WorldWideScience

Sample records for noncoding repeat expansions

  1. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  2. Electrochemical detection of DNA triplet repeat expansion

    Czech Academy of Sciences Publication Activity Database

    Fojta, Miroslav; Havran, Luděk; Vojtíšková, Marie; Paleček, Emil

    2004-01-01

    Roč. 126, č. 21 (2004), s. 6532-6533 ISSN 0002-7863 R&D Projects: GA AV ČR IAA4004402; GA AV ČR IBS5004355; GA AV ČR KJB4004302; GA AV ČR KSK4055109 Institutional research plan: CEZ:AV0Z5004920 Keywords : DNA triplet repeat expansion * PCR amplification * neurodegenerative diseases Subject RIV: BO - Biophysics Impact factor: 6.903, year: 2004

  3. Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures

    Science.gov (United States)

    McFarland, Karen N.; Liu, Jilin; Landrian, Ivette; Zeng, Desmond; Raskin, Salmo; Moscovich, Mariana; Gatto, Emilia M.; Ochoa, Adriana; Teive, Hélio A. G.; Rasmussen, Astrid; Ashizawa, Tetsuo

    2014-01-01

    Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant neurodegenerative disorder, is the result of a non-coding, pentanucleotide repeat expansion within intron 9 of the Ataxin 10 gene. SCA10 patients present with pure cerebellar ataxia; yet, some families also have a high incidence of epilepsy. SCA10 expansions containing penta- and heptanucleotide interruption motifs, termed “ATCCT interruptions,” experience large contractions during germline transmission, particularly in paternal lineages. At the same time, these alleles confer an earlier age at onset which contradicts traditional rules of genetic anticipation in repeat expansions. Previously, ATCCT interruptions have been associated with a higher prevalence of epileptic seizures in one Mexican-American SCA10 family. In a large cohort of SCA10 families, we analyzed whether ATCCT interruptions confers a greater risk for developing seizures in these families. Notably, we find that the presence of repeat interruptions within the SCA10 expansion confers a 6.3-fold increase in the risk of an SCA10 patient developing epilepsy (6.2-fold when considering patients of Mexican ancestry only) and a 13.7-fold increase in having a positive family history of epilepsy (10.5-fold when considering patients of Mexican ancestry only). We conclude that the presence of repeat interruptions in SCA10 repeat expansion indicates a significant risk for the epilepsy phenotype and should be considered during genetic counseling. PMID:24318420

  4. RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility

    OpenAIRE

    Aisling Frizzell; Jennifer H.G. Nguyen; Mark I.R. Petalcorin; Katherine D. Turner; Simon J. Boulton; Catherine H. Freudenreich; Robert S. Lahue

    2014-01-01

    SUMMARY Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG·CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vi...

  5. MicroRNAs in CAG trinucleotide repeat expansion disorders: an integrated review of the literature.

    Science.gov (United States)

    Dumitrescu, Laura; Popescu, Bogdan O

    2015-01-01

    MicroRNAs are small RNAs involved in gene silencing. They play important roles in transcriptional regulation and are selectively and abundantly expressed in the central nervous system. A considerable amount of the human genome is comprised of tandem repeating nucleotide streams. Several diseases are caused by above-threshold expansion of certain trinucleotide repeats occurring in a protein-coding or non-coding region. Though monogenic, CAG trinucleotide repeat expansion disorders have a complex pathogenesis, various combinations of multiple coexisting pathways resulting in one common final consequence: selective neurodegeneration. Mutant protein and mutant transcript gain of toxic function are considered to be the core pathogenic mechanisms. The profile of microRNAs in CAG trinucleotide repeat disorders is scarcely described, however microRNA dysregulation has been identified in these diseases and microRNA-related intereference with gene expression is considered to be involved in their pathogenesis. Better understanding of microRNAs functions and means of manipulation promises to offer further insights into the pathogenic pathways of CAG repeat expansion disorders, to point out new potential targets for drug intervention and to provide some of the much needed etiopathogenic therapeutic agents. A number of disease-modifying microRNA silencing strategies are under development, but several implementation impediments still have to be resolved. CAG targeting seems feasible and efficient in animal models and is an appealing approach for clinical practice. Preliminary human trials are just beginning.

  6. RTEL1 Inhibits Trinucleotide Repeat Expansions and Fragility

    Directory of Open Access Journals (Sweden)

    Aisling Frizzell

    2014-03-01

    Full Text Available Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG repeat expansions and fragility, likely by unwinding problematic hairpins.

  7. RTEL1 inhibits trinucleotide repeat expansions and fragility.

    Science.gov (United States)

    Frizzell, Aisling; Nguyen, Jennifer H G; Petalcorin, Mark I R; Turner, Katherine D; Boulton, Simon J; Freudenreich, Catherine H; Lahue, Robert S

    2014-03-13

    Human RTEL1 is an essential, multifunctional helicase that maintains telomeres, regulates homologous recombination, and helps prevent bone marrow failure. Here, we show that RTEL1 also blocks trinucleotide repeat expansions, the causal mutation for 17 neurological diseases. Increased expansion frequencies of (CTG⋅CAG) repeats occurred in human cells following knockdown of RTEL1, but not the alternative helicase Fbh1, and purified RTEL1 efficiently unwound triplet repeat hairpins in vitro. The expansion-blocking activity of RTEL1 also required Rad18 and HLTF, homologs of yeast Rad18 and Rad5. These findings are reminiscent of budding yeast Srs2, which inhibits expansions, unwinds hairpins, and prevents triplet-repeat-induced chromosome fragility. Accordingly, we found expansions and fragility were suppressed in yeast srs2 mutants expressing RTEL1, but not Fbh1. We propose that RTEL1 serves as a human analog of Srs2 to inhibit (CTG⋅CAG) repeat expansions and fragility, likely by unwinding problematic hairpins. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  8. The C9orf72 repeat expansion disrupts nucleocytoplasmic transport.

    Science.gov (United States)

    Zhang, Ke; Donnelly, Christopher J; Haeusler, Aaron R; Grima, Jonathan C; Machamer, James B; Steinwald, Peter; Daley, Elizabeth L; Miller, Sean J; Cunningham, Kathleen M; Vidensky, Svetlana; Gupta, Saksham; Thomas, Michael A; Hong, Ingie; Chiu, Shu-Ling; Huganir, Richard L; Ostrow, Lyle W; Matunis, Michael J; Wang, Jiou; Sattler, Rita; Lloyd, Thomas E; Rothstein, Jeffrey D

    2015-09-03

    The hexanucleotide repeat expansion (HRE) GGGGCC (G4C2) in C9orf72 is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent studies support an HRE RNA gain-of-function mechanism of neurotoxicity, and we previously identified protein interactors for the G4C2 RNA including RanGAP1. A candidate-based genetic screen in Drosophila expressing 30 G4C2 repeats identified RanGAP (Drosophila orthologue of human RanGAP1), a key regulator of nucleocytoplasmic transport, as a potent suppressor of neurodegeneration. Enhancing nuclear import or suppressing nuclear export of proteins also suppresses neurodegeneration. RanGAP physically interacts with HRE RNA and is mislocalized in HRE-expressing flies, neurons from C9orf72 ALS patient-derived induced pluripotent stem cells (iPSC-derived neurons), and in C9orf72 ALS patient brain tissue. Nuclear import is impaired as a result of HRE expression in the fly model and in C9orf72 iPSC-derived neurons, and these deficits are rescued by small molecules and antisense oligonucleotides targeting the HRE G-quadruplexes. Nucleocytoplasmic transport defects may be a fundamental pathway for ALS and FTD that is amenable to pharmacotherapeutic intervention.

  9. Germ-line CAG repeat instability causes extreme CAG repeat expansion with infantile-onset spinocerebellar ataxia type 2

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Ek, Jakob; Duno, Morten

    2013-01-01

    The spinocerebellar ataxias (SCA) are a genetically and clinically heterogeneous group of diseases, characterized by dominant inheritance, progressive cerebellar ataxia and diverse extracerebellar symptoms. A subgroup of the ataxias is caused by unstable CAG-repeat expansions in their respective ...... of paternal germ-line repeat sequence instability of the expanded SCA2 locus.European Journal of Human Genetics advance online publication, 10 October 2012; doi:10.1038/ejhg.2012.231....

  10. Complete Chloroplast Genome of Pinus massoniana (Pinaceae): Gene Rearrangements, Loss of ndh Genes, and Short Inverted Repeats Contraction, Expansion.

    Science.gov (United States)

    Ni, ZhouXian; Ye, YouJu; Bai, Tiandao; Xu, Meng; Xu, Li-An

    2017-09-11

    The chloroplast genome (CPG) of Pinus massoniana belonging to the genus Pinus (Pinaceae), which is a primary source of turpentine, was sequenced and analyzed in terms of gene rearrangements, ndh genes loss, and the contraction and expansion of short inverted repeats (IRs). P. massoniana CPG has a typical quadripartite structure that includes large single copy (LSC) (65,563 bp), small single copy (SSC) (53,230 bp) and two IRs (IRa and IRb, 485 bp). The 108 unique genes were identified, including 73 protein-coding genes, 31 tRNAs, and 4 rRNAs. Most of the 81 simple sequence repeats (SSRs) identified in CPG were mononucleotides motifs of A/T types and located in non-coding regions. Comparisons with related species revealed an inversion (21,556 bp) in the LSC region; P. massoniana CPG lacks all 11 intact ndh genes (four ndh genes lost completely; the five remained truncated as pseudogenes; and the other two ndh genes remain as pseudogenes because of short insertions or deletions). A pair of short IRs was found instead of large IRs, and size variations among pine species were observed, which resulted from short insertions or deletions and non-synchronized variations between "IRa" and "IRb". The results of phylogenetic analyses based on whole CPG sequences of 16 conifers indicated that the whole CPG sequences could be used as a powerful tool in phylogenetic analyses.

  11. Selection pressure on human STR loci and its relevance in repeat expansion disease

    KAUST Repository

    Shimada, Makoto K.

    2016-06-11

    Short Tandem Repeats (STRs) comprise repeats of one to several base pairs. Because of the high mutability due to strand slippage during DNA synthesis, rapid evolutionary change in the number of repeating units directly shapes the range of repeat-number variation according to selection pressure. However, the remaining questions include: Why are STRs causing repeat expansion diseases maintained in the human population; and why are these limited to neurodegenerative diseases? By evaluating the genome-wide selection pressure on STRs using the database we constructed, we identified two different patterns of relationship in repeat-number polymorphisms between DNA and amino-acid sequences, although both patterns are evolutionary consequences of avoiding the formation of harmful long STRs. First, a mixture of degenerate codons is represented in poly-proline (poly-P) repeats. Second, long poly-glutamine (poly-Q) repeats are favored at the protein level; however, at the DNA level, STRs encoding long poly-Qs are frequently divided by synonymous SNPs. Furthermore, significant enrichments of apoptosis and neurodevelopment were biological processes found specifically in genes encoding poly-Qs with repeat polymorphism. This suggests the existence of a specific molecular function for polymorphic and/or long poly-Q stretches. Given that the poly-Qs causing expansion diseases were longer than other poly-Qs, even in healthy subjects, our results indicate that the evolutionary benefits of long and/or polymorphic poly-Q stretches outweigh the risks of long CAG repeats predisposing to pathological hyper-expansions. Molecular pathways in neurodevelopment requiring long and polymorphic poly-Q stretches may provide a clue to understanding why poly-Q expansion diseases are limited to neurodegenerative diseases. © 2016, Springer-Verlag Berlin Heidelberg.

  12. Screening for the C9ORF72 repeat expansion in a greek frontotemporal dementia cohort.

    Science.gov (United States)

    Kartanou, Chrisoula; Karadima, Georgia; Koutsis, Georgios; Breza, Marianthi; Papageorgiou, Sokratis G; Paraskevas, George P; Kapaki, Elisabeth; Panas, Marios

    2018-02-01

    The C9orf72 repeat expansion is a common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) in European populations. A previous study has reported a high frequency of the expansion in Greek ALS. However, no data have been reported on the frequency of the expansion in Greek FTD. Currently, we investigated the frequency of the C9orfF72 expansion in a well-characterized cohort of 64 Greek FTD patients. We detected the C9orf72 repeat expansion in 9.3% of cases. Overall, 27.7% of familial and 2.2% of sporadic cases were expansion-positive. Five out of 6 cases had a diagnosis of behavioral variant FTD. All expansion-positive cases had fairly typical FTD presentations. Clinical features included motor neuron disease, Parkinsonism and hallucinations. We conclude that the overall frequency of C9orf72-positive cases in Greek FTD is high, comparable to Greek ALS, similar to some Western European, but significantly higher than some Mediterranean FTD populations.

  13. Hexanucleotide repeat expansions in C9ORF72 in the spectrum of motor neuron diseases

    NARCIS (Netherlands)

    van Rheenen, Wouter; van Blitterswijk, Marka; Huisman, Mark H. B.; Vlam, Lotte; van Doormaal, Perry T. C.; Seelen, Meinie; Medic, Jelena; Dooijes, Dennis; de Visser, Marianne; van der Kooi, Anneke J.; Raaphorst, Joost; Schelhaas, Helenius J.; van der Pol, W. Ludo; Veldink, Jan H.; van den Berg, Leonard H.

    2012-01-01

    Objective: To assess the frequency and phenotype of hexanucleotide repeat expansions in C9ORF72 in a large cohort of patients of Dutch descent with familial (fALS) and sporadic (sALS) amyotrophic lateral sclerosis (ALS), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS).

  14. C9orf72 hexanucleotide repeat expansions in Chinese sporadic amyotrophic lateral sclerosis.

    Science.gov (United States)

    He, Ji; Tang, Lu; Benyamin, Beben; Shah, Sonia; Hemani, Gib; Liu, Rong; Ye, Shan; Liu, Xiaolu; Ma, Yan; Zhang, Huagang; Cremin, Katie; Leo, Paul; Wray, Naomi R; Visscher, Peter M; Xu, Huji; Brown, Matthew A; Bartlett, Perry F; Mangelsdorf, Marie; Fan, Dongsheng

    2015-09-01

    A hexanucleotide repeat expansion (HRE) in the C9orf72 gene has been identified as the most common mutation in amyotrophic lateral sclerosis (ALS) among Caucasian populations. We sought to comprehensively evaluate genetic and epigenetic variants of C9orf72 and the contribution of the HRE in Chinese ALS cases. We performed fragment-length and repeat-primed polymerase chain reaction to determine GGGGCC copy number and expansion within the C9orf72 gene in 1092 sporadic ALS (sALS) and 1062 controls from China. We performed haplotype analysis of 23 single-nucleotide polymorphisms within and surrounding C9orf72. The C9orf72 HRE was found in 3 sALS patients (0.3%) but not in control subjects (p = 0.25). For 2 of the cases with the HRE, genotypes of 8 single-nucleotide polymorphisms flanking the HRE were inconsistent with the haplotype reported to be strongly associated with ALS in Caucasian populations. For these 2 individuals, we found hypermethylation of the CpG island upstream of the repeat, an observation not detected in other sALS patients (p HRE were highly associated with repeat lengths >8 repeats implying that both haplotypes may confer instability of repeat length. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Characterization of the repeat expansion size in C9orf72 in amyotrophic lateral sclerosis and frontotemporal dementia.

    Science.gov (United States)

    Dols-Icardo, Oriol; García-Redondo, Alberto; Rojas-García, Ricard; Sánchez-Valle, Raquel; Noguera, Aina; Gómez-Tortosa, Estrella; Pastor, Pau; Hernández, Isabel; Esteban-Pérez, Jesús; Suárez-Calvet, Marc; Antón-Aguirre, Sofía; Amer, Guillermo; Ortega-Cubero, Sara; Blesa, Rafael; Fortea, Juan; Alcolea, Daniel; Capdevila, Aura; Antonell, Anna; Lladó, Albert; Muñoz-Blanco, José Luís; Mora, Jesús S; Galán-Dávila, Lucía; Rodríguez De Rivera, Francisco Javier; Lleó, Alberto; Clarimón, Jordi

    2014-02-01

    Hexanucleotide repeat expansions within the C9orf72 gene are the most important genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The difficulty of developing a precise method to determine the expansion size has hampered the study of possible correlations between the hexanucleotide repeat number and clinical phenotype. Here we characterize, through a new non-radioactive Southern blot protocol, the expansion size range in a series of 38 ALS and 22 FTD heterozygous carriers of >30 copies of the repeat. Maximum, median and modal hexanucleotide repeat number were higher in ALS patients than in FTD patients (P< 0.05 in all comparisons). A higher median number of repeats correlated with a bigger range of repeat sizes (Spearman's ρ = 0.743, P = 1.05 × 10(-11)). We did not find any correlation between age of onset or disease duration with the repeat size in neither ALS nor FTD mutation carriers. Clinical presentation (bulbar or spinal) in ALS patients did not correlate either with the repeat length. We finally analyzed two families with affected and unaffected repeat expansion carriers, compared the size of the repeat expansion between two monozygotic (MZ) twins (one affected of ALS and the other unaffected), and examined the expansion size in two different tissues (cerebellum and peripheral blood) belonging to the same FTD patient. The results suggested that the length of the C9orf72 repeat varies between family members, including MZ twins, and among different tissues from the same individual.

  16. Searching for Grendel: origin and global spread of the C9ORF72 repeat expansion.

    Science.gov (United States)

    Pliner, Hannah A; Mann, David M; Traynor, Bryan J

    2014-03-01

    Recent advances are uncovering more and more of the genetic architecture underlying amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative condition that affects ~6,000 Americans annually. Chief among these was the discovery that a large repeat expansion in the C9ORF72 gene is responsible for an unprecedented portion of familial and sporadic ALS cases. Much has been published on how this expansion disrupts neuronal homeostasis and how gene-based therapy might be an effective treatment in the future. Nevertheless, it is instructive to look back at the origins of this important mutation. In this opinion piece, we attempt to answer three key questions concerning C9ORF72. First, how many times did the expansion occur throughout human history? Second, how old is the expansion? And finally and perhaps most importantly, how did the expansion spread throughout Europe? We speculate that the expansion occurred only once in the past, that this event took place in the Finnish population and that the Vikings and their descendants were responsible for disseminating this mutation throughout the rest of the continent.

  17. Structure and Dynamics of RNA Repeat Expansions That Cause Huntington's Disease and Myotonic Dystrophy Type 1.

    Science.gov (United States)

    Chen, Jonathan L; VanEtten, Damian M; Fountain, Matthew A; Yildirim, Ilyas; Disney, Matthew D

    2017-07-11

    RNA repeat expansions cause a host of incurable, genetically defined diseases. The most common class of RNA repeats consists of trinucleotide repeats. These long, repeating transcripts fold into hairpins containing 1 × 1 internal loops that can mediate disease via a variety of mechanism(s) in which RNA is the central player. Two of these disorders are Huntington's disease and myotonic dystrophy type 1, which are caused by r(CAG) and r(CUG) repeats, respectively. We report the structures of two RNA constructs containing three copies of a r(CAG) [r(3×CAG)] or r(CUG) [r(3×CUG)] motif that were modeled with nuclear magnetic resonance spectroscopy and simulated annealing with restrained molecular dynamics. The 1 × 1 internal loops of r(3×CAG) are stabilized by one-hydrogen bond (cis Watson-Crick/Watson-Crick) AA pairs, while those of r(3×CUG) prefer one- or two-hydrogen bond (cis Watson-Crick/Watson-Crick) UU pairs. Assigned chemical shifts for the residues depended on the identity of neighbors or next nearest neighbors. Additional insights into the dynamics of these RNA constructs were gained by molecular dynamics simulations and a discrete path sampling method. Results indicate that the global structures of the RNA are A-form and that the loop regions are dynamic. The results will be useful for understanding the dynamic trajectory of these RNA repeats but also may aid in the development of therapeutics.

  18. The Glycine-Alanine Dipeptide Repeat from C9orf72 Hexanucleotide Expansions Forms Toxic Amyloids Possessing Cell-to-Cell Transmission Properties.

    Science.gov (United States)

    Chang, Yu-Jen; Jeng, U-Ser; Chiang, Ya-Ling; Hwang, Ing-Shouh; Chen, Yun-Ru

    2016-03-04

    Hexanucleotide expansions, GGGGCC, in the non-coding regions of the C9orf72 gene were found in major frontotemporal lobar dementia and amyotrophic lateral sclerosis patients (C9FTD/ALS). In addition to possible RNA toxicity, several dipeptide repeats (DPRs) are translated through repeat-associated non-ATG-initiated translation. The DPRs, including poly(GA), poly(GR), poly(GP), poly(PR), and poly(PA), were found in the brains and spinal cords of C9FTD/ALS patients. Among the DPRs, poly(GA) is highly susceptible to form cytoplasmic inclusions, which is a characteristic of C9FTD/ALS. To elucidate DPR aggregation, we used synthetic (GA)15 DPR as a model system to examine the aggregation and structural properties in vitro. We found that (GA)15 with 15 repeats fibrillates rapidly and ultimately forms flat, ribbon-type fibrils evidenced by transmission electron microscopy and atomic force microscopy. The fibrils are capable of amyloid dye binding and contain a characteristic cross-β sheet structure, as revealed by x-ray scattering. Furthermore, using neuroblastoma cells, we demonstrated the neurotoxicity and cell-to-cell transmission property of (GA)15 DPR. Overall, our results show the structural and toxicity properties of GA DPR to facilitate future DPR-related therapeutic development. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Mouse Models of C9orf72 Hexanucleotide Repeat Expansion in Amyotrophic Lateral Sclerosis/ Frontotemporal Dementia

    Directory of Open Access Journals (Sweden)

    Ranjan Batra

    2017-07-01

    Full Text Available The presence of hexanucleotide repeat expansion (HRE in the first intron of the human C9orf72 gene is the most common genetic cause underlying both familial amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Studies aimed at elucidating the pathogenic mechanisms associated of C9orf72 FTD and ALS (C9FTD/ALS have focused on the hypothesis of RNA and protein toxic gain-of-function models, including formation of nuclear RNA foci containing GGGGCC (G4C2 HRE, inclusions containing dipeptide repeat proteins through a non-canonical repeat associated non-ATG (RAN translation mechanism, and on loss-of-function of the C9orf72 protein. Immense effort to elucidate these mechanisms has been put forth and toxic gain-of-function models have especially gained attention. Various mouse models that recapitulate distinct disease-related pathological, functional, and behavioral phenotypes have been generated and characterized. Although these models express the C9orf72 HRE mutation, there are numerous differences among them, including the transgenesis approach to introduce G4C2-repeat DNA, genomic coverage of C9orf72 features in the transgene, G4C2-repeat length after genomic stabilization, spatiotemporal expression profiles of RNA foci and RAN protein aggregates, neuropathological features, and neurodegeneration-related clinical symptoms. This review aims to (1 provide an overview of the key characteristics; (2 provide insights into potential pathological factors contributing to neurotoxicity and clinical phenotypes through systematic comparison of these models.

  20. Expansion of inverted repeat does not decrease substitution rates in Pelargonium plastid genomes.

    Science.gov (United States)

    Weng, Mao-Lun; Ruhlman, Tracey A; Jansen, Robert K

    2017-04-01

    For species with minor inverted repeat (IR) boundary changes in the plastid genome (plastome), nucleotide substitution rates were previously shown to be lower in the IR than the single copy regions (SC). However, the impact of large-scale IR expansion/contraction on plastid nucleotide substitution rates among closely related species remains unclear. We included plastomes from 22 Pelargonium species, including eight newly sequenced genomes, and used both pairwise and model-based comparisons to investigate the impact of the IR on sequence evolution in plastids. Ten types of plastome organization with different inversions or IR boundary changes were identified in Pelargonium. Inclusion in the IR was not sufficient to explain the variation of nucleotide substitution rates. Instead, the rate heterogeneity in Pelargonium plastomes was a mixture of locus-specific, lineage-specific and IR-dependent effects. Our study of Pelargonium plastomes that vary in IR length and gene content demonstrates that the evolutionary consequences of retaining these repeats are more complicated than previously suggested. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  1. Selection pressure on human STR loci and its relevance in repeat expansion disease

    KAUST Repository

    Shimada, Makoto K.; Sanbonmatsu, Ryoko; Yamaguchi-Kabata, Yumi; Yamasaki, Chisato; Suzuki, Yoshiyuki; Chakraborty, Ranajit; Gojobori, Takashi; Imanishi, Tadashi

    2016-01-01

    Short Tandem Repeats (STRs) comprise repeats of one to several base pairs. Because of the high mutability due to strand slippage during DNA synthesis, rapid evolutionary change in the number of repeating units directly shapes the range of repeat

  2. A Defective mRNA Cleavage and Polyadenylation Complex Facilitates Expansions of Transcribed (GAAn Repeats Associated with Friedreich’s Ataxia

    Directory of Open Access Journals (Sweden)

    Ryan J. McGinty

    2017-09-01

    Full Text Available Expansions of microsatellite repeats are responsible for numerous hereditary diseases in humans, including myotonic dystrophy and Friedreich’s ataxia. Whereas the length of an expandable repeat is the main factor determining disease inheritance, recent data point to genomic trans modifiers that can impact the likelihood of expansions and disease progression. Detection of these modifiers may lead to understanding and treating repeat expansion diseases. Here, we describe a method for the rapid, genome-wide identification of trans modifiers for repeat expansion in a yeast experimental system. Using this method, we found that missense mutations in the endoribonuclease subunit (Ysh1 of the mRNA cleavage and polyadenylation complex dramatically increase the rate of (GAAn repeat expansions but only when they are actively transcribed. These expansions correlate with slower transcription elongation caused by the ysh1 mutation. These results reveal an interplay between RNA processing and repeat-mediated genome instability, confirming the validity of our approach.

  3. C9ORF72 hexanucleotide repeat expansions are a frequent cause of Huntington disease phenocopies in the Greek population.

    Science.gov (United States)

    Koutsis, Georgios; Karadima, Georgia; Kartanou, Chrisoula; Kladi, Athina; Panas, Marios

    2015-01-01

    An expanded hexanucleotide repeat in C9ORF72 has been identified as the most common genetic cause of amyotrophic lateral sclerosis and/or frontotemporal dementia in many populations, including the Greek. Recently, C9ORF72 expansions were reported as the most common genetic cause of Huntington disease (HD) phenocopies in a UK population. In the present study, we screened a selected cohort of 40 Greek patients with HD phenocopies for C9ORF72 hexanucleotide repeat expansions using repeat-primed polymerase chain reaction. We identified 2 patients (5%) with pathologic expansions. The first patient had chorea, behavioral-psychiatric disturbance, cognitive impairment, and a positive family history, fulfilling the strictest criteria for HD phenocopy. The second patient was sporadic and had parkinsonism, behavioral-psychiatric disturbance, and cognitive impairment, corresponding to a broader definition of HD phenocopy. These findings identify C9ORF72 expansions as a frequent cause of HD phenocopies in the Greek population, confirming recent findings in other populations and supporting proposed diagnostic testing for C9ORF72 expansions in patients with HD-like syndromes. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. C9ORF72 G4C2-repeat expansion and frontotemporal dementia first reported case in Argentina.

    Science.gov (United States)

    Fernández Suarez, M; Surace, Ezequiel; Harris, P; Tapajoz, F; Sevlever, G; Allegri, R; Russo, G N

    2016-06-01

    We present a female patient aged 51 who developed behavioral disorders followed by cognitive impairment over 3 years. Neuropsychological, neuropsychiatric, and radiological features suggested a probable behavioral variant of frontotemporal dementia (bvFTD). A family history of amyotrophic lateral sclerosis and parkinsonism suggested the hexanucleotide repeat expansion G4C2 in C9ORF72 . We set up a two-step genotyping algorithm for the detection of the expansion using fragment-length analysis polymerase chain reaction (PCR) and repeat-primed PCR with fluorescent primers. We confirmed the presence of an expanded G4C2 allele in the patient. This represents the first documented case of bvFTD due to a C9ORF72 expansion in Argentina.

  5. Viral delivery of C9orf72 hexanucleotide repeat expansions in mice leads to repeat-length-dependent neuropathology and behavioural deficits

    Directory of Open Access Journals (Sweden)

    Saul Herranz-Martin

    2017-07-01

    Full Text Available Intronic GGGGCC repeat expansions in C9orf72 are the most common genetic cause of amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD. Two major pathologies stemming from the hexanucleotide RNA expansions (HREs have been identified in postmortem tissue: intracellular RNA foci and repeat-associated non-ATG dependent (RAN dipeptides, although it is unclear how these and other hallmarks of disease contribute to the pathophysiology of neuronal injury. Here, we describe two novel lines of mice that overexpress either 10 pure or 102 interrupted GGGGCC repeats mediated by adeno-associated virus (AAV and recapitulate the relevant human pathology and disease-related behavioural phenotypes. Similar levels of intracellular RNA foci developed in both lines of mice, but only mice expressing 102 repeats generated C9orf72 RAN pathology, neuromuscular junction (NMJ abnormalities, dispersal of the hippocampal CA1, enhanced apoptosis, and deficits in gait and cognition. Neither line of mice, however, showed extensive TAR DNA-binding protein 43 (TDP-43 pathology or neurodegeneration. Our data suggest that RNA foci pathology is not a good predictor of C9orf72 RAN dipeptide formation, and that RAN dipeptides and NMJ dysfunction are drivers of C9orf72 disease pathogenesis. These AAV-mediated models of C9orf72-associated ALS/FTD will be useful tools for studying disease pathophysiology and developing new therapeutic approaches.

  6. TGC repeat expansion in the TCF4 gene increases the risk of Fuchs' endothelial corneal dystrophy in Australian cases.

    Directory of Open Access Journals (Sweden)

    Abraham Kuot

    Full Text Available Fuchs' endothelial corneal dystrophy (FECD is a progressive, vision impairing disease. Common single nucleotide polymorphisms (SNPs and a trinucleotide repeat polymorphism, thymine-guanine-cytosine (TGC, in the TCF4 gene have been associated with the risk of FECD in some populations. We previously reported association of SNPs in TCF4 with FECD risk in the Australian population. The aim of this study was to determine whether TGC repeat polymorphism in TCF4 is associated with FECD in the Australian population. In 189 unrelated Australian cases with advanced late-onset FECD and 183 matched controls, the TGC repeat polymorphism located in intron 3 of TCF4 was genotyped using a short tandem repeat (STR assay. The repeat length was verified by direct sequencing in selected homozygous carriers. We found significant association between the expanded TGC repeat (≥ 40 repeats in TCF4 and advanced FECD (P = 2.58 × 10-22; OR = 15.66 (95% CI: 7.79-31.49. Genotypic analysis showed that 51% of cases (97 compared to 5% of controls (9 were heterozygous or homozygous for the expanded repeat allele. Furthermore, the repeat expansion showed stronger association than the most significantly associated SNP, rs613872, in TCF4, with the disease in the Australian cohort. This and haplotype analysis of both the polymorphisms suggest that considering both the polymorphisms together rather than either of the two alone would better predict susceptibility to FECD in the Australian population. This is the first study to report association of the TGC trinucleotide repeat expansion in TCF4 with advanced FECD in the Australian population.

  7. Frontotemporal dementia with the C9ORF72 hexanucleotide repeat expansion: clinical, neuroanatomical and neuropathological features

    Science.gov (United States)

    Mahoney, Colin J.; Beck, Jon; Rohrer, Jonathan D.; Lashley, Tammaryn; Mok, Kin; Shakespeare, Tim; Yeatman, Tom; Warrington, Elizabeth K.; Schott, Jonathan M.; Fox, Nick C.; Rossor, Martin N.; Hardy, John; Collinge, John; Revesz, Tamas; Mead, Simon

    2012-01-01

    An expanded hexanucleotide repeat in the C9ORF72 gene has recently been identified as a major cause of familial frontotemporal lobar degeneration and motor neuron disease, including cases previously identified as linked to chromosome 9. Here we present a detailed retrospective clinical, neuroimaging and histopathological analysis of a C9ORF72 mutation case series in relation to other forms of genetically determined frontotemporal lobar degeneration ascertained at a specialist centre. Eighteen probands (19 cases in total) were identified, representing 35% of frontotemporal lobar degeneration cases with identified mutations, 36% of cases with clinical evidence of motor neuron disease and 7% of the entire cohort. Thirty-three per cent of these C9ORF72 cases had no identified relevant family history. Families showed wide variation in clinical onset (43–68 years) and duration (1.7–22 years). The most common presenting syndrome (comprising a half of cases) was behavioural variant frontotemporal dementia, however, there was substantial clinical heterogeneity across the C9ORF72 mutation cohort. Sixty per cent of cases developed clinical features consistent with motor neuron disease during the period of follow-up. Anxiety and agitation and memory impairment were prominent features (between a half to two-thirds of cases), and dominant parietal dysfunction was also frequent. Affected individuals showed variable magnetic resonance imaging findings; however, relative to healthy controls, the group as a whole showed extensive thinning of frontal, temporal and parietal cortices, subcortical grey matter atrophy including thalamus and cerebellum and involvement of long intrahemispheric, commissural and corticospinal tracts. The neuroimaging profile of the C9ORF72 expansion was significantly more symmetrical than progranulin mutations with significantly less temporal lobe involvement than microtubule-associated protein tau mutations. Neuropathological examination in six cases

  8. DNA dynamics is likely to be a factor in the genomic nucleotide repeats expansions related to diseases.

    Directory of Open Access Journals (Sweden)

    Boian S Alexandrov

    Full Text Available Trinucleotide repeats sequences (TRS represent a common type of genomic DNA motif whose expansion is associated with a large number of human diseases. The driving molecular mechanisms of the TRS ongoing dynamic expansion across generations and within tissues and its influence on genomic DNA functions are not well understood. Here we report results for a novel and notable collective breathing behavior of genomic DNA of tandem TRS, leading to propensity for large local DNA transient openings at physiological temperature. Our Langevin molecular dynamics (LMD and Markov Chain Monte Carlo (MCMC simulations demonstrate that the patterns of openings of various TRSs depend specifically on their length. The collective propensity for DNA strand separation of repeated sequences serves as a precursor for outsized intermediate bubble states independently of the G/C-content. We report that repeats have the potential to interfere with the binding of transcription factors to their consensus sequence by altered DNA breathing dynamics in proximity of the binding sites. These observations might influence ongoing attempts to use LMD and MCMC simulations for TRS-related modeling of genomic DNA functionality in elucidating the common denominators of the dynamic TRS expansion mutation with potential therapeutic applications.

  9. Validation of a screening tool for the rapid and reliable detection of CGG trinucleotide repeat expansions in FMR1.

    Science.gov (United States)

    Basehore, Monica J; Marlowe, Natalia M; Jones, Julie R; Behlendorf, Deborah E; Laver, Thomas A; Friez, Michael J

    2012-06-01

    Most individuals with intellectual disability and/or autism are tested for Fragile X syndrome at some point in their lifetime. Greater than 99% of individuals with Fragile X have an expanded CGG trinucleotide repeat motif in the promoter region of the FMR1 gene, and diagnostic testing involves determining the size of the CGG repeat as well as methylation status when an expansion is present. Using a previously described triplet repeat-primed polymerase chain reaction, we have performed additional validation studies using two cohorts with previous diagnostic testing results available for comparison purposes. The first cohort (n=88) consisted of both males and females and had a high percentage of abnormal samples, while the second cohort (n=624) consisted of only females and was not enriched for expansion mutations. Data from each cohort were completely concordant with the results previously obtained during the course of diagnostic testing. This study further demonstrates the utility of using laboratory-developed triplet repeat-primed FMR1 testing in a clinical setting.

  10. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

    DEFF Research Database (Denmark)

    Lee, J-M; Ramos, E M; Lee, J-H

    2012-01-01

    Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound...

  11. Brain-specific noncoding RNAs are likely to originate in repeats and may play a role in up-regulating genes in cis

    DEFF Research Database (Denmark)

    Francescatto, Margherita; Vitezic, Morana; Heutink, Peter

    2014-01-01

    The mouse and human brain express a large number of noncoding RNAs (ncRNAs). Some of these are known to participate in neural progenitor cell fate determination, cell differentiation, neuronal and synaptic plasticity and transposable elements derived ncRNAs contribute to somatic variation...

  12. No CAG repeat expansion of polymerase gamma is associated with male infertility in Tamil Nadu, South India

    Science.gov (United States)

    Poongothai, J.

    2013-01-01

    Mitochondria contains a single deoxyribonucleic acid (DNA) polymerase, polymerase gamma (POLG) mapped to long arm of chromosome 15 (15q25), responsible for replication and repair of mitochondrial DNA. Exon 1 of the human POLG contains CAG trinucleotide repeat, which codes for polyglutamate. Ten copies of CAG repeat were found to be uniformly high (0.88) in different ethnic groups and considered as the common allele, whereas the mutant alleles (not -10/not -10 CAG repeats) were found to be associated with oligospermia/oligoasthenospermia in male infertility. Recent data suggested the implication of POLG CAG repeat expansion in infertility, but are debated. The aim of our study was to explore whether the not -10/not -10 variant is associated with spermatogenic failure. As few study on Indian population have been conducted so far to support this view, we investigated the distribution of the POLG CAG repeats in 61 infertile men and 60 normozoospermic control Indian men of Tamil Nadu, from the same ethnic background. This analysis interestingly revealed that the homozygous wild type genotype (10/-10) was common in infertile men (77% - 47/61) and in normozoospermic control men (71.7% - 43/60). Our study failed to confirm any influence of the POLG gene polymorphism on the efficiency of the spermatogenesis. PMID:24339545

  13. Bilateral cross-bite treated by repeated rapid maxillary expansions: a 17-year follow-up case.

    Science.gov (United States)

    Cozzani, M; Mazzotta, L; Caprioglio, A

    2014-07-01

    The objective of this paper is to show the clinical results after the repeated application of a Haas expander for rapid maxillary expansion (RME) anchored onto deciduous teeth in a 7-year-old patient that presented bilateral cross-bite, superior crowding and no space for permanent lateral incisors eruption. A first Haas expander was applied to the patient. She was told to activate it once a day, each activation was equal to 0.20 mm. After the first RME, the bilateral cross-bite was solved but still there was not enough space for lateral incisor eruption. A second and then a third Haas expander were applied, with the same activation protocol as the first one, in order to gain space in the anterior region and to achieve proper eruption of the lateral incisors. The patient was then treated with fixed appliances. At debonding the patient presented well aligned arch-forms: space for lateral incisor eruption was gained and superior crowding was solved. Bilateral cross-bite was also corrected. She was seen again 10 years and 17 years after expansions: she showed no relapse and presented a good functional occlusion that had remained stable, and an aesthetically pleasant smile, however she exhibited gingival recessions. Repeated rapid maxillary expansion, anchored onto deciduous teeth, performed in early mixed dentition represents a safe and successful treatment to correct severe bilateral cross- bites and to create space for maxillary incisor eruption.

  14. Oligonucleotides targeting TCF4 triplet repeat expansion inhibit RNA foci and mis-splicing in Fuchs' dystrophy.

    Science.gov (United States)

    Hu, Jiaxin; Rong, Ziye; Gong, Xin; Zhou, Zhengyang; Sharma, Vivek K; Xing, Chao; Watts, Jonathan K; Corey, David R; Mootha, V Vinod

    2018-03-15

    Fuchs' endothelial corneal dystrophy (FECD) is the most common repeat expansion disorder. FECD impacts 4% of U.S. population and is the leading indication for corneal transplantation. Most cases are caused by an expanded intronic CUG tract in the TCF4 gene that forms nuclear foci, sequesters splicing factors and impairs splicing. We investigated the sense and antisense RNA landscape at the FECD gene and find that the sense-expanded repeat transcript is the predominant species in patient corneas. In patient tissue, sense foci number were negatively correlated with age and showed no correlation with sex. Each endothelial cell has ∼2 sense foci and each foci is single RNA molecule. We designed antisense oligonucleotides (ASOs) to target the mutant-repetitive RNA and demonstrated potent inhibition of foci in patient-derived cells. Ex vivo treatment of FECD human corneas effectively inhibits foci and reverses pathological changes in splicing. FECD has the potential to be a model for treating many trinucleotide repeat diseases and targeting the TCF4 expansion with ASOs represents a promising therapeutic strategy to prevent and treat FECD.

  15. Expansion during PCR of short single-stranded DNA fragments carrying nonselfcomplementary dinucleotide or trinucleotide repeats

    Czech Academy of Sciences Publication Activity Database

    Reichová, Naďa; Kypr, Jaroslav

    2003-01-01

    Roč. 30, č. 3 (2003), s. 155-163 ISSN 0301-4851 R&D Projects: GA ČR GA301/01/0590 Institutional research plan: CEZ:AV0Z5004920 Keywords : DNA * PCR * expansion Subject RIV: BO - Biophysics Impact factor: 0.565, year: 2003

  16. CAG repeat expansion in Huntington disease determines age at onset in a fully dominant fashion

    Science.gov (United States)

    Lee, J.-M.; Ramos, E.M.; Lee, J.-H.; Gillis, T.; Mysore, J.S.; Hayden, M.R.; Warby, S.C.; Morrison, P.; Nance, M.; Ross, C.A.; Margolis, R.L.; Squitieri, F.; Orobello, S.; Di Donato, S.; Gomez-Tortosa, E.; Ayuso, C.; Suchowersky, O.; Trent, R.J.A.; McCusker, E.; Novelletto, A.; Frontali, M.; Jones, R.; Ashizawa, T.; Frank, S.; Saint-Hilaire, M.H.; Hersch, S.M.; Rosas, H.D.; Lucente, D.; Harrison, M.B.; Zanko, A.; Abramson, R.K.; Marder, K.; Sequeiros, J.; Paulsen, J.S.; Landwehrmeyer, G.B.; Myers, R.H.; MacDonald, M.E.; Durr, Alexandra; Rosenblatt, Adam; Frati, Luigi; Perlman, Susan; Conneally, Patrick M.; Klimek, Mary Lou; Diggin, Melissa; Hadzi, Tiffany; Duckett, Ayana; Ahmed, Anwar; Allen, Paul; Ames, David; Anderson, Christine; Anderson, Karla; Anderson, Karen; Andrews, Thomasin; Ashburner, John; Axelson, Eric; Aylward, Elizabeth; Barker, Roger A.; Barth, Katrin; Barton, Stacey; Baynes, Kathleen; Bea, Alexandra; Beall, Erik; Beg, Mirza Faisal; Beglinger, Leigh J.; Biglan, Kevin; Bjork, Kristine; Blanchard, Steve; Bockholt, Jeremy; Bommu, Sudharshan Reddy; Brossman, Bradley; Burrows, Maggie; Calhoun, Vince; Carlozzi, Noelle; Chesire, Amy; Chiu, Edmond; Chua, Phyllis; Connell, R.J.; Connor, Carmela; Corey-Bloom, Jody; Craufurd, David; Cross, Stephen; Cysique, Lucette; Santos, Rachelle Dar; Davis, Jennifer; Decolongon, Joji; DiPietro, Anna; Doucette, Nicholas; Downing, Nancy; Dudler, Ann; Dunn, Steve; Ecker, Daniel; Epping, Eric A.; Erickson, Diane; Erwin, Cheryl; Evans, Ken; Factor, Stewart A.; Farias, Sarah; Fatas, Marta; Fiedorowicz, Jess; Fullam, Ruth; Furtado, Sarah; Garde, Monica Bascunana; Gehl, Carissa; Geschwind, Michael D.; Goh, Anita; Gooblar, Jon; Goodman, Anna; Griffith, Jane; Groves, Mark; Guttman, Mark; Hamilton, Joanne; Harrington, Deborah; Harris, Greg; Heaton, Robert K.; Helmer, Karl; Henneberry, Machelle; Hershey, Tamara; Herwig, Kelly; Howard, Elizabeth; Hunter, Christine; Jankovic, Joseph; Johnson, Hans; Johnson, Arik; Jones, Kathy; Juhl, Andrew; Kim, Eun Young; Kimble, Mycah; King, Pamela; Klimek, Mary Lou; Klöppel, Stefan; Koenig, Katherine; Komiti, Angela; Kumar, Rajeev; Langbehn, Douglas; Leavitt, Blair; Leserman, Anne; Lim, Kelvin; Lipe, Hillary; Lowe, Mark; Magnotta, Vincent A.; Mallonee, William M.; Mans, Nicole; Marietta, Jacquie; Marshall, Frederick; Martin, Wayne; Mason, Sarah; Matheson, Kirsty; Matson, Wayne; Mazzoni, Pietro; McDowell, William; Miedzybrodzka, Zosia; Miller, Michael; Mills, James; Miracle, Dawn; Montross, Kelsey; Moore, David; Mori, Sasumu; Moser, David J.; Moskowitz, Carol; Newman, Emily; Nopoulos, Peg; Novak, Marianne; O'Rourke, Justin; Oakes, David; Ondo, William; Orth, Michael; Panegyres, Peter; Pease, Karen; Perlman, Susan; Perlmutter, Joel; Peterson, Asa; Phillips, Michael; Pierson, Ron; Potkin, Steve; Preston, Joy; Quaid, Kimberly; Radtke, Dawn; Rae, Daniela; Rao, Stephen; Raymond, Lynn; Reading, Sarah; Ready, Rebecca; Reece, Christine; Reilmann, Ralf; Reynolds, Norm; Richardson, Kylie; Rickards, Hugh; Ro, Eunyoe; Robinson, Robert; Rodnitzky, Robert; Rogers, Ben; Rosenblatt, Adam; Rosser, Elisabeth; Rosser, Anne; Price, Kathy; Price, Kathy; Ryan, Pat; Salmon, David; Samii, Ali; Schumacher, Jamy; Schumacher, Jessica; Sendon, Jose Luis Lópenz; Shear, Paula; Sheinberg, Alanna; Shpritz, Barnett; Siedlecki, Karen; Simpson, Sheila A.; Singer, Adam; Smith, Jim; Smith, Megan; Smith, Glenn; Snyder, Pete; Song, Allen; Sran, Satwinder; Stephan, Klaas; Stober, Janice; Sü?muth, Sigurd; Suter, Greg; Tabrizi, Sarah; Tempkin, Terry; Testa, Claudia; Thompson, Sean; Thomsen, Teri; Thumma, Kelli; Toga, Arthur; Trautmann, Sonja; Tremont, Geoff; Turner, Jessica; Uc, Ergun; Vaccarino, Anthony; van Duijn, Eric; Van Walsem, Marleen; Vik, Stacie; Vonsattel, Jean Paul; Vuletich, Elizabeth; Warner, Tom; Wasserman, Paula; Wassink, Thomas; Waterman, Elijah; Weaver, Kurt; Weir, David; Welsh, Claire; Werling-Witkoske, Chris; Wesson, Melissa; Westervelt, Holly; Weydt, Patrick; Wheelock, Vicki; Williams, Kent; Williams, Janet; Wodarski, Mary; Wojcieszek, Joanne; Wood, Jessica; Wood-Siverio, Cathy; Wu, Shuhua; Yastrubetskaya, Olga; de Yebenes, Justo Garcia; Zhao, Yong Qiang; Zimbelman, Janice; Zschiegner, Roland; Aaserud, Olaf; Abbruzzese, Giovanni; Andrews, Thomasin; Andrich, Jurgin; Antczak, Jakub; Arran, Natalie; Artiga, Maria J. Saiz; Bachoud-Lévi, Anne-Catherine; Banaszkiewicz, Krysztof; di Poggio, Monica Bandettini; Bandmann, Oliver; Barbera, Miguel A.; Barker, Roger A.; Barrero, Francisco; Barth, Katrin; Bas, Jordi; Beister, Antoine; Bentivoglio, Anna Rita; Bertini, Elisabetta; Biunno, Ida; Bjørgo, Kathrine; Bjørnevoll, Inga; Bohlen, Stefan; Bonelli, Raphael M.; Bos, Reineke; Bourne, Colin; Bradbury, Alyson; Brockie, Peter; Brown, Felicity; Bruno, Stefania; Bryl, Anna; Buck, Andrea; Burg, Sabrina; Burgunder, Jean-Marc; Burns, Peter; Burrows, Liz; Busquets, Nuria; Busse, Monica; Calopa, Matilde; Carruesco, Gemma T.; Casado, Ana Gonzalez; Catena, Judit López; Chu, Carol; Ciesielska, Anna; Clapton, Jackie; Clayton, Carole; Clenaghan, Catherine; Coelho, Miguel; Connemann, Julia; Craufurd, David; Crooks, Jenny; Cubillo, Patricia Trigo; Cubo, Esther; Curtis, Adrienne; De Michele, Giuseppe; De Nicola, A.; de Souza, Jenny; de Weert, A. Marit; de Yébenes, Justo Garcia; Dekker, M.; Descals, A. Martínez; Di Maio, Luigi; Di Pietro, Anna; Dipple, Heather; Dose, Matthias; Dumas, Eve M.; Dunnett, Stephen; Ecker, Daniel; Elifani, F.; Ellison-Rose, Lynda; Elorza, Marina D.; Eschenbach, Carolin; Evans, Carole; Fairtlough, Helen; Fannemel, Madelein; Fasano, Alfonso; Fenollar, Maria; Ferrandes, Giovanna; Ferreira, Jaoquim J.; Fillingham, Kay; Finisterra, Ana Maria; Fisher, K.; Fletcher, Amy; Foster, Jillian; Foustanos, Isabella; Frech, Fernando A.; Fullam, Robert; Fullham, Ruth; Gago, Miguel; García, RocioGarcía-Ramos; García, Socorro S.; Garrett, Carolina; Gellera, Cinzia; Gill, Paul; Ginestroni, Andrea; Golding, Charlotte; Goodman, Anna; Gørvell, Per; Grant, Janet; Griguoli, A.; Gross, Diana; Guedes, Leonor; BascuñanaGuerra, Monica; Guerra, Maria Rosalia; Guerrero, Rosa; Guia, Dolores B.; Guidubaldi, Arianna; Hallam, Caroline; Hamer, Stephanie; Hammer, Kathrin; Handley, Olivia J.; Harding, Alison; Hasholt, Lis; Hedge, Reikha; Heiberg, Arvid; Heinicke, Walburgis; Held, Christine; Hernanz, Laura Casas; Herranhof, Briggitte; Herrera, Carmen Durán; Hidding, Ute; Hiivola, Heli; Hill, Susan; Hjermind, Lena. E.; Hobson, Emma; Hoffmann, Rainer; Holl, Anna Hödl; Howard, Liz; Hunt, Sarah; Huson, Susan; Ialongo, Tamara; Idiago, Jesus Miguel R.; Illmann, Torsten; Jachinska, Katarzyna; Jacopini, Gioia; Jakobsen, Oda; Jamieson, Stuart; Jamrozik, Zygmunt; Janik, Piotr; Johns, Nicola; Jones, Lesley; Jones, Una; Jurgens, Caroline K.; Kaelin, Alain; Kalbarczyk, Anna; Kershaw, Ann; Khalil, Hanan; Kieni, Janina; Klimberg, Aneta; Koivisto, Susana P.; Koppers, Kerstin; Kosinski, Christoph Michael; Krawczyk, Malgorzata; Kremer, Berry; Krysa, Wioletta; Kwiecinski, Hubert; Lahiri, Nayana; Lambeck, Johann; Lange, Herwig; Laver, Fiona; Leenders, K.L.; Levey, Jamie; Leythaeuser, Gabriele; Lezius, Franziska; Llesoy, Joan Roig; Löhle, Matthias; López, Cristobal Diez-Aja; Lorenza, Fortuna; Loria, Giovanna; Magnet, Markus; Mandich, Paola; Marchese, Roberta; Marcinkowski, Jerzy; Mariotti, Caterina; Mariscal, Natividad; Markova, Ivana; Marquard, Ralf; Martikainen, Kirsti; Martínez, Isabel Haro; Martínez-Descals, Asuncion; Martino, T.; Mason, Sarah; McKenzie, Sue; Mechi, Claudia; Mendes, Tiago; Mestre, Tiago; Middleton, Julia; Milkereit, Eva; Miller, Joanne; Miller, Julie; Minster, Sara; Möller, Jens Carsten; Monza, Daniela; Morales, Blas; Moreau, Laura V.; Moreno, Jose L. López-Sendón; Münchau, Alexander; Murch, Ann; Nielsen, Jørgen E.; Niess, Anke; Nørremølle, Anne; Novak, Marianne; O'Donovan, Kristy; Orth, Michael; Otti, Daniela; Owen, Michael; Padieu, Helene; Paganini, Marco; Painold, Annamaria; Päivärinta, Markku; Partington-Jones, Lucy; Paterski, Laurent; Paterson, Nicole; Patino, Dawn; Patton, Michael; Peinemann, Alexander; Peppa, Nadia; Perea, Maria Fuensanta Noguera; Peterson, Maria; Piacentini, Silvia; Piano, Carla; Càrdenas, Regina Pons i; Prehn, Christian; Price, Kathleen; Probst, Daniela; Quarrell, Oliver; Quiroga, Purificacion Pin; Raab, Tina; Rakowicz, Maryla; Raman, Ashok; Raymond, Lucy; Reilmann, Ralf; Reinante, Gema; Reisinger, Karin; Retterstol, Lars; Ribaï, Pascale; Riballo, Antonio V.; Ribas, Guillermo G.; Richter, Sven; Rickards, Hugh; Rinaldi, Carlo; Rissling, Ida; Ritchie, Stuart; Rivera, Susana Vázquez; Robert, Misericordia Floriach; Roca, Elvira; Romano, Silvia; Romoli, Anna Maria; Roos, Raymond A.C.; Røren, Niini; Rose, Sarah; Rosser, Elisabeth; Rosser, Anne; Rossi, Fabiana; Rothery, Jean; Rudzinska, Monika; Ruíz, Pedro J. García; Ruíz, Belan Garzon; Russo, Cinzia Valeria; Ryglewicz, Danuta; Saft, Carston; Salvatore, Elena; Sánchez, Vicenta; Sando, Sigrid Botne; Šašinková, Pavla; Sass, Christian; Scheibl, Monika; Schiefer, Johannes; Schlangen, Christiane; Schmidt, Simone; Schöggl, Helmut; Schrenk, Caroline; Schüpbach, Michael; Schuierer, Michele; Sebastián, Ana Rojo; Selimbegovic-Turkovic, Amina; Sempolowicz, Justyna; Silva, Mark; Sitek, Emilia; Slawek, Jaroslaw; Snowden, Julie; Soleti, Francesco; Soliveri, Paola; Sollom, Andrea; Soltan, Witold; Sorbi, Sandro; Sorensen, Sven Asger; Spadaro, Maria; Städtler, Michael; Stamm, Christiane; Steiner, Tanja; Stokholm, Jette; Stokke, Bodil; Stopford, Cheryl; Storch, Alexander; Straßburger, Katrin; Stubbe, Lars; Sulek, Anna; Szczudlik, Andrzej; Tabrizi, Sarah; Taylor, Rachel; Terol, Santiago Duran-Sindreu; Thomas, Gareth; Thompson, Jennifer; Thomson, Aileen; Tidswell, Katherine; Torres, Maria M. Antequera; Toscano, Jean; Townhill, Jenny; Trautmann, Sonja; Tucci, Tecla; Tuuha, Katri; Uhrova, Tereza; Valadas, Anabela; van Hout, Monique S.E.; van Oostrom, J.C.H.; van Vugt, Jeroen P.P.; vanm, Walsem Marleen R.; Vandenberghe, Wim; Verellen-Dumoulin, Christine; Vergara, Mar Ruiz; Verstappen, C.C.P.; Verstraelen, Nichola; Viladrich, Celia Mareca; Villanueva, Clara; Wahlström, Jan; Warner, Thomas; Wehus, Raghild; Weindl, Adolf; Werner, Cornelius J.; Westmoreland, Leann; Weydt, Patrick; Wiedemann, Alexandra; Wild, Edward; Wild, Sue; Witjes-Ané, Marie-Noelle; Witkowski, Grzegorz; Wójcik, Magdalena; Wolz, Martin; Wolz, Annett; Wright, Jan; Yardumian, Pam; Yates, Shona; Yudina, Elizaveta; Zaremba, Jacek; Zaugg, Sabine W.; Zdzienicka, Elzbieta; Zielonka, Daniel; Zielonka, Euginiusz; Zinzi, Paola; Zittel, Simone; Zucker, Birgrit; Adams, John; Agarwal, Pinky; Antonijevic, Irina; Beck, Christopher; Chiu, Edmond; Churchyard, Andrew; Colcher, Amy; Corey-Bloom, Jody; Dorsey, Ray; Drazinic, Carolyn; Dubinsky, Richard; Duff, Kevin; Factor, Stewart; Foroud, Tatiana; Furtado, Sarah; Giuliano, Joe; Greenamyre, Timothy; Higgins, Don; Jankovic, Joseph; Jennings, Dana; Kang, Un Jung; Kostyk, Sandra; Kumar, Rajeev; Leavitt, Blair; LeDoux, Mark; Mallonee, William; Marshall, Frederick; Mohlo, Eric; Morgan, John; Oakes, David; Panegyres, Peter; Panisset, Michel; Perlman, Susan; Perlmutter, Joel; Quaid, Kimberly; Raymond, Lynn; Revilla, Fredy; Robertson, Suzanne; Robottom, Bradley; Sanchez-Ramos, Juan; Scott, Burton; Shannon, Kathleen; Shoulson, Ira; Singer, Carlos; Tabbal, Samer; Testa, Claudia; van, Kammen Dan; Vetter, Louise; Walker, Francis; Warner, John; Weiner, illiam; Wheelock, Vicki; Yastrubetskaya, Olga; Barton, Stacey; Broyles, Janice; Clouse, Ronda; Coleman, Allison; Davis, Robert; Decolongon, Joji; DeLaRosa, Jeanene; Deuel, Lisa; Dietrich, Susan; Dubinsky, Hilary; Eaton, Ken; Erickson, Diane; Fitzpatrick, Mary Jane; Frucht, Steven; Gartner, Maureen; Goldstein, Jody; Griffith, Jane; Hickey, Charlyne; Hunt, Victoria; Jaglin, Jeana; Klimek, Mary Lou; Lindsay, Pat; Louis, Elan; Loy, Clemet; Lucarelli, Nancy; Malarick, Keith; Martin, Amanda; McInnis, Robert; Moskowitz, Carol; Muratori, Lisa; Nucifora, Frederick; O'Neill, Christine; Palao, Alicia; Peavy, Guerry; Quesada, Monica; Schmidt, Amy; Segro, Vicki; Sperin, Elaine; Suter, Greg; Tanev, Kalo; Tempkin, Teresa; Thiede, Curtis; Wasserman, Paula; Welsh, Claire; Wesson, Melissa; Zauber, Elizabeth

    2012-01-01

    Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods: We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results: An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a well-behaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions: Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Neurology® 2012;78:690–695 PMID:22323755

  17. Cognitive and clinical characteristics of patients with amyotrophic lateral sclerosis carrying a C9orf72 repeat expansion: a population-based cohort study.

    LENUS (Irish Health Repository)

    Byrne, Susan

    2012-03-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of upper and lower motor neurons, associated with frontotemporal dementia (FTD) in about 14% of incident cases. We assessed the frequency of the recently identified C9orf72 repeat expansion in familial and apparently sporadic cases of ALS and characterised the cognitive and clinical phenotype of patients with this expansion.

  18. Strong population bottleneck and repeated demographic expansions of Populus adenopoda (Salicaceae) in subtropical China.

    Science.gov (United States)

    Fan, Liqiang; Zheng, Honglei; Milne, Richard I; Zhang, Lei; Mao, Kangshan

    2018-03-14

    Glacial refugia and inter-/postglacial recolonization routes during the Quaternary of tree species in Europe and North America are well understood, but far less is known about those of tree species in subtropical eastern Asia. Thus, we have examined the phylogeographic history of Populus adenopoda (Salicaceae), one of the few poplars that naturally occur in this subtropical area. Genetic variations across the range of the species in subtropical China were surveyed using ten nuclear microsatellite loci and four chloroplast fragments (matK, trnG-psbK, psbK-psbI and ndhC-trnV). Coalescent-based analyses were used to test demographic and migration hypotheses. In addition, species distribution models (SDMs) were constructed to infer past, present and future potential distributions of the species. Thirteen chloroplast haplotypes were detected, and haplotype-rich populations were found in central and southern parts of the species' range. STRUCTURE analyses of nuclear microsatellite loci suggest obvious lineage admixture, especially in peripheral and northern populations. DIYABC analysis suggests that the species might have experienced two independent rounds of demographic expansions and a strong bottleneck in the late Quaternary. SDMs indicate that the species' range contracted during the Last Glacial Maximum (LGM), and contracted northward but expanded eastward during the Last Interglacial (LIG). Chloroplast data and SDMs suggest that P. adenopoda might have survived in multiple glacial refugia in central and southern parts of its range during the LGM. Populations of the Yunnan-Guizhou Plateau in the southern part have high chloroplast DNA diversity, but may have contributed little to the postglacial recolonization of northern and eastern parts. The three major demographic events inferred by DIYABC coincide with the initiation of the LIG, start of the LGM and end of the LGM, respectively. The species may have experienced multiple rounds of range contraction during

  19. Revisiting genotype-phenotype overlap in neurogenetics: triplet-repeat expansions mimicking spastic paraplegias.

    Science.gov (United States)

    Bettencourt, Conceição; Quintáns, Beatriz; Ros, Raquel; Ampuero, Israel; Yáñez, Zuleima; Pascual, Samuel Ignacio; de Yébenes, Justo García; Sobrido, María-Jesús

    2012-09-01

    Hereditary spastic paraplegias (HSPs) constitute a heterogeneous group of neurological disorders, characterized primarily by progressive spasticity and weakness of the lower limbs. HSPs are caused by mutations in multiple genes (at least 48 loci and 28 causative genes). The clinical spectrum of HSPs is wide and important differences have been reported between patients with distinct mutations in the same gene, or even between different family members bearing the same mutation. Many patients with HSP present clinical deficits related to the involvement of neuronal systems other than corticospinal tracts, namely, peripheral nerves, sensory, or cerebellar pathways. These cases may be difficult to differentiate from other neurological diseases (e.g., hereditary ataxias), also genetically and clinically heterogeneous. As an illustration of how overlapping this genotype-phenotype relationship is, and the difficulties that it brings upon the development of neurogenetic algorithms and databases, we review the main clinical and genetic features of HSPs, and summarize reports on cases of triplet-repeat spinocerebellar ataxias that can mimic HSP phenotypes. This complex scenario makes the necessity of high-quality, curated mutation databases even more urgent, in order to develop adequate diagnostic guidelines, correct interpretation of genetic testing, and appropriate genetic counseling. © 2012 Wiley Periodicals, Inc.

  20. Brain white matter demyelinating lesions and amyotrophic lateral sclerosis in a patient with C9orf72 hexanucleotide repeat expansion.

