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Sample records for retrotransposon based molecular

  1. Full Length Research Paper LTR-retrotransposons-based molecular ...

    African Journals Online (AJOL)

    Long terminal repeat (LTR)-retrotransposons are mobile genetic elements that are ubiquitous in plants and constitute a major portion of their nuclear genomes. LTR-retrotransposons possess unique properties that make them appropriate for investigating relationships between closely related species and populations.

  2. Genetic variability in sunflower (Helianthus annuus L.) and in the Helianthus genus as assessed by retrotransposon-based molecular markers.

    Science.gov (United States)

    Vukich, M; Schulman, A H; Giordani, T; Natali, L; Kalendar, R; Cavallini, A

    2009-10-01

    The inter-retrotransposon amplified polymorphism (IRAP) protocol was applied for the first time within the genus Helianthus to assess intraspecific variability based on retrotransposon sequences among 36 wild accessions and 26 cultivars of Helianthus annuus L., and interspecific variability among 39 species of Helianthus. Two groups of LTRs, one belonging to a Copia-like retroelement and the other to a putative retrotransposon of unknown nature (SURE) have been isolated, sequenced and primers were designed to obtain IRAP fingerprints. The number of polymorphic bands in H. annuus wild accessions is as high as in Helianthus species. If we assume that a polymorphic band can be related to a retrotransposon insertion, this result suggests that retrotransposon activity continued after Helianthus speciation. Calculation of similarity indices from binary matrices (Shannon's and Jaccard's indices) show that variability is reduced among domesticated H. annuus. On the contrary, similarity indices among Helianthus species were as large as those observed among wild H. annuus accessions, probably related to their scattered geographic distribution. Principal component analysis of IRAP fingerprints allows the distinction between perennial and annual Helianthus species especially when the SURE element is concerned.

  3. Molecular distribution of gypsy-like retrotransposons in cotton ...

    African Journals Online (AJOL)

    PCR primers specific for conserved domains of the reverse transcriptase (RT) genes of gypsy-like retrotransposons amplified their corresponding gene in two Gossypium barbadense cultivars. Analysis with the FASTA software showed a high DNA sequence homology to pine, gypsy LTR-retrotransposon. Using the PCR ...

  4. Subtracted diversity array identifies novel molecular markers including retrotransposons for fingerprinting Echinacea species.

    Directory of Open Access Journals (Sweden)

    Alexandra Olarte

    Full Text Available Echinacea, native to the Canadian prairies and the prairie states of the United States, has a long tradition as a folk medicine for the Native Americans. Currently, Echinacea are among the top 10 selling herbal medicines in the U.S. and Europe, due to increasing popularity for the treatment of common cold and ability to stimulate the immune system. However, the genetic relationship within the species of this genus is unclear, making the authentication of the species used for the medicinal industry more difficult. We report the construction of a novel Subtracted Diversity Array (SDA for Echinacea species and demonstrate the potential of this array for isolating highly polymorphic sequences. In order to selectively isolate Echinacea-specific sequences, a Suppression Subtractive Hybridization (SSH was performed between a pool of twenty-four Echinacea genotypes and a pool of other angiosperms and non-angiosperms. A total of 283 subtracted genomic DNA (gDNA fragments were amplified and arrayed. Twenty-seven Echinacea genotypes including four that were not used in the array construction could be successfully discriminated. Interestingly, unknown samples of E. paradoxa and E. purpurea could be unambiguously identified from the cluster analysis. Furthermore, this Echinacea-specific SDA was also able to isolate highly polymorphic retrotransposon sequences. Five out of the eleven most discriminatory features matched to known retrotransposons. This is the first time retrotransposon sequences have been used to fingerprint Echinacea, highlighting the potential of retrotransposons as based molecular markers useful for fingerprinting and studying diversity patterns in Echinacea.

  5. Molecular characterization of a transcriptionally active Ty1/copia-like retrotransposon in Gossypium.

    Science.gov (United States)

    Cao, Yuefen; Jiang, Yurong; Ding, Mingquan; He, Shae; Zhang, Hua; Lin, Lifeng; Rong, Junkang

    2015-06-01

    A transcriptionally active Ty1/copia -like retrotransposon was identified in the genome of Gossypium barbadense. The different heat activation of this element was observed in two tetraploid cotton species. Most retrotransposons from plants are transcriptionally silent, or activated under certain conditions. Only a small portion of elements are transcriptionally active under regular condition. A long terminal repeat (LTR) retrotransposon was isolated from the cultivated Sea Island cotton (H7124) genome during the investigation of the function of a homeodomain leucine zipper gene (HD1) in trichome growth. Insertion of this element in HD1 gene of At sub-genome was related to the trichomeless stem in Gossypium barbadense. The element, named as GBRE-1, had all features of a typical Ty1/copia retrotransposon and possessed high similarity to the members of ONSEN retrotransposon family. It was 4997 bp long, comprising a single 4110 bp open reading frame, which encoded 1369 amino acids including the conserved domains of gag and pol. The expression of GBRE-1 was detected under regular condition in G. barbadense and G. hirsutum, and its expression level was increased under heat-stress condition in G. hirsutum. Besides, its expression pattern was similar to that of the ONSEN retrotransposon. Abundant cis-regulatory motifs related to stress-response and transcriptional regulation were found in the LTR sequence. These results suggested that GBRE-1 was a transcriptionally active retrotransposon in Gossypium. To our knowledge, this is the first report of the isolation of a complete Ty1/copia-type retrotransposon with present-day transcriptional activity in cotton.

  6. GENETIC DIVERSITY OF TRITICALE CULTIVARS BASED ON MICROSATELLITE AND RETROTRANSPOSON-BASED MARKERS

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    Želmíra Balážová

    2014-02-01

    Full Text Available The aim of our work was to detect genetic variability in the set of 59 winter and spring triticale (x Triticosecale Witt. varieties using combination of 4 wheat SSR and 4 retrotransposon-based markers. The number of alleles for SSR markers ranged from 8 to 10 with an average number of 8,75 alleles per locus. For IRAP markers the number of alleles ranged from 9 to 10 with an average number of 9,25 alleles per locus Totally, 72 alleles were detected, 37 alleles for IRAP markers and 35 alleles for SSR markers. For the assessment of genetic diversity the dendrogram, based on the hierarchical cluster analysis using UPGMA algorithm was prepared. Fifty nine triticale cultivars were grouped into two major groups. The first group contained all winter triticale varieties and in the second cluster were included all spring triticale varieties. The closest relationship was found out between two Polish winter triticale cultivars, Alekto and Pizarro. Results showed the utility of combination of microsatellite and retrotransposon-based markers for estimation of genetic diversity of triticale genotypes leading to genotype identification.

