuan

    2009-06-01

    On the basis of information theory and statistical methods, we use mutual information, n-tuple entropy and conditional entropy, combined with biological characteristics, to analyze the long range correlation and short range correlation in human Y chromosome palindromes. The magnitude distribution of the long range correlation which can be reflected by the mutual information is P5>P5a>P5b (P5a and P5b are the sequences that replace solely Alu repeats and all interspersed repeats with random uncorrelated sequences in human Y chromosome palindrome 5, respectively); and the magnitude distribution of the short range correlation which can be reflected by the n-tuple entropy and the conditional entropy is P5>P5a>P5b>random uncorrelated sequence. In other words, when the Alu repeats and all interspersed repeats replace with random uncorrelated sequence, the long range and short range correlation decrease gradually. However, the random uncorrelated sequence has no correlation. This research indicates that more repeat sequences result in stronger correlation between bases in human Y chromosome. The analyses may be helpful to understand the special structures of human Y chromosome palindromes profoundly.

  5. 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

  6. Agar-agar entrapment increases the stability of endo-β-1,4-xylanase for repeated biodegradation of xylan.

    PubMed

    Bibi, Zainab; Shahid, Faiza; Ul Qader, Shah Ali; Aman, Afsheen

    2015-04-01

    Microbial xylanases, specially endo-β-1,4-xylanase catalyzes the hydrolysis of xylan, is considered one of the most significant hydrolases. It has numerous applications but most extensively is utilized in paper and pulp industry as a bio-bleaching agent. Immobilization technique is comprehensively studied with the expectation of modifying and improving enzyme stability and characteristics for commercial purposes. Currently, matrix entrapment technique is applied to immobilize endo-β-1,4-xylanase within agar-agar gel beads produced by Geobacillus stearothermophilus KIBGE-IB29. Maximal enzyme immobilization yield was achieved at 2.5% of agar-agar concentration. Optimized conditions demonstrated an increase in the optimal reaction time from 05 min to 30 min and incubation temperature from 50 °C to 60 °C with reference to free enzyme whereas; no effect was observed for optimum pH. Entrapment technique uniquely changed the kinetic parameters of immobilized endo-β-1,4-xylanase (Km: 0.5074 mg min(-1) to 0.5230 mg min(-1) and Vmax: 4773 U min(-1) to 968 U min(-1)) as compared to free enzyme. However, immobilized enzyme displayed broad thermal stability and retained 79.0% of its initial activity at 80 °C up to 30 min whereas; free enzyme completely lost its activity at this temperature. With respect to economic feasibility, the immobilized enzyme showed impressive recycling efficiency up to six reaction cycles. PMID:25603143

  7. 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. PMID:25168471

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

    PubMed Central

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

    2015-01-01

    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. PMID:26271202

  9. 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

  10. Repetition counts: repeated exposure increases intake of a novel vegetable in UK pre-school children compared to flavour-flavour and flavour-nutrient learning.

    PubMed

    Caton, Samantha J; Ahern, Sara M; Remy, Eloise; Nicklaus, Sophie; Blundell, Pam; Hetherington, Marion M

    2013-06-01

    Children are not consuming sufficient amounts of fruits and vegetables in their habitual diet. Methods derived from associative learning theories could be effective at promoting vegetable intake in pre-school children. The objective of the present study was to compare the effectiveness of different learning strategies in promoting the intake of a novel vegetable. Children aged between 9 and 38 months were recruited from UK nurseries. The children (n 72) were randomly assigned to one of three conditions (repeated exposure, flavour-flavour learning or flavour-nutrient learning). Each child was offered ten exposures to their respective version of a novel vegetable (artichoke). Pre- and post-intervention measures of artichoke purée and carrot purée (control vegetable) intake were taken. At pre-intervention, carrot intake was significantly higher than artichoke intake (P<0·05). Intake of both vegetables increased over time (P<0·001); however, when changes in intake were investigated, artichoke intake increased significantly more than carrot intake (P<0·001). Artichoke intake increased to the same extent in all three conditions, and this effect was persistent up to 5 weeks post-intervention. Five exposures were sufficient to increase intake compared to the first exposure (P<0·001). Repeated exposure to three variants of a novel vegetable was sufficient to increase intake of this vegetable, regardless of the addition of a familiar taste or energy. Repetition is therefore a critical factor for promoting novel vegetable intake in pre-school children. PMID:23110783

  11. Heritability and heteromorphic distributions of AluI chromosome banding variants in twins

    SciTech Connect

    Huang, B.; Meyer, J.M.; Jackson-Cook, C.K.

    1995-07-03

    The heritability and heteromorphic appearance of chromosomal banding patterns induced through in situ digestion with the restriction enzyme AluI were studied by analyzing the chromosomes of 25 monozygotic and 25 dizygotic twin pairs selected at random from a juvenile twin registry. A total of 19 AluI banding variants were found to be heteromorphic, with the pericentromeric region of chromosome 3 and the satellites of chromosome 22 being most and least heteromorphic, respectively. As expected, the correlations of the semi-quantitative scores for each of the chromosomal variants were significantly higher between MZ twin pairs (ranging from 0.48 to 0.95) than DZ twin pairs (ranging from -0.02 to 0.69), suggesting that genetic factors play an important role in their appearance. This finding was confirmed in a model fitting analysis in which the heritabilities of the AluI-induced chromosome variants were found to range from 70 to 96% for 12/13 heteromorphisms studied. These consistent findings are significant in that these variants may be useful for family studies in clinical genetics. 23 refs., 6 figs., 3 tabs.

  12. 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.

  13. Rapid mapping of NotI linking clones with differential hybridization and Alu-PCR

    SciTech Connect

    Zabarovsky, E.R. |; Zabarovska, V.I.; Klein, G.

    1994-06-01

    For construction of a NotI restriction map of the humane genome, the isolation and mapping of unique NotI linking clones represent important and critical steps. Recently the authors have shown that an Alu-PCR approach can be used for isolation of NotI linking clones from defined regions of the chromosomes. This represents a useful method for isolating and analyzing a small number of clones, but it would be laborious to use it for mapping many NotI linking clones simultaneously. Here they suggest another modification of Alu-PCR for rapid concurrent mapping of many NotI linking clones. The results clearly demonstrate the utility of this approach. Seventy-one random NotI linking clones were analyzed. Among them, 65 clones (91.5%) were correctly selected and mapped using this approach. With differential hybridization and Alu-PCR, a significant portion of all human NotI linking clones (>30%) can be rapidly mapped to particular chromosomes or to defined regions of these chromosomes. 31 refs., 3 figs.

  14. 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

  15. Pharmacokinetics of repeated sodium salicylate administration to laying hens: evidence for time dependent increase in drug elimination from plasma and eggs.

    PubMed

    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

  16. A novel Alu-based real-time PCR method for the quantitative detection of plasma circulating cell-free DNA: Sensitivity and specificity for the diagnosis of myocardial infarction

    PubMed Central

    LOU, XIAOLI; HOU, YANQIANG; LIANG, DONGYU; PENG, LIANG; CHEN, HONGWEI; MA, SHANYUAN; ZHANG, LURONG

    2015-01-01

    In the present study, we aimed to develop and validate a rapid and sensitive, Alu-based real-time PCR method for the detection of circulating cell-free DNA (cfDNA). This method targeted repetitive elements of the Alu reduplicative elements in the human genome, followed by signal amplification using fluorescence quantification. Standard Alu-puc57 vectors were constructed and 5 pairs of specific primers were designed. Valuation was conducted concerning linearity, variation and recovery. We found 5 linear responses (R1–5=0.998–0.999). The average intra- and inter-assay coefficients of variance were 12.98 and 10.75%, respectively. The recovery was 82.33–114.01%, with a mean recovery index of 101.26%. This Alu-based assay was reliable, accurate and sensitive for the quantitative detection of cfDNA. Plasma from normal controls and patients with myocardial infarction (MI) were analyzed, and the baseline levels of cfDNA were higher in the MI group. The area under the receiver operating characteristic (ROC) curve for Alu1, Alu2, Alu3, Alu4, Alu5 and Alu (Alu1 + Alu2 + Alu3 + Alu4 + Alu5) was 0.887, 0.758, 0.857, 0.940, 0.968 and 0.933, respectively. The optimal cut-off value for Alu1, Alu2, Alu3, Alu4, Alu5 and Alu to predict MI was 3.71, 1.93, 0.22, 3.73, 6.13 and 6.40 log copies/ml. We demonstrate that this new method is a reliable, accurate and sensitive method for the quantitative detection of cfDNA and that it is useful for studying the regulation of cfDNA in certain pathological conditions. Alu4, Alu5 and Alu showed better sensitivity and specificity for the diagnosis of MI compared with cardiac troponin I (cTnI), creatine kinase MB (CK-MB) isoenzyme and lactate dehydrogenase (LDH). Alu5 had the best prognostic ability. PMID:25374065

  17. Inflate, Pause, Erupt, Recharge: the 2008 Alu eruption in the Erta ‘Ale volcanic system (Ethiopia)

    NASA Astrophysics Data System (ADS)

    Pagli, C.; Wright, T. J.; Ebinger, C. J.; Barnie, T. D.; Ayele, A.

    2009-12-01

    The Alu volcano is located within the Erta ‘Ale volcanic system in northern Afar (Ethiopia), about 30 km to the north of Erta ‘Ale volcano whose summit caldera hosts a persistent lava lake. On 3rd November 2008 a fissure eruption started east of Alu volcano. An unprecedented InSAR dataset, seismic records and other space satellite imagery allow us to study the temporal and spatial evolution of magma preceding, during and after the eruption. We use InSAR images from five tracks of the Envisat satellite both in descending ad ascending orbits. Small pre-eruptive inflation 3 cm/month started at Alu in July but had ceased by September 10. There was no deformation for around a month before the eruption began on November 3, 2008 at 11:10 GMT. During the eruption over 1 m of subsidence was observed at two distinct locations: at Alu and a volcanic ridge 3 km south of Alu. The co-eruptive subsidence continued for around 16 days at Alu, before deflation reversed into inflation. A swarm of earthquakes, some with magnitude (ml) > 4, occurred along the border fault escarpment, ~ 40 km west of Alu, at 22:00 GMT on November 2, and within ~4 hours a seismic activity started around Alu, leading to the eruption. The deformation was modelled with a Mogi source under Alu and a Sill under the ridge, undergoing different undergoing different volume changes from July 2008 to June 2009. In order to find the best-fit model parameters, first we modelled few selected co-eruptive interferograms with a non-linear inversion. Then, keeping fixed the model geometries we inverted a total of ~40 interferograms for the time-dependent volume change of the Mogi source and the opening of the sill, using a least-squares inversion. Results indicate that a small magma volume was intruded into Alu July-September but a time lag of ~ 1 month occurred between intrusion and eruption. Martin et al. (2008) used petrological evidence to suggest that fresh magma intruded into a magma chamber can cause volatile

  18. 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

  19. 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

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

    PubMed

    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

  1. Branched DNA-based Alu quantitative assay for cell-free plasma DNA levels in patients with sepsis or systemic inflammatory response syndrome.

    PubMed

    Hou, Yan-Qiang; Liang, Dong-Yu; Lou, Xiao-Li; Zhang, Mei; Zhang, Zhen-huan; Zhang, Lu-rong

    2016-02-01

    Cell-free circulating DNA (cf-DNA) can be detected by various of laboratory techniques. We described a branched DNA-based Alu assay for measuring cf-DNA in septic patients. Compared to healthy controls and systemic inflammatory response syndrome (SIRS) patients, serum cf-DNA levels were significantly higher in septic patients (1426.54 ± 863.79 vs 692.02 ± 703.06 and 69.66 ± 24.66 ng/mL). The areas under the receiver operating characteristic curve of cf-DNA for normal vs sepsis and SIRS vs sepsis were 0.955 (0.884-1.025), and 0.856 (0.749-0.929), respectively. There was a positive correlation between cf-DNA and interleukin 6 or procalcitonin or Acute Physiology and Chronic Health Evaluation II. The cf-DNA concentration was higher in intensive care unit nonsurviving patients compared to surviving patients (2183.33 ± 615.26 vs 972.46 ± 648.36 ng/mL; P < .05). Branched DNA-based Alu assays are feasible and useful to quantify serum cf-DNA levels. Increased cf-DNA levels in septic patients might complement C-reactive protein and procalcitonin in a multiple marker format. Cell-free circulating DNA might be a new marker in discrimination of sepsis and SIRS. PMID:26589770

  2. Increased expression of PAD2 after repeated intracerebroventricular infusions of soluble Abeta(25-35) in the Alzheimer's disease model rat brain: effect of memantine.

    PubMed

    Arif, Mohammad; Kato, Takeshi

    2009-01-01

    Peptidylarginine deiminases (PADs) convert the arginine residues in proteins into citrulline residues in a Ca(2+)-dependent manner. We previously showed that a bilateral injection of ibotenic acid into the rat nucleus basalis magnocellularis elevated the PAD2 activity in the hippocampus and striatum. In this study, we examined whether repeated intracerebroventricular infusions of soluble Abeta25-35 would affect the PAD2 expression in any regions of the rat brain. We also assessed the protective effect of memantine on Abeta-induced PAD2 alterations. The infusion of Abeta(25-35) increased the activity and protein level of PAD2 in the hippocampus, and co-treatment with memantine suppressed these changes. An immunohistochemical analysis showed that an increased level of PAD2 was coincident with GFAP-positive astrocytes and CD11b-positive microglia. In addition, immunofluoresecence staining revealed that citrullinepostive immunoreactivity coincided with the occurrence of GFAP-positive astrocytes. Co-treatment with memantine reversed the activation of the astrocytes and microglia, thus attenuating the PAD2 increment. These biochemical and immunohistochemical results suggest that PAD2 might play an important role in the pathology of early Alzheimer's disease, and may correlate with the changes in glial cells that are recovered by memantine treatment. PMID:19641855

  3. Flash x-ray test of the CMOS/SOS SCP-STAR ALU

    SciTech Connect

    Brucker, G.J.; Kertesz, C.; Miller, M.; Oey, K.K.

    1984-12-01

    This paper reports on the measurement of the x-ray upset dose rate for a subsystem which was designed to represent the ALU part of the SCP-STAR spacecraft computer. This computer was fabricated totally with radhard, CMOS/SOS devices. The test was conducted at the OWL flash x-ray facility of Physics International. The results showed that the upset dose rate for the subsystem was 9.8 x 10/sup 10/ and 1.7 x 10/sup 11/ rads(Si)/s during dynamic and static modes of operation, respectively. Subsystem interactions did not compromise the upset levels of the discrete components.

  4. Repeated exposure of infants at complementary feeding to a vegetable puree increases acceptance as effectively as flavor-flavor learning and more effectively than flavor-nutrient learning.

    PubMed

    Remy, Eloïse; Issanchou, Sylvie; Chabanet, Claire; Nicklaus, Sophie

    2013-07-01

    Children's vegetable consumption is below the public health recommendations. This study aimed to compare learning mechanisms to increase vegetable acceptance in infants at complementary feeding, namely repeated exposure (RE), flavor-flavor learning (FFL), and flavor-nutrient learning (FNL); measure the stability of the learning effect; and examine the impact of infants' feeding history on vegetable acceptance. The study was composed of a preexposure test, an exposure period, a postexposure test, and tests at 2-wk, 3-mo, and 6-mo follow-ups. At pre- and postexposure, a basic artichoke purée and carrot purée were presented to 95 French infants (6.4 ± 0.8 mo). During the exposure period, infants were randomly split into 3 groups and were exposed 10 times to the basic (RE group; 2 kJ/g; n = 32), a sweet (FFL group; 2 kJ/g; n = 32), or an energy-dense (FNL group; 6 kJ/g; n = 31) artichoke purée 2 or 3 times/wk. To evaluate acceptance, intake (g) and liking were recorded at home by parents. Between pre- and postexposure, intake of the basic artichoke purée significantly increased in the RE (+63%) and FFL (+39%) groups but not in the FNL group; liking increased only in the RE group (+21%). After exposure, artichoke was as much consumed and as much liked as carrot only in the RE group. Learning of artichoke acceptance was stable up to 3 mo postexposure. Initial artichoke intake was significantly related to the number of vegetables offered before the study started. RE is as effective as and simpler to implement than FFL and more effective than FNL for increasing vegetable acceptance at complementary feeding. PMID:23700337

  5. 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.

  6. High density physical mapping of chromosome 3p by hybridization of somatic cell hybrid derived Alu-PCR products

    SciTech Connect

    Shearman, A.M.; Andresen, J.M.; Aburatani, H.

    1994-09-01

    We have produced high density physical maps covering most of chromosome 3 using a hybridization-based approach to YAC isolation and contig assembly. The strategy has been to use a well characterized panel of somatic cell hybrids to generate probe sets distributed across the chromosome. From each of 50 somatic cell hybrids, a library of {approximately}100-600 cloned Alu-PCR products was isolated and Alu-PCR inserts from the full set of clones was spotted at high density on nylon membranes. Representative sets of unique clones from most of the hybrids were used to screen {approximately}16 genome equivalents of CEPH YACs by hybridization. These results, combined with our previous results and data from CEPH, produced contigs covering most of the chromosomes. The use of somatic cell hybrid-derived probe sets allowed easy integration of contigs with physical mapping boundaries defined by the somatic cell hybrids. We will describe various Alu-PCR strategies subsequently used to achieve closure, including successful identification of Alu-PCR products from the spotted set which lie in regions not previously covered by YAC contigs and use of Alu-PCR walking strategies to fill gaps and confirm tentative linkages. Our basic YAC screening methodology allows one individual to screen {approximately}16 genome equivalents of CEPH YACs with 96 probes/week at a material cost of less than $1 per locus. We have now mapped >2,200 loci on chromosome 3, with average interlocus distances of {approximately}50-100 kb over large regions. Alu-PCR-defined loci spaced along the chromosome at regular intervals are being converted to STSs. Our results indicate that use of a hybridization-based approach to physical mapping constitutes an efficient, accurate, high throughput method for isolating YACs and assembling YAC contigs.

  7. Repeated intermittent alcohol exposure during the third trimester-equivalent increases expression of the GABAA receptor δ subunit in cerebellar granule neurons and delays motor development in rats

    PubMed Central

    Diaz, Marvin R.; Vollmer, Cyndel C.; Zamudio-Bulcock, Paula A.; Vollmer, William; Blomquist, Samantha; Morton, Russell A.; Everett, Julie C.; Zurek, Agnieszka A.; Yu, Jieying; Orser, Beverley A.; Valenzuela, C. Fernando

    2014-01-01

    Exposure to ethanol (EtOH) during fetal development can lead to long-lasting alterations, including deficits in fine motor skills and motor learning. Studies suggest that these are, in part, a consequence of cerebellar damage. Cerebellar granule neurons (CGNs) are the gateway of information into the cerebellar cortex. Functionally, CGNs are heavily regulated by phasic and tonic GABAergic inhibition from Golgi cell interneurons; however, the effect of EtOH exposure on the development of GABAergic transmission in immature CGNs has not been investigated. To model EtOH exposure during the 3rd trimester-equivalent of human pregnancy, neonatal pups were exposed intermittently to high levels of vaporized EtOH from postnatal day (P) 2 to P12. This exposure gradually increased pup serum EtOH concentrations (SECs) to ~60 mM (~0.28 g/dl) during the 4 hours of exposure. EtOH levels gradually decreased to baseline 8 hrs after the end of exposure. Surprisingly, basal tonic and phasic GABAergic currents in CGNs were not significantly affected by postnatal alcohol exposure (PAE). However, PAE increased the expression of δ subunit expression at P28 as detected by immunohistochemical and western blot analyses. Also, electrophysiological studies with an agonist that is highly selective for δ-containing GABAA receptors, 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine-3-ol (THIP), showed an increase in THIP-induced tonic current. Behavioral studies of PAE rats did not reveal any deficits in motor coordination, except for a delay in the acquisition of the mid-air righting reflex that was apparent at P15 to P18. These findings demonstrate that repeated intermittent exposure to high levels of EtOH during the equivalent of the last trimester of human pregnancy has significant but relatively subtle effects on motor coordination and GABAergic transmission in CGNs in rats. PMID:24316160

  8. 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

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

    PubMed Central

    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.

    2016-01-01

    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. PMID:26743714

  10. 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

    2016-01-01

    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. PMID:26743714

  11. Identification of L1 ORF2p sequence important to retrotransposition using Bipartile Alu retrotransposition (BAR)

    PubMed Central

    Christian, Claiborne M.; deHaro, Dawn; Kines, Kristine J.; Sokolowski, Mark; Belancio, Victoria P.

    2016-01-01

    Long Interspersed Element 1 (LINE-1 or L1) is capable of causing genomic instability through the activity of the L1 ORF2 protein (ORF2p). This protein contains endonuclease (EN) and reverse transcriptase (RT) domains that are necessary for the retrotransposition of L1 and the Short Interspersed Element (SINE) Alu. The functional importance of approximately 50% of the ORF2p molecule remains unknown, but some of these sequences could play a role in retrotransposition, or be necessary for the enzymatic activities of the EN and/or RT domains. Conventional approaches using the full-length, contiguous ORF2p make it difficult to study the involvement of these unannotated sequences in the function of L1 ORF2p. Our lab has developed a Bipartile Alu Retrotransposition (BAR) assay that relies on separate truncated ORF2p fragments: an EN-containing and an RT-containing fragment. We validated the utility of this method for studying the ORF2p function in retrotransposition by assessing the effect of expression levels and previously characterized mutations on BAR. Using BAR, we identified two pairs of amino acids important for retrotransposition, an FF and a WD. The WD appears to play a role in cDNA synthesis by the ORF2p molecule, despite being outside the canonical RT domain. PMID:27095191

  12. Identification of L1 ORF2p sequence important to retrotransposition using Bipartile Alu retrotransposition (BAR).

    PubMed

    Christian, Claiborne M; deHaro, Dawn; Kines, Kristine J; Sokolowski, Mark; Belancio, Victoria P

    2016-06-01

    Long Interspersed Element 1 (LINE-1 or L1) is capable of causing genomic instability through the activity of the L1 ORF2 protein (ORF2p). This protein contains endonuclease (EN) and reverse transcriptase (RT) domains that are necessary for the retrotransposition of L1 and the Short Interspersed Element (SINE) Alu. The functional importance of approximately 50% of the ORF2p molecule remains unknown, but some of these sequences could play a role in retrotransposition, or be necessary for the enzymatic activities of the EN and/or RT domains. Conventional approaches using the full-length, contiguous ORF2p make it difficult to study the involvement of these unannotated sequences in the function of L1 ORF2p. Our lab has developed a Bipartile Alu Retrotransposition (BAR) assay that relies on separate truncated ORF2p fragments: an EN-containing and an RT-containing fragment. We validated the utility of this method for studying the ORF2p function in retrotransposition by assessing the effect of expression levels and previously characterized mutations on BAR. Using BAR, we identified two pairs of amino acids important for retrotransposition, an FF and a WD. The WD appears to play a role in cDNA synthesis by the ORF2p molecule, despite being outside the canonical RT domain. PMID:27095191

  13. Repeating thermocouple

    SciTech Connect

    Falk, R. A.

    1985-06-04

    Disclosed herein is a repeating use thermocouple assembly and method of making the same in which a cavity adjacent the tip of the thermocouple is filled with a thermosetting foundry sand and baked in place to provide support for the thermocouple tube without causing stresses during use which could cause breakage of the thermocouple tube.

  14. Identification of homogeneously staining regions by G-banding and chromosome microdissection, and FISH marker selection using human Alu sequence primers in a scleractinian coral Coelastrea aspera Verrill, 1866 (Cnidaria)

    PubMed Central

    Taguchi, Takahiro; Kubota, Satoshi; Mezaki, Takuma; Tagami, Erika; Sekida, Satoko; Nakachi, Shu; Okuda, Kazuo; Tominaga, Akira

    2016-01-01

    Abstract Karyotype analysis was performed on the scleractinian coral Coelastrea aspera Verrill, 1866, commonly found along temperate coasts in Japan (30–35°N) and in coastal waters in the Indian and Pacific oceans. G-banding of Coelastrea aspera was successfully performed, although the banding pattern was not as clear as that in mammals. The karyogram clearly revealed that this coral had a homogeneously staining region (hsr) in chromosome 11. This hsr consisted of ribosomal RNA (rRNA) related genes, which was demonstrated by fluorescence in situ hybridization (FISH) with probes generated using 28S ribosomal DNA (rDNA) primers and those generated through chromosome microdissection. In addition, we conducted silver-stained nucleolus organizer region (Ag-NOR) analysis and found Ag depositions in the interphase nuclei but not on rRNA gene loci and hsr(s) in the mitotic stage. The hsr of this coral was observed in approximately 50% of the metaphase spreads analyzed. This may explain the diversity of coral rDNA based on the molecular study of sequence analysis. Furthermore, it was discovered that human telomere and Alu repeated sequences were present in this Coelastrea aspera. Probes derived from human Alu sequences are expected to play an important role in the classification of corals. Overall, our data can be of great value in discriminating among scleractinian coral species and understanding their genetics, including chromosomal evolution. PMID:27186338

  15. Identification of homogeneously staining regions by G-banding and chromosome microdissection, and FISH marker selection using human Alu sequence primers in a scleractinian coral Coelastrea aspera Verrill, 1866 (Cnidaria).

    PubMed

    Taguchi, Takahiro; Kubota, Satoshi; Mezaki, Takuma; Tagami, Erika; Sekida, Satoko; Nakachi, Shu; Okuda, Kazuo; Tominaga, Akira

    2016-01-01

    Karyotype analysis was performed on the scleractinian coral Coelastrea aspera Verrill, 1866, commonly found along temperate coasts in Japan (30-35°N) and in coastal waters in the Indian and Pacific oceans. G-banding of Coelastrea aspera was successfully performed, although the banding pattern was not as clear as that in mammals. The karyogram clearly revealed that this coral had a homogeneously staining region (hsr) in chromosome 11. This hsr consisted of ribosomal RNA (rRNA) related genes, which was demonstrated by fluorescence in situ hybridization (FISH) with probes generated using 28S ribosomal DNA (rDNA) primers and those generated through chromosome microdissection. In addition, we conducted silver-stained nucleolus organizer region (Ag-NOR) analysis and found Ag depositions in the interphase nuclei but not on rRNA gene loci and hsr(s) in the mitotic stage. The hsr of this coral was observed in approximately 50% of the metaphase spreads analyzed. This may explain the diversity of coral rDNA based on the molecular study of sequence analysis. Furthermore, it was discovered that human telomere and Alu repeated sequences were present in this Coelastrea aspera. Probes derived from human Alu sequences are expected to play an important role in the classification of corals. Overall, our data can be of great value in discriminating among scleractinian coral species and understanding their genetics, including chromosomal evolution. PMID:27186338

  16. Clustered Regularly Interspaced Short Palindromic Repeat-Dependent, Biofilm-Specific Death of Pseudomonas aeruginosa Mediated by Increased Expression of Phage-Related Genes

    PubMed Central

    Heussler, Gary E.; Cady, Kyle C.; Koeppen, Katja; Bhuju, Sabin; Stanton, Bruce A.

    2015-01-01

    ABSTRACT The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (CRISPR/Cas) system is an adaptive immune system present in many archaea and bacteria. CRISPR/Cas systems are incredibly diverse, and there is increasing evidence of CRISPR/Cas systems playing a role in cellular functions distinct from phage immunity. Previously, our laboratory reported one such alternate function in which the type 1-F CRISPR/Cas system of the opportunistic pathogen Pseudomonas aeruginosa strain UCBPP-PA14 (abbreviated as P. aeruginosa PA14) inhibits both biofilm formation and swarming motility when the bacterium is lysogenized by the bacteriophage DMS3. In this study, we demonstrated that the presence of just the DMS3 protospacer and the protospacer-adjacent motif (PAM) on the P. aeruginosa genome is necessary and sufficient for this CRISPR-dependent loss of these group behaviors, with no requirement of additional DMS3 sequences. We also demonstrated that the interaction of the CRISPR system with the DMS3 protospacer induces expression of SOS-regulated phage-related genes, including the well-characterized pyocin operon, through the activity of the nuclease Cas3 and subsequent RecA activation. Furthermore, our data suggest that expression of the phage-related genes results in bacterial cell death on a surface due to the inability of the CRISPR-engaged strain to downregulate phage-related gene expression, while these phage-related genes have minimal impact on growth and viability under planktonic conditions. Deletion of the phage-related genes restores biofilm formation and swarming motility while still maintaining a functional CRISPR/Cas system, demonstrating that the loss of these group behaviors is an indirect effect of CRISPR self-targeting. PMID:25968642

  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. 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

  19. The Alu-Rich Genomic Architecture of SPAST Predisposes to Diverse and Functionally Distinct Disease-Associated CNV Alleles

    PubMed Central

    Boone, Philip M.; Yuan, Bo; Campbell, Ian M.; Scull, Jennifer C.; Withers, Marjorie A.; Baggett, Brett C.; Beck, Christine R.; Shaw, Christine J.; Stankiewicz, Pawel; Moretti, Paolo; Goodwin, Wendy E.; Hein, Nichole; Fink, John K.; Seong, Moon-Woo; Seo, Soo Hyun; Park, Sung Sup; Karbassi, Izabela D.; Batish, Sat Dev; Ordóñez-Ugalde, Andrés; Quintáns, Beatriz; Sobrido, María-Jesús; Stemmler, Susanne; Lupski, James R.