    Science.gov (United States)

    Oliveira Santos, Miguel; Caldeira, Inês; Gromicho, Marta; Pronto-Laborinho, Ana; de Carvalho, Mamede

    2017-10-01

    A hexanucleotide repeat expansion in the C9orf72 gene is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. It has been described before four patients with multiple sclerosis (MS) and C9orf72-ALS. However, C9orf72 positivity is not associated with increased risk of MS. Inflammatory pathways related to NF-κB have been linked to ALS and MS, and appear to be important in C9orf72-ALS patients. A 42-year-old woman presented with progressive bulbar symptoms for 9 months. Neurological examination disclosed spastic dysarthria, atrophic tongue with fasciculations, brisk jaw and limb tendon reflexes, and bilateral Hoffman sign. Electrophysiological assessment confirmed ALS. Brain MRI revealed multiple and bilateral juxtacortical and periventricular inflammatory changes, some with gadolinium-enhancement, configuring a probable MS-like pattern. CSF evaluation was unremarkable, with no oligoclonal bands. Visual and somatosensory evoked potentials were normal. Follow-up brain MRI 6 months later showed two new lesions in two relatively characteristic locations of MS, with no gadolinium-enhancement. Genetic screening revealed a C9orf72 expansion. As patient had no clinical manifestation of MS, a diagnosis of radiologically isolated syndrome was considered. We speculate that these demyelinating lesions might facilitate expressivity of C9orf72 expansion, through NF-κB activation. This plausible association may lead to the identification of a therapeutic target in this subgroup of C9orf72-ALS patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: A cross-sectional study

    NARCIS (Netherlands)

    E. Majounie (Elisa); A. Renton (Alan); K. Mok (Kin); E.G.P. Dopper (Elise); A. Waite (Adrian); S. Rollinson (Sara); A. Chiò (Adriano); G. Restagno (Gabriella); N. Nicolaou (Nayia); J. Simón-Sánchez (Javier); J.C. van Swieten (John); Y. Abramzon (Yevgeniya); J. Johnson (Janel); M. Sendtner (Michael); R. Pamphlett (Roger); R. Orrell (Richard); S. Mead (Simon); K.C. Sidle (Katie); H. Houlden (Henry); J.D. Rohrer (Jonathan Daniel); K.E. Morrison (Karen); H. Pall (Hardev); D. Talbot; O. Ansorge (Olaf); D.G. Hernandez (Dena); S. Arepalli (Sampath); M. Sabatelli (Mario); G. Mora (Gabriele); J.C. Corbo (Joseph); F. Giannini (Fabio); A. Calvo (Andrea); E. Englund (Elisabet); G. Borghero (Giuseppe); O.A.M. Floris; A. Remes (Anne); H. Laaksovirta (Hannu); L. McCluskey (Leo); J.Q. Trojanowski (John); V.M. Deerlin (Vivianna); G.D. Schellenberg (Gerard); M.A. Nalls (Michael); V.E. Drory (Vivian E); C.S. Lu (Chin-Song); T.-H. Yeh (Tu-Hsueh); H. Ishiura (Hiroyuki); Y. Takahashi (Yukari); S. Tsuji (Shoji); I. Le Ber (Isabelle); A. Brice; C. Drepper (Carsten); N. Williams (Nigel); J. Kirby (Janine); P.J. Shaw (Pamela); J. Hardy (John); P.J. Tienari (Pentti); P. Heutink (Peter); H. Morris (Huw); S. Pickering-Brown (Stuart); B.J. Traynor (Bryan)

    2012-01-01

    textabstractBackground: We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods: We screened 4448 patients diagnosed with

  2. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study

    NARCIS (Netherlands)

    Majounie, E.; Renton, A.E.; Mok, K.; Dopper, E.G.P.; Waite, A.; Rollinson, S.; Chio, A.; Restagno, G.; Nicolaou, N.; Simon-Sanchez, J.; van Swieten, J.C.; Abramzon, Y.; Johnson, J.O.; Sendtner, M.; Pamphlett, R.; Orrell, R.W.; Mead, S.; Sidle, K.C.; Houlden, H.; Rohrer, J.D.; Morrison, K.E.; Pall, H.; Talbot, K.; Ansorge, O.; Hernandez, D.G.; Arepalli, S.; Sabatelli, M.; Mora, G.; Corbo, M.; Giannini, F.; Calvo, A.; Englund, E.; Borghero, G.; Foris, G.L.; Remes, A.M.; Laaksovirta, H.; McCluskey, L.; Trojanowski, J.Q.; Van Deerlin, V.M.; Schellenberg, G.D.; Nalls, M.A.; Drory, V.E.; Lu, C.S.; Yeh, T.H.; Ishiura, H.; Takahashi, Y.; Tsuji, S.; Le Ber, I.; Brice, A.; Drepper, C.; Williams, N.; Kirby, J.; Shaw, P.; Hardy, J.; Tienari, P.J.; Heutink, P.; Morris, H.R.; Pickering-Brown, S.; Traynor, B.J.

    2012-01-01

    Background: We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Methods: We screened 4448 patients diagnosed with ALS (El

  3. Low-pass shotgun sequencing of the barley genome facilitates rapid identification of genes, conserved non-coding sequences and novel repeats

    Directory of Open Access Journals (Sweden)

    Graner Andreas

    2008-10-01

    Full Text Available Abstract Background Barley has one of the largest and most complex genomes of all economically important food crops. The rise of new short read sequencing technologies such as Illumina/Solexa permits such large genomes to be effectively sampled at relatively low cost. Based on the corresponding sequence reads a Mathematically Defined Repeat (MDR index can be generated to map repetitive regions in genomic sequences. Results We have generated 574 Mbp of Illumina/Solexa sequences from barley total genomic DNA, representing about 10% of a genome equivalent. From these sequences we generated an MDR index which was then used to identify and mark repetitive regions in the barley genome. Comparison of the MDR plots with expert repeat annotation drawing on the information already available for known repetitive elements revealed a significant correspondence between the two methods. MDR-based annotation allowed for the identification of dozens of novel repeat sequences, though, which were not recognised by hand-annotation. The MDR data was also used to identify gene-containing regions by masking of repetitive sequences in eight de-novo sequenced bacterial artificial chromosome (BAC clones. For half of the identified candidate gene islands indeed gene sequences could be identified. MDR data were only of limited use, when mapped on genomic sequences from the closely related species Triticum monococcum as only a fraction of the repetitive sequences was recognised. Conclusion An MDR index for barley, which was obtained by whole-genome Illumina/Solexa sequencing, proved as efficient in repeat identification as manual expert annotation. Circumventing the labour-intensive step of producing a specific repeat library for expert annotation, an MDR index provides an elegant and efficient resource for the identification of repetitive and low-copy (i.e. potentially gene-containing sequences regions in uncharacterised genomic sequences. The restriction that a particular

  4. A CGG-repeat expansion mutation in ZNF713 causes FRA7A: association with autistic spectrum disorder in two families.

    Science.gov (United States)

    Metsu, Sofie; Rainger, Jacqueline K; Debacker, Kim; Bernhard, Birgitta; Rooms, Liesbeth; Grafodatskaya, Daria; Weksberg, Rosanna; Fombonne, Eric; Taylor, Martin S; Scherer, Stephen W; Kooy, R Frank; FitzPatrick, David R

    2014-11-01

    We report de novo occurrence of the 7p11.2 folate-sensitive fragile site FRA7A in a male with an autistic spectrum disorder (ASD) due to a CGG-repeat expansion mutation (∼450 repeats) in a 5' intron of ZNF713. This expanded allele showed hypermethylation of the adjacent CpG island with reduced ZNF713 expression observed in a proband-derived lymphoblastoid cell line (LCL). His unaffected mother carried an unmethylated premutation (85 repeats). This CGG-repeat showed length polymorphism in control samples (five to 22 repeats). In a second unrelated family, three siblings with ASD and their unaffected father were found to carry FRA7A premutations, which were partially or mosaically methylated. In one of the affected siblings, mitotic instability of the premutation was observed. ZNF713 expression in LCLs in this family was increased in three of these four premutation carriers. A firm link cannot yet be established between ASD and the repeat expansion mutation but plausible pathogenic mechanisms are discussed. © 2014 WILEY PERIODICALS, INC.

  5. Hexanucleotide Repeat Expansion in C9ORF72 Is Not Detected in the Treatment-Resistant Schizophrenia Patients of Chinese Han.

    Directory of Open Access Journals (Sweden)

    Xijia Xu

    Full Text Available Hexanucleotide (GGGGCC repeat expansion in C9ORF72 (HRE causes frontotemporal lobar degeneration, frontotemporal dementia-amyotrophic lateral sclerosis, and amyotrophic lateral sclerosis. HRE was also seen in the genomes of patients suffering from several other degenerative diseases. However, whether it is present in the treatment-resistant schizophrenia patients remains unknown. Genotyping 386 patients suffering from treatment-resistant schizophrenia using the method of Repeat-Primed PCR, we reported here that no HRE was detected in the patients of Chinese Han.

  6. Defining the association of TMEM106B variants among frontotemporal lobar degeneration patients with GRN mutations and C9orf72 repeat expansions.

    Science.gov (United States)

    Lattante, Serena; Le Ber, Isabelle; Galimberti, Daniela; Serpente, Maria; Rivaud-Péchoux, Sophie; Camuzat, Agnès; Clot, Fabienne; Fenoglio, Chiara; Scarpini, Elio; Brice, Alexis; Kabashi, Edor

    2014-11-01

    TMEM106B was identified as a risk factor for frontotemporal lobar degeneration (FTD) with TAR DNA-binding protein 43 kDa inclusions. It has been reported that variants in this gene are genetic modifiers of the disease and that this association is stronger in patients carrying a GRN mutation or a pathogenic expansion in chromosome 9 open reading frame 72 (C9orf72) gene. Here, we investigated the contribution of TMEM106B polymorphisms in cohorts of FTD and FTD with amyotrophic lateral sclerosis patients from France and Italy. Patients carrying the C9orf72 expansion (n = 145) and patients with GRN mutations (n = 76) were compared with a group of FTD patients (n = 384) negative for mutations and to a group of healthy controls (n = 552). In our cohorts, the presence of the C9orf72 expansion did not correlate with TMEM106B genotypes but the association was very strong in individuals with pathogenic GRN mutations (p = 9.54 × 10(-6)). Our data suggest that TMEM106B genotypes differ in FTD patient cohorts and strengthen the protective role of TMEM106B in GRN carriers. Further studies are needed to determine whether TMEM106B polymorphisms are associated with other genetic causes for FTD, including C9orf72 repeat expansions. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. FMR1 CGG repeat expansion mutation detection and linked haplotype analysis for reliable and accurate preimplantation genetic diagnosis of fragile X syndrome.

    Science.gov (United States)

    Rajan-Babu, Indhu-Shree; Lian, Mulias; Cheah, Felicia S H; Chen, Min; Tan, Arnold S C; Prasath, Ethiraj B; Loh, Seong Feei; Chong, Samuel S

    2017-07-19

    Fragile X mental retardation 1 (FMR1) full-mutation expansion causes fragile X syndrome. Trans-generational fragile X syndrome transmission can be avoided by preimplantation genetic diagnosis (PGD). We describe a robust PGD strategy that can be applied to virtually any couple at risk of transmitting fragile X syndrome. This novel strategy utilises whole-genome amplification, followed by triplet-primed polymerase chain reaction (TP-PCR) for robust detection of expanded FMR1 alleles, in parallel with linked multi-marker haplotype analysis of 13 highly polymorphic microsatellite markers located within 1 Mb of the FMR1 CGG repeat, and the AMELX/Y dimorphism for gender identification. The assay was optimised and validated on single lymphoblasts isolated from fragile X reference cell lines, and applied to a simulated PGD case and a clinical in vitro fertilisation (IVF)-PGD case. In the simulated PGD case, definitive diagnosis of the expected results was achieved for all 'embryos'. In the clinical IVF-PGD case, delivery of a healthy baby girl was achieved after transfer of an expansion-negative blastocyst. FMR1 TP-PCR reliably detects presence of expansion mutations and obviates reliance on informative normal alleles for determining expansion status in female embryos. Together with multi-marker haplotyping and gender determination, misdiagnosis and diagnostic ambiguity due to allele dropout is minimised, and couple-specific assay customisation can be avoided.

  8. The expansion of heterochromatin blocks in rye reflects the co-amplification of tandem repeats and adjacent transposable elements

    Czech Academy of Sciences Publication Activity Database

    Evtushenko, E.V.; Levitsky, V.G.; Elisafenko, E.A.; Gunbin, K.V.; Belousov, A.I.; Šafář, Jan; Doležel, Jaroslav; Vershinin, A.V.

    2016-01-01

    Roč. 17, MAY 4 (2016), s. 337 ISSN 1471-2164 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Tandem repeats * Transposable elements * Subtelomeric heterochromatin Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.729, year: 2016

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

    Directory of Open Access Journals (Sweden)

    Guray Kuzu

    2016-07-01

    Full Text Available 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.

  10. Exploration of noncoding sequences in metagenomes.

    Directory of Open Access Journals (Sweden)

    Fabián Tobar-Tosse

    Full Text Available Environment-dependent genomic features have been defined for different metagenomes, whose genes and their associated processes are related to specific environments. Identification of ORFs and their functional categories are the most common methods for association between functional and environmental features. However, this analysis based on finding ORFs misses noncoding sequences and, therefore, some metagenome regulatory or structural information could be discarded. In this work we analyzed 23 whole metagenomes, including coding and noncoding sequences using the following sequence patterns: (G+C content, Codon Usage (Cd, Trinucleotide Usage (Tn, and functional assignments for ORF prediction. Herein, we present evidence of a high proportion of noncoding sequences discarded in common similarity-based methods in metagenomics, and the kind of relevant information present in those. We found a high density of trinucleotide repeat sequences (TRS in noncoding sequences, with a regulatory and adaptive function for metagenome communities. We present associations between trinucleotide values and gene function, where metagenome clustering correlate with microorganism adaptations and kinds of metagenomes. We propose here that noncoding sequences have relevant information to describe metagenomes that could be considered in a whole metagenome analysis in order to improve their organization, classification protocols, and their relation with the environment.

  11. The complete chloroplast genome sequence of Mahonia bealei (Berberidaceae) reveals a significant expansion of the inverted repeat and phylogenetic relationship with other angiosperms.

    Science.gov (United States)

    Ma, Ji; Yang, Bingxian; Zhu, Wei; Sun, Lianli; Tian, Jingkui; Wang, Xumin

    2013-10-10

    Mahonia bealei (Berberidaceae) is a frequently-used traditional Chinese medicinal plant with efficient anti-inflammatory ability. This plant is one of the sources of berberine, a new cholesterol-lowering drug with anti-diabetic activity. We have sequenced the complete nucleotide sequence of the chloroplast (cp) genome of M. bealei. The complete cp genome of M. bealei is 164,792 bp in length, and has a typical structure with large (LSC 73,052 bp) and small (SSC 18,591 bp) single-copy regions separated by a pair of inverted repeats (IRs 36,501 bp) of large size. The Mahonia cp genome contains 111 unique genes and 39 genes are duplicated in the IR regions. The gene order and content of M. bealei are almost unarranged which is consistent with the hypothesis that large IRs stabilize cp genome and reduce gene loss-and-gain probabilities during evolutionary process. A large IR expansion of over 12 kb has occurred in M. bealei, 15 genes (rps19, rpl22, rps3, rpl16, rpl14, rps8, infA, rpl36, rps11, petD, petB, psbH, psbN, psbT and psbB) have expanded to have an additional copy in the IRs. The IR expansion rearrangement occurred via a double-strand DNA break and subsequence repair, which is different from the ordinary gene conversion mechanism. Repeat analysis identified 39 direct/inverted repeats 30 bp or longer with a sequence identity ≥ 90%. Analysis also revealed 75 simple sequence repeat (SSR) loci and almost all are composed of A or T, contributing to a distinct bias in base composition. Comparison of protein-coding sequences with ESTs reveals 9 putative RNA edits and 5 of them resulted in non-synonymous modifications in rpoC1, rps2, rps19 and ycf1. Phylogenetic analysis using maximum parsimony (MP) and maximum likelihood (ML) was performed on a dataset composed of 65 protein-coding genes from 25 taxa, which yields an identical tree topology as previous plastid-based trees, and provides strong support for the sister relationship between Ranunculaceae and Berberidaceae

  12. Noncoding Elements: Evolution and Epigenetic Regulation

    KAUST Repository

    Seridi, Loqmane

    2016-03-09

    When the human genome project was completed, it revealed a surprising result. 98% of the genome did not code for protein of which more than 50% are repeats— later known as ”Junk DNA”. However, comparative genomics unveiled that many noncoding elements are evolutionarily constrained; thus luckily to have a role in genome stability and regulation. Though, their exact functions remained largely unknown. Several large international consortia such as the Functional Annotation of Mammalian Genomes (FANTOM) and the Encyclopedia of DNA Elements (ENCODE) were set to understand the structure and the regulation of the genome. Specifically, these endeavors aim to measure and reveal the transcribed components and functional elements of the genome. One of the most the striking findings of these efforts is that most of the genome is transcribed, including non-conserved noncoding elements and repeat elements. Specifically, we investigated the evolution and epigenetic properties of noncoding elements. 1. We compared genomes of evolutionarily distant species and showed the ubiquity of constrained noncoding elements in metazoa. 2. By integrating multi-omic data (such as transcriptome, nucleosome profiling, histone modifications), I conducted a comprehensive analysis of epigenetic properties (chromatin states) of conserved noncoding elements in insects. We showed that those elements have distinct and protective sequence features, undergo dynamic epigenetic regulation, and appear to be associated with the structural components of the chromatin, replication origins, and nuclear matrix. 3. I focused on the relationship between enhancers and repetitive elements. Using Cap Analysis of Gene Expression (CAGE) and RNASeq, I compiled a full catalog of active enhancers (a class of noncoding elements) during myogenesis of human primary cells of healthy donors and donors affected by Duchenne muscular dystrophy (DMD). Comparing the two time-courses, a significant change in the epigenetic

  13. NONCODE v2.0: decoding the non-coding.

    Science.gov (United States)

    He, Shunmin; Liu, Changning; Skogerbø, Geir; Zhao, Haitao; Wang, Jie; Liu, Tao; Bai, Baoyan; Zhao, Yi; Chen, Runsheng

    2008-01-01

    The NONCODE database is an integrated knowledge database designed for the analysis of non-coding RNAs (ncRNAs). Since NONCODE was first released 3 years ago, the number of known ncRNAs has grown rapidly, and there is growing recognition that ncRNAs play important regulatory roles in most organisms. In the updated version of NONCODE (NONCODE v2.0), the number of collected ncRNAs has reached 206 226, including a wide range of microRNAs, Piwi-interacting RNAs and mRNA-like ncRNAs. The improvements brought to the database include not only new and updated ncRNA data sets, but also an incorporation of BLAST alignment search service and access through our custom UCSC Genome Browser. NONCODE can be found under http://www.noncode.org or http://noncode.bioinfo.org.cn.

  14. Complete plastid genome sequencing of Trochodendraceae reveals a significant expansion of the inverted repeat and suggests a Paleogene divergence between the two extant species.

    Directory of Open Access Journals (Sweden)

    Yan-xia Sun

    Full Text Available The early-diverging eudicot order Trochodendrales contains only two monospecific genera, Tetracentron and Trochodendron. Although an extensive fossil record indicates that the clade is perhaps 100 million years old and was widespread throughout the Northern Hemisphere during the Paleogene and Neogene, the two extant genera are both narrowly distributed in eastern Asia. Recent phylogenetic analyses strongly support a clade of Trochodendrales, Buxales, and Gunneridae (core eudicots, but complete plastome analyses do not resolve the relationships among these groups with strong support. However, plastid phylogenomic analyses have not included data for Tetracentron. To better resolve basal eudicot relationships and to clarify when the two extant genera of Trochodendrales diverged, we sequenced the complete plastid genome of Tetracentron sinense using Illumina technology. The Tetracentron and Trochodendron plastomes possess the typical gene content and arrangement that characterize most angiosperm plastid genomes, but both genomes have the same unusual ∼4 kb expansion of the inverted repeat region to include five genes (rpl22, rps3, rpl16, rpl14, and rps8 that are normally found in the large single-copy region. Maximum likelihood analyses of an 83-gene, 88 taxon angiosperm data set yield an identical tree topology as previous plastid-based trees, and moderately support the sister relationship between Buxaceae and Gunneridae. Molecular dating analyses suggest that Tetracentron and Trochodendron diverged between 44-30 million years ago, which is congruent with the fossil record of Trochodendrales and with previous estimates of the divergence time of these two taxa. We also characterize 154 simple sequence repeat loci from the Tetracentron sinense and Trochodendron aralioides plastomes that will be useful in future studies of population genetic structure for these relict species, both of which are of conservation concern.

  15. JPH3 Repeat Expansions Cause a Progressive Akinetic-Rigid Syndrome with Severe Dementia and Putaminal Rim in a Five-Generation African-American Family

    Science.gov (United States)

    Schneider, Susanne A.; Marshall, Kate E.; Xiao, Jianfeng; LeDoux, Mark S.

    2012-01-01

    We report the clinical, neuropsychological, genetic and radiological features of a large five-generation African-American kindred from the southern United States presenting with a progressive akinetic-rigid syndrome and severe dementia, but clinically insignificant chorea, due to mutations in JPH3. Overt disease onset was in the mid-twenties to late thirties with cognitive decline, REM sleep disturbance or psychiatric features, followed by development of a levodopa-unresponsive akinetic-rigid motor syndrome. Dystonia and myoclonus were present in some subjects. A bedridden, non-verbal severely akinetic-rigid state developed within 10 to 15 years after onset. CTG repeat expansions ranged from 47 to 53. Imaging revealed generalized cerebral atrophy with severe striatal involvement and putaminal rim hyperintensity. Analysis of our kindred indicates that JPH3 mutations should be considered in the differential diagnosis of early-onset dementia and hypokinetic-rigid syndromes in individuals of African descent. Moreover, chorea may not be overtly manifest at presentation or during significant parts of the disease course. PMID:22447335

  16. Lack of expansion of triplet repeats in the FMR1, FRAXE, and FRAXF loci in male multiplex families with autism and pervasive developmental disorders

    Energy Technology Data Exchange (ETDEWEB)

    Holden, J.J.A.; Julien-Inalsingh, C. [Queen`s Univ., Kingston (Canada); Wing, M. [Ongwanada Resource Centre, Kingston (Canada)] [and others

    1996-08-09

    Sib, twin, and family studies have shown that a genetic cause exists in many cases of autism, with a portion of cases associated with a fragile X chromosome. Three folate-sensitive fragile sites in the Xq27{r_arrow}Xq28 region have been cloned and found to have polymorphic trinucleotide repeats at the respective sites; these repeats are amplified and methylated in individuals who are positive for the different fragile sites. We have tested affected boys and their mothers from 19 families with two autistic/PDD boys for amplification and/or instability of the triplet repeats at these loci and concordance of inheritance of alleles by affected brothers. In all cases, the triplet repeat numbers were within the normal range, with no individuals having expanded or premutation-size alleles. For each locus, there was no evidence for an increased frequency of concordance, indicating that mutations within these genes are unlikely to be responsible for the autistic/PDD phenotypes in the affected boys. Thus, we think it is important to retest those autistic individuals who were cytogenetically positive for a fragile X chromosome, particularly cases where there is no family history of the fragile X syndrome, using the more accurate DNA-based testing procedures. 29 refs., 1 fig., 1 tab.

  17. Repeated range expansions and inter-/postglacial recolonization routes of Sargentodoxa cuneata (Oliv.) Rehd. et Wils. (Lardizabalaceae) in subtropical China revealed by chloroplast phylogeography.

    Science.gov (United States)

    Tian, Shuang; Lei, Shu-Qing; Hu, Wan; Deng, Ling-Li; Li, Bo; Meng, Qing-Lin; Soltis, Douglas E; Soltis, Pamela S; Fan, Deng-Mei; Zhang, Zhi-Yong

    2015-04-01

    Most plant phylogeographic studies in subtropical China have stressed the importance of multiple refugia and limited admixture among refugia. Little attention has been paid to range expansion and recolonization routes in this region. In this study, we implemented a phylogeographic survey on Sargentodoxa cuneata, a widespread woody deciduous climber in subtropical China to determine if it conforms to the expansion-contraction (EC) model during the Pleistocene. Sequence variation of two chloroplast intergenic spacers (IGSs) in 369 individuals from 54 populations of S. cuneata was examined. Twenty-six chloroplast haplotypes were recovered. One of these (H5) occurred across the range of S. cuneata and was absent from only 13 populations. Sixteen of the 26 haplotypes were connected to H5 by one mutation and displayed a star-like pattern in the haplotype network. All chloroplast haplotypes clustered into two lineages (A and B) in a Bayesian tree, and most haplotypes (18 out of 26) originated during the mid-Pleistocene (0.63-1.07Ma). Demographic analyses detected a recent range expansion that occurred at 95.98ka (CI: 61.7-112.53ka) for Lineage A. The genetic signature of an ancient range expansion after the Middle Pleistocene Transition (MPT) was also evident. Three recolonization routes were identified in subtropical China. The results suggest that temperate plants in subtropical China may conform to the EC model to some extent. However, the genetic signature from multiple historical processes may complicate the phylogeographic patterns of organisms in the region due to the mild Pleistocene climate. This study provides a new perspective for understanding the evolutionary history of temperate plants in subtropical China. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Mechanism of Repeat-Associated MicroRNAs in Fragile X Syndrome

    Directory of Open Access Journals (Sweden)

    Karen Kelley

    2012-01-01

    Full Text Available The majority of the human genome is comprised of non-coding DNA, which frequently contains redundant microsatellite-like trinucleotide repeats. Many of these trinucleotide repeats are involved in triplet repeat expansion diseases (TREDs such as fragile X syndrome (FXS. After transcription, the trinucleotide repeats can fold into RNA hairpins and are further processed by Dicer endoribonuclases to form microRNA (miRNA-like molecules that are capable of triggering targeted gene-silencing effects in the TREDs. However, the function of these repeat-associated miRNAs (ramRNAs is unclear. To solve this question, we identified the first native ramRNA in FXS and successfully developed a transgenic zebrafish model for studying its function. Our studies showed that ramRNA-induced DNA methylation of the FMR1 5′-UTR CGG trinucleotide repeat expansion is responsible for both pathological and neurocognitive characteristics linked to the transcriptional FMR1 gene inactivation and the deficiency of its protein product FMRP. FMRP deficiency often causes synapse deformity in the neurons essential for cognition and memory activities, while FMR1 inactivation augments metabotropic glutamate receptor (mGluR-activated long-term depression (LTD, leading to abnormal neuronal responses in FXS. Using this novel animal model, we may further dissect the etiological mechanisms of TREDs, with the hope of providing insights into new means for therapeutic intervention.

  19. Impact of Noncoding Satellite Repeats on Pancreatic Cancer Metastasis

    Science.gov (United States)

    2015-11-01

    that certain HIV RT inhibitors ( ddC ) could block the generation of HSATII DNA/RNA hybrids, which had anti-cancer effects in 3D and in xenografts (see...effects in 3D and xenografts compared to 2D culture. Indeed, we find that using the RT inhibitor ddC or using HSATII sequence specific locked...Fig. 5: NRTI ddC differential effect in SW620 cell line grown in (A) 2D vs (B) 3D. NRTI ddC with significant reduction in SW620 xenograft (C

  20. Changes in expression of the long noncoding RNA FMR4 associate with altered gene expression during differentiation of human neural precursor cells

    Directory of Open Access Journals (Sweden)

    Veronica Julia Peschansky

    2015-08-01

    Full Text Available CGG repeat expansions in the Fragile X mental retardation 1 (FMR1 gene are responsible for a family of associated disorders characterized by either intellectual disability and autism (Fragile X Syndrome, FXS, or adult-onset neurodegeneration (Fragile X-associated Tremor/Ataxia Syndrome, FXTAS. However, the FMR1 locus is complex and encodes several long noncoding RNAs (lncRNAs, whose expression is altered by repeat expansion mutations.The role of these lncRNAs is thus far unknown; therefore we investigated the functionality of FMR4, which we previously identified. Full-length expansions of the FMR1 triplet repeat cause silencing of both FMR1 and FMR4, thus we are interested in potential loss-of-function that may add to phenotypic manifestation of FXS. Since the two transcripts do not exhibit cis-regulation of one another, we examined the potential for FMR4 to regulate target genes at distal genomic loci using gene expression microarrays. We identified FMR4-responsive genes, including the methyl-CpG-binding domain protein 4 (MBD4. Furthermore, we found that in differentiating human neural precursor cells (hNPCs, FMR4 expression is developmentally regulated in opposition to expression of both FMR1 (which is expected to share a bidirectional promoter with FMR4 and MBD4.We therefore propose that FMR4’s function is as a gene-regulatory lncRNA and that this transcript may function in normal development. Closer examination of FMR4 increases our understanding of the role of regulatory lncRNA and the consequences of FMR1 repeat expansions.

  1. Panning for Long Noncoding RNAs

    Directory of Open Access Journals (Sweden)

    Li Yang

    2013-02-01

    Full Text Available The recent advent of high-throughput approaches has revealed widespread transcription of the human genome, leading to a new appreciation of transcription regulation, especially from noncoding regions. Distinct from most coding and small noncoding RNAs, long noncoding RNAs (lncRNAs are generally expressed at low levels, are less conserved and lack protein-coding capacity. These intrinsic features of lncRNAs have not only hampered their full annotation in the past several years, but have also generated controversy concerning whether many or most of these lncRNAs are simply the result of transcriptional noise. Here, we assess these intrinsic features that have challenged lncRNA discovery and further summarize recent progress in lncRNA discovery with integrated methodologies, from which new lessons and insights can be derived to achieve better characterization of lncRNA expression regulation. Full annotation of lncRNA repertoires and the implications of such annotation will provide a fundamental basis for comprehensive understanding of pervasive functions of lncRNAs in biological regulation.

  2. The Long Non-coding RNA HOTTIP Enhances Pancreatic Cancer Cell Proliferation, Survival and Migration

    Science.gov (United States)

    ABSTRACTHOTTIP is a long non-coding RNA (lncRNA) transcribed from the 5' tip of the HOXA locus and is associated with the polycomb repressor complex 2 (PRC2) and WD repeat containing protein 5 (WDR5)/mixed lineage leukemia 1 (MLL1) chromatin modifying complexes. HOTTIP is expres...

  3. Male sterility associated with overexpression of the noncoding hsrω ...

    Indian Academy of Sciences (India)

    Unknown

    interact with these noncoding transcripts, we examined the in situ ... reduced RNA-processing activities in the nucleus. (Lakhotia et al. 1999 ... This process was repeated for 10 generations. .... wild-type testes were distributed in the anterior part and along the ..... various nuclear RNA-processing proteins to protect them.

  4. Functional interrogation of non-coding DNA through CRISPR genome editing.

    Science.gov (United States)

    Canver, Matthew C; Bauer, Daniel E; Orkin, Stuart H

    2017-05-15

    Methodologies to interrogate non-coding regions have lagged behind coding regions despite comprising the vast majority of the genome. However, the rapid evolution of clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editing has provided a multitude of novel techniques for laboratory investigation including significant contributions to the toolbox for studying non-coding DNA. CRISPR-mediated loss-of-function strategies rely on direct disruption of the underlying sequence or repression of transcription without modifying the targeted DNA sequence. CRISPR-mediated gain-of-function approaches similarly benefit from methods to alter the targeted sequence through integration of customized sequence into the genome as well as methods to activate transcription. Here we review CRISPR-based loss- and gain-of-function techniques for the interrogation of non-coding DNA. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Translation of dipeptide repeat proteins from the C9ORF72 expanded repeat is associated with cellular stress.

    Science.gov (United States)

    Sonobe, Yoshifumi; Ghadge, Ghanashyam; Masaki, Katsuhisa; Sendoel, Ataman; Fuchs, Elaine; Roos, Raymond P

    2018-08-01

    Expansion of a hexanucleotide repeat (HRE), GGGGCC, in the C9ORF72 gene is recognized as the most common cause of familial amyotrophic lateral sclerosis (FALS), frontotemporal dementia (FTD) and ALS-FTD, as well as 5-10% of sporadic ALS. Despite the location of the HRE in the non-coding region (with respect to the main C9ORF72 gene product), dipeptide repeat proteins (DPRs) that are thought to be toxic are translated from the HRE in all three reading frames from both the sense and antisense transcript. Here, we identified a CUG that has a good Kozak consensus sequence as the translation initiation codon. Mutation of this CTG significantly suppressed polyglycine-alanine (GA) translation. GA was translated when the G 4 C 2 construct was placed as the second cistron in a bicistronic construct. CRISPR/Cas9-induced knockout of a non-canonical translation initiation factor, eIF2A, impaired GA translation. Transfection of G 4 C 2 constructs induced an integrated stress response (ISR), while triggering the ISR led to a continuation of translation of GA with a decline in conventional cap-dependent translation. These in vitro observations were confirmed in chick embryo neural cells. The findings suggest that DPRs translated from an HRE in C9ORF72 aggregate and lead to an ISR that then leads to continuing DPR production and aggregation, thereby creating a continuing pathogenic cycle. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Short tandem repeats in CdLS-causing genes: distribution and ...

    Indian Academy of Sciences (India)

    and SMC3, as all STRs for these genes fall in noncoding region only. ... This indicates that more repeated STRs are at the risk of replication ... patients versus controls. ... ing from a balance between slippage events and point mutations. Proc.

  7. Battles and hijacks: Noncoding transcription in plants

    KAUST Repository

    Ariel, Federico

    2015-06-01

    Noncoding RNAs have emerged as major components of the eukaryotic transcriptome. Genome-wide analyses revealed the existence of thousands of long noncoding RNAs (lncRNAs) in several plant species. Plant lncRNAs are transcribed by the plant-specific RNA polymerases Pol IV and Pol V, leading to transcriptional gene silencing, as well as by Pol II. They are involved in a wide range of regulatory mechanisms impacting on gene expression, including chromatin remodeling, modulation of alternative splicing, fine-tuning of miRNA activity, and the control of mRNA translation or accumulation. Recently, dual noncoding transcription by alternative RNA polymerases was implicated in epigenetic and chromatin conformation dynamics. This review integrates the current knowledge on the regulatory mechanisms acting through plant noncoding transcription. © 2015 Elsevier Ltd.

  8. Battles and hijacks: Noncoding transcription in plants

    KAUST Repository

    Ariel, Federico; Romero-Barrios, Natali; Jé gu, Teddy; Benhamed, Moussa; Crespi, Martin

    2015-01-01

    splicing, fine-tuning of miRNA activity, and the control of mRNA translation or accumulation. Recently, dual noncoding transcription by alternative RNA polymerases was implicated in epigenetic and chromatin conformation dynamics. This review integrates

  9. Noncoding RNAs in Cancer Medicine

    Directory of Open Access Journals (Sweden)

    Laura Cerchia

    2006-01-01

    Full Text Available Several signalling proteins involved in cell growth and differentiation represent attractive candidate targets for cancer diagnosis and/or therapy since they can act as oncogenes. Because of their high specificity and low immunogeneicity, using artificial small noncoding RNA (ncRNAs as therapeutics has recently become a highly promising and rapidly expanding field of interest. Indeed, ncRNAs may either interfere with RNA transcription, stability, translation or directly hamper the function of the targets by binding to their surface. The recent finding that the expression of several genes is under the control of small single-stranded regulatory RNAs, including miRNAs, makes these genes as appropriate targets for ncRNA gene silencing. Furthermore, another class of small ncRNA, aptamers, act as high-affinity ligands and potential antagonists of disease-associated proteins. We will review here the recent and innovative methods that have been developed and the possible applications of ncRNAs as inhibitors or tracers in cancer medicine.

  10. Systematic analysis of coding and noncoding DNA sequences using methods of statistical linguistics

    Science.gov (United States)

    Mantegna, R. N.; Buldyrev, S. V.; Goldberger, A. L.; Havlin, S.; Peng, C. K.; Simons, M.; Stanley, H. E.

    1995-01-01

    We compare the statistical properties of coding and noncoding regions in eukaryotic and viral DNA sequences by adapting two tests developed for the analysis of natural languages and symbolic sequences. The data set comprises all 30 sequences of length above 50 000 base pairs in GenBank Release No. 81.0, as well as the recently published sequences of C. elegans chromosome III (2.2 Mbp) and yeast chromosome XI (661 Kbp). We find that for the three chromosomes we studied the statistical properties of noncoding regions appear to be closer to those observed in natural languages than those of coding regions. In particular, (i) a n-tuple Zipf analysis of noncoding regions reveals a regime close to power-law behavior while the coding regions show logarithmic behavior over a wide interval, while (ii) an n-gram entropy measurement shows that the noncoding regions have a lower n-gram entropy (and hence a larger "n-gram redundancy") than the coding regions. In contrast to the three chromosomes, we find that for vertebrates such as primates and rodents and for viral DNA, the difference between the statistical properties of coding and noncoding regions is not pronounced and therefore the results of the analyses of the investigated sequences are less conclusive. After noting the intrinsic limitations of the n-gram redundancy analysis, we also briefly discuss the failure of the zeroth- and first-order Markovian models or simple nucleotide repeats to account fully for these "linguistic" features of DNA. Finally, we emphasize that our results by no means prove the existence of a "language" in noncoding DNA.

  11. The expanding universe of noncoding RNAs.

    Science.gov (United States)

    Hannon, G J; Rivas, F V; Murchison, E P; Steitz, J A

    2006-01-01

    The 71st Cold Spring Harbor Symposium on Quantitative Biology celebrated the numerous and expanding roles of regulatory RNAs in systems ranging from bacteria to mammals. It was clearly evident that noncoding RNAs are undergoing a renaissance, with reports of their involvement in nearly every cellular process. Previously known classes of longer noncoding RNAs were shown to function by every possible means-acting catalytically, sensing physiological states through adoption of complex secondary and tertiary structures, or using their primary sequences for recognition of target sites. The many recently discovered classes of small noncoding RNAs, generally less than 35 nucleotides in length, most often exert their effects by guiding regulatory complexes to targets via base-pairing. With the ability to analyze the RNA products of the genome in ever greater depth, it has become clear that the universe of noncoding RNAs may extend far beyond the boundaries we had previously imagined. Thus, as much as the Symposium highlighted exciting progress in the field, it also revealed how much farther we must go to understand fully the biological impact of noncoding RNAs.

  12. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    evaluating the deployment repeatability builds upon the testing or analysis of deployment kinematics (Chapter 6) and adds repetition. Introduction...material yield or failure during a test. For the purposes of this chapter, zero shift will refer to permanent changes in the structure, while reversible ...the content of other chapters in this book: Gravity Compensation (Chapter 4) and Deployment Kinematics and Dynamics (Chapter 6). Repeating the

  13. Thermal expansion

    International Nuclear Information System (INIS)

    Yun, Y.

    2015-01-01

    Thermal expansion of fuel pellet is an important property which limits the lifetime of the fuels in reactors, because it affects both the pellet and cladding mechanical interaction and the gap conductivity. By fitting a number of available measured data, recommended equations have been presented and successfully used to estimate thermal expansion coefficient of the nuclear fuel pellet. However, due to large scatter of the measured data, non-consensus data have been omitted in formulating the equations. Also, the equation is strongly governed by the lack of appropriate experimental data. For those reasons, it is important to develop theoretical methodologies to better describe thermal expansion behaviour of nuclear fuel. In particular, first-principles and molecular dynamics simulations have been certainly contributed to predict reliable thermal expansion without fitting the measured data. Furthermore, the two theoretical techniques have improved on understanding the change of fuel dimension by describing the atomic-scale processes associated with lattice expansion in the fuels. (author)

  14. Long Noncoding RNAs in Lung Cancer.

    Science.gov (United States)

    Roth, Anna; Diederichs, Sven

    2016-01-01

    Despite great progress in research and treatment options, lung cancer remains the leading cause of cancer-related deaths worldwide. Oncogenic driver mutations in protein-encoding genes were defined and allow for personalized therapies based on genetic diagnoses. Nonetheless, diagnosis of lung cancer mostly occurs at late stages, and chronic treatment is followed by a fast onset of chemoresistance. Hence, there is an urgent need for reliable biomarkers and alternative treatment options. With the era of whole genome and transcriptome sequencing technologies, long noncoding RNAs emerged as a novel class of versatile, functional RNA molecules. Although for most of them the mechanism of action remains to be defined, accumulating evidence confirms their involvement in various aspects of lung tumorigenesis. They are functional on the epigenetic, transcriptional, and posttranscriptional level and are regulators of pathophysiological key pathways including cell growth, apoptosis, and metastasis. Long noncoding RNAs are gaining increasing attention as potential biomarkers and a novel class of druggable molecules. It has become clear that we are only beginning to understand the complexity of tumorigenic processes. The clinical integration of long noncoding RNAs in terms of prognostic and predictive biomarker signatures and additional cancer targets could provide a chance to increase the therapeutic benefit. Here, we review the current knowledge about the expression, regulation, biological function, and clinical relevance of long noncoding RNAs in lung cancer.

  15. Non-Coding RNAs in Hodgkin Lymphoma

    Directory of Open Access Journals (Sweden)

    Anna Cordeiro

    2017-05-01

    Full Text Available MicroRNAs (miRNAs, small non-coding RNAs that regulate gene expression by binding to the 3’-UTR of their target genes, can act as oncogenes or tumor suppressors. Recently, other types of non-coding RNAs—piwiRNAs and long non-coding RNAs—have also been identified. Hodgkin lymphoma (HL is a B cell origin disease characterized by the presence of only 1% of tumor cells, known as Hodgkin and Reed-Stenberg (HRS cells, which interact with the microenvironment to evade apoptosis. Several studies have reported specific miRNA signatures that can differentiate HL lymph nodes from reactive lymph nodes, identify histologic groups within classical HL, and distinguish HRS cells from germinal center B cells. Moreover, some signatures are associated with survival or response to chemotherapy. Most of the miRNAs in the signatures regulate genes related to apoptosis, cell cycle arrest, or signaling pathways. Here we review findings on miRNAs in HL, as well as on other non-coding RNAs.

  16. Bleomycin Can Cleave an Oncogenic Noncoding RNA.

    Science.gov (United States)

    Angelbello, Alicia J; Disney, Matthew D

    2018-01-04

    Noncoding RNAs are pervasive in cells and contribute to diseases such as cancer. A question in biomedical research is whether noncoding RNAs are targets of medicines. Bleomycin is a natural product that cleaves DNA; however, it is known to cleave RNA in vitro. Herein, an in-depth analysis of the RNA cleavage preferences of bleomycin A5 is presented. Bleomycin A5 prefers to cleave RNAs with stretches of AU base pairs. Based on these preferences and bioinformatic analysis, the microRNA-10b hairpin precursor was identified as a potential substrate for bleomycin A5. Both in vitro and cellular experiments demonstrated cleavage. Importantly, chemical cleavage by bleomycin A5 in the microRNA-10b hairpin precursors occurred near the Drosha and Dicer enzymatic processing sites and led to destruction of the microRNA. Evidently, oncogenic noncoding RNAs can be considered targets of cancer medicines and might elicit their pharmacological effects by targeting noncoding RNA. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Noncoding sequence classification based on wavelet transform analysis: part I

    Science.gov (United States)

    Paredes, O.; Strojnik, M.; Romo-Vázquez, R.; Vélez Pérez, H.; Ranta, R.; Garcia-Torales, G.; Scholl, M. K.; Morales, J. A.

    2017-09-01

    DNA sequences in human genome can be divided into the coding and noncoding ones. Coding sequences are those that are read during the transcription. The identification of coding sequences has been widely reported in literature due to its much-studied periodicity. Noncoding sequences represent the majority of the human genome. They play an important role in gene regulation and differentiation among the cells. However, noncoding sequences do not exhibit periodicities that correlate to their functions. The ENCODE (Encyclopedia of DNA elements) and Epigenomic Roadmap Project projects have cataloged the human noncoding sequences into specific functions. We study characteristics of noncoding sequences with wavelet analysis of genomic signals.

  18. Repeating Marx

    DEFF Research Database (Denmark)

    Fuchs, Christian; Monticelli, Lara

    2018-01-01

    This introduction sets out the context of the special issue “Karl Marx @ 200: Debating Capitalism & Perspectives for the Future of Radical Theory”, which was published on the occasion of Marx’s bicentenary on 5 May 2018. First, we give a brief overview of contemporary capitalism’s development...... and its crises. Second, we argue that it is important to repeat Marx today. Third, we reflect on lessons learned from 200 years of struggles for alternatives to capitalism. Fourth, we give an overview of the contributions in this special issue. Taken together, the contributions in this special issue show...... that Marx’s theory and politics remain key inspirations for understanding exploitation and domination in 21st-century society and for struggles that aim to overcome these phenomena and establishing a just and fair society. We need to repeat Marx today....

  19. Deployment Repeatability

    Science.gov (United States)

    2016-08-31

    large cohort of trials to spot unusual cases. However, deployment repeatability is inherently a nonlinear phenomenon, which makes modeling difficult...and GEMS tip position were both tracked during ground testing by a laser target tracking system. Earlier SAILMAST testing in 2005 [8] used...recalls the strategy used by SRTM, where a constellation of lights was installed at the tip of the boom and a modified star tracker was used to track tip

  20. Discrepancies in reporting the CAG repeat lengths for Huntington's disease

    DEFF Research Database (Denmark)

    Quarrell, Oliver W; Handley, Olivia; O'Donovan, Kirsty

    2011-01-01

    Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original...

  1. Expansion dynamics

    International Nuclear Information System (INIS)

    Knoll, J.

    1985-10-01

    A quantum dynamical model is suggested which describes the expansion and disassembly phase of highly excited compounds formed in energetic heavy-ion collisions. First applications in two space and one time dimensional model world are discussed and qualitatively compared to standard freeze-out concepts. (orig.)

  2. expansion method

    Indian Academy of Sciences (India)

    of a system under investigation is to model the system in terms of some ... The organization of the paper is as follows: In §2, a brief account of the (G /G)- expansion ...... It is interesting to note that from the general results, one can easily recover.

  3. Long Noncoding RNA Identification: Comparing Machine Learning Based Tools for Long Noncoding Transcripts Discrimination

    Directory of Open Access Journals (Sweden)

    Siyu Han

    2016-01-01

    Full Text Available Long noncoding RNA (lncRNA is a kind of noncoding RNA with length more than 200 nucleotides, which aroused interest of people in recent years. Lots of studies have confirmed that human genome contains many thousands of lncRNAs which exert great influence over some critical regulators of cellular process. With the advent of high-throughput sequencing technologies, a great quantity of sequences is waiting for exploitation. Thus, many programs are developed to distinguish differences between coding and long noncoding transcripts. Different programs are generally designed to be utilised under different circumstances and it is sensible and practical to select an appropriate method according to a certain situation. In this review, several popular methods and their advantages, disadvantages, and application scopes are summarised to assist people in employing a suitable method and obtaining a more reliable result.

  4. Long Non-Coding RNA in Cancer

    Directory of Open Access Journals (Sweden)

    Damjan Glavač

    2013-02-01

    Full Text Available Long non-coding RNAs (lncRNAs are pervasively transcribed in the genome and are emerging as new players in tumorigenesis due to their various functions in transcriptional, posttranscriptional and epigenetic mechanisms of gene regulation. LncRNAs are deregulated in a number of cancers, demonstrating both oncogenic and tumor suppressive roles, thus suggesting their aberrant expression may be a substantial contributor in cancer development. In this review, we will summarize their emerging role in human cancer and discuss their perspectives in diagnostics as potential biomarkers.

  5. An expanding universe of noncoding RNAs.

    Science.gov (United States)

    Storz, Gisela

    2002-05-17

    Noncoding RNAs (ncRNAs) have been found to have roles in a great variety of processes, including transcriptional regulation, chromosome replication, RNA processing and modification, messenger RNA stability and translation, and even protein degradation and translocation. Recent studies indicate that ncRNAs are far more abundant and important than initially imagined. These findings raise several fundamental questions: How many ncRNAs are encoded by a genome? Given the absence of a diagnostic open reading frame, how can these genes be identified? How can all the functions of ncRNAs be elucidated?

  6. Non-Coding RNAs and Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Cristina Vallone

    2018-03-01

    Full Text Available Non-coding RNAs (ncRNAs are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs has also been included in cancer studies. Studies on the relation between endometrial cancer (EC and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs, transfer RNAs (tRNAs, ribosomal RNAs (rRNAs, antisense RNAs (asRNAs, small nuclear RNAs (snRNAs, Piwi-interacting RNAs (piRNAs, small nucleolar RNAs (snoRNAs, competing endogenous RNAs (ceRNAs, lncRNAs, and long intergenic ncRNAs (lincRNAs have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular.

  7. Non-coding RNA in Deinococcus radiodurans

    International Nuclear Information System (INIS)

    Chen Zhongzhong; Wang Liangyan; Lin Jun; Tian Bing; Hua Yuejin

    2006-01-01

    Researches on DNA damage and repair pathways of Deinococcus radiodurans show its extreme resistance to ionizing radiation, ultraviolet radiation and reactive oxygen species. Non-coding (ncRNA) RNAs are involved in a variety of processes such as transcriptional regulations, RNA processing and modification, mRNA translation, protein transportation and stability. The conserved secondary structures of intergenic regions of Deinococcus radiodurans R1 were predicted using Stochastic Context Free Grammar (SCFG) scan strategy. Results showed that 28 ncRNA families were present in the non-coding regions of the genome of Deinococcus radiodurans R1. Among these families, IRE is the largest family, followed by Histone3, tRNA, SECIS. DicF, ctRNA-pGA1 and tmRNA are one discovered in bacteria. Results from the comparison with other organisms showed that these ncRNA can be applied to the study of biological function of Deinococcus radiodurans and supply reference for the further study of DNA damage and repair mechanisms of this bacterium. (authors)

  8. Long noncoding RNA in hematopoiesis and immunity.

    Science.gov (United States)

    Satpathy, Ansuman T; Chang, Howard Y

    2015-05-19

    Dynamic gene expression during cellular differentiation is tightly coordinated by transcriptional and post-transcriptional mechanisms. An emerging theme is the central role of long noncoding RNAs (lncRNAs) in the regulation of this specificity. Recent advances demonstrate that lncRNAs are expressed in a lineage-specific manner and control the development of several cell types in the hematopoietic system. Moreover, specific lncRNAs are induced to modulate innate and adaptive immune responses. lncRNAs can function via RNA-DNA, RNA-RNA, and RNA-protein target interactions. As a result, they affect several stages of gene regulation, including chromatin modification, mRNA biogenesis, and protein signaling. We discuss recent advances, future prospects, and challenges in understanding the roles of lncRNAs in immunity and immune-mediated diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Non-coding RNA networks in cancer.

    Science.gov (United States)

    Anastasiadou, Eleni; Jacob, Leni S; Slack, Frank J

    2018-01-01

    Thousands of unique non-coding RNA (ncRNA) sequences exist within cells. Work from the past decade has altered our perception of ncRNAs from 'junk' transcriptional products to functional regulatory molecules that mediate cellular processes including chromatin remodelling, transcription, post-transcriptional modifications and signal transduction. The networks in which ncRNAs engage can influence numerous molecular targets to drive specific cell biological responses and fates. Consequently, ncRNAs act as key regulators of physiological programmes in developmental and disease contexts. Particularly relevant in cancer, ncRNAs have been identified as oncogenic drivers and tumour suppressors in every major cancer type. Thus, a deeper understanding of the complex networks of interactions that ncRNAs coordinate would provide a unique opportunity to design better therapeutic interventions.

  10. The specificity of long noncoding RNA expression.

    Science.gov (United States)

    Gloss, Brian S; Dinger, Marcel E

    2016-01-01

    Over the last decade, long noncoding RNAs (lncRNAs) have emerged as a fundamental molecular class whose members play pivotal roles in the regulation of the genome. The observation of pervasive transcription of mammalian genomes in the early 2000s sparked a revolution in the understanding of information flow in eukaryotic cells and the incredible flexibility and dynamic nature of the transcriptome. As a molecular class, distinct loci yielding lncRNAs are set to outnumber those yielding mRNAs. However, like many important discoveries, the road leading to uncovering this diverse class of molecules that act through a remarkable repertoire of mechanisms, was not a straight one. The same characteristic that most distinguishes lncRNAs from mRNAs, i.e. their developmental-stage, tissue-, and cell-specific expression, was one of the major impediments to their discovery and recognition as potentially functional regulatory molecules. With growing numbers of lncRNAs being assigned to biological functions, the specificity of lncRNA expression is now increasingly recognized as a characteristic that imbues lncRNAs with great potential as biomarkers and for the development of highly targeted therapeutics. Here we review the history of lncRNA research and how technological advances and insight into biological complexity have gone hand-in-hand in shaping this revolution. We anticipate that as increasing numbers of these molecules, often described as the dark matter of the genome, are characterized and the structure-function relationship of lncRNAs becomes better understood, it may ultimately be feasible to decipher what these non-(protein)-coding genes encode. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Large scale analysis of small repeats via mining of the human genome

    NARCIS (Netherlands)

    van den Berg, I.; Bosnacki, D.; Hilbers, P.A.J.

    2009-01-01

    Small repetitive sequences, called tandem repeats, are abundant throughout the human genome, both in coding and in non-coding regions. Their role is still mostly unknown, but at least 20 of those repetitive sequences have been related to neurodegenerative disorders. The mutational process that is

  12. On the classification of long non-coding RNAs

    KAUST Repository

    Ma, Lina; Bajic, Vladimir B.; Zhang, Zhang

    2013-01-01

    Long non-coding RNAs (lncRNAs) have been found to perform various functions in a wide variety of important biological processes. To make easier interpretation of lncRNA functionality and conduct deep mining on these transcribed sequences

  13. Emerging properties and functional consequences of noncoding transcription

    DEFF Research Database (Denmark)

    Ard, Ryan; Allshire, Robin C; Marquardt, Sebastian

    2017-01-01

    specific lncRNAs, support grows for the notion that the act of transcription rather than the RNA product itself is functionally important in many cases. Indeed, this alternative mechanism might better explain how low-abundance lncRNAs transcribed from noncoding DNA function in organisms. Here, we highlight......Eukaryotic genomes are rich in transcription units encoding "long noncoding RNAs" (lncRNAs). The purpose of all this transcription is unclear since most lncRNAs are quickly targeted for destruction during synthesis or shortly thereafter. As debates continue over the functional significance of many...... some of the recently emerging features that distinguish coding from noncoding transcription and discuss how these differences might have important implications for the functional consequences of noncoding transcription....

  14. Hypoxic regulation of the noncoding genome and NEAT1

    Science.gov (United States)

    Choudhry, Hani

    2016-01-01

    Activation of hypoxia pathways is both associated with and contributes to an aggressive phenotype across multiple types of solid cancers. The regulation of gene transcription by hypoxia-inducible factor (HIF) is a key element in this response. HIF directly upregulates the expression of many hundreds of protein-coding genes, which act to both improve oxygen delivery and to reduce oxygen demand. However, it is now becoming apparent that many classes of noncoding RNAs are also regulated by hypoxia, with several (e.g. micro RNAs, long noncoding RNAs and antisense RNAs) under direct transcriptional regulation by HIF. These hypoxia-regulated, noncoding RNAs may act as effectors of the indirect response to HIF by acting on specific coding transcripts or by affecting generic RNA-processing pathways. In addition, noncoding RNAs may also act as modulators of the HIF pathway, either by integrating other physiological responses or, in the case of HIF-regulated, noncoding RNAs, by providing negative or positive feedback and feedforward loops that affect upstream or downstream components of the HIF cascade. These hypoxia-regulated, noncoding transcripts play important roles in the aggressive hypoxic phenotype observed in cancer. PMID:26590207

  15. Annotating pathogenic non-coding variants in genic regions.

    Science.gov (United States)

    Gelfman, Sahar; Wang, Quanli; McSweeney, K Melodi; Ren, Zhong; La Carpia, Francesca; Halvorsen, Matt; Schoch, Kelly; Ratzon, Fanni; Heinzen, Erin L; Boland, Michael J; Petrovski, Slavé; Goldstein, David B

    2017-08-09

    Identifying the underlying causes of disease requires accurate interpretation of genetic variants. Current methods ineffectively capture pathogenic non-coding variants in genic regions, resulting in overlooking synonymous and intronic variants when searching for disease risk. Here we present the Transcript-inferred Pathogenicity (TraP) score, which uses sequence context alterations to reliably identify non-coding variation that causes disease. High TraP scores single out extremely rare variants with lower minor allele frequencies than missense variants. TraP accurately distinguishes known pathogenic and benign variants in synonymous (AUC = 0.88) and intronic (AUC = 0.83) public datasets, dismissing benign variants with exceptionally high specificity. TraP analysis of 843 exomes from epilepsy family trios identifies synonymous variants in known epilepsy genes, thus pinpointing risk factors of disease from non-coding sequence data. TraP outperforms leading methods in identifying non-coding variants that are pathogenic and is therefore a valuable tool for use in gene discovery and the interpretation of personal genomes.While non-coding synonymous and intronic variants are often not under strong selective constraint, they can be pathogenic through affecting splicing or transcription. Here, the authors develop a score that uses sequence context alterations to predict pathogenicity of synonymous and non-coding genetic variants, and provide a web server of pre-computed scores.

  16. The origins and evolutionary history of human non-coding RNA regulatory networks.

    Science.gov (United States)

    Sherafatian, Masih; Mowla, Seyed Javad

    2017-04-01

    The evolutionary history and origin of the regulatory function of animal non-coding RNAs are not well understood. Lack of conservation of long non-coding RNAs and small sizes of microRNAs has been major obstacles in their phylogenetic analysis. In this study, we tried to shed more light on the evolution of ncRNA regulatory networks by changing our phylogenetic strategy to focus on the evolutionary pattern of their protein coding targets. We used available target databases of miRNAs and lncRNAs to find their protein coding targets in human. We were able to recognize evolutionary hallmarks of ncRNA targets by phylostratigraphic analysis. We found the conventional 3'-UTR and lesser known 5'-UTR targets of miRNAs to be enriched at three consecutive phylostrata. Firstly, in eukaryata phylostratum corresponding to the emergence of miRNAs, our study revealed that miRNA targets function primarily in cell cycle processes. Moreover, the same overrepresentation of the targets observed in the next two consecutive phylostrata, opisthokonta and eumetazoa, corresponded to the expansion periods of miRNAs in animals evolution. Coding sequence targets of miRNAs showed a delayed rise at opisthokonta phylostratum, compared to the 3' and 5' UTR targets of miRNAs. LncRNA regulatory network was the latest to evolve at eumetazoa.

  17. Poly-dipeptides encoded by the C9ORF72 repeats block global protein translation.

    Science.gov (United States)

    Kanekura, Kohsuke; Yagi, Takuya; Cammack, Alexander J; Mahadevan, Jana; Kuroda, Masahiko; Harms, Matthew B; Miller, Timothy M; Urano, Fumihiko

    2016-05-01

    The expansion of the GGGGCC hexanucleotide repeat in the non-coding region of the Chromosome 9 open-reading frame 72 (C9orf72) gene is the most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). This genetic alteration leads to the accumulation of five types of poly-dipeptides translated from the GGGGCC hexanucleotide repeat. Among these, poly-proline-arginine (poly-PR) and poly-glycine-arginine (poly-GR) peptides are known to be neurotoxic. However, the mechanisms of neurotoxicity associated with these poly-dipeptides are not clear. A proteomics approach identified a number of interacting proteins with poly-PR peptide, including mRNA-binding proteins, ribosomal proteins, translation initiation factors and translation elongation factors. Immunostaining of brain sections from patients with C9orf72 ALS showed that poly-GR was colocalized with a mRNA-binding protein, hnRNPA1. In vitro translation assays showed that poly-PR and poly-GR peptides made insoluble complexes with mRNA, restrained the access of translation factors to mRNA, and blocked protein translation. Our results demonstrate that impaired protein translation mediated by poly-PR and poly-GR peptides plays a role in neurotoxicity and reveal that the pathways altered by the poly-dipeptides-mRNA complexes are potential therapeutic targets for treatment of C9orf72 FTD/ALS. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. CRISPR/Cas9-mediated noncoding RNA editing in human cancers.

    Science.gov (United States)

    Yang, Jie; Meng, Xiaodan; Pan, Jinchang; Jiang, Nan; Zhou, Chengwei; Wu, Zhenhua; Gong, Zhaohui

    2018-01-02

    Cancer is characterized by multiple genetic and epigenetic alterations, including a higher prevalence of mutations of oncogenes and/or tumor suppressors. Mounting evidences have shown that noncoding RNAs (ncRNAs) are involved in the epigenetic regulation of cancer genes and their associated pathways. The clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9) system, a revolutionary genome-editing technology, has shed light on ncRNA-based cancer therapy. Here, we briefly introduce the classifications and mechanisms of CRISPR/Cas9 system. Importantly, we mainly focused on the applications of CRISPR/Cas9 system as a molecular tool for ncRNA (microRNA, long noncoding RNA and circular RNA, etc.) editing in human cancers, and the novel techniques that are based on CRISPR/Cas9 system. Additionally, the off-target effects and the corresponding solutions as well as the challenges toward CRISPR/Cas9 were also evaluated and discussed. Long- and short-ncRNAs have been employed as targets in precision oncology, and CRISPR/Cas9-mediated ncRNA editing may provide an excellent way to cure cancer.

  19. Structure of noncoding RNA is a determinant of function of RNA binding proteins in transcriptional regulation

    Directory of Open Access Journals (Sweden)

    Oyoshi Takanori

    2012-01-01

    Full Text Available Abstract The majority of the noncoding regions of mammalian genomes have been found to be transcribed to generate noncoding RNAs (ncRNAs, resulting in intense interest in their biological roles. During the past decade, numerous ncRNAs and aptamers have been identified as regulators of transcription. 6S RNA, first described as a ncRNA in E. coli, mimics an open promoter structure, which has a large bulge with two hairpin/stalk structures that regulate transcription through interactions with RNA polymerase. B2 RNA, which has stem-loops and unstructured single-stranded regions, represses transcription of mRNA in response to various stresses, including heat shock in mouse cells. The interaction of TLS (translocated in liposarcoma with CBP/p300 was induced by ncRNAs that bind to TLS, and this in turn results in inhibition of CBP/p300 histone acetyltransferase (HAT activity in human cells. Transcription regulator EWS (Ewing's sarcoma, which is highly related to TLS, and TLS specifically bind to G-quadruplex structures in vitro. The carboxy terminus containing the Arg-Gly-Gly (RGG repeat domains in these proteins are necessary for cis-repression of transcription activation and HAT activity by the N-terminal glutamine-rich domain. Especially, the RGG domain in the carboxy terminus of EWS is important for the G-quadruplex specific binding. Together, these data suggest that functions of EWS and TLS are modulated by specific structures of ncRNAs.

  20. Triplet repeat DNA structures and human genetic disease: dynamic ...

    Indian Academy of Sciences (India)

    Unknown

    formed at the loop-outs. [Sinden R R, Potaman V N, Oussatcheva E A, Pearson C E, Lyubchenko Y L and Shlyakhtenko L S 2002 Triplet repeat DNA structures .... 36–39. 40–121 Huntingtin/polyglutamine expansion. Spinocerebellar ataxia 1. SCA1. 6p23. (CAG)n. 6–44. –. 39–82 (pure) Ataxin-1/polyglutamine expansion.

  1. New technologies accelerate the exploration of non-coding RNAs in horticultural plants

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Degao; Mewalal, Ritesh; Hu, Rongbin; Tuskan, Gerald A.; Yang, Xiaohan

    2017-07-05

    Non-coding RNAs (ncRNAs), that is, RNAs not translated into proteins, are crucial regulators of a variety of biological processes in plants. While protein-encoding genes have been relatively well-annotated in sequenced genomes, accounting for a small portion of the genome space in plants, the universe of plant ncRNAs is rapidly expanding. Recent advances in experimental and computational technologies have generated a great momentum for discovery and functional characterization of ncRNAs. Here we summarize the classification and known biological functions of plant ncRNAs, review the application of next-generation sequencing (NGS) technology and ribosome profiling technology to ncRNA discovery in horticultural plants and discuss the application of new technologies, especially the new genome-editing tool clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) systems, to functional characterization of plant ncRNAs.

  2. Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells.

    Science.gov (United States)

    Burzio, Verónica A; Villota, Claudio; Villegas, Jaime; Landerer, Eduardo; Boccardo, Enrique; Villa, Luisa L; Martínez, Ronny; Lopez, Constanza; Gaete, Fancy; Toro, Viviana; Rodriguez, Ximena; Burzio, Luis O

    2009-06-09

    We reported the presence in human cells of a noncoding mitochondrial RNA that contains an inverted repeat (IR) of 815 nucleotides (nt) covalently linked to the 5' end of the mitochondrial 16S RNA (16S mtrRNA). The transcript contains a stem-loop structure and is expressed in human proliferating cells but not in resting cells. Here, we demonstrate that, in addition to this transcript, normal human proliferating cells in culture express 2 antisense mitochondrial transcripts. These transcripts also contain stem-loop structures but strikingly they are down-regulated in tumor cell lines and tumor cells present in 17 different tumor types. The differential expression of these transcripts distinguishes normal from tumor cells and might contribute a unique vision on cancer biology and diagnostics.

  3. Selective constraint on noncoding regions of hominid genomes.

    Directory of Open Access Journals (Sweden)

    Eliot C Bush

    2005-12-01

    Full Text Available An important challenge for human evolutionary biology is to understand the genetic basis of human-chimpanzee differences. One influential idea holds that such differences depend, to a large extent, on adaptive changes in gene expression. An important step in assessing this hypothesis involves gaining a better understanding of selective constraint on noncoding regions of hominid genomes. In noncoding sequence, functional elements are frequently small and can be separated by large nonfunctional regions. For this reason, constraint in hominid genomes is likely to be patchy. Here we use conservation in more distantly related mammals and amniotes as a way of identifying small sequence windows that are likely to be functional. We find that putatively functional noncoding elements defined in this manner are subject to significant selective constraint in hominids.