  7. Molecular structure of yoyo, a gypsy-like retrotransposon from the mediterranean fruit fly, Ceratitis capitata.

    Science.gov (United States)

    Zhou, Q; Haymer, D S

    We have isolated and characterized a new LTR-retrotransposon in the genome of the Mediterranean fruit fly (Medfly), Ceratitis capitata. This retrotransposon, which we named yoyo, appears to be a member of the gypsy/Ty3 class of elements. The yoyo element was originally discovered on the Y chromosome of the Medfly. Although the Y chromosome copy appears to be truncated, at least two other apparently complete copies of yoyo from other genomic locations have been isolated and characterized. The complete element is approximately 7.7 kb in size. In addition to fairly typical GAG and POL coding regions, the yoyo element contains a potential ENV gene. The presence of an ENV gene is a key feature distinguishing potential retroviral-like elements, such as gypsy (and possibly yoyo), from many other invertebrate retrotransposons previously described. In addition to the structural features of yoyo, evidence is provided to show that yoyo is capable of movement in the genome, including RFLPs showing variability in genomic localization of copies of yoyo between strains, and differences among individuals in the presence of yoyo at a specific site in the genome.

  8. Genetic structure of cultivated flax (Linum usitatissimum L. based on retrotransposon-based markers

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    Habibollahi Hadi

    2015-01-01

    Full Text Available Flax (Linum usitatissimum L. is one of the most important fiber and oil crop plants cultivated since ancient time. The flax seeds contain high amount of omega- 3-fatty acids and biologically active lignans. In spite of economic importance of cultivated flax, no information is available on its genetic variability and population structure in Iran. Therefore, we used six inter-retrotransposon amplified polymorphism (IRAP markers and 15 combined IRAP markers to reveal within and among population genetic diversity in this crop plant. We used 30 randomly selected plants in three geographical populations for present investigation. AMOVA test produced significant genetic difference (PhiPT = 0.40, P = 0.010 among the studied populations and also revealed that, 40% of total genetic variability was due to within population diversity while, 60% was due to among population genetic differentiation. Gst (0.78, P = 0.001, Hedrick, standardised fixation index (G'st = 0.83, P = 0.001, revealed that the studied populations are genetically differentiated. STRUCTURE plot based on admixture model revealed that the studied populations differed extensively in their genetic content, but some degree of shared alleles occurred between them. Some adaptive IRAP loci were identified by LFMM analysis. These loci were private alleles restricted to geographical populations. Data obtained may be used in breeding and hybridization program of flax in the country.

  9. MGEScan: a Galaxy-based system for identifying retrotransposons in genomes.

    Science.gov (United States)

    Lee, Hyungro; Lee, Minsu; Mohammed Ismail, Wazim; Rho, Mina; Fox, Geoffrey C; Oh, Sangyoon; Tang, Haixu

    2016-08-15

    : MGEScan-long terminal repeat (LTR) and MGEScan-non-LTR are successfully used programs for identifying LTRs and non-LTR retrotransposons in eukaryotic genome sequences. However, these programs are not supported by easy-to-use interfaces nor well suited for data visualization in general data formats. Here, we present MGEScan, a user-friendly system that combines these two programs with a Galaxy workflow system accelerated with MPI and Python threading on compute clusters. MGEScan and Galaxy empower researchers to identify transposable elements in a graphical user interface with ready-to-use workflows. MGEScan also visualizes the custom annotation tracks for mobile genetic elements in public genome browsers. A maximum speed-up of 3.26× is attained for execution time using concurrent processing and MPI on four virtual cores. MGEScan provides four operational modes: as a command line tool, as a Galaxy Toolshed, on a Galaxy-based web server, and on a virtual cluster on the Amazon cloud. MGEScan tutorials and source code are available at http://mgescan.readthedocs.org/ hatang@indiana.edu or syoh@ajou.ac.kr Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Genetic diversity of cultivated flax (Linum usitatissimum L.) germplasm assessed by retrotransposon-based markers.

    Science.gov (United States)

    Smýkal, P; Bačová-Kerteszová, N; Kalendar, R; Corander, J; Schulman, A H; Pavelek, M

    2011-05-01

    Retrotransposon segments were characterized and inter-retrotransposon amplified polymorphism (IRAP) markers developed for cultivated flax (Linum usitatissimum L.) and the Linum genus. Over 75 distinct long terminal repeat retrotransposon segments were cloned, the first set for Linum, and specific primers designed for them. IRAP was then used to evaluate genetic diversity among 708 accessions of cultivated flax comprising 143 landraces, 387 varieties, and 178 breeding lines. These included both traditional and modern, oil (86), fiber (351), and combined-use (271) accessions, originating from 36 countries, and 10 wild Linum species. The set of 10 most polymorphic primers yielded 141 reproducible informative data points per accession, with 52% polymorphism and a 0.34 Shannon diversity index. The maximal genetic diversity was detected among wild Linum species (100% IRAP polymorphism and 0.57 Jaccard similarity), while diversity within cultivated germplasm decreased from landraces (58%, 0.63) to breeding lines (48%, 0.85) and cultivars (50%, 0.81). Application of Bayesian methods for clustering resulted in the robust identification of 20 clusters of accessions, which were unstratified according to origin or user type. This indicates an overlap in genetic diversity despite disruptive selection for fiber versus oil types. Nevertheless, eight clusters contained high proportions (70-100%) of commercial cultivars, whereas two clusters were rich (60%) in landraces. These findings provide a basis for better flax germplasm management, core collection establishment, and exploration of diversity in breeding, as well as for exploration of the role of retrotransposons in flax genome dynamics.

  11. Development of retrotransposon-based markers IRAP and REMAP for cassava (Manihot esculenta).

    Science.gov (United States)

    Kuhn, B C; Mangolin, C A; Souto, E R; Vicient, C M; Machado, M F P S

    2016-04-07

    Retrotransposons are abundant in the genomes of plants. In the present study, inter-retrotransposon amplified polymorphism (IRAP) and retrotransposon-microsatellite amplified polymorphism (REMAP) markers were developed for the cassava genome (Manihot esculenta Crantz). Four cassava cultivars (Fécula Branca, IPR-União, Olho Junto, and Tamboara, two samples per cultivar) were used to obtain IRAP and REMAP fingerprints. Twelve designed primers were amplified alone and in combinations. The 42 IRAP/REMAP primer combinations amplified 431 DNA segments (bands; markers) of which 36 (8.36%) were polymorphic. The largest number of informative markers (16) was detected using the primers AYF2 and AYF2xAYF4. The number of bands for each primer varied from 3 to 16, with an average of 10.26 amplified segments per primer. The size of the amplified products ranged between 100 and 7000 bp. The AYF2 primer generated the highest number of amplified segments and showed the highest number of polymorphic bands (68.75%). Two samples of each cassava cultivar were used to illustrate the usefulness and the polymorphism of IRAP/REMAP markers. IRAP and REMAP markers produced a high number of reproducible bands, and might be informative and reliable for investigation of genetic diversity and relationships among cassava cultivars.