    2014-01-01

    Intragenic copy-number variants (CNVs) contribute to the allelic spectrum of both Mendelian and complex disorders. Although pathogenic deletions and duplications in SPAST (mutations in which cause autosomal-dominant spastic paraplegia 4 [SPG4]) have been described, their origins and molecular consequences remain obscure. We mapped breakpoint junctions of 54 SPAST CNVs at nucleotide resolution. Diverse combinations of exons are deleted or duplicated, highlighting the importance of particular exons for spastin function. Of the 54 CNVs, 38 (70%) appear to be mediated by an Alu-based mechanism, suggesting that the Alu-rich genomic architecture of SPAST renders this locus susceptible to various genome rearrangements. Analysis of breakpoint Alus further informs a model of Alu-mediated CNV formation characterized by small CNV size and potential involvement of mechanisms other than homologous recombination. Twelve deletions (22%) overlap part of SPAST and a portion of a nearby, directly oriented gene, predicting novel chimeric genes in these subjects’ genomes. cDNA from a subject with a SPAST final exon deletion contained multiple SPAST:SLC30A6 fusion transcripts, indicating that SPAST CNVs can have transcriptional effects beyond the gene itself. SLC30A6 has been implicated in Alzheimer disease, so these fusion gene data could explain a report of spastic paraplegia and dementia cosegregating in a family with deletion of the final exon of SPAST. Our findings provide evidence that the Alu genomic architecture of SPAST predisposes to diverse CNV alleles with distinct transcriptional—and possibly phenotypic—consequences. Moreover, we provide further mechanistic insights into Alu-mediated copy-number change that are extendable to other loci. PMID:25065914

  20. 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

  1. 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

  2. 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

  3. TLR-Independent and P2X7-Dependent Signaling Mediate Alu RNA-Induced NLRP3 Inflammasome Activation in Geographic Atrophy

    PubMed Central

    Kerur, Nagaraj; Hirano, Yoshio; Tarallo, Valeria; Fowler, Benjamin J.; Bastos-Carvalho, Ana; Yasuma, Tetsuhiro; Yasuma, Reo; Kim, Younghee; Hinton, David R.; Kirschning, Carsten J.; Gelfand, Bradley D.; Ambati, Jayakrishna

    2013-01-01

    Purpose. Accumulation of Alu RNA transcripts due to DICER1 deficiency in the retinal pigmented epithelium (RPE) promotes geographic atrophy. Recently we showed that Alu RNA activated the NLRP3 inflammasome, leading to RPE cell death via interleukin-18 (IL-18)-mediated MyD88 signaling. However, the molecular basis for NLRP3 inflammasome activation by Alu RNA is not well understood. We sought to decipher the key signaling events triggered by Alu RNA that lead to priming and activation of the NLRP3 inflammasome and, ultimately, to RPE degeneration by investigating the roles of the purinoreceptor P2X7, the transcription factor NF-κB, and the Toll-like receptors (TLRs) in these processes. Methods. Human and mouse RPE cells were transfected with a plasmid encoding an Alu element (pAlu) or an in vitro-transcribed Alu RNA. Inflammasome priming was assessed by measuring NLRP3 and IL18 mRNA levels by real-time quantitative PCR. Using immunoblotting, we assessed NF-κB activation by monitoring phosphorylation of its p65 subunit, and inflammasome activation by monitoring caspase-1 cleavage into its active form. RPE degeneration was induced in mice by subretinal transfection of pAlu or Alu RNA. The NF-κB inhibitor BAY 11-7082, the P2X7 receptor antagonist A-740003, and the NLRP3 inflammasome inhibitor glyburide were delivered by intravitreous injections. We studied wild-type (WT) C57Bl/6J, P2rx7−/−, Nfkb1−/−, and Tlr23479−/− mice. RPE degeneration was assessed by fundus photography and zonula occludens-1 (ZO-1) staining of mouse RPE. Results. Alu RNA-induced NF-κB activation, independent of TLR-1, -2, -3, -4, -6, -7, and -9 signaling, was required for priming the NLRP3 inflammasome. Nfkb1−/− and P2rx7−/− mice and WT mice treated with the pharmacological inhibitors of NF-κB, P2X7, or NLRP3, were protected against Alu RNA-induced RPE degeneration. Conclusions. NF-κB and P2X7 are critical signaling intermediates in Alu RNA-induced inflammasome priming and

  4. Partial protoporphyrinogen oxidase (PPOX) gene deletions, due to different Alu-mediated mechanisms, identified by MLPA analysis in patients with variegate porphyria

    PubMed Central

    2013-01-01

    Variegate porphyria (VP) is an autosomal dominantly inherited hepatic porphyria. The genetic defect in the PPOX gene leads to a partial defect of protoporphyrinogen oxidase, the penultimate enzyme of heme biosynthesis. Affected individuals can develop cutaneous symptoms in sun-exposed areas of the skin and/or neuropsychiatric acute attacks. The identification of the genetic defect in VP families is of crucial importance to detect the carrier status which allows counseling to prevent potentially life threatening neurovisceral attacks, usually triggered by factors such as certain drugs, alcohol or fasting. In a total of 31 Swedish VP families sequence analysis had identified a genetic defect in 26. In the remaining five families an extended genetic investigation was necessary. After the development of a synthetic probe set, MLPA analysis to screen for single exon deletions/duplications was performed. We describe here, for the first time, two partial deletions within the PPOX gene detected by MLPA analysis. One deletion affects exon 5 and 6 (c.339-197_616+320del1099) and has been identified in four families, most probably after a founder effect. The other extends from exon 5 to exon 9 (c.339-350_987+229del2609) and was found in one family. We show that both deletions are mediated by Alu repeats. Our findings emphasize the usefulness of MLPA analysis as a complement to PPOX gene sequencing analysis for comprehensive genetic diagnostics in patients with VP. PMID:23324528

  5. Differences of Variable Number Tandem Repeats in XRCC5 Promoter Are Associated with Increased or Decreased Risk of Breast Cancer in BRCA Gene Mutation Carriers

    PubMed Central

    Cui, Jian; Luo, Jiangtao; Kim, Yeong C.; Snyder, Carrie; Becirovic, Dina; Downs, Bradley; Lynch, Henry; Wang, San Ming

    2016-01-01

    Ku80 is a subunit of the Ku heterodimer that binds to DNA double-strand break ends as part of the non-homologous end joining (NHEJ) pathway. Ku80 is also involved in homologous recombination (HR) via its interaction with BRCA1. Ku80 is encoded by the XRCC5 gene that contains a variable number tandem repeat (VNTR) insertion in its promoter region. Different VNTR genotypes can alter XRCC5 expression and affect Ku80 production, thereby affecting NHEJ and HR pathways. VNTR polymorphism is associated with multiple types of sporadic cancer. In this study, we investigated its potential association with familial breast cancer at the germline level. Using PCR, PAGE, Sanger sequencing, and statistical analyses, we compared VNTR genotypes in the XRCC5 promoter between healthy individuals and three types of familial breast cancer cases: mutated BRCA1 (BRCA1+), mutated BRCA2 (BRCA2+), and wild-type BRCA1/BRCA2 (BRCAx). We observed significant differences of VNTR genotypes between control and BRCA1+ group (P < 0.0001) and BRCA2+ group (P = 0.0042) but not BRCAx group (P = 0.2185), and the differences were significant between control and cancer-affected BRCA1+ cases (P < 0.0001) and BRCA2+ cases (P = 0.0092) but not cancer-affected BRCAx cases (P = 0.4251). Further analysis indicated that 2R/2R (OR = 1.94, 95%CI = 1.26–2.95, P = 0.0096) and 2R/1R (OR = 1.58, 95%CI = 1.11–2.26, P = 0.0388) were associated with increased risk but 1R/1R (OR = 0.55, 95%CI = 0.35–0.84, P = 0.0196) and 1R/0R (OR = 0, 95%CI = 0–0.29, P = 0.0012) were associated with decreased risk in cancer-affected BRCA1+ group; 2R/1R (OR = 1.94, 95%CI = 1.14–3.32, P = 0.0242) was associated with increased risk in cancer-affected BRCA2+ group. No correlation was observed for the altered risk between cancer-affected or -unaffected carriers and between different age of cancer diagnosis in cancer-affected carriers. The frequently

  6. 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

  7. 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

  8. International distribution and age estimation of the Portuguese BRCA2 c.156_157insAlu founder mutation.

    PubMed

    Peixoto, Ana; Santos, Catarina; Pinheiro, Manuela; Pinto, Pedro; Soares, Maria José; Rocha, Patrícia; Gusmão, Leonor; Amorim, António; van der Hout, Annemarie; Gerdes, Anne-Marie; Thomassen, Mads; Kruse, Torben A; Cruger, Dorthe; Sunde, Lone; Bignon, Yves-Jean; Uhrhammer, Nancy; Cornil, Lucie; Rouleau, Etienne; Lidereau, Rosette; Yannoukakos, Drakoulis; Pertesi, Maroulio; Narod, Steven; Royer, Robert; Costa, Maurício M; Lazaro, Conxi; Feliubadaló, Lidia; Graña, Begoña; Blanco, Ignacio; de la Hoya, Miguel; Caldés, Trinidad; Maillet, Philippe; Benais-Pont, Gaelle; Pardo, Bruno; Laitman, Yael; Friedman, Eitan; Velasco, Eladio A; Durán, Mercedes; Miramar, Maria-Dolores; Valle, Ana Rodriguez; Calvo, María-Teresa; Vega, Ana; Blanco, Ana; Diez, Orland; Gutiérrez-Enríquez, Sara; Balmaña, Judith; Ramon y Cajal, Teresa; Alonso, Carmen; Baiget, Montserrat; Foulkes, William; Tischkowitz, Marc; Kyle, Rachel; Sabbaghian, Nelly; Ashton-Prolla, Patricia; Ewald, Ingrid P; Rajkumar, Thangarajan; Mota-Vieira, Luisa; Giannini, Giuseppe; Gulino, Alberto; Achatz, Maria I; Carraro, Dirce M; de Paillerets, Brigitte Bressac; Remenieras, Audrey; Benson, Cindy; Casadei, Silvia; King, Mary-Claire; Teugels, Erik; Teixeira, Manuel R

    2011-06-01

    The c.156_157insAlu BRCA2 mutation has so far only been reported in hereditary breast/ovarian cancer (HBOC) families of Portuguese origin. Since this mutation is not detectable using the commonly used screening methodologies and must be specifically sought, we screened for this rearrangement in a total of 5,443 suspected HBOC families from several countries. Whereas the c.156_157insAlu BRCA2 mutation was detected in 11 of 149 suspected HBOC families from Portugal, representing 37.9% of all deleterious mutations, in other countries it was detected only in one proband living in France and in four individuals requesting predictive testing living in France and in the USA, all being Portuguese immigrants. After performing an extensive haplotype study in carrier families, we estimate that this founder mutation occurred 558 ± 215 years ago. We further demonstrate significant quantitative differences regarding the production of the BRCA2 full length RNA and the transcript lacking exon 3 in c.156_157insAlu BRCA2 mutation carriers and in controls. The cumulative incidence of breast cancer in carriers did not differ from that of other BRCA2 and BRCA1 pathogenic mutations. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry are specifically tested for this rearrangement. PMID:20652400

  9. 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.

  10. Development of Novel High-Resolution Melting-Based Assays for Genotyping Two Alu Insertion Polymorphisms (FXIIIB and PV92).

    PubMed

    González-Giraldo, Yeimy; Rodríguez-Dueñas, Marisol; Forero, Diego A

    2016-03-01

    Insertion/Deletion polymorphisms (InDels) are a common type of genetic variation, with a growing role in population genetics and applied genomics. There is the need for the development of novel cost-effective assays for genotyping InDels of high importance. The main objective of this study was to develop high-resolution melting-based assays for genotyping two commonly studied Alu insertion polymorphisms: FXIIIB and PV92 (rs70942849 and rs3138523). Three primers (two forward and one reverse) were designed for each marker, and high-resolution melting (HRM) analyses in a qPCR platform were performed, using EvaGreen fluorescent dye. For each one of the two Alu insertion polymorphisms, HRM analyses identified distinguishable peaks for the three genotypes, allowing a robust genotyping. Results were validated using 96 DNA samples previously genotyped and the assays worked with different DNA concentrations. In this study, we developed novel cost-effective assays, using qPCR, for genotyping two Alu insertion polymorphisms (widely used as ancestry markers). Our results highlight the feasibility of using HRM analyses for genotyping InDel polymorphisms of medical and biotechnological importance. PMID:26843017

  11. 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

  12. Alu-mediated deletion of SOX10 regulatory elements in Waardenburg syndrome type 4.

    PubMed

    Bondurand, Nadége; Fouquet, Virginie; Baral, Viviane; Lecerf, Laure; Loundon, Natalie; Goossens, Michel; Duriez, Benedicte; Labrune, Philippe; Pingault, Veronique

    2012-09-01

    Waardenburg syndrome type 4 (WS4) is a rare neural crest disorder defined by the combination of Waardenburg syndrome (sensorineural hearing loss and pigmentation defects) and Hirschsprung disease (intestinal aganglionosis). Three genes are known to be involved in this syndrome, that is, EDN3 (endothelin-3), EDNRB (endothelin receptor type B), and SOX10. However, 15-35% of WS4 remains unexplained at the molecular level, suggesting that other genes could be involved and/or that mutations within known genes may have escaped previous screenings. Here, we searched for deletions within recently identified SOX10 regulatory sequences and describe the first characterization of a WS4 patient presenting with a large deletion encompassing three of these enhancers. Analysis of the breakpoint region suggests a complex rearrangement involving three Alu sequences that could be mediated by a FosTes/MMBIR replication mechanism. Taken together with recent reports, our results demonstrate that the disruption of highly conserved non-coding elements located within or at a long distance from the coding sequences of key genes can result in several neurocristopathies. This opens up new routes to the molecular dissection of neural crest disorders. PMID:22378281

  13. 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. PMID:25397699

  14. Repeated Reading.

    ERIC Educational Resources Information Center

    Moyer, Sandra B.

    1982-01-01

    The article reviews research on the use of multiple oral rereading (MOR) with reading disabled students. MOR uses daily practice on a selection of little difficulty. Its effectiveness in increasing fluency (accuracy and speed) is examined, and the role of redundancy in three types of reading models is analyzed. (CL)

  15. Triggering of repeated earthquakes

    NASA Astrophysics Data System (ADS)

    Sobolev, G. A.; Zakrzhevskaya, N. A.; Sobolev, D. G.

    2016-03-01

    Based on the analysis of the world's earthquakes with magnitudes M ≥ 6.5 for 1960-2013, it is shown that they cause global-scale coherent seismic oscillations which most distinctly manifest themselves in the period interval of 4-6 min during 1-3 days after the event. After these earthquakes, a repeated shock has an increased probability to occur in different seismically active regions located as far away as a few thousand km from the previous event, i.e., a remote interaction of seismic events takes place. The number of the repeated shocks N( t) decreases with time, which characterizes the memory of the lithosphere about the impact that has occurred. The time decay N( t) can be approximated by the linear, exponential, and powerlaw dependences. No distinct correlation between the spatial locations of the initial and repeated earthquakes is revealed. The probable triggering mechanisms of the remote interaction between the earthquakes are discussed. Surface seismic waves traveling several times around the Earth's, coherent oscillations, and global source are the most preferable candidates. This may lead to the accumulation and coalescence of ruptures in the highly stressed or weakened domains of a seismically active region, which increases the probability of a repeated earthquake.

  16. Saturation of repeated quantum measurements

    NASA Astrophysics Data System (ADS)

    Haapasalo, Erkka; Heinosaari, Teiko; Kuramochi, Yui

    2016-08-01

    We study sequential measurement scenarios where the system is repeatedly subjected to the same measurement process. We first provide examples of such repeated measurements where further repetitions of the measurement do not increase our knowledge on the system after some finite number of measurement steps. We also prove, however, that repeating the Lüders measurement of an unsharp two-outcome observable never saturates in this sense, and we characterize the observable measured in the limit of infinitely many repetitions. Our result implies that a repeated measurement can be used to correct the inherent noise of an unsharp observable.

  17. 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, andTFAM), apoptosis (BAX,BCL2, andITM2B), and oocyte maturation (BMP15,FGF8,FGF10,FGF16,FGF17, andGDF9). 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, andTFAM) and apoptosis-related (BAXandITM2B) genes, as well as ofGDF9, 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. PMID:26843447

  18. Self-reported depression is increasing among socio-economically disadvantaged adolescents – repeated cross-sectional surveys from Finland from 2000 to 2011

    PubMed Central

    2014-01-01

    Background Adolescent depression is more common in lower socio-economic groups. Whether this pattern has changed over time, is not known. We examined the prevalence of self-reported depression and its changes in socio-economic groups from 2000 to 2011 among Finnish adolescents. Methods Data were based on classroom surveys every second year from 2000–2001 to 2010–2011 using nationwide samples of 14–16-year old Finns (n = 618,084). Data were collected using self-administered questionnaires including questions on health, health behaviours, and school experiences. Depression was measured with a Finnish modification of the 13-item Beck Depression Inventory, and divided into no, mild, moderate and severe depression. The association between depression and the social background (parents’ education and employment) over time was studied using a multinomial regression analysis. Results The prevalence of self-reported severe depression slightly increased from 2000–2001 to 2010–2011 in girls. In boys a slight increase was observed when adjusting for background variables. The differences in the prevalence of depression between the social background groups persisted over the entire study period. In both sexes, severe depression nearly doubled among those adolescents whose parents were unemployed and had a low education level; among boys, the prevalence was 6.5% in 2000–2001 and 12.8% in 2010–2011, and among girls 6.4% and 11.4% respectively. Conclusion The largest increases in prevalence of severe depression are seen among socio-economically disadvantaged adolescents. This suggests that inequalities in mental health may become an increasing concern. PMID:24775269

  19. 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. PMID:26803613

  20. Deletion of the PH-domain and Leucine-rich Repeat Protein Phosphatase 1 (Phlpp1) Increases Fibroblast Growth Factor (Fgf) 18 Expression and Promotes Chondrocyte Proliferation*

    PubMed Central

    Bradley, Elizabeth W.; Carpio, Lomeli R.; Newton, Alexandra C.; Westendorf, Jennifer J.

    2015-01-01

    Endochondral ossification orchestrates formation of the vertebrate skeleton and is often induced during disease and repair processes of the musculoskeletal system. Here we show that the protein phosphatase Phlpp1 regulates endochondral ossification. Phlpp1 null mice exhibit decreased bone mass and notable changes in the growth plate, including increased BrdU incorporation and matrix production. Phosphorylation of known Phlpp1 substrates, Akt2, PKC, and p70 S6 kinase, were enhanced in ex vivo cultured Phlpp1−/− chondrocytes. Furthermore, Phlpp1 deficiency diminished FoxO1 levels leading to increased expression of Fgf18, Mek/Erk activity, and chondrocyte metabolic activity. Phlpp inhibitors also increased matrix content, Fgf18 production and Erk1/2 phosphorylation. Chemical inhibition of Fgfr-signaling abrogated elevated Erk1/2 phosphorylation and metabolic activity in Phlpp1-null cultures. These results demonstrate that Phlpp1 controls chondrogenesis via multiple mechanisms and that Phlpp1 inhibition could be a strategy to promote cartilage regeneration and repair. PMID:25953896

  1. 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.

  2. 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. PMID:27232549

  3. 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

  4. Isolation of S9 fractions from mouse and rat with increased enzyme activities after repeated administration of cytochrome P-450 and P-448 inducers.

    PubMed

    Paolini, M; Sapigni, E; Hrelia, P; Grilli, S; Cantelli-Forti, G

    1988-05-01

    Cytochrome P-450 (cyt P-450), NADPH cytochrome P-450 reductase and various microsomal monooxygenase activities [e.g. aminopyrine N-demethylase, p-nitroanisole O-demethylase, dinemorphan N-demethylase, ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase (ERD)], were determined in hepatic post-mitochondrial supernatant from mice and rats. Experiments were performed on male and female animals treated with a combination of sodium phenobarbital and beta-naphthoflavone according to the standard protocol schedule for short-term genotoxicity testing. A second inductive treatment after 2, 3, 4 or 5 weeks was provided. The increase in cyt P-450 and in all enzymatic activities measured was enhanced in both species by a second induction treatment, particularly when given after 4 weeks. ERD activity was the only monooxygenase activity which was sex-dependent, being more active in female than in male animals. To extend the biochemical data, experiments were performed with the proposed S9 fractions on styrene, which previously has proved difficult to detect in short-term in vitro mutagenicity tests. Using the new induction conditions positive results were obtained with the D7 strain of Saccharomyces cerevisiae. It was concluded that a simple pre-induction of the animals 3-4 weeks before the main induction treatment leads to a more active S9 fraction for in vitro genotoxicity studies. PMID:3045486

  5. 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

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

    PubMed

    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 with Api

  7. Alu and L1 retroelements are correlated with the tissue extent and peak rate of gene expression, respectively.

    PubMed

    Kim, Tae-Min; Jung, Yu-Chae; Rhyu, Mun-Gan

    2004-12-01

    We exploited the serial analysis of gene expression (SAGE) libraries and human genome database in silico to correlate the breadth of expression (BOE; housekeeping versus tissue-specific genes) and peak rate of expression (PRE; high versus low expressed genes) with the density distribution of the retroelements. The BOE status is linearly associated with the density of the sense Alus along the 100 kb nucleotides region upstream of a gene, whereas the PRE status is inversely correlated with the density of antisense L1s within a gene and in the up- and downstream regions of the 0-10 kb nucleotides. The radial distance of intranuclear position, which is known to serve as the global domain for transcription regulation, is reciprocally correlated with the fractions of Alu (toward the nuclear center) and L1 (toward the nuclear edge) elements in each chromosome. We propose that the BOE and PRE statuses are related to the reciprocal distribution of Alu and L1 elements that formulate local and global expression domains. PMID:15608386

  8. 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…

  9. Repeated Course Enrollments.

    ERIC Educational Resources Information Center

    Windham, Patricia

    This report resents tables of repeated course enrollment data in Florida community colleges for the fall 1993 cohort. Overall, the percent of repeats in college preparatory courses was greater than that of college credit courses. Within ICS codes, the highest percentage of credit repeat enrollments was in mathematics; the second highest was in…

  10. Increase in 2–Long Terminal Repeat Circles and Decrease in D-dimer After Raltegravir Intensification in Patients With Treated HIV Infection: A Randomized, Placebo-Controlled Trial

    PubMed Central

    Hatano, Hiroyu; Strain, Matthew C.; Scherzer, Rebecca; Bacchetti, Peter; Wentworth, Deborah; Hoh, Rebecca; Martin, Jeffrey N.; McCune, Joseph M.; Neaton, James D.; Tracy, Russell P.; Hsue, Priscilla Y.; Richman, Douglas D.; Deeks, Steven G.

    2013-01-01

    Background. The degree to which human immunodeficiency virus (HIV) continues to replicate during antiretroviral therapy (ART) is controversial. We conducted a randomized, double-blind, placebo-controlled study to assess whether raltegravir intensification reduces low-level viral replication, as defined by an increase in the level of 2–long terminal repeat (2-LTR) circles. Methods. Thirty-one subjects with an ART-suppressed plasma HIV RNA level of <40 copies/mL and a CD4+ T-cell count of ≥350 cells/mm3 for ≥1 year were randomly assigned to receive raltegravir 400 mg twice daily or placebo for 24 weeks. 2-LTR circles were analyzed by droplet digital polymerase chain reaction at weeks 0, 1, 2, and 8. Results. The median duration of ART suppression was 3.8 years. The raltegravir group had a significant increase in the level of 2-LTR circles, compared to the placebo group. The week 1 to 0 ratio was 8.8-fold higher (P = .0025) and the week 2 to 0 ratio was 5.7-fold higher (P = .023) in the raltegravir vs. placebo group. Intensification also led to a statistically significant decrease in the D-dimer level, compared to placebo (P = .045). Conclusions. Raltegravir intensification resulted in a rapid increase in the level of 2-LTR circles in a proportion of subjects, indicating that low-level viral replication persists in some individuals even after long-term ART. Intensification also reduced the D-dimer level, a coagulation biomarker that is predictive of morbidity and mortality among patients receiving treatment for HIV infection. PMID:23975885

  11. 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

  12. 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.

    2016-01-01

    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. 

  13. 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

  14. Reconfigurable multiport EPON repeater

    NASA Astrophysics Data System (ADS)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  15. Revisiting the TALE repeat.

    PubMed

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity. PMID:24622844

  16. Quantum repeated games revisited

    NASA Astrophysics Data System (ADS)

    Frąckiewicz, Piotr

    2012-03-01

    We present a scheme for playing quantum repeated 2 × 2 games based on Marinatto and Weber’s approach to quantum games. As a potential application, we study the twice repeated Prisoner’s Dilemma game. We show that results not available in the classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games proposed by Iqbal and Toor. We point out the drawbacks that make their results unacceptable.

  17. Coordinate deletion of N-glycans from the heptad repeats of the fusion F protein of Newcastle disease virus yields a hyperfusogenic virus with increased replication, virulence, and immunogenicity.

    PubMed

    Samal, Sweety; Khattar, Sunil K; Kumar, Sachin; Collins, Peter L; Samal, Siba K

    2012-03-01

    The role of N-linked glycosylation of the Newcastle disease virus (NDV) fusion (F) protein in viral replication and pathogenesis was examined by eliminating potential acceptor sites using a reverse genetics system for the moderately pathogenic strain Beaudette C (BC). The NDV-BC F protein contains six potential acceptor sites for N-linked glycosylation at residues 85, 191, 366, 447, 471, and 541 (sites Ng1 to Ng6, respectively). The sites at Ng2 and Ng5 are present in heptad repeat (HR) domains HR1 and HR2, respectively, and thus might affect fusion. Each N-glycosylation site was eliminated individually by replacing asparagine (N) with glutamine (Q), and a double mutant (Ng2 + 5) involving the two HR domains was also made. Each mutant was successfully recovered by reverse genetics except for the one involving Ng6, which is present in the cytoplasmic domain. All of the F proteins expressed by the recovered mutant viruses were efficiently cleaved and transported to the infected-cell surface. None of the individual mutations affected viral fusogenicity, but the double mutation at Ng2 and Ng5 in HR1 and HR2 increased fusogenicity >12-fold. The single mutations at sites Ng1, Ng2, and Ng5 resulted in modestly reduced multicycle growth in vitro. These three single mutations were also the most attenuating in eggs and 1-day-old chicks and were associated with decreased replication and spread in 2-week-old chickens. In contrast, the combination of the mutations at Ng2 and Ng5 yielded a virus that, compared to the BC parent, replicated >100-fold more efficiently in vitro, was more virulent in eggs and chicks, replicated more efficiently in chickens with enhanced tropism for the brain and gut, and elicited stronger humoral cell responses. These results illustrate the effects of N-glycosylation of the F protein on NDV pathobiology and suggest that the N-glycans in HR1 and HR2 coordinately downregulate viral fusion and virulence. PMID:22205748

  18. The Pentapeptide Repeat Proteins

    SciTech Connect

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  19. Honesty through repeated interactions.

    PubMed

    Rich, Patricia; Zollman, Kevin J S

    2016-04-21

    In the study of signaling, it is well known that the cost of deception is an essential element for stable honest signaling in nature. In this paper, we show how costs for deception can arise endogenously from repeated interactions between individuals. Utilizing the Sir Philip Sidney game as an illustrative case, we show that repeated interactions can sustain honesty with no observable signal costs, even when deception cannot be directly observed. We provide a number of potential experimental tests for this theory which distinguish it from the available alternatives. PMID:26869213

  20. Repeated Causal Decision Making

    ERIC Educational Resources Information Center

    Hagmayer, York; Meder, Bjorn

    2013-01-01

    Many of our decisions refer to actions that have a causal impact on the external environment. Such actions may not only allow for the mere learning of expected values or utilities but also for acquiring knowledge about the causal structure of our world. We used a repeated decision-making paradigm to examine what kind of knowledge people acquire in…

  1. Bidirectional Manchester repeater

    NASA Technical Reports Server (NTRS)

    Ferguson, J.

    1980-01-01

    Bidirectional Manchester repeater is inserted at periodic intervals along single bidirectional twisted pair transmission line to detect, amplify, and transmit bidirectional Manchester 11 code signals. Requiring only 18 TTL 7400 series IC's, some line receivers and drivers, and handful of passive components, circuit is simple and relatively inexpensive to build.

  2. Stalled DNA Replication Forks at the Endogenous GAA Repeats Drive Repeat Expansion in Friedreich's Ataxia Cells.

    PubMed

    Gerhardt, Jeannine; Bhalla, Angela D; Butler, Jill Sergesketter; Puckett, James W; Dervan, Peter B; Rosenwaks, Zev; Napierala, Marek

    2016-08-01

    Friedreich's ataxia (FRDA) is caused by the expansion of GAA repeats located in the Frataxin (FXN) gene. The GAA repeats continue to expand in FRDA patients, aggravating symptoms and contributing to disease progression. The mechanism leading to repeat expansion and decreased FXN transcription remains unclear. Using single-molecule analysis of replicated DNA, we detected that expanded GAA repeats present a substantial obstacle for the replication machinery at the FXN locus in FRDA cells. Furthermore, aberrant origin activation and lack of a proper stress response to rescue the stalled forks in FRDA cells cause an increase in 3'-5' progressing forks, which could enhance repeat expansion and hinder FXN transcription by head-on collision with RNA polymerases. Treatment of FRDA cells with GAA-specific polyamides rescues DNA replication fork stalling and alleviates expansion of the GAA repeats, implicating DNA triplexes as a replication impediment and suggesting that fork stalling might be a therapeutic target for FRDA. PMID:27425605

  3. Discovery of a new repeat family in the Callithrix jacchus genome.

    PubMed

    Konkel, Miriam K; Ullmer, Brygg; Arceneaux, Erika L; Sanampudi, Sreeja; Brantley, Sarah A; Hubley, Robert; Smit, Arian F A; Batzer, Mark A

    2016-05-01

    We identified a novel repeat family, termed Platy-1, in the Callithrix jacchus (common marmoset) genome that arose around the time of the divergence of platyrrhines and catarrhines and established itself as a repeat family in New World monkeys (NWMs). A full-length Platy-1 element is ∼100 bp in length, making it the shortest known short interspersed element (SINE) in primates, and harbors features characteristic of non-LTR retrotransposons. We identified 2268 full-length Platy-1 elements across 62 subfamilies in the common marmoset genome. Our subfamily reconstruction and phylogenetic analyses support Platy-1 propagation throughout the evolution of NWMs in the lineage leading to C. jacchus Platy-1 appears to have reached its amplification peak in the common ancestor of current day marmosets and has since moderately declined. However, identification of more than 200 Platy-1 elements identical to their respective consensus sequence, and the presence of polymorphic elements within common marmoset populations, suggests ongoing retrotransposition activity. Platy-1, a SINE, appears to have originated from an Alu element, and hence is likely derived from 7SL RNA. Our analyses illustrate the birth of a new repeat family and its propagation dynamics in the lineage leading to the common marmoset over the last 40 million years. PMID:26916108

  4. 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.

  5. 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.

  6. Genomic evolution in Barrett’s adenocarcinoma cells: critical roles of elevated hsRAD51, homologous recombination and Alu sequences in the genome

    PubMed Central

    Pal, J; Bertheau, R; Buon, L; Qazi, A; Batchu, RB; Bandyopadhyay, S; Ali-Fehmi, R; Beer, DG; Weaver, DW; Reis, RJ Shmookler; Goyal, RK; Huang, Q; Munshi, NC; Shammas, MA

    2012-01-01

    A prominent feature of most cancers including Barrett’s adenocarcinoma (BAC) is genetic instability, which is associated with development and progression of disease. In this study, we investigated the role of recombinase (hsRAD51), a key component of homologous recombination (HR)/repair, in evolving genomic changes and growth of BAC cells. We show that the expression of RAD51 is elevated in BAC cell lines and tissue specimens, relative to normal cells. HR activity is also elevated and significantly correlates with RAD51 expression in BAC cells. The suppression of RAD51 expression, by short hairpin RNA (shRNA) specifically targeting this gene, significantly prevented BAC cells from acquiring genomic changes to either copy number or heterozygosity (P<0.02) in several independent experiments employing single-nucleotide polymorphism arrays. The reduction in copy-number changes, following shRNA treatment, was confirmed by Comparative Genome Hybridization analyses of the same DNA samples. Moreover, the chromosomal distributions of mutations correlated strongly with frequencies and locations of Alu interspersed repetitive elements on individual chromosomes. We conclude that the hsRAD51 protein level is systematically elevated in BAC, contributes significantly to genomic evolution during serial propagation of these cells and correlates with disease progression. Alu sequences may serve as substrates for elevated HR during cell proliferation in vitro, as they have been reported to do during the evolution of species, and thus may provide additional targets for prevention or treatment of this disease. PMID:21423218

  7. 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…

  8. A Complete and Accurate Ab Initio Repeat Finding Algorithm.

    PubMed

    Lian, Shuaibin; Chen, Xinwu; Wang, Peng; Zhang, Xiaoli; Dai, Xianhua

    2016-03-01

    It has become clear that repetitive sequences have played multiple roles in eukaryotic genome evolution including increasing genetic diversity through mutation, changes in gene expression and facilitating generation of novel genes. However, identification of repetitive elements can be difficult in the ab initio manner. Currently, some classical ab initio tools of finding repeats have already presented and compared. The completeness and accuracy of detecting repeats of them are little pool. To this end, we proposed a new ab initio repeat finding tool, named HashRepeatFinder, which is based on hash index and word counting. Furthermore, we assessed the performances of HashRepeatFinder with other two famous tools, such as RepeatScout and Repeatfinder, in human genome data hg19. The results indicated the following three conclusions: (1) The completeness of HashRepeatFinder is the best one among these three compared tools in almost all chromosomes, especially in chr9 (8 times of RepeatScout, 10 times of Repeatfinder); (2) in terms of detecting large repeats, HashRepeatFinder also performed best in all chromosomes, especially in chr3 (24 times of RepeatScout and 250 times of Repeatfinder) and chr19 (12 times of RepeatScout and 60 times of Repeatfinder); (3) in terms of accuracy, HashRepeatFinder can merge the abundant repeats with high accuracy. PMID:26272474

  9. Divergence of satellite DNA and interspersion of dispersed repeats in the genome of the wild beet Beta procumbens.

    PubMed

    Dechyeva, Daryna; Gindullis, Frank; Schmidt, Thomas

    2003-01-01

    Several repetitive sequences of the genome of Beta procumbens Chr. Sm., a wild beet species of the section Procumbentes of the genus Beta have been isolated. According to their genomic organization, the repeats were assigned to satellite DNA and families of dispersed DNA sequences. The tandem repeats are 229-246 bp long and belong to an AluI restriction satellite designated pAp11. Monomers of this satellite DNA form subfamilies which can be distinguished by the divergence or methylation of an internal restriction site. The satellite is amplified in the section Procumbentes, but is also found in species of the section Beta including cultivated beet (Beta vulgaris). The existence of the pAp11 satellite in distantly related species suggests that the AluI sequence family is an ancient component of Beta genomes and the ancestor of the diverged satellite subfamily pEV4 in B. vulgaris. Comparative fluorescent in-situ hybridization revealed remarkable differences in the chromosomal position between B. procumbens and B. vulgaris, indicating that the pAp11 and pEV4 satellites were most likely involved in the expansion or rearrangement of the intercalary B. vulgaris heterochromatin. Furthermore, we describe the molecular structure, and genomic and chromosomal organization of two repetitive DNA families which were designated pAp4 and pAp22 and are 1354 and 582 bp long, respectively. The families consist of sequence elements which are widely dispersed along B. procumbens chromosomes with local clustering and exclusion from distal euchromatic regions. FISH on meiotic chromosomes showed that both dispersed repeats are colocalized in some chromosomal regions. The interspersion of repeats of the pAp4 and pAp22 family was studied by PCR and enabled the determination of repeat flanking sequences. Sequence analysis revealed that pAp22 is either derived from or part of a long terminal repeat (LTR) of an Athila-like retrotransposon. Southern analysis and FISH with pAp4 and pAp22 showed

  10. 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. PMID:16421768

  11. 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.