  4. Selective Constraint on Noncoding Regions of Hominid Genomes.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available An important challenge for human evolutionary biology is to understand the genetic basis of human-chimpanzee differences. One influential idea holds that such differences depend, to a large extent, on adaptive changes in gene expression. An important step in assessing this hypothesis involves gaining a better understanding of selective constraint on noncoding regions of hominid genomes. In noncoding sequence, functional elements are frequently small and can be separated by large nonfunctional regions. For this reason, constraint in hominid genomes is likely to be patchy. Here we use conservation in more distantly related mammals and amniotes as a way of identifying small sequence windows that are likely to be functional. We find that putatively functional noncoding elements defined in this manner are subject to significant selective constraint in hominids.

  5. Overexpression of long non-coding RNAs following exposure to xenobiotics in the aquatic midge Chironomus riparius

    International Nuclear Information System (INIS)

    Martínez-Guitarte, José-Luis; Planelló, Rosario; Morcillo, Gloria

    2012-01-01

    Non-coding RNAs (ncRNAs) represent an important transcriptional output of eukaryotic genomes. In addition to their functional relevance as housekeeping and regulatory elements, recent studies have suggested their involvement in rather unexpected cellular functions. The aim of this work was to analyse the transcriptional behaviour of non-coding RNAs in the toxic response to pollutants in Chironomus riparius, a reference organism in aquatic toxicology. Three well-characterized long non-coding sequences were studied: telomeric repeats, Cla repetitive elements and the SINE CTRT1. Transcription levels were evaluated by RT-PCR after 24-h exposures to three current aquatic contaminants: bisphenol A (BPA), benzyl butyl phthalate (BBP) and the heavy metal cadmium (Cd). Upregulation of telomeric transcripts was found after BPA treatments. Moreover, BPA significantly activated Cla transcription, which also appeared to be increased by cadmium, whereas BBP did not affect the transcription levels of these sequences. Transcription of SINE CTRT1 was not altered by any of the chemicals tested. These data are discussed in the light of previous studies that have shown a response by long ncRNAS (lncRNAs) to cellular stressors, indicating a relationship with environmental stimuli. Our results demonstrated for the first time the ability of bisphenol A to activate non-coding sequences mainly located at telomeres and centromeres. Overall, this study provides evidence that xenobiotics can induce specific responses in ncRNAs derived from repetitive sequences that could be relevant in the toxic response, and also suggests that ncRNAs could represent a novel class of potential biomarkers in toxicological assessment.

  6. Overexpression of long non-coding RNAs following exposure to xenobiotics in the aquatic midge Chironomus riparius

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Guitarte, Jose-Luis, E-mail: jlmartinez@ccia.uned.es [Grupo de Biologia y Toxicologia Ambiental, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia, UNED, Senda del Rey 9, 28040 Madrid (Spain); Planello, Rosario; Morcillo, Gloria [Grupo de Biologia y Toxicologia Ambiental, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia, UNED, Senda del Rey 9, 28040 Madrid (Spain)

    2012-04-15

    Non-coding RNAs (ncRNAs) represent an important transcriptional output of eukaryotic genomes. In addition to their functional relevance as housekeeping and regulatory elements, recent studies have suggested their involvement in rather unexpected cellular functions. The aim of this work was to analyse the transcriptional behaviour of non-coding RNAs in the toxic response to pollutants in Chironomus riparius, a reference organism in aquatic toxicology. Three well-characterized long non-coding sequences were studied: telomeric repeats, Cla repetitive elements and the SINE CTRT1. Transcription levels were evaluated by RT-PCR after 24-h exposures to three current aquatic contaminants: bisphenol A (BPA), benzyl butyl phthalate (BBP) and the heavy metal cadmium (Cd). Upregulation of telomeric transcripts was found after BPA treatments. Moreover, BPA significantly activated Cla transcription, which also appeared to be increased by cadmium, whereas BBP did not affect the transcription levels of these sequences. Transcription of SINE CTRT1 was not altered by any of the chemicals tested. These data are discussed in the light of previous studies that have shown a response by long ncRNAS (lncRNAs) to cellular stressors, indicating a relationship with environmental stimuli. Our results demonstrated for the first time the ability of bisphenol A to activate non-coding sequences mainly located at telomeres and centromeres. Overall, this study provides evidence that xenobiotics can induce specific responses in ncRNAs derived from repetitive sequences that could be relevant in the toxic response, and also suggests that ncRNAs could represent a novel class of potential biomarkers in toxicological assessment.

  7. Huntingtin gene repeat size variations affect risk of lifetime depression

    DEFF Research Database (Denmark)

    Gardiner, Sarah L.; van Belzen, Martine J.; Boogaard, Merel W.

    2017-01-01

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect...

  8. Non-Coding RNAs in Arabidopsis

    DEFF Research Database (Denmark)

    van Wonterghem, Miranda

    This work evolves around elucidating the mechanisms of micro RNAs (miRNAs) in Arabidopsis thaliana. I identified a new class of nuclear non-coding RNAs derived from protein coding genes. The genes are miRNA targets with extensive gene body methylation. The RNA species are nuclear localized and de...

  9. Circadian changes in long noncoding RNAs in the pineal gland

    DEFF Research Database (Denmark)

    Coon, Steven L; Munson, Peter J; Cherukuri, Praveen F

    2012-01-01

    Long noncoding RNAs (lncRNAs) play a broad range of biological roles, including regulation of expression of genes and chromosomes. Here, we present evidence that lncRNAs are involved in vertebrate circadian biology. Differential night/day expression of 112 lncRNAs (0.3 to >50 kb) occurs in the ra...

  10. Detecting non-coding selective pressure in coding regions

    Directory of Open Access Journals (Sweden)

    Blanchette Mathieu

    2007-02-01

    Full Text Available Abstract Background Comparative genomics approaches, where orthologous DNA regions are compared and inter-species conserved regions are identified, have proven extremely powerful for identifying non-coding regulatory regions located in intergenic or intronic regions. However, non-coding functional elements can also be located within coding region, as is common for exonic splicing enhancers, some transcription factor binding sites, and RNA secondary structure elements affecting mRNA stability, localization, or translation. Since these functional elements are located in regions that are themselves highly conserved because they are coding for a protein, they generally escaped detection by comparative genomics approaches. Results We introduce a comparative genomics approach for detecting non-coding functional elements located within coding regions. Codon evolution is modeled as a mixture of codon substitution models, where each component of the mixture describes the evolution of codons under a specific type of coding selective pressure. We show how to compute the posterior distribution of the entropy and parsimony scores under this null model of codon evolution. The method is applied to a set of growth hormone 1 orthologous mRNA sequences and a known exonic splicing elements is detected. The analysis of a set of CORTBP2 orthologous genes reveals a region of several hundred base pairs under strong non-coding selective pressure whose function remains unknown. Conclusion Non-coding functional elements, in particular those involved in post-transcriptional regulation, are likely to be much more prevalent than is currently known. With the numerous genome sequencing projects underway, comparative genomics approaches like that proposed here are likely to become increasingly powerful at detecting such elements.

  11. Negative thermal expansion materials

    International Nuclear Information System (INIS)

    Evans, J.S.O.

    1997-01-01

    The recent discovery of negative thermal expansion over an unprecedented temperature range in ZrW 2 O 8 (which contracts continuously on warming from below 2 K to above 1000 K) has stimulated considerable interest in this unusual phenomenon. Negative and low thermal expansion materials have a number of important potential uses in ceramic, optical and electronic applications. We have now found negative thermal expansion in a large new family of materials with the general formula A 2 (MO 4 ) 3 . Chemical substitution dramatically influences the thermal expansion properties of these materials allowing the production of ceramics with negative, positive or zero coefficients of thermal expansion, with the potential to control other important materials properties such as refractive index and dielectric constant. The mechanism of negative thermal expansion and the phase transitions exhibited by this important new class of low-expansion materials will be discussed. (orig.)

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

    Science.gov (United States)

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

    2017-03-01

    We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10 -18 ), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R 2  = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. TFIIS-Dependent Non-coding Transcription Regulates Developmental Genome Rearrangements.

    Directory of Open Access Journals (Sweden)

    Kamila Maliszewska-Olejniczak

    2015-07-01

    Full Text Available Because of their nuclear dimorphism, ciliates provide a unique opportunity to study the role of non-coding RNAs (ncRNAs in the communication between germline and somatic lineages. In these unicellular eukaryotes, a new somatic nucleus develops at each sexual cycle from a copy of the zygotic (germline nucleus, while the old somatic nucleus degenerates. In the ciliate Paramecium tetraurelia, the genome is massively rearranged during this process through the reproducible elimination of repeated sequences and the precise excision of over 45,000 short, single-copy Internal Eliminated Sequences (IESs. Different types of ncRNAs resulting from genome-wide transcription were shown to be involved in the epigenetic regulation of genome rearrangements. To understand how ncRNAs are produced from the entire genome, we have focused on a homolog of the TFIIS elongation factor, which regulates RNA polymerase II transcriptional pausing. Six TFIIS-paralogs, representing four distinct families, can be found in P. tetraurelia genome. Using RNA interference, we showed that TFIIS4, which encodes a development-specific TFIIS protein, is essential for the formation of a functional somatic genome. Molecular analyses and high-throughput DNA sequencing upon TFIIS4 RNAi demonstrated that TFIIS4 is involved in all kinds of genome rearrangements, including excision of ~48% of IESs. Localization of a GFP-TFIIS4 fusion revealed that TFIIS4 appears specifically in the new somatic nucleus at an early developmental stage, before IES excision. RT-PCR experiments showed that TFIIS4 is necessary for the synthesis of IES-containing non-coding transcripts. We propose that these IES+ transcripts originate from the developing somatic nucleus and serve as pairing substrates for germline-specific short RNAs that target elimination of their homologous sequences. Our study, therefore, connects the onset of zygotic non coding transcription to the control of genome plasticity in Paramecium

  14. Revisiting the TALE repeat.

    Science.gov (United States)

    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.

  15. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    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.

  16. Expansion joints for LMFBR

    Energy Technology Data Exchange (ETDEWEB)

    Dzenus, M.; Hundhausen, W.; Jansing, W.

    1979-10-15

    This discourse recounts efforts put into the SNR-2 project; specifically the development of compensation devices. The various prototypes of these compensation devices are described and the state of development reviewed. The expansion joints were developed on the basis of specific design criteria whereby differentiation is made between expansion joints of small and large nominal diameter. Expansion joints for installation in the sodium-filled primary piping are equipped with safety bellows in addition to the actual working bellows.

  17. Function and Application Areas in Medicine of Non-Coding RNA

    Directory of Open Access Journals (Sweden)

    Figen Guzelgul

    2009-06-01

    Full Text Available RNA is the genetic material converting the genetic code that it gets from DNA into protein. While less than 2 % of RNA is converted into protein , more than 98 % of it can not be converted into protein and named as non-coding RNAs. 70 % of noncoding RNAs consists of introns , however, the rest part of them consists of exons. Non-coding RNAs are examined in two classes according to their size and functions. Whereas they are classified as long non-coding and small non-coding RNAs according to their size , they are grouped as housekeeping non-coding RNAs and regulating non-coding RNAs according to their function. For long years ,these non-coding RNAs have been considered as non-functional. However, today, it has been proved that these non-coding RNAs play role in regulating genes and in structural, functional and catalitic roles of RNAs converted into protein. Due to its taking a role in gene silencing mechanism, particularly in medical world , non-coding RNAs have led to significant developments. RNAi technolgy , which is used in designing drugs to be used in treatment of various diseases , is a ray of hope for medical world. [Archives Medical Review Journal 2009; 18(3.000: 141-155

  18. Quantum repeated games revisited

    International Nuclear Information System (INIS)

    Frąckiewicz, Piotr

    2012-01-01

    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. (paper)

  19. Decoding the function of nuclear long non-coding RNAs.

    Science.gov (United States)

    Chen, Ling-Ling; Carmichael, Gordon G

    2010-06-01

    Long non-coding RNAs (lncRNAs) are mRNA-like, non-protein-coding RNAs that are pervasively transcribed throughout eukaryotic genomes. Rather than silently accumulating in the nucleus, many of these are now known or suspected to play important roles in nuclear architecture or in the regulation of gene expression. In this review, we highlight some recent progress in how lncRNAs regulate these important nuclear processes at the molecular level. Copyright 2010 Elsevier Ltd. All rights reserved.

  20. The noncoding-RNA landscape in cardiovascular health and disease

    OpenAIRE

    Vittoria Di Mauro; Maria Barandalla-Sobrados; Daniele Catalucci

    2018-01-01

    The cardiovascular system plays a pivotal role in regulating and maintaining homeostasis in the human body. Therefore any alteration in regulatory networks that orchestrate heart development as well as adaptation to physiological and environmental stress might result in pathological conditions, which represent the leading cause of death worldwide [1]. The latest advances in genome-wide techniques challenged the “protein-central dogma” with the discovery of the so-called non-coding RNAs (ncRNA...

  1. Functional long non-coding RNA transcription in Schizosaccharomyces pombe

    OpenAIRE

    Ard, Ryan Anthony

    2016-01-01

    Eukaryotic genomes are pervasively transcribed and frequently generate long noncoding RNAs (lncRNAs). However, most lncRNAs remain uncharacterized. In this work, a set of positionally conserved intergenic lncRNAs in the fission yeast Schizosaccharomyces pombe genome are selected for further analysis. Deleting one of these lncRNA genes (ncRNA.1343) exhibited a clear phenotype: increased drug sensitivity. Further analyses revealed that deleting ncRNA.1343 also disrupted a prev...

  2. Therapeutic targeting of non-coding RNAs in cancer

    Czech Academy of Sciences Publication Activity Database

    Slabý, O.; Laga, Richard; Sedláček, Ondřej

    2017-01-01

    Roč. 474, č. 24 (2017), s. 4219-4251 ISSN 0264-6021 R&D Projects: GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61389013 Keywords : non-coding RNA * RNA delivery * polymer carriers Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Biochemical research methods Impact factor: 3.797, year: 2016

  3. Non-coding RNAs in the Ovarian Follicle

    Directory of Open Access Journals (Sweden)

    Rosalia Battaglia

    2017-05-01

    Full Text Available The mammalian ovarian follicle is the complex reproductive unit comprising germ cell, somatic cells (Cumulus and Granulosa cells, and follicular fluid (FF: paracrine communication among the different cell types through FF ensures the development of a mature oocyte ready for fertilization. This paper is focused on non-coding RNAs in ovarian follicles and their predicted role in the pathways involved in oocyte growth and maturation. We determined the expression profiles of microRNAs in human oocytes and FF by high-throughput analysis and identified 267 microRNAs in FF and 176 in oocytes. Most of these were FF microRNAs, while 9 were oocyte specific. By bioinformatic analysis, independently performed on FF and oocyte microRNAs, we identified the most significant Biological Processes and the pathways regulated by their validated targets. We found many pathways shared between the two compartments and some specific for oocyte microRNAs. Moreover, we found 41 long non-coding RNAs able to interact with oocyte microRNAs and potentially involved in the regulation of folliculogenesis. These data are important in basic reproductive research and could also be useful for clinical applications. In fact, the characterization of non-coding RNAs in ovarian follicles could improve reproductive disease diagnosis, provide biomarkers of oocyte quality in Assisted Reproductive Treatment, and allow the development of therapies for infertility disorders.

  4. Noncoding RNA Profiles in Tobacco- and Alcohol-Associated Diseases

    Directory of Open Access Journals (Sweden)

    Nayra Soares do Amaral

    2016-12-01

    Full Text Available Tobacco and alcohol are the leading environmental risk factors in the development of human diseases, such as cancer, cardiovascular disease, and liver injury. Despite the copious amount of research on this topic, by 2030, 8.3 million deaths are projected to occur worldwide due to tobacco use. The expression of noncoding RNAs, primarily microRNAs (miRNAs and long noncoding RNAs (lncRNAs, is modulated by tobacco and alcohol consumption. Drinking alcohol and smoking cigarettes can modulate the expression of miRNAs and lncRNAs through various signaling pathways, such as apoptosis, angiogenesis, and inflammatory pathways—primarily interleukin 6 (IL-6/signal transducer and activator of transcription 3 (STAT3, which seems to play a major role in the development of diseases associated with these risk factors. Since they may be predictive and prognostic biomarkers, they can be used both as predictors of the response to therapy and as a targeted therapy. Further, circulating miRNAs might be valuable noninvasive tools that can be used to examine diseases that are related to the use of tobacco and alcohol. This review discusses the function of noncoding RNAs in cancer and other human tobacco- and alcohol-associated diseases.

  5. Gene expression and adaptive noncoding changes during human evolution.

    Science.gov (United States)

    Babbitt, Courtney C; Haygood, Ralph; Nielsen, William J; Wray, Gregory A

    2017-06-05

    Despite evidence for adaptive changes in both gene expression and non-protein-coding, putatively regulatory regions of the genome during human evolution, the relationship between gene expression and adaptive changes in cis-regulatory regions remains unclear. Here we present new measurements of gene expression in five tissues of humans and chimpanzees, and use them to assess this relationship. We then compare our results with previous studies of adaptive noncoding changes, analyzing correlations at the level of gene ontology groups, in order to gain statistical power to detect correlations. Consistent with previous studies, we find little correlation between gene expression and adaptive noncoding changes at the level of individual genes; however, we do find significant correlations at the level of biological function ontology groups. The types of function include processes regulated by specific transcription factors, responses to genetic or chemical perturbations, and differentiation of cell types within the immune system. Among functional categories co-enriched with both differential expression and noncoding adaptation, prominent themes include cancer, particularly epithelial cancers, and neural development and function.

  6. Characterization of noncoding regulatory DNA in the human genome.

    Science.gov (United States)

    Elkon, Ran; Agami, Reuven

    2017-08-08

    Genetic variants associated with common diseases are usually located in noncoding parts of the human genome. Delineation of the full repertoire of functional noncoding elements, together with efficient methods for probing their biological roles, is therefore of crucial importance. Over the past decade, DNA accessibility and various epigenetic modifications have been associated with regulatory functions. Mapping these features across the genome has enabled researchers to begin to document the full complement of putative regulatory elements. High-throughput reporter assays to probe the functions of regulatory regions have also been developed but these methods separate putative regulatory elements from the chromosome so that any effects of chromatin context and long-range regulatory interactions are lost. Definitive assignment of function(s) to putative cis-regulatory elements requires perturbation of these elements. Genome-editing technologies are now transforming our ability to perturb regulatory elements across entire genomes. Interpretation of high-throughput genetic screens that incorporate genome editors might enable the construction of an unbiased map of functional noncoding elements in the human genome.

  7. The human noncoding genome defined by genetic diversity.

    Science.gov (United States)

    di Iulio, Julia; Bartha, Istvan; Wong, Emily H M; Yu, Hung-Chun; Lavrenko, Victor; Yang, Dongchan; Jung, Inkyung; Hicks, Michael A; Shah, Naisha; Kirkness, Ewen F; Fabani, Martin M; Biggs, William H; Ren, Bing; Venter, J Craig; Telenti, Amalio

    2018-03-01

    Understanding the significance of genetic variants in the noncoding genome is emerging as the next challenge in human genomics. We used the power of 11,257 whole-genome sequences and 16,384 heptamers (7-nt motifs) to build a map of sequence constraint for the human species. This build differed substantially from traditional maps of interspecies conservation and identified regulatory elements among the most constrained regions of the genome. Using new Hi-C experimental data, we describe a strong pattern of coordination over 2 Mb where the most constrained regulatory elements associate with the most essential genes. Constrained regions of the noncoding genome are up to 52-fold enriched for known pathogenic variants as compared to unconstrained regions (21-fold when compared to the genome average). This map of sequence constraint across thousands of individuals is an asset to help interpret noncoding elements in the human genome, prioritize variants and reconsider gene units at a larger scale.

  8. R-loops: targets for nuclease cleavage and repeat instability.

    Science.gov (United States)

    Freudenreich, Catherine H

    2018-01-11

    R-loops form when transcribed RNA remains bound to its DNA template to form a stable RNA:DNA hybrid. Stable R-loops form when the RNA is purine-rich, and are further stabilized by DNA secondary structures on the non-template strand. Interestingly, many expandable and disease-causing repeat sequences form stable R-loops, and R-loops can contribute to repeat instability. Repeat expansions are responsible for multiple neurodegenerative diseases, including Huntington's disease, myotonic dystrophy, and several types of ataxias. Recently, it was found that R-loops at an expanded CAG/CTG repeat tract cause DNA breaks as well as repeat instability (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Two factors were identified as causing R-loop-dependent breaks at CAG/CTG tracts: deamination of cytosines and the MutLγ (Mlh1-Mlh3) endonuclease, defining two new mechanisms for how R-loops can generate DNA breaks (Su and Freudenreich, Proc Natl Acad Sci USA 114, E8392-E8401, 2017). Following R-loop-dependent nicking, base excision repair resulted in repeat instability. These results have implications for human repeat expansion diseases and provide a paradigm for how RNA:DNA hybrids can cause genome instability at structure-forming DNA sequences. This perspective summarizes mechanisms of R-loop-induced fragility at G-rich repeats and new links between DNA breaks and repeat instability.

  9. Repeat migration and disappointment.

    Science.gov (United States)

    Grant, E K; Vanderkamp, J

    1986-01-01

    This article investigates the determinants of repeat migration among the 44 regions of Canada, using information from a large micro-database which spans the period 1968 to 1971. The explanation of repeat migration probabilities is a difficult task, and this attempt is only partly successful. May of the explanatory variables are not significant, and the overall explanatory power of the equations is not high. In the area of personal characteristics, the variables related to age, sex, and marital status are generally significant and with expected signs. The distance variable has a strongly positive effect on onward move probabilities. Variables related to prior migration experience have an important impact that differs between return and onward probabilities. In particular, the occurrence of prior moves has a striking effect on the probability of onward migration. The variable representing disappointment, or relative success of the initial move, plays a significant role in explaining repeat migration probabilities. The disappointment variable represents the ratio of actural versus expected wage income in the year after the initial move, and its effect on both repeat migration probabilities is always negative and almost always highly significant. The repeat probabilities diminish after a year's stay in the destination region, but disappointment in the most recent year still has a bearing on the delayed repeat probabilities. While the quantitative impact of the disappointment variable is not large, it is difficult to draw comparisons since similar estimates are not available elsewhere.

  10. Long noncoding RNA in prostate, bladder, and kidney cancer.

    Science.gov (United States)

    Martens-Uzunova, Elena S; Böttcher, René; Croce, Carlo M; Jenster, Guido; Visakorpi, Tapio; Calin, George A

    2014-06-01

    Genomic regions without protein-coding potential give rise to millions of protein-noncoding RNA transcripts (noncoding RNA) that participate in virtually all cellular processes. Research over the last 10 yr has accumulated evidence that long noncoding RNAs (lncRNAs) are often altered in human urologic cancers. To review current progress in the biology and implication of lncRNAs associated with prostate, bladder, and kidney cancer. The PubMed database was searched for articles in the English language with combinations of the Medical Subject Headings terms long non coding RNA, long noncoding RNA, long untranslated RNA, cancer, neoplasms, prostate, bladder, and kidney. We summarise existing knowledge on the systematics, biology, and function of lncRNAs, particularly these involved in prostate, kidney, and bladder cancer. We also discuss the possible utilisation of lncRNAs as novel biomarkers and potential therapeutic targets in urologic malignancies and portray the major challenges and future perspectives of ongoing lncRNA research. LncRNAs are important regulators of gene expression interacting with the major pathways of cell growth, proliferation, differentiation, and survival. Alterations in the function of lncRNAs promote tumour formation, progression, and metastasis of prostate, bladder, and kidney cancer. LncRNAs can be used as noninvasive tumour markers in urologic malignancies. Increased knowledge of the molecular mechanisms by which lncRNAs perform their function in the normal and malignant cell will lead to a better understanding of tumour biology and could provide novel therapeutic targets for the treatment of urologic cancers. In this paper we reviewed current knowledge of long noncoding RNAs (lncRNAs) for the detection and treatment of urologic cancers. We conclude that lncRNAs can be used as novel biomarkers in prostate, kidney, or bladder cancer. LncRNAs hold promise as future therapeutic targets, but more research is needed to gain a better

  11. Convergence of mayer expansions

    International Nuclear Information System (INIS)

    Brydges, D.C.

    1986-01-01

    The tree graph bound of Battle and Federbush is extended and used to provide a simple criterion for the convergence of (iterated) Mayer expansions. As an application estimates on the radius of convergence of the Mayer expansion for the two-dimensional Yukawa gas (nonstable interaction) are obtained

  12. Identifying noncoding risk variants using disease-relevant gene regulatory networks.

    Science.gov (United States)

    Gao, Long; Uzun, Yasin; Gao, Peng; He, Bing; Ma, Xiaoke; Wang, Jiahui; Han, Shizhong; Tan, Kai

    2018-02-16

    Identifying noncoding risk variants remains a challenging task. Because noncoding variants exert their effects in the context of a gene regulatory network (GRN), we hypothesize that explicit use of disease-relevant GRNs can significantly improve the inference accuracy of noncoding risk variants. We describe Annotation of Regulatory Variants using Integrated Networks (ARVIN), a general computational framework for predicting causal noncoding variants. It employs a set of novel regulatory network-based features, combined with sequence-based features to infer noncoding risk variants. Using known causal variants in gene promoters and enhancers in a number of diseases, we show ARVIN outperforms state-of-the-art methods that use sequence-based features alone. Additional experimental validation using reporter assay further demonstrates the accuracy of ARVIN. Application of ARVIN to seven autoimmune diseases provides a holistic view of the gene subnetwork perturbed by the combinatorial action of the entire set of risk noncoding mutations.

  13. An expanding universe of noncoding RNAs between the poles of basic science and clinical investigations.

    Science.gov (United States)

    Weil, Patrick P; Hensel, Kai O; Weber, David; Postberg, Jan

    2016-03-01

    The Keystone Symposium 'MicroRNAs and Noncoding RNAs in Cancer', Keystone, CO, USA, 7-12 June 2015 Since the discovery of RNAi, great efforts have been undertaken to unleash the potential biomedical applicability of small noncoding RNAs, mainly miRNAs, involving their use as biomarkers for personalized diagnostics or their usability as active agents or therapy targets. The research's focus on the noncoding RNA world is now slowly moving from a phase of basic discoveries into a new phase, where every single molecule out of many hundreds of cataloged noncoding RNAs becomes dissected in order to investigate these molecules' biomedical relevance. In addition, RNA classes neglected before, such as long noncoding RNAs or circular RNAs attract more attention. Numerous timely results and hypotheses were presented at the 2015 Keystone Symposium 'MicroRNAs and Noncoding RNAs in Cancer'.

  14. Long non-coding RNAs: Mechanism of action and functional utility

    OpenAIRE

    Bhat, Shakil Ahmad; Ahmad, Syed Mudasir; Mumtaz, Peerzada Tajamul; Malik, Abrar Ahad; Dar, Mashooq Ahmad; Urwat, Uneeb; Shah, Riaz Ahmad; Ganai, Nazir Ahmad

    2016-01-01

    Recent RNA sequencing studies have revealed that most of the human genome is transcribed, but very little of the total transcriptomes has the ability to encode proteins. Long non-coding RNAs (lncRNAs) are non-coding transcripts longer than 200 nucleotides. Members of the non-coding genome include microRNA (miRNA), small regulatory RNAs and other short RNAs. Most of long non-coding RNA (lncRNAs) are poorly annotated. Recent recognition about lncRNAs highlights their effects in many biological ...

  15. The Pentapeptide Repeat Proteins

    OpenAIRE

    Vetting, Matthew W.; Hegde, Subray S.; Fajardo, J. Eduardo; Fiser, Andras; Roderick, Steven L.; Takiff, Howard E.; Blanchard, John S.

    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 Myc...

  16. Cigarette smoke exposure-associated alterations to noncoding RNA

    Directory of Open Access Journals (Sweden)

    Matthew Alan Maccani

    2012-04-01

    Full Text Available Environmental exposures vary by timing, severity, and frequency and may have a number of deleterious effects throughout the life course. The period of in utero development, for example, is one of the most crucial stages of development during which adverse environmental exposures can both alter the growth and development of the fetus as well as lead to aberrant fetal programming, increasing disease risk. During fetal development and beyond, the plethora of exposures, including nutrients, drugs, stress, and trauma, influence health, development, and survival. Recent research in environmental epigenetics has investigated the roles of environmental exposures in influencing epigenetic modes of gene regulation during pregnancy and at various stages of life. Many relatively common environmental exposures, such as cigarette smoking, alcohol consumption, and drug use, may have consequences for the expression and function of noncoding RNA (ncRNA, important post-transcriptional regulators of gene expression. A number of ncRNA have been discovered, including microRNA (miRNA, Piwi-interacting RNA (piRNA, and long noncoding RNA (long ncRNA. The best-characterized species of ncRNA are miRNA, the mature forms of which are ~22 nucleotides in length and capable of post-transcriptionally regulating target mRNA utilizing mechanisms based largely on the degree of complementarity between miRNA and target mRNA. Because miRNA can still negatively regulate gene expression when imperfectly base-paired with a target mRNA, a single miRNA can have a large number of potential mRNA targets and can regulate many different biological processes critical for health and development. The following review analyzes the current literature detailing links between cigarette smoke exposure and aberrant expression and function of noncoding RNA, assesses how such alterations may have consequences throughout the life course, and proposes future directions for this intriguing field of

  17. Controlled Thermal Expansion Alloys

    Data.gov (United States)

    National Aeronautics and Space Administration — There has always been a need for controlled thermal expansion alloys suitable for mounting optics and detectors in spacecraft applications.  These alloys help...

  18. Alteration of Epigenetic Regulation by Long Noncoding RNAs in Cancer

    Directory of Open Access Journals (Sweden)

    Mariangela Morlando

    2018-02-01

    Full Text Available Long noncoding RNAs (lncRNAs are important regulators of the epigenetic status of the human genome. Besides their participation to normal physiology, lncRNA expression and function have been already associated to many diseases, including cancer. By interacting with epigenetic regulators and by controlling chromatin topology, their misregulation may result in an aberrant regulation of gene expression that may contribute to tumorigenesis. Here, we review the functional role and mechanisms of action of lncRNAs implicated in the aberrant epigenetic regulation that has characterized cancer development and progression.

  19. Biocomputational prediction of small non-coding RNAs in Streptomyces

    Czech Academy of Sciences Publication Activity Database

    Pánek, Josef; Bobek, Jan; Mikulík, Karel; Basler, Marek; Vohradský, Jiří

    2008-01-01

    Roč. 9, č. 217 (2008), s. 1-14 ISSN 1471-2164 R&D Projects: GA ČR GP204/07/P361; GA ČR GA203/05/0106; GA ČR GA310/07/1009 Grant - others:XE(XE) EC Integrated Project ActinoGEN, LSHM-CT-2004-005224. Institutional research plan: CEZ:AV0Z50200510 Keywords : non-coding RNA * streptomyces * biocomputational prediction Subject RIV: IN - Informatics, Computer Science Impact factor: 3.926, year: 2008

  20. Annotating non-coding regions of the genome.

    Science.gov (United States)

    Alexander, Roger P; Fang, Gang; Rozowsky, Joel; Snyder, Michael; Gerstein, Mark B

    2010-08-01

    Most of the human genome consists of non-protein-coding DNA. Recently, progress has been made in annotating these non-coding regions through the interpretation of functional genomics experiments and comparative sequence analysis. One can conceptualize functional genomics analysis as involving a sequence of steps: turning the output of an experiment into a 'signal' at each base pair of the genome; smoothing this signal and segmenting it into small blocks of initial annotation; and then clustering these small blocks into larger derived annotations and networks. Finally, one can relate functional genomics annotations to conserved units and measures of conservation derived from comparative sequence analysis.

  1. Long Non-coding RNAs in Response to Genotoxic Stress

    Institute of Scientific and Technical Information of China (English)

    Xiaoman Li; Dong Pan; Baoquan Zhao; Burong Hu

    2016-01-01

    Long non-coding RNAs(lncRNAs) are increasingly involved in diverse biological processes.Upon DNA damage,the DNA damage response(DDR) elicits a complex signaling cascade,which includes the induction of lncRNAs.LncRNA-mediated DDR is involved in non-canonical and canonical manners.DNA-damage induced lncRNAs contribute to the regulation of cell cycle,apoptosis,and DNA repair,thereby playing a key role in maintaining genome stability.This review summarizes the emerging role of lncRNAs in DNA damage and repair.

  2. Repeated Causal Decision Making

    Science.gov (United States)

    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…

  3. simple sequence repeat (SSR)

    African Journals Online (AJOL)

    In the present study, 78 mapped simple sequence repeat (SSR) markers representing 11 linkage groups of adzuki bean were evaluated for transferability to mungbean and related Vigna spp. 41 markers amplified characteristic bands in at least one Vigna species. The transferability percentage across the genotypes ranged ...

  4. Fuel Thermal Expansion (FTHEXP)

    International Nuclear Information System (INIS)

    Reymann, G.A.

    1978-07-01

    A model is presented which deals with dimensional changes in LWR fuel pellets caused by changes in temperature. It is capable of dealing with any combination of UO 2 and PuO 2 in solid, liquid or mixed phase states, and includes expansion due to the solid-liquid phase change. The function FTHEXP models fuel thermal expansion as a function of temperature, fraction of PuO 2 , and the fraction of fuel which is molten

  5. Repeat Sequence Proteins as Matrices for Nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Drummy, L.; Koerner, H; Phillips, D; McAuliffe, J; Kumar, M; Farmer, B; Vaia, R; Naik, R

    2009-01-01

    Recombinant protein-inorganic nanocomposites comprised of exfoliated Na+ montmorillonite (MMT) in a recombinant protein matrix based on silk-like and elastin-like amino acid motifs (silk elastin-like protein (SELP)) were formed via a solution blending process. Charged residues along the protein backbone are shown to dominate long-range interactions, whereas the SELP repeat sequence leads to local protein/MMT compatibility. Up to a 50% increase in room temperature modulus and a comparable decrease in high temperature coefficient of thermal expansion occur for cast films containing 2-10 wt.% MMT.

  6. Noncoding origins of anthropoid traits and a new null model of transposon functionalization.

    Science.gov (United States)

    del Rosario, Ricardo C H; Rayan, Nirmala Arul; Prabhakar, Shyam

    2014-09-01

    Little is known about novel genetic elements that drove the emergence of anthropoid primates. We exploited the sequencing of the marmoset genome to identify 23,849 anthropoid-specific constrained (ASC) regions and confirmed their robust functional signatures. Of the ASC base pairs, 99.7% were noncoding, suggesting that novel anthropoid functional elements were overwhelmingly cis-regulatory. ASCs were highly enriched in loci associated with fetal brain development, motor coordination, neurotransmission, and vision, thus providing a large set of candidate elements for exploring the molecular basis of hallmark primate traits. We validated ASC192 as a primate-specific enhancer in proliferative zones of the developing brain. Unexpectedly, transposable elements (TEs) contributed to >56% of ASCs, and almost all TE families showed functional potential similar to that of nonrepetitive DNA. Three L1PA repeat-derived ASCs displayed coherent eye-enhancer function, thus demonstrating that the "gene-battery" model of TE functionalization applies to enhancers in vivo. Our study provides fundamental insights into genome evolution and the origins of anthropoid phenotypes and supports an elegantly simple new null model of TE exaptation. © 2014 del Rosario et al.; Published by Cold Spring Harbor Laboratory Press.

  7. Expression of a novel non-coding mitochondrial RNA in human proliferating cells.

    Science.gov (United States)

    Villegas, Jaime; Burzio, Veronica; Villota, Claudio; Landerer, Eduardo; Martinez, Ronny; Santander, Marcela; Martinez, Rodrigo; Pinto, Rodrigo; Vera, María I; Boccardo, Enrique; Villa, Luisa L; Burzio, Luis O

    2007-01-01

    Previously, we reported the presence in mouse cells of a mitochondrial RNA which contains an inverted repeat (IR) of 121 nucleotides (nt) covalently linked to the 5' end of the mitochondrial 16S RNA (16S mtrRNA). Here, we report the structure of an equivalent transcript of 2374 nt which is over-expressed in human proliferating cells but not in resting cells. The transcript contains a hairpin structure comprising an IR of 815 nt linked to the 5' end of the 16S mtrRNA and forming a long double-stranded structure or stem and a loop of 40 nt. The stem is resistant to RNase A and can be detected and isolated after digestion with the enzyme. This novel transcript is a non-coding RNA (ncRNA) and several evidences suggest that the transcript is synthesized in mitochondria. The expression of this transcript can be induced in resting lymphocytes stimulated with phytohaemagglutinin (PHA). Moreover, aphidicolin treatment of DU145 cells reversibly blocks proliferation and expression of the transcript. If the drug is removed, the cells re-assume proliferation and over-express the ncmtRNA. These results suggest that the expression of the ncmtRNA correlates with the replicative state of the cell and it may play a role in cell proliferation.

  8. Identification of antisense long noncoding RNAs that function as SINEUPs in human cells.

    Science.gov (United States)

    Schein, Aleks; Zucchelli, Silvia; Kauppinen, Sakari; Gustincich, Stefano; Carninci, Piero

    2016-09-20

    Mammalian genomes encode numerous natural antisense long noncoding RNAs (lncRNAs) that regulate gene expression. Recently, an antisense lncRNA to mouse Ubiquitin carboxyl-terminal hydrolase L1 (Uchl1) was reported to increase UCHL1 protein synthesis, representing a new functional class of lncRNAs, designated as SINEUPs, for SINE element-containing translation UP-regulators. Here, we show that an antisense lncRNA to the human protein phosphatase 1 regulatory subunit 12A (PPP1R12A), named as R12A-AS1, which overlaps with the 5' UTR and first coding exon of the PPP1R12A mRNA, functions as a SINEUP, increasing PPP1R12A protein translation in human cells. The SINEUP activity depends on the aforementioned sense-antisense interaction and a free right Alu monomer repeat element at the 3' end of R12A-AS1. In addition, we identify another human antisense lncRNA with SINEUP activity. Our results demonstrate for the first time that human natural antisense lncRNAs can up-regulate protein translation, suggesting that endogenous SINEUPs may be widespread and present in many mammalian species.

  9. ATXN2 trinucleotide repeat length correlates with risk of ALS

    NARCIS (Netherlands)

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

    2017-01-01

    We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we

  10. Junk DNA and the long non-coding RNA twist in cancer genetics

    NARCIS (Netherlands)

    H. Ling (Hui); K. Vincent; M. Pichler; R. Fodde (Riccardo); I. Berindan-Neagoe (Ioana); F.J. Slack (Frank); G.A. Calin (George)

    2015-01-01

    textabstractThe central dogma of molecular biology states that the flow of genetic information moves from DNA to RNA to protein. However, in the last decade this dogma has been challenged by new findings on non-coding RNAs (ncRNAs) such as microRNAs (miRNAs). More recently, long non-coding RNAs

  11. An atlas of over 90.000 conserved noncoding sequences provides insight into crucifer regulatory regions

    NARCIS (Netherlands)

    Haudry, A.; Platts, A.E.; Vello, E.; Hoen, D.R.; Leclerq, M.; Williamson, R.J.; Forczek, E.; Joly-Lopez, Z.; Steffen, J.G.; Hazzouri, K.M.; Dewar, K.; Stinchcombe, J.R.; Schoen, D.J.; Wang, X.; Schmutz, J.; Town, C.D.; Edger, P.P.; Pires, J.C.; Schumaker, K.S.; Jarvis, D.E.; Mandakova, T.; Lysak, M.; Bergh, van den E.; Schranz, M.E.; Harrison, P.M.

    2013-01-01

    Despite the central importance of noncoding DNA to gene regulation and evolution, understanding of the extent of selection on plant noncoding DNA remains limited compared to that of other organisms. Here we report sequencing of genomes from three Brassicaceae species (Leavenworthia alabamica,

  12. Resonant state expansions

    International Nuclear Information System (INIS)

    Lind, P.

    1993-02-01

    The completeness properties of the discrete set of bound state, virtual states and resonances characterizing the system of a single nonrelativistic particle moving in a central cutoff potential is investigated. From a completeness relation in terms of these discrete states and complex scattering states one can derive several Resonant State Expansions (RSE). It is interesting to obtain purely discrete expansion which, if valid, would significantly simplify the treatment of the continuum. Such expansions can be derived using Mittag-Leffler (ML) theory for a cutoff potential and it would be nice to see if one can obtain the same expansions starting from an eigenfunction theory that is not restricted to a finite sphere. The RSE of Greens functions is especially important, e.g. in the continuum RPA (CRPA) method of treating giant resonances in nuclear physics. The convergence of RSE is studied in simple cases using square well wavefunctions in order to achieve high numerical accuracy. Several expansions can be derived from each other by using the theory of analytic functions and one can the see how to obtain a natural discretization of the continuum. Since the resonance wavefunctions are oscillating with an exponentially increasing amplitude, and therefore have to be interpreted through some regularization procedure, every statement made about quantities involving such states is checked by numerical calculations.Realistic nuclear wavefunctions, generated by a Wood-Saxon potential, are used to test also the usefulness of RSE in a realistic nuclear calculation. There are some fundamental differences between different symmetries of the integral contour that defines the continuum in RSE. One kind of symmetry is necessary to have an expansion of the unity operator that is idempotent. Another symmetry must be used if we want purely discrete expansions. These are found to be of the same form as given by ML. (29 refs.)

  13. Comprehensive reconstruction andvisualization of non-coding regulatorynetworks in human

    Directory of Open Access Journals (Sweden)

    Vincenzo eBonnici

    2014-12-01

    Full Text Available Research attention has been powered to understand the functional roles of non-coding RNAs (ncRNAs. Many studies have demonstrated their deregulation in cancer and other human disorders. ncRNAs are also present in extracellular human body fluids such as serum and plasma, giving them a great potential as non-invasive biomarkers. However, non-coding RNAs have been relatively recently discovered and a comprehensive database including all of them is still missing. Reconstructing and visualizing the network of ncRNAs interactions are important steps to understand their regulatory mechanism in complex systems. This work presents ncRNA-DB, a NoSQL database that integrates ncRNAs data interactions from a large number of well established online repositories. The interactions involve RNA, DNA, proteins and diseases. ncRNA-DB is available at http://ncrnadb.scienze.univr.it/ncrnadb/. It is equipped with three interfaces: web based, command line and a Cytoscape app called ncINetView. By accessing only one resource, users can search for ncRNAs and their interactions, build a network annotated with all known ncRNAs and associated diseases, and use all visual and mining features available in Cytoscape.

  14. Dynamic Epigenetic Control of Highly Conserved Noncoding Elements

    KAUST Repository

    Seridi, Loqmane

    2014-10-07

    Background Many noncoding genomic loci have remained constant over long evolutionary periods, suggesting that they are exposed to strong selective pressures. The molecular functions of these elements have been partially elucidated, but the fundamental reason for their extreme conservation is still unknown. Results To gain new insights into the extreme selection of highly conserved noncoding elements (HCNEs), we used a systematic analysis of multi-omic data to study the epigenetic regulation of such elements during the development of Drosophila melanogaster. At the sequence level, HCNEs are GC-rich and have a characteristic oligomeric composition. They have higher levels of stable nucleosome occupancy than their flanking regions, and lower levels of mononucleosomes and H3.3, suggesting that these regions reside in compact chromatin. Furthermore, these regions showed remarkable modulations in histone modification and the expression levels of adjacent genes during development. Although HCNEs are primarily initiated late in replication, about 10% were related to early replication origins. Finally, HCNEs showed strong enrichment within lamina-associated domains. Conclusion HCNEs have distinct and protective sequence properties, undergo dynamic epigenetic regulation, and appear to be associated with the structural components of the chromatin, replication origins, and nuclear matrix. These observations indicate that such elements are likely to have essential cellular functions, and offer insights into their epigenetic properties.

  15. The interplay between noncoding RNAs and insulin in diabetes.

    Science.gov (United States)

    Tian, Yan; Xu, Jia; Du, Xiao; Fu, Xianghui

    2018-04-10

    Noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs and circular RNAs, regulate various biological processes and are involved in the initiation and progression of human diseases. Insulin, a predominant hormone secreted from pancreatic β cells, is an essential factor in regulation of systemic metabolism through multifunctional insulin signaling. Insulin production and action are tightly controlled. Dysregulations of insulin production and action can impair metabolic homeostasis, and eventually lead to the development of multiple metabolic diseases, especially diabetes. Accumulating data indicates that ncRNAs modulate β cell mass, insulin synthesis, secretion and signaling, and their role in diabetes is dramatically emerging. This review summarizes our current knowledge of ncRNAs as regulators of insulin, with particular emphasis on the implications of this interplay in the development of diabetes. We outline the role of ncRNAs in pancreatic β cell mass and function, which is critical for insulin production and secretion. We also highlight the involvement of ncRNAs in insulin signaling in peripheral tissues including liver, muscle and adipose, and discuss ncRNA-mediated inter-organ crosstalk under diabetic conditions. A more in-depth understanding of the interplay between ncRNAs and insulin may afford valuable insights and novel therapeutic strategies for treatment of diabetes, as well as other human diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Dynamic Epigenetic Control of Highly Conserved Noncoding Elements

    KAUST Repository

    Seridi, Loqmane; Ryu, Tae Woo; Ravasi, Timothy

    2014-01-01

    Background Many noncoding genomic loci have remained constant over long evolutionary periods, suggesting that they are exposed to strong selective pressures. The molecular functions of these elements have been partially elucidated, but the fundamental reason for their extreme conservation is still unknown. Results To gain new insights into the extreme selection of highly conserved noncoding elements (HCNEs), we used a systematic analysis of multi-omic data to study the epigenetic regulation of such elements during the development of Drosophila melanogaster. At the sequence level, HCNEs are GC-rich and have a characteristic oligomeric composition. They have higher levels of stable nucleosome occupancy than their flanking regions, and lower levels of mononucleosomes and H3.3, suggesting that these regions reside in compact chromatin. Furthermore, these regions showed remarkable modulations in histone modification and the expression levels of adjacent genes during development. Although HCNEs are primarily initiated late in replication, about 10% were related to early replication origins. Finally, HCNEs showed strong enrichment within lamina-associated domains. Conclusion HCNEs have distinct and protective sequence properties, undergo dynamic epigenetic regulation, and appear to be associated with the structural components of the chromatin, replication origins, and nuclear matrix. These observations indicate that such elements are likely to have essential cellular functions, and offer insights into their epigenetic properties.

  17. Bistability in self-activating genes regulated by non-coding RNAs

    International Nuclear Information System (INIS)

    Miro-Bueno, Jesus

    2015-01-01

    Non-coding RNA molecules are able to regulate gene expression and play an essential role in cells. On the other hand, bistability is an important behaviour of genetic networks. Here, we propose and study an ODE model in order to show how non-coding RNA can produce bistability in a simple way. The model comprises a single gene with positive feedback that is repressed by non-coding RNA molecules. We show how the values of all the reaction rates involved in the model are able to control the transitions between the high and low states. This new model can be interesting to clarify the role of non-coding RNA molecules in genetic networks. As well, these results can be interesting in synthetic biology for developing new genetic memories and biomolecular devices based on non-coding RNAs

  18. Expansion joints for LMFBR

    International Nuclear Information System (INIS)

    Dzenus, M.; Hundhausen, W.; Jansing, W.

    1980-01-01

    This discourse recounts efforts put into the SNR-2 project; specifically the development of compensation devices. The various prototypes of these compensation devices are described and the state of the development reviewed. Large Na (sodium)-heat transfer systems require a lot of valuable space if the component lay-out does not include compensation devices. So, in order to condense the spatial requirement as much as possible, expansion joints must be integrated into the pipe system. There are two basic types to suit the purpose: axial expansion joints and angular expansion joints. The expansion joints were developed on the basis of specific design criteria whereby differentiation is made between expansion joints of small and large nominal diameter. Expansion joints for installation in the sodium-filled primary piping are equipped with safety bellows in addition to the actual working bellows. Expansion joints must be designed and mounted in a manner to completely withstand seismic forces. The design must exclude any damage to the bellows during intermittent operations, that is, when sodium is drained the bellows' folds must be completely empty; otherwise residual solidified sodium could destroy the bellows when restarting. The expansion joints must be engineered on the basis of the following design data for the secondary system of the SNR project: working pressure: 16 bar; failure mode pressure: 5 events; failure mode: 5 sec., 28.5 bar, 520 deg. C; working temperature: 520 deg. C; temperature transients: 30 deg. C/sec.; service life: 200,000 h; number of load cycles: 10 4 ; material: 1.4948 or 1.4919; layer thickness of folds: 0.5 mm; angular deflection (DN 800): +3 deg. C or; axial expansion absorption (DN 600): ±80 mm; calculation: ASME class. The bellows' development work is not handled within this scope. The bellows are supplied by leading manufacturers, and warrant highest quality. Multiple bellows were selected on the basis of maximum elasticity - a property

  19. Accelerating the loop expansion

    International Nuclear Information System (INIS)

    Ingermanson, R.

    1986-01-01

    This thesis introduces a new non-perturbative technique into quantum field theory. To illustrate the method, I analyze the much-studied phi 4 theory in two dimensions. As a prelude, I first show that the Hartree approximation is easy to obtain from the calculation of the one-loop effective potential by a simple modification of the propagator that does not affect the perturbative renormalization procedure. A further modification then susggests itself, which has the same nice property, and which automatically yields a convex effective potential. I then show that both of these modifications extend naturally to higher orders in the derivative expansion of the effective action and to higher orders in the loop-expansion. The net effect is to re-sum the perturbation series for the effective action as a systematic ''accelerated'' non-perturbative expansion. Each term in the accelerated expansion corresponds to an infinite number of terms in the original series. Each term can be computed explicitly, albeit numerically. Many numerical graphs of the various approximations to the first two terms in the derivative expansion are given. I discuss the reliability of the results and the problem of spontaneous symmetry-breaking, as well as some potential applications to more interesting field theories. 40 refs

  20. Virial Expansion Bounds

    Science.gov (United States)

    Tate, Stephen James

    2013-10-01

    In the 1960s, the technique of using cluster expansion bounds in order to achieve bounds on the virial expansion was developed by Lebowitz and Penrose (J. Math. Phys. 5:841, 1964) and Ruelle (Statistical Mechanics: Rigorous Results. Benjamin, Elmsford, 1969). This technique is generalised to more recent cluster expansion bounds by Poghosyan and Ueltschi (J. Math. Phys. 50:053509, 2009), which are related to the work of Procacci (J. Stat. Phys. 129:171, 2007) and the tree-graph identity, detailed by Brydges (Phénomènes Critiques, Systèmes Aléatoires, Théories de Jauge. Les Houches 1984, pp. 129-183, 1986). The bounds achieved by Lebowitz and Penrose can also be sharpened by doing the actual optimisation and achieving expressions in terms of the Lambert W-function. The different bound from the cluster expansion shows some improvements for bounds on the convergence of the virial expansion in the case of positive potentials, which are allowed to have a hard core.

  1. Conformal expansions and renormalons

    Energy Technology Data Exchange (ETDEWEB)

    Rathsman, J.

    2000-02-07

    The coefficients in perturbative expansions in gauge theories are factorially increasing, predominantly due to renormalons. This type of factorial increase is not expected in conformal theories. In QCD conformal relations between observables can be defined in the presence of a perturbative infrared fixed-point. Using the Banks-Zaks expansion the authors study the effect of the large-order behavior of the perturbative series on the conformal coefficients. The authors find that in general these coefficients become factorially increasing. However, when the factorial behavior genuinely originates in a renormalon integral, as implied by a postulated skeleton expansion, it does not affect the conformal coefficients. As a consequence, the conformal coefficients will indeed be free of renormalon divergence, in accordance with previous observations concerning the smallness of these coefficients for specific observables. The authors further show that the correspondence of the BLM method with the skeleton expansion implies a unique scale-setting procedure. The BLM coefficients can be interpreted as the conformal coefficients in the series relating the fixed-point value of the observable with that of the skeleton effective charge. Through the skeleton expansion the relevance of renormalon-free conformal coefficients extends to real-world QCD.

  2. Alanine repeats influence protein localization in splicing speckles and paraspeckles.

    Science.gov (United States)

    Chang, Shuo-Hsiu; Chang, Wei-Lun; Lu, Chia-Chen; Tarn, Woan-Yuh

    2014-12-16

    Mammalian splicing regulatory protein RNA-binding motif protein 4 (RBM4) has an alanine repeat-containing C-terminal domain (CAD) that confers both nuclear- and splicing speckle-targeting activities. Alanine-repeat expansion has pathological potential. Here we show that the alanine-repeat tracts influence the subnuclear targeting properties of the RBM4 CAD in cultured human cells. Notably, truncation of the alanine tracts redistributed a portion of RBM4 to paraspeckles. The alanine-deficient CAD was sufficient for paraspeckle targeting. On the other hand, alanine-repeat expansion reduced the mobility of RBM4 and impaired its splicing activity. We further took advantage of the putative coactivator activator (CoAA)-RBM4 conjoined splicing factor, CoAZ, to investigate the function of the CAD in subnuclear targeting. Transiently expressed CoAZ formed discrete nuclear foci that emerged and subsequently separated-fully or partially-from paraspeckles. Alanine-repeat expansion appeared to prevent CoAZ separation from paraspeckles, resulting in their complete colocalization. CoAZ foci were dynamic but, unlike paraspeckles, were resistant to RNase treatment. Our results indicate that the alanine-rich CAD, in conjunction with its conjoined RNA-binding domain(s), differentially influences the subnuclear localization and biogenesis of RBM4 and CoAZ. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Gene conversion homogenizes the CMT1A paralogous repeats

    Directory of Open Access Journals (Sweden)

    Hurles Matthew E

    2001-12-01

    Full Text Available Abstract Background Non-allelic homologous recombination between paralogous repeats is increasingly being recognized as a major mechanism causing both pathogenic microdeletions and duplications, and structural polymorphism in the human genome. It has recently been shown empirically that gene conversion can homogenize such repeats, resulting in longer stretches of absolute identity that may increase the rate of non-allelic homologous recombination. Results Here, a statistical test to detect gene conversion between pairs of non-coding sequences is presented. It is shown that the 24 kb Charcot-Marie-Tooth type 1A paralogous repeats (CMT1A-REPs exhibit the imprint of gene conversion processes whilst control orthologous sequences do not. In addition, Monte Carlo simulations of the evolutionary divergence of the CMT1A-REPs, incorporating two alternative models for gene conversion, generate repeats that are statistically indistinguishable from the observed repeats. Bounds are placed on the rate of these conversion processes, with central values of 1.3 × 10-4 and 5.1 × 10-5 per generation for the alternative models. Conclusions This evidence presented here suggests that gene conversion may have played an important role in the evolution of the CMT1A-REP paralogous repeats. The rates of these processes are such that it is probable that homogenized CMT1A-REPs are polymorphic within modern populations. Gene conversion processes are similarly likely to play an important role in the evolution of other segmental duplications and may influence the rate of non-allelic homologous recombination between them.

  4. Instability of (CTGn•(CAGn trinucleotide repeats and DNA synthesis

    Directory of Open Access Journals (Sweden)

    Liu Guoqi

    2012-02-01

    Full Text Available Abstract Expansion of (CTGn•(CAGn trinucleotide repeat (TNR microsatellite sequences is the cause of more than a dozen human neurodegenerative diseases. (CTGn and (CAGn repeats form imperfectly base paired hairpins that tend to expand in vivo in a length-dependent manner. Yeast, mouse and human models confirm that (CTGn•(CAGn instability increases with repeat number, and implicate both DNA replication and DNA damage response mechanisms in (CTGn•(CAGn TNR expansion and contraction. Mutation and knockdown models that abrogate the expression of individual genes might also mask more subtle, cumulative effects of multiple additional pathways on (CTGn•(CAGn instability in whole animals. The identification of second site genetic modifiers may help to explain the variability of (CTGn•(CAGn TNR instability patterns between tissues and individuals, and offer opportunities for prognosis and treatment.

  5. Thermal expansion data

    International Nuclear Information System (INIS)

    Taylor, D.

    1984-01-01

    This paper gives regression data for a modified second order polynomial fitted to the expansion data of, and percentage expansions for dioxides with (a) the fluorite and antifluorite structure: AmO 2 , BkO 2 , CeO 2 , CmO 2 , HfO 2 , Li 2 O, NpO 2 , PrO 2 , PuO 2 , ThO 2 , UO 2 , ZrO 2 , and (b) the rutile structure: CrO 2 , GeO 2 , IrO 2 , MnO 2 , NbO 2 , PbO 2 , SiO 2 , SnO 2 , TeO 2 , TiO 2 and VO 2 . Reduced expansion curves for the dioxides showed only partial grouping into iso-electronic series for the fluorite structures and showed that the 'law of corresponding states' did not apply to the rutile structures. (author)

  6. Short-lived non-coding transcripts (SLiTs): Clues to regulatory long non-coding RNA.

    Science.gov (United States)

    Tani, Hidenori

    2017-03-22

    Whole transcriptome analyses have revealed a large number of novel long non-coding RNAs (lncRNAs). Although the importance of lncRNAs has been documented in previous reports, the biological and physiological functions of lncRNAs remain largely unknown. The role of lncRNAs seems an elusive problem. Here, I propose a clue to the identification of regulatory lncRNAs. The key point is RNA half-life. RNAs with a long half-life (t 1/2 > 4 h) contain a significant proportion of ncRNAs, as well as mRNAs involved in housekeeping functions, whereas RNAs with a short half-life (t 1/2 regulatory ncRNAs and regulatory mRNAs. This novel class of ncRNAs with a short half-life can be categorized as Short-Lived non-coding Transcripts (SLiTs). I consider that SLiTs are likely to be rich in functionally uncharacterized regulatory RNAs. This review describes recent progress in research into SLiTs.

  7. Uniform gradient expansions

    CERN Document Server

    Giovannini, Massimo

    2015-01-01

    Cosmological singularities are often discussed by means of a gradient expansion that can also describe, during a quasi-de Sitter phase, the progressive suppression of curvature inhomogeneities. While the inflationary event horizon is being formed the two mentioned regimes coexist and a uniform expansion can be conceived and applied to the evolution of spatial gradients across the protoinflationary boundary. It is argued that conventional arguments addressing the preinflationary initial conditions are necessary but generally not sufficient to guarantee a homogeneous onset of the conventional inflationary stage.

  8. Low-temperature thermal expansion

    International Nuclear Information System (INIS)

    Collings, E.W.

    1986-01-01

    This chapter discusses the thermal expansion of insulators and metals. Harmonicity and anharmonicity in thermal expansion are examined. The electronic, magnetic, an other contributions to low temperature thermal expansion are analyzed. The thermodynamics of the Debye isotropic continuum, the lattice-dynamical approach, and the thermal expansion of metals are discussed. Relative linear expansion at low temperatures is reviewed and further calculations of the electronic thermal expansion coefficient are given. Thermal expansions are given for Cu, Al and Ti. Phenomenologic thermodynamic relationships are also discussed

  9. The primary structures of two yeast enolase genes. Homology between the 5' noncoding flanking regions of yeast enolase and glyceraldehyde-3-phosphate dehydrogenase genes.

    Science.gov (United States)

    Holland, M J; Holland, J P; Thill, G P; Jackson, K A

    1981-02-10

    Segments of yeast genomic DNA containing two enolase structural genes have been isolated by subculture cloning procedures using a cDNA hybridization probe synthesized from purified yeast enolase mRNA. Based on restriction endonuclease and transcriptional maps of these two segments of yeast DNA, each hybrid plasmid contains a region of extensive nucleotide sequence homology which forms hybrids with the cDNA probe. The DNA sequences which flank this homologous region in the two hybrid plasmids are nonhomologous indicating that these sequences are nontandemly repeated in the yeast genome. The complete nucleotide sequence of the coding as well as the flanking noncoding regions of these genes has been determined. The amino acid sequence predicted from one reading frame of both structural genes is extremely similar to that determined for yeast enolase (Chin, C. C. Q., Brewer, J. M., Eckard, E., and Wold, F. (1981) J. Biol. Chem. 256, 1370-1376), confirming that these isolated structural genes encode yeast enolase. The nucleotide sequences of the coding regions of the genes are approximately 95% homologous, and neither gene contains an intervening sequence. Codon utilization in the enolase genes follows the same biased pattern previously described for two yeast glyceraldehyde-3-phosphate dehydrogenase structural genes (Holland, J. P., and Holland, M. J. (1980) J. Biol. Chem. 255, 2596-2605). DNA blotting analysis confirmed that the isolated segments of yeast DNA are colinear with yeast genomic DNA and that there are two nontandemly repeated enolase genes per haploid yeast genome. The noncoding portions of the two enolase genes adjacent to the initiation and termination codons are approximately 70% homologous and contain sequences thought to be involved in the synthesis and processing messenger RNA. Finally there are regions of extensive homology between the two enolase structural genes and two yeast glyceraldehyde-3-phosphate dehydrogenase structural genes within the 5

  10. Lace expansion for dummies

    NARCIS (Netherlands)

    Bolthausen, Erwin; Van Der Hofstad, Remco; Kozma, Gady

    2018-01-01

    We show Green's function asymptotic upper bound for the two-point function of weakly self-Avoiding walk in d >4, revisiting a classic problem. Our proof relies on Banach algebras to analyse the lace-expansion fixed point equation and is simpler than previous approaches in that it avoids Fourier

  11. OPEC future capacity expansions

    International Nuclear Information System (INIS)

    Sandrea, I.

    2005-01-01

    This conference presentation examined OPEC future capacity expansions including highlights from 2000-2004 from the supply perspective and actions by OPEC; OPEC spare capacity in 2005/2006; medium-term capacity expansion and investments; long-term scenarios, challenges and opportunities; and upstream policies in member countries. Highlights from the supply perspective included worst than expected non-OPEC supply response; non-OPEC supply affected by a number of accidents and strikes; geopolitical tensions; and higher than expected demand for OPEC crude. OPEC's actions included closer relationship with other producers and consumers; capacity expansions in 2004 and 2005/2006; and OPEC kept the market well supplied with crude in 2004. The presentation also provided data using graphical charts on OPEC net capacity additions until 2005/2006; OPEC production versus spare capacity from 2003 to 2005; OPEC production and capacity to 2010; and change in required OPEC production from 2005-2020. Medium term expansion to 2010 includes over 60 projects. Medium-term risks such as project execution, financing, costs, demand, reserves, depletion, integration of Iraq, and geopolitical tensions were also discussed. The presentation concluded that in the long term, large uncertainties remain; the peak of world supply is not imminent; and continued and enhanced cooperation is essential to market stability. tabs., figs

  12. AUTO-EXPANSIVE FLOW

    Science.gov (United States)

    Physics suggests that the interplay of momentum, continuity, and geometry in outward radial flow must produce density and concomitant pressure reductions. In other words, this flow is intrinsically auto-expansive. It has been proposed that this process is the key to understanding...

  13. Flavivirus RNAi suppression: decoding non-coding RNA.

    Science.gov (United States)

    Pijlman, Gorben P

    2014-08-01

    Flaviviruses are important human pathogens that are transmitted by invertebrate vectors, mostly mosquitoes and ticks. During replication in their vector, flaviviruses are subject to a potent innate immune response known as antiviral RNA interference (RNAi). This defense mechanism is associated with the production of small interfering (si)RNA that lead to degradation of viral RNA. To what extent flaviviruses would benefit from counteracting antiviral RNAi is subject of debate. Here, the experimental evidence to suggest the existence of flavivirus RNAi suppressors is discussed. I will highlight the putative role of non-coding, subgenomic flavivirus RNA in suppression of RNAi in insect and mammalian cells. Novel insights from ongoing research will reveal how arthropod-borne viruses modulate innate immunity including antiviral RNAi. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Decoding the non-coding RNAs in Alzheimer's disease.