  12. High-throughput retrotransposon-based fluorescent markers: improved information content and allele discrimination

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    Baker David

    2009-07-01

    Full Text Available Abstract Background Dense genetic maps, together with the efficiency and accuracy of their construction, are integral to genetic studies and marker assisted selection for plant breeding. High-throughput multiplex markers that are robust and reproducible can contribute to both efficiency and accuracy. Multiplex markers are often dominant and so have low information content, this coupled with the pressure to find alternatives to radio-labelling, has led us to adapt the SSAP (sequence specific amplified polymorphism marker method from a 33P labelling procedure to fluorescently tagged markers analysed from an automated ABI 3730 xl platform. This method is illustrated for multiplexed SSAP markers based on retrotransposon insertions of pea and is applicable for the rapid and efficient generation of markers from genomes where repetitive element sequence information is available for primer design. We cross-reference SSAP markers previously generated using the 33P manual PAGE system to fluorescent peaks, and use these high-throughput fluorescent SSAP markers for further genetic studies in Pisum. Results The optimal conditions for the fluorescent-labelling method used a triplex set of primers in the PCR. These included a fluorescently labelled specific primer together with its unlabelled counterpart, plus an adapter-based primer with two bases of selection on the 3' end. The introduction of the unlabelled specific primer helped to optimise the fluorescent signal across the range of fragment sizes expected, and eliminated the need for extensive dilutions of PCR amplicons. The software (GeneMarker Version 1.6 used for the high-throughput data analysis provided an assessment of amplicon size in nucleotides, peak areas and fluorescence intensity in a table format, so providing additional information content for each marker. The method has been tested in a small-scale study with 12 pea accessions resulting in 467 polymorphic fluorescent SSAP markers of which

  13. PwRn1, a novel Ty3/gypsy-like retrotransposon of Paragonimus westermani: molecular characters and its differentially preserved mobile potential according to host chromosomal polyploidy

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    Kong Yoon

    2008-10-01

    Full Text Available Abstract Background Retrotransposons have been known to involve in the remodeling and evolution of host genome. These reverse transcribing elements, which show a complex evolutionary pathway with diverse intermediate forms, have been comprehensively analyzed from a wide range of host genomes, while the information remains limited to only a few species in the phylum Platyhelminthes. Results A LTR retrotransposon and its homologs with a strong phylogenetic affinity toward CsRn1 of Clonorchis sinensis were isolated from a trematode parasite Paragonimus westermani via a degenerate PCR method and from an insect species Anopheles gambiae by in silico analysis of the whole mosquito genome, respectively. These elements, designated PwRn1 and AgCR-1 – AgCR-14 conserved unique features including a t-RNATrp primer binding site and the unusual CHCC signature of Gag proteins. Their flanking LTRs displayed >97% nucleotide identities and thus, these elements were likely to have expanded recently in the trematode and insect genomes. They evolved heterogeneous expression strategies: a single fused ORF, two separate ORFs with an identical reading frame and two ORFs overlapped by -1 frameshifting. Phylogenetic analyses suggested that the elements with the separate ORFs had evolved from an ancestral form(s with the overlapped ORFs. The mobile potential of PwRn1 was likely to be maintained differentially in association with the karyotype of host genomes, as was examined by the presence/absence of intergenomic polymorphism and mRNA transcripts. Conclusion Our results on the structural diversity of CsRn1-like elements can provide a molecular tool to dissect a more detailed evolutionary episode of LTR retrotransposons. The PwRn1-associated genomic polymorphism, which is substantial in diploids, will also be informative in addressing genomic diversification following inter-/intra-specific hybridization in P. westermani populations.

  14. Isolation of two new retrotransposon sequences and development of molecular and cytological markers for Dasypyrum villosum (L.).

    Science.gov (United States)

    Zhang, Jie; Jiang, Yun; Xuan, Pu; Guo, Yuanlin; Deng, Guangbing; Yu, Maoqun; Long, Hai

    2017-10-01

    Dasypyrum villosum is a valuable genetic resource for wheat improvement. With the aim to efficiently monitor the D. villosum chromatin introduced into common wheat, two novel retrotransposon sequences were isolated by RAPD, and were successfully converted to D. villosum-specific SCAR markers. In addition, we constructed a chromosomal karyotype of D. villosum. Our results revealed that different accessions of D. villosum showed slightly different signal patterns, indicating that distribution of repeats did not diverge significantly among D. villosum accessions. The two SCAR markers and FISH karyotype of D. villosum could be used for efficient and precise identification of D. villosum chromatin in wheat breeding.

  15. Retrotransposon-based S-SAP as a platform for the analysis of genetic variation and linkage in globe artichoke

    National Research Council Canada - National Science Library

    Acquadro, Alberto; Portis, Ezio; Moglia, Andrea; Magurno, Franco; Lanteri, Sergio

    2006-01-01

    .... Their activity generates a considerable degree of sequence polymorphism. Here, we report the cloning of CYRE-5, a long-terminal repeat carrying retrotransposon-like sequence in Cynara cardunculus L...

  16. Inter-retrotransposon-amplified polymorphism markers for germplasm characterization in Manihot esculenta (Euphorbiaceae).

    Science.gov (United States)

    Oliveira-Silva, A M; Silva, G F; Dias, M C; Clement, C R; Sousa, N R

    2014-05-16

    Manioc, Manihot esculenta, is economically important in many tropical and subtropical countries. The genetic variability of the species has not been fully explored, and new information may help expand its use. Molecular markers based on retrotransposons have good potential for analysis of genetic diversity given their abundance in the genome. Eight long terminal repeat retrotransposons were selected for the development of inter-retrotransposon-amplified polymorphism markers. To test these primers, we analyzed 32 varieties from Anori, 30 from Manicoré and 10 Mandiocabas from the Manioc Germplasm Bank at Embrapa Western Amazonia. The six informative primer pairs yielded 20- 60 polymorphic bands, averaging 92% polymorphism (51.7-98.4) and 0.37 heterozygosity (0.17 to 0.40), with a Shannon information index of 0.54 (0.26-0.59). These markers can be used to explore the genetic diversity of manioc.

  17. DIRS and Ngaro Retrotransposons in Fungi.

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    Anna Muszewska

    Full Text Available Retrotransposons with a tyrosine recombinase (YR have been discovered recently and lack thorough annotation in fungi. YR retrotransposons are divided into 3 groups: DIRS, Ngaro and VIPER (known only from kinetoplastida. We used comparative genomics to investigate the evolutionary patterns of retrotransposons in the fungal kingdom. The identification of both functional and remnant elements provides a unique view on both recent and past transposition activity. Our searches covering a wide range of fungal genomes allowed us to identify 2241 YR retrotransposons. Based on CLANS clustering of concatenated sequences of the reverse transcriptase (RT, RNase H (RH, DNA N-6-adenine-methyltransferase (MT and YR protein domains we propose a revised classification of YR elements expanded by two new categories of Ngaro elements. A phylogenetic analysis of 477 representatives supports this observation and additionally demonstrates that DIRS and Ngaro abundance changed independently in Basidiomycota and Blastocladiomycota/Mucoromycotina/Kixellomycotina. Interestingly, a single remnant Ngaro element could be identified in an Ascomycota genome. Our analysis revealed also that 3 Pucciniomycotina taxa, known for their overall mobile element abundance and big genome size, encode an elevated number of Ngaro retrotransposons. Considering the presence of DIRS elements in all analyzed Mucoromycotina, Kickxellomycotina and Blastocladiomycota genomes one might assume a common origin of fungal DIRS retrotransposons with a loss in Dicarya. Ngaro elements described to date from Opisthokonta, seem to have invaded the common ancestor of Agaricomycotina and Pucciniomycotina after Ustilagomycotina divergence. Yet, most of analyzed genomes are devoid of YR elements and most identified retrotransposons are incomplete.