  12. Repeated measures with zeros.

    PubMed

    Berk, K N; Lachenbruch, P A

    2002-08-01

    Consider repeated measures data with many zeros. For the case with one grouping factor and one repeated measure, we examine several models, assuming that the nonzero data are roughly lognormal. One of the simplest approaches is to model the zeros as left-censored observations from the lognormal distribution. A random effect is assumed for subjects. The censored model makes a strong assumption about the relationship between the zeros and the nonzero values. To check on this, you can instead assume that some of the zeros are 'true' zeros and model them as Bernoulli. Then the other values are modeled with a censored lognormal. A logistic model is used for the Bernoulli p, the probability of a true nonzero. The fit of the pure left-censored lognormal can be assessed by testing the hypothesis that p is 1, as described by Moulton and Halsey. The model can also be simplified by omitting the censoring, leaving a logistic model for the zeros and a lognormal model for the nonzero values. This is approximately equivalent to modeling the zero and nonzero values separately, a two-part model. In contrast to the censored model, this model assumes only a slight relationship (a covariance component) between the occurrence of zeros and the size of the nonzero values. The models are compared in terms of an example with data from children's private speech. PMID:12197298

  13. Rapid automatic detection and alignment of repeats in protein sequences.

    PubMed

    Heger, A; Holm, L

    2000-11-01

    Many large proteins have evolved by internal duplication and many internal sequence repeats correspond to functional and structural units. We have developed an automatic algorithm, RADAR, for segmenting a query sequence into repeats. The segmentation procedure has three steps: (i) repeat length is determined by the spacing between suboptimal self-alignment traces; (ii) repeat borders are optimized to yield a maximal integer number of repeats, and (iii) distant repeats are validated by iterative profile alignment. The method identifies short composition biased as well as gapped approximate repeats and complex repeat architectures involving many different types of repeats in the query sequence. No manual intervention and no prior assumptions on the number and length of repeats are required. Comparison to the Pfam-A database indicates good coverage, accurate alignments, and reasonable repeat borders. Screening the Swissprot database revealed 3,000 repeats not annotated in existing domain databases. A number of these repeats had been described in the literature but most were novel. This illustrates how in times when curated databases grapple with ever increasing backlogs, automatic (re)analysis of sequences provides an efficient way to capture this important information. PMID:10966575

  14. Ubiquitous transposon-like repeats B1 and B2 of the mouse genome: B2 sequencing.

    PubMed Central

    Krayev, A S; Markusheva, T V; Kramerov, D A; Ryskov, A P; Skryabin, K G; Bayev, A A; Georgiev, G P

    1982-01-01

    Mouse genome contains two major families of short interspersed repeats in more than 10(5) copies scattered throughout the whole genome. They are referred to as B1 and B2 sequences since they were first isolated from the genome library by means of a dsRNA-B probe /1/. In this work, two copies of the B2 family were sequenced and compared with the previously sequenced B1 repeat /2/. A B2 ubiquitous repeat is ca. 190 bp long. The members of the family deviate in 3-5% of nucleotides from the consensus sequence. B2 contains regions of homology to the RNA polymerase III split promoter and to 4.5S snRNA I. Both B1 and B2 contain regions which resemble junctions between exons and introns. In contrast to B1, B2 does not contain apparent homologies to papova viral replication origins and a human Alu sequence. One side of the B2 repeat is represented by a very AT-rich sequence (ca. 30 bp long) followed with an oligo (dA) stretch 10-15 nucleotides long. This region of the repeat is the most variable one. The whole unit is flanked with 15-16 bp direct repeats different in sequenced copies of B2. The same is true of some copies of the B1 family. The properties of B1 and B2 repeats suggest that they may represent a novel class of transposon-like elements in eukaryotic genome. A possible role of B-type repeats in genome reorganization, DNA replication and pre-mRNA processing is discussed. PMID:6296779

  15. 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…

  16. Cumulative Intertrial Inhibition in Repeated Visual Search

    ERIC Educational Resources Information Center

    Takeda, Yuji

    2007-01-01

    In the present study the author examined visual search when the items remain visible across trials but the location of the target varies. Reaction times for inefficient search cumulatively increased with increasing numbers of repeated search trials, suggesting that inhibition for distractors carried over successive trials. This intertrial…

  17. 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

  18. Structural and Energetic Characterization of the Ankyrin Repeat Protein Family

    PubMed Central

    Parra, R. Gonzalo; Espada, Rocío; Verstraete, Nina; Ferreiro, Diego U.

    2015-01-01

    Ankyrin repeat containing proteins are one of the most abundant solenoid folds. Usually implicated in specific protein-protein interactions, these proteins are readily amenable for design, with promising biotechnological and biomedical applications. Studying repeat protein families presents technical challenges due to the high sequence divergence among the repeating units. We developed and applied a systematic method to consistently identify and annotate the structural repetitions over the members of the complete Ankyrin Repeat Protein Family, with increased sensitivity over previous studies. We statistically characterized the number of repeats, the folding of the repeat-arrays, their structural variations, insertions and deletions. An energetic analysis of the local frustration patterns reveal the basic features underlying fold stability and its relation to the functional binding regions. We found a strong linear correlation between the conservation of the energetic features in the repeat arrays and their sequence variations, and discuss new insights into the organization and function of these ubiquitous proteins. PMID:26691182

  19. Repeated Transmissions In Mobile/Satellite Communications

    NASA Technical Reports Server (NTRS)

    Yan, Tsun-Yee; Clare, Loren P.

    1988-01-01

    Repetition increases throughput and decreases delay. Paper discusses theoretical performance of communication system for land-mobile stations with satellite relay using ALOHA random-access protocol modified for repeated transimssions. Methods and conclusions contribute to general understanding of packet communications in fading channels.

  20. Genesis, effects and fates of repeats in prokaryotic genomes.

    PubMed

    Treangen, Todd J; Abraham, Anne-Laure; Touchon, Marie; Rocha, Eduardo P C

    2009-05-01

    DNA repeats are causes and consequences of genome plasticity. Repeats are created by intrachromosomal recombination or horizontal transfer. They are targeted by recombination processes leading to amplifications, deletions and rearrangements of genetic material. The identification and analysis of repeats in nearly 700 genomes of bacteria and archaea is facilitated by the existence of sequence data and adequate bioinformatic tools. These have revealed the immense diversity of repeats in genomes, from those created by selfish elements to the ones used for protection against selfish elements, from those arising from transient gene amplifications to the ones leading to stable duplications. Experimental works have shown that some repeats do not carry any adaptive value, while others allow functional diversification and increased expression. All repeats carry some potential to disorganize and destabilize genomes. Because recombination and selection for repeats vary between genomes, the number and types of repeats are also quite diverse and in line with ecological variables, such as host-dependent associations or population sizes, and with genetic variables, such as the recombination machinery. From an evolutionary point of view, repeats represent both opportunities and problems. We describe how repeats are created and how they can be found in genomes. We then focus on the functional and genomic consequences of repeats that dictate their fate. PMID:19396957

  1. Blood Donation by Elderly Repeat Blood Donors

    PubMed Central

    Zeiler, Thomas; Lander-Kox, Jutta; Alt, Timo

    2014-01-01

    Summary Background Upper age limits for blood donors are intended to protect elderly blood donors from donor reactions. However, due to a lack of data about adverse reactions in elderly blood donors, upper age limits are arbitrary and vary considerably between different countries. Methods Here we present data from 171,231 voluntary repeat whole blood donors beyond the age of 68 years. Results Blood donations from repeat blood donors beyond the age of 68 years increased from 2,114 in 2005 to 38,432 in 2012 (from 0,2% to 4.2% of all whole blood donations). Adverse donor reactions in repeat donors decreased with age and were lower than in the whole group (0.26%), even in donors older than 71 years (0.16%). However, from the age of 68 years, the time to complete recovery after donor reactions increased. Donor deferrals were highest in young blood donors (21.4%), but increased again in elderly blood donors beyond 71 years (12.6%). Conclusion Blood donation by regular repeat blood donors older than 71 years may be safely continued. However, due to a lack of data for donors older than 75 years, blood donation in these donors should be handled with great caution. PMID:25254019

  2. All-photonic quantum repeaters

    PubMed Central

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

    2015-01-01

    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. PMID:25873153

  3. Sequence repeats and protein structure

    NASA Astrophysics Data System (ADS)

    Hoang, Trinh X.; Trovato, Antonio; Seno, Flavio; Banavar, Jayanth R.; Maritan, Amos

    2012-11-01

    Repeats are frequently found in known protein sequences. The level of sequence conservation in tandem repeats correlates with their propensities to be intrinsically disordered. We employ a coarse-grained model of a protein with a two-letter amino acid alphabet, hydrophobic (H) and polar (P), to examine the sequence-structure relationship in the realm of repeated sequences. A fraction of repeated sequences comprises a distinct class of bad folders, whose folding temperatures are much lower than those of random sequences. Imperfection in sequence repetition improves the folding properties of the bad folders while deteriorating those of the good folders. Our results may explain why nature has utilized repeated sequences for their versatility and especially to design functional proteins that are intrinsically unstructured at physiological temperatures.

  4. 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.

  5. All-photonic quantum repeaters.

    PubMed

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

    2015-01-01

    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. PMID:25873153

  6. Estimating repeatability of egg size

    USGS Publications Warehouse

    Flint, P.L.; Rockwell, R.F.; Sedinger, J.S.

    2001-01-01

    Measures of repeatability have long been used to assess patterns of variation in egg size within and among females. We compared different analytical approaches for estimating repeatability of egg size of Black Brant. Separate estimates of repeatability for eggs of each clutch size and laying sequence number varied from 0.49 to 0.64. We suggest that using the averaging egg size within clutches results in underestimation of variation within females and thereby overestimates repeatability. We recommend a nested design that partitions egg-size variation within clutches, among clutches within females, and among females. We demonstrate little variation in estimates of repeatability resulting from a nested model controlling for egg laying sequence and a nested model in which we assumed laying sequence was unknown.

  7. Increased risk of severe fluoropyrimidine-associated toxicity in patients carrying a G to C substitution in the first 28-bp tandem repeat of the thymidylate synthase 2R allele.

    PubMed

    Meulendijks, Didier; Jacobs, Bart A W; Aliev, Abidin; Pluim, Dick; van Werkhoven, Erik; Deenen, Maarten J; Beijnen, Jos H; Cats, Annemieke; Schellens, Jan H M

    2016-01-01

    The fluoropyrimidines act by inhibiting thymidylate synthase (TS). Recent studies have shown that patients' risk of severe fluoropyrimidine-associated toxicity is affected by polymorphisms in the 5'-untranslated region of TYMS, the gene encoding TS. A G>C substitution in the promoter enhancer region of TYMS, rs183205964 (known as the 2RC allele), markedly reduces TS activity in vitro, but its clinical relevance is unknown. We determined rs183205964 in 1605 patients previously enrolled in a prospective multicenter study. Associations between putative low TS expression genotypes (3RC/2RC, 2RG/2RC, and 2RC/2RC) and severe toxicity were investigated using univariable and multivariable logistic regression. Activity of TS and TYMS gene expression were determined in peripheral blood mononuclear cells (PBMCs) of a patient carrying genotype 2RC/2RC and of a control group of healthy individuals. Among 1,605 patients, 28 patients (1.7%) carried the 2RC allele. Twenty patients (1.2%) carried a risk-associated genotype (2RG/2RC, n=13; 3RC/2RC, n=6; and 2RC/2RC, n=1), the eight remaining patients had genotype 3RG/2RC. Early severe toxicity and toxicity-related hospitalization were significantly more frequent in risk-associated genotype carriers (OR 3.0, 95%CI 1.04-8.93, p=0.043 and OR 3.8, 95%CI 1.19-11.9, p=0.024, respectively, in multivariable analysis). The patient with genotype 2RC/2RC was hospitalized twice and had severe febrile neutropenia, diarrhea, and hand-foot syndrome. Baseline TS activity and gene expression in PBMCs of this patient, and a healthy individual with the 2RC allele, were found to be within the normal range. Our study suggests that patients carrying rs183205964 are at strongly increased risk of severe, potentially life-threatening, toxicity when treated with fluoropyrimidines. PMID:26189437

  8. Telomeric Repeat Mutagenicity in Human Somatic Cells is Modulated by Repeat Orientation and G-Quadruplex Stability

    PubMed Central

    Damerla, Rama Rao; Knickelbein, Kelly E.; Kepchia, Devin; Jackson, Abbe; Armitage, Bruce A.; Eckert, Kristin A.; Opresko, Patricia L.

    2010-01-01

    Telomeres consisting of tandem guanine-rich repeats can form secondary DNA structures called G-quadruplexes that represent potential targets for DNA repair enzymes. While G-quadruplexes interfere with DNA synthesis in vitro, the impact of G-quadruplex formation on telomeric repeat replication in human cells is not clear. We investigated the mutagenicity of telomeric repeats as a function of G-quadruplex folding opportunity and thermal stability using a shuttle vector mutagenesis assay. Since single stranded DNA during lagging strand replication increases the opportunity for G-quadruplex folding, we tested vectors with G-rich sequences on the lagging versus the leading strand. Contrary to our prediction, vectors containing human [TTAGGG]10 repeats with a G-rich lagging strand were significantly less mutagenic than vectors with a G-rich leading strand, after replication in normal human cells. We show by UV melting experiments that G-quadruplexes from ciliates [TTGGGG]4 and [TTTTGGGG]4 are thermally more stable compared to human [TTAGGG]4. Consistent with this, replication of vectors with ciliate [TTGGGG]10 repeats yielded a 3-fold higher mutant rate compared to the human [TTAGGG]10 vectors. Furthermore, we observed significantly more mutagenic events in the ciliate repeats compared to the human repeats. Our data demonstrate that increased G-quadruplex opportunity (repeat orientation) in human telomeric repeats decreased mutagenicity, while increased thermal stability of telomeric G-qaudruplexes was associated with increased mutagenicity. PMID:20800555

  9. 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.

  10. [Tandem repeats in rodents genome and their mapping].

    PubMed

    Ostromyshenskii, D I; Kuznetsova, L S; Komissarov, A S; Kartavtseva, I V; Podgornaya, L

    2015-01-01

    Tandemly-repeated sequences represent a unique class of eukaryotic DNA. Their content in the genome of higher eukaryotes mounts to tens of percents. However, the evolution of this class of sequences is poorly-studied. In our paper, 62 families of Mus musculus tandem repeats are analyzed by bioinformatic methods, and 7 of them are analyzed by fluorescence in situ hybridization. It is shown that the same tandem repeat sets co-occure only in closely related species of mice. But even in such species we observe differences in localization on the chromosomes and the number of individual tandem repeats. With increasing evolutionary distance only some of the tandem repeat families remain common for different species. It is shown, that the use of a combination of bioinformatics and molecular biology techniques is very perspective for further studies of the evolution of tandem repeats. PMID:26035967

  11. 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. PMID:27382061

  12. Protein Repeats from First Principles.

    PubMed

    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

  13. 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

  14. Protein Repeats from First Principles

    NASA Astrophysics Data System (ADS)

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

    2016-04-01

    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.

  15. Multicolor FISH mapping with Alu-PCR-amplified YAC clone DNA determines the order of markers in the BRCA1 region on chromosome 17q12-q21

    SciTech Connect

    Flejter, W.J.; Glover, T.W.; Barcroft, C.L.; Guo, Sun Wei; Boehnke, M.; Chandrasekharappa, S.; Collins, F.S. Howard Hughes Medical Institute, Ann Arbor, MI ); Lynch, E.D. ); Hayes, S. ); Weber, B.L. )

    1993-09-01

    A gene designated BRCA1, implicated in the susceptibility to early-onset familial breast cancer, has recently been localized to chromosome 17q12-q21. To date, the order of DNA markers mapped within this region has been based on genetic linkage analysis. The authors report the use of multicolor fluorescence in situ hybridization to establish a physically based map of five polymorphic DNA markers and 10 cloned genes spanning this region. Three cosmid clones and Alu-PCR-Generated products derived from 12 yeast artificial chromosome clones representing each of these markers were used in two-color mapping experiments to determine an initial proximity of markers relative to each other on metaphase chromosomes. Interphase mapping was then employed to determine the order and orientation of closely spaced loci by direct visualization of fluorescent signals following hybridization of three probes, each detected in a different color. Statistical analysis of the combined data suggests that the order of markers in the BRCA1 regions is cen-THRA1-TOP2-GAS-OF2-17HSD-248yg9-RNU2-OF3-PPY/p131-EPB3-Mfd188-WNT3-HOX2-GP3A-tel. This map is consistent with that determined by radiation-reduced hybrid mapping and will facilitate positional cloning strategies in efforts to isolate and characterize the BRCA1 gene. 27 refs., 2 figs., 3 tabs.

  16. Identification of an AluY-mediated deletion of exon 5 in the CPOX gene by MLPA analysis in patients with hereditary coproporphyria.

    PubMed

    Barbaro, M; Kotajärvi, M; Harper, P; Floderus, Y

    2012-03-01

    Hereditary coproporphyria (HCP) is an autosomal dominantly inherited hepatic porphyria, caused by a mutation in the coproporphyrinogen oxidase (CPOX) gene. The genetic defect leads to a partial defect of CPOX, the sixth enzyme involved in haem biosynthesis. Affected individuals can develop acute life-threatening attacks of neurovisceral symptoms and/or more rarely cutaneous symptoms such as skin fragility and blistering. The identification of the genetic defect in HCP families is of crucial importance to detect the carrier status which allows counselling to prevent possible triggering factors, e.g. certain drugs, alcohol, or fasting. In a total of nine Swedish HCP families, routine gene sequence analysis had identified a causative mutation in only five. In the present study, using an in-house developed synthetic probe set for multiplex ligation-dependent probe amplification (MLPA) analysis, we detected a deletion of the fifth exon in the CPOX gene in the remaining four families. The deletion is 3381 bp in size and has originated by an Alu-mediated mechanism. This finding emphasizes the usefulness of MLPA analysis as a complement to gene sequencing for comprehensive genetic diagnostics in HCP patients. PMID:21231929

  17. 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. PMID:11131404

  18. Hypermnesia: the role of repeated testing.

    PubMed

    Roediger, H L; Payne, D G

    1982-01-01

    The present study was designed to determine whether the increased recall of pictures across repeated tests (hypermnesia) is due to increasing strength of imaginal traces during the retention interval or to increased retrieval practice from prior tests. Subjects studied 60 pictures and then recalled them after various delays that were filled with instructions and, in two cases, reading a passage. Recall on a first test showed no change with retention interval. With retention interval held constant, however, the number of pictures recalled varied directly with the number of prior tests subjects had been given. This finding points up the critical nature of retrieval factors in producing hypermnesia. PMID:6210744

  19. Variable Glutamine-Rich Repeats Modulate Transcription Factor Activity

    PubMed Central

    Gemayel, Rita; Chavali, Sreenivas; Pougach, Ksenia; Legendre, Matthieu; Zhu, Bo; Boeynaems, Steven; van der Zande, Elisa; Gevaert, Kris; Rousseau, Frederic; Schymkowitz, Joost; Babu, M. Madan; Verstrepen, Kevin J.

    2015-01-01

    Summary Excessive expansions of glutamine (Q)-rich repeats in various human proteins are known to result in severe neurodegenerative disorders such as Huntington’s disease and several ataxias. However, the physiological role of these repeats and the consequences of more moderate repeat variation remain unknown. Here, we demonstrate that Q-rich domains are highly enriched in eukaryotic transcription factors where they act as functional modulators. Incremental changes in the number of repeats in the yeast transcriptional regulator Ssn6 (Cyc8) result in systematic, repeat-length-dependent variation in expression of target genes that result in direct phenotypic changes. The function of Ssn6 increases with its repeat number until a certain threshold where further expansion leads to aggregation. Quantitative proteomic analysis reveals that the Ssn6 repeats affect its solubility and interactions with Tup1 and other regulators. Thus, Q-rich repeats are dynamic functional domains that modulate a regulator’s innate function, with the inherent risk of pathogenic repeat expansions. PMID:26257283

  20. Diversity and evolution of centromere repeats in the maize genome.

    PubMed

    Bilinski, Paul; Distor, Kevin; Gutierrez-Lopez, Jose; Mendoza, Gabriela Mendoza; Shi, Jinghua; Dawe, R Kelly; Ross-Ibarra, Jeffrey

    2015-03-01

    Centromere repeats are found in most eukaryotes and play a critical role in kinetochore formation. Though centromere repeats exhibit considerable diversity both within and among species, little is understood about the mechanisms that drive centromere repeat evolution. Here, we use maize as a model to investigate how a complex history involving polyploidy, fractionation, and recent domestication has impacted the diversity of the maize centromeric repeat CentC. We first validate the existence of long tandem arrays of repeats in maize and other taxa in the genus Zea. Although we find considerable sequence diversity among CentC copies genome-wide, genetic similarity among repeats is highest within these arrays, suggesting that tandem duplications are the primary mechanism for the generation of new copies. Nonetheless, clustering analyses identify similar sequences among distant repeats, and simulations suggest that this pattern may be due to homoplasious mutation. Although the two ancestral subgenomes of maize have contributed nearly equal numbers of centromeres, our analysis shows that the majority of all CentC repeats derive from one of the parental genomes, with an even stronger bias when examining the largest assembled contiguous clusters. Finally, by comparing maize with its wild progenitor teosinte, we find that the abundance of CentC likely decreased after domestication, while the pericentromeric repeat Cent4 has drastically increased. PMID:25190528

  1. Intragenic tandem repeat variation between Legionella pneumophila strains

    PubMed Central

    Coil, David A; Vandersmissen, Liesbeth; Ginevra, Christophe; Jarraud, Sophie; Lammertyn, Elke; Anné, Jozef

    2008-01-01

    Background Bacterial genomes harbour a large number of tandem repeats, yet the possible phenotypic effects of those found within the coding region of genes are only beginning to be examined. Evidence exists from other organisms that these repeats can be involved in the evolution of new genes, gene regulation, adaptation, resistance to environmental stresses, and avoidance of the immune system. Results In this study, we have investigated the presence and variability in copy number of intragenic tandemly repeated sequences in the genome of Legionella pneumophila, the etiological agent of a severe pneumonia known as Legionnaires' disease. Within the genome of the Philadelphia strain, we have identified 26 intragenic tandem repeat sequences using conservative selection criteria. Of these, seven were "polymorphic" in terms of repeat copy number between a large number of L. pneumophila serogroup 1 strains. These strains were collected from a wide variety of environments and patients in several geographical regions. Within this panel of strains, all but one of these seven genes exhibited statistically different patterns in repeat copy number between samples from different origins (environmental, clinical, and hot springs). Conclusion These results support the hypothesis that intragenic tandem repeats could play a role in virulence and adaptation to different environments. While tandem repeats are an increasingly popular focus of molecular typing studies in prokaryotes, including in L. pneumophila, this study is the first examining the difference in tandem repeat distribution as a function of clinical or environmental origin. PMID:19077205

  2. Limitations on quantum key repeaters.

    PubMed

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

    2015-01-01

    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. PMID:25903096

  3. 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.

  4. Repeating seismic events in China.

    PubMed

    Schaff, David P; Richards, Paul G

    2004-02-20

    About 10% of seismic events in and near China from 1985 to 2000 were repeating events not more than about 1 kilometer from each other. We cross-correlated seismograms from approximately 14,000 earthquakes and explosions and measured relative arrival times to approximately 0.01 second, enabling lateral location precision of about 100 to 300 meters. Such precision is important for seismic hazard studies, earthquake physics, and nuclear test ban verification. Recognition and measurement of repeating signals in archived data and the resulting improvement in location specificity quantifies the inaccuracy of current procedures for picking onset times and locating events. PMID:14976310

  5. Interoperability in encoded quantum repeater networks

    NASA Astrophysics Data System (ADS)

    Nagayama, Shota; Choi, Byung-Soo; Devitt, Simon; Suzuki, Shigeya; Van Meter, Rodney

    2016-04-01

    The future of quantum repeater networking will require interoperability between various error-correcting codes. A few specific code conversions and even a generalized method are known, however, no detailed analysis of these techniques in the context of quantum networking has been performed. In this paper we analyze a generalized procedure to create Bell pairs encoded heterogeneously between two separate codes used often in error-corrected quantum repeater network designs. We begin with a physical Bell pair and then encode each qubit in a different error-correcting code, using entanglement purification to increase the fidelity. We investigate three separate protocols for preparing the purified encoded Bell pair. We calculate the error probability of those schemes between the Steane [[7,1,3

  6. Pure laparoscopic hepatectomy as repeat surgery and repeat hepatectomy

    PubMed Central

    Isetani, Masashi; Morise, Zenichi; Kawabe, Norihiko; Tomishige, Hirokazu; Nagata, Hidetoshi; Kawase, Jin; Arakawa, Satoshi

    2015-01-01

    AIM: To assess clinical outcomes of laparoscopic hepatectomy (LH) in patients with a history of upper abdominal surgery and repeat hepatectomy. METHODS: This study compared the perioperative courses of patients receiving LH at our institution that had or had not previously undergone upper abdominal surgery. Of the 80 patients who underwent LH, 22 had prior abdominal surgeries, including hepatectomy (n = 12), pancreatectomy (n = 3), cholecystectomy and common bile duct excision (n = 1), splenectomy (n = 1), total gastrectomy (n = 1), colectomy with the involvement of transverse colon (n = 3), and extended hysterectomy with extensive lymph-node dissection up to the upper abdomen (n = 1). Clinical indicators including operating time, blood loss, hospital stay, and morbidity were compared among the groups. RESULTS: Eighteen of the 22 patients who had undergone previous surgery had severe adhesions in the area around the liver. However, there were no conversions to laparotomy in this group. In the 58 patients without a history of upper abdominal surgery, the median operative time was 301 min and blood loss was 150 mL. In patients with upper abdominal surgical history or repeat hepatectomy, the operative times were 351 and 301 min, and blood loss was 100 and 50 mL, respectively. The median postoperative stay was 17, 13 and 12 d for patients with no history of upper abdominal surgery, patients with a history, and patients with repeat hepatectomy, respectively. There were five cases with complications in the group with no surgical history, compared to only one case in the group with a prior history. There were no statistically significant differences in the perioperative results between the groups with and without upper abdominal surgical history, or with repeat hepatectomy. CONCLUSION: LH is feasible and safe in patients with a history of upper abdominal surgery or repeat hepatectomy. PMID:25624731

  7. Genome wide analysis of acute myeloid leukemia reveal leukemia specific methylome and subtype specific hypomethylation of repeats.

    PubMed

    Saied, Marwa H; Marzec, Jacek; Khalid, Sabah; Smith, Paul; Down, Thomas A; Rakyan, Vardhman K; Molloy, Gael; Raghavan, Manoj; Debernardi, Silvana; Young, Bryan D

    2012-01-01

    Methylated DNA immunoprecipitation followed by high-throughput sequencing (MeDIP-seq) has the potential to identify changes in DNA methylation important in cancer development. In order to understand the role of epigenetic modulation in the development of acute myeloid leukemia (AML) we have applied MeDIP-seq to the DNA of 12 AML patients and 4 normal bone marrows. This analysis revealed leukemia-associated differentially methylated regions that included gene promoters, gene bodies, CpG islands and CpG island shores. Two genes (SPHKAP and DPP6) with significantly methylated promoters were of interest and further analysis of their expression showed them to be repressed in AML. We also demonstrated considerable cytogenetic subtype specificity in the methylomes affecting different genomic features. Significantly distinct patterns of hypomethylation of certain interspersed repeat elements were associated with cytogenetic subtypes. The methylation patterns of members of the SINE family tightly clustered all leukemic patients with an enrichment of Alu repeats with a high CpG density (P<0.0001). We were able to demonstrate significant inverse correlation between intragenic interspersed repeat sequence methylation and gene expression with SINEs showing the strongest inverse correlation (R(2) = 0.7). We conclude that the alterations in DNA methylation that accompany the development of AML affect not only the promoters, but also the non-promoter genomic features, with significant demethylation of certain interspersed repeat DNA elements being associated with AML cytogenetic subtypes. MeDIP-seq data were validated using bisulfite pyrosequencing and the Infinium array. PMID:22479372

  8. 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…

  9. 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

  10. Environmental stress induces trinucleotide repeat mutagenesis in human cells.

    PubMed

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

    2015-03-24

    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

  11. 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

  12. Repeatability observations from a time-lapse seismic survey

    USGS Publications Warehouse

    Walters, S.L.; Miller, R.D.; Raef, A.E.

    2006-01-01

    Time-lapse seismic surveys have proven extremely valuable in recent years, having numerous economical and environmental applications. To fully utilize this monitoring technique, problems associated with recording repeatability must be minimized. Much work has been done to equalize data from one survey to the next via processing techniques (Huang et al., 1998). The purpose of this study is to investigate the potential for minimized processing, allowing study of extremely small changes in subsurface characteristics. The goal is to evaluate source and receiver terrain combination to optimize signal repeatability, and to improve deconvolution with the ground force to suppress different types of noise and increase repeatability. ?? 2005 Society of Exploration Geophysicists.