    Science.gov (United States)

    Schonrock, Nicole; Götz, Jürgen

    2012-11-01

    Non-coding RNAs (ncRNAs) are integral components of biological networks with fundamental roles in regulating gene expression. They can integrate sequence information from the DNA code, epigenetic regulation and functions of multimeric protein complexes to potentially determine the epigenetic status and transcriptional network in any given cell. Humans potentially contain more ncRNAs than any other species, especially in the brain, where they may well play a significant role in human development and cognitive ability. This review discusses their emerging role in Alzheimer's disease (AD), a human pathological condition characterized by the progressive impairment of cognitive functions. We discuss the complexity of the ncRNA world and how this is reflected in the regulation of the amyloid precursor protein and Tau, two proteins with central functions in AD. By understanding this intricate regulatory network, there is hope for a better understanding of disease mechanisms and ultimately developing diagnostic and therapeutic tools.

  15. Paraspeckles: Where Long Noncoding RNA Meets Phase Separation.

    Science.gov (United States)

    Fox, Archa H; Nakagawa, Shinichi; Hirose, Tetsuro; Bond, Charles S

    2018-02-01

    Long noncoding RNA (lncRNA) molecules are some of the newest and least understood players in gene regulation. Hence, we need good model systems with well-defined RNA and protein components. One such system is paraspeckles - protein-rich nuclear organelles built around a specific lncRNA scaffold. New discoveries show how paraspeckles are formed through multiple RNA-protein and protein-protein interactions, some of which involve extensive polymerization, and others with multivalent interactions driving phase separation. Once formed, paraspeckles influence gene regulation through sequestration of component proteins and RNAs, with subsequent depletion in other compartments. Here we focus on the dual aspects of paraspeckle structure and function, revealing an emerging role for these dynamic bodies in a multitude of cellular settings. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Functions and mechanisms of long noncoding RNAs in lung cancer

    Directory of Open Access Journals (Sweden)

    Peng ZZ

    2016-07-01

    Full Text Available Zhenzi Peng, Chunfang Zhang, Chaojun Duan Institute of Medical Sciences, Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha, People’s Republic of China Abstract: Lung cancer is a heterogeneous disease, and there is a lack of adequate biomarkers for diagnosis. Long noncoding RNAs (lncRNAs are emerging as an important set of molecules because of their roles in various key pathophysiological pathways, including cell growth, apoptosis, and metastasis. We review the current knowledge of the lncRNAs in lung cancer. In-depth analyses of lncRNAs in lung cancer have increased the number of potential effective biomarkers, thus providing options to increase the therapeutic benefit. In this review, we summarize the functions, mechanisms, and regulatory networks of lncRNAs in lung cancer, providing a basis for further research in this field. Keywords: ncRNA, tumorigenesis, biomarker, network, proliferation, apoptosis 

  17. Role of Exosomal Noncoding RNAs in Lung Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tao Sun

    2015-01-01

    Full Text Available Lung cancer is the major cause of cancer death worldwide. Novel, recently discovered classes of noncoding RNAs (ncRNAs have diverse functional and regulatory activities and increasing evidence suggests crucial roles for deregulated ncRNAs in the onset and progression of cancer, including lung cancer. Exosomes are small extracellular membrane vesicles of endocytic origin that are released by many cells and are found in most body fluids. Tumor-derived exosomes mediate tumorigenesis by facilitating tumor growth and metastasis. MicroRNAs (miRNAs are a subclass of ncRNAs that are present in exosomes. miRNAs are taken up by neighboring or distant cells and modulate various functions of recipient cells. Here, we review exosome-derived ncRNAs with a focus on miRNAs and their role in lung cancer biology.

  18. Systematic identification of long noncoding RNAs expressed during zebrafish embryogenesis

    DEFF Research Database (Denmark)

    Pauli, Andrea; Valen, Eivind; Lin, Michael F.

    2012-01-01

    Long non-coding RNAs (lncRNAs) comprise a diverse class of transcripts that structurally resemble mRNAs but do not encode proteins. Recent genome-wide studies in human and mouse have annotated lncRNAs expressed in cell lines and adult tissues, but a systematic analysis of lncRNAs expressed during...... of genes with developmental functions. The temporal expression profile of lncRNAs revealed two novel properties: lncRNAs are expressed in narrower time windows than protein-coding genes and are specifically enriched in early-stage embryos. In addition, several lncRNAs show tissue-specific expression...... and distinct subcellular localization patterns. Integrative computational analyses associated individual lncRNAs with specific pathways and functions, ranging from cell cycle regulation to morphogenesis. Our study provides the first systematic identification of lncRNAs in a vertebrate embryo and forms...

  19. Long noncoding RNAs as Organizers of Nuclear Architecture.

    Science.gov (United States)

    Cheng, Lu; Ming, Hui; Zhu, Minzhe; Wen, Bo

    2016-03-01

    In the eukaryotic cell nucleus, chromatin and its associated macromolecules must be organized into a higher-ordered conformation to function normally. However, mechanisms underlying the organization and dynamics of the nucleus remain unclear. Long noncoding RNAs (lncRNAs), i.e., transcripts longer than 200 nucleotides with little or no protein-coding capacity, are increasingly recognized as important regulators in diverse biological processes. Recent studies have shown that some lncRNAs are involved in various aspects of genome organization, including the facilitation of chromosomal interactions and establishment of nuclear bodies, suggesting that lncRNAs act as general organizers of the nuclear architecture. Here, we discuss recent advances in this emerging and intriguing field.

  20. Evaluation of Agency Non-Code Layered Pressure Vessels (LPVs)

    Science.gov (United States)

    Prosser, William H.

    2014-01-01

    In coordination with the Office of Safety and Mission Assurance and the respective Center Pressure System Managers (PSMs), the NASA Engineering and Safety Center (NESC) was requested to formulate a consensus draft proposal for the development of additional testing and analysis methods to establish the technical validity, and any limitation thereof, for the continued safe operation of facility non-code layered pressure vessels. The PSMs from each NASA Center were asked to participate as part of the assessment team by providing, collecting, and reviewing data regarding current operations of these vessels. This report contains the outcome of the assessment and the findings, observations, and NESC recommendations to the Agency and individual NASA Centers.

  1. Novel Approach to Analyzing MFE of Noncoding RNA Sequences.

    Science.gov (United States)

    George, Tina P; Thomas, Tessamma

    2016-01-01

    Genomic studies have become noncoding RNA (ncRNA) centric after the study of different genomes provided enormous information on ncRNA over the past decades. The function of ncRNA is decided by its secondary structure, and across organisms, the secondary structure is more conserved than the sequence itself. In this study, the optimal secondary structure or the minimum free energy (MFE) structure of ncRNA was found based on the thermodynamic nearest neighbor model. MFE of over 2600 ncRNA sequences was analyzed in view of its signal properties. Mathematical models linking MFE to the signal properties were found for each of the four classes of ncRNA analyzed. MFE values computed with the proposed models were in concordance with those obtained with the standard web servers. A total of 95% of the sequences analyzed had deviation of MFE values within ±15% relative to those obtained from standard web servers.

  2. Rfam: annotating families of non-coding RNA sequences.

    Science.gov (United States)

    Daub, Jennifer; Eberhardt, Ruth Y; Tate, John G; Burge, Sarah W

    2015-01-01

    The primary task of the Rfam database is to collate experimentally validated noncoding RNA (ncRNA) sequences from the published literature and facilitate the prediction and annotation of new homologues in novel nucleotide sequences. We group homologous ncRNA sequences into "families" and related families are further grouped into "clans." We collate and manually curate data cross-references for these families from other databases and external resources. Our Web site offers researchers a simple interface to Rfam and provides tools with which to annotate their own sequences using our covariance models (CMs), through our tools for searching, browsing, and downloading information on Rfam families. In this chapter, we will work through examples of annotating a query sequence, collating family information, and searching for data.

  3. Repeatability of Cryogenic Multilayer Insulation

    Science.gov (United States)

    Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

    2017-12-01

    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation (MLI) has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five Glenn Research Center (GRC) provided coupons with 25 layers was shown to be +/- 8.4% whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0%. A second group of 10 coupons has been fabricated by Yetispace and tested by Florida State University, the repeatability between coupons has been shown to be +/- 15-25%. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  4. The Long Noncoding RNA Landscape of the Mouse Eye.

    Science.gov (United States)

    Chen, Weiwei; Yang, Shuai; Zhou, Zhonglou; Zhao, Xiaoting; Zhong, Jiayun; Reinach, Peter S; Yan, Dongsheng

    2017-12-01

    Long noncoding RNAs (lncRNAs) are important regulators of diverse biological functions. However, an extensive in-depth analysis of their expression profile and function in mammalian eyes is still lacking. Here we describe comprehensive landscapes of stage-dependent and tissue-specific lncRNA expression in the mouse eye. Affymetrix transcriptome array profiled lncRNA signatures from six different ocular tissue subsets (i.e., cornea, lens, retina, RPE, choroid, and sclera) in newborn and 8-week-old mice. Quantitative RT-PCR analysis validated array findings. Cis analyses and Gene Ontology (GO) annotation of protein-coding genes adjacent to signature lncRNA loci clarified potential lncRNA roles in maintaining tissue identity and regulating eye maturation during the aforementioned phase. In newborn and 8-week-old mice, we identified 47,332 protein-coding and noncoding gene transcripts. LncRNAs comprise 19,313 of these transcripts annotated in public data banks. During this maturation phase of these six different tissue subsets, more than 1000 lncRNAs expression levels underwent ≥2-fold changes. qRT-PCR analysis confirmed part of the gene microarray analysis results. K-means clustering identified 910 lncRNAs in the P0 groups and 686 lncRNAs in the postnatal 8-week-old groups, suggesting distinct tissue-specific lncRNA clusters. GO analysis of protein-coding genes proximal to lncRNA signatures resolved close correlations with their tissue-specific functional maturation between P0 and 8 weeks of age in the 6 tissue subsets. Characterizating maturational changes in lncRNA expression patterns as well as tissue-specific lncRNA signatures in six ocular tissues suggest important contributions made by lncRNA to the control of developmental processes in the mouse eye.

  5. EG-10LONG NON-CODING RNAs IN GLIOBLASTOMA

    Science.gov (United States)

    Pastori, Chiara; Kapranov, Philipp; Penas, Clara; Laurent, Georges St.; Ayad, Nagi; Wahlestedt, Claes

    2014-01-01

    Glioblastoma (GBM) is the most common, aggressive and incurable primary brain tumor in adults. Genome studies have confirmed that GBM is extremely heterogeneous with many genetically different subgroups. Consequently, there is much current interest in epigenetic drugs that may be active across genetically distinct tumors. In support of this, some epigenetic drugs has recently shown efficacy against several cancers including glioblastoma. Much recent interest has also been devoted to long non-coding RNAs (lncRNAs), which can modulate gene expression regulating chromatin architecture, in part through the interaction with epigenetic protein machineries. To date, however, only a few lncRNAs have been studied in human cancer. We therefore embarked on a comprehensive genomic and functional analysis of lncRNAs in GBM. Using the Helicos Single Molecule Sequencing platform glioblastoma samples were sequenced resulting in the identification of hundreds of dysregulated lncRNAs. Among these the lncRNA HOTAIR was found massively increased in GBM. This observation parallels findings in other cancers where HOTAIR's increased expression has been linked to poor prognosis due to metastatic events. Interestingly, here we show that in glioblastoma HOTAIR does not promote metastasis, but instead sustains the ability of these cells to proliferate. In fact, we demonstrate that HOTAIR knockdown in GBM strongly impairs cell proliferation and induces apoptosis in vitro and in vivo. Further, we implicate HOTAIR in the mechanism of action of certain epigenetic drugs. In summary, long noncoding RNAs (newly discovered epigenomic factors) play a vital role in GBM and deserve attention as entirely novel drug targets as well as biomarkers.

  6. The Non-Coding Regulatory RNA Revolution in Archaea

    Directory of Open Access Journals (Sweden)

    Diego Rivera Gelsinger

    2018-03-01

    Full Text Available Small non-coding RNAs (sRNAs are ubiquitously found in the three domains of life playing large-scale roles in gene regulation, transposable element silencing and defense against foreign elements. While a substantial body of experimental work has been done to uncover function of sRNAs in Bacteria and Eukarya, the functional roles of sRNAs in Archaea are still poorly understood. Recently, high throughput studies using RNA-sequencing revealed that sRNAs are broadly expressed in the Archaea, comprising thousands of transcripts within the transcriptome during non-challenged and stressed conditions. Antisense sRNAs, which overlap a portion of a gene on the opposite strand (cis-acting, are the most abundantly expressed non-coding RNAs and they can be classified based on their binding patterns to mRNAs (3′ untranslated region (UTR, 5′ UTR, CDS-binding. These antisense sRNAs target many genes and pathways, suggesting extensive roles in gene regulation. Intergenic sRNAs are less abundantly expressed and their targets are difficult to find because of a lack of complete overlap between sRNAs and target mRNAs (trans-acting. While many sRNAs have been validated experimentally, a regulatory role has only been reported for very few of them. Further work is needed to elucidate sRNA-RNA binding mechanisms, the molecular determinants of sRNA-mediated regulation, whether protein components are involved and how sRNAs integrate with complex regulatory networks.

  7. Noncoding DNA in lipofection of HeLa cells-a few insights.

    Science.gov (United States)

    Symens, Nathalie; Rejman, Joanna; Lucas, Bart; Demeester, Joseph; De Smedt, Stefaan C; Remaut, Katrien

    2013-03-04

    In cationic carrier-mediated gene delivery, the disproportional relationship between the quantity of delivered DNA and the amount of encoded protein produced is a well-known phenomenon. The numerous intracellular barriers which need to be overcome by pDNA to reach the nucleoplasm play a major role in it. In contrast to what one would expect, a partial replacement of coding pDNA by noncoding DNA does not lead to a decrease in transfection efficiency. The mechanism underlying this observation is still unclear. Therefore, we investigated which constituents of the transfection process might contribute to this phenomenon. Our data reveal that the topology of the noncoding plasmid DNA plays a major role. Noncoding pDNA can be used only in a supercoiled form to replace coding pDNA in Lipofectamine lipoplexes, without a loss in transfection levels. When noncoding pDNA is linearized or partly digested, it diminishes the transfection potential of coding pDNA, as does noncoding salmon DNA. The difference in transfection efficiencies could not be attributed to diverse physicochemical characteristics of the Lipofectamine lipoplexes containing different types of noncoding DNA or to the extent of their internalization. At the level of endosomal release, however, nucleic acid release from the endosomal compartment proceeds faster when lipoplexes contain noncoding salmon DNA. Since the half-life of pDNA in the cytosol hardly exceeds 90 min, it is conceivable that prolonged release of coding pDNA from complexes carrying supercoiled noncoding pDNA may explain its positive effect on transfection, while this depot effect does not exist when noncoding salmon DNA is used.

  8. Properties of non-coding DNA and identification of putative cis-regulatory elements in Theileria parva

    Directory of Open Access Journals (Sweden)

    Guo Xiang

    2008-12-01

    Full Text Available Abstract Background Parasites in the genus Theileria cause lymphoproliferative diseases in cattle, resulting in enormous socio-economic losses. The availability of the genome sequences and annotation for T. parva and T. annulata has facilitated the study of parasite biology and their relationship with host cell transformation and tropism. However, the mechanism of transcriptional regulation in this genus, which may be key to understanding fundamental aspects of its parasitology, remains poorly understood. In this study, we analyze the evolution of non-coding sequences in the Theileria genome and identify conserved sequence elements that may be involved in gene regulation of these parasitic species. Results Intergenic regions and introns in Theileria are short, and their length distributions are considerably right-skewed. Intergenic regions flanked by genes in 5'-5' orientation tend to be longer and slightly more AT-rich than those flanked by two stop codons; intergenic regions flanked by genes in 3'-5' orientation have intermediate values of length and AT composition. Intron position is negatively correlated with intron length, and positively correlated with GC content. Using stringent criteria, we identified a set of high-quality orthologous non-coding sequences between T. parva and T. annulata, and determined the distribution of selective constraints across regions, which are shown to be higher close to translation start sites. A positive correlation between constraint and length in both intergenic regions and introns suggests a tight control over length expansion of non-coding regions. Genome-wide searches for functional elements revealed several conserved motifs in intergenic regions of Theileria genomes. Two such motifs are preferentially located within the first 60 base pairs upstream of transcription start sites in T. parva, are preferentially associated with specific protein functional categories, and have significant similarity to know

  9. Molecular analysis of the eTG trinucleotide repeat in South African ...

    African Journals Online (AJOL)

    -4 When amplified, this trinucleotide repeat is responsible for DNA instability and molecular pathology. A similar mechanism of trinucleotide repeat expansion has been described in fragile X mental retardation syndrome. (CGG):·· spinobulbar muscular atrophy (CAG)' and, more. MRC Human Ecogenetics Research Unit, ...

  10. Genetic Contributors to Intergenerational CAG Repeat Instability in Huntington's Disease Knock-In Mice.

    Science.gov (United States)

    Neto, João Luís; Lee, Jong-Min; Afridi, Ali; Gillis, Tammy; Guide, Jolene R; Dempsey, Stephani; Lager, Brenda; Alonso, Isabel; Wheeler, Vanessa C; Pinto, Ricardo Mouro

    2017-02-01

    Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat in exon 1 of the HTT gene. Longer repeat sizes are associated with increased disease penetrance and earlier ages of onset. Intergenerationally unstable transmissions are common in HD families, partly underlying the genetic anticipation seen in this disorder. HD CAG knock-in mouse models also exhibit a propensity for intergenerational repeat size changes. In this work, we examine intergenerational instability of the CAG repeat in over 20,000 transmissions in the largest HD knock-in mouse model breeding datasets reported to date. We confirmed previous observations that parental sex drives the relative ratio of expansions and contractions. The large datasets further allowed us to distinguish effects of paternal CAG repeat length on the magnitude and frequency of expansions and contractions, as well as the identification of large repeat size jumps in the knock-in models. Distinct degrees of intergenerational instability were observed between knock-in mice of six background strains, indicating the occurrence of trans-acting genetic modifiers. We also found that lines harboring a neomycin resistance cassette upstream of Htt showed reduced expansion frequency, indicative of a contributing role for sequences in cis, with the expanded repeat as modifiers of intergenerational instability. These results provide a basis for further understanding of the mechanisms underlying intergenerational repeat instability. Copyright © 2017 by the Genetics Society of America.

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

    Science.gov (United States)

    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.

  12. Repeat Customer Success in Extension

    Science.gov (United States)

    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…

  13. 78 FR 65594 - Vehicular Repeaters

    Science.gov (United States)

    2013-11-01

    ... coordinators estimate the effect on coordination fees? Does the supposed benefit that mobile repeater stations... allow the licensing and operation of vehicular repeater systems and other mobile repeaters by public... email: [email protected] or phone: 202-418- 0530 or TTY: 202-418-0432. For detailed instructions for...

  14. The Non-Coding RNA Ontology (NCRO): a comprehensive resource for the unification of non-coding RNA biology.

    Science.gov (United States)

    Huang, Jingshan; Eilbeck, Karen; Smith, Barry; Blake, Judith A; Dou, Dejing; Huang, Weili; Natale, Darren A; Ruttenberg, Alan; Huan, Jun; Zimmermann, Michael T; Jiang, Guoqian; Lin, Yu; Wu, Bin; Strachan, Harrison J; He, Yongqun; Zhang, Shaojie; Wang, Xiaowei; Liu, Zixing; Borchert, Glen M; Tan, Ming

    2016-01-01

    In recent years, sequencing technologies have enabled the identification of a wide range of non-coding RNAs (ncRNAs). Unfortunately, annotation and integration of ncRNA data has lagged behind their identification. Given the large quantity of information being obtained in this area, there emerges an urgent need to integrate what is being discovered by a broad range of relevant communities. To this end, the Non-Coding RNA Ontology (NCRO) is being developed to provide a systematically structured and precisely defined controlled vocabulary for the domain of ncRNAs, thereby facilitating the discovery, curation, analysis, exchange, and reasoning of data about structures of ncRNAs, their molecular and cellular functions, and their impacts upon phenotypes. The goal of NCRO is to serve as a common resource for annotations of diverse research in a way that will significantly enhance integrative and comparative analysis of the myriad resources currently housed in disparate sources. It is our belief that the NCRO ontology can perform an important role in the comprehensive unification of ncRNA biology and, indeed, fill a critical gap in both the Open Biological and Biomedical Ontologies (OBO) Library and the National Center for Biomedical Ontology (NCBO) BioPortal. Our initial focus is on the ontological representation of small regulatory ncRNAs, which we see as the first step in providing a resource for the annotation of data about all forms of ncRNAs. The NCRO ontology is free and open to all users, accessible at: http://purl.obolibrary.org/obo/ncro.owl.

  15. Expansion at Olympic Dam

    International Nuclear Information System (INIS)

    Lewis, C.

    1997-01-01

    The Olympic Dam orebody is the 6th largest copper and the single largest uranium orebody in the world. Mine production commenced in June 1988, at an annual production rate of around 45,000 tonnes of copper and 1,000 tonnes of uranium. Western Mining Corporation announced in 1996 a proposed $1.25 billion expansion of the Olympic Dam operation to raise the annual production capacity of the mine to 200,000 tonnes of copper, approximately 3,700 tonnes of uranium, 75,000 ounces of gold and 950,000 ounces of silver by 2001. Further optimisation work has identified a faster track expansion route, with an increase in the capital cost to $1.487 billion but improved investment outcome, a new target completion date of end 1999, and a new uranium output of 4,600 tonnes per annum from that date

  16. Financing electricity expansion

    International Nuclear Information System (INIS)

    Hyman, L.S.

    1994-01-01

    Expansion of electricity supply is associated with economic development. The installation and enlargement of power systems in developing countries entails a huge financial burden, however. Energy consumers in such countries must pay not only for supplies but for the cost of raising the capital for expansion on the international markets. Estimates are presented for the capital expenditure for electricity supply over the period 1990 to 2020 for the major world regions, using approximations for the cost of plant and capital and for the returns earned. These data lead to the conclusion that the five regions with the lowest per capita incomes are those which will need the major part of the capital expenditure and the highest percentage of external finance. (6 tables) (UK)

  17. Bigravity from gradient expansion

    International Nuclear Information System (INIS)

    Yamashita, Yasuho; Tanaka, Takahiro

    2016-01-01

    We discuss how the ghost-free bigravity coupled with a single scalar field can be derived from a braneworld setup. We consider DGP two-brane model without radion stabilization. The bulk configuration is solved for given boundary metrics, and it is substituted back into the action to obtain the effective four-dimensional action. In order to obtain the ghost-free bigravity, we consider the gradient expansion in which the brane separation is supposed to be sufficiently small so that two boundary metrics are almost identical. The obtained effective theory is shown to be ghost free as expected, however, the interaction between two gravitons takes the Fierz-Pauli form at the leading order of the gradient expansion, even though we do not use the approximation of linear perturbation. We also find that the radion remains as a scalar field in the four-dimensional effective theory, but its coupling to the metrics is non-trivial.

  18. Expansion of magnetic clouds

    International Nuclear Information System (INIS)

    Suess, S.T.

    1987-01-01

    Magnetic clouds are a carefully defined subclass of all interplanetary signatures of coronal mass ejections whose geometry is thought to be that of a cylinder embedded in a plane. It has been found that the total magnetic pressure inside the clouds is higher than the ion pressure outside, and that the clouds are expanding at 1 AU at about half the local Alfven speed. The geometry of the clouds is such that even though the magnetic pressure inside is larger than the total pressure outside, expansion will not occur because the pressure is balanced by magnetic tension - the pinch effect. The evidence for expansion of clouds at 1 AU is nevertheless quite strong so another reason for its existence must be found. It is demonstrated that the observations can be reproduced by taking into account the effects of geometrical distortion of the low plasma beta clouds as they move away from the Sun

  19. IKEA's International Expansion

    OpenAIRE

    Harapiak, Clayton

    2013-01-01

    This case concerns a global retailing firm that is dealing with strategic management and marketing issues. Applying a scenario of international expansion, this case provides a thorough analysis of the current business environment for IKEA. Utilizing a variety of methods (e.g. SWOT, PESTLE, McKinsey Matrix) the overall objective is to provide students with the opportunity to apply their research skills and knowledge regarding a highly competitive industry to develop strategic marketing strateg...

  20. Symmetric eikonal expansion

    International Nuclear Information System (INIS)

    Matsuki, Takayuki

    1976-01-01

    Symmetric eikonal expansion for the scattering amplitude is formulated for nonrelativistic and relativistic potential scatterings and also for the quantum field theory. The first approximations coincide with those of Levy and Sucher. The obtained scattering amplitudes are time reversal invariant for all cases and are crossing symmetric for the quantum field theory in each order of approximation. The improved eikonal phase introduced by Levy and Sucher is also derived from the different approximation scheme from the above. (auth.)

  1. Series expansions without diagrams

    International Nuclear Information System (INIS)

    Bhanot, G.; Creutz, M.; Horvath, I.; Lacki, J.; Weckel, J.

    1994-01-01

    We discuss the use of recursive enumeration schemes to obtain low- and high-temperature series expansions for discrete statistical systems. Using linear combinations of generalized helical lattices, the method is competitive with diagrammatic approaches and is easily generalizable. We illustrate the approach using Ising and Potts models. We present low-temperature series results in up to five dimensions and high-temperature series in three dimensions. The method is general and can be applied to any discrete model

  2. Targeting Non-Coding RNAs in Plants with the CRISPR-Cas Technology is a Challenge yet Worth Accepting.

    Science.gov (United States)

    Basak, Jolly; Nithin, Chandran

    2015-01-01

    Non-coding RNAs (ncRNAs) have emerged as versatile master regulator of biological functions in recent years. MicroRNAs (miRNAs) are small endogenous ncRNAs of 18-24 nucleotides in length that originates from long self-complementary precursors. Besides their direct involvement in developmental processes, plant miRNAs play key roles in gene regulatory networks and varied biological processes. Alternatively, long ncRNAs (lncRNAs) are a large and diverse class of transcribed ncRNAs whose length exceed that of 200 nucleotides. Plant lncRNAs are transcribed by different RNA polymerases, showing diverse structural features. Plant lncRNAs also are important regulators of gene expression in diverse biological processes. There has been a breakthrough in the technology of genome editing, the CRISPR-Cas9 (clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9) technology, in the last decade. CRISPR loci are transcribed into ncRNA and eventually form a functional complex with Cas9 and further guide the complex to cleave complementary invading DNA. The CRISPR-Cas technology has been successfully applied in model plants such as Arabidopsis and tobacco and important crops like wheat, maize, and rice. However, all these studies are focused on protein coding genes. Information about targeting non-coding genes is scarce. Hitherto, the CRISPR-Cas technology has been exclusively used in vertebrate systems to engineer miRNA/lncRNAs, but it is still relatively unexplored in plants. While briefing miRNAs, lncRNAs and applications of the CRISPR-Cas technology in human and animals, this review essentially elaborates several strategies to overcome the challenges of applying the CRISPR-Cas technology in editing ncRNAs in plants and the future perspective of this field.

  3. Targeting non-coding RNAs in Plants with the CRISPR-Cas technology is a challenge yet worth accepting

    Directory of Open Access Journals (Sweden)

    Jolly eBasak

    2015-11-01

    Full Text Available Non-coding RNAs (ncRNAs have emerged as versatile master regulator of biological functions in recent years. MicroRNAs (miRNAs are small endogenous ncRNAs of 18-24 nucleotides in length that originates from long self-complementary precursors. Besides their direct involvement in developmental processes, plant miRNAs play key roles in gene regulatory networks and varied biological processes. Alternatively, long ncRNAs (lncRNAs are a large and diverse class of transcribed ncRNAs whose length exceed that of 200 nucleotides. Plant lncRNAs are transcribed by different RNA polymerases, showing diverse structural features. Plant lncRNAs also are important regulators of gene expression in diverse biological processes. There has been a breakthrough in the technology of genome editing, the CRISPR-Cas9 (clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 technology, in the last decade. CRISPR loci are transcribed into ncRNA and eventually form a functional complex with Cas9 and further guide the complex to cleave complementary invading DNA. The CRISPR-Cas technology has been successfully applied in model plants such as Arabidopsis and tobacco and important crops like wheat, maize and rice. However, all these studies are focused on protein coding genes. Information about targeting non-coding genes is scarce. Hitherto, the CRISPR-Cas technology has been exclusively used in vertebrate systems to engineer miRNA/lncRNAs, but it is still relatively unexplored in plants. While briefing miRNAs, lncRNAs and applications of the CRISPR-Cas technology in human and animals, this review essentially elaborates several strategies to overcome the challenges of applying the CRISPR-Cas technology in editing ncRNAs in plants and the future perspective of this field.

  4. Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease

    DEFF Research Database (Denmark)

    Lindquist, S. G.; Duno, M.; Batbayli, M.

    2013-01-01

    Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21-linked frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS). We here report the prevalence of the expansion in a hospital-based cohort and associated clinical...

  5. Reprogramming Antagonizes the Oncogenicity of HOXA13-Long Noncoding RNA HOTTIP Axis in Gastric Cancer Cells.

    Science.gov (United States)

    Wu, Deng-Chyang; Wang, Sophie S W; Liu, Chung-Jung; Wuputra, Kenly; Kato, Kohsuke; Lee, Yen-Liang; Lin, Ying-Chu; Tsai, Ming-Ho; Ku, Chia-Chen; Lin, Wen-Hsin; Wang, Shin-Wei; Kishikawa, Shotaro; Noguchi, Michiya; Wu, Chu-Chieh; Chen, Yi-Ting; Chai, Chee-Yin; Lin, Chen-Lung Steve; Kuo, Kung-Kai; Yang, Ya-Han; Miyoshi, Hiroyuki; Nakamura, Yukio; Saito, Shigeo; Nagata, Kyosuke; Lin, Chang-Shen; Yokoyama, Kazunari K

    2017-10-01

    Reprogramming of cancer cells into induced pluripotent stem cells (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP7 promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase, WD repeat-containing protein 5, and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells. By contrast, HOXA13 inhibited BMP7 expression in iPSLCs via the corecruitment of HOXA13, enhancer of zeste homolog 2, Jumonji and AT rich interactive domain 2, and lncRNA HoxA transcript antisense RNA (HOTAIR) to various cis-element of the BMP7 promoter. Knockdown experiments demonstrated that HOTTIP contributed positively, but HOTAIR regulated negatively to HOXA13-mediated BMP7 expression in cancer cells and iPSLCs, respectively. These findings indicate that the recruitment of HOXA13-HOTTIP and HOXA13-HOTAIR to different sites in the BMP7 promoter is crucial for the oncogenic fate of human gastric cells. Reprogramming with octamer-binding protein 4 and Jun dimerization protein 2 can inhibit tumorigenesis by switching off BMP7. Stem Cells 2017;35:2115-2128. © 2017 The Authors Stem Cells published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  6. Ups and Downs: Mechanisms of Repeat Instability in the Fragile X-Related Disorders

    Directory of Open Access Journals (Sweden)

    Xiao-Nan Zhao

    2016-09-01

    Full Text Available The Fragile X-related disorders (FXDs are a group of clinical conditions resulting from the expansion of a CGG/CCG-repeat tract in exon 1 of the Fragile X mental retardation 1 (FMR1 gene. While expansions of the repeat tract predominate, contractions are also seen with the net result being that individuals can show extensive repeat length heterogeneity in different tissues. The mechanisms responsible for expansion and contraction are still not well understood. This review will discuss what is known about these processes and current evidence that supports a model in which expansion arises from the interaction of components of the base excision repair, mismatch repair and transcription coupled repair pathways.

  7. Toward understanding non-coding RNA roles in intracranial aneurysms and subarachnoid hemorrhage

    Directory of Open Access Journals (Sweden)

    Huang Fengzhen

    2017-05-01

    Full Text Available Subarachnoid hemorrhage (SAH is a common and frequently life-threatening cerebrovascular disease, which is mostly related with a ruptured intracranial aneurysm. Its complications include rebleeding, early brain injury, cerebral vasospasm, delayed cerebral ischemia, chronic hydrocephalus, and also non neurological problems. Non-coding RNAs (ncRNAs, comprising of microRNAs (miRNAs, small interfering RNAs (siRNAs and long non-coding RNAs (lncRNAs, play an important role in intracranial aneurysms and SAH. Here, we review the non-coding RNAs expression profile and their related mechanisms in intracranial aneurysms and SAH. Moreover, we suggest that these non-coding RNAs function as novel molecular biomarkers to predict intracranial aneurysms and SAH, and may yield new therapies after SAH in the future.

  8. Non-Coding Transcript Heterogeneity in Mesothelioma: Insights from Asbestos-Exposed Mice.

    Science.gov (United States)

    Felley-Bosco, Emanuela; Rehrauer, Hubert

    2018-04-11

    Mesothelioma is an aggressive, rapidly fatal cancer and a better understanding of its molecular heterogeneity may help with making more efficient therapeutic strategies. Non-coding RNAs represent a larger part of the transcriptome but their contribution to diseases is not fully understood yet. We used recently obtained RNA-seq data from asbestos-exposed mice and performed data mining of publicly available datasets in order to evaluate how non-coding RNA contribute to mesothelioma heterogeneity. Nine non-coding RNAs are specifically elevated in mesothelioma tumors and contribute to human mesothelioma heterogeneity. Because some of them have known oncogenic properties, this study supports the concept of non-coding RNAs as cancer progenitor genes.

  9. Repeated causal decision making.

    Science.gov (United States)

    Hagmayer, York; Meder, Björn

    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 such situations and how they use their knowledge to adapt to changes in the decision context. Our studies show that decision makers' behavior is strongly contingent on their causal beliefs and that people exploit their causal knowledge to assess the consequences of changes in the decision problem. A high consistency between hypotheses about causal structure, causally expected values, and actual choices was observed. The experiments show that (a) existing causal hypotheses guide the interpretation of decision feedback, (b) consequences of decisions are used to revise existing causal beliefs, and (c) decision makers use the experienced feedback to induce a causal model of the choice situation even when they have no initial causal hypotheses, which (d) enables them to adapt their choices to changes of the decision problem. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

  10. Expansions for Coulomb wave functions

    NARCIS (Netherlands)

    Boersma, J.

    1969-01-01

    In this paper we derive a number of expansions for Whittaker functions, regular and irregular Coulomb wave functions. The main result consists of a new expansion for the irregular Coulomb wave functions of orders zero and one in terms of regular Coulomb wave functions. The latter expansions are

  11. Non-coding RNAs in endometriosis: a narrative review.

    Science.gov (United States)

    Panir, Kavita; Schjenken, John E; Robertson, Sarah A; Hull, M Louise

    2018-04-25

    Endometriosis is a benign gynaecological disorder, which affects 10% of reproductive-aged women and is characterized by endometrial cells from the lining of the uterus being found outside the uterine cavity. However, the pathophysiological mechanisms causing the development of this heterogeneous disease remain enigmatic, and a lack of effective biomarkers necessitates surgical intervention for diagnosis. There is international recognition that accurate non-invasive diagnostic tests and more effective therapies are urgently needed. Non-coding RNA (ncRNA) molecules, which are important regulators of cellular function, have been implicated in many chronic conditions. In endometriosis, transcriptome profiling of tissue samples and functional in vivo and in vitro studies demonstrate that ncRNAs are key contributors to the disease process. In this review, we outline the biogenesis of various ncRNAs relevant to endometriosis and then summarize the evidence indicating their roles in regulatory pathways that govern disease establishment and progression. Articles from 2000 to 2016 were selected for relevance, validity and quality, from results obtained in PubMed, MEDLINE and Google Scholar using the following search terms: ncRNA and reproduction; ncRNA and endometriosis; miRNA and endometriosis; lncRNA and endometriosis; siRNA and endometriosis; endometriosis; endometrial; cervical; ovary; uterus; reproductive tract. All articles were independently screened for eligibility by the authors. This review integrates extensive information from all relevant published studies focusing on microRNAs, long ncRNAs and short inhibitory RNAs in endometriosis. We outline the biological function and synthesis of microRNAs, long ncRNAs and short inhibitory RNAs and provide detailed findings from human research as well as functional studies carried out both in vitro and in vivo, including animal models. Although variability in findings between individual studies exists, collectively, the

  12. Expansion of all multitrace tree level EYM amplitudes

    Science.gov (United States)

    Du, Yi-Jian; Feng, Bo; Teng, Fei

    2017-12-01

    In this paper, we investigate the expansion of tree level multitrace Einstein-Yang-Mills (EYM) amplitudes. First, we propose two types of recursive expansions of tree level EYM amplitudes with an arbitrary number of gluons, gravitons and traces by those amplitudes with fewer traces or/and gravitons. Then we give many support evidence, including proofs using the Cachazo-He-Yuan (CHY) formula and Britto-Cachazo-Feng-Witten (BCFW) recursive relation. As a byproduct, two types of generalized BCJ relations for multitrace EYM are further proposed, which will be useful in the BCFW proof. After one applies the recursive expansions repeatedly, any multitrace EYM amplitudes can be given in the Kleiss-Kuijf (KK) basis of tree level color ordered Yang-Mills (YM) amplitudes. Thus the Bern-Carrasco-Johansson (BCJ) numerators, as the expansion coefficients, for all multitrace EYM amplitudes are naturally constructed.

  13. Purifying selection acts on coding and non-coding sequences of paralogous genes in Arabidopsis thaliana.

    Science.gov (United States)

    Hoffmann, Robert D; Palmgren, Michael

    2016-06-13

    Whole-genome duplications in the ancestors of many diverse species provided the genetic material for evolutionary novelty. Several models explain the retention of paralogous genes. However, how these models are reflected in the evolution of coding and non-coding sequences of paralogous genes is unknown. Here, we analyzed the coding and non-coding sequences of paralogous genes in Arabidopsis thaliana and compared these sequences with those of orthologous genes in Arabidopsis lyrata. Paralogs with lower expression than their duplicate had more nonsynonymous substitutions, were more likely to fractionate, and exhibited less similar expression patterns with their orthologs in the other species. Also, lower-expressed genes had greater tissue specificity. Orthologous conserved non-coding sequences in the promoters, introns, and 3' untranslated regions were less abundant at lower-expressed genes compared to their higher-expressed paralogs. A gene ontology (GO) term enrichment analysis showed that paralogs with similar expression levels were enriched in GO terms related to ribosomes, whereas paralogs with different expression levels were enriched in terms associated with stress responses. Loss of conserved non-coding sequences in one gene of a paralogous gene pair correlates with reduced expression levels that are more tissue specific. Together with increased mutation rates in the coding sequences, this suggests that similar forces of purifying selection act on coding and non-coding sequences. We propose that coding and non-coding sequences evolve concurrently following gene duplication.

  14. Robust identification of noncoding RNA from transcriptomes requires phylogenetically-informed sampling.

    Directory of Open Access Journals (Sweden)

    Stinus Lindgreen

    2014-10-01

    Full Text Available Noncoding RNAs are integral to a wide range of biological processes, including translation, gene regulation, host-pathogen interactions and environmental sensing. While genomics is now a mature field, our capacity to identify noncoding RNA elements in bacterial and archaeal genomes is hampered by the difficulty of de novo identification. The emergence of new technologies for characterizing transcriptome outputs, notably RNA-seq, are improving noncoding RNA identification and expression quantification. However, a major challenge is to robustly distinguish functional outputs from transcriptional noise. To establish whether annotation of existing transcriptome data has effectively captured all functional outputs, we analysed over 400 publicly available RNA-seq datasets spanning 37 different Archaea and Bacteria. Using comparative tools, we identify close to a thousand highly-expressed candidate noncoding RNAs. However, our analyses reveal that capacity to identify noncoding RNA outputs is strongly dependent on phylogenetic sampling. Surprisingly, and in stark contrast to protein-coding genes, the phylogenetic window for effective use of comparative methods is perversely narrow: aggregating public datasets only produced one phylogenetic cluster where these tools could be used to robustly separate unannotated noncoding RNAs from a null hypothesis of transcriptional noise. Our results show that for the full potential of transcriptomics data to be realized, a change in experimental design is paramount: effective transcriptomics requires phylogeny-aware sampling.

  15. At the intersection of non-coding transcription, DNA repair, chromatin structure, and cellular senescence

    Directory of Open Access Journals (Sweden)

    Ryosuke eOhsawa

    2013-07-01

    Full Text Available It is well accepted that non-coding RNAs play a critical role in regulating gene expression. Recent paradigm-setting studies are now revealing that non-coding RNAs, other than microRNAs, also play intriguing roles in the maintenance of chromatin structure, in the DNA damage response, and in adult human stem cell aging. In this review, we will discuss the complex inter-dependent relationships among non-coding RNA transcription, maintenance of genomic stability, chromatin structure and adult stem cell senescence. DNA damage-induced non-coding RNAs transcribed in the vicinity of the DNA break regulate recruitment of the DNA damage machinery and DNA repair efficiency. We will discuss the correlation between non-coding RNAs and DNA damage repair efficiency and the potential role of changing chromatin structures around double-strand break sites. On the other hand, induction of non-coding RNA transcription from the repetitive Alu elements occurs during human stem cell aging and hinders efficient DNA repair causing entry into senescence. We will discuss how this fine balance between transcription and genomic instability may be regulated by the dramatic changes to chromatin structure that accompany cellular senescence.

  16. The Asian Rice Gall Midge (Orseolia oryzae Mitogenome Has Evolved Novel Gene Boundaries and Tandem Repeats That Distinguish Its Biotypes.

    Directory of Open Access Journals (Sweden)

    Isha Atray

    Full Text Available The complete mitochondrial genome of the Asian rice gall midge, Orseolia oryzae (Diptera; Cecidomyiidae was sequenced, annotated and analysed in the present study. The circular genome is 15,286 bp with 13 protein-coding genes, 22 tRNAs and 2 ribosomal RNA genes, and a 578 bp non-coding control region. All protein coding genes used conventional start codons and terminated with a complete stop codon. The genome presented many unusual features: (1 rearrangement in the order of tRNAs as well as protein coding genes; (2 truncation and unusual secondary structures of tRNAs; (3 presence of two different repeat elements in separate non-coding regions; (4 presence of one pseudo-tRNA gene; (5 inversion of the rRNA genes; (6 higher percentage of non-coding regions when compared with other insect mitogenomes. Rearrangements of the tRNAs and protein coding genes are explained on the basis of tandem duplication and random loss model and why intramitochondrial recombination is a better model for explaining rearrangements in the O. oryzae mitochondrial genome is discussed. Furthermore, we evaluated the number of iterations of the tandem repeat elements found in the mitogenome. This led to the identification of genetic markers capable of differentiating rice gall midge biotypes and the two Orseolia species investigated.

  17. Radial expansion and multifragmentation

    International Nuclear Information System (INIS)

    Angelique, J.C.; Bizard, G.; Bougault, R.; Brou, R.; Buta, A.; Colin, J.; Cussol, D.; Durand, D.; Kerambrun, A.; Le Brun, C.; Lecolley, J.F.; Lopez, O.; Louvel, M.; Meslin, C.; Nakagawa, T.; Patry, J.P.; Peter, J.; Popescu, R.; Regimbart, R.; Steckmeyer, J.C.; Tamain, B.; Vient, E.; Yuasa-Nakagawa, K.; Wieloch, A.

    1998-01-01

    The light systems 36 Ar + 27 Al and 64 Zn + nat Ti were measured at several bombarding energies between ∼ 35 and 95 MeV/nucleon. It was found that the predominant part of the cross section is due to binary collisions. In this paper the focus is placed on the properties of the quasi-projectile nuclei. In the central collisions the excitation energies of the quasi-projectile reach values exceeding largely 10 MeV/nucleon. The slope of the high energy part of the distribution can give only an upper limit of the apparent temperature (the average temperature along the decay chain). The highly excited quasi-projectile may get rapidly fragmented rather than sequentially. The heavy fragments are excited and can emit light particles (n, p, d, t, 3 He, α,...) what perturbs additionally the spectrum of these particles. Concerning the expansion energy, one can determine the average kinetic energies of the product (in the quasi-projectile-framework) and compare with simulation values. To fit the experimental data an additional radial expansion energy is to be considered. The average expansion energy depends slightly on the impact parameter but it increases with E * / A, ranging from 0.4 to 1,2 MeV/nucleon for an excitation energy increasing from 7 to 10.5 MeV/nucleon. This collective radial energy seems to be independent of the fragment mass, what is possibly valid for the case of larger quasi-projectile masses. The origin of the expansion is to be determined. It may be due to a compression in the interaction zone at the initial stage of the collision, which propagates in the quasi-projectile and quasi-target, or else, may be due, simply, to the increase of thermal energy leading to a rapid fragment emission. The sequential de-excitation calculation overestimates light particle emission and consequently heavy residues, particularly, at higher excitation energies. This disagreement indicates that a sequential process can not account for the di-excitation of very hot nuclei

  18. Rethinking expansive learning

    DEFF Research Database (Denmark)

    Kolbæk, Ditte; Lundh Snis, Ulrika

    Abstract: This paper analyses an online community of master’s students taking a course in ICT and organisational learning. The students initiated and facilitated an educational design for organisational learning called Proactive Review in the organisation where they are employed. By using an online...... discussion forum on Google groups, they created new ways of reflecting and learning. We used netnography to select qualitative postings from the online community and expansive learning concepts for data analysis. The findings show how students changed practices of organisational learning...

  19. Load regulating expansion fixture

    International Nuclear Information System (INIS)

    Wagner, L.M.; Strum, M.J.

    1998-01-01

    A free standing self contained device for bonding ultra thin metallic films, such as 0.001 inch beryllium foils is disclosed. The device will regulate to a predetermined load for solid state bonding when heated to a bonding temperature. The device includes a load regulating feature, whereby the expansion stresses generated for bonding are regulated and self adjusting. The load regulator comprises a pair of friction isolators with a plurality of annealed copper members located there between. The device, with the load regulator, will adjust to and maintain a stress level needed to successfully and economically complete a leak tight bond without damaging thin foils or other delicate components. 1 fig

  20. Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

    KAUST Repository

    Viterbo, David

    2016-03-16

    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.

  1. Replication Stalling and Heteroduplex Formation within CAG/CTG Trinucleotide Repeats by Mismatch Repair

    KAUST Repository

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

    2016-01-01

    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.

  2. Dynamic Nature of Noncoding RNA Regulation of Adaptive Immune Response

    Directory of Open Access Journals (Sweden)

    Franca Citarella

    2013-08-01

    Full Text Available Immune response plays a fundamental role in protecting the organism from infections; however, dysregulation often occurs and can be detrimental for the organism, leading to a variety of immune-mediated diseases. Recently our understanding of the molecular and cellular networks regulating the immune response, and, in particular, adaptive immunity, has improved dramatically. For many years, much of the focus has been on the study of protein regulators; nevertheless, recent evidence points to a fundamental role for specific classes of noncoding RNAs (ncRNAs in regulating development, activation and homeostasis of the immune system. Although microRNAs (miRNAs are the most comprehensive and well-studied, a number of reports suggest the exciting possibility that long ncRNAs (lncRNAs could mediate host response and immune function. Finally, evidence is also accumulating that suggests a role for miRNAs and other small ncRNAs in autocrine, paracrine and exocrine signaling events, thus highlighting an elaborate network of regulatory interactions mediated by different classes of ncRNAs during immune response. This review will explore the multifaceted roles of ncRNAs in the adaptive immune response. In particular, we will focus on the well-established role of miRNAs and on the emerging role of lncRNAs and circulating ncRNAs, which all make indispensable contributions to the understanding of the multilayered modulation of the adaptive immune response.

  3. Long Noncoding RNA PANDA Positively Regulates Proliferation of Osteosarcoma Cells.

    Science.gov (United States)

    Kotake, Yojiro; Goto, Taiki; Naemura, Madoka; Inoue, Yasutoshi; Okamoto, Haruna; Tahara, Keiichiro

    2017-01-01

    A long noncoding RNA, p21-associated ncRNA DNA damage-activated (PANDA), associates with nuclear transcription factor Y subunit alpha (NF-YA) and inhibits its binding to promoters of apoptosis-related genes, thereby repressing apoptosis in normal human fibroblasts. Here, we show that PANDA is involved in regulating proliferation in the U2OS human osteosarcoma cell line. U2OS cells were transfected with siRNAs against PANDA 72 h later and they were subjected to reverse transcription-polymerase chain reaction (RT-PCR), quantitative RT-PCR and cell-cycle analysis. PANDA was highly expressed in U2OS cells, and its expression was induced by DNA damage. Silencing PANDA caused arrest at the G 1 phase of the cell cycle, leading to inhibition of cell proliferation. Quantitative RT-PCR showed that silencing PANDA increased mRNA levels of the cyclin-dependent kinase inhibitor p18, which caused G 1 phase arrest. These results suggest that PANDA promotes G 1 -S transition by repressing p18 transcription, and thus promotes U2OS cell proliferation. Copyright© 2017 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. On the classification of long non-coding RNAs

    KAUST Repository

    Ma, Lina

    2013-06-01

    Long non-coding RNAs (lncRNAs) have been found to perform various functions in a wide variety of important biological processes. To make easier interpretation of lncRNA functionality and conduct deep mining on these transcribed sequences, it is convenient to classify lncRNAs into different groups. Here, we summarize classification methods of lncRNAs according to their four major features, namely, genomic location and context, effect exerted on DNA sequences, mechanism of functioning and their targeting mechanism. In combination with the presently available function annotations, we explore potential relationships between different classification categories, and generalize and compare biological features of different lncRNAs within each category. Finally, we present our view on potential further studies. We believe that the classifications of lncRNAs as indicated above are of fundamental importance for lncRNA studies, helpful for further investigation of specific lncRNAs, for formulation of new hypothesis based on different features of lncRNA and for exploration of the underlying lncRNA functional mechanisms. © 2013 Landes Bioscience.

  5. Rethinking the central dogma: noncoding RNAs are biologically relevant.

    Science.gov (United States)

    Robinson, Victoria L

    2009-01-01

    Non-coding RNAs (ncRNAs) are a large class of functional molecules with over 100 unique classes described to date. ncRNAs are diverse in terms of their function and size. A relatively new class of small ncRNA, called microRNAs (miRNA), have received a great deal of attention in the literature in recent years. miRNAs are endogenously encoded gene families that demonstrate striking evolutionary conservation. miRNAs serve essential and diverse physiological functions such as differentiation and development, proliferation, maintaining cell type phenotypes, and many others. The discovery and ongoing investigation of miRNAs is part of a revolution in biology that is changing the basic concepts of gene expression and RNA functionality. A single miRNA can participate in controlling the expression of up to several hundred protein-coding genes by interacting with mRNAs, generally in 3' untranslated regions. Our new and developing understanding of miRNAs, and other ncRNAs, promises to lead to significant contributions to medicine. Specifically, miRNAs are likely to serve as the basis for novel therapies and diagnostic tools.

  6. Adaptive evolution of conserved noncoding elements in mammals.

    Directory of Open Access Journals (Sweden)

    Su Yeon Kim

    2007-09-01

    Full Text Available Conserved noncoding elements (CNCs are an abundant feature of vertebrate genomes. Some CNCs have been shown to act as cis-regulatory modules, but the function of most CNCs remains unclear. To study the evolution of CNCs, we have developed a statistical method called the "shared rates test" to identify CNCs that show significant variation in substitution rates across branches of a phylogenetic tree. We report an application of this method to alignments of 98,910 CNCs from the human, chimpanzee, dog, mouse, and rat genomes. We find that approximately 68% of CNCs evolve according to a null model where, for each CNC, a single parameter models the level of constraint acting throughout the phylogeny linking these five species. The remaining approximately 32% of CNCs show departures from the basic model including speed-ups and slow-downs on particular branches and occasionally multiple rate changes on different branches. We find that a subset of the significant CNCs have evolved significantly faster than the local neutral rate on a particular branch, providing strong evidence for adaptive evolution in these CNCs. The distribution of these signals on the phylogeny suggests that adaptive evolution of CNCs occurs in occasional short bursts of evolution. Our analyses suggest a large set of promising targets for future functional studies of adaptation.

  7. Associating schizophrenia, long non-coding RNAs and neurostructural dynamics

    Science.gov (United States)

    Merelo, Veronica; Durand, Dante; Lescallette, Adam R.; Vrana, Kent E.; Hong, L. Elliot; Faghihi, Mohammad Ali; Bellon, Alfredo

    2015-01-01

    Several lines of evidence indicate that schizophrenia has a strong genetic component. But the exact nature and functional role of this genetic component in the pathophysiology of this mental illness remains a mystery. Long non-coding RNAs (lncRNAs) are a recently discovered family of molecules that regulate gene transcription through a variety of means. Consequently, lncRNAs could help us bring together apparent unrelated findings in schizophrenia; namely, genomic deficiencies on one side and neuroimaging, as well as postmortem results on the other. In fact, the most consistent finding in schizophrenia is decreased brain size together with enlarged ventricles. This anomaly appears to originate from shorter and less ramified dendrites and axons. But a decrease in neuronal arborizations cannot explain the complex pathophysiology of this psychotic disorder; however, dynamic changes in neuronal structure present throughout life could. It is well recognized that the structure of developing neurons is extremely plastic. This structural plasticity was thought to stop with brain development. However, breakthrough discoveries have shown that neuronal structure retains some degree of plasticity throughout life. What the neuroscientific field is still trying to understand is how these dynamic changes are regulated and lncRNAs represent promising candidates to fill this knowledge gap. Here, we present evidence that associates specific lncRNAs with schizophrenia. We then discuss the potential role of lncRNAs in neurostructural dynamics. Finally, we explain how dynamic neurostructural modifications present throughout life could, in theory, reconcile apparent unrelated findings in schizophrenia. PMID:26483630

  8. Associating schizophrenia, long non-coding RNAs and neurostructural dynamics

    Directory of Open Access Journals (Sweden)

    Veronica eMerelo

    2015-09-01

    Full Text Available Several lines of evidence indicate that schizophrenia has a strong genetic component. But the exact nature and functional role of this genetic component in the pathophysiology of this mental illness remains a mystery. Long non-coding RNAs (lncRNAs are a recently discovered family of molecules that regulate gene transcription through a variety of means. Consequently, lncRNAs could help us bring together apparent unrelated findings in schizophrenia; namely, genomic deficiencies on one side and neuroimaging, as well as postmortem results on the other. In fact, the most consistent finding in schizophrenia is decreased brain size together with enlarged ventricles. This anomaly appears to originate from shorter and less ramified dendrites and axons. But a decrease in neuronal arborizations cannot explain the complex pathophysiology of this psychotic disorder; however, dynamic changes in neuronal structure present throughout life could. It is well recognized that the structure of developing neurons is extremely plastic. This structural plasticity was thought to stop with brain development. However, breakthrough discoveries have shown that neuronal structure retains some degree of plasticity throughout life. What the neuroscientific field is still trying to understand is how these dynamic changes are regulated and lncRNAs represent promising candidates to fill this knowledge gap. Here, we present evidence that associates specific lncRNAs with schizophrenia. We then discuss the potential role of lncRNAs in neurostructural dynamics. Finally, we explain how dynamic neurostructural modifications present throughout life could, in theory, reconcile apparent unrelated findings in schizophrenia.

  9. Regulatory Non-Coding RNAs in Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Alessandro Rosa

    2013-07-01

    Full Text Available The most part of our genome encodes for RNA transcripts are never translated into proteins. These include families of RNA molecules with a regulatory function, which can be arbitrarily subdivided in short (less than 200 nucleotides and long non-coding RNAs (ncRNAs. MicroRNAs, which act post-transcriptionally to repress the function of target mRNAs, belong to the first group. Included in the second group are multi-exonic and polyadenylated long ncRNAs (lncRNAs, localized either in the nucleus, where they can associate with chromatin remodeling complexes to regulate transcription, or in the cytoplasm, acting as post-transcriptional regulators. Pluripotent stem cells, such as embryonic stem cells (ESCs or induced pluripotent stem cells (iPSCs, represent useful systems for modeling normal development and human diseases, as well as promising tools for regenerative medicine. To fully explore their potential, however, a deep understanding of the molecular basis of stemness is crucial. In recent years, increasing evidence of the importance of regulation by ncRNAs in pluripotent cells is accumulating. In this review, we will discuss recent findings pointing to multiple roles played by regulatory ncRNAs in ESC and iPSCs, where they act in concert with signaling pathways, transcriptional regulatory circuitries and epigenetic factors to modulate the balance between pluripotency and differentiation.

  10. Expression Signatures of Long Noncoding RNAs in Adolescent Idiopathic Scoliosis

    Directory of Open Access Journals (Sweden)

    Xiao-Yang Liu

    2015-01-01

    Full Text Available Purpose. Adolescent idiopathic scoliosis (AIS, the most common pediatric spinal deformity, is considered a complex genetic disease. Causing genes and pathogenesis of AIS are still unclear. This study was designed to identify differentially expressed long noncoding RNAs (lncRNAs involving the pathogenesis of AIS. Methods. We first performed comprehensive screening of lncRNA and mRNA in AIS patients and healthy children using Agilent human lncRNA + mRNA Array V3.0 microarray. LncRNAs expression in different AIS patients was further evaluated using quantitative PCR. Results. A total of 139 lncRNAs and 546 mRNAs were differentially expressed between AIS patients and healthy control. GO and Pathway analysis showed that these mRNAs might be involved in bone mineralization, neuromuscular junction, skeletal system morphogenesis, nucleotide and nucleic acid metabolism, and regulation of signal pathway. Four lncRNAs (ENST00000440778.1, ENST00000602322.1, ENST00000414894.1, and TCONS_00028768 were differentially expressed between different patients when grouped according to age, height, classification, severity of scoliosis, and Risser grade. Conclusions. This study demonstrates the abnormal expression of lncRNAs and mRNAs in AIS, and the expression of some lncRNAs was related to clinical features. This study is helpful for further understanding of lncRNAs in pathogenesis, treatment, and prognosis of AIS.

  11. DNA watermarks in non-coding regulatory sequences

    Directory of Open Access Journals (Sweden)

    Pyka Martin

    2009-07-01

    Full Text Available Abstract Background DNA watermarks can be applied to identify the unauthorized use of genetically modified organisms. It has been shown that coding regions can be used to encrypt information into living organisms by using the DNA-Crypt algorithm. Yet, if the sequence of interest presents a non-coding DNA sequence, either the function of a resulting functional RNA molecule or a regulatory sequence, such as a promoter, could be affected. For our studies we used the small cytoplasmic RNA 1 in yeast and the lac promoter region of Escherichia coli. Findings The lac promoter was deactivated by the integrated watermark. In addition, the RNA molecules displayed altered configurations after introducing a watermark, but surprisingly were functionally intact, which has been verified by analyzing the growth characteristics of both wild type and watermarked scR1 transformed yeast cells. In a third approach we introduced a second overlapping watermark into the lac promoter, which did not affect the promoter activity. Conclusion Even though the watermarked RNA and one of the watermarked promoters did not show any significant differences compared to the wild type RNA and wild type promoter region, respectively, it cannot be generalized that other RNA molecules or regulatory sequences behave accordingly. Therefore, we do not recommend integrating watermark sequences into regulatory regions.

  12. Expression and Functional Studies on the Noncoding RNA, PRINS

    Directory of Open Access Journals (Sweden)

    Márta Széll

    2012-12-01

    Full Text Available PRINS, a noncoding RNA identified earlier by our research group, contributes to psoriasis susceptibility and cellular stress response. We have now studied the cellular and histological distribution of PRINS by using in situ hybridization and demonstrated variable expressions in different human tissues and a consistent staining pattern in epidermal keratinocytes and in vitro cultured keratinocytes. To identify the cellular function(s of PRINS, we searched for a direct interacting partner(s of this stress-induced molecule. In HaCaT and NHEK cell lysates, the protein proved to be nucleophosmin (NPM protein as a potential physical interactor with PRINS. Immunohistochemical experiments revealed an elevated expression of NPM in the dividing cells of the basal layers of psoriatic involved skin samples as compared with healthy and psoriatic uninvolved samples. Others have previously shown that NPM is a ubiquitously expressed nucleolar phosphoprotein which shuttles to the nucleoplasm after UV-B irradiation in fibroblasts and cancer cells. We detected a similar translocation of NPM in UV-B-irradiated cultured keratinocytes. The gene-specific silencing of PRINS resulted in the retention of NPM in the nucleolus of UV-B-irradiated keratinocytes; suggesting that PRINS may play a role in the NPM-mediated cellular stress response in the skin.

  13. The noncoding-RNA landscape in cardiovascular health and disease

    Directory of Open Access Journals (Sweden)

    Vittoria Di Mauro

    2018-03-01

    Full Text Available The cardiovascular system plays a pivotal role in regulating and maintaining homeostasis in the human body. Therefore any alteration in regulatory networks that orchestrate heart development as well as adaptation to physiological and environmental stress might result in pathological conditions, which represent the leading cause of death worldwide [1]. The latest advances in genome-wide techniques challenged the “protein-central dogma” with the discovery of the so-called non-coding RNAs (ncRNAs. Despite their lack of protein coding potential, ncRNAs have been largely demonstrated to regulate the majority of biological processes and have also been largely implicated in cardiovascular disorders. This review will first discuss the important mechanistic aspects of some of the classes of ncRNAs such as biogenesis, mechanism of action, as well as their involvement in cardiac diseases. The ncRNA potential uses as therapeutic molecules, with a specific focus on the latest technologies for their in vivo delivery as drug targets, will be described.

  14. In Vivo Enhancer Analysis Chromosome 16 Conserved NoncodingSequences

    Energy Technology Data Exchange (ETDEWEB)

    Pennacchio, Len A.; Ahituv, Nadav; Moses, Alan M.; Nobrega,Marcelo; Prabhakar, Shyam; Shoukry, Malak; Minovitsky, Simon; Visel,Axel; Dubchak, Inna; Holt, Amy; Lewis, Keith D.; Plajzer-Frick, Ingrid; Akiyama, Jennifer; De Val, Sarah; Afzal, Veena; Black, Brian L.; Couronne, Olivier; Eisen, Michael B.; Rubin, Edward M.

    2006-02-01

    The identification of enhancers with predicted specificitiesin vertebrate genomes remains a significant challenge that is hampered bya lack of experimentally validated training sets. In this study, weleveraged extreme evolutionary sequence conservation as a filter toidentify putative gene regulatory elements and characterized the in vivoenhancer activity of human-fish conserved and ultraconserved1 noncodingelements on human chromosome 16 as well as such elements from elsewherein the genome. We initially tested 165 of these extremely conservedsequences in a transgenic mouse enhancer assay and observed that 48percent (79/165) functioned reproducibly as tissue-specific enhancers ofgene expression at embryonic day 11.5. While driving expression in abroad range of anatomical structures in the embryo, the majority of the79 enhancers drove expression in various regions of the developingnervous system. Studying a set of DNA elements that specifically droveforebrain expression, we identified DNA signatures specifically enrichedin these elements and used these parameters to rank all ~;3,400human-fugu conserved noncoding elements in the human genome. The testingof the top predictions in transgenic mice resulted in a three-foldenrichment for sequences with forebrain enhancer activity. These datadramatically expand the catalogue of in vivo-characterized human geneenhancers and illustrate the future utility of such training sets for avariety of iological applications including decoding the regulatoryvocabulary of the human genome.

  15. The noncoding human genome and the future of personalised medicine.

    Science.gov (United States)

    Cowie, Philip; Hay, Elizabeth A; MacKenzie, Alasdair

    2015-01-30

    Non-coding cis-regulatory sequences act as the 'eyes' of the genome and their role is to perceive, organise and relay cellular communication information to RNA polymerase II at gene promoters. The evolution of these sequences, that include enhancers, silencers, insulators and promoters, has progressed in multicellular organisms to the extent that cis-regulatory sequences make up as much as 10% of the human genome. Parallel evidence suggests that 75% of polymorphisms associated with heritable disease occur within predicted cis-regulatory sequences that effectively alter the 'perception' of cis-regulatory sequences or render them blind to cell communication cues. Cis-regulatory sequences also act as major functional targets of epigenetic modification thus representing an important conduit through which changes in DNA-methylation affects disease susceptibility. The objectives of the current review are (1) to describe what has been learned about identifying and characterising cis-regulatory sequences since the sequencing of the human genome; (2) to discuss their role in interpreting cell signalling pathways pathways; and (3) outline how this role may be altered by polymorphisms and epigenetic changes. We argue that the importance of the cis-regulatory genome for the interpretation of cellular communication pathways cannot be overstated and understanding its role in health and disease will be critical for the future development of personalised medicine.

  16. Thermal expansion of granite rocks

    International Nuclear Information System (INIS)

    Stephansson, O.