  18. Genetic bottlenecks in Turkish okra germplasm and utility of iPBS retrotransposon markers for genetic diversity assessment.

    Science.gov (United States)

    Yıldız, M; Koçak, M; Baloch, F S

    2015-09-08

    Lack of requisite genetic variation in Turkish okra has necessitated the use of different types of markers for estimating the genetic diversity and identifying the source of variation. Transposable elements, present abundantly in plant genomes, generate genomic diversity through their replication and are thus an excellent source of molecular markers. We hypothesized that inter-primer binding site (iPBS)-retrotransposons could be the source of variation because of their genome plasticity nature. In the present study, genetic diversity of 66 okra landraces was analyzed using iPBS-retrotransposon markers. iPBS-retrotransposons detected 88 bands with 40.2% polymorphism and an average of 6.8 bands per primer. Gene diversity and Shannon's information index ranged from 0.01 to 0.13 and 0.02 to 0.21 for iPBS-retrotransposons and from 0.06 to 0.46 and 0.14 to 0.65 for simple sequence repeat (SSR) markers, respectively. Polymorphism information content value for retrotransposons varied between 0.12 and 0.99, while that for SSR was from 0.52 to 0.81. Neighbor joining analysis based on retrotransposons and SSRs divided all the accessions into four clusters; however, SSR markers were more efficient in clustering the landraces based on their origin. Using the STRUCTURE software for determining population structure, and two populations (at the number of hypothetical subpopulations, K = 2) were identified among the landraces. Low genetic diversity in Turkish okra highlights the need for the introduction of plants from countries with greater genetic diversity for these crops. This study also demonstrates the utility and role of iPBS-retrotransposons, a dominant and ubiquitous part of eukaryotic genomes, for diversity studies in okra.

  19. Sequencing the extrachromosomal circular mobilome reveals retrotransposon activity in plants.

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    Sophie Lanciano

    2017-02-01

    Full Text Available Retrotransposons are mobile genetic elements abundant in plant and animal genomes. While efficiently silenced by the epigenetic machinery, they can be reactivated upon stress or during development. Their level of transcription not reflecting their transposition ability, it is thus difficult to evaluate their contribution to the active mobilome. Here we applied a simple methodology based on the high throughput sequencing of extrachromosomal circular DNA (eccDNA forms of active retrotransposons to characterize the repertoire of mobile retrotransposons in plants. This method successfully identified known active retrotransposons in both Arabidopsis and rice material where the epigenome is destabilized. When applying mobilome-seq to developmental stages in wild type rice, we identified PopRice as a highly active retrotransposon producing eccDNA forms in the wild type endosperm. The mobilome-seq strategy opens new routes for the characterization of a yet unexplored fraction of plant genomes.

  20. Molecular analysis of utility of a retrotransposon, p-SINE1-r2 in the Asian wild rice and weedy rice populations.

    Science.gov (United States)

    Prathepha, Preecha

    2009-02-01

    The distribution of a retrotransposon, p-SINE1-r2 located at the waxy locus was analyzed by the PCR assay in the perennial wild rice (Oryza rufipogon) which inhabited in four isolated and six disturbed populations and in the weedy rice population. The level of clonality of the wild rice species was determined in populations subject to level of water supply and another disturbance. The results showed that all four isolated populations carried the genotype (-/-) and (-/+), while three genotypes (-/-), (-/+) and (+/+) was found on the six populations which grown near by rice fields. This finding was strongly supported the idea that the original wild rice populations of O. rufipogon exhibited prominent genotype (-/-) and (-/+) and mainly propagated by vegetative reproduction and the allele (+) which found in the wild rice plant with the genotype (+/+) may originated from gene flow from cultivated rice to wild rice. Weedy rice accessions used in this study showed the three genotypes based on this DNA locus. The distribution of this DNA locus in wild rice and weedy rice populations were deviated from the Hardy-Weinberg equilibrium. The perennial wild rice populations were annually under season drought (March to May of the year in Thailand, Laos and Cambodia), they tended to have small size clones with relatively high clonal diversity (i.e., number of genotypes), except for the population from Cambodia, which carried only the genotype (-/+). Although DNA maker used to detect genetic variation at population levels is too small, but this locus is very sensitive enough to be a useful indicator for genetic variation at the population level.

  1. Characterization of a genome-specific Gypsy-like retrotransposon ...

    Indian Academy of Sciences (India)

    Characterization of a genome-specific Gypsy-like retrotransposon sequence and development of a molecular marker specific for Dasypyrum villosum (L.) Jie Zhang, Hai Long, Zhifen Pan, Junjun Liang, Shuiyang Yu, Guangbing Deng, Maoqun Yu. J. Genet. 92, 103–108. Table 1. Plant materials used in this study. Species.

  2. Retrotransposon vectors for gene delivery in plants

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    Hou Yi

    2010-08-01

    Full Text Available Abstract Background Retrotransposons are abundant components of plant genomes, and although some plant retrotransposons have been used as insertional mutagens, these mobile genetic elements have not been widely exploited for plant genome manipulation. In vertebrates and yeast, retrotransposons and retroviruses are routinely altered to carry additional genes that are copied into complementary (cDNA through reverse transcription. Integration of cDNA results in gene delivery; recombination of cDNA with homologous chromosomal sequences can create targeted gene modifications. Plant retrotransposon-based vectors, therefore, may provide new opportunities for plant genome engineering. Results A retrotransposon vector system was developed for gene delivery in plants based on the Tnt1 element from Nicotiana tabacum. Mini-Tnt1 transfer vectors were constructed that lack coding sequences yet retain the 5' and 3' long terminal repeats (LTRs and adjacent cis sequences required for reverse transcription. The internal coding region of Tnt1 was replaced with a neomycin phosphotransferase gene to monitor replication by reverse transcription. Two different mini-Tnt1 s were developed: one with the native 5' LTR and the other with a chimeric 5' LTR that had the first 233 bp replaced by the CaMV 35 S promoter. After transfer into tobacco protoplasts, both vectors undergo retrotransposition using GAG and POL proteins provided in trans by endogenous Tnt1 elements. The transposition frequencies of mini-Tnt1 vectors are comparable with native Tnt1 elements, and like the native elements, insertion sites are within or near coding sequences. In this paper, we provide evidence that template switching occurs during mini-Tnt1 reverse transcription, indicating that multiple copies of Tnt1 mRNA are packaged into virus-like particles. Conclusions Our data demonstrate that mini-Tnt1 vectors can replicate efficiently in tobacco cells using GAG and POL proteins provided in trans by

  3. High-Resolution NMR Analysis of the Conformations of Native and Base Analog Substituted Retroviral and LTR-Retrotransposon PPT Primers

    Science.gov (United States)

    Yi-Brunozzi, Hye Young; Brinson, Robert G.; Brabazon, Danielle M.; Lener, Daniela; Le Grice, Stuart F.J.; Marino, John P.