  13. Mechanisms of RNA-induced toxicity in CAG repeat disorders.

    PubMed

    Nalavade, R; Griesche, N; Ryan, D P; Hildebrand, S; Krauss, S

    2013-01-01

    Several inherited neurodegenerative disorders are caused by CAG trinucleotide repeat expansions, which can be located either in the coding region or in the untranslated region (UTR) of the respective genes. Polyglutamine diseases (polyQ diseases) are caused by an expansion of a stretch of CAG repeats within the coding region, translating into a polyQ tract. The polyQ tract expansions result in conformational changes, eventually leading to aggregate formation. It is widely believed that the aggregation of polyQ proteins is linked with disease development. In addition, in the last couple of years, it has been shown that RNA-mediated mechanisms also have a profound role in neurotoxicity in both polyQ diseases and diseases caused by elongated CAG repeat motifs in their UTRs. Here, we review the different molecular mechanisms assigned to mRNAs with expanded CAG repeats. One aspect is the mRNA folding of CAG repeats. Furthermore, pathogenic mechanisms assigned to CAG repeat mRNAs are discussed. First, we discuss mechanisms that involve the sequestration of the diverse proteins to the expanded CAG repeat mRNA molecules. As a result of this, several cellular mechanisms are aberrantly regulated. These include the sequestration of MBNL1, leading to misregulated splicing; sequestration of nucleolin, leading to reduced cellular rRNA; and sequestration of proteins of the siRNA machinery, resulting in the production of short silencing RNAs that affect gene expression. Second, we discuss the effect of expanded CAG repeats on the subcellular localization, transcription and translation of the CAG repeat mRNA itself. Here we focus on the MID1 protein complex that triggers an increased translation of expanded CAG repeat mRNAs and a mechanism called repeat-associated non-ATG translation, which leads to proteins aberrantly translated from CAG repeat mRNAs. In addition, therapeutic approaches for CAG repeat disorders are discussed. Together, all the findings summarized here show that

  14. Mechanisms of RNA-induced toxicity in CAG repeat disorders

    PubMed Central

    Nalavade, R; Griesche, N; Ryan, D P; Hildebrand, S; Krauß, S

    2013-01-01

    Several inherited neurodegenerative disorders are caused by CAG trinucleotide repeat expansions, which can be located either in the coding region or in the untranslated region (UTR) of the respective genes. Polyglutamine diseases (polyQ diseases) are caused by an expansion of a stretch of CAG repeats within the coding region, translating into a polyQ tract. The polyQ tract expansions result in conformational changes, eventually leading to aggregate formation. It is widely believed that the aggregation of polyQ proteins is linked with disease development. In addition, in the last couple of years, it has been shown that RNA-mediated mechanisms also have a profound role in neurotoxicity in both polyQ diseases and diseases caused by elongated CAG repeat motifs in their UTRs. Here, we review the different molecular mechanisms assigned to mRNAs with expanded CAG repeats. One aspect is the mRNA folding of CAG repeats. Furthermore, pathogenic mechanisms assigned to CAG repeat mRNAs are discussed. First, we discuss mechanisms that involve the sequestration of the diverse proteins to the expanded CAG repeat mRNA molecules. As a result of this, several cellular mechanisms are aberrantly regulated. These include the sequestration of MBNL1, leading to misregulated splicing; sequestration of nucleolin, leading to reduced cellular rRNA; and sequestration of proteins of the siRNA machinery, resulting in the production of short silencing RNAs that affect gene expression. Second, we discuss the effect of expanded CAG repeats on the subcellular localization, transcription and translation of the CAG repeat mRNA itself. Here we focus on the MID1 protein complex that triggers an increased translation of expanded CAG repeat mRNAs and a mechanism called repeat-associated non-ATG translation, which leads to proteins aberrantly translated from CAG repeat mRNAs. In addition, therapeutic approaches for CAG repeat disorders are discussed. Together, all the findings summarized here show that

  15. 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.

  16. 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.

  17. 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. PMID:26934226

  18. Repeatability of agronomic traits in Panicum maximum (Jacq.) hybrids.

    PubMed

    Braz, T G S; Fonseca, D M; Jank, L; Cruz, C D; Martuscello, J A

    2015-01-01

    When evaluating plants, in particular perennial species, it is common to obtain repeated measures of a given trait from the same individual to evaluate the traits' repeatability in successive harvests. The degree of correlation among these measures defines the coefficient of repeatability, which has been widely utilized in the study of forage traits of interest for breeding. The objective of the present study was to evaluate the repeatability of agronomic traits in Panicum maximum hybrids. Hybrids from three progenies totaling 320 hybrids were evaluated in an incomplete-block design, with consideration of production and morpho-agronomic traits. Of the production traits, total dry matter and leaf dry matter showed the highest repeatability and varied from 0.540 to 0.769, whereas stem dry matter had lower coefficients (0.265-0.632). Among the morpho-agronomic traits, plant height and incidence of Bipolaris maydis had higher coefficients (0.118-0.460). The repeatability values of the agronomic traits were low-to-moderate, and six evaluations were sufficient to provide accuracy in the selection of hybrids regarding total dry matter, leaf dry matter, plant height, and incidence of B. maydis, whereas the other traits require more repeated measures to increase reliability in the prediction of their response. PMID:26782581

  19. The repeatability of behaviour: a meta-analysis

    PubMed Central

    Bell, Alison M.; Hankison, Shala J.; Laskowski, Kate L.

    2014-01-01

    There is increasing interest in individual differences in animal behaviour. Recent research now suggests that an individual’s behaviour, once considered to be plastic, may be more predictable than previously thought. Here, we take advantage of the large number of studies that have estimated the repeatability of various behaviours to evaluate whether there is good evidence for consistent individual differences in behaviour and to answer some outstanding questions about possible factors that can influence repeatability. Specifically, we use meta-analysis to ask whether different types of behaviours were more repeatable than others, and if repeatability estimates depended on taxa, sex, age, field versus laboratory, the number of measures and the interval between measures. Some of the overall patterns that were revealed by this analysis were that repeatability estimates were higher in the field compared to the laboratory and repeatability was higher when the interval between observations was short. Mate preference behaviour was one of the best studied but least repeatable behaviours. Our findings prompt new insights into the relative flexibility of different types of behaviour and offer suggestions for the design and analysis of future research. PMID:24707058

  20. RNA FISH for detecting expanded repeats in human diseases.

    PubMed

    Urbanek, Martyna O; Krzyzosiak, Wlodzimierz J

    2016-04-01

    RNA fluorescence in situ hybridization (FISH) is a widely used technique for detecting transcripts in fixed cells and tissues. Many variants of RNA FISH have been proposed to increase signal strength, resolution and target specificity. The current variants of this technique facilitate the detection of the subcellular localization of transcripts at a single molecule level. Among the applications of RNA FISH are studies on nuclear RNA foci in diseases resulting from the expansion of tri-, tetra-, penta- and hexanucleotide repeats present in different single genes. The partial or complete retention of mutant transcripts forming RNA aggregates within the nucleoplasm has been shown in multiple cellular disease models and in the tissues of patients affected with these atypical mutations. Relevant diseases include, among others, myotonic dystrophy type 1 (DM1) with CUG repeats, Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3) with CAG repeats, fragile X-associated tremor/ataxia syndrome (FXTAS) with CGG repeats, myotonic dystrophy type 2 (DM2) with CCUG repeats, amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) with GGGGCC repeats and spinocerebellar ataxia type 32 (SCA32) with GGCCUG. In this article, we summarize the results obtained with FISH to examine RNA nuclear inclusions. We provide a detailed protocol for detecting RNAs containing expanded CAG and CUG repeats in different cellular models, including fibroblasts, lymphoblasts, induced pluripotent stem cells and murine and human neuronal progenitors. We also present the results of the first single-molecule FISH application in a cellular model of polyglutamine disease. PMID:26615955

  1. 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.

  2. Telomerase Repeated Amplification Protocol (TRAP)

    PubMed Central

    Mender, Ilgen; Shay, Jerry W.

    2016-01-01

    Telomeres are found at the end of eukaryotic linear chromosomes, and proteins that bind to telomeres protect DNA from being recognized as double-strand breaks thus preventing end-to-end fusions (Griffith et al., 1999). However, due to the end replication problem and other factors such as oxidative damage, the limited life span of cultured cells (Hayflick limit) results in progressive shortening of these protective structures (Hayflick and Moorhead, 1961; Olovnikov, 1973). The ribonucleoprotein enzyme complex telomerase-consisting of a protein catalytic component hTERT and a functional RNA component hTR or hTERC- counteracts telomere shortening by adding telomeric repeats to the end of chromosomes in ~90% of primary human tumors and in some transiently proliferating stem-like cells (Shay and Wright, 1996; Shay and Wright, 2001). This results in continuous proliferation of cells which is a hallmark of cancer. Therefore, telomere biology has a central role in aging, cancer progression/metastasis as well as targeted cancer therapies. There are commonly used methods in telomere biology such as Telomere Restriction Fragment (TRF) (Mender and Shay, 2015b), Telomere Repeat Amplification Protocol (TRAP) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this detailed protocol we describe Telomere Repeat Amplification Protocol (TRAP). The TRAP assay is a popular method to determine telomerase activity in mammalian cells and tissue samples (Kim et al., 1994). The TRAP assay includes three steps: extension, amplification, and detection of telomerase products. In the extension step, telomeric repeats are added to the telomerase substrate (which is actually a non telomeric oligonucleotide, TS) by telomerase. In the amplification step, the extension products are amplified by the polymerase chain reaction (PCR) using specific primers (TS upstream primer and ACX downstream primer) and in the detection step, the presence or absence of telomerase is

  3. 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.

  4. Repeated, but Not Acute, Stress Suppresses Inflammatory Plasma Extravasation

    NASA Astrophysics Data System (ADS)

    Strausbaugh, Holly J.; Dallman, Mary F.; Levine, Jon D.

    1999-12-01

    Clinical findings suggest that inflammatory disease symptoms are aggravated by ongoing, repeated stress, but not by acute stress. We hypothesized that, compared with single acute stressors, chronic repeated stress may engage different physiological mechanisms that exert qualitatively different effects on the inflammatory response. Because inhibition of plasma extravasation, a critical component of the inflammatory response, has been associated with increased disease severity in experimental arthritis, we tested for a potential repeated stress-induced inhibition of plasma extravasation. Repeated, but not single, exposures to restraint stress produced a profound inhibition of bradykinin-induced synovial plasma extravasation in the rat. Experiments examining the mechanism of inhibition showed that the effect of repeated stress was blocked by adrenalectomy, but not by adrenal medullae denervation, suggesting that the adrenal cortex mediates this effect. Consistent with known effects of stress and with mediation by the adrenal cortex, restraint stress evoked repeated transient elevations of plasma corticosterone levels. This elevated corticosterone was necessary and sufficient to produce inhibition of plasma extravasation because the stress-induced inhibition was blocked by preventing corticosterone synthesis and, conversely, induction of repeated transient elevations in plasma corticosterone levels mimicked the effects of repeated stress. These data suggest that repetition of a mild stressor can induce changes in the physiological state of the animal that enable a previously innocuous stressor to inhibit the inflammatory response. These findings provide a potential explanation for the clinical association between repeated stress and aggravation of inflammatory disease symptoms and provide a model for study of the biological mechanisms underlying the stress-induced aggravation of chronic inflammatory diseases.

  5. Electromyographic analysis of repeated bouts of eccentric exercise.

    PubMed

    McHugh, M P; Connolly, D A; Eston, R G; Gartman, E J; Gleim, G W

    2001-03-01

    The repeated bout effect refers to the protective effect provided by a single bout of eccentric exercise against muscle damage from a similar subsequent bout. The aim of this study was to determine if the repeated bout was associated with an increase in motor unit activation relative to force production, an increased recruitment of slow-twitch motor units or increased motor unit synchronization. Surface electromyographic (EMG) signals were recorded from the hamstring muscles during two bouts of submaximal isokinetic (2.6 rad x s(-1)) eccentric (11 men, 9 women) or concentric (6 men, 4 women) contractions separated by 2 weeks. The EMG per unit torque and median frequency were analysed. The initial bout of eccentric exercise resulted in strength loss, pain and muscle tenderness, while the repeated eccentric bout resulted in a slight increase in strength, no pain and no muscle tenderness (bout x time effects, P < 0.05). Strength, pain and tenderness were unaffected by either bout of concentric exercise. The EMG per unit torque and median frequency were not different between the initial and repeated bouts of eccentric exercise. The EMG per unit torque and median frequency increased during both bouts of eccentric exercise (P < 0.01) but did not change during either concentric bout. In conclusion, there was no evidence that the repeated bout effect was due to a neural adaptation. PMID:11256821

  6. Community Protection Policies and Repeat Sexual Offenses in Florida.

    PubMed

    Levenson, Jill S; Zgoba, Kristen M

    2016-08-01

    The purpose of this study was to investigate the impact of sexual offender management policies on sex crime repeat arrest rates in Florida. Aggregate data for the period 1990 to 2010 were provided by the Florida Department of Law Enforcement. The repeat offense rate was defined as the proportion of arrests each year that were committed by individuals with a previous conviction in the same crime category. The average yearly repeat offense rate for sex crimes was 6.5%, which was consistently and significantly lower than rates for other crimes: 8.3% for non-sex assaults, 15.1% for robbery, 29.8% for drug offenses, and 11.6% for DUI. The average annual sexual repeat arrest rate prior to and after the implementation of sexual offender registration laws in 1997 was 4.9% and 7.5%, respectively, indicating a statistically significant increase. The average annual repeat arrest rates for non-sex assaults, robberies, drug crimes, and DUIs also increased after 1997. No significant differences were found when comparing the average annual percent change for sexual re-arrest (+3.47%) with non-sexual assault (+3.93%), robbery (-.73%), drug offenses (+1.59%), and DUI (+1.14). Sex crime repeat arrests in Florida do not appear to show a decline attributable to sex offender management policies implemented since 1997. PMID:25759428

  7. 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

  8. 47 CFR 22.1015 - Repeater operation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Repeater operation. 22.1015 Section 22.1015 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Offshore Radiotelephone Service § 22.1015 Repeater operation. Offshore central stations may be used as repeater stations provided that...

  9. 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.

  10. 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.

  11. 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.

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

    PubMed

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

    2016-05-01

    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. PMID:26947150

  13. 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. PMID:26465749

  14. Repeatability and oblique flow response characteristics of current meters

    USGS Publications Warehouse

    Fulford, Janice M.; Thibodeaux, Kirk G.; Kaehrle, William R.

    1993-01-01

    Laboratory investigation into the precision and accuracy of various mechanical-current meters are presented. Horizontal-axis and vertical-axis meters that are used for the measurement of point velocities in streams and rivers were tested. Meters were tested for repeatability and response to oblique flows. Both horizontal- and vertical-axis meters were found to under- and over-register oblique flows with errors generally increasing as the velocity and angle of flow increased. For the oblique flow tests, magnitude of errors were smallest for horizontal-axis meters. Repeatability of all meters tested was good, with the horizontal- and vertical-axis meters performing similarly.

  15. 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

  16. Transcription of two classes of rat growth hormone gene-associated repetitive DNA: differences in activity and effects of tandem repeat structure.

    PubMed Central

    Gutierrez-Hartmann, A; Lieberburg, I; Gardner, D; Baxter, J D; Cathala, G G

    1984-01-01

    The rat growth hormone (rGH) gene contains two classes of repetitive DNA arranged as clusters within intron B and the 3' flanking region. The major family is equivalent to the CHO type 2 DNA. The second ("truncated repeat", TR) is a truncated version of the first and occurs in certain neural-specific transcripts and genes ("identifier" elements, ID). Here we report, using the HeLa cell-free transcription assay, that RNA polymerase III (Pol III) efficiently initiates at internal promoters within a tandem array of rGH gene repetitive DNA monomers and results in a novel organization of overlapping Class III transcription units. Transcription competition studies revealed that the rat type 2 structures share Pol III transcription factors with a tRNA gene, a human Alu repeat, and a mutant VA1 gene. Also, the rGH type 2 but not the TR DNA efficiently promotes Pol III initiation, yet other TR members, which differ only in flanking DNA, are transcribed. Thus, the rGH gene is strikingly enriched with 10 repetitive DNA monomers; multimeric type 2 elements are actively transcribed; rGH-TR sequences are expressed only as part of larger transcripts promoted by type 2 DNA; and, type 2 DNA uses tRNA gene transcription factors. These studies show that flanking sequences, promoter organization and factor competition may all affect rat repetitive DNA expression. Images PMID:6091058

  17. Aging and repeated thought suppression success.

    PubMed

    Lambert, Ann E; Smyth, Frederick L; Beadel, Jessica R; Teachman, Bethany A

    2013-01-01

    Intrusive thoughts and attempts to suppress them are common, but while suppression may be effective in the short-term, it can increase thought recurrence in the long-term. Because intentional suppression involves controlled processing, and many aspects of controlled processing decline with age, age differences in thought suppression outcomes may emerge, especially over repeated thought suppression attempts as cognitive resources are expended. Using multilevel modeling, we examined age differences in reactions to thought suppression attempts across four thought suppression sequences in 40 older and 42 younger adults. As expected, age differences were more prevalent during suppression than during free monitoring periods, with younger adults indicating longer, more frequent thought recurrences and greater suppression difficulty. Further, younger adults' thought suppression outcomes changed over time, while trajectories for older adults' were relatively stable. Results are discussed in terms of older adults' reduced thought recurrence, which was potentially afforded by age-related changes in reactive control and distractibility. PMID:23776442

  18. 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

  19. Observations of Soft Gamma Repeaters

    NASA Technical Reports Server (NTRS)

    Kouveliotou, Chryssa

    2005-01-01

    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 emitting hundreds of predominantly soft (kl'=30 kev), short (0.1 - 100 ms long) events. Their quiescent source X-ray light curves exhibit pulsations in the narrow range of 5-1 1 s; estimates of these rotational period rate changes (spin-down) indicate that their magnetic fields are extremely high, of the order of 10A14-10A15 G. Such high B-field objects, dubbed "magnetars", had been predicted to exist in 1992, but the first concrete observational evidence was obtained in 1998 for two of these sources. Very recently, SGR1806-20 emitted a giant flare, which was detected in the radio with a multitude of telescopes under an extensive international campaign. These observations have revealed exciting new results, never seen before in any of the other magnetar sources. I will discuss here these results and their relevance to our understanding of the nature of magnetars.

  20. 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. PMID:27015469

  1. Repeated Sprints: An Independent Not Dependent Variable.

    PubMed

    Taylor, Jonathan M; Macpherson, Tom W; Spears, Iain R; Weston, Matthew

    2016-07-01

    The ability to repeatedly perform sprints has traditionally been viewed as a key performance measure in team sports, and the relationship between repeated-sprint ability (RSA) and performance has been explored extensively. However, when reviewing the repeated-sprint profile of team-sports match play it appears that the occurrence of repeated-sprint bouts is sparse, indicating that RSA is not as important to performance as commonly believed. Repeated sprints are, however, a potent and time-efficient training strategy, effective in developing acceleration, speed, explosive leg power, aerobic power, and high-intensity-running performance--all of which are crucial to team-sport performance. As such, we propose that repeated-sprint exercise in team sports should be viewed as an independent variable (eg, a means of developing fitness) as opposed to a dependent variable (eg, a means of assessing fitness/performance). PMID:27197118

  2. Strengthening concept learning by repeated testing

    PubMed Central

    Wiklund-Hörnqvist, Carola; Jonsson, Bert; Nyberg, Lars

    2014-01-01

    The aim of this study was to examine whether repeated testing with feedback benefits learning compared to rereading of introductory psychology key-concepts in an educational context. The testing effect was examined immediately after practice, after 18 days, and at a five-week delay in a sample of undergraduate students (n = 83). The results revealed that repeated testing with feedback significantly enhanced learning compared to rereading at all delays, demonstrating that repeated retrieval enhances retention compared to repeated encoding in the short- and the long-term. In addition, the effect of repeated testing was beneficial for students irrespectively of working memory capacity. It is argued that teaching methods involving repeated retrieval are important to consider by the educational system. PMID:24313425

  3. 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.

  4. Understanding and identifying amino acid repeats.

    PubMed

    Luo, Hong; Nijveen, Harm

    2014-07-01

    Amino acid repeats (AARs) are abundant in protein sequences. They have particular roles in protein function and evolution. Simple repeat patterns generated by DNA slippage tend to introduce length variations and point mutations in repeat regions. Loss of normal and gain of abnormal function owing to their variable length are potential risks leading to diseases. Repeats with complex patterns mostly refer to the functional domain repeats, such as the well-known leucine-rich repeat and WD repeat, which are frequently involved in protein–protein interaction. They are mainly derived from internal gene duplication events and stabilized by ‘gate-keeper’ residues, which play crucial roles in preventing inter-domain aggregation. AARs are widely distributed in different proteomes across a variety of taxonomic ranges, and especially abundant in eukaryotic proteins. However, their specific evolutionary and functional scenarios are still poorly understood. Identifying AARs in protein sequences is the first step for the further investigation of their biological function and evolutionary mechanism. In principle, this is an NP-hard problem, as most of the repeat fragments are shaped by a series of sophisticated evolutionary events and become latent periodical patterns. It is not possible to define a uniform criterion for detecting and verifying various repeat patterns. Instead, different algorithms based on different strategies have been developed to cope with different repeat patterns. In this review, we attempt to describe the amino acid repeat-detection algorithms currently available and compare their strategies based on an in-depth analysis of the biological significance of protein repeats. PMID:23418055

  5. 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

  6. Approaching improved adhesive bonding repeatability

    NASA Astrophysics Data System (ADS)

    Schlette, Christian; Müller, Tobias; Roβmann, Jürgen; Brecher, Christian

    2016-03-01

    Today, the precision of micro-optics assembly is mostly limited by the accuracy of the bonding process ― and in the case of adhesive bonding by the prediction and compensation of adhesive shrinkage during curing. In this contribution, we present a novel approach to address adhesive bonding based on hybrid control system theory. In hybrid control, dynamic systems are described as "plants" which produce discrete and/or continuous outputs from given discrete and/or continuous inputs, thus yielding a hybrid state space description of the system. The task of hybrid controllers is to observe the plant and to generate a discrete and/or continuous input sequence that guides or holds the plant in a desired target state region while avoiding invalid or unwanted intermediate states. Our approach is based on a series of experiments carried out in order to analyze, define and decouple the dependencies of adhesive shrinkage on multiple parameters, such as application geometries, fixture forces and UV intensities. As some of the dependencies describe continuous effects (e.g. shrinkage from UV intensity) and other dependencies describe discrete state transitions (e.g. fixture removal during curing), the resulting model of the overall bonding process is a hybrid dynamic system in the general case. For this plant model, we then propose a concept of sampling-based parameter search as a basis to design suitable hybrid controllers, which have the potential to optimize process control for a selection of assembly steps, thus improving the repeatability of related production steps like beam-shaping optics or mounting of turning mirrors for fiber coupling.

  7. Repeated Interactive Read-Alouds in Preschool and Kindergarten

    ERIC Educational Resources Information Center

    McGee, Lea M.; Schickedanz, Judith A.

    2007-01-01

    Repeated interactive read-alouds, a systematic method of reading aloud, allow teachers to scaffold children's understanding of the book being read, model strategies for making inferences and explanations, and teach vocabulary and concepts. A storybook is read three times in slightly different ways in order to increase the amount and quality of…

  8. Repeated intravenous doxapram induces phrenic motor facilitation

    PubMed Central

    Sandhu, MS; Lee, KZ; Gonzalez-Rothi, EJ; Fuller, DD

    2013-01-01

    Doxapram is a respiratory stimulant used to treat hypoventilation. Here we investigated whether doxapram could also trigger respiratory neuroplasticity. Specifically, we hypothesized that intermittent delivery of doxapram at low doses would lead to long-lasting increases (i.e., facilitation) of phrenic motor output in anesthetized, vagotomized, and mechanically-ventilated rats. Doxapram was delivered intravenously in a single bolus (2 or 6 mg/kg) or as a series of 3 injections (2 mg/kg) at 5 min intervals. Control groups received pH-matched saline injections (vehicle) or no treatment (anesthesia time control). Doxapram evoked an immediate increase in phrenic output in all groups, but a persistent increase in burst amplitude only occurred after repeated dosing with 2 mg/kg. At 60 min following the last injection, phrenic burst amplitude was 168±24% of baseline (%BL) in the group receiving 3 injections (P < 0.05 vs. controls), but was 103±8%BL and 112±4%BL in the groups receiving a single dose of 2 or 6 mg/kg, respectively. Following bilateral section of the carotid sinus nerves, the acute phrenic response to doxapram (2 mg/kg) was reduced by 68% suggesting that at low doses the drug was acting primarily via the carotid chemoreceptors. We conclude that intermittent application of doxapram can trigger phrenic neuroplasticity, and this approach might be of use in the context of respiratory rehabilitation following neurologic injury. PMID:24013015

  9. Intra-Genomic Variation in the Ribosomal Repeats of Nematodes

    PubMed Central

    Bik, Holly M.; Fournier, David; Sung, Way; Bergeron, R. Daniel; Thomas, W. Kelley

    2013-01-01

    Ribosomal loci represent a major tool for investigating environmental diversity and community structure via high-throughput marker gene studies of eukaryotes (e.g. 18S rRNA). Since the estimation of species’ abundance is a major goal of environmental studies (by counting numbers of sequences), understanding the patterns of rRNA copy number across species will be critical for informing such high-throughput approaches. Such knowledge is critical, given that ribosomal RNA genes exist within multi-copy repeated arrays in a genome. Here we measured the repeat copy number for six nematode species by mapping the sequences from whole genome shotgun libraries against reference sequences for their rRNA repeat. This revealed a 6-fold variation in repeat copy number amongst taxa investigated, with levels of intragenomic variation ranging from 56 to 323 copies of the rRNA array. By applying the same approach to four C. elegans mutation accumulation lines propagated by repeated bottlenecking for an average of ~400 generations, we find on average a 2-fold increase in repeat copy number (rate of increase in rRNA estimated at 0.0285-0.3414 copies per generation), suggesting that rRNA repeat copy number is subject to selection. Within each Caenorhabditis species, the majority of intragenomic variation found across the rRNA repeat was observed within gene regions (18S, 28S, 5.8S), suggesting that such intragenomic variation is not a product of selection for rRNA coding function. We find that the dramatic variation in repeat copy number among these six nematode genomes would limit the use of rRNA in estimates of organismal abundance. In addition, the unique pattern of variation within a single genome was uncorrelated with patterns of divergence between species, reflecting a strong signature of natural selection for rRNA function. A better understanding of the factors that control or affect copy number in these arrays, as well as their rates and patterns of evolution, will be

  10. Repeat Gamma Knife surgery for vestibular schwannomas

    PubMed Central

    Lonneville, Sarah; Delbrouck, Carine; Renier, Cécile; Devriendt, Daniel; Massager, Nicolas

    2015-01-01

    Background: Gamma Knife (GK) surgery is a recognized treatment option for the management of small to medium-sized vestibular schwannoma (VS) associated with high-tumor control and low morbidity. When a radiosurgical treatment fails to stop tumor growth, repeat GK surgery can be proposed in selected cases. Methods: A series of 27 GK retreatments was performed in 25 patients with VS; 2 patients underwent three procedures. The median time interval between GK treatments was 45 months. The median margin dose used for the first, second, and third GK treatments was 12 Gy, 12 Gy, and 14 Gy, respectively. Six patients (4 patients for the second irradiation and 2 patients for the third irradiation) with partial tumor regrowth were treated only on the growing part of the tumor using a median margin dose of 13 Gy. The median tumor volume was 0.9, 2.3, and 0.7 cc for the first, second, and third treatments, respectively. Stereotactic positron emission tomography (PET) guidance was used for dose planning in 6 cases. Results: Mean follow-up duration was 46 months (range 24–110). At the last follow-up, 85% of schwannomas were controlled. The tumor volume decreased, remained unchanged, or increased after retreatment in 15, 8, and 4 cases, respectively. Four patients had PET during follow-up, and all showed a significant metabolic decrease of the tumor. Hearing was not preserved after retreatment in any patients. New facial or trigeminal palsy did not occur after retreatment. Conclusions: Our results support the long-term efficacy and low morbidity of repeat GK treatment for selected patients with tumor growth after initial treatment. PMID:26500799

  11. Effects of repeated production on vowel distinctiveness within nonwords

    PubMed Central

    Sasisekaran, Jayanthi; Munson, Benjamin

    2012-01-01

    In the present study acoustic distinctiveness of vowels within nonwords with repeated production was investigated. Participants were 9 males and 15 females divided into two groups. Participants repeated 6 nonwords varying in phonemic composition. The mean Euclidean distance (MED) of the vowels from each production of a nonword from the center of the F1/F2 space was calculated. The changes in MED with repeated production were analyzed using linear mixed effects regression. Results revealed an increase in MED, indicating greater vowel dispersion, for the three-syllable nonwords and a significant decrease, i.e., greater reduction, in vowel dispersion for the six-syllable nonwords. Findings support the dynamic influence of sublexical processes on phonetic realization in speech production. PMID:22502490

  12. Evolution Analysis of Simple Sequence Repeats in Plant Genome

    PubMed Central

    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. PMID:26630570

  13. All Repeats are Not Equal: A Module-Based Approach to Guide Repeat Protein Design

    PubMed Central

    Regan, Lynne

    2013-01-01

    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 3 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 armadillio repeat (ARM) 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. PMID:23434848

  14. 47 CFR 97.205 - Repeater station.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO SERVICE Special Operations § 97.205 Repeater station. (a) Any amateur station licensed to a holder of a Technician, General, Advanced or Amateur Extra Class operator license may be a repeater. A holder of...

  15. 47 CFR 97.205 - Repeater station.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO SERVICE Special Operations § 97.205 Repeater station. (a) Any amateur station licensed to a holder of a Technician, General, Advanced or Amateur Extra Class operator license may be a repeater. A holder of...

  16. 47 CFR 97.205 - Repeater station.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO SERVICE Special Operations § 97.205 Repeater station. (a) Any amateur station licensed to a holder of a Technician, General, Advanced or Amateur Extra Class operator license may be a repeater. A holder of...

  17. 47 CFR 97.205 - Repeater station.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO SERVICE Special Operations § 97.205 Repeater station. (a) Any amateur station licensed to a holder of a Technician, General, Advanced or Amateur Extra Class operator license may be a repeater. A holder of...

  18. 47 CFR 97.205 - Repeater station.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES AMATEUR RADIO SERVICE Special Operations § 97.205 Repeater station. (a) Any amateur station licensed to a holder of a Technician, General, Advanced or Amateur Extra Class operator license may be a repeater. A holder of...

  19. The Effects of Repeaters on Test Equating.

    ERIC Educational Resources Information Center

    Andrulis, Richard S.; And Others

    The purpose of this investigation was to establish the effects of repeaters on test equating. Since consideration was not given to repeaters in test equating, such as in the derivation of equations by Angoff (1971), the hypothetical effect needed to be established. A case study was examined which showed results on a test as expected; overall mean…

  20. The Effects of Repeaters on Test Equating.

    ERIC Educational Resources Information Center

    Andrulis, Richard S.; And Others

    1978-01-01

    The effects of repeaters (testees included in both administrations of two forms of a test) on the test equating process are examined. It is shown that repeaters do effect test equating and tend to lower the cutoff point for passing the test. (JKS)

  1. Evaluating a Group Repeated Reading Intervention

    ERIC Educational Resources Information Center

    Klubnik, Cynthia Adele

    2009-01-01

    Fluency has been identified as an important component of effective reading instruction, and repeated reading has been shown to improve oral reading fluency. In order to improve the efficiency of repeated reading interventions, more research is needed on the effectiveness of small group reading interventions. An alternating treatments, single…

  2. Laparoscopic repeat hepatectomy after right hepatopancreaticoduodenectomy.

    PubMed

    Igami, Tsuyoshi; Komaya, Kenichi; Hirose, Tomoaki; Ebata, Tomoki; Yokoyama, Yukihiro; Sugawara, Gen; Mizuno, Takashi; Yamaguchi, Junpei; Nagino, Masato

    2016-08-01

    Although laparoscopic hepatectomy is widely accepted for primary hepatectomy, the clinical value of laparoscopic hepatectomy for repeat hepatectomy is still challenging. We herein describe our experience with laparoscopic repeat hepatectomy after right hepatopancreaticoduodenectomy. A 72-year-old woman who had undergone right hepatopancreaticoduodenectomy for perihilar cholangiocarcinoma 31 months prior was diagnosed with liver metastasis in segment 3. We performed laparoscopic repeat hepatectomy. Because mild adhesions in the left side of the abdominal cavity were detected by laparoscopy, the planned procedure was accomplished. The operative time and intraoperative blood loss were 139 min and less than 1 mL, respectively. The patient was discharged at 6 days after surgery and was healthy with no evidence of recurrence at 21 months after laparoscopic repeat hepatectomy. Laparoscopic repeat hepatectomy is a suitable and safe procedure for minor hepatectomy, provided that careful technique is used after the working space is secured under pneumoperitoneum. PMID:27221034

  3. 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.