    1978-04-01

    The thermal expansion of rocks is strongly controlled by the thermal expansion of the minerals. The theoretical thermal expansion of the Stripa Granite is gound to be 21 . 10 -6 [deg C] -1 at 25 deg C and 38 . 10 -6 [deg C] -1 at 400 deg C. The difference in expansion for the rock forming minerals causes micro cracking at heating. The expansion due to micro cracks is found to be of the same order as the mineral expansion. Most of the micro cracks will close at pressures of the order of 10 - 20 MPa. The thermal expansion of a rock mass including the effect of joints is determined in the pilot heater test in the Stripa Mine

  17. Provincial hydro expansions

    Energy Technology Data Exchange (ETDEWEB)

    Froschauer, K J

    1993-01-01

    A study of the development of five provincial hydroelectric utilities in Canada indicates that power companies and the state invited manufacturers to use hydroelectricity and natural resources in order to diversify provincial economies. These hydro expansions also show that utilities and government designed hydro projects to serve continental requirements; serving both objectives became problematic. It is argued that when the Canadian state and firms such as utilities use hydro expansions to serve both continentalism and industrialization, then at best they foster dependent industrialization and staple processing. At worst, they overbuild the infrastructure to generate provincial surplus energy for continental, rather than national, integration. Hydro developments became subject to state intervention in Canada mainly through the failures of private utilities to provide power for the less-lucrative industrial markets within provincial subregions. Although the state and utilities invited foreign firms to manufacture hydro equipment within the provinces and others to use electricity to diversify production beyond resource processing, such a diversification did not occur. Since 1962, ca 80% of industrial energy was used to semi-process wood-derived products, chemicals, and metals. The idea for a national power network became undermined by interprovincial political-economic factors and since 1963, the federal national/continential power policy prevailed. 187 refs., 6 figs., 52 tabs.

  18. Measuring of tube expansion

    International Nuclear Information System (INIS)

    Vogeleer, J. P.

    1985-01-01

    The expansion of the primary tubes or sleeves of the steam generator of a nuclear reactor plant are measured while the tubes or sleeves are being expanded. A primary tube or sleeve is expanded by high pressure of water which flows through a channel in an expander body. The water is supplied through an elongated conductor and is introduced through a connector on the shank connected to the conductor at its outer end. A wire extends through the mandrel and through the conductor to the end of the connector. At its inner end the wire is connected to a tapered pin which is subject to counteracting forces produced by the pressure of the water. The force on the side where the wire is connected to the conductor is smaller than on the opposite side. The tapered pin is moved in the direction of the higher force and extrudes the wire outwardly of the conductor. The tapered surface of the tapered pin engages transverse captive plungers which are maintained in engagement with the expanding tube or sleeve as they are moved outwardly by the tapered pin. The wire and the connector extend out of the generator and, at its outer end, the wire is connected to an indicator which measures the extent to which the wire is moved by the tapered pin, thus measuring the expansion of the tube or sleeve as it progresses

  19. Potentials and limitations of histone repeat sequences for phylogenetic reconstruction of Sophophora.

    Science.gov (United States)

    Baldo, A M; Les, D H; Strausbaugh, L D

    1999-11-01

    Simplified DNA sequence acquisition has provided many new data sets that are useful for phylogenetic reconstruction, including single- and multiple-copy nuclear and organellar genes. Although transcribed regions receive much attention, nontranscribed regions have recently been added to the repertoire of sequences suitable for phylogenetic studies, especially for closely related taxa. We evaluated the efficacy of a small portion of the histone repeat for phylogenetic reconstruction among Drosophila species. Histone repeats in invertebrates offer distinct advantages similar to those of widely used ribosomal repeats. First, the units are tandemly repeated and undergo concerted evolution. Second, histone repeats include both highly conserved coding and variable intergenic regions. This composition facilitates application of "universal" primers spanning potentially informative sites. We examined a small region of the histone repeat, including the intergenic spacer segments of coding regions from the divergently transcribed H2A and H2B histone genes. The spacer (about 230 bp) exists as a mosaic with highly conserved functional motifs interspersed with rapidly diverging regions; the former aid in alignment of the spacer. There are no ambiguities in alignment of coding regions. Coding and noncoding regions were analyzed together and separately for phylogenetic information. Parsimony, distance, and maximum-likelihood methods successfully retrieve the corroborated phylogeny for the taxa examined. This study demonstrates the resolving power of a small histone region which may now be added to the growing collection of phylogenetically useful DNA sequences.

  20. Thermal expansion of coking coals

    Energy Technology Data Exchange (ETDEWEB)

    Orlik, M.; Klimek, J. (Vyzkumny a Zkusebni Ustav Nova Hut, Ostrava (Czechoslovakia))

    1992-12-01

    Analyzes expansion of coal mixtures in coke ovens during coking. Methods for measuring coal expansion on both a laboratory and pilot plant scale are comparatively evaluated. The method, developed, tested and patented in Poland by the Institute for Chemical Coal Processing in Zabrze (Polish standard PN-73/G-04522), is discussed. A laboratory device developed by the Institute for measuring coal expansion is characterized. Expansion of black coal from 10 underground mines in the Ostrava-Karvina coal district and from 9 coal mines in the Upper Silesia basin in Poland is comparatively evaluated. Investigations show that coal expansion reaches a maximum for coal types with a volatile matter ranging from 20 to 25%. With increasing volatile matter in coal, its expansion decreases. Coal expansion increases with increasing swelling index. Coal expansion corresponds with coal dilatation. With increasing coal density its expansion increases. Coal mixtures should be selected in such a way that their expansion does not cause a pressure exceeding 40 MPa. 11 refs.

  1. Identity Expansion and Transcendence

    Directory of Open Access Journals (Sweden)

    William Sims Bainbridge

    2014-05-01

    Full Text Available Emerging developments in communications and computing technology may transform the nature of human identity, in the process rendering obsolete the traditional philosophical and scientific frameworks for understanding the nature of individuals and groups.  Progress toward an evaluation of this possibility and an appropriate conceptual basis for analyzing it may be derived from two very different but ultimately connected social movements that promote this radical change. One is the governmentally supported exploration of Converging Technologies, based in the unification of nanoscience, biology, information science and cognitive science (NBIC. The other is the Transhumanist movement, which has been criticized as excessively radical yet is primarily conducted as a dignified intellectual discussion within a new school of philosophy about human enhancement.  Together, NBIC and Transhumanism suggest the immense transformative power of today’s technologies, through which individuals may explore multiple identities by means of online avatars, semi-autonomous intelligent agents, and other identity expansions.

  2. Film repeats in radiology department

    International Nuclear Information System (INIS)

    Suwan, A. Z.; Al-Shakharah, A. I

    1997-01-01

    During a one year period, 4910 radiographs of 55780 films were repeated. The objective of our study was to analyse and to classify the causes in order to minimize the repeats, cut the expenses and to provide optimal radiographs for accurate diagnosis. Analysis of the different factors revealed that, 43.6% of film repeats in our service were due to faults in exposure factors, centering comprises 15.9% of the repeats, while too much collimation was responsible for 7.6% of these repeats. All of which can be decreased by awareness and programmed training of technicians. Film blurring caused by patient motion was also responsible for 4.9% for radiographs reexamination, which can be minimized by detailed explanation to the patient and providing the necessary privacy. Fogging of X-Ray films by improper storage or inadequate handling or processing faults were responsible for 14.5% in repeats in our study. Methods and criteria for proper storage and handling of films were discussed. Recommendation for using modern day-light and laser processor has been high lighted. Artefacts are noticeably high in our cases, due to spinal dresses and frequent usage of precious metals for c osmotic purposes in this part of the world. The repeated films comprise 8.8% of all films We conclude that, the main factor responsible for repeats of up to 81.6% of cases was the technologists, thus emphasizing the importance of adequate training of the technologists. (authors). 15 refs., 9 figs., 1 table

  3. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

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

  4. Repeated Prescribed Burning in Aspen

    Science.gov (United States)

    Donald A. Perala

    1974-01-01

    Infrequent burning weather, low flammability of the aspen-hardwood association, and prolific sprouting and seeding of shrubs and hardwoods made repeated dormant season burning a poor tool to convert good site aspen to conifers. Repeat fall burns for wildlife habitat maintenance is workable if species composition changes are not important.

  5. DNA Replication Dynamics of the GGGGCC Repeat of the C9orf72 Gene.

    Science.gov (United States)

    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. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Tevatron serial data repeater system

    International Nuclear Information System (INIS)

    Ducar, R.J.

    1981-01-01

    A ten megabit per second serial data repeater system has been developed for the 6.28km Tevatron accelerator. The repeaters are positioned at each of the thirty service buildings and accommodate control and abort system communications as well as distribution of the Tevatron time and energy clocks. The repeaters are transparent to the particular protocol of the transmissions. Serial data are encoded locally as unipolar two volt signals employing the self-clocking Manchester Bi-Phase code. The repeaters modulate the local signals to low-power bursts of 50 MHz rf carrier for the 260m transmission between service buildings. The repeaters also demodulate the transmission and restructure the data for local utilization. The employment of frequency discrimination techniques yields high immunity to the characteristic noise spectrum

  7. All-photonic quantum repeaters

    Science.gov (United States)

    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

  8. Repeatability of visual acuity measurement.

    Science.gov (United States)

    Raasch, T W; Bailey, I L; Bullimore, M A

    1998-05-01

    This study investigates features of visual acuity chart design and acuity testing scoring methods which affect the validity and repeatability of visual acuity measurements. Visual acuity was measured using the Sloan and British Standard letter series, and Landolt rings. Identifiability of the different letters as a function of size was estimated, and expressed in the form of frequency-of-seeing curves. These functions were then used to simulate acuity measurements with a variety of chart designs and scoring criteria. Systematic relationships exist between chart design parameters and acuity score, and acuity score repeatability. In particular, an important feature of a chart, that largely determines the repeatability of visual acuity measurement, is the amount of size change attributed to each letter. The methods used to score visual acuity performance also affect repeatability. It is possible to evaluate acuity score validity and repeatability using the statistical principles discussed here.

  9. Long Non-Coding RNAs: A Novel Paradigm for Toxicology.

    Science.gov (United States)

    Dempsey, Joseph L; Cui, Julia Yue

    2017-01-01

    Long non-coding RNAs (lncRNAs) are over 200 nucleotides in length and are transcribed from the mammalian genome in a tissue-specific and developmentally regulated pattern. There is growing recognition that lncRNAs are novel biomarkers and/or key regulators of toxicological responses in humans and animal models. Lacking protein-coding capacity, the numerous types of lncRNAs possess a myriad of transcriptional regulatory functions that include cis and trans gene expression, transcription factor activity, chromatin remodeling, imprinting, and enhancer up-regulation. LncRNAs also influence mRNA processing, post-transcriptional regulation, and protein trafficking. Dysregulation of lncRNAs has been implicated in various human health outcomes such as various cancers, Alzheimer's disease, cardiovascular disease, autoimmune diseases, as well as intermediary metabolism such as glucose, lipid, and bile acid homeostasis. Interestingly, emerging evidence in the literature over the past five years has shown that lncRNA regulation is impacted by exposures to various chemicals such as polycyclic aromatic hydrocarbons, benzene, cadmium, chlorpyrifos-methyl, bisphenol A, phthalates, phenols, and bile acids. Recent technological advancements, including next-generation sequencing technologies and novel computational algorithms, have enabled the profiling and functional characterizations of lncRNAs on a genomic scale. In this review, we summarize the biogenesis and general biological functions of lncRNAs, highlight the important roles of lncRNAs in human diseases and especially during the toxicological responses to various xenobiotics, evaluate current methods for identifying aberrant lncRNA expression and molecular target interactions, and discuss the potential to implement these tools to address fundamental questions in toxicology. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e

  10. Novel classes of non-coding RNAs and cancer

    Directory of Open Access Journals (Sweden)

    Sana Jiri

    2012-05-01

    Full Text Available Abstract For the many years, the central dogma of molecular biology has been that RNA functions mainly as an informational intermediate between a DNA sequence and its encoded protein. But one of the great surprises of modern biology was the discovery that protein-coding genes represent less than 2% of the total genome sequence, and subsequently the fact that at least 90% of the human genome is actively transcribed. Thus, the human transcriptome was found to be more complex than a collection of protein-coding genes and their splice variants. Although initially argued to be spurious transcriptional noise or accumulated evolutionary debris arising from the early assembly of genes and/or the insertion of mobile genetic elements, recent evidence suggests that the non-coding RNAs (ncRNAs may play major biological roles in cellular development, physiology and pathologies. NcRNAs could be grouped into two major classes based on the transcript size; small ncRNAs and long ncRNAs. Each of these classes can be further divided, whereas novel subclasses are still being discovered and characterized. Although, in the last years, small ncRNAs called microRNAs were studied most frequently with more than ten thousand hits at PubMed database, recently, evidence has begun to accumulate describing the molecular mechanisms by which a wide range of novel RNA species function, providing insight into their functional roles in cellular biology and in human disease. In this review, we summarize newly discovered classes of ncRNAs, and highlight their functioning in cancer biology and potential usage as biomarkers or therapeutic targets.

  11. MicroRNA-encoding long non-coding RNAs

    Directory of Open Access Journals (Sweden)

    Zhu Xiaopeng

    2008-05-01

    Full Text Available Abstract Background Recent analysis of the mouse transcriptional data has revealed the existence of ~34,000 messenger-like non-coding RNAs (ml-ncRNAs. Whereas the functional properties of these ml-ncRNAs are beginning to be unravelled, no functional information is available for the large majority of these transcripts. Results A few ml-ncRNA have been shown to have genomic loci that overlap with microRNA loci, leading us to suspect that a fraction of ml-ncRNA may encode microRNAs. We therefore developed an algorithm (PriMir for specifically detecting potential microRNA-encoding transcripts in the entire set of 34,030 mouse full-length ml-ncRNAs. In combination with mouse-rat sequence conservation, this algorithm detected 97 (80 of them were novel strong miRNA-encoding candidates, and for 52 of these we obtained experimental evidence for the existence of their corresponding mature microRNA by microarray and stem-loop RT-PCR. Sequence analysis of the microRNA-encoding RNAs revealed an internal motif, whose presence correlates strongly (R2 = 0.9, P-value = 2.2 × 10-16 with the occurrence of stem-loops with characteristics of known pre-miRNAs, indicating the presence of a larger number microRNA-encoding RNAs (from 300 up to 800 in the ml-ncRNAs population. Conclusion Our work highlights a unique group of ml-ncRNAs and offers clues to their functions.

  12. Kinetic models of gene expression including non-coding RNAs

    Energy Technology Data Exchange (ETDEWEB)

    Zhdanov, Vladimir P., E-mail: zhdanov@catalysis.r

    2011-03-15

    In cells, genes are transcribed into mRNAs, and the latter are translated into proteins. Due to the feedbacks between these processes, the kinetics of gene expression may be complex even in the simplest genetic networks. The corresponding models have already been reviewed in the literature. A new avenue in this field is related to the recognition that the conventional scenario of gene expression is fully applicable only to prokaryotes whose genomes consist of tightly packed protein-coding sequences. In eukaryotic cells, in contrast, such sequences are relatively rare, and the rest of the genome includes numerous transcript units representing non-coding RNAs (ncRNAs). During the past decade, it has become clear that such RNAs play a crucial role in gene expression and accordingly influence a multitude of cellular processes both in the normal state and during diseases. The numerous biological functions of ncRNAs are based primarily on their abilities to silence genes via pairing with a target mRNA and subsequently preventing its translation or facilitating degradation of the mRNA-ncRNA complex. Many other abilities of ncRNAs have been discovered as well. Our review is focused on the available kinetic models describing the mRNA, ncRNA and protein interplay. In particular, we systematically present the simplest models without kinetic feedbacks, models containing feedbacks and predicting bistability and oscillations in simple genetic networks, and models describing the effect of ncRNAs on complex genetic networks. Mathematically, the presentation is based primarily on temporal mean-field kinetic equations. The stochastic and spatio-temporal effects are also briefly discussed.

  13. Thermal expansion of beryllium oxide

    International Nuclear Information System (INIS)

    Solodukhin, A.V.; Kruzhalov, A.V.; Mazurenko, V.G.; Maslov, V.A.; Medvedev, V.A.; Polupanova, T.I.

    1987-01-01

    Precise measurements of temperature dependence of the coefficient of linear expansion in the 22-320 K temperature range on beryllium oxide monocrystals are conducted. A model of thermal expansion is suggested; the range of temperature dependence minimum of the coefficient of thermal expansion is well described within the frames of this model. The results of the experiment may be used for investigation of thermal stresses in crystals

  14. Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers

    Directory of Open Access Journals (Sweden)

    Alejandra Sandoval-Bórquez

    2015-01-01

    Full Text Available Gastric cancer is the fifth most common cancer and the third leading cause of cancer-related death, whose patterns vary among geographical regions and ethnicities. It is a multifactorial disease, and its development depends on infection by Helicobacter pylori (H. pylori and Epstein-Barr virus (EBV, host genetic factors, and environmental factors. The heterogeneity of the disease has begun to be unraveled by a comprehensive mutational evaluation of primary tumors. The low-abundance of mutations suggests that other mechanisms participate in the evolution of the disease, such as those found through analyses of noncoding genomics. Noncoding genomics includes single nucleotide polymorphisms (SNPs, regulation of gene expression through DNA methylation of promoter sites, miRNAs, other noncoding RNAs in regulatory regions, and other topics. These processes and molecules ultimately control gene expression. Potential biomarkers are appearing from analyses of noncoding genomics. This review focuses on noncoding genomics and potential biomarkers in the context of gastric cancer and the gastric precancerous cascade.

  15. Impact of nutrition on noncoding RNA epigenetics in breast and gynecological cancer

    Directory of Open Access Journals (Sweden)

    Rosanna H. E. Krakowsky

    2015-05-01

    Full Text Available Cancer is the second leading cause of death in females. According to the American Cancer Society, there are 327,660 new cases in breast and gynecological cancers estimated in 2014, placing emphasis on the need for cancer prevention and new cancer treatment strategies. One important approach to cancer prevention involves phytochemicals, biologically active compounds derived from plants. A variety of studies on the impact of dietary compounds found in cruciferous vegetables, green tea and spices like curry and black pepper have revealed epigenetic changes in female cancers. Thus, an important emerging topic comprises epigenetic changes due to the modulation of noncoding RNA levels. Since it has been shown that noncoding RNAs such as microRNAs and long noncoding RNAs are aberrantly expressed in cancer and furthermore are linked to distinct cancer phenotypes, understanding the effects of dietary compounds and supplements on the epigenetic modulator noncoding RNA is of great interest. This article reviews the current findings on nutrition-induced changes in breast and gynecological cancers at the noncoding RNA level.

  16. Disruption of Higher Order DNA Structures in Friedreich's Ataxia (GAA)(n) Repeats by PNA or LNA Targeting

    DEFF Research Database (Denmark)

    Bergquist, Helen; Rocha, Cristina S. J.; Alvarez-Asencio, Ruben

    2016-01-01

    Expansion of (GAA)n repeats in the first intron of the Frataxin gene is associated with reduced mRNA and protein levels and the development of Friedreich’s ataxia. (GAA)n expansions form non-canonical structures, including intramolecular triplex (H-DNA), and R-loops and are associated with epigen...

  17. The role of epigenetics and long noncoding RNA MIAT in neuroendocrine prostate cancer.

    Science.gov (United States)

    Crea, Francesco; Venalainen, Erik; Ci, Xinpei; Cheng, Hongwei; Pikor, Larissa; Parolia, Abhijit; Xue, Hui; Nur Saidy, Nur Ridzwan; Lin, Dong; Lam, Wan; Collins, Colin; Wang, Yuzhuo

    2016-05-01

    Neuroendocrine prostate cancer (NEPC) is the most lethal prostatic neoplasm. NEPC is thought to originate from the transdifferentiation of AR-positive adenocarcinoma cells. We have previously shown that an epigenetic/noncoding interactome (ENI) orchestrates cancer cells' plasticity, thereby allowing the emergence of metastatic, drug-resistant neoplasms. The primary objective of this manuscript is to discuss evidence indicating that some components of the ENI (Polycomb genes, miRNAs) play a key role in NEPC initiation and progression. Long noncoding RNAs represent vast and largely unexplored component of the ENI. Their role in NEPC has not been investigated. We show preliminary evidence indicating that a lncRNA (MIAT) is selectively upregulated in NEPCs and might interact with Polycomb genes. Our results indicate that long noncoding RNAs can be exploited as new biomarkers and therapeutic targets for NEPC.

  18. Analysis of repeated measures data

    CERN Document Server

    Islam, M Ataharul

    2017-01-01

    This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

  19. Repeated DNA sequences in fungi

    Energy Technology Data Exchange (ETDEWEB)

    Dutta, S K

    1974-11-01

    Several fungal species, representatives of all broad groups like basidiomycetes, ascomycetes and phycomycetes, were examined for the nature of repeated DNA sequences by DNA:DNA reassociation studies using hydroxyapatite chromatography. All of the fungal species tested contained 10 to 20 percent repeated DNA sequences. There are approximately 100 to 110 copies of repeated DNA sequences of approximately 4 x 10/sup 7/ daltons piece size of each. Repeated DNA sequence homoduplexes showed on average 5/sup 0/C difference of T/sub e/50 (temperature at which 50 percent duplexes dissociate) values from the corresponding homoduplexes of unfractionated whole DNA. It is suggested that a part of repetitive sequences in fungi constitutes mitochondrial DNA and a part of it constitutes nuclear DNA. (auth)

  20. Renormalization group and Mayer expansions

    International Nuclear Information System (INIS)

    Mack, G.

    1984-02-01

    Mayer expansions promise to become a powerful tool in exact renormalization group calculations. Iterated Mayer expansions were sucessfully used in the rigorous analysis of 3-dimensional U(1) lattice gauge theory by Goepfert and the author, and it is hoped that they will also be useful in the 2-dimensional nonlinear sigma-model, and elsewhere. (orig.)

  1. Isotropic Negative Thermal Expansion Metamaterials.

    Science.gov (United States)

    Wu, Lingling; Li, Bo; Zhou, Ji

    2016-07-13

    Negative thermal expansion materials are important and desirable in science and engineering applications. However, natural materials with isotropic negative thermal expansion are rare and usually unsatisfied in performance. Here, we propose a novel method to achieve two- and three-dimensional negative thermal expansion metamaterials via antichiral structures. The two-dimensional metamaterial is constructed with unit cells that combine bimaterial strips and antichiral structures, while the three-dimensional metamaterial is fabricated by a multimaterial 3D printing process. Both experimental and simulation results display isotropic negative thermal expansion property of the samples. The effective coefficient of negative thermal expansion of the proposed models is demonstrated to be dependent on the difference between the thermal expansion coefficient of the component materials, as well as on the circular node radius and the ligament length in the antichiral structures. The measured value of the linear negative thermal expansion coefficient of the three-dimensional sample is among the largest achieved in experiments to date. Our findings provide an easy and practical approach to obtaining materials with tunable negative thermal expansion on any scale.

  2. Renormalization group and mayer expansions

    International Nuclear Information System (INIS)

    Mack, G.

    1984-01-01

    Mayer expansions promise to become a powerful tool in exact renormalization group calculations. Iterated Mayer expansions were sucessfully used in the rigorous analysis of 3-dimensional U (1) lattice gauge theory by Gopfert and the author, and it is hoped that they will also be useful in the 2-dimensional nonlinear σ-model, and elsewhere

  3. On summation of perturbation expansions

    International Nuclear Information System (INIS)

    Horzela, A.

    1985-04-01

    The problem of the restoration of physical quantities defined by divergent perturbation expansions is analysed. The Pad'e and Borel summability is proved for alternating perturbation expansions with factorially growing coefficients. The proof is based on the methods of the classical moments theory. 17 refs. (author)

  4. Induction of long noncoding RNA MALAT1 in hypoxic mice

    Directory of Open Access Journals (Sweden)

    Lelli A

    2015-10-01

    Full Text Available Aurelia Lelli,1,2,* Karen A Nolan,1,2,* Sara Santambrogio,1,2 Ana Filipa Gonçalves,1,2 Miriam J Schönenberger,1,2 Anna Guinot,1,2 Ian J Frew,1,2 Hugo H Marti,3 David Hoogewijs,1,2,4 Roland H Wenger1,2 1Institute of Physiology and Zurich Center for Human Physiology (ZIHP, University of Zurich, Zurich, Switzerland; 2National Center of Competence in Research "Kidney.CH", Zurich, Switzerland; 3Institute of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany; 4Institute of Physiology, University of Duisburg-Essen, Essen, Germany *These authors contributed equally to this work Abstract: Long thought to be “junk DNA”, in recent years it has become clear that a substantial fraction of intergenic genomic DNA is actually transcribed, forming long noncoding RNA (lncRNA. Like mRNA, lncRNA can also be spliced, capped, and polyadenylated, affecting a multitude of biological processes. While the molecular mechanisms underlying the function of lncRNAs have just begun to be elucidated, the conditional regulation of lncRNAs remains largely unexplored. In genome-wide studies our group and others recently found hypoxic transcriptional induction of a subset of lncRNAs, whereof nuclear-enriched abundant/autosomal transcript 1 (NEAT1 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1 appear to be the lncRNAs most ubiquitously and most strongly induced by hypoxia in cultured cells. Hypoxia-inducible factor (HIF-2 rather than HIF-1 seems to be the preferred transcriptional activator of these lncRNAs. For the first time, we also found strong induction primarily of MALAT1 in organs of mice exposed to inspiratory hypoxia. Most abundant hypoxic levels of MALAT1 lncRNA were found in kidney and testis. In situ hybridization revealed that the hypoxic induction in the kidney was confined to proximal rather than distal tubular epithelial cells. Direct oxygen-dependent regulation of MALAT1 lncRNA was confirmed using isolated primary

  5. Repeat-mediated epigenetic dysregulation of the FMR1 gene in the fragile X-related disorders.

    Science.gov (United States)

    Usdin, Karen; Kumari, Daman

    2015-01-01

    The fragile X-related disorders are members of the Repeat Expansion Diseases, a group of genetic conditions resulting from an expansion in the size of a tandem repeat tract at a specific genetic locus. The repeat responsible for disease pathology in the fragile X-related disorders is CGG/CCG and the repeat tract is located in the 5' UTR of the FMR1 gene, whose protein product FMRP, is important for the proper translation of dendritic mRNAs in response to synaptic activation. There are two different pathological FMR1 allele classes that are distinguished only by the number of repeats. Premutation alleles have 55-200 repeats and confer risk of fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency. Full mutation alleles on the other hand have >200 repeats and result in fragile X syndrome, a disorder that affects learning and behavior. Different symptoms are seen in carriers of premutation and full mutation alleles because the repeat number has paradoxical effects on gene expression: Epigenetic changes increase transcription from premutation alleles and decrease transcription from full mutation alleles. This review will cover what is currently known about the mechanisms responsible for these changes in FMR1 expression and how they may relate to other Repeat Expansion Diseases that also show repeat-mediated changes in gene expression.

  6. Fostering repeat donations in Ghana.

    Science.gov (United States)

    Owusu-Ofori, S; Asenso-Mensah, K; Boateng, P; Sarkodie, F; Allain, J-P

    2010-01-01

    Most African countries are challenged in recruiting and retaining voluntary blood donors by cost and other complexities and in establishing and implementing national blood policies. The availability of replacement donors who are a cheaper source of blood has not enhanced repeat voluntary donor initiatives. An overview of activities for recruiting and retaining voluntary blood donors was carried out. Donor records from mobile sessions were reviewed from 2002 to 2008. A total of 71,701 blood donations; 45,515 (63.5%) being voluntary donations with 11,680 (25%) repeat donations were collected during the study period. Donations from schools and colleges contributed a steady 60% of total voluntary whilst radio station blood drives increased contribution from 10 to 27%. Though Muslim population is less than 20%, blood collection was above the 30-donation cost-effectiveness threshold with a repeat donation trend reaching 60%. In contrast Christian worshippers provided donations. Repeat donation trends amongst school donors and radio blood drives were 20% and 70% respectively. Repeat donations rates have been variable amongst different blood donor groups in Kumasi, Ghana. The impact of community leaders in propagating altruism cannot be overemphasized. Programs aiming at motivating replacement donors to be repeat donors should be developed and assessed. Copyright 2009 The International Association for Biologicals. All rights reserved.

  7. Predicting effects of noncoding variants with deep learning-based sequence model.

    Science.gov (United States)

    Zhou, Jian; Troyanskaya, Olga G

    2015-10-01

    Identifying functional effects of noncoding variants is a major challenge in human genetics. To predict the noncoding-variant effects de novo from sequence, we developed a deep learning-based algorithmic framework, DeepSEA (http://deepsea.princeton.edu/), that directly learns a regulatory sequence code from large-scale chromatin-profiling data, enabling prediction of chromatin effects of sequence alterations with single-nucleotide sensitivity. We further used this capability to improve prioritization of functional variants including expression quantitative trait loci (eQTLs) and disease-associated variants.

  8. Contribution of ATXN2 intermediary polyQ expansions in a spectrum of neurodegenerative disorders.

    Science.gov (United States)

    Lattante, Serena; Millecamps, Stéphanie; Stevanin, Giovanni; Rivaud-Péchoux, Sophie; Moigneu, Carine; Camuzat, Agnès; Da Barroca, Sandra; Mundwiller, Emeline; Couarch, Philippe; Salachas, François; Hannequin, Didier; Meininger, Vincent; Pasquier, Florence; Seilhean, Danielle; Couratier, Philippe; Danel-Brunaud, Véronique; Bonnet, Anne-Marie; Tranchant, Christine; LeGuern, Eric; Brice, Alexis; Le Ber, Isabelle; Kabashi, Edor

    2014-09-09

    The aim of this study was to establish the frequency of ATXN2 polyglutamine (polyQ) expansion in large cohorts of patients with amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and progressive supranuclear palsy (PSP), and to evaluate whether ATXN2 could act as a modifier gene in patients carrying the C9orf72 expansion. We screened a large cohort of French patients (1,144 ALS, 203 FTD, 168 FTD-ALS, and 109 PSP) for ATXN2 CAG repeat length. We included in our cohort 322 carriers of the C9orf72 expansion (202 ALS, 63 FTD, and 57 FTD-ALS). We found a significant association with intermediate repeat size (≥29 CAG) in patients with ALS (both familial and sporadic) and, for the first time, in patients with familial FTD-ALS. Of interest, we found the co-occurrence of pathogenic C9orf72 expansion in 23.2% of ATXN2 intermediate-repeat carriers, all in the FTD-ALS and familial ALS subgroups. In the cohort of C9orf72 carriers, 3.1% of patients also carried an intermediate ATXN2 repeat length. ATXN2 repeat lengths in patients with PSP and FTD were found to be similar to the controls. ATXN2 intermediary repeat length is a strong risk factor for ALS and FTD-ALS. Furthermore, we propose that ATXN2 polyQ expansions could act as a strong modifier of the FTD phenotype in the presence of a C9orf72 repeat expansion, leading to the development of clinical signs featuring both FTD and ALS. © 2014 American Academy of Neurology.

  9. Sequence variations in C9orf72 downstream of the hexanucleotide repeat region and its effect on repeat-primed PCR interpretation

    DEFF Research Database (Denmark)

    Nordin, Angelica; Akimoto, Chizuru; Wuolikainen, Anna

    2017-01-01

    A large GGGGCC-repeat expansion mutation (HREM) in C9orf72 is the most common known cause of ALS and FTD in European populations. Sequence variations immediately downstream of the HREM region have previously been observed and have been suggested to be one reason for difficulties in interpreting R...

  10. A genome-wide signature of positive selection in ancient and recent invasive expansions of the honey bee Apis mellifera.

    Science.gov (United States)

    Zayed, Amro; Whitfield, Charles W

    2008-03-04

    Apis mellifera originated in Africa and extended its range into Eurasia in two or more ancient expansions. In 1956, honey bees of African origin were introduced into South America, their descendents admixing with previously introduced European bees, giving rise to the highly invasive and economically devastating "Africanized" honey bee. Here we ask whether the honey bee's out-of-Africa expansions, both ancient and recent (invasive), were associated with a genome-wide signature of positive selection, detected by contrasting genetic differentiation estimates (F(ST)) between coding and noncoding SNPs. In native populations, SNPs in protein-coding regions had significantly higher F(ST) estimates than those in noncoding regions, indicating adaptive evolution in the genome driven by positive selection. This signal of selection was associated with the expansion of honey bees from Africa into Western and Northern Europe, perhaps reflecting adaptation to temperate environments. We estimate that positive selection acted on a minimum of 852-1,371 genes or approximately 10% of the bee's coding genome. We also detected positive selection associated with the invasion of African-derived honey bees in the New World. We found that introgression of European-derived alleles into Africanized bees was significantly greater for coding than noncoding regions. Our findings demonstrate that Africanized bees exploited the genetic diversity present from preexisting introductions in an adaptive way. Finally, we found a significant negative correlation between F(ST) estimates and the local GC content surrounding coding SNPs, suggesting that AT-rich genes play an important role in adaptive evolution in the honey bee.

  11. The diversity and evolution of Wolbachia ankyrin repeat domain genes.

    Directory of Open Access Journals (Sweden)

    Stefanos Siozios

    Full Text Available Ankyrin repeat domain-encoding genes are common in the eukaryotic and viral domains of life, but they are rare in bacteria, the exception being a few obligate or facultative intracellular Proteobacteria species. Despite having a reduced genome, the arthropod strains of the alphaproteobacterium Wolbachia contain an unusually high number of ankyrin repeat domain-encoding genes ranging from 23 in wMel to 60 in wPip strain. This group of genes has attracted considerable attention for their astonishing large number as well as for the fact that ankyrin proteins are known to participate in protein-protein interactions, suggesting that they play a critical role in the molecular mechanism that determines host-Wolbachia symbiotic interactions. We present a comparative evolutionary analysis of the wMel-related ankyrin repeat domain-encoding genes present in different Drosophila-Wolbachia associations. Our results show that the ankyrin repeat domain-encoding genes change in size by expansion and contraction mediated by short directly repeated sequences. We provide examples of intra-genic recombination events and show that these genes are likely to be horizontally transferred between strains with the aid of bacteriophages. These results confirm previous findings that the Wolbachia genomes are evolutionary mosaics and illustrate the potential that these bacteria have to generate diversity in proteins potentially involved in the symbiotic interactions.

  12. ChloroSSRdb: a repository of perfect and imperfect chloroplastic simple sequence repeats (cpSSRs) of green plants.

    Science.gov (United States)

    Kapil, Aditi; Rai, Piyush Kant; Shanker, Asheesh

    2014-01-01

    Simple sequence repeats (SSRs) are regions in DNA sequence that contain repeating motifs of length 1-6 nucleotides. These repeats are ubiquitously present and are found in both coding and non-coding regions of genome. A total of 534 complete chloroplast genome sequences (as on 18 September 2014) of Viridiplantae are available at NCBI organelle genome resource. It provides opportunity to mine these genomes for the detection of SSRs and store them in the form of a database. In an attempt to properly manage and retrieve chloroplastic SSRs, we designed ChloroSSRdb which is a relational database developed using SQL server 2008 and accessed through ASP.NET. It provides information of all the three types (perfect, imperfect and compound) of SSRs. At present, ChloroSSRdb contains 124 430 mined SSRs, with majority lying in non-coding region. Out of these, PCR primers were designed for 118 249 SSRs. Tetranucleotide repeats (47 079) were found to be the most frequent repeat type, whereas hexanucleotide repeats (6414) being the least abundant. Additionally, in each species statistical analyses were performed to calculate relative frequency, correlation coefficient and chi-square statistics of perfect and imperfect SSRs. In accordance with the growing interest in SSR studies, ChloroSSRdb will prove to be a useful resource in developing genetic markers, phylogenetic analysis, genetic mapping, etc. Moreover, it will serve as a ready reference for mined SSRs in available chloroplast genomes of green plants. Database URL: www.compubio.in/chlorossrdb/ © The Author(s) 2014. Published by Oxford University Press.

  13. Plasma expansion: fundamentals and applications

    International Nuclear Information System (INIS)

    Engeln, R; Mazouffre, S; Vankan, P; Bakker, I; Schram, D C

    2002-01-01

    The study of plasma expansion is interesting from a fundamental point of view as well as from a more applied point of view. We here give a short overview of the way properties like density, velocity and temperature behave in an expanding thermal plasma. Experimental data show that the basic phenomena of plasma expansion are to some extent similar to those of the expansion of a hot neutral gas. From the application point of view, we present first results on the use of an expanding thermal plasma in the plasma-activated catalysis of ammonia, from N 2 -H 2 mixtures

  14. Huntingtin gene repeat size variations affect risk of lifetime depression.

    Science.gov (United States)

    Gardiner, Sarah L; van Belzen, Martine J; Boogaard, Merel W; van Roon-Mom, Willeke M C; Rozing, Maarten P; van Hemert, Albert M; Smit, Johannes H; Beekman, Aartjan T F; van Grootheest, Gerard; Schoevers, Robert A; Oude Voshaar, Richard C; Roos, Raymund A C; Comijs, Hannie C; Penninx, Brenda W J H; van der Mast, Roos C; Aziz, N Ahmad

    2017-12-11

    Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = -0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

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

    2014-01-01

    The Gd 5 Ge 2 Si 2 alloy and the off-stoichiometric Ni 50 Mn 35 In 15 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 Gd 5 Ge 2 Si 2 and Ni 50 Mn 35 In 15 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

  18. Extensive localization of long noncoding RNAs to the cytosol and mono- and polyribosomal complexes

    NARCIS (Netherlands)

    Heesch, S. van; Iterson, M. van; Jacobi, J.; Boymans, S.; Essers, P.B.; Bruijn, E. de; Hao, W.; Macinnes, A.W.; Cuppen, E.; Simonis, M.

    2014-01-01

    BACKGROUND: Long noncoding RNAs (lncRNAs) form an abundant class of transcripts, but the function of the majority of them remains elusive. While it has been shown that some lncRNAs are bound by ribosomes, it has also been convincingly demonstrated that these transcripts do not code for proteins. To

  19. LncRNAWiki: harnessing community knowledge in collaborative curation of human long non-coding RNAs

    KAUST Repository

    Ma, L.; Li, A.; Zou, D.; Xu, X.; Xia, L.; Yu, J.; Bajic, Vladimir B.; Zhang, Z.

    2014-01-01

    Long non-coding RNAs (lncRNAs) perform a diversity of functions in numerous important biological processes and are implicated in many human diseases. In this report we present lncRNAWiki (http://lncrna.big.ac.cn), a wiki-based platform that is open

  20. Long non-coding RNAs: Mechanism of action and functional utility

    Directory of Open Access Journals (Sweden)

    Shakil Ahmad Bhat

    2016-10-01

    Full Text Available Recent RNA sequencing studies have revealed that most of the human genome is transcribed, but very little of the total transcriptomes has the ability to encode proteins. Long non-coding RNAs (lncRNAs are non-coding transcripts longer than 200 nucleotides. Members of the non-coding genome include microRNA (miRNA, small regulatory RNAs and other short RNAs. Most of long non-coding RNA (lncRNAs are poorly annotated. Recent recognition about lncRNAs highlights their effects in many biological and pathological processes. LncRNAs are dysfunctional in a variety of human diseases varying from cancerous to non-cancerous diseases. Characterization of these lncRNA genes and their modes of action may allow their use for diagnosis, monitoring of progression and targeted therapies in various diseases. In this review, we summarize the functional perspectives as well as the mechanism of action of lncRNAs. Keywords: LncRNA, X-chromosome inactivation, Genome imprinting, Transcription regulation, Cancer, Immunity

  1. Clinical implication of long noncoding RNA 91H expression profile in osteosarcoma patients

    Directory of Open Access Journals (Sweden)

    Xia WK

    2016-07-01

    Full Text Available Wen-Kai Xia,1 Qing-Feng Lin,2 Dong Shen,2 Zhi-Li Liu,2 Jun Su,2 Wei-Dong Mao2 1Department of Nephrology, 2Department of Oncology, The Affiliated Jiangyin Hospital, School of Medicine, Southeast University, Jiangyin, Jiangsu, People’s Republic of China Abstract: Long noncoding RNAs have been documented as having widespread roles in carcinogenesis and cancer progression. However, roles of long noncoding RNAs in osteosarcoma remain unclear. This study is to investigate the clinical relevance and biological functions of long noncoding RNA 91H in osteosarcoma. Herein, we confirmed that 91H expression was notably increased in osteosarcoma patients and cell lines compared to healthy controls and normal human bone cell lines. High expression of 91H was significantly correlated with advanced clinical stage, chemotherapy after surgery, and tumor size >5 cm. Furthermore, 91H was an independent prognostic factor for overall survival in osteosarcoma patients after treatments. Additionally, the knockdown of 91H expression inhibited osteosarcoma cells’ proliferation and promoted their apoptosis in vitro. In summary, these findings indicate that 91H may be a novel biomarker for risk prognostication and also provide a clue to the molecular etiology of osteosarcoma. Keywords: long noncoding RNA, 91H, osteosarcoma, survival

  2. Extracellular vesicle associated long non-coding RNAs functionally enhance cell viability

    Directory of Open Access Journals (Sweden)

    Chris Hewson

    2016-10-01

    Full Text Available Cells communicate with one another to create microenvironments and share resources. One avenue by which cells communicate is through the action of exosomes. Exosomes are extracellular vesicles that are released by one cell and taken up by neighbouring cells. But how exosomes instigate communication between cells has remained largely unknown. We present evidence here that particular long non-coding RNA molecules are preferentially packaged into exosomes. We also find that a specific class of these exosome associated non-coding RNAs functionally modulate cell viability by direct interactions with l-lactate dehydrogenase B (LDHB, high-mobility group protein 17 (HMG-17, and CSF2RB, proteins involved in metabolism, nucleosomal architecture and cell signalling respectively. Knowledge of this endogenous cell to cell pathway, those proteins interacting with exosome associated non-coding transcripts and their interacting domains, could lead to a better understanding of not only cell to cell interactions but also the development of exosome targeted approaches in patient specific cell-based therapies. Keywords: Non-coding RNA, Extracellular RNA, Exosomes, Retroelement, Pseudogene

  3. Progressive changes in non-coding RNA profile in leucocytes with age

    Science.gov (United States)

    Muñoz-Culla, Maider; Irizar, Haritz; Gorostidi, Ana; Alberro, Ainhoa; Osorio-Querejeta, Iñaki; Ruiz-Martínez, Javier; Olascoaga, Javier; de Munain, Adolfo López; Otaegui, David

    2017-01-01

    It has been observed that immune cell deterioration occurs in the elderly, as well as a chronic low-grade inflammation called inflammaging. These cellular changes must be driven by numerous changes in gene expression and in fact, both protein-coding and non-coding RNA expression alterations have been observed in peripheral blood mononuclear cells from elder people. In the present work we have studied the expression of small non-coding RNA (microRNA and small nucleolar RNA -snoRNA-) from healthy individuals from 24 to 79 years old. We have observed that the expression of 69 non-coding RNAs (56 microRNAs and 13 snoRNAs) changes progressively with chronological age. According to our results, the age range from 47 to 54 is critical given that it is the period when the expression trend (increasing or decreasing) of age-related small non-coding RNAs is more pronounced. Furthermore, age-related miRNAs regulate genes that are involved in immune, cell cycle and cancer-related processes, which had already been associated to human aging. Therefore, human aging could be studied as a result of progressive molecular changes, and different age ranges should be analysed to cover the whole aging process. PMID:28448962

  4. p53-dependent non-coding RNA networks in chronic lymphocytic leukemia

    NARCIS (Netherlands)

    Blume, C. J.; Hotz-Wagenblatt, A.; Hüllein, J.; Sellner, L.; Jethwa, A.; Stolz, T.; Slabicki, M.; Lee, K.; Sharathchandra, A.; Benner, A.; Dietrich, S.; Oakes, C. C.; Dreger, P.; te Raa, D.; Kater, A. P.; Jauch, A.; Merkel, O.; Oren, M.; Hielscher, T.; Zenz, T.

    2015-01-01

    Mutations of the tumor suppressor p53 lead to chemotherapy resistance and a dismal prognosis in chronic lymphocytic leukemia (CLL). Whereas p53 targets are used to identify patient subgroups with impaired p53 function, a comprehensive assessment of non-coding RNA targets of p53 in CLL is missing. We

  5. allele of the noncoding hsrω gene of Drosophila melanogaster is not ...

    Indian Academy of Sciences (India)

    , Martinez P. et al. 2000 Identification of genes that modify ataxin-1-induced neurodegeneration. Nature 408, 101–. 106. Lakhotia S. C. 2003 The non-coding, developmentally active and stress inducible hsrω gene of Drosophila melanogaster ...

  6. Noncoding RNA of Glutamine Synthetase I Modulates Antibiotic Production in Streptomyces coelicolor A3(2)

    NARCIS (Netherlands)

    D'Alia, Davide; Nieselt, Kay; Steigele, Stephan; Mueller, Jonas; Verburg, Ilse; Takano, Eriko; Alia, Davide D’; Müller, Jonas

    Overexpression of antisense chromosomal cis-encoded noncoding RNAss (ncRNAs) in glutamine synthetase I resulted in a decrease in growth, protein synthesis, and antibiotic production in Streptomyces coelicolor. In addition, we predicted 3,597 cis-encoded ncRNAs and validated 13 of them

  7. Identification of putative noncoding RNA genes in the Burkholderia cenocepacia J2315 genome

    DEFF Research Database (Denmark)

    Coenye, T.; Drevinek, P.; Mahenthiralingam, E.

    2007-01-01

    Noncoding RNA (ncRNA) genes are not involved in the production of mRNA and proteins, but produce transcripts that function directly as structural or regulatory RNAs. In the present study, the presence of ncRNA genes in the genome of Burkholderia cenocepacia J2315 was evaluated by combining...

  8. Non-coding RNA may be associated with cytoplasmic male sterility in Silene vulgaris

    Czech Academy of Sciences Publication Activity Database

    Stone, James D.; Koloušková, Pavla; Sloan, D.B.; Štorchová, Helena

    2017-01-01

    Roč. 68, č. 7 (2017), s. 1599-1612 ISSN 0022-0957 R&D Projects: GA ČR(CZ) GA16-09220S Institutional support: RVO:61389030 Keywords : Cytoplasmic male sterility * Editing * Mitochondrion * Non-coding RNA * Silene vulgaris * Splicing * Transcriptome Subject RIV: EF - Botanics OBOR OECD: Plant sciences, botany Impact factor: 5.830, year: 2016

  9. Warp drive with zero expansion

    Energy Technology Data Exchange (ETDEWEB)

    Natario, Jose [Department of Mathematics, Instituto Superior Tecnico (Portugal)

    2002-03-21

    It is commonly believed that Alcubierre's warp drive works by contracting space in front of the warp bubble and expanding the space behind it. We show that this contraction/expansion is but a marginal consequence of the choice made by Alcubierre and explicitly construct a similar spacetime where no contraction/expansion occurs. Global and optical properties of warp-drive spacetimes are also discussed.

  10. Expansion lyre-shaped tube

    International Nuclear Information System (INIS)

    Andro, Jean.

    1973-01-01

    The invention relates the expansion lyre-shaped tube portions formed in dudgeoned tubular bundles between two bottom plates. An expansion lyre comprises at least two sets of tubes of unequal lengths coplanar and symmetrical with respect to the main tube axis, with connecting portions between the tubes forming said sets. The invention applies to apparatus such as heat exchangers, heaters, superheaters or breeders [fr

  11. Estimates of expansion time scales

    International Nuclear Information System (INIS)

    Jones, E.M.

    1979-01-01

    Monte Carlo simulations of the expansion of a spacefaring civilization show that descendants of that civilization should be found near virtually every useful star in the Galaxy in a time much less than the current age of the Galaxy. Only extreme assumptions about local population growth rates, emigration rates, or ship ranges can slow or halt an expansion. The apparent absence of extraterrestrials from the solar system suggests that no such civilization has arisen in the Galaxy. 1 figure

  12. Strategic Complexity and Global Expansion

    DEFF Research Database (Denmark)

    Oladottir, Asta Dis; Hobdari, Bersant; Papanastassiou, Marina

    2012-01-01

    The purpose of this paper is to analyse the determinants of global expansion strategies of newcomer Multinational Corporations (MNCs) by focusing on Iceland, Israel and Ireland. We argue that newcomer MNCs from small open economies pursue complex global expansion strategies (CGES). We distinguish....... The empirical evidence suggests that newcomer MNCs move away from simplistic dualities in the formulation of their strategic choices towards more complex options as a means of maintaining and enhancing their global competitiveness....

  13. Range expansion of heterogeneous populations.

    Science.gov (United States)

    Reiter, Matthias; Rulands, Steffen; Frey, Erwin

    2014-04-11

    Risk spreading in bacterial populations is generally regarded as a strategy to maximize survival. Here, we study its role during range expansion of a genetically diverse population where growth and motility are two alternative traits. We find that during the initial expansion phase fast-growing cells do have a selective advantage. By contrast, asymptotically, generalists balancing motility and reproduction are evolutionarily most successful. These findings are rationalized by a set of coupled Fisher equations complemented by stochastic simulations.

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

    Directory of Open Access Journals (Sweden)

    Charlotte Rehm

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

  15. Noncoding RNA in the Transcriptional Landscape of Human Neural Progenitor Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Patrick eHecht

    2015-10-01

    Full Text Available Increasing evidence suggests that noncoding RNAs play key roles in cellular processes, particularly in the brain. The present study used RNA sequencing to identify the transcriptional landscape of two human neural progenitor cell lines, SK-N-SH and ReNcell CX, as they differentiate into human cortical projection neurons. Protein coding genes were found to account for 54.8% and 57.0% of expressed genes, respectively, and alignment of RNA sequencing reads revealed that only 25.5-28.1% mapped to exonic regions of the genome. Differential expression analysis in the two cell lines identified altered gene expression in both protein coding and noncoding RNAs as they undergo neural differentiation with 222 differentially expressed genes observed in SK-N-SH cells and 19 differentially expressed genes in ReNcell CX. Interestingly, genes showing differential expression in SK-N-SH cells are enriched in genes implicated in autism spectrum disorder, but not in gene sets related to cancer or Alzheimer’s disease. Weighted gene co-expression network analysis (WGCNA was used to detect modules of co-expressed protein coding and noncoding RNAs in SK-N-SH cells and found four modules to be associated with neural differentiation. These modules contain varying levels of noncoding RNAs ranging from 10.7% to 49.7% with gene ontology suggesting roles in numerous cellular processes important for differentiation. These results indicate that noncoding RNAs are highly expressed in human neural progenitor cells and likely hold key regulatory roles in gene networks underlying neural differentiation and neurodevelopmental disorders.

  16. Identification of coding and non-coding mutational hotspots in cancer genomes.

    Science.gov (United States)

    Piraino, Scott W; Furney, Simon J

    2017-01-05

    The identification of mutations that play a causal role in tumour development, so called "driver" mutations, is of critical importance for understanding how cancers form and how they might be treated. Several large cancer sequencing projects have identified genes that are recurrently mutated in cancer patients, suggesting a role in tumourigenesis. While the landscape of coding drivers has been extensively studied and many of the most prominent driver genes are well characterised, comparatively less is known about the role of mutations in the non-coding regions of the genome in cancer development. The continuing fall in genome sequencing costs has resulted in a concomitant increase in the number of cancer whole genome sequences being produced, facilitating systematic interrogation of both the coding and non-coding regions of cancer genomes. To examine the mutational landscapes of tumour genomes we have developed a novel method to identify mutational hotspots in tumour genomes using both mutational data and information on evolutionary conservation. We have applied our methodology to over 1300 whole cancer genomes and show that it identifies prominent coding and non-coding regions that are known or highly suspected to play a role in cancer. Importantly, we applied our method to the entire genome, rather than relying on predefined annotations (e.g. promoter regions) and we highlight recurrently mutated regions that may have resulted from increased exposure to mutational processes rather than selection, some of which have been identified previously as targets of selection. Finally, we implicate several pan-cancer and cancer-specific candidate non-coding regions, which could be involved in tumourigenesis. We have developed a framework to identify mutational hotspots in cancer genomes, which is applicable to the entire genome. This framework identifies known and novel coding and non-coding mutional hotspots and can be used to differentiate candidate driver regions from

  17. Non-coding RNAs and epigenome: de novo DNA methylation, allelic exclusion and X-inactivation

    Directory of Open Access Journals (Sweden)

    V. A. Halytskiy

    2013-12-01

    Full Text Available Non-coding RNAs are widespread class of cell RNAs. They participate in many important processes in cells – signaling, posttranscriptional silencing, protein biosynthesis, splicing, maintenance of genome stability, telomere lengthening, X-inactivation. Nevertheless, activity of these RNAs is not restricted to posttranscriptional sphere, but cover also processes that change or maintain the epigenetic information. Non-coding RNAs can directly bind to the DNA targets and cause their repression through recruitment of DNA methyltransferases as well as chromatin modifying enzymes. Such events constitute molecular mechanism of the RNA-dependent DNA methylation. It is possible, that the RNA-DNA interaction is universal mechanism triggering DNA methylation de novo. Allelic exclusion can be also based on described mechanism. This phenomenon takes place, when non-coding RNA, which precursor is transcribed from one allele, triggers DNA methylation in all other alleles present in the cell. Note, that miRNA-mediated transcriptional silencing resembles allelic exclusion, because both miRNA gene and genes, which can be targeted by this miRNA, contain elements with the same sequences. It can be assumed that RNA-dependent DNA methylation and allelic exclusion originated with the purpose of counteracting the activity of mobile genetic elements. Probably, thinning and deregulation of the cellular non-coding RNA pattern allows reactivation of silent mobile genetic elements resulting in genome instability that leads to ageing and carcinogenesis. In the course of X-inactivation, DNA methylation and subsequent hete­rochromatinization of X chromosome can be triggered by direct hybridization of 5′-end of large non-coding RNA Xist with DNA targets in remote regions of the X chromosome.

  18. Coordination in continuously repeated games

    NARCIS (Netherlands)

    Weeren, A.J.T.M.; Schumacher, J.M.; Engwerda, J.C.

    1995-01-01

    In this paper we propose a model to describe the effectiveness of coordination in a continuously repeated two-player game. We study how the choice of a decision rule by a coordinator affects the strategic behavior of the players, resulting in more or less cooperation. Our model requires the analysis

  19. Repeated checking causes memory distrust

    NARCIS (Netherlands)

    van den Hout, M.; Kindt, M.

    2003-01-01

    This paper attempts to explain why in obsessive-compulsive disorder (OCD) checkers distrust in memory persists despite extensive checking. It is argued that: (1) repeated checking increases familiarity with the issues checked; (2) increased familiarity promotes conceptual processing which inhibits

  20. Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism

    Directory of Open Access Journals (Sweden)

    Agathi-Vasiliki Goula

    2013-07-01

    Full Text Available More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER.

  1. A single-surface electrochemical biosensor for the detection of DNA triplet repeat expansion

    Czech Academy of Sciences Publication Activity Database

    Fojta, Miroslav; Horáková Brázdilová, Petra; Cahová, Kateřina; Pečinka, Petr

    2006-01-01

    Roč. 18, č. 2 (2006), s. 141-151 ISSN 1040-0397 R&D Projects: GA MPO(CZ) 1H-PK/42; GA AV ČR(CZ) IAA4004402 Institutional research plan: CEZ:AV0Z50040507 Keywords : DNA hybridization * electrochemical biosensor * enzyme-linked assay Subject RIV: BO - Biophysics Impact factor: 2.444, year: 2006

  2. The genetic analysis of repeated measures II: The Karhunen-Loeve expansion.

    NARCIS (Netherlands)

    Molenaar, P.C.M.; Boomsma, D.I.

    1987-01-01

    Outlines the Karhunen-Loeve (N. Ahmed and K. R. Rao, 1975) approach to the genetic analysis of time series of arbitrary length and with arbitrary covariance function. This approach is based on the simultaneous eigenvalue decomposition of the covariance matrices of the original time series obtained

  3. On genus expansion of superpolynomials

    Energy Technology Data Exchange (ETDEWEB)

    Mironov, Andrei, E-mail: mironov@itep.ru [Lebedev Physics Institute, Moscow 119991 (Russian Federation); ITEP, Moscow 117218 (Russian Federation); National Research Nuclear University MEPhI, Moscow 115409 (Russian Federation); Morozov, Alexei, E-mail: morozov@itep.ru [ITEP, Moscow 117218 (Russian Federation); National Research Nuclear University MEPhI, Moscow 115409 (Russian Federation); Sleptsov, Alexei, E-mail: sleptsov@itep.ru [ITEP, Moscow 117218 (Russian Federation); Laboratory of Quantum Topology, Chelyabinsk State University, Chelyabinsk 454001 (Russian Federation); KdVI, University of Amsterdam (Netherlands); Smirnov, Andrey, E-mail: asmirnov@math.columbia.edu [ITEP, Moscow 117218 (Russian Federation); Columbia University, Department of Mathematics, New York (United States)

    2014-12-15

    Recently it was shown that the (Ooguri–Vafa) generating function of HOMFLY polynomials is the Hurwitz partition function, i.e. that the dependence of the HOMFLY polynomials on representation R is naturally captured by symmetric group characters (cut-and-join eigenvalues). The genus expansion and expansion through Vassiliev invariants explicitly demonstrate this phenomenon. In the present paper we claim that the superpolynomials are not functions of such a type: symmetric group characters do not provide an adequate linear basis for their expansions. Deformation to superpolynomials is, however, straightforward in the multiplicative basis: the Casimir operators are β-deformed to Hamiltonians of the Calogero–Moser–Sutherland system. Applying this trick to the genus and Vassiliev expansions, we observe that the deformation is fully straightforward only for the thin knots. Beyond the family of thin knots additional algebraically independent terms appear in the Vassiliev and genus expansions. This can suggest that the superpolynomials do in fact contain more information about knots than the colored HOMFLY and Kauffman polynomials. However, even for the thin knots the beta-deformation is non-innocent: already in the simplest examples it seems inconsistent with the positivity of colored superpolynomials in non-(anti)symmetric representations, which also happens in I. Cherednik's (DAHA-based) approach to the torus knots.

  4. Low-Normal FMR1 CGG Repeat Length: Phenotypic Associations

    Directory of Open Access Journals (Sweden)

    Marsha eMailick

    2014-09-01

    Full Text Available This population-based study investigates genotype-phenotype correlations of low-normal CGG repeats in the fragile X mental retardation 1 (FMR1 gene. FMR1 plays an important role in brain development and function, and encodes FMRP (fragile X mental retardation protein, an RNA-binding protein that regulates protein synthesis impacting activity-dependent synaptic development and plasticity. Most past research has focused on CGG premutation expansions (41 to 200 CGG repeats and on fragile X syndrome (200+ CGG repeats, with considerably less attention on the other end of the spectrum of CGG repeats. Using existing data, older adults with 23 or fewer CGG repeats (2 SDs below the mean were compared with age-peers who have normal numbers of CGGs (24-40 with respect to cognition, mental health, cancer, and having children with disabilities. Men (n = 341 with an allele in the low-normal range and women (n = 46 with two low-normal alleles had significantly more difficulty with their memory and ability to solve day to day problems. Women with both FMR1 alleles in the low-normal category had significantly elevated odds of feeling that they need to drink more to get the same effect as in the past. These women also had two and one-half times the odds of having had breast cancer and four times the odds of uterine cancer. Men and women with low-normal CGGs had higher odds of having a child with a disability, either a developmental disability or a mental health condition. These findings are in line with the hypothesis that there is a need for tight neuronal homeostatic control mechanisms for optimal cognitive and behavioral functioning, and more generally that low numbers as well as high numbers of CGG repeats may be problematic for health.

  5. TALEN-Induced Double-Strand Break Repair of CTG Trinucleotide Repeats

    Directory of Open Access Journals (Sweden)

    Valentine Mosbach

    2018-02-01

    Full Text Available Trinucleotide repeat expansions involving CTG/CAG triplets are responsible for several neurodegenerative disorders, including myotonic dystrophy and Huntington’s disease. Because expansions trigger the disease, contracting repeat length could be a possible approach to gene therapy for these disorders. Here, we show that a TALEN-induced double-strand break was very efficient at contracting expanded CTG repeats in yeast. We show that RAD51, POL32, and DNL4 are dispensable for double-strand break repair within CTG repeats, the only required genes being RAD50, SAE2, and RAD52. Resection was totally abolished in the absence of RAD50 on both sides of the break, whereas it was reduced in a sae2Δ mutant on the side of the break containing the longest repeat tract, suggesting that secondary structures at double-strand break ends must be removed by the Mre11-Rad50 complex and Sae2. Following the TALEN double-strand break, single-strand annealing occurred between both sides of the repeat tract, leading to repeat contraction.

  6. Non-radioactive detection of trinucleotide repeat size variability.

    Science.gov (United States)

    Tomé, Stéphanie; Nicole, Annie; Gomes-Pereira, Mario; Gourdon, Genevieve

    2014-03-06

    Many human diseases are associated with the abnormal expansion of unstable trinucleotide repeat sequences. The mechanisms of trinucleotide repeat size mutation have not been fully dissected, and their understanding must be grounded on the detailed analysis of repeat size distributions in human tissues and animal models. Small-pool PCR (SP-PCR) is a robust, highly sensitive and efficient PCR-based approach to assess the levels of repeat size variation, providing both quantitative and qualitative data. The method relies on the amplification of a very low number of DNA molecules, through sucessive dilution of a stock genomic DNA solution. Radioactive Southern blot hybridization is sensitive enough to detect SP-PCR products derived from single template molecules, separated by agarose gel electrophoresis and transferred onto DNA membranes. We describe a variation of the detection method that uses digoxigenin-labelled locked nucleic acid probes. This protocol keeps the sensitivity of the original method, while eliminating the health risks associated with the manipulation of radiolabelled probes, and the burden associated with their regulation, manipulation and waste disposal.

  7. Genic non-coding microsatellites in the rice genome: characterization, marker design and use in assessing genetic and evolutionary relationships among domesticated groups

    Directory of Open Access Journals (Sweden)

    Singh Nagendra

    2009-03-01

    Full Text Available Abstract Background Completely sequenced plant genomes provide scope for designing a large number of microsatellite markers, which are useful in various aspects of crop breeding and genetic analysis. With the objective of developing genic but non-coding microsatellite (GNMS markers for the rice (Oryza sativa L. genome, we characterized the frequency and relative distribution of microsatellite repeat-motifs in 18,935 predicted protein coding genes including 14,308 putative promoter sequences. Results We identified 19,555 perfect GNMS repeats with densities ranging from 306.7/Mb in chromosome 1 to 450/Mb in chromosome 12 with an average of 357.5 GNMS per Mb. The average microsatellite density was maximum in the 5' untranslated regions (UTRs followed by those in introns, promoters, 3'UTRs and minimum in the coding sequences (CDS. Primers were designed for 17,966 (92% GNMS repeats, including 4,288 (94% hypervariable class I types, which were bin-mapped on the rice genome. The GNMS markers were most polymorphic in the intronic region (73.3% followed by markers in the promoter region (53.3% and least in the CDS (26.6%. The robust polymerase chain reaction (PCR amplification efficiency and high polymorphic potential of GNMS markers over genic coding and random genomic microsatellite markers suggest their immediate use in efficient genotyping applications in rice. A set of these markers could assess genetic diversity and establish phylogenetic relationships among domesticated rice cultivar groups. We also demonstrated the usefulness of orthologous and paralogous conserved non-coding microsatellite (CNMS markers, identified in the putative rice promoter sequences, for comparative physical mapping and understanding of evolutionary and gene regulatory complexities among rice and other members of the grass family. The divergence between long-grained aromatics and subspecies japonica was estimated to be more recent (0.004 Mya compared to short

  8. Online learning in repeated auctions

    OpenAIRE

    Weed, Jonathan; Perchet, Vianney; Rigollet, Philippe

    2015-01-01

    Motivated by online advertising auctions, we consider repeated Vickrey auctions where goods of unknown value are sold sequentially and bidders only learn (potentially noisy) information about a good's value once it is purchased. We adopt an online learning approach with bandit feedback to model this problem and derive bidding strategies for two models: stochastic and adversarial. In the stochastic model, the observed values of the goods are random variables centered around the true value of t...