    2009-01-01

    Summary A purine-rich region of the plus-strand RNA genome of retroviruses and long terminal repeat (LTR)-containing retrotransposons, known as the polypurine tract (PPT), is resistant to hydrolysis by the RNase H domain of reverse transcriptase (RT) and ultimately serves as a primer for plus-strand DNA synthesis. The mechanisms underlying PPT resistance and selective processing remain largely unknown. Here, two RNA/DNA hybrids derived from the PPTs of HIV-1 and Ty3 were probed using high-resolution NMR for preexisting structural distortions in the absence of RT. The PPTs were selectively modified through base-pair changes or by incorporation of the thymine isostere, 2,4-difluoro-5-methyl-benzene (dF), into the DNA strand. Although both wild-type (WT) and mutated hybrids adopted global A-form-like helical geometries, observed structural perturbations in the base-pair and dF-modified hybrids suggested that the PPT hybrids may function as structurally coupled domains. PMID:18355725

  4. LTR retrotransposons in fungi.

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    Anna Muszewska

    Full Text Available Transposable elements with long terminal direct repeats (LTR TEs are one of the best studied groups of mobile elements. They are ubiquitous elements present in almost all eukaryotic genomes. Their number and state of conservation can be a highlight of genome dynamics. We searched all published fungal genomes for LTR-containing retrotransposons, including both complete, functional elements and remnant copies. We identified a total of over 66,000 elements, all of which belong to the Ty1/Copia or Ty3/Gypsy superfamilies. Most of the detected Gypsy elements represent Chromoviridae, i.e. they carry a chromodomain in the pol ORF. We analyzed our data from a genome-ecology perspective, looking at the abundance of various types of LTR TEs in individual genomes and at the highest-copy element from each genome. The TE content is very variable among the analyzed genomes. Some genomes are very scarce in LTR TEs (8000 elements. The data shows that transposon expansions in fungi usually involve an increase both in the copy number of individual elements and in the number of element types. The majority of the highest-copy TEs from all genomes are Ty3/Gypsy transposons. Phylogenetic analysis of these elements suggests that TE expansions have appeared independently of each other, in distant genomes and at different taxonomical levels. We also analyzed the evolutionary relationships between protein domains encoded by the transposon pol ORF and we found that the protease is the fastest evolving domain whereas reverse transcriptase and RNase H evolve much slower and in correlation with each other.

  5. Repetitive DNA and Plant Domestication: Variation in Copy Number and Proximity to Genes of LTR-Retrotransposons among Wild and Cultivated Sunflower (Helianthus annuus) Genotypes.

    Science.gov (United States)

    Mascagni, Flavia; Barghini, Elena; Giordani, Tommaso; Rieseberg, Loren H; Cavallini, Andrea; Natali, Lucia

    2015-11-24

    The sunflower (Helianthus annuus) genome contains a very large proportion of transposable elements, especially long terminal repeat retrotransposons. However, knowledge on the retrotransposon-related variability within this species is still limited. We used next-generation sequencing (NGS) technologies to perform a quantitative and qualitative survey of intraspecific variation of the retrotransposon fraction of the genome across 15 genotypes--7 wild accessions and 8 cultivars--of H. annuus. By mapping the Illumina reads of the 15 genotypes onto a library of sunflower long terminal repeat retrotransposons, we observed considerable variability in redundancy among genotypes, at both superfamily and family levels. In another analysis, we mapped Illumina paired reads to two sets of sequences, that is, long terminal repeat retrotransposons and protein-encoding sequences, and evaluated the extent of retrotransposon proximity to genes in the sunflower genome by counting the number of paired reads in which one read mapped to a retrotransposon and the other to a gene. Large variability among genotypes was also ascertained for retrotransposon proximity to genes. Both long terminal repeat retrotransposon redundancy and proximity to genes varied among retrotransposon families and also between cultivated and wild genotypes. Such differences are discussed in relation to the possible role of long terminal repeat retrotransposons in the domestication of sunflower. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  6. Forward and reverse genetics: The LORE1 retrotransposon insertion mutants

    DEFF Research Database (Denmark)

    Fukai, Eigo; Malolepszy, Anna; Sandal, Niels Nørgaard

    2014-01-01

    The endogenous Lotus retrotransposon 1 (LORE1) transposes in the germ line of Lotus japonicus plants that carry an active element. This feature of LORE1 has been exploited for generation of a large non-transgenic insertion mutant population, where insertions have been annotated using next......-generation sequencing approaches. The LORE1 mutant lines are freely available and can be ordered online. Endogenous retrotransposons are also active in many other plant species. Based on the methods developed for LORE1 mutagenesis, it should be simple to establish similar systems in other species, once an appropriate...

  7. Nanoplatform-based molecular imaging

    National Research Council Canada - National Science Library

    Chen, Xiaoyuan

    2011-01-01

    "Nanoplathform-Based Molecular Imaging provides rationale for using nanoparticle-based probes for molecular imaging, then discusses general strategies for this underutilized, yet promising, technology...

  8. Exon-trapping mediated by the human retrotransposon SVA.

    Science.gov (United States)

    Hancks, Dustin C; Ewing, Adam D; Chen, Jesse E; Tokunaga, Katsushi; Kazazian, Haig H

    2009-11-01

    Although most human retrotransposons are inactive, both inactive and active retrotransposons drive genome evolution and may influence transcription through various mechanisms. In humans, three retrotransposon families are still active, but one of these, SVA, remains mysterious. Here we report the identification of a new subfamily of SVA, which apparently formed after an alternative splicing event where the first exon of the MAST2 gene spliced into an intronic SVA and subsequently retrotransposed. Additional examples of SVA retrotransposing upstream exons due to splicing into SVA were also identified in other primate genomes. After molecular and computational experiments, we found a number of functional 3' splice sites within many different transcribed SVAs across the human and chimpanzee genomes. Using a minigene splicing construct containing an SVA, we observed splicing in cell culture, along with SVA exonization events that introduced premature termination codons (PTCs). These data imply that an SVA residing within an intron in the same orientation as the gene may alter normal gene transcription either by gene-trapping or by introducing PTCs through exonization, possibly creating differences within and across species.

  9. LTR retrotransposons in rice (Oryza sativa, L.: recent burst amplifications followed by rapid DNA loss

    Directory of Open Access Journals (Sweden)

    Panaud Olivier

    2007-07-01

    Full Text Available Abstract Background LTR retrotransposons are one of the main causes for plant genome size and structure evolution, along with polyploidy. The characterization of their amplification and subsequent elimination of the genomes is therefore a major goal in plant evolutionary genomics. To address the extent and timing of these forces, we performed a detailed analysis of 41 LTR retrotransposon families in rice. Results Using a new method to estimate the insertion date of both truncated and complete copies, we estimated these two forces more accurately than previous studies based on other methods. We show that LTR retrotransposons have undergone bursts of amplification within the past 5 My. These bursts vary both in date and copy number among families, revealing that each family has a particular amplification history. The number of solo LTR varies among families and seems to correlate with LTR size, suggesting that solo LTR formation is a family-dependent process. The deletion rate estimate leads to the prediction that the half-life of LTR retrotransposon sequences evolving neutrally is about 19 My in rice, suggesting that other processes than the formation of small deletions are prevalent in rice DNA removal. Conclusion Our work provides insights into the dynamics of LTR retrotransposons in the rice genome. We show that transposable element families have distinct amplification patterns, and that the turn-over of LTR retrotransposons sequences is rapid in the rice genome.