  4. 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…

  5. Repeated blast exposures cause brain DNA fragmentation in mice.

    PubMed

    Wang, Ying; Arun, Peethambaran; Wei, Yanling; Oguntayo, Samuel; Gharavi, Robert; Valiyaveettil, Manojkumar; Nambiar, Madhusoodana P; Long, Joseph B

    2014-03-01

    The pathophysiology of blast-induced traumatic brain injury (TBI) and subsequent behavioral deficits are not well understood. Unraveling the mechanisms of injury is critical to derive effective countermeasures against this form of neurotrauma. Preservation of the integrity of cellular DNA is crucial for the function and survival of cells. We evaluated the effect of repeated blast exposures on the integrity of brain DNA and tested the utility of cell-free DNA (CFD) in plasma as a biomarker for the diagnosis and prognosis of blast-induced polytrauma. The results revealed time-dependent breakdown in cellular DNA in different brain regions, with the maximum damage at 24 h post-blast exposures. CFD levels in plasma showed a significant transient increase, which was largely independent of the timing and severity of brain DNA damage; maximum levels were recorded at 2 h after repeated blast exposure and returned to baseline at 24 h. A positive correlation was observed between the righting reflex time and CFD level in plasma at 2 h after blast exposure. Brain DNA damage subsequent to repeated blast was associated with decreased mitochondrial membrane potential, increased release of cytochrome C, and up-regulation of caspase-3, all of which are indicative of cellular apoptosis. Shock-wave-induced DNA damage and initiation of mitochondrial-driven cellular apoptosis in the brain after repeated blast exposures indicate that therapeutic strategies directed toward inhibition of DNA damage or instigation of DNA repair may be effective countermeasures. PMID:24074345

  6. 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.

  7. Continuity of care. Opportunity for residents to see repeat patients.

    PubMed Central

    Bell, N. R.; Szafran, O.

    1995-01-01

    OBJECTIVE: To examine the opportunity for first-year family medicine residents to experience continuity of care during family medicine block time and half-day returns. DESIGN: Retrospective analysis of patient encounter data during the 1987-1988 and 1991-1992 academic years to determine how much contact residents had with repeat patients. SETTING: Two family medicine teaching centres in Edmonton. PARTICIPANTS: First-year family medicine residents: 24 residents during 1987-1988 and 24 during 1991-1992. MAIN OUTCOME MEASURES: Number of patient-resident contacts and number of repeat contacts. RESULTS: During the 4-month block time and half-day return, residents had repeat contact with 25.9% and 20.3% of the patients seen. These patients provided 48.3% and 37.7% of all visits at Centres A and B, respectively. CONCLUSION: Increasing block time from 2 to 4 months resulted in only a slight increase in repeat contact with patients. Half-day returns did not appear to enhance the opportunity for continuity of care. PMID:8563505

  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. Characteristics of LGV repeaters: analysis of LGV surveillance data

    PubMed Central

    Rönn, Minttu; Hughes, Gwenda; White, Peter; Simms, Ian; Ison, Catherine; Ward, Helen

    2014-01-01

    Objectives A number of individuals have acquired lymphogranuloma venereum (LGV) infection multiple times since its re-emergence. We describe the characteristics of reinfections and those who acquire them. Methods The LGV Enhanced Surveillance system collected detailed information on LGV episodes in the UK from 2004 to 2010. Using logistic regression we compared the baseline characteristics of men who have sex with men (MSM) who had a repeat LGV episode (‘repeaters’) to MSM with a single reported episode (‘non-repeaters’). Results There were 66 individuals among the 1281 MSM (5.2%) with LGV episode who had a recorded reinfection during the data collection period. Those who acquired LGV reinfection were more likely to be HIV positive (97% vs 79%), visit a clinic in London (OR 2.0, 95% CI 1.1 to 3.8), and have hepatitis C (OR 2.2, 95% CI 1.1 to 4.6) or concurrent gonorrhoea (OR 2.2, 95% CI 1.2 to 3.8) on their first recorded LGV episode. Repeaters reported higher levels of unprotected sex, but behavioural variables were not significantly different between repeaters and non-repeaters. Conclusions Among LGV repeaters, risk behaviour alone did not explain subsequent reinfection. LGV repeaters have a high level of other sexually transmitted infections (STIs) which may be linked to their central position in the sexual network that contributes to their heightened risk of STI acquisition. Given the low prevalence of LGV in the general MSM population, momentary increases in incidence in subsets of the population may be an important factor for LGV risk where the overall level of sexual risk behaviour is higher. Validating this would require research into sexual network structures. PMID:24431182

  10. C9ORF72 Intermediate Repeat Copies Are a Significant Risk Factor for Parkinson Disease

    PubMed Central

    Nuytemans, Karen; Bademci, Güney; Kohli, Martin M; Beecham, Gary W; Wang, Liyong; Young, Juan I; Nahab, Fatta; Martin, Eden R; Gilbert, John R; Benatar, Michael; Haines, Jonathan L; Scott, William K; Züchner, Stephan; Pericak-Vance, Margaret A; Vance, Jeffery M

    2013-01-01

    We set out to determine whether expansions in the C9ORF72 repeat found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) families are associated with Parkinson disease (PD). We determined the repeat size in a total of 889 clinically ascertained patients (including PD and essential tremor plus Parkinsonism (ETP)) and 1144 controls using a repeat-primed PCR assay. We found that large C9ORF72 repeat expansions (>30 repeats) were not contributing to PD risk. However, PD and ETP cases had a significant increase in intermediate (>20 to 30+) repeat copies compared to controls. Overall, 14 cases (13 PD, 1 ETP) and three controls had >20 repeat copies (Fisher's exact test p = 0.002). Further, seven cases and no controls had >23 repeat copies (p = 0.003). Our results suggest that intermediate copy numbers of the C9ORF72 repeat contribute to risk for PD and ETP. This also suggests that PD, ALS and FTD share some pathophysiological mechanisms of disease. Further studies are needed to elucidate the contribution of the C9ORF72 repeat in the overall PD population and to determine whether other common genetic risk factors exist between these neurodegenerative disorders. PMID:23845100

  11. Finding and Characterizing Repeats in Plant Genomes.

    PubMed

    Nicolas, Jacques; Peterlongo, Pierre; Tempel, Sébastien

    2016-01-01

    Plant genomes contain a particularly high proportion of repeated structures of various types. This chapter proposes a guided tour of available software that can help biologists to look for these repeats and check some hypothetical models intended to characterize their structures. Since transposable elements are a major source of repeats in plants, many methods have been used or developed for this large class of sequences. They are representative of the range of tools available for other classes of repeats and we have provided a whole section on this topic as well as a selection of the main existing software. In order to better understand how they work and how repeats may be efficiently found in genomes, it is necessary to look at the technical issues involved in the large-scale search of these structures. Indeed, it may be hard to keep up with the profusion of proposals in this dynamic field and the rest of the chapter is devoted to the foundations of the search for repeats and more complex patterns. The second section introduces the key concepts that are useful for understanding the current state of the art in playing with words, applied to genomic sequences. This can be seen as the first stage of a very general approach called linguistic analysis that is interested in the analysis of natural or artificial texts. Words, the lexical level, correspond to simple repeated entities in texts or strings. In fact, biologists need to represent more complex entities where a repeat family is built on more abstract structures, including direct or inverted small repeats, motifs, composition constraints as well as ordering and distance constraints between these elementary blocks. In terms of linguistics, this corresponds to the syntactic level of a language. The last section introduces concepts and practical tools that can be used to reach this syntactic level in biological sequence analysis. PMID:26519414

  12. Do gamma-ray burst sources repeat?

    NASA Technical Reports Server (NTRS)

    Meegan, C. A.; Hartmann, D. H.; Brainerd, J. J.; Briggs, M.; Paciesas, W. S.; Pendleton, G.; Kouveliotou, C.; Fishman, G.; Blumenthal, G.; Brock, M.

    1994-01-01

    The demonstration of repeated gamma-ray bursts from an individual source would severely constrain burst source models. Recent reports 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 ad 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 bursts cannot be excluded.

  13. Repeat participation among normal healthy research volunteers: professional guinea pigs in clinical trials?

    PubMed

    Tishler, Carl L; Bartholomae, Suzanne

    2003-01-01

    The recent death of a normal healthy volunteer, as well as the increased use of normal volunteers as research subjects, has heightened the attention given to the participation of normal volunteers in clinical research. An overlooked sub-population of normal healthy volunteers are repeat, veteran volunteers. This essay discusses ethical and methodological issues associated with the use of repeat volunteers in research, along with existing guidelines regarding the use of repeat healthy volunteers, and concludes with recommendations for safeguarding repeat volunteers and ideas supporting centralized recruiting. PMID:14593220

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

    PubMed

    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

  15. 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

  16. Transfer of flowering and Kousa dogwood simple sequence repeats (SSRs) to selected Cornus (Cornaceae) species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cross species transferability of simple sequence repeats (SSRs) is common and allows SSRs isolated from one species to be applied to closely related species increasing the utility of previously isolated SSRs. Simple sequence repeats are popular PCR-based markers that are valued for their abundance, ...

  17. 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. PMID:26695179

  18. 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

  19. 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

  20. [Repeated action of hyperbaria on rat blood system].

    PubMed

    Maslova, M N; Klimova, V K

    2014-01-01

    There are considered reactions of male Wistar rat blood system to repeated action of nitrogen-oxygen hyperbaria (pressure 0.5 MPa, density of gas medium 6 g/l, pO2 = 0.02-0.03 MPa). Rats were placed into a barochamber for 5 h 24, 72, and 120 h after the first exposition (control in air without the increased pressure). Parameters of red blood were studied and the general state of the animals was estimated. It has been established that after the first hyperbaria séance the stress-reaction develops in rats with all objective stress parameters (level of corticosteroids and content of ascorbic acid in adrenals). At repeated exposure after 24 h the almost complete normalization of all stress parameters was observed, except for the increased hemoglobin content in plasma as a result of impair of permeability of erythrocytic membranes. After repeated actions 72 and 120 h later, the stress parameters manifested again. After exposure 120 h later, the general state of animals was sharply deteriorated they did not move in the "open" field, could not be hold on a horizontal bar, and mainly were lying. The performed control with the immobilization stress showed that after the initial stress-reaction the rats were recovered completely and at repeated exposures no changes were observed in the blood system and in the general state of the animals. We belive that the hyperbaria-produced stress is connected with difficult breathing under pressure. Thereby, the repeated action of hyperbaria is a harmful factor and habituation to it does not occur. PMID:25782286

  1. Repeat radiosurgery for cerebral arteriovenous malformations.

    PubMed

    Awad, Ahmed J; Walcott, Brian P; Stapleton, Christopher J; Ding, Dale; Lee, Cheng-Chia; Loeffler, Jay S

    2015-06-01

    We perform a systematic review of repeat 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, repeat radiosurgery can be considered if sufficient time has passed to allow for a full appreciation of treatment effects, usually at least 3years. A systematic review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 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 19.42Gy and 19.06Gy, 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 80months. Time to complete obliteration after the repeat treatment ranged from 21 to 40.8months. The most common complications of repeat 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 3 years following the initial treatment, allowing for full realization of effects from the initial treatment prior to commencing therapy. PMID:25913746

  2. Nociceptive Reactions in Rats during Repeated Stress Exposure.

    PubMed

    Kozlov, A Yu; Abramova, A Yu; Chekhlov, V V; Grigorchuk, O S; Pertsov, S S

    2015-10-01

    Changes in nociceptive sensitivity of rats with various behavioral patterns in the open-field test were studied after repeated stress exposure on the model of daily 4-h immobilization for 8 days. The tail-flick latency in response to light-heat stimulation in passive and active specimens decreased most significantly on days 2 and 7, respectively. However, this parameter did not differ from the baseline on day 8 of observations. Vocalization threshold during electrocutaneous stimulation in behaviorally active animals did not change over the first 7 days of repeated stress exposure, but increased significantly on day 8 of the study. The emotional component of nociception in passive animals increased on day 3, but decreased on days 4 and 6 of the experiment. Therefore, repeated stress exposure in rats is mainly accompanied by an increase in the perceptual component of nociception. Variations in the emotional component of nociceptive sensitivity after stress loads are manifested in the initial increase and subsequent decrease in this parameter. The observed changes are more pronounced in behaviorally passive rats than in active animals. These data illustrate the specifics of stress-induced changes in nociception of specimens with various individual and typological characteristics. Our results hold much promise for the development of new individual approaches to modulation of pain sensitivity in humans under conditions of negative emotiogenic exposures. PMID:26519267

  3. Comparison of CTG repeat length expansion and clinical progression of myotonic dystrophy over a five year period.

    PubMed Central

    Martorell, L; Martinez, J M; Carey, N; Johnson, K; Baiget, M

    1995-01-01

    Myotonic dystrophy (DM) is associated with an underlying CTG trinucleotide repeat expansion at a locus on chromosome 19q13.3. We have determined the repeat length in 23 DM patients with varying clinical severity of symptoms and various sizes of repeat amplification. We confirm that as in previous studies there is no strong correlation between repeat length and clinical symptoms but find that the repeat length in peripheral blood cells of patients increases over a time span of five years indicating continuing mitotic instability of the repeat throughout life. Repeat length progression does not appear to be indicative of clinical progression but age probably is. The degree of expansion correlates with the initial repeat size and 50% of the patients with continuing expansions showed clinical progression of their disease symptoms over the five year study period. Images PMID:7473648

  4. How many populations set foot through the Patagonian door? Genetic composition of the current population of Bahía Blanca (Argentina) based on data from 19 Alu polymorphisms.

    PubMed

    Resano, M; Esteban, E; González-Pérez, E; Vía, M; Athanasiadis, G; Avena, S; Goicoechea, A; Bartomioli, M; Fernández, V; Cabrera, A; Dejean, C; Carnese, F; Moral, P

    2007-01-01

    The city of Bahía Blanca occupies a strategic place in Argentina south of the Pampean region in the north-east corner of the Patagonia. Since 1828, this city has been the historical and political border between Amerindian lands in the south, and the lands of European colonists. Nowadays, Bahía Blanca is an urban population mainly composed by descendents of immigrants from Spain and other European countries with apparently low admixture with Amerindians. In view of the unexpectedly high Amerindian admixture levels (about 46.7%) suggested by mtDNA data, and protein markers (19.5%), we analyzed a set of 19 Alu polymorphisms (18 autosomal, 1 of Chromosome Y) in a well-documented genealogical sample from Bahía Blanca. The genotyped sample was made up of 119 unrelated healthy individuals whose birth place and grandparent origins were fully documented. According to available genealogical records, the total sample has been subdivided into two groups: Bahía Blanca Original (64 individuals with all 4 gandparents born in Argentina) and Bahía Blanca Mix (55 individuals with one to three grandparents born out of Argentina). Allele frequencies and gene diversity values in Bahía Blanca fit well into the European ranges. Population relationships have been tested for 8 Alu markers, whose variation has been described in several Amerindian and European samples. Reynolds genetic distances underline the significant genetic similarity of Bahía Blanca to Europeans (mean distance 0.044) and their differentiation from Amerindians (0.146). Interestingly enough, when the general sample is divided, Bahía Blanca Original appears slightly closer to Amerindians (0.127) in contrast to Bahía Blanca Mix (0.161). Furthermore, the genetic relationships depicted through a principal components analysis emphasize the relative similarity of Bahía Blanca Original to Amerindians. A thorough knowledge of the sample origins has allowed us to make a subtle distinction of the genetic composition of

  5. 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

  6. 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

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

    PubMed Central

    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. PMID:26783496

  8. 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.

  9. Analysis of repeat-protein folding using nearest-neighbor statistical mechanical models

    PubMed Central

    Aksel, Tural; Barrick, Doug

    2010-01-01

    The linear “Ising” model, which has been around for nearly a century, treats the behavior of linear arrays of repetitive, interacting subunits. Linear “repeat-proteins” have only been described in the last decade or so, and their folding energies have only been characterized very recently. Owing to their repetitive structures, linear repeat-proteins are particularly well suited for analysis by the nearest-neighbor Ising formalism. After briefly describing the historical origins and applications of the Ising model to biopolymers, and introducing repeat protein structure, this chapter will focus on the application of the linear Ising model to repeat proteins. When applied to homopolymers, the model can be represented and applied in a fairly simplified form. When applied to heteropolymers, where differences in energies among individual subunits (i.e. repeats) must be included, some (but not all) of this simplicity is lost. Derivations of the linear Ising model for both homopolymer and heteropolymer repeat-proteins will be presented. With the increased complexity required for analysis of heteropolymeric repeat proteins, the ability to resolve different energy terms from experimental data can be compromised. Thus, a simple matrix approach will be developed to help inform on the degree to which different thermodynamic parameters can be extracted from a particular set of unfolding curves. Finally, we will describe the application of these models to analyze repeat-protein folding equilibria, focusing on simplified repeat proteins based on “consensus” sequence information. PMID:19289204

  10. 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.

  11. DNA Instability Maintains the Repeat Length of the Yeast RNA Polymerase II C-terminal Domain.

    PubMed

    Morrill, Summer A; Exner, Alexandra E; Babokhov, Michael; Reinfeld, Bradley I; Fuchs, Stephen M

    2016-05-27

    The C-terminal domain (CTD) of RNA polymerase II in eukaryotes is comprised of tandemly repeating units of a conserved seven-amino acid sequence. The number of repeats is, however, quite variable across different organisms. Furthermore, previous studies have identified evidence of rearrangements within the CTD coding region, suggesting that DNA instability may play a role in regulating or maintaining CTD repeat number. The work described here establishes a clear connection between DNA instability and CTD repeat number in Saccharomyces cerevisiae First, analysis of 36 diverse S. cerevisiae isolates revealed evidence of numerous past rearrangements within the DNA sequence that encodes the CTD. Interestingly, the total number of CTD repeats was relatively static (24-26 repeats in all strains), suggesting a balancing act between repeat expansion and contraction. In an effort to explore the genetic plasticity within this region, we measured the rates of repeat expansion and contraction using novel reporters and a doxycycline-regulated expression system for RPB1 In efforts to determine the mechanisms leading to CTD repeat variability, we identified the presence of DNA secondary structures, specifically G-quadruplex-like DNA, within the CTD coding region. Furthermore, we demonstrated that mutating PIF1, a G-quadruplex-specific helicase, results in increased CTD repeat length polymorphisms. We also determined that RAD52 is necessary for CTD repeat expansion but not contraction, identifying a role for recombination in repeat expansion. Results from these DNA rearrangements may help explain the CTD copy number variation seen across eukaryotes, as well as support a model of CTD expansion and contraction to maintain CTD integrity and overall length. PMID:27026700

  12. DNA Instability Maintains the Repeat Length of the Yeast RNA Polymerase II C-terminal Domain*

    PubMed Central

    Morrill, Summer A.; Exner, Alexandra E.; Babokhov, Michael; Reinfeld, Bradley I.

    2016-01-01

    The C-terminal domain (CTD) of RNA polymerase II in eukaryotes is comprised of tandemly repeating units of a conserved seven-amino acid sequence. The number of repeats is, however, quite variable across different organisms. Furthermore, previous studies have identified evidence of rearrangements within the CTD coding region, suggesting that DNA instability may play a role in regulating or maintaining CTD repeat number. The work described here establishes a clear connection between DNA instability and CTD repeat number in Saccharomyces cerevisiae. First, analysis of 36 diverse S. cerevisiae isolates revealed evidence of numerous past rearrangements within the DNA sequence that encodes the CTD. Interestingly, the total number of CTD repeats was relatively static (24–26 repeats in all strains), suggesting a balancing act between repeat expansion and contraction. In an effort to explore the genetic plasticity within this region, we measured the rates of repeat expansion and contraction using novel reporters and a doxycycline-regulated expression system for RPB1. In efforts to determine the mechanisms leading to CTD repeat variability, we identified the presence of DNA secondary structures, specifically G-quadruplex-like DNA, within the CTD coding region. Furthermore, we demonstrated that mutating PIF1, a G-quadruplex-specific helicase, results in increased CTD repeat length polymorphisms. We also determined that RAD52 is necessary for CTD repeat expansion but not contraction, identifying a role for recombination in repeat expansion. Results from these DNA rearrangements may help explain the CTD copy number variation seen across eukaryotes, as well as support a model of CTD expansion and contraction to maintain CTD integrity and overall length. PMID:27026700

  13. 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.

  14. 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.

  15. Variable efficacy of repeated annual influenza vaccination.

    PubMed

    Smith, D J; Forrest, S; Ackley, D H; Perelson, A S

    1999-11-23

    Conclusions have differed in studies that have compared vaccine efficacy in groups receiving influenza vaccine for the first time to efficacy in groups vaccinated more than once. For example, the Hoskins study [Hoskins, T. W., Davis, J. R., Smith, A. J., Miller, C. L. & Allchin, A. (1979) Lancet i, 33-35] concluded that repeat vaccination was not protective in the long term, whereas the Keitel study [Keitel, W. A., Cate, T. R., Couch, R. B., Huggins, L. L. & Hess, K. R. (1997) Vaccine 15, 1114-1122] concluded that repeat vaccination provided continual protection. We propose an explanation, the antigenic distance hypothesis, and test it by analyzing seven influenza outbreaks that occurred during the Hoskins and Keitel studies. The hypothesis is that variation in repeat vaccine efficacy is due to differences in antigenic distances among vaccine strains and between the vaccine strains and the epidemic strain in each outbreak. To test the hypothesis, antigenic distances were calculated from historical hemagglutination inhibition assay tables, and a computer model of the immune response was used to predict the vaccine efficacy of individuals given different vaccinations. The model accurately predicted the observed vaccine efficacies in repeat vaccinees relative to the efficacy in first-time vaccinees (correlation 0.87). Thus, the antigenic distance hypothesis offers a parsimonious explanation of the differences between and within the Hoskins and Keitel studies. These results have implications for the selection of influenza vaccine strains, and also for vaccination strategies for other antigenically variable pathogens that might require repeated vaccination. PMID:10570188

  16. Quantum key distribution over probabilistic quantum repeaters

    NASA Astrophysics Data System (ADS)

    Amirloo, Jeyran; Razavi, Mohsen; Majedi, A. Hamed

    2010-09-01

    A feasible route toward implementing long-distance quantum key distribution (QKD) systems relies on probabilistic schemes for entanglement distribution and swapping as proposed in the work of Duan, Lukin, Cirac, and Zoller (DLCZ) [Nature (London)NATUAS0028-083610.1038/35106500 414, 413 (2001)]. Here, we calculate the conditional throughput and fidelity of entanglement for DLCZ quantum repeaters by accounting for the DLCZ self-purification property in the presence of multiple excitations in the ensemble memories as well as loss and other sources of inefficiency in the channel and measurement modules. We then use our results to find the generation rate of secure key bits for QKD systems that rely on DLCZ quantum repeaters. We compare the key generation rate per logical memory employed in the two cases with and without a repeater node. We find the crossover distance beyond which the repeater system outperforms the nonrepeater one. That provides us with the optimum internode distancing in quantum repeater systems. We also find the optimal excitation probability at which the QKD rate peaks. Such an optimum probability, in most regimes of interest, is insensitive to the total distance.

  17. 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

  18. The effects of age and delay on responses to repeated questions in forensic interviews with children alleging sexual abuse.

    PubMed

    Andrews, Samantha J; Lamb, Michael E

    2014-04-01

    We examined transcripts of forensic interviews with 115 children aged between 3 and 12 years, interviewed between 1 day and 18 months after allegedly experiencing a single incident of sexual abuse. Repeated questions were categorized with respect to the reasons why interviewers asked questions again, how interviewers asked repeated questions, and how children responded. On average, interviewers asked 3 repeated questions per interview. As age increased, the frequency of question repetition declined but there was no association between repetition and delay. Interviewers most often repeated questions for clarification (53.1%), but questions were also repeated frequently to challenge children's previous responses (23.7%), and for no apparent reason (20.1%). In response, children typically repeated (54.1%) or elaborated on (31.5%) their previous answers; they contradicted themselves less often (10.8%). Questions repeated using suggestive prompts were more likely to elicit contradictions. There was no association between age or delay and the reasons why questions were repeated, how they were repeated, and how children responded. These findings emphasize the importance of training forensic interviewers to repeat questions only when the children or interviewers seek clarification and to encourage children who are anxious or reluctant to disclose. All repeated questions should be open-ended and interviewers should explain to children why questions are being repeated. PMID:24341834

  19. 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.

  20. 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.

  1. Nucleic acid recognition by tandem helical repeats.

    PubMed

    Rubinson, Emily H; Eichman, Brandt F

    2012-02-01

    Protein domains constructed from tandem α-helical repeats have until recently been primarily associated with protein scaffolds or RNA recognition. Recent crystal structures of human mitochondrial termination factor MTERF1 and Bacillus cereus alkylpurine DNA glycosylase AlkD bound to DNA revealed two new superhelical tandem repeat architectures capable of wrapping around the double helix in unique ways. Unlike DNA sequence recognition motifs that rely mainly on major groove read-out, MTERF and ALK motifs locate target sequences and aberrant nucleotides within DNA by resculpting the double-helix through extensive backbone contacts. Comparisons between MTERF and ALK repeats, together with recent advances in ssRNA recognition by Pumilio/FBF (PUF) domains, provide new insights into the fundamental principles of protein-nucleic acid recognition. PMID:22154606

  2. Extreme repeated mating as a counter-adaptation to sexual conflict?

    PubMed Central

    Laird, G; Gwynne, D T; Andrade, M C B

    2004-01-01

    The Australian scaly cricket, Ornebius aperta, can copulate over 50 times with the same partner; the benefits of such extreme repeated copulation are unclear. We support the hypothesis that repeated copulation increases insemination success, as the number of sperm transferred increases with each spermatophore. This probably increases paternity for males, as on average a female mates with over 40 males. Despite intense sperm competition each ejaculate has only a few hundred sperm, orders of magnitude less than in related crickets. We show that all sperm are transferred from each spermatophore in the few seconds before a female removes and eats it. Repeated copulation increases effective copulation duration while a small ejaculate ensures that this strategy is not excessively costly. Thus repeated copulation in these crickets may have arisen as a counter-adaptation to female-imposed limits on copulation. PMID:15801587

  3. 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.

  4. 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.

  5. 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.

  6. 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. PMID:25359175

  7. 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

  8. Repeated Witnessing of Conspecifics in Pain: Effects on Emotional Contagion.

    PubMed

    Carrillo, Maria; Migliorati, Filippo; 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

  9. 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

  10. Replication stalling and heteroduplex formation within CAG/CTG trinucleotide repeats by mismatch repair.

    PubMed

    Viterbo, David; Michoud, Grégoire; Mosbach, Valentine; Dujon, Bernard; Richard, Guy-Franck

    2016-06-01

    Trinucleotide repeat expansions are responsible for at least two dozen neurological disorders. Mechanisms leading to these large expansions of repeated DNA are still poorly understood. It was proposed that transient stalling of the replication fork by the repeat tract might trigger slippage of the newly-synthesized strand over its template, leading to expansions or contractions of the triplet repeat. However, such mechanism was never formally proven. Here we show that replication fork pausing and CAG/CTG trinucleotide repeat instability are not linked, stable and unstable repeats exhibiting the same propensity to stall replication forks when integrated in a yeast natural chromosome. We found that replication fork stalling was dependent on the integrity of the mismatch-repair system, especially the Msh2p-Msh6p complex, suggesting that direct interaction of MMR proteins with secondary structures formed by trinucleotide repeats in vivo, triggers replication fork pauses. We also show by chromatin immunoprecipitation that Msh2p is enriched at trinucleotide repeat tracts, in both stable and unstable orientations, this enrichment being dependent on MSH3 and MSH6. Finally, we show that overexpressing MSH2 favors the formation of heteroduplex regions, leading to an increase in contractions and expansions of CAG/CTG repeat tracts during replication, these heteroduplexes being dependent on both MSH3 and MSH6. These heteroduplex regions were not detected when a mutant msh2-E768A gene in which the ATPase domain was mutated was overexpressed. Our results unravel two new roles for mismatch-repair proteins: stabilization of heteroduplex regions and transient blocking of replication forks passing through such repeats. Both roles may involve direct interactions between MMR proteins and secondary structures formed by trinucleotide repeat tracts, although indirect interactions may not be formally excluded. PMID:27045900

  11. 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.

  12. 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

  13. 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

  14. Structures of designed armadillo-repeat proteins show propagation of inter-repeat interface effects.

    PubMed

    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

  15. Human adaptation to repeated cold immersions.

    PubMed Central

    Golden, F S; Tipton, M J

    1988-01-01

    1. The present investigation was designed to examine human adaptation to intermittent severe cold exposure and to assess the effect of exercise on any adaptation obtained. 2. Sixteen subjects were divided into two equal groups. Each subject performed ten head-out immersions; two into thermoneutral water which was then cooled until they shivered vigorously, and eight into water at 15 degrees C for 40 min. During the majority of the 15 degrees C immersions, one group (dynamic group) exercised whilst the other (static group) rested. 3. Results showed that both groups responded to repeated cold immersions with a reduction in their initial responses to cold. The time course of these reductions varied, however, between responses. 4. Only the static group developed a reduced metabolic response to prolonged resting immersion. 5. It is concluded that repeated resting exposure to cold was the more effective way of producing an adaptation. The performance of exercise during repeated exposure to cold prevented the development of an adaptive reduction in the metabolic response to cold during a subsequent resting immersion. In addition, many of the adaptations obtained during repeated resting exposure were overridden or masked during a subsequent exercising immersion. PMID:3411500

  16. History repeats itself: genomic divergence in copepods.

    PubMed

    Renaut, Sébastien; Dion-Côté, Anne-Marie

    2016-04-01

    Press stop, erase everything from now till some arbitrary time in the past and start recording life as it evolves once again. Would you see the same tape of life playing itself over and over, or would a different story unfold every time? The late Steven Jay Gould called this experiment replaying the tape of life and argued that any replay of the tape would lead evolution down a pathway radically different from the road actually taken (Gould 1989). This thought experiment has puzzled evolutionary biologists for a long time: how repeatable are evolutionary events? And if history does indeed repeat itself, what are the factors that may help us predict the path taken? A powerful means to address these questions at a small evolutionary scale is to study closely related populations that have evolved independently, under similar environmental conditions. This is precisely what Pereira et al. () set out to do using marine copepods Tigriopus californicus, and present their results in this issue of Molecular Ecology. They show that evolution can be repeatable and even partly predictable, at least at the molecular level. As expected from theory, patterns of divergence were shaped by natural selection. At the same time, strong genetic drift due to small population sizes also constrained evolution down a similar evolutionary road, and probably contributed to repeatable patterns of genomic divergence. PMID:27012819

  17. 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…

  18. 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

  19. A Structured Group Program for Repeat Dieters.

    ERIC Educational Resources Information Center

    McNamara, Kathleen

    1989-01-01

    Describes a structured group program for women who repeatedly diet and may be at risk of developing more serious eating disorders. Discusses sessions focusing on eating behavior as well as internal factors that contribute to low body esteem and food and weight preoccupation. Evaluates effectiveness of program by self-reports of members of two…

  20. 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…

  1. 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. PMID:26733936

  2. 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…

  3. Repeat abortions in New York City, 2010.

    PubMed

    Toprani, Amita; Cadwell, Betsy L; Li, Wenhui; Sackoff, Judith; Greene, Carolyn; Begier, Elizabeth

    2015-06-01

    This study aims to describe factors associated with the number of past abortions obtained by New York City (NYC) abortion patients in 2010. We calculated rates of first and repeat abortion by age, race/ethnicity, and neighborhood-level poverty and the mean number of self-reported past abortions by age, race/ethnicity, neighborhood-level poverty, number of living children, education, payment method, marital status, and nativity. We used negative binomial regression to predict number of past abortions by patient characteristics. Of the 76,614 abortions reported for NYC residents in 2010, 57% were repeat abortions. Repeat abortions comprised >50% of total abortions among the majority of sociodemographic groups we examined. Overall, mean number of past abortions was 1.3. Mean number of past abortions was higher for women aged 30-34 years (1.77), women with ≥5 children (2.50), and black non-Hispanic women (1.52). After multivariable regression, age, race/ethnicity, and number of children were the strongest predictors of number of past abortions. This analysis demonstrates that, although socioeconomic disparities exist, all abortion patients are at high risk for repeat unintended pregnancy and abortion. PMID:25779755

  4. Building Fluency through the Repeated Reading Method

    ERIC Educational Resources Information Center

    Cohen, Joshua

    2011-01-01

    For the last two years the author has used Repeated Reading (RR) to teach reading fluency in English as a Foreign Language classrooms in colleges and universities in Japan. RR is a method where the student reads and rereads a text silently or aloud from two to four times to reach a predetermined level of speed, accuracy, and comprehension. RR…

  5. 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.

  6. 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…

  7. 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.