  9. Low Thermal Expansion Glass Ceramics

    CERN Document Server

    Bach, Hans

    2005-01-01

    This book appears in the authoritative series reporting the international research and development activities conducted by the Schott group of companies. This series provides an overview of Schott's activities for scientists, engineers, and managers from all branches of industry worldwide in which glasses and glass ceramics are of interest. Each volume begins with a chapter providing a general idea of the current problems, results, and trends relating to the subjects treated. This new extended edition describes the fundamental principles, the manufacturing process, and applications of low thermal expansion glass ceramics. The composition, structure, and stability of polycrystalline materials having a low thermal expansion are described, and it is shown how low thermal expansion glass ceramics can be manufactured from appropriately chosen glass compositions. Examples illustrate the formation of this type of glass ceramic by utilizing normal production processes together with controlled crystallization. Thus g...

  10. Low thermal expansion glass ceramics

    CERN Document Server

    1995-01-01

    This book is one of a series reporting on international research and development activities conducted by the Schott group of companies With the series, Schott aims to provide an overview of its activities for scientists, engineers, and managers from all branches of industry worldwide where glasses and glass ceramics are of interest Each volume begins with a chapter providing a general idea of the current problems, results, and trends relating to the subjects treated This volume describes the fundamental principles, the manufacturing process, and applications of low thermal expansion glass ceramics The composition, structure, and stability of polycrystalline materials having a low thermal expansion are described, and it is shown how low thermal expansion glass ceramics can be manufactured from appropriately chosen glass compositions Examples illustrate the formation of this type of glass ceramic by utilizing normal production processes together with controlled crystallization Thus glass ceramics with thermal c...

  11. Regulation of gas infrastructure expansion

    International Nuclear Information System (INIS)

    De Joode, J.

    2012-01-01

    The topic of this dissertation is the regulation of gas infrastructure expansion in the European Union (EU). While the gas market has been liberalised, the gas infrastructure has largely remained in the regulated domain. However, not necessarily all gas infrastructure facilities - such as gas storage facilities, LNG import terminals and certain gas transmission pipelines - need to be regulated, as there may be scope for competition. In practice, the choice of regulation of gas infrastructure expansion varies among different types of gas infrastructure facilities and across EU Member States. Based on a review of economic literature and on a series of in-depth case studies, this study explains these differences in choices of regulation from differences in policy objectives, differences in local circumstances and differences in the intrinsic characteristics of the infrastructure projects. An important conclusion is that there is potential for a larger role for competition in gas infrastructure expansion.

  12. A repeating fast radio burst.

    Science.gov (United States)

    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.

  13. The loop expansion as a divergent-power-series expansion

    International Nuclear Information System (INIS)

    Murai, N.

    1981-01-01

    The loop expansion should be divergent, possibly an asymptotic one, in the Euclidean path integral formulation. This consideration is important in applications of the symmetric and mass-independent renormalization. The [1,1] Pade approximant is calculated in a PHI 4 model. Its classical vacua may be not truely stable for nonzero coupling constant. (author)

  14. Cosmological expansion and local physics

    International Nuclear Information System (INIS)

    Faraoni, Valerio; Jacques, Audrey

    2007-01-01

    The interplay between cosmological expansion and local attraction in a gravitationally bound system is revisited in various regimes. First, weakly gravitating Newtonian systems are considered, followed by various exact solutions describing a relativistic central object embedded in a Friedmann universe. It is shown that the 'all or nothing' behavior recently discovered (i.e., weakly coupled systems are comoving while strongly coupled ones resist the cosmic expansion) is limited to the de Sitter background. New exact solutions are presented which describe black holes perfectly comoving with a generic Friedmann universe. The possibility of violating cosmic censorship for a black hole approaching the big rip is also discussed

  15. Temperature expansions for magnetic systems

    International Nuclear Information System (INIS)

    Cangemi, D.; Dunne, G.

    1996-01-01

    We derive finite temperature expansions for relativistic fermion systems in the presence of background magnetic fields, and with nonzero chemical potential. We use the imaginary-time formalism for the finite temperature effects, the proper-time method for the background field effects, and zeta function regularization for developing the expansions. We emphasize the essential difference between even and odd dimensions, focusing on 2+1 and 3+1 dimensions. We concentrate on the high temperature limit, but we also discuss the T=0 limit with nonzero chemical potential. Copyright copyright 1996 Academic Press, Inc

  16. Bearing-Mounting Concept Accommodates Thermal Expansion

    Science.gov (United States)

    Nespodzany, Robert; Davis, Toren S.

    1995-01-01

    Pins or splines allow radial expansion without slippage. Design concept for mounting rotary bearing accommodates differential thermal expansion between bearing and any structure(s) to which bearing connected. Prevents buildup of thermal stresses by allowing thermal expansion to occur freely but accommodating expansion in such way not to introduce looseness. Pin-in-slot configuration also maintains concentricity.

  17. Catalog of Differentially Expressed Long Non-Coding RNA following Activation of Human and Mouse Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Benoit T. Roux

    2017-08-01

    Full Text Available Despite increasing evidence to indicate that long non-coding RNAs (lncRNAs are novel regulators of immunity, there has been no systematic attempt to identify and characterize the lncRNAs whose expression is changed following the induction of the innate immune response. To address this issue, we have employed next-generation sequencing data to determine the changes in the lncRNA profile in four human (monocytes, macrophages, epithelium, and chondrocytes and four mouse cell types (RAW 264.7 macrophages, bone marrow-derived macrophages, peritoneal macrophages, and splenic dendritic cells following exposure to the pro-inflammatory mediators, lipopolysaccharides (LPS, or interleukin-1β. We show differential expression of 204 human and 210 mouse lncRNAs, with positional analysis demonstrating correlation with immune-related genes. These lncRNAs are predominantly cell-type specific, composed of large regions of repeat sequences, and show poor evolutionary conservation. Comparison within the human and mouse sequences showed less than 1% sequence conservation, although we identified multiple conserved motifs. Of the 204 human lncRNAs, 21 overlapped with syntenic mouse lncRNAs, of which five were differentially expressed in both species. Among these syntenic lncRNA was IL7-AS (antisense, which was induced in multiple cell types and shown to regulate the production of the pro-inflammatory mediator interleukin-6 in both human and mouse cells. In summary, we have identified and characterized those lncRNAs that are differentially expressed following activation of the human and mouse innate immune responses and believe that these catalogs will provide the foundation for the future analysis of the role of lncRNAs in immune and inflammatory responses.

  18. An integrative approach to predicting the functional effects of small indels in non-coding regions of the human genome.

    Science.gov (United States)

    Ferlaino, Michael; Rogers, Mark F; Shihab, Hashem A; Mort, Matthew; Cooper, David N; Gaunt, Tom R; Campbell, Colin

    2017-10-06

    Small insertions and deletions (indels) have a significant influence in human disease and, in terms of frequency, they are second only to single nucleotide variants as pathogenic mutations. As the majority of mutations associated with complex traits are located outside the exome, it is crucial to investigate the potential pathogenic impact of indels in non-coding regions of the human genome. We present FATHMM-indel, an integrative approach to predict the functional effect, pathogenic or neutral, of indels in non-coding regions of the human genome. Our method exploits various genomic annotations in addition to sequence data. When validated on benchmark data, FATHMM-indel significantly outperforms CADD and GAVIN, state of the art models in assessing the pathogenic impact of non-coding variants. FATHMM-indel is available via a web server at indels.biocompute.org.uk. FATHMM-indel can accurately predict the functional impact and prioritise small indels throughout the whole non-coding genome.

  19. Nezha, a novel active miniature inverted-repeat transposable element in cyanobacteria

    International Nuclear Information System (INIS)

    Zhou Fengfeng; Tran Thao; Xu Ying

    2008-01-01

    Miniature inverted-repeat transposable elements (MITEs) were first identified in plants and exerted extensive proliferations throughout eukaryotic and archaeal genomes. But very few MITEs have been characterized in bacteria. We identified a novel MITE, called Nezha, in cyanobacteria Anabaena variabilis ATCC 29413 and Nostoc sp. PCC 7120. Nezha, like most previously known MITEs in other organisms, is small in size, non-coding, carrying TIR and DR signals, and of potential to form a stable RNA secondary structure, and it tends to insert into A+T-rich regions. Recent transpositions of Nezha were observed in A. variabilis ATCC 29413 and Nostoc sp. PCC 7120, respectively. Nezha might have proliferated recently with aid from the transposase encoded by ISNpu3-like elements. A possible horizontal transfer event of Nezha from cyanobacteria to Polaromonas JS666 is also observed

  20. Energy expansion planning by considering electrical and thermal expansion simultaneously

    International Nuclear Information System (INIS)

    Abbasi, Ali Reza; Seifi, Ali Reza

    2014-01-01

    Highlights: • This paper focused on the expansion planning optimization of energy systems. • Employing two form of energy: the expansion of electrical and thermal energies. • The main objective is to minimize the costs. • A new Modified Honey Bee Mating Optimization (MHBMO) algorithm is applied. - Abstract: This study focused on the expansion planning optimization of energy systems employing two forms of energy: the expansion of electrical and thermal energies simultaneously. The main objective of this investigation is confirming network adequacy by adding new equipment to the network, over a given planning horizon. The main objective of the energy expansion planning (EEP) is to minimize the real energy loss, voltage deviation and the total cost of installation equipments. Since the objectives are different and incommensurable, it is difficult to solve the problem by the conventional approaches that may optimize a single objective. So, the meta-heuristic algorithm is applied to this problem. Here, Honey Bee Mating Optimization algorithm (HBMO) as a new evolutionary optimization algorithm is utilized. In order to improve the total ability of HBMO for the global search and exploration, a new modification process is suggested such a way that the algorithm will search the total search space globally. Also, regarding the uncertainties of the new complicated energy systems, in this paper for the first time, the EEP problem is investigated in a stochastic environment by the use of probabilistic load flow technique based on Point Estimate Method (PEM). In order to evaluate the feasibility and effectiveness of the proposed algorithm, two modified test systems are used as case studies

  1. The Thermal Expansion Of Feldspars

    Science.gov (United States)

    Hovis, G. L.; Medford, A.; Conlon, M.

    2009-12-01

    Hovis and others (1) investigated the thermal expansion of natural and synthetic AlSi3 feldspars and demonstrated that the coefficient of thermal expansion (α) decreases significantly, and linearly, with increasing room-temperature volume (VRT). In all such feldspars, therefore, chemical expansion limits thermal expansion. The scope of this work now has been broadened to include plagioclase and Ba-K feldspar crystalline solutions. X-ray powder diffraction data have been collected between room temperature and 925 °C on six plagioclase specimens ranging in composition from anorthite to oligoclase. When combined with thermal expansion data for albite (2,3,4) a steep linear trend of α as a function of VRT emerges, reflecting how small changes in composition dramatically affect expansion behavior. The thermal expansion data for five synthetic Ba-K feldspars ranging in composition from 20 to 100 mole percent celsian, combined with data for pure K-feldspar (3,4), show α-VRT relationships similar in nature to the plagioclase series, but with a slope and intercept different from the latter. Taken as a group all Al2Si2 feldspars, including anorthite and celsian from the present study along with Sr- (5) and Pb-feldspar (6) from other workers, show very limited thermal expansion that, unlike AlSi3 feldspars, has little dependence on the divalent-ion (or M-) site occupant. This apparently is due to the necessitated alternation of Al and Si in the tetrahedral sites of these minerals (7), which in turn locks the tetrahedral framework and makes the M-site occupant nearly irrelevant to expansion behavior. Indeed, in feldspar series with coupled chemical substitution it is the change away from a 1:1 Al:Si ratio that gives feldspars greater freedom to expand. Overall, the relationships among α, chemical composition, and room-temperature volume provide useful predictive tools for estimating feldspar thermal expansion and give insight into the controls of expansion behavior in

  2. Base excision repair of chemotherapeutically-induced alkylated DNA damage predominantly causes contractions of expanded GAA repeats associated with Friedreich's ataxia.

    Directory of Open Access Journals (Sweden)

    Yanhao Lai

    Full Text Available Expansion of GAA·TTC repeats within the first intron of the frataxin gene is the cause of Friedreich's ataxia (FRDA, an autosomal recessive neurodegenerative disorder. However, no effective treatment for the disease has been developed as yet. In this study, we explored a possibility of shortening expanded GAA repeats associated with FRDA through chemotherapeutically-induced DNA base lesions and subsequent base excision repair (BER. We provide the first evidence that alkylated DNA damage induced by temozolomide, a chemotherapeutic DNA damaging agent can induce massive GAA repeat contractions/deletions, but only limited expansions in FRDA patient lymphoblasts. We showed that temozolomide-induced GAA repeat instability was mediated by BER. Further characterization of BER of an abasic site in the context of (GAA20 repeats indicates that the lesion mainly resulted in a large deletion of 8 repeats along with small expansions. This was because temozolomide-induced single-stranded breaks initially led to DNA slippage and the formation of a small GAA repeat loop in the upstream region of the damaged strand and a small TTC loop on the template strand. This allowed limited pol β DNA synthesis and the formation of a short 5'-GAA repeat flap that was cleaved by FEN1, thereby leading to small repeat expansions. At a later stage of BER, the small template loop expanded into a large template loop that resulted in the formation of a long 5'-GAA repeat flap. Pol β then performed limited DNA synthesis to bypass the loop, and FEN1 removed the long repeat flap ultimately causing a large repeat deletion. Our study indicates that chemotherapeutically-induced alkylated DNA damage can induce large contractions/deletions of expanded GAA repeats through BER in FRDA patient cells. This further suggests the potential of developing chemotherapeutic alkylating agents to shorten expanded GAA repeats for treatment of FRDA.

  3. Long noncoding RNAs: Undeciphered cellular codes encrypting keys of colorectal cancer pathogenesis

    Science.gov (United States)

    Kim, Taewan; Croce, Carlo M.

    2018-01-01

    Long noncoding RNAs are non-protein coding transcripts longer than 200 nucleotides in length. By the advance in genetic and bioinformatic technologies, the new genomic landscape including noncoding transcripts has been revealed. Despite their non-capacity to be translated into proteins, lncRNAs have a versatile functions through various mechanisms interacting with other cellular molecules including DNA, protein, and RNA. Recent research interest and endeavor have identified the functional role of lncRNAs in various diseases including cancer. Colorectal cancer (CRC) is not only one of the most frequent cancer but also one of the cancer types with remarkable achievements in lncRNA research. Of the numerous notable lncRNAs identified and characterized in CRC, we will focus on key lncRNAs with the high potential as CRC-specific biomarkers in this review. PMID:29306015

  4. Non-Coding RNAs are Differentially Expressed by Nocardia brasiliensis in Vitro and in Experimental Actinomycetoma.

    Science.gov (United States)

    Cruz-Rabadán, Josué S; Miranda-Ríos, Juan; Espín-Ocampo, Guadalupe; Méndez-Tovar, Luis J; Maya-Pineda, Héctor Rubén; Hernández-Hernández, Francisca

    2017-01-01

    Nocardia spp. are common soil-inhabiting bacteria that frequently infect humans through traumatic injuries or inhalation routes and cause infections, such as actinomycetoma and nocardiosis, respectively. Nocardia brasiliensis is the main aetiological agent of actinomycetoma in various countries. Many bacterial non-coding RNAs are regulators of genes associated with virulence factors. The aim of this work was to identify non-coding RNAs (ncRNAs) expressed during infection conditions and in free-living form ( in vitro ) in Nocardia brasiliensis . The N. brasiliensis transcriptome (predominately brasiliensis infection compared with the in vitro conditions. The results of this work suggest a possible role for these transcripts in the regulation of virulence genes in actinomycetoma pathogenesis.

  5. Laminar and Temporal Expression Dynamics of Coding and Noncoding RNAs in the Mouse Neocortex

    Directory of Open Access Journals (Sweden)

    Sofia Fertuzinhos

    2014-03-01

    Full Text Available The hallmark of the cerebral neocortex is its organization into six layers, each containing a characteristic set of cell types and synaptic connections. The transcriptional events involved in laminar development and function still remain elusive. Here, we employed deep sequencing of mRNA and small RNA species to gain insights into transcriptional differences among layers and their temporal dynamics during postnatal development of the mouse primary somatosensory neocortex. We identify a number of coding and noncoding transcripts with specific spatiotemporal expression and splicing patterns. We also identify signature trajectories and gene coexpression networks associated with distinct biological processes and transcriptional overlap between these processes. Finally, we provide data that allow the study of potential miRNA and mRNA interactions. Overall, this study provides an integrated view of the laminar and temporal expression dynamics of coding and noncoding transcripts in the mouse neocortex and a resource for studies of neurodevelopment and transcriptome.

  6. Crude oil pipeline expansion summary

    International Nuclear Information System (INIS)

    2005-02-01

    The Canadian Association of Petroleum Producers has been working with producers to address issues associated with the development of new pipeline capacity from western Canada. This document presents an assessment of the need for additional oil pipeline capacity given the changing mix of crude oil types and forecasted supply growth. It is of particular interest to crude oil producers and contributes to current available information for market participants. While detailed, the underlying analysis does not account for all the factors that may come into play when individual market participants make choices about which expansions they may support. The key focus is on the importance of timely expansion. It was emphasized that if pipeline expansions lags the crude supply growth, then the consequences would be both significant and unacceptable. Obstacles to timely expansion are also discussed. The report reviews the production and supply forecasts, the existing crude oil pipeline infrastructure, opportunities for new market development, requirements for new pipeline capacity and tolling options for pipeline development. tabs., figs., 1 appendix

  7. Asymptotic Expansions - Methods and Applications

    International Nuclear Information System (INIS)

    Harlander, R.

    1999-01-01

    Different viewpoints on the asymptotic expansion of Feynman diagrams are reviewed. The relations between the field theoretic and diagrammatic approaches are sketched. The focus is on problems with large masses or large external momenta. Several recent applications also for other limiting cases are touched upon. Finally, the pros and cons of the different approaches are briefly discussed. (author)

  8. Model of clinker capacity expansion

    CSIR Research Space (South Africa)

    Stylianides, T

    1998-10-01

    Full Text Available This paper describes a model which has been applied in practice to determine an optimal plan for clinker capacity expansion. The problem was formulated as an integer linear program aiming to determine the optimal number, size and location of kilns...

  9. The bootstrap and edgeworth expansion

    CERN Document Server

    Hall, Peter

    1992-01-01

    This monograph addresses two quite different topics, in the belief that each can shed light on the other. Firstly, it lays the foundation for a particular view of the bootstrap. Secondly, it gives an account of Edgeworth expansion. Chapter 1 is about the bootstrap, witih almost no mention of Edgeworth expansion; Chapter 2 is about Edgeworth expansion, with scarcely a word about the bootstrap; and Chapters 3 and 4 bring these two themes together, using Edgeworth expansion to explore and develop the properites of the bootstrap. The book is aimed a a graduate level audience who has some exposure to the methods of theoretical statistics. However, technical details are delayed until the last chapter (entitled "Details of Mathematical Rogour"), and so a mathematically able reader without knowledge of the rigorous theory of probability will have no trouble understanding the first four-fifths of the book. The book simultaneously fills two gaps in the literature; it provides a very readable graduate level account of t...

  10. On Fourier re-expansions

    OpenAIRE

    Liflyand, E.

    2012-01-01

    We study an extension to Fourier transforms of the old problem on absolute convergence of the re-expansion in the sine (cosine) Fourier series of an absolutely convergent cosine (sine) Fourier series. The results are obtained by revealing certain relations between the Fourier transforms and their Hilbert transforms.

  11. On persistently positively expansive maps

    Directory of Open Access Journals (Sweden)

    Alexander Arbieto

    2010-06-01

    Full Text Available In this paper, we prove that any C¹-persistently positively expansive map is expanding. This improves a result due to Sakai (Sakai 2004.Neste artigo, mostramos que todo mapa C¹-persistentemente positivamente expansivo e expansor. Isto melhora um resultado devido a Sakai (Sakai 2004.

  12. The role of non-coding RNAs in cytoplasmic male sterility in flowering plants

    Czech Academy of Sciences Publication Activity Database

    Štorchová, Helena

    2017-01-01

    Roč. 18, č. 11 (2017), č. článku 2429. E-ISSN 1422-0067 R&D Projects: GA ČR GA16-09220S Institutional support: RVO:61389030 Keywords : Cytoplasmic male sterility * Gene expression * Global transcriptome * Non-coding RNA * Pollen development Subject RIV: EF - Botanics OBOR OECD: Plant sciences, botany Impact factor: 3.226, year: 2016

  13. Overexpression of Long Non-Coding RNA TUG1 Promotes Colon Cancer Progression

    OpenAIRE

    Zhai, Hui-yuan; Sui, Ming-hua; Yu, Xiao; Qu, Zhen; Hu, Jin-chen; Sun, Hai-qing; Zheng, Hai-tao; Zhou, Kai; Jiang, Li-xin

    2016-01-01

    Background Colon cancer is one of the most prevalent and deadly cancers worldwide. It is still necessary to further define the mechanisms and explore therapeutic targets of colon cancer. Dysregulation of long noncoding RNAs (lncRNAs) has been shown to be correlated with diverse biological processes, including tumorigenesis. This study aimed to characterize the biological mechanism of taurine-upregulated gene 1 (TUG1) in colon cancer. Material/Methods qRT-PCR was used to analyze the expression...

  14. Identification and characterization of long intergenic noncoding RNAs in bovine mammary glands.

    Science.gov (United States)

    Tong, Chao; Chen, Qiaoling; Zhao, Lili; Ma, Junfei; Ibeagha-Awemu, Eveline M; Zhao, Xin

    2017-06-19

    Mammary glands of dairy cattle produce milk for the newborn offspring and for human consumption. Long intergenic noncoding RNAs (lincRNAs) play various functions in eukaryotic cells. However, types and roles of lincRNAs in bovine mammary glands are still poorly understood. Using computational methods, 886 unknown intergenic transcripts (UITs) were identified from five RNA-seq datasets from bovine mammary glands. Their non-coding potentials were predicted by using the combination of four software programs (CPAT, CNCI, CPC and hmmscan), with 184 lincRNAs identified. By comparison to the NONCODE2016 database and a domestic-animal long noncoding RNA database (ALDB), 112 novel lincRNAs were revealed in bovine mammary glands. Many lincRNAs were found to be located in quantitative trait loci (QTL). In particular, 36 lincRNAs were found in 172 milk related QTLs, whereas one lincRNA was within clinical mastitis QTL region. In addition, targeted genes for 10 lincRNAs with the highest fragments per kilobase of transcript per million fragments mapped (FPKM) were predicted by LncTar for forecasting potential biological functions of these lincRNAs. Further analyses indicate involvement of lincRNAs in several biological functions and different pathways. Our study has provided a panoramic view of lincRNAs in bovine mammary glands and suggested their involvement in many biological functions including susceptibility to clinical mastitis as well as milk quality and production. This integrative annotation of mammary gland lincRNAs broadens and deepens our understanding of bovine mammary gland biology.

  15. Non-coding, mRNA-like RNAs database Y2K.

    Science.gov (United States)

    Erdmann, V A; Szymanski, M; Hochberg, A; Groot, N; Barciszewski, J

    2000-01-01

    In last few years much data has accumulated on various non-translatable RNA transcripts that are synthesised in different cells. They are lacking in protein coding capacity and it seems that they work mainly or exclusively at the RNA level. All known non-coding RNA transcripts are collected in the database: http://www. man.poznan.pl/5SData/ncRNA/index.html

  16. Hominoid-specific de novo protein-coding genes originating from long non-coding RNAs.

    Directory of Open Access Journals (Sweden)

    Chen Xie

    2012-09-01

    Full Text Available Tinkering with pre-existing genes has long been known as a major way to create new genes. Recently, however, motherless protein-coding genes have been found to have emerged de novo from ancestral non-coding DNAs. How these genes originated is not well addressed to date. Here we identified 24 hominoid-specific de novo protein-coding genes with precise origination timing in vertebrate phylogeny. Strand-specific RNA-Seq analyses were performed in five rhesus macaque tissues (liver, prefrontal cortex, skeletal muscle, adipose, and testis, which were then integrated with public transcriptome data from human, chimpanzee, and rhesus macaque. On the basis of comparing the RNA expression profiles in the three species, we found that most of the hominoid-specific de novo protein-coding genes encoded polyadenylated non-coding RNAs in rhesus macaque or chimpanzee with a similar transcript structure and correlated tissue expression profile. According to the rule of parsimony, the majority of these hominoid-specific de novo protein-coding genes appear to have acquired a regulated transcript structure and expression profile before acquiring coding potential. Interestingly, although the expression profile was largely correlated, the coding genes in human often showed higher transcriptional abundance than their non-coding counterparts in rhesus macaque. The major findings we report in this manuscript are robust and insensitive to the parameters used in the identification and analysis of de novo genes. Our results suggest that at least a portion of long non-coding RNAs, especially those with active and regulated transcription, may serve as a birth pool for protein-coding genes, which are then further optimized at the transcriptional level.

  17. An expanding universe of the non-coding genome in cancer biology.

    Science.gov (United States)

    Xue, Bin; He, Lin

    2014-06-01

    Neoplastic transformation is caused by accumulation of genetic and epigenetic alterations that ultimately convert normal cells into tumor cells with uncontrolled proliferation and survival, unlimited replicative potential and invasive growth [Hanahan,D. et al. (2011) Hallmarks of cancer: the next generation. Cell, 144, 646-674]. Although the majority of the cancer studies have focused on the functions of protein-coding genes, emerging evidence has started to reveal the importance of the vast non-coding genome, which constitutes more than 98% of the human genome. A number of non-coding RNAs (ncRNAs) derived from the 'dark matter' of the human genome exhibit cancer-specific differential expression and/or genomic alterations, and it is increasingly clear that ncRNAs, including small ncRNAs and long ncRNAs (lncRNAs), play an important role in cancer development by regulating protein-coding gene expression through diverse mechanisms. In addition to ncRNAs, nearly half of the mammalian genomes consist of transposable elements, particularly retrotransposons. Once depicted as selfish genomic parasites that propagate at the expense of host fitness, retrotransposon elements could also confer regulatory complexity to the host genomes during development and disease. Reactivation of retrotransposons in cancer, while capable of causing insertional mutagenesis and genome rearrangements to promote oncogenesis, could also alter host gene expression networks to favor tumor development. Taken together, the functional significance of non-coding genome in tumorigenesis has been previously underestimated, and diverse transcripts derived from the non-coding genome could act as integral functional components of the oncogene and tumor suppressor network. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Shrub expansion in SW Greenland under modest regional warming

    DEFF Research Database (Denmark)

    Jørgensen, Rasmus Halfdan; Meilby, Henrik; Kollmann, Johannes

    2013-01-01

    Shrub expansion has been observed widely in tundra areas across the Arctic. This phenomenon has been partially attributed to increasing temperatures over the past century. However, relationships among shrub expansion, grazing, and human disturbance have been studied little. SW Greenland...... is a subarctic to low-arctic region with a long and complex land-use history and only modest temperature increases over the past 50 years (0.2 °C decade-1), but changes in shrub cover have not previously been studied in this region. We compiled historical photographs of vegetation in SW Greenland (1898......–1974) and repeated the photos in 2010 and 2011. Sixty-four photo pairs were cropped into 133 smaller units and classified by aspect, substrate stability, muskoxen grazing, and human disturbance. The photo material was evaluated by 22 experts with respect to changes in shrub cover, revealing a general increase across...

  19. Chromosome preference of disease genes and vectorization for the prediction of non-coding disease genes.

    Science.gov (United States)

    Peng, Hui; Lan, Chaowang; Liu, Yuansheng; Liu, Tao; Blumenstein, Michael; Li, Jinyan

    2017-10-03

    Disease-related protein-coding genes have been widely studied, but disease-related non-coding genes remain largely unknown. This work introduces a new vector to represent diseases, and applies the newly vectorized data for a positive-unlabeled learning algorithm to predict and rank disease-related long non-coding RNA (lncRNA) genes. This novel vector representation for diseases consists of two sub-vectors, one is composed of 45 elements, characterizing the information entropies of the disease genes distribution over 45 chromosome substructures. This idea is supported by our observation that some substructures (e.g., the chromosome 6 p-arm) are highly preferred by disease-related protein coding genes, while some (e.g., the 21 p-arm) are not favored at all. The second sub-vector is 30-dimensional, characterizing the distribution of disease gene enriched KEGG pathways in comparison with our manually created pathway groups. The second sub-vector complements with the first one to differentiate between various diseases. Our prediction method outperforms the state-of-the-art methods on benchmark datasets for prioritizing disease related lncRNA genes. The method also works well when only the sequence information of an lncRNA gene is known, or even when a given disease has no currently recognized long non-coding genes.

  20. Noncoding RNAs and HIV: viral manipulation of host dark matter to shape the cellular environment

    Directory of Open Access Journals (Sweden)

    Samantha eBarichievy

    2015-03-01

    Full Text Available On October 28th 1943 Winston Churchill said we shape our buildings, and afterwards our buildings shape us (Humes, 1994. Churchill was pondering how and when to rebuild the British House of Commons, which had been destroyed by enemy bombs on May 10th 1941. The old House had been small and insufficient to hold all its members, but was restored to its original form in 1950 in order to recapture the convenience and dignity that the building had shaped into its parliamentary members. The circular loop whereby buildings or dwellings are shaped and go on to shape those that reside in them is also true of pathogens and their hosts. As obligate parasites, pathogens need to alter their cellular host environments to ensure survival. Typically pathogens modify cellular transcription profiles and in doing so, the pathogen in turn is affected, thereby closing the loop. As key orchestrators of gene expression, noncoding RNAs provide a vast and extremely precise set of tools for pathogens to target in order to shape the cellular environment. This review will focus on host noncoding RNAs that are manipulated by the infamous intracellular pathogen, the Human Immunodeficiency Virus (HIV. We will briefly describe both short and long host noncoding RNAs and discuss how HIV gains control of these factors to ensure widespread dissemination throughout the host as well as the establishment of lifelong, chronic infection.

  1. A small noncoding RNA signature found in exosomes of GBM patient serum as a diagnostic tool.

    Science.gov (United States)

    Manterola, Lorea; Guruceaga, Elizabeth; Gállego Pérez-Larraya, Jaime; González-Huarriz, Marisol; Jauregui, Patricia; Tejada, Sonia; Diez-Valle, Ricardo; Segura, Victor; Samprón, Nicolás; Barrena, Cristina; Ruiz, Irune; Agirre, Amaia; Ayuso, Angel; Rodríguez, Javier; González, Alvaro; Xipell, Enric; Matheu, Ander; López de Munain, Adolfo; Tuñón, Teresa; Zazpe, Idoya; García-Foncillas, Jesús; Paris, Sophie; Delattre, Jean Yves; Alonso, Marta M

    2014-04-01

    Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor in adults, and its prognosis remains dismal despite intensive research and therapeutic advances. Diagnostic biomarkers would be clinically meaningful to allow for early detection of the tumor and for those cases in which surgery is contraindicated or biopsy results are inconclusive. Recent findings show that GBM cells release microvesicles that contain a select subset of cellular proteins and RNA. The aim of this hypothesis-generating study was to assess the diagnostic potential of miRNAs found in microvesicles isolated from the serum of GBM patients. To control disease heterogeneity, we used patients with newly diagnosed GBM. In the discovery stage, PCR-based TaqMan Low Density Arrays followed by individual quantitative reverse transcriptase polymerase chain reaction were used to test the differences in the miRNA expression levels of serum microvesicles among 25 GBM patients and healthy controls paired by age and sex. The detected noncoding RNAs were then validated in another 50 GBM patients. We found that the expression levels of 1 small noncoding RNA (RNU6-1) and 2 microRNAs (miR-320 and miR-574-3p) were significantly associated with a GBM diagnosis. In addition, RNU6-1 was consistently an independent predictor of a GBM diagnosis. Altogether our results uncovered a small noncoding RNA signature in microvesicles isolated from GBM patient serum that could be used as a fast and reliable differential diagnostic biomarker.

  2. Methods for Using Small Non-Coding RNAs to Improve Recombinant Protein Expression in Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Sarah Inwood

    2018-01-01

    Full Text Available The ability to produce recombinant proteins by utilizing different “cell factories” revolutionized the biotherapeutic and pharmaceutical industry. Chinese hamster ovary (CHO cells are the dominant industrial producer, especially for antibodies. Human embryonic kidney cells (HEK, while not being as widely used as CHO cells, are used where CHO cells are unable to meet the needs for expression, such as growth factors. Therefore, improving recombinant protein expression from mammalian cells is a priority, and continuing effort is being devoted to this topic. Non-coding RNAs are RNA segments that are not translated into a protein and often have a regulatory role. Since their discovery, major progress has been made towards understanding their functions. Non-coding RNA has been investigated extensively in relation to disease, especially cancer, and recently they have also been used as a method for engineering cells to improve their protein expression capability. In this review, we provide information about methods used to identify non-coding RNAs with the potential of improving recombinant protein expression in mammalian cell lines.

  3. Quantification of non-coding RNA target localization diversity and its application in cancers.

    Science.gov (United States)

    Cheng, Lixin; Leung, Kwong-Sak

    2018-04-01

    Subcellular localization is pivotal for RNAs and proteins to implement biological functions. The localization diversity of protein interactions has been studied as a crucial feature of proteins, considering that the protein-protein interactions take place in various subcellular locations. Nevertheless, the localization diversity of non-coding RNA (ncRNA) target proteins has not been systematically studied, especially its characteristics in cancers. In this study, we provide a new algorithm, non-coding RNA target localization coefficient (ncTALENT), to quantify the target localization diversity of ncRNAs based on the ncRNA-protein interaction and protein subcellular localization data. ncTALENT can be used to calculate the target localization coefficient of ncRNAs and measure how diversely their targets are distributed among the subcellular locations in various scenarios. We focus our study on long non-coding RNAs (lncRNAs), and our observations reveal that the target localization diversity is a primary characteristic of lncRNAs in different biotypes. Moreover, we found that lncRNAs in multiple cancers, differentially expressed cancer lncRNAs, and lncRNAs with multiple cancer target proteins are prone to have high target localization diversity. Furthermore, the analysis of gastric cancer helps us to obtain a better understanding that the target localization diversity of lncRNAs is an important feature closely related to clinical prognosis. Overall, we systematically studied the target localization diversity of the lncRNAs and uncovered its association with cancer.

  4. nRC: non-coding RNA Classifier based on structural features.

    Science.gov (United States)

    Fiannaca, Antonino; La Rosa, Massimo; La Paglia, Laura; Rizzo, Riccardo; Urso, Alfonso

    2017-01-01

    Non-coding RNA (ncRNA) are small non-coding sequences involved in gene expression regulation of many biological processes and diseases. The recent discovery of a large set of different ncRNAs with biologically relevant roles has opened the way to develop methods able to discriminate between the different ncRNA classes. Moreover, the lack of knowledge about the complete mechanisms in regulative processes, together with the development of high-throughput technologies, has required the help of bioinformatics tools in addressing biologists and clinicians with a deeper comprehension of the functional roles of ncRNAs. In this work, we introduce a new ncRNA classification tool, nRC (non-coding RNA Classifier). Our approach is based on features extraction from the ncRNA secondary structure together with a supervised classification algorithm implementing a deep learning architecture based on convolutional neural networks. We tested our approach for the classification of 13 different ncRNA classes. We obtained classification scores, using the most common statistical measures. In particular, we reach an accuracy and sensitivity score of about 74%. The proposed method outperforms other similar classification methods based on secondary structure features and machine learning algorithms, including the RNAcon tool that, to date, is the reference classifier. nRC tool is freely available as a docker image at https://hub.docker.com/r/tblab/nrc/. The source code of nRC tool is also available at https://github.com/IcarPA-TBlab/nrc.

  5. Long noncoding RNAs responsive to Fusarium oxysporum infection in Arabidopsis thaliana.

    Science.gov (United States)

    Zhu, Qian-Hao; Stephen, Stuart; Taylor, Jennifer; Helliwell, Chris A; Wang, Ming-Bo

    2014-01-01

    Short noncoding RNAs have been demonstrated to play important roles in regulation of gene expression and stress responses, but the repertoire and functions of long noncoding RNAs (lncRNAs) remain largely unexplored, particularly in plants. To explore the role of lncRNAs in disease resistance, we used a strand-specific RNA-sequencing approach to identify lncRNAs responsive to Fusarium oxysporum infection in Arabidopsis thaliana. Antisense transcription was found in c. 20% of the annotated A. thaliana genes. Several noncoding natural antisense transcripts responsive to F. oxysporum infection were found in genes implicated in disease defense. While the majority of the novel transcriptionally active regions (TARs) were adjacent to annotated genes and could be an extension of the annotated transcripts, 159 novel intergenic TARs, including 20 F. oxysporum-responsive lncTARs, were identified. Ten F. oxysporum-induced lncTARs were functionally characterized using T-DNA insertion or RNA-interference knockdown lines, and five were demonstrated to be related to disease development. Promoter analysis suggests that some of the F. oxysporum-induced lncTARs are direct targets of transcription factor(s) responsive to pathogen attack. Our results demonstrated that strand-specific RNA sequencing is a powerful tool for uncovering hidden levels of transcriptome and that IncRNAs are important components of the antifungal networks in A. thaliana. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  6. Both noncoding and protein-coding RNAs contribute to gene expression evolution in the primate brain.

    Science.gov (United States)

    Babbitt, Courtney C; Fedrigo, Olivier; Pfefferle, Adam D; Boyle, Alan P; Horvath, Julie E; Furey, Terrence S; Wray, Gregory A

    2010-01-18

    Despite striking differences in cognition and behavior between humans and our closest primate relatives, several studies have found little evidence for adaptive change in protein-coding regions of genes expressed primarily in the brain. Instead, changes in gene expression may underlie many cognitive and behavioral differences. Here, we used digital gene expression: tag profiling (here called Tag-Seq, also called DGE:tag profiling) to assess changes in global transcript abundance in the frontal cortex of the brains of 3 humans, 3 chimpanzees, and 3 rhesus macaques. A substantial fraction of transcripts we identified as differentially transcribed among species were not assayed in previous studies based on microarrays. Differentially expressed tags within coding regions are enriched for gene functions involved in synaptic transmission, transport, oxidative phosphorylation, and lipid metabolism. Importantly, because Tag-Seq technology provides strand-specific information about all polyadenlyated transcripts, we were able to assay expression in noncoding intragenic regions, including both sense and antisense noncoding transcripts (relative to nearby genes). We find that many noncoding transcripts are conserved in both location and expression level between species, suggesting a possible functional role. Lastly, we examined the overlap between differential gene expression and signatures of positive selection within putative promoter regions, a sign that these differences represent adaptations during human evolution. Comparative approaches may provide important insights into genes responsible for differences in cognitive functions between humans and nonhuman primates, as well as highlighting new candidate genes for studies investigating neurological disorders.

  7. Boundary Associated Long Noncoding RNA Mediates Long-Range Chromosomal Interactions.

    Directory of Open Access Journals (Sweden)

    Ifeoma Jane Nwigwe

    Full Text Available CCCTC binding factor (CTCF is involved in organizing chromosomes into mega base-sized, topologically associated domains (TADs along with other factors that define sub-TAD organization. CTCF-Cohesin interactions have been shown to be critical for transcription insulation activity as it stabilizes long-range interactions to promote proper gene expression. Previous studies suggest that heterochromatin boundary activity of CTCF may be independent of Cohesin, and there may be additional mechanisms for defining topological domains. Here, we show that a boundary site we previously identified known as CTCF binding site 5 (CBS5 from the homeotic gene cluster A (HOXA locus exhibits robust promoter activity. This promoter activity from the CBS5 boundary element generates a long noncoding RNA that we designate as boundary associated long noncoding RNA-1 (blncRNA1. Functional characterization of this RNA suggests that the transcript stabilizes long-range interactions at the HOXA locus and promotes proper expression of HOXA genes. Additionally, our functional analysis also shows that this RNA is not needed in the stabilization of CTCF-Cohesin interactions however CTCF-Cohesin interactions are critical in the transcription of blncRNA1. Thus, the CTCF-associated boundary element, CBS5, employs both Cohesin and noncoding RNA to establish and maintain topologically associated domains at the HOXA locus.

  8. Improving repeatability by improving quality

    Energy Technology Data Exchange (ETDEWEB)

    Ronen, Shuki; Ackers, Mark; Schlumberger, Geco-Prakla; Brink, Mundy

    1998-12-31

    Time lapse (4-D) seismic is a promising tool for reservoir characterization and monitoring. The method is apparently simple: to acquire data repeatedly over the same reservoir, process and interpret the data sets, then changes between the data sets indicate changes in the reservoir. A problem with time lapse seismic data is that reservoirs are a relatively small part of the earth and important reservoir changes may cause very small differences to the time lapse data. The challenge is to acquire and process economical time lapse data such that reservoir changes can be detected above the noise of varying acquisition and environment. 7 refs., 9 figs.

  9. Telomerase Repeated Amplification Protocol (TRAP).

    Science.gov (United States)

    Mender, Ilgen; Shay, Jerry W

    2015-11-20

    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

  10. Coordinated hybrid automatic repeat request

    KAUST Repository

    Makki, Behrooz

    2014-11-01

    We develop a coordinated hybrid automatic repeat request (HARQ) approach. With the proposed scheme, if a user message is correctly decoded in the first HARQ rounds, its spectrum is allocated to other users, to improve the network outage probability and the users\\' fairness. The results, which are obtained for single- and multiple-antenna setups, demonstrate the efficiency of the proposed approach in different conditions. For instance, with a maximum of M retransmissions and single transmit/receive antennas, the diversity gain of a user increases from M to (J+1)(M-1)+1 where J is the number of users helping that user.

  11. Molecular chaperones enhance the degradation of expanded polyglutamine repeat androgen receptor in a cellular model of spinal and bulbar muscular atrophy

    NARCIS (Netherlands)

    Bailey, CK; Andriola, IFM; Kampinga, HH; Merry, DE

    2002-01-01

    Spinal and bulbar muscular atrophy (SBMA) is one of a growing number of neurodegenerative diseases caused by a polyglutamine-encoding CAG trinucleotide repeat expansion, and is caused by an expansion within exon 1 of the androgen receptor (AR) gene. The family of polyglutamine diseases is

  12. Simultaneous and independent detection of C9ORF72 alleles with low and high number of GGGGCC repeats using an optimised protocol of Southern blot hybridisation.

    Science.gov (United States)

    Buchman, Vladimir L; Cooper-Knock, Johnathan; Connor-Robson, Natalie; Higginbottom, Adrian; Kirby, Janine; Razinskaya, Olga D; Ninkina, Natalia; Shaw, Pamela J

    2013-04-08

    Sizing of GGGGCC hexanucleotide repeat expansions within the C9ORF72 locus, which account for approximately 10% of all amyotrophic lateral sclerosis (ALS) cases, is urgently required to answer fundamental questions about mechanisms of pathogenesis in this important genetic variant. Currently employed PCR protocols are limited to discrimination between the presence and absence of a modified allele with more than 30 copies of the repeat, while Southern hybridisation-based methods are confounded by the somatic heterogeneity commonly present in blood samples, which might cause false-negative or ambiguous results. We describe an optimised Southern hybridisation-based protocol that allows confident detection of the presence of a C9ORF72 repeat expansion alongside independent assessment of its heterogeneity and the number of repeat units. The protocol can be used with either a radiolabeled or non-radiolabeled probe. Using this method we have successfully sized the C9ORF72 repeat expansion in lymphoblastoid cells, peripheral blood, and post-mortem central nervous system (CNS) tissue from ALS patients. It was also possible to confidently demonstrate the presence of repeat expansion, although of different magnitude, in both C9ORF72 alleles of the genome of one patient. The suggested protocol has sufficient advantages to warrant adoption as a standard for Southern blot hybridisation analysis of GGGGCC repeat expansions in the C9ORF72 locus.

  13. C9orf72 expansion presenting as an eating disorder.

    Science.gov (United States)

    Sanders, Peter; Ewing, Isobel; Ahmad, Kate

    2016-03-01

    This report describes a 64-year-old woman with a strong family history of motor neuron disease, whose diagnosis of behavioural variant frontotemporal dementia was delayed due to her initial presentation with atypical manifestations, including restriction of oral intake resulting in low weight, disordered eating and anxiety. Upon investigation, she was found to be a carrier of the C9orf72 hexanucleotide repeat expansion. Our case supports previous publications asserting that C9orf72 mutation carriers manifest with diverse clinical syndromes, and expands the phenotype to include anorexia and food refusal as potential features of the condition. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  14. Dispersion Measure Variation of Repeating Fast Radio Burst Sources

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yuan-Pei; Zhang, Bing, E-mail: yypspore@gmail.com, E-mail: zhang@physics.unlv.edu [Kavli Institute for Astronomy and Astrophysics, Peking University, Beijing 100871 (China)

    2017-09-20

    The repeating fast radio burst (FRB) 121102 was recently localized in a dwarf galaxy at a cosmological distance. The dispersion measure (DM) derived for each burst from FRB 121102 so far has not shown significant evolution, even though an apparent increase was recently seen with newly detected VLA bursts. It is expected that more repeating FRB sources may be detected in the future. In this work, we investigate a list of possible astrophysical processes that might cause DM variation of a particular FRB source. The processes include (1) cosmological scale effects such as Hubble expansion and large-scale structure fluctuations; (2) FRB local effects such as gas density fluctuation, expansion of a supernova remnant (SNR), a pulsar wind nebula, and an H ii region; and (3) the propagation effect due to plasma lensing. We find that the DM variations contributed by the large-scale structure are extremely small, and any observable DM variation is likely caused by the plasma local to the FRB source. In addition to mechanisms that decrease DM over time, we suggest that an FRB source in an expanding SNR around a nearly neutral ambient medium during the deceleration (Sedov–Taylor and snowplow) phases or in a growing H ii region can increase DM. Some effects (e.g., an FRB source moving in an H ii region or plasma lensing) can produce either positive or negative DM variations. Future observations of DM variations of FRB 121102 and other repeating FRB sources can provide important clues regarding the physical origin of these sources.

  15. Dispersion Measure Variation of Repeating Fast Radio Burst Sources

    International Nuclear Information System (INIS)

    Yang, Yuan-Pei; Zhang, Bing

    2017-01-01

    The repeating fast radio burst (FRB) 121102 was recently localized in a dwarf galaxy at a cosmological distance. The dispersion measure (DM) derived for each burst from FRB 121102 so far has not shown significant evolution, even though an apparent increase was recently seen with newly detected VLA bursts. It is expected that more repeating FRB sources may be detected in the future. In this work, we investigate a list of possible astrophysical processes that might cause DM variation of a particular FRB source. The processes include (1) cosmological scale effects such as Hubble expansion and large-scale structure fluctuations; (2) FRB local effects such as gas density fluctuation, expansion of a supernova remnant (SNR), a pulsar wind nebula, and an H ii region; and (3) the propagation effect due to plasma lensing. We find that the DM variations contributed by the large-scale structure are extremely small, and any observable DM variation is likely caused by the plasma local to the FRB source. In addition to mechanisms that decrease DM over time, we suggest that an FRB source in an expanding SNR around a nearly neutral ambient medium during the deceleration (Sedov–Taylor and snowplow) phases or in a growing H ii region can increase DM. Some effects (e.g., an FRB source moving in an H ii region or plasma lensing) can produce either positive or negative DM variations. Future observations of DM variations of FRB 121102 and other repeating FRB sources can provide important clues regarding the physical origin of these sources.

  16. Nonparametric additive regression for repeatedly measured data

    KAUST Repository

    Carroll, R. J.; Maity, A.; Mammen, E.; Yu, K.

    2009-01-01

    We develop an easily computed smooth backfitting algorithm for additive model fitting in repeated measures problems. Our methodology easily copes with various settings, such as when some covariates are the same over repeated response measurements

  17. Exponential Expansion in Evolutionary Economics

    DEFF Research Database (Denmark)

    Frederiksen, Peter; Jagtfelt, Tue

    2013-01-01

    This article attempts to solve current problems of conceptual fragmentation within the field of evolutionary economics. One of the problems, as noted by a number of observers, is that the field suffers from an assemblage of fragmented and scattered concepts (Boschma and Martin 2010). A solution...... to this problem is proposed in the form of a model of exponential expansion. The model outlines the overall structure and function of the economy as exponential expansion. The pictographic model describes four axiomatic concepts and their exponential nature. The interactive, directional, emerging and expanding...... concepts are described in detail. Taken together it provides the rudimentary aspects of an economic system within an analytical perspective. It is argued that the main dynamic processes of the evolutionary perspective can be reduced to these four concepts. The model and concepts are evaluated in the light...

  18. Production expansion continues to accelerate

    International Nuclear Information System (INIS)

    Anon.

    1992-01-01

    This paper reports that Saudi Arabian Oil Co. (Saudi Aramco) is continuing its accelerated Crude Oil Expansion Program initiated in 1989 that aims at achieving a 10 million bpd productive capacity by 1995. In addition to major engineering, construction and renovation work related to production expansion, Saudi Aramco drilling and workover operations have been markedly expanded. Since January 1991, rig activity has doubled. As an indication of aging of Saudi production, projects include modernizing current injection water treatment facilities, installing a new seawater injection plant on the Persian Gulf, installing dewatering facilities in a number of locations and installing a pilot gas lift project. In addition, equipment orders indicate the new discoveries south of Riyadh may also need the assistance of water injection from inception of production

  19. Shrub expansion in SW Greenland

    DEFF Research Database (Denmark)

    Jørgensen, Rasmus Halfdan

    Arctic regions have experienced higher temperatures in recent decades, and the warming trend is projected to continue in the coming years. Arctic ecosystems are considered to be particularly vulnerable to climate change. Expansion of shrubs has been observed widely in tundra areas across the Arctic......, and has a range of ecosystem effects where it occurs. Shrub expansion has to a large extend been attributed to increasing temperatures over the past century, while grazing and human disturbance have received less attention. Alnus viridis ssp. crispa is a common arctic species that contributes...... to increasing shrub cover. Despite this, there is only limited experimental evidence that growth of the species responds to warming. Plant populations in fragmented and isolated locations could face problems adapting to a warming climate due to limited genetic variation and restricted migration from southern...

  20. RELIABILITY OF LENTICULAR EXPANSION COMPENSATORS

    Directory of Open Access Journals (Sweden)

    Gabriel BURLACU,

    2011-11-01

    Full Text Available Axial lenticular compensators are made to take over the longitudinal heat expansion, shock , vibration and noise, made elastic connections for piping systems. In order to have a long life for installations it is necessary that all elements, including lenticular compensators, have a good reliability. This desire can be did by technology of manufactoring and assembly of compensators, the material for lenses and by maintenance.of compensator

  1. Unusual structures are present in DNA fragments containing super-long Huntingtin CAG repeats.

    Directory of Open Access Journals (Sweden)

    Daniel Duzdevich

    2011-02-01

    Full Text Available 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.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."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.

  2. Topological characteristics of helical repeat proteins

    NARCIS (Netherlands)

    Groves, M R; Barford, D

    The recent elucidation of protein structures based upon repeating amino acid motifs, including the armadillo motif, the HEAT motif and tetratricopeptide repeats, reveals that they belong to the class of helical repeat proteins. These proteins share the common property of being assembled from tandem

  3. Digital storage of repeated signals

    International Nuclear Information System (INIS)

    Prozorov, S.P.

    1984-01-01

    An independent digital storage system designed for repeated signal discrimination from background noises is described. The signal averaging is performed off-line in the real time mode by means of multiple selection of the investigated signal and integration in each point. Digital values are added in a simple summator and the result is recorded the storage device with the volume of 1024X20 bit from where it can be output on an oscillograph, a plotter or transmitted to a compUter for subsequent processing. The described storage is reliable and simple device on one base of which the systems for the nuclear magnetic resonapce signal acquisition in different experiments are developed

  4. Hungarian repeat station survey, 2010

    Directory of Open Access Journals (Sweden)

    Péter Kovács

    2013-03-01

    Full Text Available The last Hungarian repeat station survey was completed between October 2010 and February 2011. Declination, inclination and the total field were observed using one-axial DMI fluxgate magnetometer mounted on Zeiss20A theodolite and GSM 19 Overhauser magnetometer. The magnetic elements of the sites were reduced to the epoch of 2010.5 on the basis of the continuous recordings of Tihany Geophysical Observatory. In stations located far from the reference observatory, the observations were carried out in the morning and afternoon in order to decrease the effect of the distant temporal correction. To further increase the accuracy, on-site dIdD variometer has also been installed near the Aggtelek station, in the Baradla cave, during the survey of the easternmost sites. The paper presents the technical details and the results of our last campaign. The improvement of the accuracy of the temporal reduction by the use of the local variometer is also reported.

  5. Linear Synchronous Motor Repeatability Tests

    International Nuclear Information System (INIS)

    Ward, C.R.

    2002-01-01

    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

  6. Two-dimensional quantum repeaters

    Science.gov (United States)

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

    2016-11-01

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

  7. Hybrid FRC under repeated loading

    International Nuclear Information System (INIS)

    Komlos, K.; Babal, B.; Nuernbergerova, T.

    1993-01-01

    Fibre reinforced concretes (FRC) containing several volume fractions in different ratios of two types of fibres - polypropylene and steel, were tested under repeated loading. Mechanical properties of specimens - cubes 150/150/150 mm (for compressive strength), prisms 100/100/400 (for flexural strength), short cylinders 150/60 mm (for impact strength) have been experimentally investigated before and after cyclic loading at the age of 28 days curing time. Mix proportions were designed after DIN 1045 with max. aggregate size 8 mm and grading curve B 8. Portland Cement PC 400 in the amount of 450 kg. m -3 was applied and W/C ratio 0.55. Workability of mixes was measured by Vebe method and regulated by plasticizing admixture Ligoplast Na. Maximum hybrid fibre volume fraction (polypropylene + steel) was 1.0%. Dynamic forces generated in Schenck testing machine with frequency 16 Hz had sinusoidal wave form varying between 0.7 and 0.1 of static mechanical characteristics. The number of cycles in all tests was 10 5 . The residual MOR at static four point bending test and working diagram force-deflection was carried out as well. The impact properties after repeated loading in compression were tested by means of falling weight test. Relationships between composition of fibre composites with different combination of polypropylene (0.2, 0.3, 0.5% by volume) and steel (0.5, 0.7, and 0.8% by volume) fibre content were obtained and technological properties of mixes as well. (author)

  8. Quality control during repeated fryings

    Directory of Open Access Journals (Sweden)

    Cuesta, C.

    1998-08-01

    Full Text Available Most of the debate ¡s about how the slow or frequent turnover of fresh fat affects the deterioration, of fat used in frying. Then, the modification of different oils used in repeated fryings of potatoes without or with turnover of fresh oil, under similar frying conditions, was evaluated by two criteria: by measuring the total polar component isolated by column chromatography and by the evaluation of the specific compounds related to thermoxidative and hydrolytic alteration by High Performance Size Exclusion Chromatography (HPSEC. The results indicate that with frequent turnover of fresh oil, the critical level of 25% of polar material is rarely reached, and there are fewer problems with fat deterioration because the frying tended to increase the level of polar material and thermoxidative compounds (polymers and dimers of triglycerides and oxidized triglycerides in the fryer oil during the first fryings, followed by minor changes and a tendency to reach a near-steady state in successive fryings. However, in repeated frying of potatoes using a null turnover the alteration rate was higher being linear the relationship found between polar material or the different thermoxidative compounds and the number of fryings. On the other hand chemical reactions produced during deep-fat frying can be minimized by using proper oils. In addition the increased level of consumers awareness toward fat composition and its impact on human health could had an impact on the selection of fats for snacks and for industry. In this way monoenic fats are the most adequate from a nutritional point of view and for its oxidative stability during frying.

  9. A Power Series Expansion and Its Applications

    Science.gov (United States)

    Chen, Hongwei

    2006-01-01

    Using the power series solution of a differential equation and the computation of a parametric integral, two elementary proofs are given for the power series expansion of (arcsin x)[squared], as well as some applications of this expansion.

  10. The leucine-rich repeat structure.

    Science.gov (United States)

    Bella, J; Hindle, K L; McEwan, P A; Lovell, S C

    2008-08-01

    The leucine-rich repeat is a widespread structural motif of 20-30 amino acids with a characteristic repetitive sequence pattern rich in leucines. Leucine-rich repeat domains are built from tandems of two or more repeats and form curved solenoid structures that are particularly suitable for protein-protein interactions. Thousands of protein sequences containing leucine-rich repeats have been identified by automatic annotation methods. Three-dimensional structures of leucine-rich repeat domains determined to date reveal a degree of structural variability that translates into the considerable functional versatility of this protein superfamily. As the essential structural principles become well established, the leucine-rich repeat architecture is emerging as an attractive framework for structural prediction and protein engineering. This review presents an update of the current understanding of leucine-rich repeat structure at the primary, secondary, tertiary and quaternary levels and discusses specific examples from recently determined three-dimensional structures.

  11. Definite behavioral variant of frontotemporal dementia with C9ORF72 expansions despite positive Alzheimer's disease cerebrospinal fluid biomarkers.

    Science.gov (United States)

    Wallon, David; Rovelet-Lecrux, Anne; Deramecourt, Vincent; Pariente, Jeremie; Auriacombe, Sophie; Le Ber, Isabelle; Schraen, Suzanna; Pasquier, Florence; Campion, Dominique; Hannequin, Didier

    2012-01-01

    Hexanucleotide expansion repeats in the C9ORF72 gene are a major cause of familial and, to a lesser extent, sporadic frontotemporal lobar degeneration (FTLD), amyotrophic lateral sclerosis (ALS), and FTLD-ALS. To examine whether C9ORF72 expansions could be involved in early-onset Alzheimer's disease (EOAD), we genotyped the hexanucleotide repeat region in a large cohort of 114 EOAD patients who all had positive AD cerebrospinal fluid (CSF) biomarkers. We found hexanucleotide expansion repeats of the C9ORF72 gene in 3 out of 114 patients (2.6%). We raise several hypotheses to explain our results and discuss the current status of AD CSF biomarkers in the dementia diagnostic algorithm.

  12. Psychiatric symptoms and CAG expansion in Huntington`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Weber, M.W.; Schmid, W.; Spiegel, R. [Univ. of Zuerich (Switzerland)

    1996-02-16

    The mutation responsible for Huntington`s disease (HD) is an elongated CAG repeat in the coding region of the IT15 gene. A PCR-based test with high sensitivity and accuracy is now available to identify asymptomatic gene carriers and patients. An inverse correlation between CAG copy number and age at disease onset has been found in a large number of affected individuals. The influence of the CAG repeat expansion on other phenotypic manifestations, especially specific psychiatric symptoms has not been studied intensively. In order to elucidate this situation we investigated the relation between CAG copy number and distinct psychiatric phenotypes found in 79 HD-patients. None of the four differentiated categories (personality change, psychosis, depression, and nonspecific alterations) showed significant differences in respect to size of the CAG expansion. In addition, no influence of individual sex on psychiatric presentation could be found. On the other hand in patients with personality changes maternal transmission was significantly more frequent compared with all other groups. Therefore we suggest that clinical severity of psychiatric features in HD is not directly dependent on the size of the dynamic mutation involved. The complex pathogenetic mechanisms leading to psychiatric alterations are still unknown and thus genotyping does not provide information about expected psychiatric symptoms in HD gene carriers. 40 refs., 1 fig., 2 tabs.

  13. Confinement of Reinforced-Concrete Columns with Non-Code Compliant Confining Reinforcement plus Supplemental Pen-Binder

    Directory of Open Access Journals (Sweden)

    Anang Kristianto

    2012-11-01

    Full Text Available One of the important requirements for earthquake resistant building related to confinement is the use of seismic hooks in the hoop or confining reinforcement of reinforced-concrete column elements. However, installation of a confining reinforcement with a 135-degree hook is not easy. Therefore, in practice, many construction workers apply a confining reinforcement with a 90-degreehook (non-code compliant. Based on research and records of recent earthquakes in Indonesia, the use of a non-code compliant confining reinforcement for concrete columns produces structures with poor seismic performance. This paper presents a study that introduces an additional element that is expected to improve the effectiveness of concrete columns confined with a non-code compliant confining reinforcement. The additional element, named a pen-binder, is used to keep the non-code compliant confining reinforcement in place. The effectiveness of this element under pure axial concentric loading was investigatedcomprehensively.The specimens tested in this study were 18 concrete columns,with a cross-section of 170 mm x 170 mm and a height of 480 mm. The main test variables were the material type of the pen-binder, the angle of the hook, and the confining reinforcement configuration.The test results indicate that adding pen-binders can effectively improve the strength and ductility of the column specimens confined with a non-code compliant confining reinforcement

  14. ncRNA-class Web Tool: Non-coding RNA feature extraction and pre-miRNA classification web tool

    KAUST Repository

    Kleftogiannis, Dimitrios A.; Theofilatos, Konstantinos A.; Papadimitriou, Stergios; Tsakalidis, Athanasios K.; Likothanassis, Spiridon D.; Mavroudi, Seferina P.

    2012-01-01

    Until recently, it was commonly accepted that most genetic information is transacted by proteins. Recent evidence suggests that the majority of the genomes of mammals and other complex organisms are in fact transcribed into non-coding RNAs (ncRNAs), many of which are alternatively spliced and/or processed into smaller products. Non coding RNA genes analysis requires the calculation of several sequential, thermodynamical and structural features. Many independent tools have already been developed for the efficient calculation of such features but to the best of our knowledge there does not exist any integrative approach for this task. The most significant amount of existing work is related to the miRNA class of non-coding RNAs. MicroRNAs (miRNAs) are small non-coding RNAs that play a significant role in gene regulation and their prediction is a challenging bioinformatics problem. Non-coding RNA feature extraction and pre-miRNA classification Web Tool (ncRNA-class Web Tool) is a publicly available web tool ( http://150.140.142.24:82/Default.aspx ) which provides a user friendly and efficient environment for the effective calculation of a set of 58 sequential, thermodynamical and structural features of non-coding RNAs, plus a tool for the accurate prediction of miRNAs. © 2012 IFIP International Federation for Information Processing.

  15. IW-Scoring: an Integrative Weighted Scoring framework for annotating and prioritizing genetic variations in the noncoding genome.

    Science.gov (United States)

    Wang, Jun; Dayem Ullah, Abu Z; Chelala, Claude

    2018-01-30

    The vast majority of germline and somatic variations occur in the noncoding part of the genome, only a small fraction of which are believed to be functional. From the tens of thousands of noncoding variations detectable in each genome, identifying and prioritizing driver candidates with putative functional significance is challenging. To address this, we implemented IW-Scoring, a new Integrative Weighted Scoring model to annotate and prioritise functionally relevant noncoding variations. We evaluate 11 scoring methods, and apply an unsupervised spectral approach for subsequent selective integration into two linear weighted functional scoring schemas for known and novel variations. IW-Scoring produces stable high-quality performance as the best predictors for three independent data sets. We demonstrate the robustness of IW-Scoring in identifying recurrent functional mutations in the TERT promoter, as well as disease SNPs in proximity to consensus motifs and with gene regulatory effects. Using follicular lymphoma as a paradigmatic cancer model, we apply IW-Scoring to locate 11 recurrently mutated noncoding regions in 14 follicular lymphoma genomes, and validate 9 of these regions in an extension cohort, including the promoter and enhancer regions of PAX5. Overall, IW-Scoring demonstrates greater versatility in identifying trait- and disease-associated noncoding variants. Scores from IW-Scoring as well as other methods are freely available from http://www.snp-nexus.org/IW-Scoring/. © The Author(s) 2018. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Strain expansion-reduction approach

    Science.gov (United States)

    Baqersad, Javad; Bharadwaj, Kedar

    2018-02-01

    Validating numerical models are one of the main aspects of engineering design. However, correlating million degrees of freedom of numerical models to the few degrees of freedom of test models is challenging. Reduction/expansion approaches have been traditionally used to match these degrees of freedom. However, the conventional reduction/expansion approaches are only limited to displacement, velocity or acceleration data. While in many cases only strain data are accessible (e.g. when a structure is monitored using strain-gages), the conventional approaches are not capable of expanding strain data. To bridge this gap, the current paper outlines a reduction/expansion technique to reduce/expand strain data. In the proposed approach, strain mode shapes of a structure are extracted using the finite element method or the digital image correlation technique. The strain mode shapes are used to generate a transformation matrix that can expand the limited set of measurement data. The proposed approach can be used to correlate experimental and analytical strain data. Furthermore, the proposed technique can be used to expand real-time operating data for structural health monitoring (SHM). In order to verify the accuracy of the approach, the proposed technique was used to expand the limited set of real-time operating data in a numerical model of a cantilever beam subjected to various types of excitations. The proposed technique was also applied to expand real-time operating data measured using a few strain gages mounted to an aluminum beam. It was shown that the proposed approach can effectively expand the strain data at limited locations to accurately predict the strain at locations where no sensors were placed.