  10. Evolutionary genomics revealed interkingdom distribution of Tcn1-like chromodomain-containing Gypsy LTR retrotransposons among fungi and plants

    Directory of Open Access Journals (Sweden)

    Blinov Alexander

    2010-04-01

    Full Text Available Abstract Background Chromodomain-containing Gypsy LTR retrotransposons or chromoviruses are widely distributed among eukaryotes and have been found in plants, fungi and vertebrates. The previous comprehensive survey of chromoviruses from mosses (Bryophyta suggested that genomes of non-seed plants contain the clade which is closely related to the retrotransposons from fungi. The origin, distribution and evolutionary history of this clade remained unclear mainly due to the absence of information concerning the diversity and distribution of LTR retrotransposons in other groups of non-seed plants as well as in fungal genomes. Results In present study we preformed in silico analysis of chromodomain-containing LTR retrotransposons in 25 diverse fungi and a number of plant species including spikemoss Selaginella moellendorffii (Lycopodiophyta coupled with an experimental survey of chromodomain-containing Gypsy LTR retrotransposons from diverse non-seed vascular plants (lycophytes, ferns, and horsetails. Our mining of Gypsy LTR retrotransposons in genomic sequences allowed identification of numerous families which have not been described previously in fungi. Two new well-supported clades, Galahad and Mordred, as well as several other previously unknown lineages of chromodomain-containing Gypsy LTR retrotransposons were described based on the results of PCR-mediated survey of LTR retrotransposon fragments from ferns, horsetails and lycophytes. It appeared that one of the clades, namely Tcn1 clade, was present in basidiomycetes and non-seed plants including mosses (Bryophyta and lycophytes (genus Selaginella. Conclusions The interkingdom distribution is not typical for chromodomain-containing LTR retrotransposons clades which are usually very specific for a particular taxonomic group. Tcn1-like LTR retrotransposons from fungi and non-seed plants demonstrated high similarity to each other which can be explained by strong selective constraints and the

  11. Phylogenetic and molecular evolutionary analyses of gypsy group ...

    African Journals Online (AJOL)

    Gypsy group retrotransposons in the Egyptian cotton, Gossypium barbadense, was examined by phylogenetic and molecular evolutionary analyses. DNA sequences of gypsy group retrotransposons in two G. barbadense cultivars revealed that these sequences are heterogeneous and represent two distinct families.

  12. Directed DNA shuffling of retrovirus and retrotransposon integrase protein domains.

    Directory of Open Access Journals (Sweden)

    Xiaojie Qi

    Full Text Available Chimeric proteins are used to study protein domain functions and to recombine protein domains for novel or optimal functions. We used a library of chimeric integrase proteins to study DNA integration specificity. The library was constructed using a directed shuffling method that we adapted from fusion PCR. This method easily and accurately shuffles multiple DNA gene sequences simultaneously at specific base-pair positions, such as protein domain boundaries. It produced all 27 properly-ordered combinations of the amino-terminal, catalytic core, and carboxyl-terminal domains of the integrase gene from human immunodeficiency virus, prototype foamy virus, and Saccharomyces cerevisiae retrotransposon Ty3. Retrotransposons can display dramatic position-specific integration specificity compared to retroviruses. The yeast retrotransposon Ty3 integrase interacts with RNA polymerase III transcription factors to target integration at the transcription initiation site. In vitro assays of the native and chimeric proteins showed that human immunodeficiency virus integrase was active with heterologous substrates, whereas prototype foamy virus and Ty3 integrases were not. This observation was consistent with a lower substrate specificity for human immunodeficiency virus integrase than for other retrovirus integrases. All eight chimeras containing the Ty3 integrase carboxyl-terminal domain, a candidate targeting domain, failed to target strand transfer in the presence of the targeting protein, suggesting that multiple domains of the Ty3 integrase cooperate in this function.

  13. SVA retrotransposons as modulators of gene expression.

    Science.gov (United States)

    Quinn, John P; Bubb, Vivien J

    2014-01-01

    Endogenous mobile genetic elements can give rise to de novo germline or somatic mutations that can have dramatic consequences for genome regulation both local and possibly more globally based on the site of integration. However if we consider them as "normal genetic" components of the reference genome then they are likely to modify local chromatin structure which would have an effect on gene regulation irrelevant of their ability to further transpose. As such they can be treated as any other domain involved in a gene × environment interaction. Similarly their evolutionary appearance in the reference genome would supply a driver for species specific responses/traits. Our recent data would suggest the hominid specific subset of retrotransposons, SINE-VNTR-Alu (SVA), can function as transcriptional regulatory domains both in vivo and in vitro when analyzed in reporter gene constructs. Of particular interest in the SVA element, were the variable number tandem repeat (VNTR) domains which as their name suggests can be polymorphic. We and others have previously shown that VNTRs can be both differential regulators and biomarkers of disease based on the genotype of the repeat. Here, we provide an overview of why polymorphism in the SVA elements, in particular the VNTRs, could alter gene expression patterns that could be mechanistically associated with different traits in evolution or disease progression in humans.

  14. SVA retrotransposons as potential modulators of neuropeptide gene expression.

    Science.gov (United States)

    Gianfrancesco, Olympia; Bubb, Vivien J; Quinn, John P

    2017-08-01

    Many facets of human behaviour are likely to have developed in part due to evolutionary changes in the regulation of neuropeptide and other brain-related genes. This has allowed species-specific expression patterns and unique epigenetic modulation in response to our environment, regulating response not only at the molecular level, but also contributing to differences in behaviour between individuals. As such, genetic variants or epigenetic changes that may alter neuropeptide gene expression are predicted to play a role in behavioural conditions and psychiatric illness. It is therefore of interest to identify regulatory elements that have the potential to drive differential gene expression. Retrotransposons are mobile genetic elements that are known to be drivers of genomic diversity, with the ability to alter expression of nearby genes. In particular, the SINE-VNTR-Alu (SVA) class of retrotransposons is specific to hominids, and its appearance and expansion across the genome has been associated with the evolution of numerous behavioural traits, presumably through their ability to confer unique regulatory properties at the site of their insertion. We review the evidence for SVAs as regulatory elements, exploring how polymorphic variation within these repetitive sequences can drive allele specific gene expression, which would be associated with changes in behaviour and disease risk through the alteration of molecular pathways that are central to healthy brain function. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Retrotransposons and non-protein coding RNAs

    DEFF Research Database (Denmark)

    Mourier, Tobias; Willerslev, Eske

    2009-01-01

    does not merely represent spurious transcription. We review examples of functional RNAs transcribed from retrotransposons, and address the collection of non-protein coding RNAs derived from transposable element sequences, including numerous human microRNAs and the neuronal BC RNAs. Finally, we review...