  8. A study on the trinucleotide repeat associated with Huntington`s disease in the Chinese

    SciTech Connect

    Bing-wen Soong; Jih-tsuu Wang

    1994-09-01

    Analysis of the polymorphic (CAG)n repeat in the hungingtin gene in the chinese confirmed the presence of an expanded repeat on all Huntington`s disease chromosomes. Measurement of the specific CAG repeat sequence in 34 HD chromosomes from 15 unrelated families and 190 control chromosomes from the Chinese population showed a range from 9 to 29 repeats in normal subjects and 40 to 58 in affected subjects. The size distributions of normal and affected alleles did not overlap. A clear correlation bewteen early onset of symptoms and very high repeat number was seen, but the spread of the age-at-onset in the major repeat range producing characteristic HD it too wide to be of diagnostic value. There was also variability in the transmitted repeat size for both sexes in the HD size range. Maternal HD alleles showed a moderate instability with a preponderance of size decrease, while paternal HD alleles had a tendency to increase in repeat size on transmission, the degree of which appeared proportional to the initial size.

  9. CGG repeat-associated translation mediates neurodegeneration in fragile X tremor ataxia syndrome.

    PubMed

    Todd, Peter K; Oh, Seok Yoon; Krans, Amy; He, Fang; Sellier, Chantal; Frazer, Michelle; Renoux, Abigail J; Chen, Kai-chun; Scaglione, K Matthew; Basrur, Venkatesha; Elenitoba-Johnson, Kojo; Vonsattel, Jean P; Louis, Elan D; Sutton, Michael A; Taylor, J Paul; Mills, Ryan E; Charlet-Berguerand, Nicholas; Paulson, Henry L

    2013-05-01

    Fragile X-associated tremor ataxia syndrome (FXTAS) results from a CGG repeat expansion in the 5' UTR of FMR1. This repeat is thought to elicit toxicity as RNA, yet disease brains contain ubiquitin-positive neuronal inclusions, a pathologic hallmark of protein-mediated neurodegeneration. We explain this paradox by demonstrating that CGG repeats trigger repeat-associated non-AUG-initiated (RAN) translation of a cryptic polyglycine-containing protein, FMRpolyG. FMRpolyG accumulates in ubiquitin-positive inclusions in Drosophila, cell culture, mouse disease models, and FXTAS patient brains. CGG RAN translation occurs in at least two of three possible reading frames at repeat sizes ranging from normal (25) to pathogenic (90), but inclusion formation only occurs with expanded repeats. In Drosophila, CGG repeat toxicity is suppressed by eliminating RAN translation and enhanced by increased polyglycine protein production. These studies expand the growing list of nucleotide repeat disorders in which RAN translation occurs and provide evidence that RAN translation contributes to neurodegeneration. PMID:23602499

  10. Accuracy of velocities from repeated GPS measurements

    NASA Astrophysics Data System (ADS)

    Akarsu, V.; Sanli, D. U.; Arslan, E.

    2015-04-01

    Today repeated GPS measurements are still in use, because we cannot always employ GPS permanent stations due to a variety of limitations. One area of study that uses velocities/deformation rates from repeated GPS measurements is the monitoring of crustal motion. This paper discusses the quality of the velocities derived using repeated GPS measurements for the aim of monitoring crustal motion. From a global network of International GNSS Service (IGS) stations, we processed GPS measurements repeated monthly and annually spanning nearly 15 years and estimated GPS velocities for GPS baseline components latitude, longitude and ellipsoidal height. We used web-based GIPSY for the processing. Assuming true deformation rates can only be determined from the solutions of 24 h observation sessions, we evaluated the accuracy of the deformation rates from 8 and 12 h sessions. We used statistical hypothesis testing to assess the velocities derived from short observation sessions. In addition, as an alternative control method we checked the accuracy of GPS solutions from short observation sessions against those of 24 h sessions referring to statistical criteria that measure the accuracy of regression models. Results indicate that the velocities of the vertical component are completely affected when repeated GPS measurements are used. The results also reveal that only about 30% of the 8 h solutions and about 40% of 12 h solutions for the horizontal coordinates are acceptable for velocity estimation. The situation is much worse for the vertical component in which none of the solutions from campaign measurements are acceptable for obtaining reliable deformation rates.

  11. Biokinetics in repeated-dosing in vitro drug toxicity studies.

    PubMed

    Kramer, Nynke I; Di Consiglio, Emma; Blaauboer, Bas J; Testai, Emanuela

    2015-12-25

    The aim of the EU FP7 Predict-IV project was to improve the predictivity of in vitro assays for unwanted effects of drugs after repeated dosing. The project assessed the added benefit of integrating long-lived in vitro organotypic cell systems with 'omics' technologies and in silico modelling, including systems biology and pharmacokinetic assessments. RPTEC/TERT1 kidney cells, primary rat and human hepatocytes, HepaRG liver cells and 2D and 3D primary brain cultures were dosed daily or every other day for 14 days to a selection of drugs varying in their mechanism of pharmacological action. Since concentration-effect relationships not only depend on the activity of the drug or the sensitivity of the target, but also on the distribution of compounds in the in vitro system, the concentration of a selection of drugs in cells, microtitre plate plastic and medium was measured over time. Results, reviewed in this paper, indicate that lipophilic drugs bind significantly to plastic labware. A few drugs, including less lipophilic drugs, bind to cell-attachment matrices. Chemicals that reach high concentrations in cells, including cyclosporin A and amiodarone, significantly accumulate over time after repeated dosing, partly explaining their increased toxicity after repeated dosing, compared to a single dose. PMID:26362508

  12. Nanoparticle role on the repeatability of stimuli-responsive nanocomposites

    PubMed Central

    Ahn, Sungsook; Lee, Sang Joon

    2014-01-01

    Repeatability of the responsiveness with time is one important concern for effective durable functions of stimuli-responsive materials. Although the increase in the yield and tensile strength of the hybrid composite materials by nanoparticle (NP) incorporation has been reported, exact NP effect on stimuli-responsiveness is rarely reported. In this study, a set of nanoscale actuating system is demonstrated by a thermo-sensitive process operated by polyethylene glycol (PEG) linked by gold nanoparticle (AuNP). This designed nanocomposite exclusively provides an artificial on/off gate function for selective passages of permeate molecules. The results demonstrate high repetition efficiency with sharp responding in a timely manner. In terms of the morphology changes induced by repeated swelling-deswelling mechanics, the nanocomposite exhibits phase separation between AuNP clusters and PEG domains. This leads to a delay in responsiveness in a cumulative way with time. Acting as stable junction points in the nanocomposite network structures, the incorporated AuNPs contribute to maintain repeatability in responsiveness. This study contributes to new-concept smart material design and fundamental understanding on the hybrid nanomaterials for various applications in terms of a dynamic mechanical behavior. PMID:25315841

  13. Inhibition of breast cancer cell proliferation in repeated and non-repeated treatment with zoledronic acid

    PubMed Central

    2012-01-01

    Background Zoledronic acid is used to treat bone metastases and has been shown to reduce skeletal-related events and exert antitumor activity. The present in vitro study investigates the mechanism of action of Zoledronic Acid on breast cancer cell lines with different hormonal and HER2 patterns. Furthermore, we investigated the efficacy of repeated versus non-repeated treatments. Methods The study was performed on 4 breast cancer cell lines (BRC-230, SkBr3, MCF-7 and MDA-MB-231). Non-repeated treatment (single exposure of 168 hrs’ duration) with zoledronic acid was compared with repeated treatment (separate exposures, each of 48 hrs’ duration, for a total of 168 hrs) at different dosages. A dose–response profile was generated using sulforhodamine B assay. Apoptosis was evaluated by TUNEL assay and biomolecular characteristics were analyzed by western blot. Results Zoledronic acid produced a dose-dependent inhibition of proliferation in all cell lines. Anti-proliferative activity was enhanced with the repeated treatment, proving to be statistically significant in the triple-negative lines. In these lines repeated treatment showed a cytocidal effect, with apoptotic cell death caused by caspase 3, 8 and 9 activation and decreased RAS and pMAPK expression. Apoptosis was not observed in estrogen receptor-positive line: p21 overexpression suggested a slowing down of cell cycle. A decrease in RAS and pMAPK expression was seen in HER2-overexpressing line after treatment. Conclusions The study suggests that zoledronic acid has an antitumor activity in breast cancer cell lines. Its mechanism of action involves the decrease of RAS and RHO, as in osteoclasts. Repeated treatment enhances antitumor activity compared to non-repeated treatment. Repeated treatment has a killing effect on triple-negative lines due to apoptosis activation. Further research is warranted especially in the treatment of triple-negative breast cancer. PMID:23173568

  14. Repeatability in the assessment of multi-segment foot kinematics.

    PubMed

    Deschamps, Kevin; Staes, Filip; Bruyninckx, Herman; Busschots, Ellen; Jaspers, Ellen; Atre, Ameya; Desloovere, Kaat

    2012-02-01

    A recently published systematic review on 3D multi-segment foot models has illustrated the lack of repeatability studies providing evidence for appropriate clinical decision making. The aim of the current study was to assess the repeatability of the recently published model developed by Leardini et al. [10]. Foot kinematics of six healthy adults were analyzed through a repeated-measures design including two therapists with different levels of experience and four test sessions. For the majority of the parameters moderate or good repeatability was observed for the within-day and between-day sessions. A trend towards consistently higher within- and between-day variability was observed for the junior compared to the senior clinician. The mean inter-session variability of the relative 3D rotations ranged between 0.9-4.2° and 1.6-5.0° for respectively the senior and junior clinician whereas for the absolute angles this variability increased to respectively 2.0-6.2° and 2.6-7.8°. Mean inter-therapist standard deviations ranged between 2.2° and 6.5° for the relative 3D rotations and between 2.8° and 7.6° for the absolute 3D rotations. The ratio of inter-therapist to inter-trial errors ranged between 1.8 and 5.5 for the relative 3D rotations and between 2.4 and 9.7 for the absolute 3D rotations. Absolute angle representation of the planar angles was found to be more difficult. Observations from the current study indicate that an adequate normative database can be installed in gait laboratories, however, it should be stressed that experience of therapists is important and gait laboratories should therefore be encouraged to put effort in training their clinicians. PMID:22100210

  15. Striatal patch compartment lesions reduce stereotypy following repeated cocaine administration.

    PubMed

    Murray, Ryan C; Logan, Mary C; Horner, Kristen A

    2015-08-27

    Stereotypy can be characterized as inflexible, repetitive behaviors that occur following repeated exposure to psychostimulants, such as cocaine (COC). Stereotypy may be related to preferential activation of the patch (striosome) compartment of striatum, as enhanced relative activation of the patch compartment has been shown to positively correlate with the emergence of stereotypy following repeated psychostimulant treatment. However, the specific contribution of the patch compartment to COC-induced stereotypy following repeated exposure is unknown. To elucidate the involvement of the patch compartment to the development of stereotypy following repeated COC exposure, we determined if destruction of this sub-region altered COC-induced behaviors. The neurons of the patch compartment were ablated by bilateral infusion of the neurotoxin dermorphin-saporin (DERM-SAP; 17 ng/μl) into the striatum. Animals were allowed to recover for eight days following the infusion, and then were given daily injections of COC (25mg/kg) or saline for one week, followed by a weeklong drug-free period. Animals were then given a challenge dose of saline or COC, observed for 2h in activity chambers and sacrificed. The number of mu-labeled patches in the striatum were reduced by DERM-SAP pretreatment. In COC-treated animals DERM-SAP pretreatment significantly reduced the immobilization and intensity of stereotypy but increased locomotor activity. DERM-SAP pretreatment attenuated COC-induced c-Fos expression in the patch compartment, while enhancing COC-induced c-Fos expression in the matrix compartment. These data indicate that the patch compartment contributes to repetitive behavior and suggests that alterations in activity in the patch vs matrix compartments may underlie to this phenomenon. PMID:26100338

  16. Preservice science teachers' experiences with repeated, guided inquiry

    NASA Astrophysics Data System (ADS)

    Slack, Amy B.

    The purpose of this study was to examine preservice science teachers' experiences with repeated scientific inquiry (SI) activities. The National Science Education Standards (National Research Council, 1996) stress students should understand and possess the abilities to do SI. For students to meet these standards, science teachers must understand and be able to perform SI; however, previous research demonstrated that many teachers have naive understandings in this area. Teacher preparation programs provide an opportunity to facilitate the development of inquiry understandings and abilities. In this study, preservice science teachers had experiences with two inquiry activities that were repeated three times each. The research questions for this study were (a) How do preservice science teachers' describe their experiences with repeated, guided inquiry activities? (b) What are preservice science teachers' understandings and abilities of SI? This study was conducted at a large, urban university in the southeastern United States. The 5 participants had bachelor's degrees in science and were enrolled in a graduate science education methods course. The researcher was one of the course instructors but did not lead the activities. Case study methodology was used. Data was collected from a demographic survey, an open-ended questionnaire with follow-up interviews, the researcher's observations, participants' lab notes, personal interviews, and participants' journals. Data were coded and analyzed through chronological data matrices to identify patterns in participants' experiences. The five domains identified in this study were understandings of SI, abilities to conduct SI, personal feelings about the experience, science content knowledge, and classroom implications. Through analysis of themes identified within each domain, the four conclusions made about these preservice teachers' experiences with SI were that the experience increased their abilities to conduct inquiry

  17. DNA Replication Dynamics of the GGGGCC Repeat of the C9orf72 Gene*

    PubMed Central

    Thys, Ryan Griffin; Wang, Yuh-Hwa

    2015-01-01

    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. PMID:26463209

  18. 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. PMID:26463209

  19. CAG Repeat Number in the Androgen Receptor Gene and Prostate Cancer

    PubMed Central

    Madjunkova, S; Eftimov, A; Georgiev, V; Petrovski, D; Dimovski, AJ; Plaseska-Karanfilska, D

    2012-01-01

    Prostate cancer (PC) is the second leading cause of cancer deaths in men. The effects of androgens on prostatic tissue are mediated by the androgen receptor (AR) gene. The 5′ end of exon 1 of the AR gene includes a polymorphic CAG triplet repeat that numbers between 10 to 36 in the normal population. The length of the CAG repeats is inversely related to the transactivation function of the AR gene. There is controversy over association between short CAG repeat numbers in the AR gene and PC. This retrospective case-control study evaluates the possible effect of short CAG repeats on the AR gene in prostate cancer risk in Macedonian males. A total of 392 male subjects, 134 PC patients, 106 patients with benign prostatic hyperplasia (BPH) and 152 males from the general Macedonian population were enrolled in this study. The CAG repeat length was determined by fluorescent polymerase chain reaction (PCR) amplification of exon1 of the AR gene followed by capillary electrophoresis (CE) on a genetic analyzer. The mean repeat length in PC patients was 21.5 ± 2.65, in controls 22.28 ± 2.86 (p = 0.009) and in BPH patients 22.1 ± 2.52 (p = 0.038). Short CAG repeats (<19) were found in 21.64% of PC patients vs. 9.43% in BPH patients (p = 0.0154). We also found an association of low Gleason score (<7) with short CAG repeat (<19) in PC patients (p = 0.0306), and no association between the age at diagnosis of PC and BPH and CAG repeat length. These results suggest that reduced CAG repeat length may be associated with increased prostate cancer risk in Macedonian men. PMID:24052720

  20. Learning with repeated-game strategies.

    PubMed

    Ioannou, Christos A; Romero, Julian

    2014-01-01

    We use the self-tuning Experience Weighted Attraction model with repeated-game strategies as a computer testbed to examine the relative frequency, speed of convergence and progression of a set of repeated-game strategies in four symmetric 2 × 2 games: Prisoner's Dilemma, Battle of the Sexes, Stag-Hunt, and Chicken. In the Prisoner's Dilemma game, we find that the strategy with the most occurrences is the "Grim-Trigger." In the Battle of the Sexes game, a cooperative pair that alternates between the two pure-strategy Nash equilibria emerges as the one with the most occurrences. In the Stag-Hunt and Chicken games, the "Win-Stay, Lose-Shift" and "Grim-Trigger" strategies are the ones with the most occurrences. Overall, the pairs that converged quickly ended up at the cooperative outcomes, whereas the ones that were extremely slow to reach convergence ended up at non-cooperative outcomes. PMID:25126053

  1. Quantum repeater with continuous variable encoding

    NASA Astrophysics Data System (ADS)

    Li, Linshu; Albert, Victor V.; Michael, Marios; Muralidharan, Sreraman; Zou, Changling; Jiang, Liang

    2016-05-01

    Quantum communication enables faithful quantum state transfer between different parties and protocols for cryptographic purposes. However, quantum communication over long distances (>1000km) remains challenging due to optical channel attenuation. This calls for investigation on developing novel encoding schemes that correct photon loss errors efficiently. In this talk, we introduce the generalization of multi-component Schrödinger cat states and propose to encode quantum information in these cat states for ultrafast quantum repeaters. We detail the quantum error correction procedures at each repeater station and characterize the performance of this novel encoding scheme given practical imperfections, such as coupling loss. A comparison with other quantum error correcting codes for bosonic modes will be discussed.

  2. 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. PMID:24575886

  3. [VESTIBULAR FUNCTION AFTER REPEATED SPACE FLIGHTS].

    PubMed

    Naumov, I A; Kornilova, L N; Glukhikh, D O; Pavlova, A S; Khabarova, E V; Ekimovsky, G A; Vasin, A V

    2015-01-01

    Results of the vestibular function testing of 32 cosmonauts on return from repeated 125- to 215-day space flights (SF) on the International space station are presented. The cosmonauts were tested twice before flight (baseline data collection) and on days 1-2, 4-5 and 8-9 after landing. Electro- and video-oculography were used to register simultaneously eye and head movements. It was found that deadaptation following a repeated stay in long-duration SF takes statistically much shorter time. Most often, atypical vestibular disorders and changed patterns of the otolith-semicircular canal interaction are observed in cosmonauts who have made their maiden flights to microgravity. PMID:26934788

  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. 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.

  6. 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

  7. 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.

  8. A New Property of Repeating Decimals

    ERIC Educational Resources Information Center

    Arledge, Jane; Tekansik, Sarah

    2008-01-01

    As extended by Ginsberg, Midi's theorem says that if the repeated section of a decimal expansion of a prime is split into appropriate blocks and these are added, the result is a string of nines. We show that if the expansion of 1/p[superscript n+1] is treated the same way, instead of being a string of nines, the sum is related to the period of…

  9. 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. PMID:26208520

  10. Androgen receptor polymorphism (CAG repeats) and androgenicity.

    PubMed

    Canale, D; Caglieresi, C; Moschini, C; Liberati, C D; Macchia, E; Pinchera, A; Martino, E

    2005-09-01

    Objective Polymorphism of the androgen receptor (AR) has been related to various pathophysiological conditions, such as osteoporosis and infertility. The objectives of this study were to evaluate the frequency of distribution in a normal Italian population and to assess CAG repeats (CAGr) in other conditions, such as hypoandrogenism, potentially influenced by AR polymorphism. Patients and measurements CAGr polymorphism was determined in a group of 91 healthy normoandrogenized subjects, 29 hypoandrogenized patients (hypoplasia of prostate and seminal vesicles, reduced beard or body hair, etc.) and 29 infertile patients by direct sequencing. Results The mean (+/- SD) number of CAG repeats [(CAGr)n] was 21.5 (+/- 1.7) in the control group, 21.4 (+/- 2.0) in the infertile patients and 24.0 (+/- 2.9) in the hypoandrogenic males. The difference was statistically significant between this last group and the other two (P < 0.0001), while there was no difference between normal controls and infertile patients. The frequency distribution showed a shift towards higher CAG length in hypoandrogenized patients compared to controls and infertile patients. If we used a cut-off point of 24.9 (2 SD above the mean), the percentage of patients with 25 or more CAGr repeats was 38% among hypoandrogenized patients, 7% among infertile patients and 5% among the control group. In hypoandrogenized subjects (CAGr)n correlated slightly with testis and prostate volume. The number of CAG repeats was not associated with any of the hormonal parameters, including testosterone, evaluated in the three groups. Conclusions Our normal population, representing subjects from Central Italy, is superimposable on other European populations with regard to (CAGr)n distribution. Hypoandrogenic males have a shift in the frequency distribution towards longer (CAGr)n. Infertile patients are not statistically different from the control group. These findings suggest that, given the same amount of circulating

  11. 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.

  12. 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.

  13. Multiplexing schemes for quantum repeater networks

    NASA Astrophysics Data System (ADS)

    Aparicio, Luciano; Van Meter, Rodney

    2011-08-01

    When built, quantum repeaters will allow the distribution of entangled quantum states across large distances, playing a vital part in many proposed quantum technologies. Enabling multiple users to connect through the same network will be key to their real-world deployment. Previous work on repeater technologies has focussed only on simple entanglment production, without considering the issues of resource scarcity and competition that necessarily arise in a network setting. In this paper we simulated a thirteen-node network with up to five flows sharing different parts of the network, measuring the total throughput and fairness for each case. Our results suggest that the Internet-like approach of statistical multiplexing use of a congested link gives the highest aggregate throughput. Time division multiplexing and buffer space multiplexing were slightly less effective, but all three schemes allow the sum of multiple flows to substantially exceed that of any one flow, improving over circuit switching by taking advantage of resources that are forced to remain idle in circuit switching. All three schemes proved to have excellent fairness. The high performance, fairness and simplicity of implementation support a recommendation of statistical multiplexing for shared quantum repeater networks.

  14. 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

  15. 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.

  16. Characteristics of intergenerational contractions of the CTG repeat in myotonic dystropy

    SciTech Connect

    Ashizawa, T.; Anvret, M.; Grandell, U.; Baiget, M.; Cobo, A.M.; Barcelo, J.M.; Korneluk, R.G.; Dallapiccola, B.; Novelli, G.; Fenwick, R.G. Jr.

    1994-03-01

    In myotonic dystropy (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. The authors have examined 1,489 DM parent-offspring pairs, of which 95 (6.4%) showed such contractions in peripheral blood leukocytes (PBL). In 56 of th 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 asymptomatic offspring. The contraction occurred in 76 (10%) of 753 paternal transmission 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 (r[sup 2] = .50, P [much lt].001), and the slope of linear regression was steeper in paternal ([minus].62) than in maternal ([minus].30) transmissions (P [much lt].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). The authors 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. 43 refs., 1 fig., 4 tabs.

  17. 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

  18. Sensitization and Tolerance Following Repeated Exposure to Caffeine and Alcohol in Mice

    PubMed Central

    May, Christina E.; Haun, Harold L.; Griffin, William C.

    2015-01-01

    Introduction Energy drinks are popular mixers with alcohol. While energy drinks contain many ingredients, caffeine is an important pharmacologically active component and is generally present in larger amounts than in other caffeinated beverages. In these studies, we investigated the hypothesis that caffeine would influence the effects of alcohol (ethanol) on conditioned taste aversion, ataxia and locomotor activity after repeated exposure. Methods Four groups of mice were exposed by oral gavage twice daily to vehicle, ethanol (4 g/kg), caffeine (15 mg/kg), or the ethanol/caffeine combination. Conditioned taste aversion to saccharin and ataxia in the parallel rod task were evaluated after 8 or 16 gavages, respectively, using ethanol (1–3 g/kg) or ethanol/caffeine (3mg/kg + 2 g/kg) challenges. In addition, locomotor activity was evaluated initially and after repeated exposure to oral gavage of these drugs and doses. Results Repeated oral gavage of ethanol produced significant locomotor sensitization, with those mice increasing total distance traveled by 2-fold. The locomotor response to caffeine, while significantly greater than vehicle gavage, did not change with repeated exposure. On the other hand, repeated gavage of caffeine/ethanol combination produced a substantial increase in total distance traveled after repeated exposure (~4-fold increase). After repeated ethanol exposure, there was significant tolerance to ethanol in the conditioned taste aversion and parallel rod tests. However, neither a history of caffeine exposure nor including caffeine influenced ethanol-induced conditioned taste aversion. Interestingly, a history of caffeine exposure increased the ataxic response to the caffeine/ethanol combination and appeared to reduce the ataxic response to high doses of ethanol. Conclusion The data support the general hypothesis that repeated exposure to caffeine influences the response to ethanol. Together with previously published work, these data indicate

  19. Repeated buckling of composite shear panels

    NASA Technical Reports Server (NTRS)

    Singer, Josef; Weller, Tanchum

    1990-01-01

    Failures in service of aerospace structures and research at the Technion Aircraft Structures Laboratory have revealed that repeatedly buckled stiffened shear panels might be susceptible to premature fatigue failures. Extensive experimental and analytical studies have been performed at Technion on repeated buckling, far in excess of initial buckling, for both metal and composite shear panels with focus on the influence of the surrounding structure. The core of the experimental investigation consisted of repeated buckling and postbuckling tests on Wagner beams in a three-point loading system under realistic test conditions. The effects of varying sizes of stiffeners, of the magnitude of initial buckling loads, of the panel aspect ratio and of the cyclic shearing force, V sub cyc, were studied. The cyclic to critical shear buckling ratios, (V sub cyc/V sub cr) were on the high side, as needed for efficient panel design, yet all within possible flight envelopes. The experiments were supplemented by analytical and numerical analyses. For the metal shear panels the test and numerical results were synthesized into prediction formulas, which relate the life of the metal shear panels to two cyclic load parameters. The composite shear panels studied were hybrid beams with graphite/epoxy webs bonded to aluminum alloy frames. The test results demonstrated that composite panels were less fatigue sensitive than comparable metal ones, and that repeated buckling, even when causing extensive damage, did not reduce the residual strength by more than 20 percent. All the composite panels sustained the specified fatigue life of 250,000 cycles. The effect of local unstiffened holes on the durability of repeatedly buckled shear panels was studied for one series of the metal panels. Tests on 2024 T3 aluminum panels with relatively small unstiffened holes in the center of the panels demonstrated premature fatigue failure, compared to panels without holes. Preliminary tests on two graphite

  20. The role of variable DNA tandem repeats in bacterial adaptation.

    PubMed

    Zhou, Kai; Aertsen, Abram; Michiels, Chris W

    2014-01-01

    DNA tandem repeats (TRs), also designated as satellite DNA, are inter- or intragenic nucleotide sequences that are repeated two or more times in a head-to-tail manner. Because TR tracts are prone to strand-slippage replication and recombination events that cause the TR copy number to increase or decrease, loci containing TRs are hypermutable. An increasing number of examples illustrate that bacteria can exploit this instability of TRs to reversibly shut down or modulate the function of specific genes, allowing them to adapt to changing environments on short evolutionary time scales without an increased overall mutation rate. In this review, we discuss the prevalence and distribution of inter- and intragenic TRs in bacteria and the mechanisms of their instability. In addition, we review evidence demonstrating a role of TR variations in bacterial adaptation strategies, ranging from immune evasion and tissue tropism to the modulation of environmental stress tolerance. Nevertheless, while bioinformatic analysis reveals that most bacterial genomes contain a few up to several dozens of intra- and intergenic TRs, only a small fraction of these have been functionally studied to date. PMID:23927439

  1. 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

  2. The guanine-rich fragile X chromosome repeats are reluctant to form tetraplexes

    PubMed Central

    Fojtík, Petr; Kejnovská, Iva; Vorlíčková, Michaela

    2004-01-01

    Using circular dichroism spectroscopy, UV absorption spectroscopy and polyacrylamide gel electrophoresis, we studied conformational properties of guanine-rich DNA strands of the fragile X chromosome repeats d(GGC)n, d(GCG)n and d(CGG)n, with n = 2, 4, 8 and 16. These strands are generally considered in the literature to form guanine tetraplexes responsible for the repeat expansion. However, we show in this paper that the repeats are reluctant to form tetraplexes. At physiological concentrations of either Na+ or K+ ions, the hexamers and dodecamers associate to form homoduplexes and the longer repeats generate homoduplexes and hairpins. The tetraplexes are rarely observed being relatively most stable with d(GGC)n and least stable with d(GCG)n. The tetraplexes are exclusively formed in the presence of K+ ions, at salt concentrations higher than physiological, more easily at higher than physiological temperatures, and they arise with extremely long kinetics (even days). Moreover, the capability to form tetraplexes sharply diminishes with the oligonucleotide length. These facts make the concept of the tetraplex appearance in this motif in vivo very improbable. Rather, a hairpin of the fragile X repeats, whose stability increases with the repeat length, is the probable structure responsible for the repeat expansion in genomes. PMID:14718550

  3. Variable number of tandem repeats in clinical strains of Haemophilus influenzae.

    PubMed Central

    van Belkum, A; Scherer, S; van Leeuwen, W; Willemse, D; van Alphen, L; Verbrugh, H

    1997-01-01

    An algorithm capable of identifying short repeat motifs was developed and used to screen the whole genome sequence available for Haemophilus influenzae, since some of these repeats have been shown to affect bacterial virulence. Various di- to hexanucleotide repeats were identified, confirming and extending previous findings on the existence of variable-number-of-tandem-repeat loci (VNTRs). Repeats with units of 7 or 8 nucleotides were not encountered. For all of the 3- to 6-nucleotide repeats in the H. influenzae chromosome, PCR tests capable of detecting allelic polymorphisms were designed. Fourteen of 18 of the potential VNTRs were indeed highly polymorphic when different strains were screened. Two of the potential VNTRs appeared to be short and homogeneous in length; another one may be specific for the H. influenzae Rd strain only. One of the primer sets generated fingerprint-type DNA banding patterns. The various repeat types differed with respect to intrinsic stability as well. It was noted for separate colonies derived from a single clinical specimen or strains passaged for several weeks on chocolate agar plates that the lengths of the VNTRs did not change. When several strains from different patients infected during an outbreak of lung disease were analyzed, increased but limited variation was encountered in all VNTR sites analyzed. One of the 5-nucleotide VNTRs proved to be hypervariable. This variability may reflect the molecular basis of a mechanism used by H. influenzae bacteria to successfully colonize and infect different human individuals. PMID:9393791

  4. Assessments of recent tundra change based on repeated vegetation surveys

    NASA Astrophysics Data System (ADS)

    Elmendorf, S.; Henry, G.; Thetundra Vegetation Change Group

    2010-12-01

    Results from experimental warming studies suggest tundra vegetation will respond rapidly and dramatically to climate warming, and indeed, NDVI data from remote sensing and repeat aerial photography suggest such changes may already be occurring. NDVI changes, however, may reflect responses to a variety of processes. Repeat measurements of permanently marked plots offer an invaluable opportunity to monitor detailed changes in vegetation composition and abundance. Here, we report results from a synthesis of repeat measurements of 195 permanent plots in Arctic and alpine tundra plant communities in North America (90 plots), Europe (82 plots), Asia (10 plots), Australia (12 plots), and Antarctica (1 plot) that were revisited at least twice between 1980 and 2010, with an average timespan of 13 years between first and last sampling periods. Annual air-temperature warming over the sampling period varied considerably among sites, ranging from slight cooling to increases of nearly 2°C per decade. In our preliminary analyses, we found significant tundra-wide increases in vegetation height as well as abundance of evergreen shrubs and graminoids, but declines in mosses. We anticipated that changes in vegetation height, abundance of deciduous shrubs, and percent of vegetated ground would be highest in areas where climate warming is occurring most rapidly, but found no support for these predictions in our observational dataset. It is possible that local vegetation dynamics in these areas are affected more by other longer-term non-equilibrium processes such as recovery from glaciation, or an alternative suite of local drivers, such as snow cover, precipitation, disturbance or herbivory.

  5. Topoisomerase 1 and Single-Strand Break Repair Modulate Transcription-Induced CAG Repeat Contraction in Human Cells ▿ †

    PubMed Central

    Hubert, Leroy; Lin, Yunfu; Dion, Vincent; Wilson, John H.