  17. Targeted deletion of the 9p21 noncoding coronary artery disease risk interval in mice

    Energy Technology Data Exchange (ETDEWEB)

    Visel, Axel; Zhu, Yiwen; May, Dalit; Afzal, Veena; Gong, Elaine; Attanasio, Catia; Blow, Matthew J.; Cohen, Jonathan C.; Rubin, Edward M.; Pennacchio, Len A.

    2010-01-01

    Sequence polymorphisms in a 58kb interval on chromosome 9p21 confer a markedly increased risk for coronary artery disease (CAD), the leading cause of death worldwide 1,2. The variants have a substantial impact on the epidemiology of CAD and other life?threatening vascular conditions since nearly a quarter of Caucasians are homozygous for risk alleles. However, the risk interval is devoid of protein?coding genes and the mechanism linking the region to CAD risk has remained enigmatic. Here we show that deletion of the orthologous 70kb noncoding interval on mouse chromosome 4 affects cardiac expression of neighboring genes, as well as proliferation properties of vascular cells. Chr4delta70kb/delta70kb mice are viable, but show increased mortality both during development and as adults. Cardiac expression of two genes near the noncoding interval, Cdkn2a and Cdkn2b, is severely reduced in chr4delta70kb/delta70kb mice, indicating that distant-acting gene regulatory functions are located in the noncoding CAD risk interval. Allelespecific expression of Cdkn2b transcripts in heterozygous mice revealed that the deletion affects expression through a cis-acting mechanism. Primary cultures of chr4delta70kb/delta70kb aortic smooth muscle cells exhibited excessive proliferation and diminished senescence, a cellular phenotype consistent with accelerated CAD pathogenesis. Taken together, our results provide direct evidence that the CAD risk interval plays a pivotal role in regulation of cardiac Cdkn2a/b expression and suggest that this region affects CAD progression by altering the dynamics of vascular cell proliferation.

  18. CONDOR: a database resource of developmentally associated conserved non-coding elements

    Directory of Open Access Journals (Sweden)

    Smith Sarah

    2007-08-01

    Full Text Available Abstract Background Comparative genomics is currently one of the most popular approaches to study the regulatory architecture of vertebrate genomes. Fish-mammal genomic comparisons have proved powerful in identifying conserved non-coding elements likely to be distal cis-regulatory modules such as enhancers, silencers or insulators that control the expression of genes involved in the regulation of early development. The scientific community is showing increasing interest in characterizing the function, evolution and language of these sequences. Despite this, there remains little in the way of user-friendly access to a large dataset of such elements in conjunction with the analysis and the visualization tools needed to study them. Description Here we present CONDOR (COnserved Non-coDing Orthologous Regions available at: http://condor.fugu.biology.qmul.ac.uk. In an interactive and intuitive way the website displays data on > 6800 non-coding elements associated with over 120 early developmental genes and conserved across vertebrates. The database regularly incorporates results of ongoing in vivo zebrafish enhancer assays of the CNEs carried out in-house, which currently number ~100. Included and highlighted within this set are elements derived from duplication events both at the origin of vertebrates and more recently in the teleost lineage, thus providing valuable data for studying the divergence of regulatory roles between paralogs. CONDOR therefore provides a number of tools and facilities to allow scientists to progress in their own studies on the function and evolution of developmental cis-regulation. Conclusion By providing access to data with an approachable graphics interface, the CONDOR database presents a rich resource for further studies into the regulation and evolution of genes involved in early development.

  19. Mutations in noncoding regions of GJB1 are a major cause of X-linked CMT

    Science.gov (United States)

    Tomaselli, Pedro J.; Rossor, Alexander M.; Horga, Alejandro; Jaunmuktane, Zane; Carr, Aisling; Saveri, Paola; Piscosquito, Giuseppe; Pareyson, Davide; Laura, Matilde; Blake, Julian C.; Poh, Roy; Polke, James; Houlden, Henry

    2017-01-01

    Objective: To determine the prevalence and clinical and genetic characteristics of patients with X-linked Charcot-Marie-Tooth disease (CMT) due to mutations in noncoding regions of the gap junction β-1 gene (GJB1). Methods: Mutations were identified by bidirectional Sanger sequence analysis of the 595 bases of the upstream promoter region, and 25 bases of the 3′ untranslated region (UTR) sequence in patients in whom mutations in the coding region had been excluded. Clinical and neurophysiologic data were retrospectively collected. Results: Five mutations were detected in 25 individuals from 10 kindreds representing 11.4% of all cases of CMTX1 diagnosed in our neurogenetics laboratory between 1996 and 2016. Four pathogenic mutations, c.-17G>A, c.-17+1G>T, c.-103C>T, and c.-146-90_146-89insT were detected in the 5′UTR. A novel mutation, c.*15C>T, was detected in the 3′ UTR of GJB1 in 2 unrelated families with CMTX1 and is the first pathogenic mutation in the 3′UTR of any myelin-associated CMT gene. Mutations segregated with the phenotype, were at sites predicted to be pathogenic, and were not present in the normal population. Conclusions: Mutations in noncoding DNA are a major cause of CMTX1 and highlight the importance of mutations in noncoding DNA in human disease. Next-generation sequencing platforms for use in inherited neuropathy should therefore include coverage of these regions. PMID:28283593

  20. Nuclear fuel reprocessing expansion strategies

    International Nuclear Information System (INIS)

    Gallagher, J.M.

    1975-01-01

    A description is given of an effort to apply the techniques of operations research and energy system modeling to the problem of determination of cost-effective strategies for capacity expansion of the domestic nuclear fuel reprocessing industry for the 1975 to 2000 time period. The research also determines cost disadvantages associated with alternative strategies that may be attractive for political, social, or ecological reasons. The sensitivity of results to changes in cost assumptions was investigated at some length. Reactor fuel types covered by the analysis include the Light Water Reactor (LWR), High-Temperature Gas-Cooled Reactor (HTGR), and the Fast Breeder Reactor (FBR)

  1. Thermal expansion of LATGS crystals

    International Nuclear Information System (INIS)

    Kassem, M.E.; Kandil, S.H.; Hamed, A.E.; Stankowska, J.

    1989-04-01

    The thermal expansion of triglycine sulphate crystals doped with L-α alanine (LATGS) has been studied around the phase transition temperature (30-60 deg. C) using thermomechanical analysis TMA. With increasing the content of admixture, the transition temperature (T c ) was shifted towards higher values, while the relative changes in the dimension of the crystals (ΔL/L 0 ) of the studied directions varied both in the para- and ferroelectric phases. The transition width in the case of doped crystals was found to be broad, and this broadening increases with increasing the content of L-α alanine. (author). 12 refs, 3 figs

  2. Contribution of thermal expansion and

    Directory of Open Access Journals (Sweden)

    O.I.Pursky

    2007-01-01

    Full Text Available A theoretical model is developed to describe the experimental results obtained for the isobaric thermal conductivity of rare gas solids (RGS. The isobaric thermal conductivity of RGS has been analysed within Debye approximation with regard to the effect of thermal expansion. The suggested model takes into consideration the fact that thermal conductivity is determined by U-processes while above the phonon mobility edge it is determined by "diffusive" modes migrating randomly from site to site. The mobility edge ω0 is determined from the condition that the phonon mean-free path restricted by the U-processes cannot be smaller than half of the phonon wavelength.

  3. The prognostic potential and carcinogenesis of long non-coding RNA TUG1 in human cholangiocarcinoma

    OpenAIRE

    Xu, Yi; Leng, Kaiming; Li, Zhenglong; Zhang, Fumin; Zhong, Xiangyu; Kang, Pengcheng; Jiang, Xingming; Cui, Yunfu

    2017-01-01

    Cholangiocarcinoma (CCA) is a fatal disease with increasing worldwide incidence and is characterized by poor prognosis due to its poor response to conventional chemotherapy or radiotherapy. Long non-coding RNAs (lncRNAs) play key roles in multiple human cancers, including CCA. Cancer progression related lncRNA taurine-up-regulated gene 1 (TUG1) was reported to be involved in human carcinomas. However, the impact of TUG1 in CCA is unclear. The aim of this study was to explore the expression pa...

  4. Interplay of noncoding RNAs, mRNAs, and proteins during the growth of eukaryotic cells

    International Nuclear Information System (INIS)

    Zhdanov, V. P.

    2010-01-01

    Numerous biological functions of noncoding RNAs (ncRNAs) in eukaryotic cells are based primarily on their ability to pair with target mRNAs and then either to prevent translation or to result in rapid degradation of the mRNA-ncRNA complex. Using a general model describing this scenario, we show that ncRNAs may help to maintain constant mRNA and protein concentrations during the growth of cells. The possibility of observation of this effect on the global scale is briefly discussed.

  5. The Functional Characterization of Long Noncoding RNA SPRY4-IT1 in Human Melanoma Cells

    OpenAIRE

    Mazar, Joseph; Zhao, Wei; Khalil, Ahmad M.; Lee, Bongyong; Shelley, John; Govindarajan, Subramaniam S.; Yamamoto, Fumiko; Ratnam, Maya; Aftab, Muhammad Nauman; Collins, Sheila; Finck, Brian N.; Han, Xianlin; Mattick, John S.; Dinger, Marcel E.; Perera, Ranjan J.

    2014-01-01

    Expression of the long noncoding RNA (lncRNA) SPRY4-IT1 is low in normal human melanocytes but high in melanoma cells. siRNA knockdown of SPRY4-IT1 blocks melanoma cell invasion and proliferation, and increases apoptosis. To investigate its function further, we affinity purified SPRY4-IT1 from melanoma cells and used mass spectrometry to identify the protein lipin 2, an enzyme that converts phosphatidate to diacylglycerol (DAG), as a major binding partner. SPRY4-IT1 knockdown increases the ac...

  6. Integration and visualization of non-coding RNA and protein interaction networks

    OpenAIRE

    Junge, Alexander; Refsgaard, Jan Christian; Garde, Christian; Pan, Xiaoyong; Santos Delgado, Alberto; Anthon, Christian; Alkan, Ferhat; von Mering, Christian; Workman, Christopher; Jensen, Lars Juhl; Gorodkin, Jan

    2015-01-01

    Non-coding RNAs (ncRNAs) fulfill a diverse set of biological functions relying on interactions with other molecular entities. The advent of new experimental and computational approaches makes it possible to study ncRNAs and their associations on an unprecedented scale. We present RAIN (RNA Association and Interaction Networks) - a database that combines ncRNA-ncRNA, ncRNA-mRNA and ncRNA-protein interactions with large-scale protein association networks available in the STRING database. By int...

  7. Highly conserved non-coding sequences are associated with vertebrate development.

    Directory of Open Access Journals (Sweden)

    Adam Woolfe

    2005-01-01

    Full Text Available In addition to protein coding sequence, the human genome contains a significant amount of regulatory DNA, the identification of which is proving somewhat recalcitrant to both in silico and functional methods. An approach that has been used with some success is comparative sequence analysis, whereby equivalent genomic regions from different organisms are compared in order to identify both similarities and differences. In general, similarities in sequence between highly divergent organisms imply functional constraint. We have used a whole-genome comparison between humans and the pufferfish, Fugu rubripes, to identify nearly 1,400 highly conserved non-coding sequences. Given the evolutionary divergence between these species, it is likely that these sequences are found in, and furthermore are essential to, all vertebrates. Most, and possibly all, of these sequences are located in and around genes that act as developmental regulators. Some of these sequences are over 90% identical across more than 500 bases, being more highly conserved than coding sequence between these two species. Despite this, we cannot find any similar sequences in invertebrate genomes. In order to begin to functionally test this set of sequences, we have used a rapid in vivo assay system using zebrafish embryos that allows tissue-specific enhancer activity to be identified. Functional data is presented for highly conserved non-coding sequences associated with four unrelated developmental regulators (SOX21, PAX6, HLXB9, and SHH, in order to demonstrate the suitability of this screen to a wide range of genes and expression patterns. Of 25 sequence elements tested around these four genes, 23 show significant enhancer activity in one or more tissues. We have identified a set of non-coding sequences that are highly conserved throughout vertebrates. They are found in clusters across the human genome, principally around genes that are implicated in the regulation of development

  8. Integration and visualization of non-coding RNA and protein interaction networks

    DEFF Research Database (Denmark)

    Junge, Alexander; Refsgaard, Jan Christian; Garde, Christian

    Non-coding RNAs (ncRNAs) fulfill a diverse set of biological functions relying on interactions with other molecular entities. The advent of new experimental and computational approaches makes it possible to study ncRNAs and their associations on an unprecedented scale. We present RAIN (RNA Associ......) co-occurrences found by text mining Medline abstracts. Each resource was assigned a reliability score by assessing its agreement with a gold standard set of microRNA-target interactions. RAIN is available at: http://rth.dk/resources/rain...

  9. Evaluation of Agency Non-Code Layered Pressure Vessels (LPVs) . Volume 2; Appendices

    Science.gov (United States)

    Prosser, William H.

    2014-01-01

    In coordination with the Office of Safety and Mission Assurance and the respective Center Pressure System Managers (PSMs), the NASA Engineering and Safety Center (NESC) was requested to formulate a consensus draft proposal for the development of additional testing and analysis methods to establish the technical validity, and any limitation thereof, for the continued safe operation of facility non-code layered pressure vessels. The PSMs from each NASA Center were asked to participate as part of the assessment team by providing, collecting, and reviewing data regarding current operations of these vessels. This document contains the appendices to the main report.

  10. Long noncoding RNAs(lncRNAs) and the molecular hallmarks of aging.

    Science.gov (United States)

    Grammatikakis, Ioannis; Panda, Amaresh C; Abdelmohsen, Kotb; Gorospe, Myriam

    2014-12-01

    During aging, progressive deleterious changes increase the risk of disease and death. Prominent molecular hallmarks of aging are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, cellular senescence, stem cell exhaustion, and altered intercellular communication. Long noncoding RNAs (lncRNAs) play important roles in a wide range of biological processes, including age-related diseases like cancer, cardiovascular pathologies, and neurodegenerative disorders. Evidence is emerging that lncRNAs influence the molecular processes that underlie age-associated phenotypes. Here, we review our current understanding of lncRNAs that control the development of aging traits.

  11. Roles, Functions, and Mechanisms of Long Non-coding RNAs in Cancer

    Directory of Open Access Journals (Sweden)

    Yiwen Fang

    2016-02-01

    Full Text Available Long non-coding RNAs (lncRNAs play important roles in cancer. They are involved in chromatin remodeling, as well as transcriptional and post-transcriptional regulation, through a variety of chromatin-based mechanisms and via cross-talk with other RNA species. lncRNAs can function as decoys, scaffolds, and enhancer RNAs. This review summarizes the characteristics of lncRNAs, including their roles, functions, and working mechanisms, describes methods for identifying and annotating lncRNAs, and discusses future opportunities for lncRNA-based therapies using antisense oligonucleotides.

  12. High thermal expansion, sealing glass

    Science.gov (United States)

    Brow, R.K.; Kovacic, L.

    1993-11-16

    A glass composition is described for hermetically sealing to high thermal expansion materials such as aluminum alloys, stainless steels, copper, and copper/beryllium alloys, which includes between about 10 and about 25 mole percent Na[sub 2]O, between about 10 and about 25 mole percent K[sub 2]O, between about 5 and about 15 mole percent Al[sub 2]O[sub 3], between about 35 and about 50 mole percent P[sub 2]O[sub 5] and between about 5 and about 15 mole percent of one of PbO, BaO, and mixtures thereof. The composition, which may also include between 0 and about 5 mole percent Fe[sub 2]O[sub 3] and between 0 and about 10 mole percent B[sub 2]O[sub 3], has a thermal expansion coefficient in a range of between about 160 and 210[times]10[sup [minus]7]/C and a dissolution rate in a range of between about 2[times]10[sup [minus]7] and 2[times]10[sup [minus]9]g/cm[sup 2]-min. This composition is suitable to hermetically seal to metallic electrical components which will be subjected to humid environments over an extended period of time.

  13. Nonperturbative path integral expansion II

    International Nuclear Information System (INIS)

    Kaiser, H.J.

    1976-05-01

    The Feynman path integral representation of the 2-point function for a self-interacting Bose field is investigated using an expansion ('Path Integral Expansion', PIE) of the exponential of the kinetic term of the Lagrangian. This leads to a series - illustrated by a graph scheme - involving successively a coupling of more and more points of the lattice space commonly employed in the evaluation of path integrals. The values of the individual PIE graphs depend of course on the lattice constant. Two methods - Pade approximation and Borel-type extrapolation - are proposed to extract information about the continuum limit from a finite-order PIE. A more flexible PIE is possible by expanding besides the kinetic term a suitably chosen part of the interaction term too. In particular, if the co-expanded part is a mass term the calculation becomes only slightly more complicated than in the original formulation and the appearance of the graph scheme is unchanged. A significant reduction of the number of graphs and an improvement of the convergence of the PIE can be achieved by performing certain sums over an infinity of graph elements. (author)

  14. Orion: Detecting regions of the human non-coding genome that are intolerant to variation using population genetics.

    Science.gov (United States)

    Gussow, Ayal B; Copeland, Brett R; Dhindsa, Ryan S; Wang, Quanli; Petrovski, Slavé; Majoros, William H; Allen, Andrew S; Goldstein, David B

    2017-01-01

    There is broad agreement that genetic mutations occurring outside of the protein-coding regions play a key role in human disease. Despite this consensus, we are not yet capable of discerning which portions of non-coding sequence are important in the context of human disease. Here, we present Orion, an approach that detects regions of the non-coding genome that are depleted of variation, suggesting that the regions are intolerant of mutations and subject to purifying selection in the human lineage. We show that Orion is highly correlated with known intolerant regions as well as regions that harbor putatively pathogenic variation. This approach provides a mechanism to identify pathogenic variation in the human non-coding genome and will have immediate utility in the diagnostic interpretation of patient genomes and in large case control studies using whole-genome sequences.

  15. Ultra-low thermal expansion realized in giant negative thermal expansion materials through self-compensation

    OpenAIRE

    Fei-Ran Shen; Hao Kuang; Feng-Xia Hu; Hui Wu; Qing-Zhen Huang; Fei-Xiang Liang; Kai-Ming Qiao; Jia Li; Jing Wang; Yao Liu; Lei Zhang; Min He; Ying Zhang; Wen-Liang Zuo; Ji-Rong Sun

    2017-01-01

    Materials with zero thermal expansion (ZTE) or precisely tailored thermal expansion are in urgent demand of modern industries. However, the overwhelming majority of materials show positive thermal expansion. To develop ZTE or negative thermal expansion (NTE) materials as compensators has become an important challenge. Here, we present the evidence for the realization of ultra-low thermal expansion in Mn–Co–Ge–In particles. The bulk with the Ni2In-type hexagonal structure undergoes giant NTE o...

  16. Sequencing illustrates the transcriptional response of Legionella pneumophila during infection and identifies seventy novel small non-coding RNAs.

    LENUS (Irish Health Repository)

    Weissenmayer, Barbara A

    2011-01-01

    Second generation sequencing has prompted a number of groups to re-interrogate the transcriptomes of several bacterial and archaeal species. One of the central findings has been the identification of complex networks of small non-coding RNAs that play central roles in transcriptional regulation in all growth conditions and for the pathogen\\'s interaction with and survival within host cells. Legionella pneumophila is a gram-negative facultative intracellular human pathogen with a distinct biphasic lifestyle. One of its primary environmental hosts in the free-living amoeba Acanthamoeba castellanii and its infection by L. pneumophila mimics that seen in human macrophages. Here we present analysis of strand specific sequencing of the transcriptional response of L. pneumophila during exponential and post-exponential broth growth and during the replicative and transmissive phase of infection inside A. castellanii. We extend previous microarray based studies as well as uncovering evidence of a complex regulatory architecture underpinned by numerous non-coding RNAs. Over seventy new non-coding RNAs could be identified; many of them appear to be strain specific and in configurations not previously reported. We discover a family of non-coding RNAs preferentially expressed during infection conditions and identify a second copy of 6S RNA in L. pneumophila. We show that the newly discovered putative 6S RNA as well as a number of other non-coding RNAs show evidence for antisense transcription. The nature and extent of the non-coding RNAs and their expression patterns suggests that these may well play central roles in the regulation of Legionella spp. specific traits and offer clues as to how L. pneumophila adapts to its intracellular niche. The expression profiles outlined in the study have been deposited into Genbank\\'s Gene Expression Omnibus (GEO) database under the series accession GSE27232.

  17. Long intergenic non-coding RNA TUG1 is overexpressed in urothelial carcinoma of the bladder.

    Science.gov (United States)

    Han, Yonghua; Liu, Yuchen; Gui, Yaoting; Cai, Zhiming

    2013-04-01

    Long intergenic non-coding RNAs (lincRNAs) are a class of non-coding RNAs that regulate gene expression via chromatin reprogramming. Taurine Up-regulated Gene 1 (TUG1) is a lincRNA that is associated with chromatin-modifying complexes and plays roles in gene regulation. In this study, we determined the expression patterns of TUG1 and the cell proliferation inhibition and apoptosis induced by silencing TUG1 in urothelial carcinoma of the bladder. The expression levels of TUG1 were determined using Real-Time qPCR in a total of 44 patients with bladder urothelial carcinomas. Bladder urothelial carcinoma T24 and 5637 cells were transfected with TUG1 siRNA or negative control siRNA. Cell proliferation was evaluated using MTT assay. Apoptosis was determined using ELISA assay. TUG1 was up-regulated in bladder urothelial carcinoma compared to paired normal urothelium. High TUG1 expression levels were associated with high grade and stage carcinomas. Cell proliferation inhibition and apoptosis induction were observed in TUG1 siRNA-transfected bladder urothelial carcinoma T24 and 5637 cells. Our data suggest that lincRNA TUG1 is emerging as a novel player in the disease state of bladder urothelial carcinoma. TUG1 may have potential roles as a biomarker and/or a therapeutic target in bladder urothelial carcinoma. Copyright © 2012 Wiley Periodicals, Inc.

  18. 3' terminal diversity of MRP RNA and other human noncoding RNAs revealed by deep sequencing.

    Science.gov (United States)

    Goldfarb, Katherine C; Cech, Thomas R

    2013-09-21

    Post-transcriptional 3' end processing is a key component of RNA regulation. The abundant and essential RNA subunit of RNase MRP has been proposed to function in three distinct cellular compartments and therefore may utilize this mode of regulation. Here we employ 3' RACE coupled with high-throughput sequencing to characterize the 3' terminal sequences of human MRP RNA and other noncoding RNAs that form RNP complexes. The 3' terminal sequence of MRP RNA from HEK293T cells has a distinctive distribution of genomically encoded termini (including an assortment of U residues) with a portion of these selectively tagged by oligo(A) tails. This profile contrasts with the relatively homogenous 3' terminus of an in vitro transcribed MRP RNA control and the differing 3' terminal profiles of U3 snoRNA, RNase P RNA, and telomerase RNA (hTR). 3' RACE coupled with deep sequencing provides a valuable framework for the functional characterization of 3' terminal sequences of noncoding RNAs.

  19. 3′ terminal diversity of MRP RNA and other human noncoding RNAs revealed by deep sequencing

    Science.gov (United States)

    2013-01-01

    Background Post-transcriptional 3′ end processing is a key component of RNA regulation. The abundant and essential RNA subunit of RNase MRP has been proposed to function in three distinct cellular compartments and therefore may utilize this mode of regulation. Here we employ 3′ RACE coupled with high-throughput sequencing to characterize the 3′ terminal sequences of human MRP RNA and other noncoding RNAs that form RNP complexes. Results The 3′ terminal sequence of MRP RNA from HEK293T cells has a distinctive distribution of genomically encoded termini (including an assortment of U residues) with a portion of these selectively tagged by oligo(A) tails. This profile contrasts with the relatively homogenous 3′ terminus of an in vitro transcribed MRP RNA control and the differing 3′ terminal profiles of U3 snoRNA, RNase P RNA, and telomerase RNA (hTR). Conclusions 3′ RACE coupled with deep sequencing provides a valuable framework for the functional characterization of 3′ terminal sequences of noncoding RNAs. PMID:24053768

  20. Decoding the usefulness of non-coding RNAs as breast cancer markers.

    Science.gov (United States)

    Amorim, Maria; Salta, Sofia; Henrique, Rui; Jerónimo, Carmen

    2016-09-15

    Although important advances in the management of breast cancer (BC) have been recently accomplished, it still constitutes the leading cause of cancer death in women worldwide. BC is a heterogeneous and complex disease, making clinical prediction of outcome a very challenging task. In recent years, gene expression profiling emerged as a tool to assist in clinical decision, enabling the identification of genetic signatures that better predict prognosis and response to therapy. Nevertheless, translation to routine practice has been limited by economical and technical reasons and, thus, novel biomarkers, especially those requiring non-invasive or minimally invasive collection procedures, while retaining high sensitivity and specificity might represent a significant development in this field. An increasing amount of evidence demonstrates that non-coding RNAs (ncRNAs), particularly microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are aberrantly expressed in several cancers, including BC. miRNAs are of particular interest as new, easily accessible, cost-effective and non-invasive tools for precise management of BC patients because they circulate in bodily fluids (e.g., serum and plasma) in a very stable manner, enabling BC assessment and monitoring through liquid biopsies. This review focus on how ncRNAs have the potential to answer present clinical needs in the personalized management of patients with BC and comprehensively describes the state of the art on the role of ncRNAs in the diagnosis, prognosis and prediction of response to therapy in BC.

  1. Principles of Long Noncoding RNA Evolution Derived from Direct Comparison of Transcriptomes in 17 Species

    Directory of Open Access Journals (Sweden)

    Hadas Hezroni

    2015-05-01

    Full Text Available The inability to predict long noncoding RNAs from genomic sequence has impeded the use of comparative genomics for studying their biology. Here, we develop methods that use RNA sequencing (RNA-seq data to annotate the transcriptomes of 16 vertebrates and the echinoid sea urchin, uncovering thousands of previously unannotated genes, most of which produce long intervening noncoding RNAs (lincRNAs. Although in each species, >70% of lincRNAs cannot be traced to homologs in species that diverged >50 million years ago, thousands of human lincRNAs have homologs with similar expression patterns in other species. These homologs share short, 5′-biased patches of sequence conservation nested in exonic architectures that have been extensively rewired, in part by transposable element exonization. Thus, over a thousand human lincRNAs are likely to have conserved functions in mammals, and hundreds beyond mammals, but those functions require only short patches of specific sequences and can tolerate major changes in gene architecture.

  2. Comprehensive Reconstruction and Visualization of Non-Coding Regulatory Networks in Human

    Science.gov (United States)

    Bonnici, Vincenzo; Russo, Francesco; Bombieri, Nicola; Pulvirenti, Alfredo; Giugno, Rosalba

    2014-01-01

    Research attention has been powered to understand the functional roles of non-coding RNAs (ncRNAs). Many studies have demonstrated their deregulation in cancer and other human disorders. ncRNAs are also present in extracellular human body fluids such as serum and plasma, giving them a great potential as non-invasive biomarkers. However, non-coding RNAs have been relatively recently discovered and a comprehensive database including all of them is still missing. Reconstructing and visualizing the network of ncRNAs interactions are important steps to understand their regulatory mechanism in complex systems. This work presents ncRNA-DB, a NoSQL database that integrates ncRNAs data interactions from a large number of well established on-line repositories. The interactions involve RNA, DNA, proteins, and diseases. ncRNA-DB is available at http://ncrnadb.scienze.univr.it/ncrnadb/. It is equipped with three interfaces: web based, command-line, and a Cytoscape app called ncINetView. By accessing only one resource, users can search for ncRNAs and their interactions, build a network annotated with all known ncRNAs and associated diseases, and use all visual and mining features available in Cytoscape. PMID:25540777

  3. The emerging role of non-coding RNAs in drug addiction

    Directory of Open Access Journals (Sweden)

    Gregory Charles Sartor

    2012-06-01

    Full Text Available Prolonged drug use causes long-lasting neuroadaptations in reward-related brain areas that contribute to addiction. Despite significant amount of research dedicated to understanding the underlying mechanisms of addiction, the molecular underpinnings remain unclear. At the same time, much of the pervasive transcription that encompasses the human genome occurs in the nervous system and contributes to its heterogeneity and complexity. Recent evidence suggests that non-coding RNAs (ncRNAs play an important and dynamic role in transcriptional regulation, epigenetic signaling, stress response, and plasticity in the nervous system. Dysregulation of ncRNAs are thought to contribute to many, and perhaps all, neurological disorders, including addiction. Here, we review recent insights in the functional relevance of ncRNAs, including both microRNAs (miRNAs and long non-coding RNAs (lncRNAs, and then illustrate specific examples of ncRNA regulation in the context of drug addiction. We conclude that ncRNAs are importantly involved in the persistent neuroadaptations associated with addiction-related behaviors, and that therapies that target specific ncRNAs may represent new avenues for the treatment of drug addiction.

  4. Long non-coding RNA expression profile in cervical cancer tissues

    Science.gov (United States)

    Zhu, Hua; Chen, Xiangjian; Hu, Yan; Shi, Zhengzheng; Zhou, Qing; Zheng, Jingjie; Wang, Yifeng

    2017-01-01

    Cervical cancer (CC), one of the most common types of cancer of the female population, presents an enormous challenge in diagnosis and treatment. Long non-coding (lnc)RNAs, non-coding (nc)RNAs with length >200 nucleotides, have been identified to be associated with multiple types of cancer, including CC. This class of nc transcripts serves an important role in tumor suppression and oncogenic signaling pathways. In the present study, the microarray method was used to obtain the expression profile of lncRNAs and protein-coding mRNAs and to compare the expression of lncRNAs between CC tissues and corresponding adjacent non-cancerous tissues in order to screen potential lncRNAs for associations with CC. Overall, 3356 lncRNAs with significantly different expression pattern in CC tissues compared with adjacent non-cancerous tissues were identified, while 1,857 of them were upregulated. These differentially expressed lncRNAs were additionally classified into 5 subgroups. Reverse transcription quantitative polymerase chain reactions were performed to validate the expression pattern of 5 random selected lncRNAs, and 2lncRNAs were identified to have significantly different expression in CC samples compared with adjacent non-cancerous tissues. This finding suggests that those lncRNAs with different expression may serve important roles in the development of CC, and the expression data may provide information for additional study on the involvement of lncRNAs in CC. PMID:28789353

  5. Noncoded amino acids in protein engineering: Structure-activity relationship studies of hirudin-thrombin interaction.

    Science.gov (United States)

    De Filippis, Vincenzo; Acquasaliente, Laura; Pontarollo, Giulia; Peterle, Daniele

    2018-01-01

    The advent of recombinant DNA technology allowed to site-specifically insert, delete, or mutate almost any amino acid in a given protein, significantly improving our knowledge of protein structure, stability, and function. Nevertheless, a quantitative description of the physical and chemical basis that makes a polypeptide chain to efficiently fold into a stable and functionally active conformation is still elusive. This mainly originates from the fact that nature combined, in a yet unknown manner, different properties (i.e., hydrophobicity, conformational propensity, polarizability, and hydrogen bonding capability) into the 20 standard natural amino acids, thus making difficult, if not impossible, to univocally relate the change in protein stability or function to the alteration of physicochemical properties caused by amino acid exchange(s). In this view, incorporation of noncoded amino acids with tailored side chains, allowing to finely tune the structure at a protein site, would facilitate to dissect the effects of a given mutation in terms of one or a few physicochemical properties, thus much expanding the scope of physical organic chemistry in the study of proteins. In this review, relevant applications from our laboratory will be presented on the use of noncoded amino acids in structure-activity relationships studies of hirudin binding to thrombin. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

  6. The roles of non-coding RNAs in cardiac regenerative medicine

    Directory of Open Access Journals (Sweden)

    Oi Kuan Choong

    2017-06-01

    Full Text Available The emergence of non-coding RNAs (ncRNAs has challenged the central dogma of molecular biology that dictates that the decryption of genetic information starts from transcription of DNA to RNA, with subsequent translation into a protein. Large numbers of ncRNAs with biological significance have now been identified, suggesting that ncRNAs are important in their own right and their roles extend far beyond what was originally envisaged. ncRNAs do not only regulate gene expression, but are also involved in chromatin architecture and structural conformation. Several studies have pointed out that ncRNAs participate in heart disease; however, the functions of ncRNAs still remain unclear. ncRNAs are involved in cellular fate, differentiation, proliferation and tissue regeneration, hinting at their potential therapeutic applications. Here, we review the current understanding of both the biological functions and molecular mechanisms of ncRNAs in heart disease and describe some of the ncRNAs that have potential heart regeneration effects. Keywords: Non-coding RNAs, Cardiac regeneration, Cardiac fate, Proliferation, Differentiation, Reprograming

  7. The Regulatory Effects of Long Noncoding RNA-ANCR on Dental Tissue-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Qian Jia

    2016-01-01

    Full Text Available Long noncoding RNAs (lncRNA have been recognized as important regulators in diverse biological processes, such as transcriptional regulation, stem cell proliferation, and differentiation. Previous study has demonstrated that lncRNA-ANCR (antidifferentiation ncRNA plays a key role in regulating the proliferation and osteogenic differentiation of periodontal ligament stem cells (PDLSCs. However, little is known about the role of ANCR in regulating other types of dental tissue-derived stem cells (DTSCs behaviours (including proliferation and multiple-potential of differentiation. In this study, we investigated the regulatory effects of lncRNA-ANCR on the proliferation and differentiation (including osteogenic, adipogenic, and neurogenic differentiation of DTSCs, including dental pulp stem cells (DPSCs, PDLSCs, and stem cells from the apical papilla (SCAP by downregulation of lncRNA-ANCR. We found that downregulation of ANCR exerted little effect on proliferation of DPSCs and SCAP but promoted the osteogenic, adipogenic, and neurogenic differentiation of DTSCs. These data provide an insight into the regulatory effects of long noncoding RNA-ANCR on DTSCs and indicate that ANCR is a very important regulatory factor in stem cell differentiation.

  8. Estradiol-Induced Transcriptional Regulation of Long Non-Coding RNA, HOTAIR.

    Science.gov (United States)

    Bhan, Arunoday; Mandal, Subhrangsu S

    2016-01-01

    HOTAIR (HOX antisense intergenic RNA) is a 2.2 kb long non-coding RNA (lncRNA), transcribed from the antisense strand of homeobox C (HOXC) gene locus in chromosome 12. HOTAIR acts as a scaffolding lncRNA. It interacts and guides various chromatin-modifying complexes such as PRC2 (polycomb-repressive complex 2) and LSD1 (lysine-specific demethylase 1) to the target gene promoters leading to their gene silencing. Various studies have demonstrated that HOTAIR overexpression is associated with breast cancer. Recent studies from our laboratory demonstrate that HOTAIR is required for viability of breast cancer cells and is transcriptionally regulated by estradiol (E2) in vitro and in vivo. This chapter describes protocols for analysis of the HOTAIR promoter, cloning, transfection and dual luciferase assays, knockdown of protein synthesis by antisense oligonucleotides, and chromatin immunoprecipitation (ChIP) assay. These protocols are useful for studying the estrogen-mediated transcriptional regulation of lncRNA HOTAIR, as well as other protein coding genes and non-coding RNAs.

  9. Regulation of the Apolipoprotein Gene Cluster by a Long Noncoding RNA

    Directory of Open Access Journals (Sweden)

    Paul Halley

    2014-01-01

    Full Text Available Apolipoprotein A1 (APOA1 is the major protein component of high-density lipoprotein (HDL in plasma. We have identified an endogenously expressed long noncoding natural antisense transcript, APOA1-AS, which acts as a negative transcriptional regulator of APOA1 both in vitro and in vivo. Inhibition of APOA1-AS in cultured cells resulted in the increased expression of APOA1 and two neighboring genes in the APO cluster. Chromatin immunoprecipitation (ChIP analyses of a ∼50 kb chromatin region flanking the APOA1 gene demonstrated that APOA1-AS can modulate distinct histone methylation patterns that mark active and/or inactive gene expression through the recruitment of histone-modifying enzymes. Targeting APOA1-AS with short antisense oligonucleotides also enhanced APOA1 expression in both human and monkey liver cells and induced an increase in hepatic RNA and protein expression in African green monkeys. Furthermore, the results presented here highlight the significant local modulatory effects of long noncoding antisense RNAs and demonstrate the therapeutic potential of manipulating the expression of these transcripts both in vitro and in vivo.

  10. A critical role for noncoding 5S rRNA in regulating Mdmx stability.

    Science.gov (United States)

    Li, Muyang; Gu, Wei

    2011-09-16

    Both p53 and Mdmx are ubiquitinated and degraded by the same E3 ligase Mdm2; interestingly, however, while p53 is rapidly degraded by Mdm2, Mdmx is a stable protein in most cancer cells. Thus, the mechanism by which Mdmx is degraded by Mdm2 needs further elucidation. Here, we identified the noncoding 5S rRNA as a major component of Mdmx-associated complexes from human cells. We show that 5S rRNA acts as a natural inhibitor of Mdmx degradation by Mdm2. RNAi-mediated knockdown of endogenous 5S rRNA, while not affecting p53 levels, significantly induces Mdmx degradation and, subsequently, activates p53-dependent growth arrest. Notably, 5S rRNA binds the RING domain of Mdmx and blocks its ubiquitination by Mdm2, whereas Mdm2-mediated p53 ubiquitination remains intact. These results provide insights into the differential effects on p53 and Mdmx by Mdm2 in vivo and reveal a critical role for noncoding 5S rRNA in modulating the p53-Mdmx axis. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Long Non-Coding RNAs Associated with Metabolic Traits in Human White Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Hui Gao

    2018-04-01

    Full Text Available Long non-coding RNAs (lncRNAs belong to a recently discovered class of molecules proposed to regulate various cellular processes. Here, we systematically analyzed their expression in human subcutaneous white adipose tissue (WAT and found that a limited set was differentially expressed in obesity and/or the insulin resistant state. Two lncRNAs herein termed adipocyte-specific metabolic related lncRNAs, ASMER-1 and ASMER-2 were enriched in adipocytes and regulated by both obesity and insulin resistance. Knockdown of either ASMER-1 or ASMER-2 by antisense oligonucleotides in in vitro differentiated human adipocytes revealed that both genes regulated adipogenesis, lipid mobilization and adiponectin secretion. The observed effects could be attributed to crosstalk between ASMERs and genes within the master regulatory pathways for adipocyte function including PPARG and INSR. Altogether, our data demonstrate that lncRNAs are modulators of the metabolic and secretory functions in human fat cells and provide an emerging link between WAT and common metabolic conditions. Keywords: White adipose tissue, Adipocytes, Long non-coding RNAs, Metabolic traits, Lipolysis, Adiponectin

  12. Non-Coding RNAs: Multi-Tasking Molecules in the Cell

    Directory of Open Access Journals (Sweden)

    Anita Quintal Gomes

    2013-07-01

    Full Text Available In the last years it has become increasingly clear that the mammalian transcriptome is highly complex and includes a large number of small non-coding RNAs (sncRNAs and long noncoding RNAs (lncRNAs. Here we review the biogenesis pathways of the three classes of sncRNAs, namely short interfering RNAs (siRNAs, microRNAs (miRNAs and PIWI-interacting RNAs (piRNAs. These ncRNAs have been extensively studied and are involved in pathways leading to specific gene silencing and the protection of genomes against virus and transposons, for example. Also, lncRNAs have emerged as pivotal molecules for the transcriptional and post-transcriptional regulation of gene expression which is supported by their tissue-specific expression patterns, subcellular distribution, and developmental regulation. Therefore, we also focus our attention on their role in differentiation and development. SncRNAs and lncRNAs play critical roles in defining DNA methylation patterns, as well as chromatin remodeling thus having a substantial effect in epigenetics. The identification of some overlaps in their biogenesis pathways and functional roles raises the hypothesis that these molecules play concerted functions in vivo, creating complex regulatory networks where cooperation with regulatory proteins is necessary. We also highlighted the implications of biogenesis and gene expression deregulation of sncRNAs and lncRNAs in human diseases like cancer.

  13. Evaluation of temporary non-code repairs in safety class 3 piping systems

    International Nuclear Information System (INIS)

    Godha, P.C.; Kupinski, M.; Azevedo, N.F.

    1996-01-01

    Temporary non-ASME Code repairs in safety class 3 pipe and piping components are permissible during plant operation in accordance with Nuclear Regulatory Commission Generic Letter 90-05. However, regulatory acceptance of such repairs requires the licensee to undertake several timely actions. Consistent with the requirements of GL 90-05, this paper presents an overview of the detailed evaluation and relief request process. The technical criteria encompasses both ductile and brittle piping materials. It also lists appropriate evaluation methods that a utility engineer can select to perform a structural integrity assessment for design basis loading conditions to support the use of temporary non-Code repair for degraded piping components. Most use of temporary non-code repairs at a nuclear generating station is in the service water system which is an essential safety related system providing the ultimate heat sink for various plant systems. Depending on the plant siting, the service water system may use fresh water or salt water as the cooling medium. Various degradation mechanisms including general corrosion, erosion/corrosion, pitting, microbiological corrosion, galvanic corrosion, under-deposit corrosion or a combination thereof continually challenge the pressure boundary structural integrity. A good source for description of corrosion degradation in cooling water systems is provided in a cited reference

  14. The interplay of long non-coding RNAs and MYC in cancer

    Directory of Open Access Journals (Sweden)

    Michael J. Hamilton

    2015-12-01

    Full Text Available Long non-coding RNAs (lncRNAs are a class of RNA molecules that are changing how researchers view eukaryotic gene regulation. Once considered to be non-functional products of low-level aberrant transcription from non-coding regions of the genome, lncRNAs are now viewed as important epigenetic regulators and several lncRNAs have now been demonstrated to be critical players in the development and/or maintenance of cancer. Similarly, the emerging variety of interactions between lncRNAs and MYC, a well-known oncogenic transcription factor linked to most types of cancer, have caught the attention of many biomedical researchers. Investigations exploring the dynamic interactions between lncRNAs and MYC, referred to as the lncRNA-MYC network, have proven to be especially complex. Genome-wide studies have shown that MYC transcriptionally regulates many lncRNA genes. Conversely, recent reports identified lncRNAs that regulate MYC expression both at the transcriptional and post-transcriptional levels. These findings are of particular interest because they suggest roles of lncRNAs as regulators of MYC oncogenic functions and the possibility that targeting lncRNAs could represent a novel avenue to cancer treatment. Here, we briefly review the current understanding of how lncRNAs regulate chromatin structure and gene transcription, and then focus on the new developments in the emerging field exploring the lncRNA-MYC network in cancer.

  15. Malignant transformation of colonic epithelial cells by a colon-derived long noncoding RNA

    International Nuclear Information System (INIS)

    Franklin, Jeffrey L.; Rankin, Carl R.; Levy, Shawn; Snoddy, Jay R.; Zhang, Bing; Washington, Mary Kay; Thomson, J. Michael; Whitehead, Robert H.; Coffey, Robert J.

    2013-01-01

    Highlights: •Non-coding RNAs are found in the colonic crypt progenitor compartment. •Colonocytes transformed by ncNRFR are highly invasive and metastatic. •ncNRFR has a region similar to the miRNA, let-7 family. •ncNRFR expression alters let-7 activity as measured by reporter construct. •ncNRFR expression upregulates let-7b targets. -- Abstract: Recent progress has been made in the identification of protein-coding genes and miRNAs that are expressed in and alter the behavior of colonic epithelia. However, the role of long non-coding RNAs (lncRNAs) in colonic homeostasis is just beginning to be explored. By gene expression profiling of post-mitotic, differentiated tops and proliferative, progenitor-compartment bottoms of microdissected adult mouse colonic crypts, we identified several lncRNAs more highly expressed in crypt bottoms. One identified lncRNA, designated non-coding Nras functional RNA (ncNRFR), resides within the Nras locus but appears to be independent of the Nras coding transcript. Stable overexpression of ncNRFR in non-transformed, conditionally immortalized mouse colonocytes results in malignant transformation, as determined by growth in soft agar and formation of highly invasive tumors in nude mice. Moreover, ncNRFR appears to inhibit the function of the tumor suppressor let-7. These results suggest precise regulation of ncNRFR is necessary for proper cell growth in the colonic crypt, and its misregulation results in neoplastic transformation

  16. Integrated Analysis of Long Noncoding RNA and Coding RNA Expression in Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Wei Cao

    2013-01-01

    Full Text Available Tumorigenesis is a complex dynamic biological process that includes multiple steps of genetic and epigenetic alterations, aberrant expression of noncoding RNA, and changes in the expression profiles of coding genes. We call the collection of those perturbations in genome space the “cancer initiatome.” Long noncoding RNAs (lncRNAs are pervasively transcribed in the genome and they have key regulatory functions in chromatin remodeling and gene expression. Spatiotemporal variation in the expression of lncRNAs has been observed in development and disease states, including cancer. A few dysregulated lncRNAs have been studied in cancers, but the role of lncRNAs in the cancer initiatome remains largely unknown, especially in esophageal squamous cell carcinoma (ESCC. We conducted a genome-wide screen of the expression of lncRNAs and coding RNAs from ESCC and matched adjacent nonneoplastic normal tissues. We identified differentially expressed lncRNAs and coding RNAs in ESCC relative to their matched normal tissue counterparts and validated the result using polymerase chain reaction analysis. Furthermore, we identified differentially expressed lncRNAs that are co-located and co-expressed with differentially expressed coding RNAs in ESCC and the results point to a potential interaction between lncRNAs and neighboring coding genes that affect ether lipid metabolism, and the interaction may contribute to the development of ESCC. These data provide compelling evidence for a potential novel genomic biomarker of esophageal squamous cell cancer.

  17. Non-coding RNAs and heme oxygenase-1 in vaccinia virus infection

    International Nuclear Information System (INIS)

    Meseda, Clement A.; Srinivasan, Kumar; Wise, Jasen; Catalano, Jennifer; Yamada, Kenneth M.; Dhawan, Subhash

    2014-01-01

    Highlights: • Heme oxygenase-1 (HO-1) induction inhibited vaccinia virus infection of macrophages. • Reduced infectivity inversely correlated with increased expression of non-coding RNAs. • The regulation of HO-1 and ncRNAs suggests a novel host defense response against vaccinia virus infection. - Abstract: Small nuclear RNAs (snRNAs) are <200 nucleotide non-coding uridylate-rich RNAs. Although the functions of many snRNAs remain undetermined, a population of snRNAs is produced during the early phase of infection of cells by vaccinia virus. In the present study, we demonstrate a direct correlation between expression of the cytoprotective enzyme heme oxygenase-1 (HO-1), suppression of selective snRNA expression, and inhibition of vaccinia virus infection of macrophages. Hemin induced HO-1 expression, completely reversed virus-induced host snRNA expression, and suppressed vaccinia virus infection. This involvement of specific virus-induced snRNAs and associated gene clusters suggests a novel HO-1-dependent host-defense pathway in poxvirus infection

  18. Comprehensive discovery of noncoding RNAs in acute myeloid leukemia cell transcriptomes.

    Science.gov (United States)

    Zhang, Jin; Griffith, Malachi; Miller, Christopher A; Griffith, Obi L; Spencer, David H; Walker, Jason R; Magrini, Vincent; McGrath, Sean D; Ly, Amy; Helton, Nichole M; Trissal, Maria; Link, Daniel C; Dang, Ha X; Larson, David E; Kulkarni, Shashikant; Cordes, Matthew G; Fronick, Catrina C; Fulton, Robert S; Klco, Jeffery M; Mardis, Elaine R; Ley, Timothy J; Wilson, Richard K; Maher, Christopher A

    2017-11-01

    To detect diverse and novel RNA species comprehensively, we compared deep small RNA and RNA sequencing (RNA-seq) methods applied to a primary acute myeloid leukemia (AML) sample. We were able to discover previously unannotated small RNAs using deep sequencing of a library method using broader insert size selection. We analyzed the long noncoding RNA (lncRNA) landscape in AML by comparing deep sequencing from multiple RNA-seq library construction methods for the sample that we studied and then integrating RNA-seq data from 179 AML cases. This identified lncRNAs that are completely novel, differentially expressed, and associated with specific AML subtypes. Our study revealed the complexity of the noncoding RNA transcriptome through a combined strategy of strand-specific small RNA and total RNA-seq. This dataset will serve as an invaluable resource for future RNA-based analyses. Copyright © 2017 ISEH – Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

  19. MYC Targeted Long Noncoding RNA DANCR Promotes Cancer in Part by Reducing p21 Levels.

    Science.gov (United States)

    Lu, Yunqi; Hu, Zhongyi; Mangala, Lingegowda S; Stine, Zachary E; Hu, Xiaowen; Jiang, Dahai; Xiang, Yan; Zhang, Youyou; Pradeep, Sunila; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; DeMarzo, Angelo M; Sood, Anil K; Zhang, Lin; Dang, Chi V

    2018-01-01

    The MYC oncogene broadly promotes transcription mediated by all nuclear RNA polymerases, thereby acting as a positive modifier of global gene expression. Here, we report that MYC stimulates the transcription of DANCR, a long noncoding RNA (lncRNA) that is widely overexpressed in human cancer. We identified DANCR through its overexpression in a transgenic model of MYC-induced lymphoma, but found that it was broadly upregulated in many human cancer cell lines and cancers, including most notably in prostate and ovarian cancers. Mechanistic investigations indicated that DANCR limited the expression of cell-cycle inhibitor p21 (CDKN1A) and that the inhibitory effects of DANCR loss on cell proliferation could be partially rescued by p21 silencing. In a xenograft model of human ovarian cancer, a nanoparticle-mediated siRNA strategy to target DANCR in vivo was sufficient to strongly inhibit tumor growth. Our observations expand knowledge of how MYC drives cancer cell proliferation by identifying DANCR as a critical lncRNA widely overexpressed in human cancers. Significance: These findings expand knowledge of how MYC drives cancer cell proliferation by identifying an oncogenic long noncoding RNA that is widely overexpressed in human cancers. Cancer Res; 78(1); 64-74. ©2017 AACR . ©2017 American Association for Cancer Research.

  20. Evolutionary analysis reveals regulatory and functional landscape of coding and non-coding RNA editing.

    Science.gov (United States)

    Zhang, Rui; Deng, Patricia; Jacobson, Dionna; Li, Jin Billy

    2017-02-01

    Adenosine-to-inosine RNA editing diversifies the transcriptome and promotes functional diversity, particularly in the brain. A plethora of editing sites has been recently identified; however, how they are selected and regulated and which are functionally important are largely unknown. Here we show the cis-regulation and stepwise selection of RNA editing during Drosophila evolution and pinpoint a large number of functional editing sites. We found that the establishment of editing and variation in editing levels across Drosophila species are largely explained and predicted by cis-regulatory elements. Furthermore, editing events that arose early in the species tree tend to be more highly edited in clusters and enriched in slowly-evolved neuronal genes, thus suggesting that the main role of RNA editing is for fine-tuning neurological functions. While nonsynonymous editing events have been long recognized as playing a functional role, in addition to nonsynonymous editing sites, a large fraction of 3'UTR editing sites is evolutionarily constrained, highly edited, and thus likely functional. We find that these 3'UTR editing events can alter mRNA stability and affect miRNA binding and thus highlight the functional roles of noncoding RNA editing. Our work, through evolutionary analyses of RNA editing in Drosophila, uncovers novel insights of RNA editing regulation as well as its functions in both coding and non-coding regions.

  1. Fragile X mental retardation protein participates in non-coding RNA pathways.

    Science.gov (United States)

    Li, En-Hui; Zhao, Xin; Zhang, Ce; Liu, Wei

    2018-02-20

    Fragile X syndrome is one of the most common forms of inherited intellectual disability. It is caused by mutations of the Fragile X mental retardation 1(FMR1) gene, resulting in either the loss or abnormal expression of the Fragile X mental retardation protein (FMRP). Recent research showed that FMRP participates in non-coding RNA pathways and plays various important roles in physiology, thereby extending our knowledge of the pathogenesis of the Fragile X syndrome. Initial studies showed that the Drosophila FMRP participates in siRNA and miRNA pathways by interacting with Dicer, Ago1 and Ago2, involved in neural activity and the fate determination of the germline stem cells. Subsequent studies showed that the Drosophila FMRP participates in piRNA pathway by interacting with Aub, Ago1 and Piwi in the maintenance of normal chromatin structures and genomic stability. More recent studies showed that FMRP is associated with lncRNA pathway, suggesting a potential role for the involvement in the clinical manifestations. In this review, we summarize the novel findings and explore the relationship between FMRP and non-coding RNA pathways, particularly the piRNA pathway, thereby providing critical insights on the molecular pathogenesis of Fragile X syndrome, and potential translational applications in clinical management of the disease.

  2. Comprehensive reconstruction and visualization of non-coding regulatory networks in human.

    Science.gov (United States)

    Bonnici, Vincenzo; Russo, Francesco; Bombieri, Nicola; Pulvirenti, Alfredo; Giugno, Rosalba

    2014-01-01

    Research attention has been powered to understand the functional roles of non-coding RNAs (ncRNAs). Many studies have demonstrated their deregulation in cancer and other human disorders. ncRNAs are also present in extracellular human body fluids such as serum and plasma, giving them a great potential as non-invasive biomarkers. However, non-coding RNAs have been relatively recently discovered and a comprehensive database including all of them is still missing. Reconstructing and visualizing the network of ncRNAs interactions are important steps to understand their regulatory mechanism in complex systems. This work presents ncRNA-DB, a NoSQL database that integrates ncRNAs data interactions from a large number of well established on-line repositories. The interactions involve RNA, DNA, proteins, and diseases. ncRNA-DB is available at http://ncrnadb.scienze.univr.it/ncrnadb/. It is equipped with three interfaces: web based, command-line, and a Cytoscape app called ncINetView. By accessing only one resource, users can search for ncRNAs and their interactions, build a network annotated with all known ncRNAs and associated diseases, and use all visual and mining features available in Cytoscape.

  3. Ontological function annotation of long non-coding RNAs through hierarchical multi-label classification.

    Science.gov (United States)

    Zhang, Jingpu; Zhang, Zuping; Wang, Zixiang; Liu, Yuting; Deng, Lei

    2018-05-15

    Long non-coding RNAs (lncRNAs) are an enormous collection of functional non-coding RNAs. Over the past decades, a large number of novel lncRNA genes have been identified. However, most of the lncRNAs remain function uncharacterized at present. Computational approaches provide a new insight to understand the potential functional implications of lncRNAs. Considering that each lncRNA may have multiple functions and a function may be further specialized into sub-functions, here we describe NeuraNetL2GO, a computational ontological function prediction approach for lncRNAs using hierarchical multi-label classification strategy based on multiple neural networks. The neural networks are incrementally trained level by level, each performing the prediction of gene ontology (GO) terms belonging to a given level. In NeuraNetL2GO, we use topological features of the lncRNA similarity network as the input of the neural networks and employ the output results to annotate the lncRNAs. We show that NeuraNetL2GO achieves the best performance and the overall advantage in maximum F-measure and coverage on the manually annotated lncRNA2GO-55 dataset compared to other state-of-the-art methods. The source code and data are available at http://denglab.org/NeuraNetL2GO/. leideng@csu.edu.cn. Supplementary data are available at Bioinformatics online.

  4. Expansion of passive safety function

    International Nuclear Information System (INIS)

    Inai, Nobuhiko; Nei, Hiromichi; Kumada, Toshiaki.

    1995-01-01

    Expansion of the use of passive safety functions is proposed. Two notions are presented. One is that, in the design of passive safety nuclear reactors where aversion of active components is stressed, some active components are purposely introduced, by which a system is built in such a way that it behaves in an apparently passive manner. The second notion is that, instead of using a passive safety function alone, a passive safety function is combined with some active components, relating the passivity in the safety function with enhanced controllability in normal operation. The nondormant system which the authors propose is one example of the first notion. This is a system in which a standby safety system is a portion of the normal operation system. An interpretation of the nondormant system via synergetics is made. As an example of the second notion, a PIUS density lock aided with active components is proposed and is discussed

  5. On the Equisummability of Hermite and Fourier Expansions

    Indian Academy of Sciences (India)

    We prove an equisummability result for the Fourier expansions and Hermite expansions as well as special Hermite expansions. We also prove the uniform boundedness of the Bochner-Riesz means associated to the Hermite expansions for polyradial functions.

  6. [Tissular expansion in giant congenital nevi treatment].

    Science.gov (United States)

    Nguyen Van Nuoi, V; Francois-Fiquet, C; Diner, P; Sergent, B; Zazurca, F; Franchi, G; Buis, J; Vazquez, M-P; Picard, A; Kadlub, N

    2014-08-01

    Surgical management of giant melanotic naevi remains a surgical challenge. Tissue expansion provides tissue of the same quality for the repair of defects. The aim of this study is to review tissular expansion for giant melanotic naevi. We conducted a retrospective study from 2000 to 2012. All children patients who underwent a tissular expansion for giant congenital naevi had been included. Epidemiological data, surgical procedure, complication rate and results had been analysed. Thirty-tree patients had been included; they underwent 61 procedures with 79 tissular-expansion prosthesis. Previous surgery, mostly simple excision had been performed before tissular expansion. Complete naevus excision had been performed in 63.3% of the cases. Complications occurred in 45% of the cases, however in 50% of them were minor. Iterative surgery increased the complication rate. Tissular expansion is a valuable option for giant congenital naevus. However, complication rate remained high, especially when iterative surgery is needed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. Repeatability & Workability Evaluation of SIGMOD 2009

    KAUST Repository

    Manegold, Stefan

    2010-12-15

    SIGMOD 2008 was the first database conference that offered to test submitters\\' programs against their data to verify the repeatability of the experiments published [1]. Given the positive feedback concerning the SIGMOD 2008 repeatability initiative, SIGMOD 2009 modified and expanded the initiative with a workability assessment.

  8. simple sequence repeats (EST-SSR)

    African Journals Online (AJOL)

    Yomi

    2012-01-19

    Jan 19, 2012 ... 212 primer pairs selected, based on repeat patterns of n≥8 for di-, tri-, tetra- and penta-nucleotide repeat ... Cluster analysis revealed a high genetic similarity among the sugarcane (Saccharum spp.) breeding lines which could reduce the genetic gain in ..... The multiple allele characteristic of SSR com-.

  9. Repeatability & Workability Evaluation of SIGMOD 2009

    KAUST Repository

    Manegold, Stefan; Manolescu, Ioana; Afanasiev, Loredana; Feng, Jieling; Gou, G.; Hadjieleftheriou, Marios; Harizopoulos, Stavros; Kalnis, Panos; Karanasos, Konstantinos; Laurent, Dominique; Lupu, M.; Onose, N.; Ré , C.; Sans, Virginie; Senellart, Pierre; Wu, T.; Shasha, Dennis E.

    2010-01-01

    SIGMOD 2008 was the first database conference that offered to test submitters' programs against their data to verify the repeatability of the experiments published [1]. Given the positive feedback concerning the SIGMOD 2008 repeatability initiative, SIGMOD 2009 modified and expanded the initiative with a workability assessment.

  10. Unraveling the Role of RNA Mediated Toxicity of C9orf72 Repeats in C9-FTD/ALS

    Directory of Open Access Journals (Sweden)

    Vijay Kumar

    2017-12-01

    Full Text Available The most frequent genetic cause of amyotrophic lateral sclerosis (ALS and frontotemporal dementia (FTD is intronic hexanucleotide (G4C2 repeat expansions (HRE in the C9orf72 gene. The non-exclusive pathogenic mechanisms by which C9orf72 repeat expansions contribute to these neurological disorders include loss of C9orf72 function and gain-of-function determined by toxic RNA molecules and dipeptides repeats protein toxicity. The expanded repeats are transcribed bidirectionally and forms RNA foci in the central nervous system, and sequester key RNA-binding proteins (RBPs leading to impairment in RNA processing events. Many studies report widespread transcriptome changes in ALS carrying a C9orf72 repeat expansion. Here we review the contribution of RNA foci interaction with RBPs as well as transcriptome changes involved in the pathogenesis of C9orf72- associated FTD/ALS. These informations are essential to elucidate the pathology and therapeutic intervention of ALS and/or FTD.

  11. Simulation program for multiple expansion Stirling machines

    International Nuclear Information System (INIS)

    Walker, G.; Weiss, M.; Fauvel, R.; Reader, G.; Bingham, E.R.

    1992-01-01

    Multiple expansion Stirling machines have been a topic of interest at the University of Calgary for some years. Recently a second-order computer simulation program with integral graphics package for Stirling cryocoolers with up to four stages of expansion were developed and made available to the Stirling community. Adaptation of the program to multiple expansion Stirling power systems is anticipated. This paper briefly introduces the program and presents a specimen result

  12. Semiclassical expansions for confined N fermion systems

    International Nuclear Information System (INIS)

    Krivine, H.; Martorell, J.; Casas, M.

    1989-01-01

    A new derivation of the Wigner Kirkwood expansion for N-fermion systems is presented, showing explicitly the connection to the WKB approximation for a single level. This allows to study separately the two ansatz required to obtain the semiclassical expansions: the asymptotic expansions in powers of ℎ and the smoothing of quantal effects. We discuss the one dimensional and three dimensional, with spherical symmetry, cases. Applications for standard potentials used in nuclear physics are described in detail

  13. Thermal and hygroscopic expansion characteristics of bamboo

    OpenAIRE

    Huang, Puxi; Chang, Wen-shao; Ansell, Martin P.; Bowen, Chris R.; Chew, John Y. M.; Adamak, Vana i

    2017-01-01

    The expansion and contraction of bamboo caused by temperature and moisture variations must be evaluated\\ud if bamboo is to be utilised as a building material. However, detailed expansion data, especially data in the ascent and\\ud descent processes of temperature and moisture are unexplored. The aim of this study is to investigate the expansion\\ud characteristics of Phyllostachys edulis (Moso bamboo) in ascent and descent processes of temperature and moisture.\\ud The measurement of linear ther...

  14. $\\delta$-Expansion at Finite Temperature

    OpenAIRE

    Ramos, Rudnei O.

    1996-01-01

    We apply the $\\delta$-expansion perturbation scheme to the $\\lambda \\phi^{4}$ self-interacting scalar field theory in 3+1 D at finite temperature. In the $\\delta$-expansion the interaction term is written as $\\lambda (\\phi^{2})^{ 1 + \\delta}$ and $\\delta$ is considered as the perturbation parameter. We compute within this perturbative approach the renormalized mass at finite temperature at a finite order in $\\delta$. The results are compared with the usual loop-expansion at finite temperature.

  15. Chromatic Derivatives, Chromatic Expansions and Associated Spaces

    OpenAIRE

    Ignjatovic, Aleksandar

    2009-01-01

    This paper presents the basic properties of chromatic derivatives and chromatic expansions and provides an appropriate motivation for introducing these notions. Chromatic derivatives are special, numerically robust linear differential operators which correspond to certain families of orthogonal polynomials. Chromatic expansions are series of the corresponding special functions, which possess the best features of both the Taylor and the Shannon expansions. This makes chromatic derivatives and ...

  16. Thermal expansion in small metallic particles

    International Nuclear Information System (INIS)

    Ivanov, A.S.

    1985-01-01

    An anomalously low thermal expansion observable in small particles is attributed to extending effect of the shell. It is shown that the coefficient of thermal expansion of the oxide-film-coated aluminium particles calculated using elastic constants and coefficients of thermal expansion of massive materials agres well with those measured experimentally. The linear dilatation of the shell, its stress to rupture and the values of the structural tension are estimated vs the temperature

  17. UK 2009-2010 repeat station report

    Directory of Open Access Journals (Sweden)

    Thomas J.G. Shanahan

    2013-03-01

    Full Text Available The British Geological Survey is responsible for conducting the UK geomagnetic repeat station programme. Measurements made at the UK repeat station sites are used in conjunction with the three UK magnetic observatories: Hartland, Eskdalemuir and Lerwick, to produce a regional model of the local field each year. The UK network of repeat stations comprises 41 stations which are occupied at approximately 3-4 year intervals. Practices for conducting repeat station measurements continue to evolve as advances are made in survey instrumentation and as the usage of the data continues to change. Here, a summary of the 2009 and 2010 UK repeat station surveys is presented, highlighting the measurement process and techniques, density of network, reduction process and recent results.