  16. Creation of a novel telomere-cutting endonuclease based on the EN domain of telomere-specific non-long terminal repeat retrotransposon, TRAS1

    Directory of Open Access Journals (Sweden)

    Yoshitake Kazutoshi

    2010-04-01

    Full Text Available Abstract Background The ends of chromosomes, termed telomeres consist of repetitive DNA. The telomeric sequences shorten with cell division and, when telomeres are critically abbreviated, cells stop proliferating. However, in cancer cells, by the expression of telomerase which elongates telomeres, the cells can continue proliferating. Many approaches for telomere shortening have been pursued in the past, but to our knowledge, cutting telomeres in vivo has not so far been demonstrated. In addition, there is lack of information on the cellular effects of telomere shortening in human cells. Results Here, we created novel chimeric endonucleases to cut telomeres by fusing the endonuclease domain (TRAS1EN of the silkworm's telomere specific non-long terminal repeat retrotransposon TRAS1 to the human telomere-binding protein, TRF1. An in vitro assay demonstrated that the TRAS1EN-TRF1 chimeric endonucleases (T-EN and EN-T cut the human (TTAGGGn repeats specifically. The concentration of TRAS1EN-TRF1 chimeric endonucleases necessary for the cleavage of (TTAGGGn repeats was about 40-fold lower than that of TRAS1EN alone. When TRAS1EN-TRF1 endonucleases were introduced into human U2OS cancer cells using adenovirus vectors, the enzymes localized at telomeres of nuclei, cleaved and shortened the telomeric DNA by double-strand breaks. When human U2OS and HFL-1 fibroblast cells were infected with EN-T recombinant adenovirus, their cellular proliferation was suppressed for about 2 weeks after infection. In contrast, the TRAS1EN mutant (H258A chimeric endonuclease fused with TRF1 (ENmut-T did not show the suppression effect. The EN-T recombinant adenovirus induced telomere shortening in U2OS cells, activated the p53-dependent pathway and caused the senescence associated cellular responses, while the ENmut-T construct did not show such effects. Conclusions A novel TRAS1EN-TRF1 chimeric endonuclease (EN-T cuts the human telomeric repeats (TTAGGGn specifically in

  17. Use of Repetitive Sequences for Molecular and Cytogenetic Characterization of Avena Species from Portugal.

    Science.gov (United States)

    Tomás, Diana; Rodrigues, Joana; Varela, Ana; Veloso, Maria Manuela; Viegas, Wanda; Silva, Manuela

    2016-02-04

    Genomic diversity of Portuguese accessions of Avena species--diploid A. strigosa and hexaploids A. sativa and A. sterilis--was evaluated through molecular and cytological analysis of 45S rDNA, and other repetitive sequences previously studied in cereal species--rye subtelomeric sequence (pSc200) and cereal centromeric sequence (CCS1). Additionally, retrotransposons and microsatellites targeting methodologies--IRAP (inter-retrotransposon amplified polymorphism) and REMAP (retrotransposon-microsatellite amplified polymorphism)--were performed. A very high homology was detected for ribosomal internal transcribed sequences (ITS1 and ITS2) between the species analyzed, although nucleolar organizing regions (NOR) fluorescent in situ hybridization (FISH) analysis revealed distinct number of Nor loci between diploid and hexaploid species. Moreover, morphological diversity, evidenced by FISH signals with different sizes, was observed between distinct accessions within each species. pSc200 sequences were for the first time isolated from Avena species but proven to be highly similar in all genotypes analyzed. The use of primers designed for CCS1 unraveled a sequence homologous to the Ty3/gypsy retrotransposon Cereba, that was mapped to centromeric regions of diploid and hexaploid species, being however restricted to the more related A and D haplomes. Retrotransposon-based methodologies disclosed species- and accessions-specific bands essential for the accurate discrimination of all genotypes studied. Centromeric, IRAP and REMAP profiles therefore allowed accurate assessment of inter and intraspecific variability, demonstrating the potential of these molecular markers on future oat breeding programs.

  18. Use of Repetitive Sequences for Molecular and Cytogenetic Characterization of Avena Species from Portugal

    Science.gov (United States)

    Tomás, Diana; Rodrigues, Joana; Varela, Ana; Veloso, Maria Manuela; Viegas, Wanda; Silva, Manuela

    2016-01-01

    Genomic diversity of Portuguese accessions of Avena species—diploid A. strigosa and hexaploids A. sativa and A. sterilis—was evaluated through molecular and cytological analysis of 45S rDNA, and other repetitive sequences previously studied in cereal species—rye subtelomeric sequence (pSc200) and cereal centromeric sequence (CCS1). Additionally, retrotransposons and microsatellites targeting methodologies—IRAP (inter-retrotransposon amplified polymorphism) and REMAP (retrotransposon-microsatellite amplified polymorphism)—were performed. A very high homology was detected for ribosomal internal transcribed sequences (ITS1 and ITS2) between the species analyzed, although nucleolar organizing regions (NOR) fluorescent in situ hybridization (FISH) analysis revealed distinct number of Nor loci between diploid and hexaploid species. Moreover, morphological diversity, evidenced by FISH signals with different sizes, was observed between distinct accessions within each species. pSc200 sequences were for the first time isolated from Avena species but proven to be highly similar in all genotypes analyzed. The use of primers designed for CCS1 unraveled a sequence homologous to the Ty3/gypsy retrotransposon Cereba, that was mapped to centromeric regions of diploid and hexaploid species, being however restricted to the more related A and D haplomes. Retrotransposon-based methodologies disclosed species- and accessions-specific bands essential for the accurate discrimination of all genotypes studied. Centromeric, IRAP and REMAP profiles therefore allowed accurate assessment of inter and intraspecific variability, demonstrating the potential of these molecular markers on future oat breeding programs. PMID:26861283

  19. Retrotransposon Proliferation Coincident with the Evolution of Dioecy in Asparagus

    Directory of Open Access Journals (Sweden)

    Alex Harkess

    2016-09-01

    Full Text Available Current phylogenetic sampling reveals that dioecy and an XY sex chromosome pair evolved once, or possibly twice, in the genus Asparagus. Although there appear to be some lineage-specific polyploidization events, the base chromosome number of 2n = 2× = 20 is relatively conserved across the Asparagus genus. Regardless, dioecious species tend to have larger genomes than hermaphroditic species. Here, we test whether this genome size expansion in dioecious species is related to a polyploidization and subsequent chromosome fusion, or to retrotransposon proliferation in dioecious species. We first estimate genome sizes, or use published values, for four hermaphrodites and four dioecious species distributed across the phylogeny, and show that dioecious species typically have larger genomes than hermaphroditic species. Utilizing a phylogenomic approach, we find no evidence for ancient polyploidization contributing to increased genome sizes of sampled dioecious species. We do find support for an ancient whole genome duplication (WGD event predating the diversification of the Asparagus genus. Repetitive DNA content of the four hermaphroditic and four dioecious species was characterized based on randomly sampled whole genome shotgun sequencing, and common elements were annotated. Across our broad phylogenetic sampling, Ty-1 Copia retroelements, in particular, have undergone a marked proliferation in dioecious species. In the absence of a detectable WGD event, retrotransposon proliferation is the most likely explanation for the precipitous increase in genome size in dioecious Asparagus species.