    2011-01-01

    Expanded trinucleotide repeats are responsible for a number of neurodegenerative diseases, such as Huntington disease and myotonic dystrophy type 1. The mechanisms that underlie repeat instability in the germ line and in the somatic tissues of human patients are undefined. Using a selection assay based on contraction of CAG repeat tracts in human cells, we screened the Prestwick chemical library in a moderately high-throughput assay and identified 18 novel inducers of repeat contraction. A subset of these compounds targeted pathways involved in the management of DNA supercoiling associated with transcription. Further analyses using both small molecule inhibitors and small interfering RNA (siRNA)-mediated knockdowns demonstrated the involvement of topoisomerase 1 (TOP1), tyrosyl-DNA phosphodiesterase 1 (TDP1), and single-strand break repair (SSBR) in modulating transcription-dependent CAG repeat contractions. The TOP1-TDP1-SSBR pathway normally functions to suppress repeat instability, since interfering with it stimulated repeat contractions. We further showed that the increase in repeat contractions when the TOP1-TDP1-SSBR pathway is compromised arises via transcription-coupled nucleotide excision repair, a previously identified contributor to transcription-induced repeat instability. These studies broaden the scope of pathways involved in transcription-induced CAG repeat instability and begin to define their interrelationships. PMID:21628532

  6. 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. PMID:25774031

  7. Simple sequence repeats in Haemophilus influenzae.

    PubMed

    Power, Peter M; Sweetman, W A; Gallacher, N J; Woodhall, M R; Kumar, G A; Moxon, E R; Hood, D W

    2009-03-01

    Simple sequence repeat (SSRs) of DNA are subject to high rates of mutation and are important mediators of adaptation in Haemophilus influenzae. Previous studies of the Rd KW20 genome identified the primacy of tetranucleotide SSRs in mediating phase variation (the rapid reversible switching of gene expression) of surface exposed structures such as lipopolysaccharide. The recent sequencing of the genomes of multiple strains of H. influenzae allowed the comparison of the SSRs (repeat units of one to nine nucleotides in length) in detail across four complete H. influenzae genomes and then comparison with a further 12 genomes when they became available. The SSR loci were broadly classified into three groups: (1) those that did not vary; (2) those for which some variation between strains was observed but this could not be linked to variation of gene expression; and (3) those that both varied and were located in regions consistent with mediating phase variable gene expression. Comparative analysis of 988 SSR associated loci confirmed that tetranucleotide repeats were the major mediators of phase variation and extended the repertoire of known tetranucleotide SSR loci by identifying ten previously uncharacterised tetranucleotide SSR loci with the potential to mediate phase variation which were unequally distributed across the H. influenzae pan-genome. Further, analysis of non-tetranucleotide SSR in the 16 strains revealed a number of mononucleotide, dinucleotide, pentanucleotide, heptanucleotide, and octanucleotide SSRs which were consistent with these tracts mediating phase variation. This study substantiates previous findings as to the important role that tetranucleotide SSRs play in H. influenzae biology. Two Brazilian isolates showed the most variation in their complement of SSRs suggesting the possibility of geographic and phenotypic influences on SSR distribution. PMID:19095084

  8. Capping motifs stabilize the leucine-rich repeat protein PP32 and rigidify adjacent repeats.

    PubMed

    Dao, Thuy P; Majumdar, Ananya; Barrick, Doug

    2014-06-01

    Capping motifs are found to flank most β-strand-containing repeat proteins. To better understand the roles of these capping motifs in organizing structure and stability, we carried out folding and solution NMR studies on the leucine-rich repeat (LRR) domain of PP32, which is composed of five tandem LRR, capped by α-helical and β-hairpin motifs on the N- and C-termini. We were able to purify PP32 constructs lacking either cap and containing destabilizing substitutions. Removing the C-cap results in complete unfolding of PP32. Removing the N-cap has a much less severe effect, decreasing stability but retaining much of its secondary structure. In contrast, the dynamics and tertiary structure of the first two repeats are significantly perturbed, based on (1)H-(15)N relaxation studies, chemical shift perturbations, and residual dipolar couplings. However, more distal repeats (3 to C-cap) retain their native tertiary structure. In this regard, the N-cap drives the folding of adjacent repeats from what appears to be a molten-globule-like state. This interpretation is supported by extensive analysis using core packing substitutions in the full-length and N-cap-truncated PP32. This work highlights the importance of caps to the stability and structural integrity of β-strand-containing LRR proteins, and emphasizes the different contributions of the N- and C-terminal caps. PMID:24659532

  9. Cataractogenesis after Repeat Laser in situ Keratomileusis

    PubMed Central

    Mansour, Ahmad M.; Ghabra, Marwan

    2012-01-01

    There has been the unsubstantiated clinical impression that laser refractive surgery accelerates cataract development along with solid experimental data about the cataractogenic effects of excimer laser treatment. We present the first documented case of significant cataract formation in a young myope after repeat excimer laser ablation necessitating phacoemulsification with a posterior chamber implant. Proposed explanations include focusing of the ablation wave on the posterior capsule (acoustic wave lens epithelial damage), photooxidative stress of the lens (ultraviolet and inflammatory oxidative stress), and corticosteroid-induced cataract (lens toxicity). PMID:22949915

  10. Mars orbits with daily repeating ground traces

    NASA Technical Reports Server (NTRS)

    Noreen, Gary K.; Kerridge, Stuart; Diehl, Roger; neelon, Joseph; Ely, Todd; Turner, Andrew

    2003-01-01

    This paper derives orbits at Mars with ground traces that repeat at the same times every solar day (sol). A relay orbiter in such an orbit would pass over insitu probes at the same times every sol, ensuring consistent coverage and simplifying mission design and operations. 42 orbits in five classes are characteried: 14 cicular equatorial prograde orbits; 14 circular equatorial retrograde orbits; 11 circular sun synchrounous orbits; 2 eccentroc equatorial orbits; 1 eccentric critcally inclined orbit. the paper reports on the performance of a relay orbiter in some of the orbits.

  11. Innovative collaboration to prevent repeated adolescent pregnancies.

    PubMed

    Saunders, R B; Brown, H N

    1997-01-01

    Nurse educators from a university setting and staff from the county health department collaborated to establish an innovative program to prevent repeated pregnancy in adolescents. Called Dollar-A-Day and patterned after the original in Denver, CO, the program was operated jointly for 5 years and today continues to operate under the auspices of the health department. Success of the venture is attributed to use of skills in assessment, building, managing, and evaluating, as described by Loxley (1997). These elements were used to construct a context for collaboration. PMID:9397869

  12. Multifunctional protein: cardiac ankyrin repeat protein*

    PubMed Central

    Zhang, Na; Xie, Xiao-jie; Wang, Jian-an

    2016-01-01

    Cardiac ankyrin repeat protein (CARP) not only serves as an important component of muscle sarcomere in the cytoplasm, but also acts as a transcription co-factor in the nucleus. Previous studies have demonstrated that CARP is up-regulated in some cardiovascular disorders and muscle diseases; however, its role in these diseases remains controversial now. In this review, we will discuss the continued progress in the research related to CARP, including its discovery, structure, and the role it plays in cardiac development and heart diseases. PMID:27143260

  13. 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.

  14. An investigation of electromagnetic launcher repeatability

    NASA Astrophysics Data System (ADS)

    Heyse, Mark W.; Cornette, James B.; Brown, Jere L.

    1992-07-01

    Electromagnetic launcher (EML) performance repeatability has been identified as a potential development issue for several years. Investigation of this issue has been difficult because an EML that is powered on a relatively continuous basis to provide long duration operation has not been available. A battery charged capacitor power system has enabled long duration, 6 to 7 seconds, EML experiments. This paper provides a summary of an experiment to investigate EML launch to launch performance consistency. A series of 8 ten-shot bursts, each separated by 15 to 30 minutes, performed in a single day using a single set of bore materials is the subject of this paper.

  15. An investigation of electromagnetic launch repeatability

    NASA Astrophysics Data System (ADS)

    Cornette, James B.; Heyse, Mark W.; Brown, Jere L.

    1993-01-01

    Electromagnetic launcher (EML) performance repeatability has been identified as a potential development issue for several years. Investigation of this issue has been difficult because an EML that is powered on a relatively continuous basis to provide long duration operation has not been available. A battery charged capacitor power system has enabled long duration, 6 to 7 seconds, EML experiments. This paper provides a summary of an experiment to investigate EML launch to launch performance consistency. A series of 8 ten-shot bursts, each separated by 15 to 30 minutes, performed in a single day using a single set of bore materials is the subject of this paper.

  16. 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.

  17. Entanglement replication via quantum repeated interactions

    NASA Astrophysics Data System (ADS)

    Wendenbaum, Pierre; Platini, Thierry; Karevski, Dragi

    2015-04-01

    We study entanglement creation between two independent XX chains, which are repeatedly coupled locally to spin-1/2 Bell pairs. We show analytically that in the steady state the entanglement of the Bell pairs is perfectly transferred to the chains, generating large-scale interchain pair correlations. However, before the steady state is reached, within a growing causal region around the interacting locus the chains are found in a current driven nonequilibrium steady state (NESS). In the NESS, the chains cross entanglement decays exponentially with respect to the distance to the boundary sites with a typical length scale which is inversely proportional to the driving current.

  18. Repeated dose toxicity of alfa-cypermethrin in rats.

    PubMed

    Manna, S; Bhattacharyya, D; Mandal, T K; Das, S

    2004-09-01

    The present study was performed to investigate the subacute effect of alpha-cypermethrin (alpha-CP) in rats. Alfacypermethrin a synthetic pyrethroid insecticide, dissolved in dimethyl sulfoxide (DMSO) and oral LD50 was investigated after administering orally different doses in rats and was determined as 145 mg/kg. Other groups of rats were given repeated daily oral dose (1/10 LD50) of alpha-CP for 30 days. The animals were sacrificed on 31st day. Activities of various enzymes, cytochrome P450 and b5 contents in liver, hepatic antioxidant status, tissue residue concentration, haemogram and pathological changes were studied. It increased the serum aminotransaminases (AST, ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) activities and blood glucose level significantly. alpha-CP decreased RBC count, PCV and Hb level significantly. It significantly decreased cytochrome P450 in liver. Residues were present in different tissues. It increased malondialdehyde (MDA) level, while decreased the activities of catalase (CAT), superoxide dismutase (SOD) and glycogen level in liver significantly. Mild to moderate histological alterations were observed in lungs, liver, stomach, kidneys, testes and cerebellum. So repeated daily oral doses of alpha-CP at 1/10LD50 altered the biochemical parameters, decreased cytochrome P450 content, antioxidant status, which correlated with histopathological changes of tissues. PMID:15365239

  19. 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.

  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. 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.

  2. 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

    Hill, EC, Housh, TJ, Camic, CL, Smith, CM, Cochrane, KC, Jenkins, NDM, Cramer, JT, Schmidt, RJ, and Johnson, GO. Effects of velocity on electromyographic, mechanomyographic, and torque responses to repeated eccentric muscle actions. J Strength Cond Res 30(6): 1743-1751, 2016-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. PMID:26566165

  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. PMID:22749539

  4. Size of the unstable CTG repeat sequence in relation to phenotype and parental transmission in myotonic dystrophy

    SciTech Connect

    Harley, H.G.; Rundle, S.A.; MacMillan, J.C.; Myring, J.; Brook, J.D.; Crow, S.; Reardon, W.; Fenton, I.; Shaw, D.J.; Harper, P.S. )

    1993-06-01

    A clinical and molecular analysis of 439 individuals affected with myotonic dystrophy, from 101 kindreds, has shown that the size of the unstable CTG repeat detected in nearly all cases of myotonic dystrophy is related both to age at onset of the disorder and to the severity of the phenotype. The largest repeat sizes (1.5--6.0 kb) are seen in patients with congenital myotonic dystrophy, while the minimally affected patients have repeat sizes of < 0.5 kb. Comparison of parent-child pairs has shown that most offspring have an earlier age at onset and a larger repeat size than their parents, with only 4 of 182 showing a definite decrease in repeat size, accompanied by a later age at onset or less severe phenotype. Increase in repeat size from parent to child is similar for both paternal and maternal transmissions when the increase is expressed as a proportion of the parental repeat size. Analysis of congenitally affected cases shows not only that they have, on average, the largest repeat sizes but also that their mothers have larger mean repeat sizes, supporting previous suggestions that a maternal effect is involved in the pathogenesis of this form of the disorder. 23 refs., 5 figs.

  5. Psychological and cumulative cardiovascular effects of repeated angry rumination and visuospatial suppression.

    PubMed

    McClelland, Andrew B; Jones, Kenneth V; Douglas Gregg, M Elizabeth

    2009-11-01

    Brooding rumination is associated with depressed mood, increased negative affect, prolonged anger and inhibited cardiovascular (CV) recovery. Distraction from rumination on a stressful interpersonal encounter is associated with faster CV recovery and decreased negative affect. Studies have suggested that a concurrent visuospatial (VS) task inhibits the maintenance of imagery associated with the perseveration of intrusive negative memories. 120 healthy participants were recruited for the study. As an analogue of repeated angry rumination, the authors explored the effects of repeated visual recall of a provocative confederate and the subsequent impact of two visuospatial (VS) distraction tasks on negative affect, blood pressure (BP) and heart rate (HR). Repeated recall of the provocation generated repeatedly elevated HR with a cumulative trend that may have CV disease risk implications for chronic ruminators. VS distraction did not aid recovery compared with the Control task. PMID:19732797

  6. Get real: Effects of repeated simulation and emotion on the perceived plausibility of future experiences

    PubMed Central

    Szpunar, Karl K.; Schacter, Daniel L.

    2012-01-01

    People frequently imagine specific interpersonal experiences that might occur in their futures. The present study used a novel experimental paradigm to examine the influence of repeated simulation of future interpersonal experiences on subjective assessments of plausibility for positive, negative, and neutral events. The results demonstrate that repeated simulation increases estimates of plausibility for emotional, but not neutral, future interpersonal experiences. Additional correlational analyses reveal that increases in plausibility for emotional events are associated with concurrent increases in ease of simulation, event detail, and arousal. Implications for daily life and affective disorders such as depression and anxiety are noted. PMID:22686637

  7. Enhanced ad hoc wireless connectivity in complex environment using small radio repeater systems

    NASA Astrophysics Data System (ADS)

    Sarabandi, Kamal; Song, Young Jun; Oh, Jungsuek

    2011-06-01

    Ad hoc communication among small robotic platforms in complex indoor environment is further challenged by three limiting factors: 1) limited power, 2) small size antennas, and 3) near-ground operation. In complex environments such as indoor scenarios often times the line-of-sight communication cannot be established and the wireless connectivity must rely on multi-path propagation. As a result, the propagation path-loss is much higher than free-space, and more power will be needed to obtain the need coverage. Near ground operation also leads to increased path-loss. To maintain the network connectivity without increasing the required power a novel high gain miniaturized radio repeater is presented. Unlike existing repeater systems, this system utilizes two closely spaced low profile miniaturized planar antennas capable of producing omnidirectional and vertical radiation patterns as well as a channel isolator layer that serves to decouple the adjacent antennas. The meta-material based channel isolator serves as an electromagnetic shield, thus enabling it to be built in a sub-wavelength size of 0.07λ0 2 × λ0/70, the smallest repeater ever built. Also wave propagation simulations have been conducted to determine the required gain of such repeaters so to ensure the signal from the repeater is the dominant component. A prototype of the small radio repeater is fabricated to verify the design performance through a standard free-space measurement setup.

  8. Sequence analysis of Vicia faba repeated DNA, the FokI repeat element.

    PubMed Central

    Kato, A; Yakura, K; Tanifuji, S

    1984-01-01

    A type of highly repeated DNA sequences present in the genome of Vicia faba was detected by digestion its nuclear DNA with FokI endonuclease and fractionating the digests on polyacrylamide gels. Four fragments of 59, 108, 177 and 246 bp of the FokI repeated sequences were collected from the gels and their primary structures were determined by the method of Maxam and Gilbert. These repeated DNA sequences were shown to be a multiple tandem array of a 59 bp sequence element. And its nucleotide sequence was almost completely conserved among all the sequence members of each the size class and also among these classes. This sequence element consists of a duplet of an about the duplet has an incomplete dyad symmetrical structure. Images PMID:6089113

  9. Characteristics of repeatedly assaultive psychiatric inpatients.

    PubMed

    Convit, A; Isay, D; Otis, D; Volavka, J

    1990-10-01

    Investigations of assaults in psychiatric hospitals have found that a small proportion of inpatients are responsible for a large percentage of the violence that occurs. In a large state hospital patients who were repeatedly violent (recidivists) were compared with patients who were violent only once or twice (nonrecidivists), and the relationships between repeatedly violent behavior and gender, age, and diagnosis were examined. All reports of violent incidents over a six-month period for a population of 1,552 inpatients--a total of 497 incidents involving 313 patients--were reviewed. Seventy patients were involved in three or more incidents each and were responsible for 53 percent of all violence. Recidivist men inflicted serious injuries at a rate ten times higher than that for all the other violent patients. Recidivist women were significantly younger than nonrecidivist assaultive women and were about the same mean age as the assaultive men. Recidivist women were also more likely to have organic brain disorder or personality disorder. PMID:2242874

  10. Nanostructured functional films from engineered repeat proteins

    PubMed Central

    Grove, Tijana Z.; Regan, Lynne; Cortajarena, Aitziber L.

    2013-01-01

    Fundamental advances in biotechnology, medicine, environment, electronics and energy require methods for precise control of spatial organization at the nanoscale. Assemblies that rely on highly specific biomolecular interactions are an attractive approach to form materials that display novel and useful properties. Here, we report on assembly of films from the designed, rod-shaped, superhelical, consensus tetratricopeptide repeat protein (CTPR). We have designed three peptide-binding sites into the 18 repeat CTPR to allow for further specific and non-covalent functionalization of films through binding of fluorescein labelled peptides. The fluorescence signal from the peptide ligand bound to the protein in the solid film is anisotropic, demonstrating that CTPR films can impose order on otherwise isotropic moieties. Circular dichroism measurements show that the individual protein molecules retain their secondary structure in the film, and X-ray scattering, birefringence and atomic force microscopy experiments confirm macroscopic alignment of CTPR molecules within the film. This work opens the door to the generation of innovative biomaterials with tailored structure and function. PMID:23594813

  11. Dangling chain elastomers as repeatable fibrillar adhesives.

    PubMed

    Sitti, Metin; Cusick, Brian; Aksak, Burak; Nese, Alper; Lee, Hyung-il; Dong, Hongchen; Kowalewski, Tomasz; Matyjaszewski, Krzysztof

    2009-10-01

    This work reports on repeatable adhesive materials prepared by controlled grafting of dangling hetero chains from polymer elastomers. The dangling chain elastomer system was prepared by grafting poly(n-butyl acrylate) (PBA) chains from prefunctionalized polydimethylsiloxane (PDMS) elastomer networks using atom transfer radical polymerization. To study the effects of chain growth and network strain as they relate to network adhesion mechanics, various lengths of PBA chains with degree of polymerizations (DP) of 65, 281, 508, and 1200 were incorporated into the PDMS matrix. PBA chains with a DP value of 281 grafted from a flat PDMS substrate showed the highest (approximately 3.5-fold) enhancement of nano- and macroscale adhesion relative to a flat raw (ungrafted and not prefunctionalized) PDMS substrate. Moreover, to study the effect of PBA dangling chains on adhesion in fibrillar elastomer structures inspired by gecko foot hairs, a dip-transfer fabrication method was used to graft PBA chains with a DP value of 296 from the tip endings of mushroom-shaped PDMS micropillars. A PBA chain covered micropillar array showed macroscale adhesion enhancement up to approximately 7 times relative to the flat ungrafted prefunctionalized PDMS control substrate, showing additional nonoptimized approximately 2-fold adhesion enhancement due to fibrillar structuring and mushroom-shaped tip ending. These dangling hetero chains on elastomer micro-/nanofibrillar structures may provide a novel fabrication platform for multilength scale, repeatable, and high-strength fibrillar adhesives inspired by gecko foot hairs. PMID:20355863

  12. Learning with repeated-game strategies

    PubMed Central

    Ioannou, Christos A.; Romero, Julian

    2014-01-01

    We use the self-tuning Experience Weighted Attraction model with repeated-game strategies as a computer testbed to examine the relative frequency, speed of convergence and progression of a set of repeated-game strategies in four symmetric 2 × 2 games: Prisoner's Dilemma, Battle of the Sexes, Stag-Hunt, and Chicken. In the Prisoner's Dilemma game, we find that the strategy with the most occurrences is the “Grim-Trigger.” In the Battle of the Sexes game, a cooperative pair that alternates between the two pure-strategy Nash equilibria emerges as the one with the most occurrences. In the Stag-Hunt and Chicken games, the “Win-Stay, Lose-Shift” and “Grim-Trigger” strategies are the ones with the most occurrences. Overall, the pairs that converged quickly ended up at the cooperative outcomes, whereas the ones that were extremely slow to reach convergence ended up at non-cooperative outcomes. PMID:25126053

  13. 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.

  14. 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.

  15. Distribution of repeat unit differences between alleles at tandem repeat microsatellite loci

    SciTech Connect

    Jin, L. |; Zhong, Y.; Chakraborty, R.

    1994-09-01

    PCR-based assays of tandemly repeated microsatellite loci detect genetic variation from which alleles may be scored by their repeat unit lengths. Comparison of allele sizes from such data yields a probability distribution (P{sub k}) of repeat unit differences (k) between alleles segregating in a population. We show that this distribution (P{sub k}; k = 0, 1,2,...) provides insight regarding the mechanism of production of new alleles at such loci and the demographic history of populations, far better than that obtained from other summary measures (e.g., heterozygosity, number of alleles, and the range of allele sizes). The distributions of P{sub k} under multi-step stepwise models of mutation are analytically derived, which show that when a population is at equilibrium under the mutation-drift balance, the distribution of repeat unit differences between alleles is positively skewed with a mode larger than zero. However, when the heterozygosity at a locus is low (say, less than 40%), P{sub k} is a monotonically decreasing function of k. Applications of this theory to data on repeat unit sizes at over 1,240 microsatellite loci from the Caucasians, categorized by the average heterozygosity of loci, indicate that at most microsatellite loci new alleles are produced by stepwise mutations, and this is consistent with the replication slippage mechanism of mutations. The repeat size changes of mutants are probably within one or two units of alleles from which the mutants arise. Distributions of P{sub k} at microsatellite loci located within genes show evidence of allele size constraints. No significant evidence of recent expansion of population sizes in the Caucasians is detected by the distribution of P{sub k}.

  16. New insights into the genetic instability in CCTG repeats.

    PubMed

    Guo, Pei; Lam, Sik Lok

    2015-10-01

    Tetranucleotide CCTG repeat expansion is associated with myotonic dystrophy type 2, which is an inherited and progressive muscle degeneration disease. Yet, no cure is available and the molecular mechanism of repeat expansion remains elusive. In this study, we used high-resolution nuclear magnetic resonance spectroscopy to reveal a mini-dumbbell structure formed by two CCTG repeats. Upon slippage in the nascent strand during DNA replication, the formation of the mini-dumbbell provides a possible pathway for a two-repeat expansion. In addition, fast exchange between two competing mini-dumbbells among three repeats results in a mini-loop structure that accounts for one-repeat expansion. These mini-dumbbell and mini-loop intermediates can also co-exist at multiple sites in CCTG repeats, leading to three or larger size repeat expansions. PMID:26384951

  17. 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. PMID:23838981

  18. 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.

  19. 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.

  20. Cognitive and neural correlates of the 5-repeat allele of the dopamine D4 receptor gene in a population lacking the 7-repeat allele.

    PubMed

    Takeuchi, Hikaru; Tomita, Hiroaki; Taki, Yasuyuki; Kikuchi, Yoshie; Ono, Chiaki; Yu, Zhiqian; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

    2015-04-15

    The 5-repeat allele of a common length polymorphism in the gene that encodes the dopamine D4 receptor (DRD4) is robustly associated with the risk of attention deficit hyperactivity disorder (ADHD) and substantially exists in Asian populations, which have a lower ADHD prevalence. In this study, we investigated the effect of this allele on microstructural properties of the brain and on its functional activity during externally directed attention-demanding tasks and creative performance in the 765 Asian subjects. For this purpose, we employed diffusion tensor imaging, N-back functional magnetic resonance imaging paradigms, and a test to measure creativity by divergent thinking. The 5-repeat allele was significantly associated with increased originality in the creative performance, increased mean diffusivity (the measure of how the tissue includes water molecules instead of neural and vessel components) in the widespread gray and white matter areas of extensive areas, particularly those where DRD4 is expressed, and reduced task-induced deactivation in the areas that are deactivated during the tasks in the course of both the attention-demanding working memory task and simple sensorimotor task. The observed neural characteristics of 5-repeat allele carriers may lead to an increased risk of ADHD and behavioral deficits. Furthermore, the increased originality of creative thinking observed in the 5-repeat allele carriers may support the notion of the side of adaptivity of the widespread risk allele of psychiatric diseases. PMID:25659462

  1. Variation of the neurofilament medium KSP repeat sub-domain across mammalian species: implications for altering axonal structure.

    PubMed

    Barry, D M; Carpenter, C; Yager, C; Golik, B; Barry, K J; Shen, H; Mikse, O; Eggert, L S; Schulz, D J; Garcia, M L

    2010-01-01

    The evolution of larger mammals resulted in a corresponding increase in peripheral nerve length. To ensure optimal nervous system functionality and survival, nerve conduction velocities were likely to have increased to maintain the rate of signal propagation. Increases of conduction velocities may have required alterations in one of the two predominant properties that affect the speed of neuronal transmission: myelination or axonal diameter. A plausible mechanism to explain faster conduction velocities was a concomitant increase in axonal diameter with evolving axonal length. The carboxy terminal tail domain of the neurofilament medium subunit is a determinant of axonal diameter in large caliber myelinated axons. Sequence analysis of mammalian orthologs indicates that the neurofilament medium carboxy terminal tail contains a variable lysine-serine-proline (KSP) repeat sub-domain flanked by two highly conserved sub-domains. The number of KSP repeats within this region of neurofilament medium varies among species. Interestingly, the number of repeats does not change within a species, suggesting that selective pressure conserved the number of repeats within a species. Mapping KSP repeat numbers onto consensus phylogenetic trees reveals independent KSP expansion events across several mammalian clades. Linear regression analyses identified three subsets of mammals, one of which shows a positive correlation in the number of repeats with head-body length. For this subset of mammals, we hypothesize that variations in the number of KSP repeats within neurofilament medium carboxy terminal tail may have contributed to an increase in axonal caliber, increasing nerve conduction velocity as larger mammals evolved. PMID:20008369

  2. 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

  3. 47 CFR 80.1179 - On-board repeater limitations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 5 2012-10-01 2012-10-01 false On-board repeater limitations. 80.1179 Section... SERVICES STATIONS IN THE MARITIME SERVICES Voluntary Radio Installations On-Board Communications § 80.1179 On-board repeater limitations. When an on-board repeater is used, the following limitations must...

  4. 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…

  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. 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…

  7. 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.

  8. Repeatability of Marine CSEM Imaging for Reservoir Monitoring

    NASA Astrophysics Data System (ADS)

    Black, N.; Wilson, G. A.; Zhdanov, M. S.

    2011-12-01

    Recent studies have inferred the feasibility of time-lapse controlled-source electromagnetic (CSEM) methods for the monitoring of offshore oil and gas fields. However, survey repeatability is difficult as transmitter and receiver positions will vary, and the resistivity of the water column may vary with season. Moreover, cultural noise due to sub-sea infrastructure may increase as the field is developed. These effects will influence the CSEM data. Using Archie's Law, rock and fluid properties from dynamic reservoir simulations of the Harding field in the North Sea were converted to resistivity, from preproduction in 1996 to decommissioning in 2016. CSEM data were simulated for each state, where the transmitters and receivers were varied within the tolerance of today's best practice. Even with imperfect survey repeatability, we demonstrate how 3D imaging can be used for monitoring the oil-water contact from preproduction to the end of oil production in 2011, and for monitoring of the gas-water contact from 2011 to 2016 during gas production.

  9. Source-monitoring accuracy across repeated tests following directed forgetting.

    PubMed

    Goernert, Phillip N

    2005-05-01

    The repeated recall of items from lists that participants were earlier instructed to either remember or to forget was examined in two experiments. RR participants (those instructed to remember both lists they were presented) tended to recall more List 1 items than FR participants (those instructed to forget the first list and to remember the second list). FR participants recalled more List 2 items than did RR participants, but only when directed to report those items (Experiment 1), not when directed to report items from both lists (Experiment 2). Participants experienced difficulty correctly reporting the list source of items they recalled and incorrect source recall increased across tests, showing hypermnesia. This later result underscores the need for caution when assessing the accuracy of information retrieved from multiple sources across repeated tests. Together, the data patterns provide support for the retrieval dynamics account of hypermnesia, the context-change account of directed forgetting, and limited support for the retrieval inhibition view of directed forgetting. PMID:15969833

  10. 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.

  11. Towards highly multimode optical quantum memory for quantum repeaters

    NASA Astrophysics Data System (ADS)

    Jobez, Pierre; Timoney, Nuala; Laplane, Cyril; Etesse, Jean; Ferrier, Alban; Goldner, Philippe; Gisin, Nicolas; Afzelius, Mikael

    2016-03-01

    Long-distance quantum communication through optical fibers is currently limited to a few hundreds of kilometres due to fiber losses. Quantum repeaters could extend this limit to continental distances. Most approaches to quantum repeaters require highly multimode quantum memories in order to reach high communication rates. The atomic frequency comb memory scheme can in principle achieve high temporal multimode storage, without sacrificing memory efficiency. However, previous demonstrations have been hampered by the difficulty of creating high-resolution atomic combs, which reduces the efficiency for multimode storage. In this article we present a comb preparation method that allows one to increase the multimode capacity for a fixed memory bandwidth. We apply the method to a 3+151Eu -doped Y2SiO5 crystal, in which we demonstrate storage of 100 modes for 51 μ s using the AFC echo scheme (a delay-line memory) and storage of 50 modes for 0.541 ms using the AFC spin-wave memory (an on-demand memory). We also briefly discuss the ultimate multimode limit imposed by the optical decoherence rate, for a fixed memory bandwidth.

  12. Backward estimation of exposure to organochlorines using repeated measurements.

    PubMed Central

    Karmaus, Wilfried; Fussman, Christopher; Muttineni, Jyotsna; Zhu, Xiaobei

    2004-01-01

    Great Lakes sport-caught fish are contaminated with various organochlorines (OCs) such as polychlorinated biphenyls (PCBs). Through consumption of these fish, humans are subject to continuing levels of OC contamination. To assess potential adverse effects of past exposure, we compared three different backward extrapolation models. The data originated from OC determinations in a cohort of anglers and their families. Repeated PCB measurements collected in the 1970s, 1980s, and 1990s were used when testing the backward extrapolations. We applied a simple and a complex decay model based on assumptions used in previous studies; a third was a regression model incorporating markers of OC intake and loss. These techniques provided past exposure estimates. Intraclass correlation coefficients (ICCs) were calculated comparing measured and estimated PCB values. ICC values for the regression model equations were 0.77 and 0.89; ICC values for the simple and complex decay models were significantly lower, with ranges of 0.07-0.45 and -0.14-0.69, respectively. Plots showing trends of OC concentrations in fish and humans indicate comparable increases and decreases of PCB in fish and humans, with fish concentrations peaking approximately 10 years before that in humans. Our findings suggest that one should be cautious when using simple backward extrapolation techniques to estimate OC exposure in situations involving changing environmental exposures. Whenever repeated measurements are available, regression analyses seem to produce more accurate backward estimations of exposure. PMID:15121515

  13. Semiconductor structures for repeated velocity overshoot

    NASA Astrophysics Data System (ADS)

    Cooper, J. A., Jr.; Capasso, F.; Thornber, K. K.

    1982-12-01

    The conditions required for obtaining repeated velocity overshoot in semiconductors are discussed. Two classes of structures that provide these conditions are considered. The structures are seen as holding promise for achieving average drift velocities well in excess of the maximum steady-state velocity over distances ranging from submicron to tens of microns. In structures of the first class, the stairstep in potential is achieved by using a graded bandgap that is similar to the avalanche photodetector described by Williams et al. (1982), where the composition is graded from GaAs to Al(0.2)Ga(0.8)As. The second class of structures uses alternating planar doped charge sheets, as described by Malik et al. (1980).

  14. [The repeat reliability of somatosensory evoked potentials].