  18. Disjoint sum expansion method in FTA

    International Nuclear Information System (INIS)

    Ruan Keqiang

    1987-01-01

    An expansion formula for transforming boolean algebraic expressions into disjoint form was proved. Based on this expansion formula, a method for transforming system failure function into disjoint form was devised. The fact that the expansion can be done for several elements simulatneously makes the method flexible and fast. Some examples from fault tree analysis (FTA) and network analysis were examined by the new method to show its algorithm and its merit. Besides, by means of the proved expansion formula some boolean algebraic relations can proved very easily

  19. Thermal expansion of L-ascorbic acid

    Science.gov (United States)

    Nicolaï, B.; Barrio, M.; Tamarit, J.-Ll.; Céolin, R.; Rietveld, I. B.

    2017-04-01

    The specific volume of vitamin C has been investigated by X-ray powder diffraction as a function of temperature from 110 K up to complete degradation around 440 K. Its thermal expansion is relatively small in comparison with other organic compounds with an expansivity α v of 1.2(3) × 10-4 K-1. The structure consists of strongly bound molecules in the ac plane through a dense network of hydrogen bonds. The thermal expansion is anisotropic. Along the b axis, the expansion has most leeway and is about 10 times larger than in the other directions.

  20. Adiabatic supernova expansion into the circumstellar medium

    International Nuclear Information System (INIS)

    Band, D.L.; Liang, E.P.

    1987-01-01

    We perform one dimensional numerical simulations with a Lagrangian hydrodynamics code of the adiabatic expansion of a supernova into the surrounding medium. The early expansion follows Chevalier's analytic self-similar solution until the reverse shock reaches the ejecta core. We follow the expansion as it evolves towards the adiabatic blast wave phase. Some memory of the earlier phases of expansion is retained in the interior even when the outer regions expand as a blast wave. We find the results are sensitive to the initial configuration of the ejecta and to the placement of gridpoints. 6 refs., 2 figs

  1. Identification of small non-coding RNA classes expressed in swine whole blood during HP-PRRSV infection

    Science.gov (United States)

    It has been established that reduced susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) has a genetic component. This genetic component may take the form of small non-coding RNAs (sncRNA), which are molecules that function as regulators of gene expression. Various sncRNAs ...

  2. Specificity Protein (Sp) Transcription Factors and Metformin Regulate Expression of the Long Non-coding RNA HULC

    Science.gov (United States)

    There is evidence that specificity protein 1 (Sp1) transcription factor (TF) regulates expression of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) cells. RNA interference (RNAi) studies showed that among several lncRNAs expressed in HepG2, SNU-449 and SK-Hep-1...

  3. microRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus

    DEFF Research Database (Denmark)

    Leucci, Eleonora; Patella, Francesca; Waage, Johannes

    2013-01-01

    -coding RNAs. Here we report that microRNA-9 (miR-9) regulates the expression of the Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT-1), one of the most abundant and conserved long non-coding RNAs. Intriguingly, we find that miR-9 targets AGO2-mediated regulation of MALAT1 in the nucleus. Our...

  4. Overview of long non-coding RNA and mRNA expression in response to methamphetamine treatment in vitro

    NARCIS (Netherlands)

    Xiong, Kun; Long, Lingling; Zhang, Xudong; Qu, Hongke; Deng, Haixiao; Ding, Yanjun; Cai, Jifeng; Wang, Shuchao; Wang, Mi; Liao, Lvshuang; Huang, Jufang; Yi, Chun-Xia; Yan, Jie

    2017-01-01

    Long non-coding RNAs (IncRNAs) display multiple functions including regulation of neuronal injury. However, their impact in methamphetamine (METH)-induced neurotoxicity has rarely been reported. Here, using microarray analysis, we investigated the expression profiling of lncRNAs and mRNAs in primary

  5. Non-Coding RNAs in Castration-Resistant Prostate Cancer: Regulation of Androgen Receptor Signaling and Cancer Metabolism.

    Science.gov (United States)

    Shih, Jing-Wen; Wang, Ling-Yu; Hung, Chiu-Lien; Kung, Hsing-Jien; Hsieh, Chia-Ling

    2015-12-04

    Hormone-refractory prostate cancer frequently relapses from therapy and inevitably progresses to a bone-metastatic status with no cure. Understanding of the molecular mechanisms conferring resistance to androgen deprivation therapy has the potential to lead to the discovery of novel therapeutic targets for type of prostate cancer with poor prognosis. Progression to castration-resistant prostate cancer (CRPC) is characterized by aberrant androgen receptor (AR) expression and persistent AR signaling activity. Alterations in metabolic activity regulated by oncogenic pathways, such as c-Myc, were found to promote prostate cancer growth during the development of CRPC. Non-coding RNAs represent a diverse family of regulatory transcripts that drive tumorigenesis of prostate cancer and various other cancers by their hyperactivity or diminished function. A number of studies have examined differentially expressed non-coding RNAs in each stage of prostate cancer. Herein, we highlight the emerging impacts of microRNAs and long non-coding RNAs linked to reactivation of the AR signaling axis and reprogramming of the cellular metabolism in prostate cancer. The translational implications of non-coding RNA research for developing new biomarkers and therapeutic strategies for CRPC are also discussed.

  6. An internal duplication in the 5' noncoding region of strain H: a bovine viral diarrhoea virus (BVDV) isolated from pigs

    NARCIS (Netherlands)

    Gennip, van H.G.P.; Widjojoatmodjo, M.N.; Smit, de A.J.; Moormann, R.J.M.

    1999-01-01

    A pig pestivirus isolate, strain H, was characterized by using reverse transcription-PCR (RT-PCR) and direct sequencing of the amplicons. A duplication of 74 nucleotides was found at the 5' terminus of the 5' noncoding (NC) region, which was also found in RNA isolates from tonsils from two other

  7. An Abundant Class of Non-coding DNA Can Prevent Stochastic Gene Silencing in the C. elegans Germline

    DEFF Research Database (Denmark)

    Frøkjær-Jensen, Christian; Jain, Nimit; Hansen, Loren

    2016-01-01

    /or structure. Here, we demonstrate that a pervasive non-coding DNA feature in Caenorhabditis elegans, characterized by 10-base pair periodic An/Tn-clusters (PATCs), can license transgenes for germline expression within repressive chromatin domains. Transgenes containing natural or synthetic PATCs are resistant...

  8. Myotonin protein-kinase [AGC]n trinucleotide repeat in seven nonhuman primates

    Energy Technology Data Exchange (ETDEWEB)

    Novelli, G.; Sineo, L.; Pontieri, E. [Catholic Univ. of Rome (Italy)]|[Univ. of Milan (Italy)]|[Univ. Florence (Italy)] [and others

    1994-09-01

    Myotonic dystrophy (DM) is due to a genomic instability of a trinucleotide [AGC]n motif, located at the 3{prime} UTR region of a protein-kinase gene (myotonin protein kinase, MT-PK). The [AGC] repeat is meiotically and mitotically unstable, and it is directly related to the manifestations of the disorder. Although a gene dosage effect of the MT-PK has been demonstrated n DM muscle, the mechanism(s) by which the intragenic repeat expansion leads to disease is largely unknown. This non-standard mutational event could reflect an evolutionary mechanism widespread among animal genomes. We have isolated and sequenced the complete 3{prime}UTR region of the MT-PK gene in seven primates (macaque, orangutan, gorilla, chimpanzee, gibbon, owl monkey, saimiri), and examined by comparative sequence nucleotide analysis the [AGC]n intragenic repeat and the surrounding nucleotides. The genomic organization, including the [AGC]n repeat structure, was conserved in all examined species, excluding the gibbon (Hylobates agilis), in which the [AGC]n upstream sequence (GGAA) is replaced by a GA dinucleotide. The number of [AGC]n in the examined species ranged between 7 (gorilla) and 13 repeats (owl monkeys), with a polymorphism informative content (PIC) similar to that observed in humans. These results indicate that the 3{prime}UTR [AGC] repeat within the MT-PK gene is evolutionarily conserved, supporting that this region has important regulatory functions.

  9. Identification of Novel Long Non-coding and Circular RNAs in Human Papillomavirus-Mediated Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Hongbo Wang

    2017-09-01

    Full Text Available Cervical cancer is the third most common cancer worldwide and the fourth leading cause of cancer-associated mortality in women. Accumulating evidence indicates that long non-coding RNAs (lncRNAs and circular RNAs (circRNAs may play key roles in the carcinogenesis of different cancers; however, little is known about the mechanisms of lncRNAs and circRNAs in the progression and metastasis of cervical cancer. In this study, we explored the expression profiles of lncRNAs, circRNAs, miRNAs, and mRNAs in HPV16 (human papillomavirus genotype 16 mediated cervical squamous cell carcinoma and matched adjacent non-tumor (ATN tissues from three patients with high-throughput RNA sequencing (RNA-seq. In total, we identified 19 lncRNAs, 99 circRNAs, 28 miRNAs, and 304 mRNAs that were commonly differentially expressed (DE in different patients. Among the non-coding RNAs, 3 lncRNAs and 44 circRNAs are novel to our knowledge. Functional enrichment analysis showed that DE lncRNAs, miRNAs, and mRNAs were enriched in pathways crucial to cancer as well as other gene ontology (GO terms. Furthermore, the co-expression network and function prediction suggested that all 19 DE lncRNAs could play different roles in the carcinogenesis and development of cervical cancer. The competing endogenous RNA (ceRNA network based on DE coding and non-coding RNAs showed that each miRNA targeted a number of lncRNAs and circRNAs. The link between part of the miRNAs in the network and cervical cancer has been validated in previous studies, and these miRNAs targeted the majority of the novel non-coding RNAs, thus suggesting that these novel non-coding RNAs may be involved in cervical cancer. Taken together, our study shows that DE non-coding RNAs could be further developed as diagnostic and therapeutic biomarkers of cervical cancer. The complex ceRNA network also lays the foundation for future research of the roles of coding and non-coding RNAs in cervical cancer.

  10. Identification of Novel Long Non-coding and Circular RNAs in Human Papillomavirus-Mediated Cervical Cancer

    Science.gov (United States)

    Wang, Hongbo; Zhao, Yingchao; Chen, Mingyue; Cui, Jie

    2017-01-01

    Cervical cancer is the third most common cancer worldwide and the fourth leading cause of cancer-associated mortality in women. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) may play key roles in the carcinogenesis of different cancers; however, little is known about the mechanisms of lncRNAs and circRNAs in the progression and metastasis of cervical cancer. In this study, we explored the expression profiles of lncRNAs, circRNAs, miRNAs, and mRNAs in HPV16 (human papillomavirus genotype 16) mediated cervical squamous cell carcinoma and matched adjacent non-tumor (ATN) tissues from three patients with high-throughput RNA sequencing (RNA-seq). In total, we identified 19 lncRNAs, 99 circRNAs, 28 miRNAs, and 304 mRNAs that were commonly differentially expressed (DE) in different patients. Among the non-coding RNAs, 3 lncRNAs and 44 circRNAs are novel to our knowledge. Functional enrichment analysis showed that DE lncRNAs, miRNAs, and mRNAs were enriched in pathways crucial to cancer as well as other gene ontology (GO) terms. Furthermore, the co-expression network and function prediction suggested that all 19 DE lncRNAs could play different roles in the carcinogenesis and development of cervical cancer. The competing endogenous RNA (ceRNA) network based on DE coding and non-coding RNAs showed that each miRNA targeted a number of lncRNAs and circRNAs. The link between part of the miRNAs in the network and cervical cancer has been validated in previous studies, and these miRNAs targeted the majority of the novel non-coding RNAs, thus suggesting that these novel non-coding RNAs may be involved in cervical cancer. Taken together, our study shows that DE non-coding RNAs could be further developed as diagnostic and therapeutic biomarkers of cervical cancer. The complex ceRNA network also lays the foundation for future research of the roles of coding and non-coding RNAs in cervical cancer. PMID:28970820

  11. Hubble expansion in static spacetime

    International Nuclear Information System (INIS)

    Rossler, Otto E.; Froehlich, Dieter; Movassagh, Ramis; Moore, Anthony

    2007-01-01

    A recently proposed mechanism for light-path expansion in a static spacetime is based on the moving-lenses paradigm. Since the latter is valid independently of whether space expands or not, a static universe can be used to better see the implications. The moving-lenses paradigm is related to the paradigm of dynamical friction. If this is correct, a Hubble-like law is implicit. It is described quantitatively. A bent in the Hubble-like line is predictably implied. The main underlying assumption is Price's Principle (PI 3 ). If the theory is sound, the greatest remaining problem in cosmology becomes the origin of hydrogen. Since Blandford's jet production mechanism for quasars is too weak, a generalized Hawking radiation hidden in the walls of cosmic voids is invoked. A second prediction is empirical: slow pattern changes in the cosmic microwave background. A third is ultra-high redshifts for Giacconi quasars. Bruno's eternal universe in the spirit of Augustine becomes a bit less outlandish

  12. Primordial vorticity and gradient expansion

    CERN Document Server

    Giovannini, Massimo

    2012-01-01

    The evolution equations of the vorticities of the electrons, ions and photons in a pre-decoupling plasma are derived, in a fully inhomogeneous geometry, by combining the general relativistic gradient expansion and the drift approximation within the Adler-Misner-Deser decomposition. The vorticity transfer between the different species is discussed in this novel framework and a set of general conservation laws, connecting the vorticities of the three-component plasma with the magnetic field intensity, is derived. After demonstrating that a source of large-scale vorticity resides in the spatial gradients of the geometry and of the electromagnetic sources, the total vorticity is estimated to lowest order in the spatial gradients and by enforcing the validity of the momentum constraint. By acknowledging the current bounds on the tensor to scalar ratio in the (minimal) tensor extension of the $\\Lambda$CDM paradigm the maximal comoving magnetic field induced by the total vorticity turns out to be, at most, of the or...

  13. Negative thermal expansion materials: technological key for control of thermal expansion

    OpenAIRE

    Koshi Takenaka

    2012-01-01

    Most materials expand upon heating. However, although rare, some materials contract upon heating. Such negative thermal expansion (NTE) materials have enormous industrial merit because they can control the thermal expansion of materials. Recent progress in materials research enables us to obtain materials exhibiting negative coefficients of linear thermal expansion over −30 ppm K−1. Such giant NTE is opening a new phase of control of thermal expansion in composites. Specifically examining pra...

  14. Nras Overexpression Results in Granulocytosis, T-Cell Expansion and Early Lethality in Mice

    DEFF Research Database (Denmark)

    Lassen, Louise Berkhoudt; Gonzalez, Borja Ballarin; Schmitz, Alexander

    2012-01-01

    NRAS is a proto-oncogene involved in numerous myeloid malignancies. Here, we report on a mouse line bearing a single retroviral long terminal repeat inserted into Nras. This genetic modification resulted in an increased level of wild type Nras mRNA giving the possibility of studying the function ...... the increment in immature myeloid cells detected in these mice. The short latency period indicates that Nras overexpression alone is sufficient to cause dose-dependent granulocytosis and T-cell expansion....

  15. The long noncoding RNA Tug1 connects metabolic changes with kidney disease in podocytes.

    Science.gov (United States)

    Li, Szu Yuan; Susztak, Katalin

    2016-11-01

    An increasing amount of evidence suggests that metabolic alterations play a key role in chronic kidney disease (CKD) pathogenesis. In this issue of the JCI, Long et al. report that the long noncoding RNA (lncRNA) taurine-upregulated 1 (Tug1) contributes to CKD development. The authors show that Tug1 regulates mitochondrial function in podocytes by epigenetic targeting of expression of the transcription factor PPARγ coactivator 1α (PGC-1α, encoded by Ppargc1a). Transgenic overexpression of Tug1 specifically in podocytes ameliorated diabetes-induced CKD in mice. Together, these results highlight an important connection between lncRNA-mediated metabolic alterations in podocytes and kidney disease development.

  16. From structure prediction to genomic screens for novel non-coding RNAs

    DEFF Research Database (Denmark)

    Gorodkin, Jan; Hofacker, Ivo L.

    2011-01-01

    Abstract: Non-coding RNAs (ncRNAs) are receiving more and more attention not only as an abundant class of genes, but also as regulatory structural elements (some located in mRNAs). A key feature of RNA function is its structure. Computational methods were developed early for folding and prediction....... This and the increased amount of available genomes have made it possible to employ structure-based methods for genomic screens. The field has moved from folding prediction of single sequences to computational screens for ncRNAs in genomic sequence using the RNA structure as the main characteristic feature. Whereas early...... upon some of the concepts in current methods that have been applied in genomic screens for de novo RNA structures in searches for novel ncRNA genes and regulatory RNA structure on mRNAs. We discuss the strengths and weaknesses of the different strategies and how they can complement each other....

  17. Authentication of Botanical Origin in Herbal Teas by Plastid Noncoding DNA Length Polymorphisms.

    Science.gov (United States)

    Uncu, Ali Tevfik; Uncu, Ayse Ozgur; Frary, Anne; Doganlar, Sami

    2015-07-01

    The aim of this study was to develop a DNA barcode assay to authenticate the botanical origin of herbal teas. To reach this aim, we tested the efficiency of a PCR-capillary electrophoresis (PCR-CE) approach on commercial herbal tea samples using two noncoding plastid barcodes, the trnL intron and the intergenic spacer between trnL and trnF. Barcode DNA length polymorphisms proved successful in authenticating the species origin of herbal teas. We verified the validity of our approach by sequencing species-specific barcode amplicons from herbal tea samples. Moreover, we displayed the utility of PCR-CE assays coupled with sequencing to identify the origin of undeclared plant material in herbal tea samples. The PCR-CE assays proposed in this work can be applied as routine tests for the verification of botanical origin in herbal teas and can be extended to authenticate all types of herbal foodstuffs.

  18. A Looking-Glass of Non-Coding RNAs in Oral Cancer

    Science.gov (United States)

    Irimie, Alexandra Iulia; Braicu, Cornelia; Sonea, Laura; Zimta, Alina Andreea; Diudea, Diana; Buduru, Smaranda; Berindan-Neagoe, Ioana

    2017-01-01

    Oral cancer is a multifactorial pathology and is characterized by the lack of efficient treatment and accurate diagnostic tools. This is mainly due the late diagnosis; therefore, reliable biomarkers for the timely detection of the disease and patient stratification are required. Non-coding RNAs (ncRNAs) are key elements in the physiological and pathological processes of various cancers, which is also reflected in oral cancer development and progression. A better understanding of their role could give a more thorough perspective on the future treatment options for this cancer type. This review offers a glimpse into the ncRNA involvement in oral cancer, which can help the medical community tap into the world of ncRNAs and lay the ground for more powerful diagnostic, prognostic and treatment tools for oral cancer that will ultimately help build a brighter future for these patients. PMID:29206174

  19. Long non-coding RNA expression profiles in hereditary haemorrhagic telangiectasia

    DEFF Research Database (Denmark)

    Tørring, Pernille M; Larsen, Martin Jakob; Kjeldsen, Anette D

    2014-01-01

    transcriptome, we wanted to assess whether lncRNAs play a role in the molecular pathogenesis of HHT manifestations. By microarray technology, we profiled lncRNA transcripts from HHT nasal telangiectasial and non-telangiectasial tissue using a paired design. The microarray probes were annotated using the GENCODE...... v.16 dataset, identifying 4,810 probes mapping to 2,811 lncRNAs. Comparing HHT telangiectasial tissue with HHT non-telangiectasial tissue, we identified 42 lncRNAs that are differentially expressed (qUsing GREAT, a tool that assumes cis-regulation, we showed that differently expressed lncRNAs...... to the TGF-β signalling pathway. The exact mechanism of how haploinsufficiency of ENG and ACVRL1 leads to HHT manifestations remains to be identified. As long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and constitute a sizable fraction of the human...

  20. MASTR: multiple alignment and structure prediction of non-coding RNAs using simulated annealing

    DEFF Research Database (Denmark)

    Lindgreen, Stinus; Gardner, Paul P; Krogh, Anders

    2007-01-01

    function that considers sequence conservation, covariation and basepairing probabilities. The results show that the method is very competitive to similar programs available today, both in terms of accuracy and computational efficiency. AVAILABILITY: Source code available from http://mastr.binf.ku.dk/......MOTIVATION: As more non-coding RNAs are discovered, the importance of methods for RNA analysis increases. Since the structure of ncRNA is intimately tied to the function of the molecule, programs for RNA structure prediction are necessary tools in this growing field of research. Furthermore......, it is known that RNA structure is often evolutionarily more conserved than sequence. However, few existing methods are capable of simultaneously considering multiple sequence alignment and structure prediction. RESULT: We present a novel solution to the problem of simultaneous structure prediction...

  1. Long noncoding RNA lnc-sox5 modulates CRC tumorigenesis by unbalancing tumor microenvironment.

    Science.gov (United States)

    Wu, Kaiming; Zhao, Zhenxian; Liu, Kuanzhi; Zhang, Jian; Li, Guanghua; Wang, Liang

    2017-07-03

    Long non-coding RNAs (LncRNAs) have been recently regarded as systemic regulators in multiple biologic processes including tumorigenesis. In this study, we observed the expression of lncRNA lnc-sox5 was significantly increased in colorectal cancer (CRC). Despite the CRC cell growth, cell cycle and cell apoptosis was not affected by lnc-sox5 knock-down, lnc-sox5 knock-down suppressed CRC cell migration and invasion. In addition, xenograft animal model suggested that lnc-sox5 knock-down significantly suppressed the CRC tumorigenesis. Our results also showed that the expression of indoleamine 2,3-dioxygenase 1 (IDO1) was significantly reduced by lnc-sox5 knock-down and therefore modulated the infiltration and cytotoxicity of CD3 + CD8 + T cells. Taken together, these results suggested that lnc-sox5 unbalances tumor microenvironment to regulate colorectal cancer progression.

  2. Non-coding RNAs: New therapeutic targets and opportunities for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Cuiyun

    2016-02-01

    Full Text Available Non-coding RNAs (ncRNA are RNA molecules without protein coding functions owing to the lack of an open reading frame (ORF. Based on the length, ncRNAs can be divided into long and short ncRNAs; short ncRNAs include miRNAs and piRNAs. Hepatocellular carcinoma (HCC is among the most frequent forms of cancer worldwide and its incidence is increasing rapidly. Studies have found that ncRNAs are likely to play a crucial role in a variety of biological processes including the pathogenesis and progression of HCC. In this review, we summarized the regulation mechanism and biological functions of ncRNAs in HCC with respect to its application in HCC diagnosis, therapy and prognosis.

  3. Human Long Noncoding RNA Regulation of Stem Cell Potency and Differentiation

    Directory of Open Access Journals (Sweden)

    Seahyoung Lee

    2017-01-01

    Full Text Available Because of their capability of differentiation into lineage-specific cells, stem cells are an attractive therapeutic modality in regenerative medicine. To develop an effective stem cell-based therapeutic strategy with predictable results, deeper understanding of the underlying molecular mechanisms of stem cell differentiation and/or pluripotency maintenance is required. Thus, reviewing the key factors involved in the transcriptional and epigenetic regulation of stem cell differentiation and maintenance is important. Accumulating data indicate that long noncoding RNAs (lncRNAs mediate numerous biological processes, including stem cell differentiation and maintenance. Here, we review recent findings on the human lncRNA regulation of stem cell potency and differentiation. Although the clinical implication of these lncRNAs is only beginning to be elucidated, it is anticipated that lncRNAs will become important therapeutic targets in the near future.

  4. Fluorogenic RNA Mango aptamers for imaging small non-coding RNAs in mammalian cells.

    Science.gov (United States)

    Autour, Alexis; C Y Jeng, Sunny; D Cawte, Adam; Abdolahzadeh, Amir; Galli, Angela; Panchapakesan, Shanker S S; Rueda, David; Ryckelynck, Michael; Unrau, Peter J

    2018-02-13

    Despite having many key roles in cellular biology, directly imaging biologically important RNAs has been hindered by a lack of fluorescent tools equivalent to the fluorescent proteins available to study cellular proteins. Ideal RNA labelling systems must preserve biological function, have photophysical properties similar to existing fluorescent proteins, and be compatible with established live and fixed cell protein labelling strategies. Here, we report a microfluidics-based selection of three new high-affinity RNA Mango fluorogenic aptamers. Two of these are as bright or brighter than enhanced GFP when bound to TO1-Biotin. Furthermore, we show that the new Mangos can accurately image the subcellular localization of three small non-coding RNAs (5S, U6, and a box C/D scaRNA) in fixed and live mammalian cells. These new aptamers have many potential applications to study RNA function and dynamics both in vitro and in mammalian cells.

  5. Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease

    International Nuclear Information System (INIS)

    Akiyama, Benjamin M.; Laurence, Hannah M.; University of Colorado, Aurora, CO; University of California, Davis, CA; Massey, Aaron R.

    2016-01-01

    The outbreak of Zika virus (ZIKV) and associated fetal microcephaly mandates efforts to understand the molecular processes of infection. Related flaviviruses produce noncoding subgenomic flaviviral RNAs (sfRNAs) that are linked to pathogenicity in fetal mice. These viruses make sfRNAs by co-opting a cellular exonuclease via structured RNAs called xrRNAs. We found that ZIKV-infected monkey and human epithelial cells, mouse neurons, and mosquito cells produce sfRNAs. The RNA structure that is responsible for ZIKV sfRNA production forms a complex fold that is likely found in many pathogenic flaviviruses. Mutations that disrupt the structure affect exonuclease resistance in vitro and sfRNA formation during infection. The complete ZIKV xrRNA structure clarifies the mechanism of exonuclease resistance and identifies features that may modulate function in diverse flaviviruses.

  6. MetastamiRs: Non-Coding MicroRNAs Driving Cancer Invasion and Metastasis

    Directory of Open Access Journals (Sweden)

    Sergio Rodriguez-Cuevas

    2012-01-01

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs of ~22 nucleotides that function as negative regulators of gene expression by either inhibiting translation or inducing deadenylation-dependent degradation of target transcripts. Notably, deregulation of miRNAs expression is associated with the initiation and progression of human cancers where they act as oncogenes or tumor suppressors contributing to tumorigenesis. Abnormal miRNA expression may provide potential diagnostic and prognostic tumor biomarkers and new therapeutic targets in cancer. Recently, several miRNAs have been shown to initiate invasion and metastasis by targeting multiple proteins that are major players in these cellular events, thus they have been denominated as metastamiRs. Here, we present a review of the current knowledge of miRNAs in cancer with a special focus on metastamiRs. In addition we discuss their potential use as novel specific markers for cancer progression.

  7. The functional role of long non-coding RNA in digestive system carcinomas.

    Science.gov (United States)

    Wang, Guang-Yu; Zhu, Yuan-Yuan; Zhang, Yan-Qiao

    2014-09-01

    In recent years, long non-coding RNAs (lncRNAs) are emerging as either oncogenes or tumor suppressor genes. Recent evidences suggest that lncRNAs play a very important role in digestive system carcinomas. However, the biological function of lncRNAs in the vast majority of digestive system carcinomas remains unclear. Recently, increasing studies has begun to explore their molecular mechanisms and regulatory networks that they are implicated in tumorigenesis. In this review, we highlight the emerging functional role of lncRNAs in digestive system carcinomas. It is becoming clear that lncRNAs will be exciting and potentially useful for diagnosis and treatment of digestive system carcinomas, some of these lncRNAs might function as both diagnostic markers and the treatment targets of digestive system carcinomas.

  8. Prognostic value of long noncoding RNA MALAT1 in digestive system malignancies.

    Science.gov (United States)

    Zhai, Hui; Li, Xiao-Mei; Maimaiti, Ailifeire; Chen, Qing-Jie; Liao, Wu; Lai, Hong-Mei; Liu, Fen; Yang, Yi-Ning

    2015-01-01

    MALAT1, a newly discovered long noncoding RNA (lncRNA), has been reported to be highly expressed in many types of cancers. This meta-analysis summarizes its potential prognostic value in digestive system malignancies. A quantitative meta-analysis was performed through a systematic search in PubMed, Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI) for eligible papers on the prognostic impact of MALAT1 in digestive system malignancies from inception to Apr. 25, 2015. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to summarize the effect. Five studies were included in the study, with a total of 527 patients. A significant association was observed between MALAT1 abundance and poor overall survival (OS) of patients with digestive system malignancies, with pooled hazard ratio (HR) of 7.68 (95% confidence interval [CI]: 4.32-13.66, Pdigestive system malignancies.

  9. Long Non-Coding RNAs Embedded in the Rb and p53 Pathways

    Energy Technology Data Exchange (ETDEWEB)

    Subramanian, Murugan; Jones, Matthew F.; Lal, Ashish, E-mail: ashish.lal@nih.gov [Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 (United States)

    2013-12-04

    In recent years, long non-coding RNAs (lncRNAs) have gained significant attention as a novel class of gene regulators. Although a small number of lncRNAs have been shown to regulate gene expression through diverse mechanisms including transcriptional regulation, mRNA splicing and translation, the physiological function and mechanism of action of the vast majority are not known. Profiling studies in cell lines and tumor samples have suggested a potential role of lncRNAs in cancer. Indeed, distinct lncRNAs have been shown to be embedded in the p53 and Rb networks, two of the major tumor suppressor pathways that control cell cycle progression and survival. Given the fact that inactivation of Rb and p53 is a hallmark of human cancer, in this review we discuss recent evidence on the function of lncRNAs in the Rb and p53 signaling pathways.

  10. Long Non-Coding RNAs Embedded in the Rb and p53 Pathways

    International Nuclear Information System (INIS)

    Subramanian, Murugan; Jones, Matthew F.; Lal, Ashish

    2013-01-01

    In recent years, long non-coding RNAs (lncRNAs) have gained significant attention as a novel class of gene regulators. Although a small number of lncRNAs have been shown to regulate gene expression through diverse mechanisms including transcriptional regulation, mRNA splicing and translation, the physiological function and mechanism of action of the vast majority are not known. Profiling studies in cell lines and tumor samples have suggested a potential role of lncRNAs in cancer. Indeed, distinct lncRNAs have been shown to be embedded in the p53 and Rb networks, two of the major tumor suppressor pathways that control cell cycle progression and survival. Given the fact that inactivation of Rb and p53 is a hallmark of human cancer, in this review we discuss recent evidence on the function of lncRNAs in the Rb and p53 signaling pathways

  11. Bistability and oscillations in gene regulation mediated by small noncoding RNAs.

    Directory of Open Access Journals (Sweden)

    Dengyu Liu

    Full Text Available The interplay of small noncoding RNAs (sRNAs, mRNAs, and proteins has been shown to play crucial roles in almost all cellular processes. As key post-transcriptional regulators of gene expression, the mechanisms and roles of sRNAs in various cellular processes still need to be fully understood. When participating in cellular processes, sRNAs mainly mediate mRNA degradation or translational repression. Here, we show how the dynamics of two minimal architectures is drastically affected by these two mechanisms. A comparison is also given to reveal the implication of the fundamental differences. This study may help us to analyze complex networks assembled by simple modules more easily. A better knowledge of the sRNA-mediated motifs is also of interest for bio-engineering and artificial control.

  12. Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer

    DEFF Research Database (Denmark)

    Martens-Uzunova, E S; Jalava, S E; Dits, N F

    2011-01-01

    Prostate cancer (PCa) is the most frequent male malignancy and the second most common cause of cancer-related death in Western countries. Current clinical and pathological methods are limited in the prediction of postoperative outcome. It is becoming increasingly evident that small non-coding RNA...... signatures of 102 fresh-frozen patient samples during PCa progression by miRNA microarrays. Both platforms were cross-validated by quantitative reverse transcriptase-PCR. Besides the altered expression of several miRNAs, our deep sequencing analyses revealed strong differential expression of small nucleolar...... RNAs (snoRNAs) and transfer RNAs (tRNAs). From microarray analysis, we derived a miRNA diagnostic classifier that accurately distinguishes normal from cancer samples. Furthermore, we were able to construct a PCa prognostic predictor that independently forecasts postoperative outcome. Importantly...

  13. Evaluation of Agency Non-Code Layered Pressure Vessels (LPVs). Corrected Copy, Aug. 25, 2014

    Science.gov (United States)

    Prosser, William H.

    2014-01-01

    In coordination with the Office of Safety and Mission Assurance and the respective Center Pressure System Managers (PSMs), the NASA Engineering and Safety Center (NESC) was requested to formulate a consensus draft proposal for the development of additional testing and analysis methods to establish the technical validity, and any limitation thereof, for the continued safe operation of facility non-code layered pressure vessels. The PSMs from each NASA Center were asked to participate as part of the assessment team by providing, collecting, and reviewing data regarding current operations of these vessels. This report contains the outcome of the assessment and the findings, observations, and NESC recommendations to the Agency and individual NASA Centers.

  14. A Looking-Glass of Non-Coding RNAs in Oral Cancer

    Directory of Open Access Journals (Sweden)

    Alexandra Iulia Irimie

    2017-12-01

    Full Text Available Oral cancer is a multifactorial pathology and is characterized by the lack of efficient treatment and accurate diagnostic tools. This is mainly due the late diagnosis; therefore, reliable biomarkers for the timely detection of the disease and patient stratification are required. Non-coding RNAs (ncRNAs are key elements in the physiological and pathological processes of various cancers, which is also reflected in oral cancer development and progression. A better understanding of their role could give a more thorough perspective on the future treatment options for this cancer type. This review offers a glimpse into the ncRNA involvement in oral cancer, which can help the medical community tap into the world of ncRNAs and lay the ground for more powerful diagnostic, prognostic and treatment tools for oral cancer that will ultimately help build a brighter future for these patients.

  15. Heterochromatin Reorganization during Early Mouse Development Requires a Single-Stranded Noncoding Transcript

    Directory of Open Access Journals (Sweden)

    Miguel Casanova

    2013-09-01

    Full Text Available The equalization of pericentric heterochromatin from distinct parental origins following fertilization is essential for genome function and development. The recent implication of noncoding transcripts in this process raises questions regarding the connection between RNA and the nuclear organization of distinct chromatin environments. Our study addresses the interrelationship between replication and transcription of the two parental pericentric heterochromatin (PHC domains and their reorganization during early embryonic development. We demonstrate that the replication of PHC is dispensable for its clustering at the late two-cell stage. In contrast, using parthenogenetic embryos, we show that pericentric transcripts are essential for this reorganization independent of the chromatin marks associated with the PHC domains. Finally, our discovery that only reverse pericentric transcripts are required for both the nuclear reorganization of PHC and development beyond the two-cell stage challenges current views on heterochromatin organization.

  16. Pms2 suppresses large expansions of the (GAA·TTCn sequence in neuronal tissues.

    Directory of Open Access Journals (Sweden)

    Rebecka L Bourn

    Full Text Available Expanded trinucleotide repeat sequences are the cause of several inherited neurodegenerative diseases. Disease pathogenesis is correlated with several features of somatic instability of these sequences, including further large expansions in postmitotic tissues. The presence of somatic expansions in postmitotic tissues is consistent with DNA repair being a major determinant of somatic instability. Indeed, proteins in the mismatch repair (MMR pathway are required for instability of the expanded (CAG·CTG(n sequence, likely via recognition of intrastrand hairpins by MutSβ. It is not clear if or how MMR would affect instability of disease-causing expanded trinucleotide repeat sequences that adopt secondary structures other than hairpins, such as the triplex/R-loop forming (GAA·TTC(n sequence that causes Friedreich ataxia. We analyzed somatic instability in transgenic mice that carry an expanded (GAA·TTC(n sequence in the context of the human FXN locus and lack the individual MMR proteins Msh2, Msh6 or Pms2. The absence of Msh2 or Msh6 resulted in a dramatic reduction in somatic mutations, indicating that mammalian MMR promotes instability of the (GAA·TTC(n sequence via MutSα. The absence of Pms2 resulted in increased accumulation of large expansions in the nervous system (cerebellum, cerebrum, and dorsal root ganglia but not in non-neuronal tissues (heart and kidney, without affecting the prevalence of contractions. Pms2 suppressed large expansions specifically in tissues showing MutSα-dependent somatic instability, suggesting that they may act on the same lesion or structure associated with the expanded (GAA·TTC(n sequence. We conclude that Pms2 specifically suppresses large expansions of a pathogenic trinucleotide repeat sequence in neuronal tissues, possibly acting independently of the canonical MMR pathway.

  17. Pms2 suppresses large expansions of the (GAA·TTC)n sequence in neuronal tissues.

    Science.gov (United States)

    Bourn, Rebecka L; De Biase, Irene; Pinto, Ricardo Mouro; Sandi, Chiranjeevi; Al-Mahdawi, Sahar; Pook, Mark A; Bidichandani, Sanjay I

    2012-01-01

    Expanded trinucleotide repeat sequences are the cause of several inherited neurodegenerative diseases. Disease pathogenesis is correlated with several features of somatic instability of these sequences, including further large expansions in postmitotic tissues. The presence of somatic expansions in postmitotic tissues is consistent with DNA repair being a major determinant of somatic instability. Indeed, proteins in the mismatch repair (MMR) pathway are required for instability of the expanded (CAG·CTG)(n) sequence, likely via recognition of intrastrand hairpins by MutSβ. It is not clear if or how MMR would affect instability of disease-causing expanded trinucleotide repeat sequences that adopt secondary structures other than hairpins, such as the triplex/R-loop forming (GAA·TTC)(n) sequence that causes Friedreich ataxia. We analyzed somatic instability in transgenic mice that carry an expanded (GAA·TTC)(n) sequence in the context of the human FXN locus and lack the individual MMR proteins Msh2, Msh6 or Pms2. The absence of Msh2 or Msh6 resulted in a dramatic reduction in somatic mutations, indicating that mammalian MMR promotes instability of the (GAA·TTC)(n) sequence via MutSα. The absence of Pms2 resulted in increased accumulation of large expansions in the nervous system (cerebellum, cerebrum, and dorsal root ganglia) but not in non-neuronal tissues (heart and kidney), without affecting the prevalence of contractions. Pms2 suppressed large expansions specifically in tissues showing MutSα-dependent somatic instability, suggesting that they may act on the same lesion or structure associated with the expanded (GAA·TTC)(n) sequence. We conclude that Pms2 specifically suppresses large expansions of a pathogenic trinucleotide repeat sequence in neuronal tissues, possibly acting independently of the canonical MMR pathway.

  18. Development of analog watch with minute repeater

    Science.gov (United States)

    Okigami, Tomio; Aoyama, Shigeru; Osa, Takashi; Igarashi, Kiyotaka; Ikegami, Tomomi

    A complementary metal oxide semiconductor with large scale integration was developed for an electronic minute repeater. It is equipped with the synthetic struck sound circuit to generate natural struck sound necessary for the minute repeater. This circuit consists of an envelope curve drawing circuit, frequency mixer, polyphonic mixer, and booster circuit made by using analog circuit technology. This large scale integration is a single chip microcomputer with motor drivers and input ports in addition to the synthetic struck sound circuit, and it is possible to make an electronic system of minute repeater at a very low cost in comparison with the conventional type.

  19. Finnish Higher Education Expansion and Regional Policy

    Science.gov (United States)

    Saarivirta, Toni

    2010-01-01

    This paper concentrates on the expansion of Finnish higher education between the 1960s and 1970s, exposes its background in the light of the policy decisions that were made, compares the unique features of this expansion with those of certain other countries, discusses the impact of the controlled "top down" governance of higher…

  20. The δ expansion for stochastic quantization

    International Nuclear Information System (INIS)

    Bender, C.M.; Cooper, F.; Milton, K.A.; Department of Physics, Brown University, Providence, Rhode Island 02912; Theoretical Division, Los Alamos National Laboratory, Los Alamos, New Mexic o 87545; Department of Physics, The Ohio State University, Columbus, Ohio 43210; Department of Physics and Astronomy, University of Oklahoma, Norman, Oklaho ma 73019)

    1989-01-01

    Using a recently proposed perturbation expansion called the δ expansion, we show how to solve the Langevin equation associated with a gphi 4 field theory. We illustrate the technique in zero- and one-dimensional space-time, and then generalize this approach to d dimensions

  1. The heavy quark expansion of QCD

    International Nuclear Information System (INIS)

    Falk, A.F.

    1997-01-01

    These lectures contain an elementary introduction to heavy quark symmetry and the heavy quark expansion. Applications such as the expansion of heavy meson decay constants and the treatment of inclusive and exclusive semileptonic B decays are included. Heavy hadron production via nonperturbative fragmentation processes is also discussed. 54 refs., 7 figs

  2. The heavy quark expansion of QCD

    Energy Technology Data Exchange (ETDEWEB)

    Falk, A.F. [Johns Hopkins Univ., Baltimore, MD (United States). Dept. of Physics and Astronomy

    1997-06-01

    These lectures contain an elementary introduction to heavy quark symmetry and the heavy quark expansion. Applications such as the expansion of heavy meson decay constants and the treatment of inclusive and exclusive semileptonic B decays are included. Heavy hadron production via nonperturbative fragmentation processes is also discussed. 54 refs., 7 figs.

  3. Thermal expansion of doped lanthanum gallates

    Indian Academy of Sciences (India)

    Administrator

    Since the components are in intimate mechanical contact, any stress generated due to their thermal expansion mis- match during thermal cycling could lead to catastrophic failure of the cell. The functional materials must have similar thermal expansions to avoid mechanical stresses. Hence it is useful to study the thermal ...

  4. Platform Expansion Design as Strategic Choice

    DEFF Research Database (Denmark)

    Staykova, Kalina S.; Damsgaard, Jan

    2016-01-01

    In this paper, we address how the strategic choice of platform expansion design impacts the subse-quent platform strategy. We identify two distinct approaches to platform expansion – platform bun-dling and platform constellations, which currently co-exist. The purpose of this paper is to outline...

  5. Series expansion of the modified Einstein Procedure

    Science.gov (United States)

    Seema Chandrakant Shah-Fairbank

    2009-01-01

    This study examines calculating total sediment discharge based on the Modified Einstein Procedure (MEP). A new procedure based on the Series Expansion of the Modified Einstein Procedure (SEMEP) has been developed. This procedure contains four main modifications to MEP. First, SEMEP solves the Einstein integrals quickly and accurately based on a series expansion. Next,...

  6. Roles of Non-Coding RNA in Sugarcane-Microbe Interaction.

    Science.gov (United States)

    Thiebaut, Flávia; Rojas, Cristian A; Grativol, Clícia; Calixto, Edmundo P da R; Motta, Mariana R; Ballesteros, Helkin G F; Peixoto, Barbara; de Lima, Berenice N S; Vieira, Lucas M; Walter, Maria Emilia; de Armas, Elvismary M; Entenza, Júlio O P; Lifschitz, Sergio; Farinelli, Laurent; Hemerly, Adriana S; Ferreira, Paulo C G

    2017-12-20

    Studies have highlighted the importance of non-coding RNA regulation in plant-microbe interaction. However, the roles of sugarcane microRNAs (miRNAs) in the regulation of disease responses have not been investigated. Firstly, we screened the sRNA transcriptome of sugarcane infected with Acidovorax avenae . Conserved and novel miRNAs were identified. Additionally, small interfering RNAs (siRNAs) were aligned to differentially expressed sequences from the sugarcane transcriptome. Interestingly, many siRNAs aligned to a transcript encoding a copper-transporter gene whose expression was induced in the presence of A. avenae , while the siRNAs were repressed in the presence of A. avenae . Moreover, a long intergenic non-coding RNA was identified as a potential target or decoy of miR408. To extend the bioinformatics analysis, we carried out independent inoculations and the expression patterns of six miRNAs were validated by quantitative reverse transcription-PCR (qRT-PCR). Among these miRNAs, miR408-a copper-microRNA-was downregulated. The cleavage of a putative miR408 target, a laccase, was confirmed by a modified 5'RACE (rapid amplification of cDNA ends) assay. MiR408 was also downregulated in samples infected with other pathogens, but it was upregulated in the presence of a beneficial diazotrophic bacteria. Our results suggest that regulation by miR408 is important in sugarcane sensing whether microorganisms are either pathogenic or beneficial, triggering specific miRNA-mediated regulatory mechanisms accordingly.

  7. Maternally expressed gene 3, an imprinted noncoding RNA gene, is associated with meningioma pathogenesis and progression.

    Science.gov (United States)

    Zhang, Xun; Gejman, Roger; Mahta, Ali; Zhong, Ying; Rice, Kimberley A; Zhou, Yunli; Cheunsuchon, Pornsuk; Louis, David N; Klibanski, Anne

    2010-03-15

    Meningiomas are common tumors, representing 15% to 25% of all central nervous system tumors. NF2 gene inactivation on chromosome 22 has been shown as an early event in tumorigenesis; however, few factors underlying tumor growth and progression have been identified. The chromosomal abnormalities of 14q32 are often associated with meningioma pathogenesis and progression; therefore, it has been proposed that an as yet unidentified tumor suppressor is present at this locus. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 which encodes a noncoding RNA with an antiproliferative function. We found that MEG3 mRNA is highly expressed in normal arachnoidal cells. However, MEG3 is not expressed in the majority of human meningiomas or the human meningioma cell lines IOMM-Lee and CH157-MN. There is a strong association between loss of MEG3 expression and tumor grade. Allelic loss at the MEG3 locus is also observed in meningiomas, with increasing prevalence in higher grade tumors. In addition, there is an increase in CpG methylation within the promoter and the imprinting control region of MEG3 gene in meningiomas. Functionally, MEG3 suppresses DNA synthesis in both IOMM-Lee and CH157-MN cells by approximately 60% in bromodeoxyuridine incorporation assays. Colony-forming efficiency assays show that MEG3 inhibits colony formation in CH157-MN cells by approximately 80%. Furthermore, MEG3 stimulates p53-mediated transactivation in these cell lines. Therefore, these data are consistent with the hypothesis that MEG3, which encodes a noncoding RNA, may be a tumor suppressor gene at chromosome 14q32 involved in meningioma progression via a novel mechanism.

  8. Roles of Non-Coding RNA in Sugarcane-Microbe Interaction

    Science.gov (United States)

    Grativol, Clícia; Motta, Mariana R.; Ballesteros, Helkin G. F.; Peixoto, Barbara; Vieira, Lucas M.; Walter, Maria Emilia; de Armas, Elvismary M.; Entenza, Júlio O. P.; Lifschitz, Sergio; Farinelli, Laurent; Hemerly, Adriana S.

    2017-01-01

    Studies have highlighted the importance of non-coding RNA regulation in plant-microbe interaction. However, the roles of sugarcane microRNAs (miRNAs) in the regulation of disease responses have not been investigated. Firstly, we screened the sRNA transcriptome of sugarcane infected with Acidovorax avenae. Conserved and novel miRNAs were identified. Additionally, small interfering RNAs (siRNAs) were aligned to differentially expressed sequences from the sugarcane transcriptome. Interestingly, many siRNAs aligned to a transcript encoding a copper-transporter gene whose expression was induced in the presence of A. avenae, while the siRNAs were repressed in the presence of A. avenae. Moreover, a long intergenic non-coding RNA was identified as a potential target or decoy of miR408. To extend the bioinformatics analysis, we carried out independent inoculations and the expression patterns of six miRNAs were validated by quantitative reverse transcription-PCR (qRT-PCR). Among these miRNAs, miR408—a copper-microRNA—was downregulated. The cleavage of a putative miR408 target, a laccase, was confirmed by a modified 5′RACE (rapid amplification of cDNA ends) assay. MiR408 was also downregulated in samples infected with other pathogens, but it was upregulated in the presence of a beneficial diazotrophic bacteria. Our results suggest that regulation by miR408 is important in sugarcane sensing whether microorganisms are either pathogenic or beneficial, triggering specific miRNA-mediated regulatory mechanisms accordingly. PMID:29657296

  9. CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC

    International Nuclear Information System (INIS)

    Congrains, Ada; Kamide, Kei; Katsuya, Tomohiro; Yasuda, Osamu; Oguro, Ryousuke; Yamamoto, Koichi; Ohishi, Mitsuru; Rakugi, Hiromi

    2012-01-01

    Highlights: ► ANRIL maps in the strongest susceptibility locus for cardiovascular disease. ► Silencing of ANRIL leads to altered expression of tissue remodeling-related genes. ► The effects of ANRIL on gene expression are splicing variant specific. ► ANRIL affects progression of cardiovascular disease by regulating proliferation and apoptosis pathways. -- Abstract: ANRIL is a newly discovered non-coding RNA lying on the strongest genetic susceptibility locus for cardiovascular disease (CVD) in the chromosome 9p21 region. Genome-wide association studies have been linking polymorphisms in this locus with CVD and several other major diseases such as diabetes and cancer. The role of this non-coding RNA in atherosclerosis progression is still poorly understood. In this study, we investigated the implication of ANRIL in the modulation of gene sets directly involved in atherosclerosis. We designed and tested siRNA sequences to selectively target two exons (exon 1 and exon 19) of the transcript and successfully knocked down expression of ANRIL in human aortic vascular smooth muscle cells (HuAoVSMC). We used a pathway-focused RT-PCR array to profile gene expression changes caused by ANRIL knock down. Notably, the genes affected by each of the siRNAs were different, suggesting that different splicing variants of ANRIL might have distinct roles in cell physiology. Our results suggest that ANRIL splicing variants play a role in coordinating tissue remodeling, by modulating the expression of genes involved in cell proliferation, apoptosis, extra-cellular matrix remodeling and inflammatory response to finally impact in the risk of cardiovascular disease and other pathologies.

  10. Developmental programming of long non-coding RNAs during postnatal liver maturation in mice.

    Directory of Open Access Journals (Sweden)

    Lai Peng

    Full Text Available The liver is a vital organ with critical functions in metabolism, protein synthesis, and immune defense. Most of the liver functions are not mature at birth and many changes happen during postnatal liver development. However, it is unclear what changes occur in liver after birth, at what developmental stages they occur, and how the developmental processes are regulated. Long non-coding RNAs (lncRNAs are involved in organ development and cell differentiation. Here, we analyzed the transcriptome of lncRNAs in mouse liver from perinatal (day -2 to adult (day 60 by RNA-Sequencing, with an attempt to understand the role of lncRNAs in liver maturation. We found around 15,000 genes expressed, including about 2,000 lncRNAs. Most lncRNAs were expressed at a lower level than coding RNAs. Both coding RNAs and lncRNAs displayed three major ontogenic patterns: enriched at neonatal, adolescent, or adult stages. Neighboring coding and non-coding RNAs showed the trend to exhibit highly correlated ontogenic expression patterns. Gene ontology (GO analysis revealed that some lncRNAs enriched at neonatal ages have their neighbor protein coding genes also enriched at neonatal ages and associated with cell proliferation, immune activation related processes, tissue organization pathways, and hematopoiesis; other lncRNAs enriched at adolescent ages have their neighbor protein coding genes associated with different metabolic processes. These data reveal significant functional transition during postnatal liver development and imply the potential importance of lncRNAs in liver maturation.

  11. Roles of Non-Coding RNA in Sugarcane-Microbe Interaction

    Directory of Open Access Journals (Sweden)

    Flávia Thiebaut

    2017-12-01

    Full Text Available Studies have highlighted the importance of non-coding RNA regulation in plant-microbe interaction. However, the roles of sugarcane microRNAs (miRNAs in the regulation of disease responses have not been investigated. Firstly, we screened the sRNA transcriptome of sugarcane infected with Acidovorax avenae. Conserved and novel miRNAs were identified. Additionally, small interfering RNAs (siRNAs were aligned to differentially expressed sequences from the sugarcane transcriptome. Interestingly, many siRNAs aligned to a transcript encoding a copper-transporter gene whose expression was induced in the presence of A. avenae, while the siRNAs were repressed in the presence of A. avenae. Moreover, a long intergenic non-coding RNA was identified as a potential target or decoy of miR408. To extend the bioinformatics analysis, we carried out independent inoculations and the expression patterns of six miRNAs were validated by quantitative reverse transcription-PCR (qRT-PCR. Among these miRNAs, miR408—a copper-microRNA—was downregulated. The cleavage of a putative miR408 target, a laccase, was confirmed by a modified 5′RACE (rapid amplification of cDNA ends assay. MiR408 was also downregulated in samples infected with other pathogens, but it was upregulated in the presence of a beneficial diazotrophic bacteria. Our results suggest that regulation by miR408 is important in sugarcane sensing whether microorganisms are either pathogenic or beneficial, triggering specific miRNA-mediated regulatory mechanisms accordingly.

  12. Long non-coding RNA expression profiling of mouse testis during postnatal development.

    Directory of Open Access Journals (Sweden)

    Jin Sun

    Full Text Available Mammalian testis development and spermatogenesis play critical roles in male fertility and continuation of a species. Previous research into the molecular mechanisms of testis development and spermatogenesis has largely focused on the role of protein-coding genes and small non-coding RNAs, such as microRNAs and piRNAs. Recently, it has become apparent that large numbers of long (>200 nt non-coding RNAs (lncRNAs are transcribed from mammalian genomes and that lncRNAs perform important regulatory functions in various developmental processes. However, the expression of lncRNAs and their biological functions in post-natal testis development remain unknown. In this study, we employed microarray technology to examine lncRNA expression profiles of neonatal (6-day-old and adult (8-week-old mouse testes. We found that 8,265 lncRNAs were expressed above background levels during post-natal testis development, of which 3,025 were differentially expressed. Candidate lncRNAs were identified for further characterization by an integrated examination of genomic context, gene ontology (GO enrichment of their associated protein-coding genes, promoter analysis for epigenetic modification, and evolutionary conservation of elements. Many lncRNAs overlapped or were adjacent to key transcription factors and other genes involved in spermatogenesis, such as Ovol1, Ovol2, Lhx1, Sox3, Sox9, Plzf, c-Kit, Wt1, Sycp2, Prm1 and Prm2. Most differentially expressed lncRNAs exhibited epigenetic modification marks similar to protein-coding genes and tend to be expressed in a tissue-specific manner. In addition, the majority of differentially expressed lncRNAs harbored evolutionary conserved elements. Taken together, our findings represent the first systematic investigation of lncRNA expression in the mammalian testis and provide a solid foundation for further research into the molecular mechanisms of lncRNAs function in mammalian testis development and spermatogenesis.

  13. Non-coding RNAs and plant male sterility: current knowledge and future prospects.

    Science.gov (United States)

    Mishra, Ankita; Bohra, Abhishek

    2018-02-01

    Latest outcomes assign functional role to non-coding (nc) RNA molecules in regulatory networks that confer male sterility to plants. Male sterility in plants offers great opportunity for improving crop performance through application of hybrid technology. In this respect, cytoplasmic male sterility (CMS) and sterility induced by photoperiod (PGMS)/temperature (TGMS) have greatly facilitated development of high-yielding hybrids in crops. Participation of non-coding (nc) RNA molecules in plant reproductive development is increasingly becoming evident. Recent breakthroughs in rice definitively associate ncRNAs with PGMS and TGMS. In case of CMS, the exact mechanism through which the mitochondrial ORFs exert influence on the development of male gametophyte remains obscure in several crops. High-throughput sequencing has enabled genome-wide discovery and validation of these regulatory molecules and their target genes, describing their potential roles performed in relation to CMS. Discovery of ncRNA localized in plant mtDNA with its possible implication in CMS induction is intriguing in this respect. Still, conclusive evidences linking ncRNA with CMS phenotypes are currently unavailable, demanding complementing genetic approaches like transgenics to substantiate the preliminary findings. Here, we review the recent literature on the contribution of ncRNAs in conferring male sterility to plants, with an emphasis on microRNAs. Also, we present a perspective on improved understanding about ncRNA-mediated regulatory pathways that control male sterility in plants. A refined understanding of plant male sterility would strengthen crop hybrid industry to deliver hybrids with improved performance.

  14. CVD-associated non-coding RNA, ANRIL, modulates expression of atherogenic pathways in VSMC

    Energy Technology Data Exchange (ETDEWEB)

    Congrains, Ada; Kamide, Kei [Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine (Japan); Katsuya, Tomohiro [Clinical Gene Therapy, Osaka University Graduate School of Medicine (Japan); Yasuda, Osamu [Department of Cardiovascular Clinical and Translational Research, Kumamoto University Hospital (Japan); Oguro, Ryousuke; Yamamoto, Koichi [Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine (Japan); Ohishi, Mitsuru, E-mail: ohishi@geriat.med.osaka-u.ac.jp [Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine (Japan); Rakugi, Hiromi [Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine (Japan)

    2012-03-23

    Highlights: Black-Right-Pointing-Pointer ANRIL maps in the strongest susceptibility locus for cardiovascular disease. Black-Right-Pointing-Pointer Silencing of ANRIL leads to altered expression of tissue remodeling-related genes. Black-Right-Pointing-Pointer The effects of ANRIL on gene expression are splicing variant specific. Black-Right-Pointing-Pointer ANRIL affects progression of cardiovascular disease by regulating proliferation and apoptosis pathways. -- Abstract: ANRIL is a newly discovered non-coding RNA lying on the strongest genetic susceptibility locus for cardiovascular disease (CVD) in the chromosome 9p21 region. Genome-wide association studies have been linking polymorphisms in this locus with CVD and several other major diseases such as diabetes and cancer. The role of this non-coding RNA in atherosclerosis progression is still poorly understood. In this study, we investigated the implication of ANRIL in the modulation of gene sets directly involved in atherosclerosis. We designed and tested siRNA sequences to selectively target two exons (exon 1 and exon 19) of the transcript and successfully knocked down expression of ANRIL in human aortic vascular smooth muscle cells (HuAoVSMC). We used a pathway-focused RT-PCR array to profile gene expression changes caused by ANRIL knock down. Notably, the genes affected by each of the siRNAs were different, suggesting that different splicing variants of ANRIL might have distinct roles in cell physiology. Our results suggest that ANRIL splicing variants play a role in coordinating tissue remodeling, by modulating the expression of genes involved in cell proliferation, apoptosis, extra-cellular matrix remodeling and inflammatory response to finally impact in the risk of cardiovascular disease and other pathologies.

  15. Lnc2Catlas: an atlas of long noncoding RNAs associated with risk of cancers.

    Science.gov (United States)

    Ren, Chao; An, Gaole; Zhao, Chenghui; Ouyang, Zhangyi; Bo, Xiaochen; Shu, Wenjie

    2018-01-30

    Lnc2Catlas ( http://lnc2catlas.bioinfotech.org/ ) is an atlas of long noncoding RNAs (lncRNAs) associated with cancer risk. LncRNAs are a class of functional noncoding RNAs with lengths over 200 nt and play a vital role in diverse biological processes. Increasing evidence shows that lncRNA dysfunction is associated with many human cancers/diseases. It is therefore important to understand the underlying relationship between lncRNAs and cancers. To this end, we developed Lnc2Catlas to compile quantitative associations between lncRNAs and cancers using three computational methods, assessing secondary structure disruption, lncRNA-protein interactions, and co-expression networks. Lnc2Catlas was constructed based on 27,670 well-annotated lncRNAs, 31,749,216 SNPs, 1,473 cancer-associated proteins, and 10,539 expression profiles of 33 cancers from The Cancer Genome Atlas (TCGA). Lnc2Catlas contains 247,124 lncRNA-SNP pairs, over two millions lncRNA-protein interactions, and 6,902 co-expression clusters. We deposited Lnc2Catlas on Alibaba Cloud and developed interactive, mobile device-compatible, user-friendly interfaces to help users search and browse Lnc2Catlas with ultra-low latency. Lnc2Catlas can aid in the investigation of associations between lncRNAs and cancers and can provide candidate lncRNAs for further experimental validation. Lnc2Catlas will facilitate an understanding of the associations between lncRNAs and cancer and will help reveal the critical role of lncRNAs in cancer.

  16. Maxwell superalgebras and Abelian semigroup expansion

    Directory of Open Access Journals (Sweden)

    P.K. Concha

    2014-09-01

    Full Text Available The Abelian semigroup expansion is a powerful and simple method to derive new Lie algebras from a given one. Recently it was shown that the S-expansion of so(3,2 leads us to the Maxwell algebra M. In this paper we extend this result to superalgebras, by proving that different choices of abelian semigroups S lead to interesting D=4 Maxwell Superalgebras. In particular, the minimal Maxwell superalgebra sM and the N-extended Maxwell superalgebra sM(N recently found by the Maurer–Cartan expansion procedure, are derived alternatively as an S-expansion of osp(4|N. Moreover, we show that new minimal Maxwell superalgebras type sMm+2 and their N-extended generalization can be obtained using the S-expansion procedure.

  17. Use of expansion joints in power stations

    International Nuclear Information System (INIS)

    Birker; Rommerswinkel.

    1976-01-01

    The paper discusses the mode of action of different systems of expansion joints. Special regard is given to the problems of expansion of pipelines of high rated diameter as employed in today's large power plant turbines. Due to the limited space available, the important role of the spring rate of the bellows for the reaction forces and moments acting on the connection points is pointed out. Apart from this details are given on the fabrication and materials selection of expansion joint bellows, and problems are discussed which arise in connection with the mechanical or hydraulic deformation of bellows with one or more walls. The non-destructive methods now in use for the testing of expansion pipe joints are mentioned along with experiments to test their behaviour under changing loads. The paper concludes on some remarks concerning proper transport, storage and installation of expansion pipe joints. (orig./AK) [de

  18. Maxwell superalgebras and Abelian semigroup expansion

    Energy Technology Data Exchange (ETDEWEB)

    Concha, P.K.; Rodríguez, E.K. [Departamento de Física, Universidad de Concepción, Casilla 160-C, Concepción (Chile); Dipartimento di Scienza Applicata e Tecnologia (DISAT), Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129 Torino (Italy); Istituto Nazionale di Fisica Nucleare (INFN), Sezione di Torino, Via Pietro Giuria, 1, 10125 Torino (Italy)

    2014-09-15

    The Abelian semigroup expansion is a powerful and simple method to derive new Lie algebras from a given one. Recently it was shown that the S-expansion of so(3,2) leads us to the Maxwell algebra M. In this paper we extend this result to superalgebras, by proving that different choices of abelian semigroups S lead to interesting D=4 Maxwell Superalgebras. In particular, the minimal Maxwell superalgebra sM and the N-extended Maxwell superalgebra sM{sup (N)} recently found by the Maurer–Cartan expansion procedure, are derived alternatively as an S-expansion of osp(4|N). Moreover, we show that new minimal Maxwell superalgebras type sM{sub m+2} and their N-extended generalization can be obtained using the S-expansion procedure.

  19. Simultaneous sequencing of coding and noncoding RNA reveals a human transcriptome dominated by a small number of highly expressed noncoding genes.

    Science.gov (United States)

    Boivin, Vincent; Deschamps-Francoeur, Gabrielle; Couture, Sonia; Nottingham, Ryan M; Bouchard-Bourelle, Philia; Lambowitz, Alan M; Scott, Michelle S; Abou-Elela, Sherif

    2018-07-01

    Comparing the abundance of one RNA molecule to another is crucial for understanding cellular functions but most sequencing techniques can target only specific subsets of RNA. In this study, we used a new fragmented ribodepleted TGIRT sequencing method that uses a thermostable group II intron reverse transcriptase (TGIRT) to generate a portrait of the human transcriptome depicting the quantitative relationship of all classes of nonribosomal RNA longer than 60 nt. Comparison between different sequencing methods indicated that FRT is more accurate in ranking both mRNA and noncoding RNA than viral reverse transcriptase-based sequencing methods, even those that specifically target these species. Measurements of RNA abundance in different cell lines using this method correlate with biochemical estimates, confirming tRNA as the most abundant nonribosomal RNA biotype. However, the single most abundant transcript is 7SL RNA, a component of the signal recognition particle. S tructured n on c oding RNAs (sncRNAs) associated with the same biological process are expressed at similar levels, with the exception of RNAs with multiple functions like U1 snRNA. In general, sncRNAs forming RNPs are hundreds to thousands of times more abundant than their mRNA counterparts. Surprisingly, only 50 sncRNA genes produce half of the non-rRNA transcripts detected in two different cell lines. Together the results indicate that the human transcriptome is dominated by a small number of highly expressed sncRNAs specializing in functions related to translation and splicing. © 2018 Boivin et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  20. Preventing Repeat Teen Births PSA (:60)

    Centers for Disease Control (CDC) Podcasts

    This 60 second public service announcement is based on the April 2013 CDC Vital Signs report, which discusses repeat teen births and ways teens, parents and guardians, health care providers, and communities can help prevent them.