    PubMed

    Strenge, H

    1989-09-01

    The test-immediate-retest reliability of latency and amplitude values of cervical and cortical somatosensory evoked potentials (SEP) to median nerve stimulation was assessed in 86 normal subjects aged 15 to 71 years. In addition to the stability of data between repeat trials within one test session the standard errors of measurement and the interpretable differences for SEP measures were calculated according to measurement theory. The study revealed retest correlations rtt greater than 0.80 for all latency measures of the cervical and cortical SEPs and all cortical amplitude parameters. The highest stability was found for the latency measures of the cervical components P10, N11, N13, the cortical components P16 and N20 and for the amplitude N20/P25. PMID:2507277

  15. 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. PMID:24491104

  16. Trochlear Nerve Schwannoma With Repeated Intratumoral Hemorrhage.

    PubMed

    Liu, Pengfei; Bao, Yuhai; Zhang, Wenchuan

    2016-09-01

    Trochlear nerve schwannoma is extremely rare, with only 35 pathologically confirmed patients being reported in the literature. Here, the authors report a patient of trochlear nerve schwannoma in the prepontine cistern manifesting as facial pain and double vision and presenting the image characteristics of repeated intratumoral hemorrhage, which has never been reported in the literature. Total tumor along with a portion of the trochlear nerve was removed by using a retrosigmoid approach. Facial pain disappeared after operation, and the diplopia remained. Follow-up studies have shown no tumor recurrence for 2 years and the simultaneous alleviation of diplopia. Information regarding the clinical presentation, radiological features and surgical outcomes of trochlear nerve schwannoma are discussed and reviewed in the paper. PMID:27607129

  17. 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. PMID:23111906

  18. Increasing the dimensions of metrology

    NASA Astrophysics Data System (ADS)

    Maurer, Wilhelm; Blaesing-Bangert, Carola; Paul, Hans-Helmut

    1990-06-01

    In any process that generates or measures pattern-placement (overlay), these parameters need to be regarded at least as two-dimensional. We show this on our procedure bringing a mask repeater under statistical process control SPC). In order to increase the accuracy of the overlay measurement process itself, plate bending has to be included as a third dimension. By taking the third dimension into account, the LMS 2000 Metrology System significantly reduces the maximum uncertainity of measurement results.

  19. Digital genotyping of macrosatellites and multicopy genes reveals novel biological functions associated with copy number variation of large tandem repeats.

    PubMed

    Brahmachary, Manisha; Guilmatre, Audrey; Quilez, Javier; Hasson, Dan; Borel, Christelle; Warburton, Peter; Sharp, Andrew J

    2014-06-01

    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 modulating

  20. The hidden price of repeated traumatic exposure.

    PubMed

    Levy-Gigi, Einat; Richter-Levin, Gal

    2014-07-01

    Neuroimaging studies have demonstrated reduced hippocampal volume in trauma-exposed individuals without posttraumatic stress disorder (PTSD). However, the implications of such a deficit in this non-clinical population are still unclear. Animal and human models of PTSD suggest that hippocampal deficit may result in impaired learning and use of associations between contextual information and aversive events. Previous study has shown that individuals with PTSD have a selective impairment in reversing the negative outcome of context-related information. The aim of this study was to test whether non-PTSD individuals who are repeatedly exposed to traumatic events display similar impairment. To that end, we compared the performance of active-duty firefighters who are frequently exposed to traumatic events as part of their occupational routine and civilian matched-controls with no history of trauma-exposure. We used a novel cue-context reversal paradigm, which separately evaluates reversal of negative and positive outcomes of cue and context-related information. As predicted, we found that while both trauma-exposed firefighters and unexposed matched-controls were able to acquire and retain stimulus-outcome associations, firefighters struggled to learn that a previously negative context is later associated with a positive outcome. This impairment did not correlate with levels of PTSD, anxiety or depressive symptoms. The results suggest that similar to individuals with PTSD, highly exposed individuals fail to associate traumatic outcomes with their appropriate context. This impairment may reflect a possible hidden price of repeated traumatic exposure, which is not necessarily associated with PTSD diagnosis, and may affect the way highly exposed individuals interpret and react to their environment. PMID:24810272

  1. Repeated predictable stress causes resilience against colitis-induced behavioral changes in mice

    PubMed Central

    Hassan, Ahmed M.; Jain, Piyush; Reichmann, Florian; Mayerhofer, Raphaela; Farzi, Aitak; Schuligoi, Rufina; Holzer, Peter

    2014-01-01

    Inflammatory bowel disease is associated with an increased risk of mental disorders and can be exacerbated by stress. In this study which was performed with male 10-week old C57Bl/6N mice, we used dextran sulfate sodium (DSS)-induced colitis to evaluate behavioral changes caused by intestinal inflammation, to assess the interaction between repeated psychological stress (water avoidance stress, WAS) and colitis in modifying behavior, and to analyze neurochemical correlates of this interaction. A 7-day treatment with DSS (2% in drinking water) decreased locomotion and enhanced anxiety-like behavior in the open field test and reduced social interaction. Repeated exposure to WAS for 7 days had little influence on behavior but prevented the DSS-induced behavioral disturbances in the open field and SI tests. In contrast, repeated WAS did not modify colon length, colonic myeloperoxidase content and circulating proinflammatory cytokines, parameters used to assess colitis severity. DSS-induced colitis was associated with an increase in circulating neuropeptide Y (NPY), a rise in the hypothalamic expression of cyclooxygenase-2 mRNA and a decrease in the hippocampal expression of NPY mRNA, brain-derived neurotrophic factor mRNA and mineralocorticoid receptor mRNA. Repeated WAS significantly decreased the relative expression of corticotropin-releasing factor mRNA in the hippocampus. The effect of repeated WAS to blunt the DSS-evoked behavioral disturbances was associated with a rise of circulating corticosterone and an increase in the expression of hypothalamic NPY mRNA. These results show that experimental colitis leads to a particular range of behavioral alterations which can be prevented by repeated WAS, a model of predictable chronic stress, while the severity of colitis remains unabated. We conclude that the mechanisms underlying the resilience effect of repeated WAS involves hypothalamic NPY and the hypothalamic-pituitary-adrenal axis. PMID:25414650

  2. Mutations in polI but not mutSLH destabilize Haemophilus influenzae tetranucleotide repeats.

    PubMed

    Bayliss, Christopher D; van de Ven, Tamsin; Moxon, E Richard

    2002-03-15

    Haemophilus influenzae (Hi), an obligate upper respiratory tract commensal/pathogen, uses phase variation (PV) to adapt to host environment changes. Switching occurs by slippage of nucleotide repeats (microsatellites) within genes coding for virulence molecules. Most such microsatellites in Hi are tetranucleotide repeats, but an exception is the dinucleotide repeats in the pilin locus. To investigate the effects on PV rates of mutations in genes for mismatch repair (MMR), insertion/deletion mutations of mutS, mutL, mutH, dam, polI, uvrD, mfd and recA were constructed in Hi strain Rd. Only inactivation of polI destabilized tetranucleotide (5'AGTC) repeat tracts of chromosomally located reporter constructs, whereas inactivation of mutS, but not polI, destabilized dinucleotide (5'AT) repeats. Deletions of repeats were predominant in polI mutants, which we propose are due to end-joining occurring without DNA polymerization during polI-deficient Okazaki fragment processing. The high prevalence of tetranucleotides mediating PV is an exceptional feature of the Hi genome. The refractoriness to MMR of hypermutation in Hi tetranucleotides facilitates adaptive switching without the deleterious increase in global mutation rates that accompanies a mutator genotype. PMID:11889052

  3. Novel Y-chromosome Short Tandem Repeat Variants Detected Through the Use of Massively Parallel Sequencing.

    PubMed

    Warshauer, David H; Churchill, Jennifer D; Novroski, Nicole; King, Jonathan L; Budowle, Bruce

    2015-08-01

    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

  4. 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

  5. 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

  6. 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.

  7. A Repeated Impact Method and Instrument to Evaluate the Impact Fatigue Property of Drillpipe

    NASA Astrophysics Data System (ADS)

    Lin, Yuanhua; Li, Qiang; Sun, Yongxing; Zhu, Hongjun; Zhou, Ying; Xie, Juan; Shi, Taihe

    2013-04-01

    It is well known that drillpipe failures are a pendent problem in drilling engineering. Most of drillpipe failures are low amplitude-repeated impact fatigue failures. The traditional method is using Charpy impact test to describe the fracture property of drillpipe, but it cannot veritably characterize the impact fatigue property of drillpipe under low amplitude-repeated impact. Based on the Charpy impact and other methods, a repeated impact method and instrument have been proposed to simulate the low amplitude-repeated impact of downhole conditions for drillpipe. Then, a series of tests have been performed using this instrument. Test results demonstrate the drillpipe upset transition area nonhomogeneity is more severe than drillpipe body, which is the key factor that leads to washout and fracture frequently of it. As the one time impact energy increases, the repeated impact times decrease exponentially, therefore, the rotational speed has a great effect on the fatigue life of drillpipe, and it is vital to select a suitable rotational speed for drilling jobs. In addition, based on SEM fractographs we found that the fracture surface of repeated impact is similar to the fatigue fracture, and there are many low cycle fatigue characteristic features on fracture surface that reveal very good agreement with the features of drillpipe fatigue failures in the field.

  8. Studies of an expanded trinucleotide repeat in transgenic mice

    SciTech Connect

    Bingham, P.; Wang, S.; Merry, D.

    1994-09-01

    Spinal and bulbar muscular atrophy (SBMA) is a progressive motor neuron disease caused by expansion of a trinucleotide repeat in the androgen receptor gene (AR{sup exp}). AR{sup exp} repeats expand further or contract in approximately 25% of transmissions. Analogous {open_quotes}dynamic mutations{close_quotes} have been reported in other expanded trinucleotide repeat disorders. We have been developing a mouse model of this disease using a transgenic approach. Expression of the SBMA AR was documented in transgenic mice with an inducible promoter. No phenotypic effects of transgene expression were observed. We have extended our previous results on stability of the expanded trinucleotide repeat in transgenic mice in two lines carrying AR{sup exp}. Tail DNA was amplified by PCR using primers spanning the repeat on 60 AR{sup exp} transgenic mice from four different transgenic lines. Migration of the PCR product through an acrylamide gel showed no change of the 45 CAG repeat length in any progeny. Similarly, PCR products from 23 normal repeat transgenics showed no change from the repeat length of the original construct. Unlike the disease allele in humans, the expanded repeat AR cDNA in transgenic mice showed no change in repeat length with transmission. The relative stability of CAG repeats seen in the transgenic mice may indicate either differences in the fidelity of replicative enzymes, or differences in error identification and repair between mice and humans. Integration site or structural properties of the transgene itself might also play a role.

  9. 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

  10. Association of estrogen receptor β and estrogen-related receptor α gene polymorphisms with bone mineral density in postmenopausal women.

    PubMed

    Shoukry, Amira; Shalaby, Sally M; Etewa, Rasha L; Ahmed, Hanan S; Abdelrahman, Hossam M

    2015-07-01

    The aim of the study was to investigate the possible association of AluI and RsaI polymorphisms of estrogen receptor β (ER-β) gene and 23-bp nucleotide repeat polymorphism of estrogen-related receptor α (ERRα) gene with bone mineral density (BMD) in postmenopausal Egyptian women. Two-hundred postmenopausal osteoporotic women as cases and 180 healthy age-matched postmenopausal women as controls were genotyped by PCR fragment length polymorphism for AluI, allele-specific PCR for RsaI, and by sizing of PCR products on agarose gels for ERRα repeats. sRANKL levels were estimated by ELISA. BMD measurements for spine and femoral neck were performed by dual energy X-ray absorptiometry. A significant difference between women with osteoporosis and controls regarding allele and genotype distributions of AluI G/A (OR 2.37, 95 % CI 1.77-3.18 and p < 0.001 for A allele) and ERRα polymorphisms (for the two repeats allele OR 2.08, 95 % CI 1.09-4.00, and p = 0.02). Osteoporotic women with the AluI AA + GA genotype or with the EERα 2,2 genotype had significantly lower BMD than did women with the other genotypes. Moreover, there was a significant increase of the mean values of sRANKL in carriers of AluI A, RsaI A alleles and in patients having 2,2 genotypes of ERRα (p < 0.001, p < 0.001, p = 0.02, respectively). We demonstrated an association of ER-β AluI G/A and ERRα 23-repeats polymorphisms with BMD in postmenopausal Egyptian women. A possible effect of ER-β and ERRα polymorphisms on the levels of sRANKL was estimated. PMID:25903400

  11. ED Patients with Prolonged Complaints and Repeat ED Visits Have an Increased Risk of Depression

    PubMed Central

    Brickman, Kristopher R.; Bahl, Rajiv; Marcinkowski, Nathan F.; Ammons, Katelyn R.; Akpunonu, Peter

    2016-01-01

    Introduction The objective of this study was to explore associations between presenting chief complaints of prolonged symptomatology, patient usage of the emergency department (ED), and underlying depression so that emergency physicians may better target patients for depression screening. Methods A convenience sample of ED patients were administered the Beck Depression Inventory-II (BDI-II) to assess for depression. We correlated completed BDI-II surveys to patient information including demographics, pertinent history of present illness information, and past medical history. Results Out of 425 participants screened, we identified complaints of two weeks or longer in 92 patients (22%). Of these patients, mild to severe depression was recognized in over half of the population (47), yet only nine patients reported a prior depression diagnosis. These 92 patients also visited the ED three times as frequently as those patients with more acute complaints (p<0.001). Finally, our study showed that patients with mild to severe depression had three times as many ED visits compared to patients with minimal or no depression (p<0.001). Conclusion Patients with complaints of symptomatology two weeks or longer are more likely to have underlying depression when presenting to the ED. Patients with three or more ED visits within the past year also have a greater incidence of underlying depression. We found a strong correlation between complaints with symptomatology of two weeks or longer and multiple ED visits, in which underlying depression may have contributed to these patients’ ED visits. PMID:27625727

  12. Analysis of separate isolates of Bordetella pertussis repeated DNA sequences.

    PubMed

    McPheat, W L; Hanson, J H; Livey, I; Robertson, J S

    1989-06-01

    Two independent isolates of a Bordetella pertussis repeated DNA unit were sequenced and shown to be an insertion sequence element with five nucleotide differences between the two copies. The sequences were 1053 bp in length with near-perfect terminal inverted repeats of 28 bp, had three open reading frames, and were each flanked by short direct repeats. The two insertion sequences showed considerable homology to two other B. pertussis repeated DNA sequences reported recently: IS481 and a 530 bp repeated DNA unit. The B. pertussis insertion sequence would appear to comprise a group of closely related sequences differing mainly in flanking direct repeats and the terminal inverted repeats. The two isolates reported here, which were from the adenylate cyclase and agglutinogen 2 regions of the genome, were numbered IS48lvl and IS48lv2 respectively. PMID:2559151

  13. Drift induced by repeated hydropeaking waves in controlled conditions

    NASA Astrophysics Data System (ADS)

    Maiolini, Bruno; Bruno, M. Cristina; Biffi, Sofia; Cashman, Matthew J.

    2014-05-01

    Repeated hydropeaking events characterize most alpine rivers downstream of power plants fed by high elevation reservoirs. The effects of hydropeaking on the benthic communities are well known, and usually each hydropeaking wave causes an increase in tractive force and changes in temperature and water quality. Simulations of hydropeaking in artificial system can help to disentangle the direct effects of the modified flow regime from impacts associated with other associated physio-chemical changes, and with the effects of river regulation and land-use changes that often accompany water resource development. In September 2013 we conducted a set of controlled simulations in five steel flumes fed by an Alpine stream (Fersina stream, Adige River catchment, Trentino, Italy), where benthic invertebrates can freely colonize the flumes. One flume was used as control with no change in flow, in the other four flumes we simulated an hydropeaking wave lasting six hours, and repeated for five consecutive days. Flow was increased by twice baseflow in two flumes, and three times in the other two. We collected benthic samples before the beginning (morning of day 1) and after the end (afternoon of day 5) of the set of simulations to evaluate changes in the benthic communities due to induced drift migration. During each simulation, we collected drifting organisms at short time intervals to assess the responses to: 1) the initial discharge increase, 2) the persistence of high flows for several hours; 3) the decrease of discharge to the baseflow; 4) the change in drift with each successive day. Preliminary results indicate typical strong increases of catastrophic drift on the onset of each simulated hydropeaking, drift responses proportional to the absolute discharge increase, a decrease in the drift responses over successive days. Different taxa responded with different patterns: taxa which resist tractive force increased in drift only during the periods of baseflow that follow the

  14. Exercise-induced muscle damage and potential mechanisms for the repeated bout effect.

    PubMed

    McHugh, M P; Connolly, D A; Eston, R G; Gleim, G W

    1999-03-01

    Unfamiliar, predominantly eccentric exercise, frequently results in muscle damage. A repeated bout of similar eccentric exercise results in less damage and is referred to as the 'repeated bout effect'. Despite numerous studies that have clearly demonstrated the repeated bout effect, there is little consensus as to the actual mechanism. In general, the adaptation has been attributed to neural, connective tissue or cellular adaptations. Other possible mechanisms include, adaptation in excitation-contraction coupling or adaptation in the inflammatory response. The 'neural theory' predicts that the initial damage is a result of high stress on a relatively small number of active fast-twitch fibres. For the repeated bout, an increase in motor unit activation and/or a shift to slow-twitch fibre activation distributes the contractile stress over a larger number of active fibres. Although eccentric training results in marked increases in motor unit activation, specific adaptations to a single bout of eccentric exercise have not been examined. The 'connective tissue theory' predicts that muscle damage occurs when the noncontractile connective tissue elements are disrupted and myofibrillar integrity is lost. Indirect evidence suggests that remodelling of the intermediate filaments and/or increased intramuscular connective tissue are responsible for the repeated bout effect. The 'cellular theory' predicts that muscle damage is the result of irreversible sarcomere strain during eccentric contractions. Sarcomere lengths are thought to be highly non-uniform during eccentric contractions, with some sarcomeres stretched beyond myofilament overlap. Loss of contractile integrity results in sarcomere strain and is seen as the initial stage of damage. Some data suggest that an increase in the number of sarcomeres connected in series, following an initial bout, reduces sarcomere strain during a repeated bout and limits the subsequent damage. It is unlikely that one theory can explain

  15. Temporal decorrelation in repeat pass-radar interferometry

    NASA Technical Reports Server (NTRS)

    Villasenor, John; Zebker, Howard

    1992-01-01

    Correlation in pass-to-pass, interferometric radar can be degraded by thermal noise, lack of parallelism between the radar flight tracks, spatial baseline noise, and surficial change. The effects of decorrelation due to thermal noise can be easily evaluated and removed, while those due slight angular changes between flight tracks are negligible for data acquired using near-repeat orbits. Empirical results obtained using images of Death Valley confirm that as the baseline increases, the overall correlation decreases due to spatial baseline noise. It is shown that areas of Cottonball Basin in Death Valley remained unchanged over the three-week period for which data was obtained, while a heavily forested area in Oregon exhibited significant temporal decorrelation. Lava in central Oregon also appeared to decorrelate. The results demonstrate that generation of height maps of heavily vegetated areas using pass-to-pass interferometry is practical, provided that the time between passes is at most several weeks.

  16. Reactivity to nicotine cues over repeated cue reactivity sessions.

    PubMed

    LaRowe, Steven D; Saladin, Michael E; Carpenter, Matthew J; Upadhyaya, Himanshu P

    2007-12-01

    The present study investigated whether reactivity to nicotine-related cues would attenuate across four experimental sessions held 1 week apart. Participants were nineteen non-treatment seeking, nicotine-dependent males. Cue reactivity sessions were performed in an outpatient research center using in vivo cues consisting of standardized smoking-related paraphernalia (e.g., cigarettes) and neutral comparison paraphernalia (e.g., pencils). Craving ratings were collected before and after both cue presentations while physiological measures (heart rate, skin conductance) were collected before and during the cue presentations. Although craving levels decreased across sessions, smoking-related cues consistently evoked significantly greater increases in craving relative to neutral cues over all four experimental sessions. Skin conductance was higher in response to smoking cues, though this effect was not as robust as that observed for craving. Results suggest that, under the described experimental parameters, craving can be reliably elicited over repeated cue reactivity sessions. PMID:17537583

  17. Molecular tandem repeat strategy for elucidating mechanical properties of high-strength proteins.

    PubMed

    Jung, Huihun; Pena-Francesch, Abdon; Saadat, Alham; Sebastian, Aswathy; Kim, Dong Hwan; Hamilton, Reginald F; Albert, Istvan; Allen, Benjamin D; Demirel, Melik C

    2016-06-01

    Many globular and structural proteins have repetitions in their sequences or structures. However, a clear relationship between these repeats and their contribution to the mechanical properties remains elusive. We propose a new approach for the design and production of synthetic polypeptides that comprise one or more tandem copies of a single unit with distinct amorphous and ordered regions. Our designed sequences are based on a structural protein produced in squid suction cups that has a segmented copolymer structure with amorphous and crystalline domains. We produced segmented polypeptides with varying repeat number, while keeping the lengths and compositions of the amorphous and crystalline regions fixed. We showed that mechanical properties of these synthetic proteins could be tuned by modulating their molecular weights. Specifically, the toughness and extensibility of synthetic polypeptides increase as a function of the number of tandem repeats. This result suggests that the repetitions in native squid proteins could have a genetic advantage for increased toughness and flexibility. PMID:27222581

  18. Conformational modulation mediated by polyglutamine expansion in CAG repeat expansion disease-associated proteins.

    PubMed

    Verani, Margherita; Bustamante, Maria; Martufi, Paola; Daldin, Manuel; Cariulo, Cristina; Azzollini, Lucia; Fodale, Valentina; Puglisi, Francesca; Weiss, Andreas; Macdonald, Douglas; Petricca, Lara; Caricasole, Andrea

    2016-09-16

    We have previously reported TR-FRET based immunoassays to detect a conformational change imparted on huntingtin protein by the polyglutamine expansion, which we confirmed using biophysical methodologies. Using these immunoassays, we now report that polyglutamine expansion influences the conformational properties of other polyglutamine disease proteins, exemplified by the androgen receptor (associated with spinal bulbar muscular atrophy) and TATA binding protein (associated with spinocerebellar ataxia 17). Using artificial constructs bearing short or long polyglutamine expansions or a multimerized, unrelated epitope (mimicking the increase in anti-polyglutamine antibody epitopes present in polyglutamine repeats of increasing length) we confirmed that the conformational TR-FRET based immunoassay detects an intrinsic conformational property of polyglutamine repeats. The TR-FRET based conformational immunoassay may represent a rapid, scalable tool to identify modulators of polyglutamine-mediated conformational change in different proteins associated with CAG triplet repeat disorders. PMID:27520369

  19. Repeated targeting of the same hosts by a brood parasite compromises host egg rejection

    PubMed Central

    Stevens, Martin; Troscianko, Jolyon; Spottiswoode, Claire N.

    2013-01-01

    Cuckoo eggs famously mimic those of their foster parents to evade rejection from discriminating hosts. Here we test whether parasites benefit by repeatedly parasitizing the same host nest. This should make accurate rejection decisions harder, regardless of the mechanism that hosts use to identify foreign eggs. Here we find strong support for this prediction in the African tawny-flanked prinia (Prinia subflava), the most common host of the cuckoo finch (Anomalospiza imberbis). We show experimentally that hosts reject eggs that differ from an internal template, but crucially, as the proportion of foreign eggs increases, hosts are less likely to reject them and require greater differences in appearance to do so. Repeated parasitism by the same cuckoo finch female is common in host nests and likely to be an adaptation to increase the probability of host acceptance. Thus, repeated parasitism interacts with egg mimicry to exploit cognitive and sensory limitations in host defences. PMID:24064931

  20. Detection of repeating and "anti-repeating" earthquakes in the Bucaramanga Nest

    NASA Astrophysics Data System (ADS)

    Barrett, S. A.; Prieto, G.; Beroza, G. C.

    2011-12-01

    The Bucaramanga Nest, beneath northern Colombia represents the densest concentration of intermediate-depth earthquakes in the world. The roughly 11 km3 volume produces approximately 15 events per day, yielding an active catalog of seismicity well separated from surrounding seismic activity. We correlate template-event waveforms from known earthquakes to continuous records from the Colombian National (RSNC) seismic network. Typical repeating events are identified as well as the more curious "anti-repeat" events for which seismograms show reversed polarity and nearly perfect anti-correlation. These events are of particular interest as they are not known for shallow, crustal earthquake populations. By compiling a more complete catalog of earthquakes, and by developing precise relative locations, we seek to understand the temporal and size variations of these recurring events in the Bucaramanga Nest.

  1. Comparison of simple sequence repeats in 19 Archaea.

    PubMed

    Trivedi, S

    2006-01-01

    All organisms that have been studied until now have been found to have differential distribution of simple sequence repeats (SSRs), with more SSRs in intergenic than in coding sequences. SSR distribution was investigated in Archaea genomes where complete chromosome sequences of 19 Archaea were analyzed with the program SPUTNIK to find di- to penta-nucleotide repeats. The number of repeats was determined for the complete chromosome sequences and for the coding and non-coding sequences. Different from what has been found for other groups of organisms, there is an abundance of SSRs in coding regions of the genome of some Archaea. Dinucleotide repeats were rare and CG repeats were found in only two Archaea. In general, trinucleotide repeats are the most abundant SSR motifs; however, pentanucleotide repeats are abundant in some Archaea. Some of the tetranucleotide and pentanucleotide repeat motifs are organism specific. In general, repeats are short and CG-rich repeats are present in Archaea having a CG-rich genome. Among the 19 Archaea, SSR density was not correlated with genome size or with optimum growth temperature. Pentanucleotide density had an inverse correlation with the CG content of the genome. PMID:17183484

  2. REPdenovo: Inferring De Novo Repeat Motifs from Short Sequence Reads

    PubMed Central

    Chu, Chong; Nielsen, Rasmus; Wu, Yufeng

    2016-01-01

    Repeat elements are important components of eukaryotic genomes. One limitation in our understanding of repeat elements is that most analyses rely on reference genomes that are incomplete and often contain missing data in highly repetitive regions that are difficult to assemble. To overcome this problem we develop a new method, REPdenovo, which assembles repeat sequences directly from raw shotgun sequencing data. REPdenovo can construct various types of repeats that are highly repetitive and have low sequence divergence within copies. We show that REPdenovo is substantially better than existing methods both in terms of the number and the completeness of the repeat sequences that it recovers. The key advantage of REPdenovo is that it can reconstruct long repeats from sequence reads. We apply the method to human data and discover a number of potentially new repeats sequences that have been missed by previous repeat annotations. Many of these sequences are incorporated into various parasite genomes, possibly because the filtering process for host DNA involved in the sequencing of the parasite genomes failed to exclude the host derived repeat sequences. REPdenovo is a new powerful computational tool for annotating genomes and for addressing questions regarding the evolution of repeat families. The software tool, REPdenovo, is available for download at https://github.com/Reedwarbler/REPdenovo. PMID:26977803

  3. Kinetics of D-lactic acid production by Sporolactobacillus sp. strain CASD using repeated batch fermentation.

    PubMed

    Zhao, Bo; Wang, Limin; Li, Fengsong; Hua, Dongliang; Ma, Cuiqing; Ma, Yanhe; Xu, Ping

    2010-08-01

    D-lactic acid was produced by Sporolactobacillus sp. strain CASD in repeated batch fermentation with one- and two-reactor systems. The strain showed relatively high energy consumption in its growth-related metabolism in comparison with other lactic acid producers. When the fermentation was repeated with 10% (v/v) of previous culture to start a new batch, D-lactic acid production shifted from being cell-maintenance-dependent to cell-growth-dependent. In comparison with the one-reactor system, D-lactic acid production increased approximately 9% in the fourth batch of the two-reactor system. Strain CASD is an efficient D-lactic acid producer with increased growth rate at the early stage of repeated cycles, which explains the strain's physiological adaptation to repeated batch culture and improved performance in the two-reactor fermentation system. From a kinetic point of view, two-reactor fermentation system was shown to be an alternative for conventional one-reactor repeated batch operation. PMID:20374976

  4. Children's eyewitness memory: repeating post-event misinformation reduces the distinctiveness of a witnessed event.

    PubMed

    Bright-Paul, Alexandra; Jarrold, Christopher

    2012-01-01

    Children may incorporate misinformation into reports of witnessed events, particularly if the misinformation is repeated. One explanation is that the misinformation trace is strengthened by repetition. Alternatively, repeating misinformation may reduce the discriminability between event and misinformation sources, increasing interference between them. We tested trace strength and distinctiveness accounts by showing 5- and 6-year-olds an event and then presenting either the "same" or "varying" items of post-event misinformation across three iterations. Performance was compared to a baseline in which misinformation was presented once. Repeating the same misinformation increased suggestibility when misinformation was erroneously attributed to both event and misinformation sources, supporting a trace strength interpretation. However, suggestibility measured by attributing misinformation solely to the event, was lower when misinformation was presented repeatedly rather than once. In contrast, identification of the correct source of the event was less likely if the misinformation was repeated, whether the same or different across iterations. Thus a reduction in the distinctiveness of sources disrupted memory for the event source. Moreover, there was strong association between memory for the event and a measure of distinctiveness of sources, which takes into account both the number of confusable source and their apparent temporal spacing from the point of retrieval. PMID:22963045

  5. Relationship of Prepharmacy Repeat Course History to Students’ Early Academic Difficulty in a Pharmacy Curriculum

    PubMed Central

    Mort, Jane R.; Brandenburger, Thomas; Lempola, Allison

    2015-01-01

    Objective. To examine the relationship between students’ prepharmacy repeat course history and their academic difficulties early in a professional pharmacy program in conjunction with other prerequisite success variables known to predict academic difficulty. Methods. For students admitted to a pharmacy program in 2010 and 2011 (n=160), admission variables [eg, prepharmacy coursework, grade point average (GPA)] and pharmacy program academic difficulty data (ie, academic difficulty defined as a pharmacy GPA in the bottom quartile of the class after 3 semesters of pharmacy course work) were extracted. Regression analysis was employed to examine the relationship between admission variables and academic difficulty. Results. Twenty-six percent of the students (n=42) repeated a course, and 50% of these students (n=21) repeated more than one course. All of the admissions variables studied were found to individually increase the odds of a student having academic difficulty early in the pharmacy program. Specifically, repeat of a prepharmacy course increased the odds of academic difficulty threefold. Conclusion. Repeating prepharmacy coursework appears to be a strong indicator of future academic difficulties early in a professional pharmacy program. PMID:26889066

  6. MODELING THE EFFECTS OF UPDATING THE INFLUENZA VACCINE ON THE EFFICACY OF REPEATED VACCINATION.

    SciTech Connect

    D. SMITH; A. LAPEDES; ET AL

    2000-11-01

    The accumulated wisdom is to update the vaccine strain to the expected epidemic strain only when there is at least a 4-fold difference [measured by the hemagglutination inhibition (HI) assay] between the current vaccine strain and the expected epidemic strain. In this study we investigate the effect, on repeat vaccines, of updating the vaccine when there is a less than 4-fold difference. Methods: Using a computer model of the immune response to repeated vaccination, we simulated updating the vaccine on a 2-fold difference and compared this to not updating the vaccine, in each case predicting the vaccine efficacy in first-time and repeat vaccines for a variety of possible epidemic strains. Results: Updating the vaccine strain on a 2-fold difference resulted in increased vaccine efficacy in repeat vaccines compared to leaving the vaccine unchanged. Conclusions: These results suggest that updating the vaccine strain on a 2-fold difference between the existing vaccine strain and the expected epidemic strain will increase vaccine efficacy in repeat vaccines compared to leaving the vaccine unchanged.

  7. Does routine repeat testing of critical laboratory values improve their accuracy?

    PubMed Central

    Baradaran Motie, Pooya; Zare-Mirzaie, Ali; Shayanfar, Nasrin; Kadivar, Maryam

    2015-01-01

    Background: Routine repeat testing of critical laboratory values is very common these days to increase their accuracy and to avoid reporting false or infeasible results. We figure that repeat testing of critical laboratory values has any benefits or not. Methods: We examined 2233 repeated critical laboratory values in 13 different hematology and chemistry tests including: hemoglobin, white blood cell, platelet, international normalized ratio, partial thromboplastin time, glucose, potassium, sodium, phosphorus, magnesium, calcium, total bilirubin and direct bilirubin. The absolute d