  20. Retrotransposon Proliferation Coincident with the Evolution of Dioecy in Asparagus.

    Science.gov (United States)

    Harkess, Alex; Mercati, Francesco; Abbate, Loredana; McKain, Michael; Pires, J Chris; Sala, Tea; Sunseri, Francesco; Falavigna, Agostino; Leebens-Mack, Jim

    2016-09-08

    Current phylogenetic sampling reveals that dioecy and an XY sex chromosome pair evolved once, or possibly twice, in the genus Asparagus Although there appear to be some lineage-specific polyploidization events, the base chromosome number of 2n = 2× = 20 is relatively conserved across the Asparagus genus. Regardless, dioecious species tend to have larger genomes than hermaphroditic species. Here, we test whether this genome size expansion in dioecious species is related to a polyploidization and subsequent chromosome fusion, or to retrotransposon proliferation in dioecious species. We first estimate genome sizes, or use published values, for four hermaphrodites and four dioecious species distributed across the phylogeny, and show that dioecious species typically have larger genomes than hermaphroditic species. Utilizing a phylogenomic approach, we find no evidence for ancient polyploidization contributing to increased genome sizes of sampled dioecious species. We do find support for an ancient whole genome duplication (WGD) event predating the diversification of the Asparagus genus. Repetitive DNA content of the four hermaphroditic and four dioecious species was characterized based on randomly sampled whole genome shotgun sequencing, and common elements were annotated. Across our broad phylogenetic sampling, Ty-1 Copia retroelements, in particular, have undergone a marked proliferation in dioecious species. In the absence of a detectable WGD event, retrotransposon proliferation is the most likely explanation for the precipitous increase in genome size in dioecious Asparagus species. Copyright © 2016 Harkess et al.

  1. Analysis of heterogeneity of Copia-like retrotransposons in the genome of cassava (Manihot esculenta Crantz).

    Science.gov (United States)

    Gbadegesin, Micheal A; Beeching, John R

    2011-12-20

    Retrotransposons are ubiquitous in eukaryotic genomes and now proving to be useful genetic tools for genetic diversity and phylogenetic analyses, especially in plants. In order to assess the diversity of Ty1/Copia-like retrotransposons of cassava, we used PCR primers anchored on the conserved domains of reverse transcriptases (RTs) to amplify cassava Ty1/Copia-like RT. The PCR product was cloned and sequenced. Sequences analysis of the clones revealed the presence of 69 families of Ty1/Copia-like retrotransposon in the genome of cassava. Comparative analyses of the predicted amino acid sequences of these clones with those of other plants showed that retroelements of this class are very heterogeneous in cassava. Cassava is widely grown for its edible roots in the tropical and subtropical regions of the world. Cassava roots, though poor in protein, are rich in starch (makes up about 80% of the dry matter), vitamin C, carotenes, calcium and potassium. It has a great commercial importance as a source of starch and starch based products. Realizing the importance of cassava, it stands out as a crop to benefit from biotechnology development. Heterogeneity of Mecops (Manihot esculenta copia-like Retrotransposons) showed that they may be useful for genetic diversity and phylogenetic analyses of cassava germplasm.

  2. Retrotransposons are specified as DNA replication origins in the gene-poor regions of Arabidopsis heterochromatin.

    Science.gov (United States)

    Vergara, Zaida; Sequeira-Mendes, Joana; Morata, Jordi; Peiró, Ramón; Hénaff, Elizabeth; Costas, Celina; Casacuberta, Josep M; Gutierrez, Crisanto

    2017-08-21

    Genomic stability depends on faithful genome replication. This is achieved by the concerted activity of thousands of DNA replication origins (ORIs) scattered throughout the genome. The DNA and chromatin features determining ORI specification are not presently known. We have generated a high-resolution genome-wide map of 3230 ORIs in cultured Arabidopsis thaliana cells. Here, we focused on defining the features associated with ORIs in heterochromatin. In pericentromeric gene-poor domains ORIs associate almost exclusively with the retrotransposon class of transposable elements (TEs), in particular of the Gypsy family. ORI activity in retrotransposons occurs independently of TE expression and while maintaining high levels of H3K9me2 and H3K27me1, typical marks of repressed heterochromatin. ORI-TEs largely colocalize with chromatin signatures defining GC-rich heterochromatin. Importantly, TEs with active ORIs contain a local GC content higher than the TEs lacking them. Our results lead us to conclude that ORI colocalization with retrotransposons is determined by their transposition mechanism based on transcription, and a specific chromatin landscape. Our detailed analysis of ORIs responsible for heterochromatin replication has implications on the mechanisms of ORI specification in other multicellular organisms in which retrotransposons are major components of heterochromatin and of the entire genome. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Copia and Gypsy retrotransposons activity in sunflower (Helianthus annuus L.)

    Science.gov (United States)

    2009-01-01

    Background Retrotransposons are heterogeneous sequences, widespread in eukaryotic genomes, which refer to the so-called mobile DNA. They resemble retroviruses, both in their structure and for their ability to transpose within the host genome, of which they make up a considerable portion. Copia- and Gypsy-like retrotransposons are the two main classes of retroelements shown to be ubiquitous in plant genomes. Ideally, the retrotransposons life cycle results in the synthesis of a messenger RNA and then self-encoded proteins to process retrotransposon mRNA in double stranded extra-chromosomal cDNA copies which may integrate in new chromosomal locations. Results The RT-PCR and IRAP protocol were applied to detect the presence of Copia and Gypsy retrotransposon transcripts and of new events of integration in unstressed plants of a sunflower (Helianthus annuus L.) selfed line. Results show that in sunflower retrotransposons transcription occurs in all analyzed organs (embryos, leaves, roots, and flowers). In one out of sixty-four individuals analyzed, retrotransposons transcription resulted in the integration of a new element into the genome. Conclusion These results indicate that the retrotransposon life cycle is firmly controlled at a post transcriptional level. A possible silencing mechanism is discussed. PMID:20030800

  4. Mono-allelic retrotransposon insertion addresses epigenetic transcriptional repression in human genome.

    Science.gov (United States)

    Byun, Hyang-Min; Heo, Kyu; Mitchell, Kasey J; Yang, Allen S

    2012-02-02

    Retrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution. Their ability to move within genomes gives retrotransposons to affect genome instability. we examined the polymorphic inserted AluYa5, evolutionary young Alu, in the progesterone receptor gene to determine the effects of Alu insertion on molecular environment. We used mono-allelic inserted cell lines which carry both Alu-present and Alu-absent alleles. To determine the epigenetic change and gene expression, we performed restriction enzyme digestion, Pyrosequencing, and Chromatin Immunoprecipitation. We observed that the polymorphic insertion of evolutionally young Alu causes increasing levels of DNA methylation in the surrounding genomic area and generates inactive histone tail modifications. Consequently the Alu insertion deleteriously inactivates the neighboring gene expression. The mono-allelic Alu insertion cell line clearly showed that polymorphic inserted repetitive elements cause the inactivation of neighboring gene expression, bringing aberrant epigenetic changes.

  5. Nucleic acid based molecular devices.

    Science.gov (United States)

    Krishnan, Yamuna; Simmel, Friedrich C

    2011-03-28

    In biology, nucleic acids are carriers of molecular information: DNA's base sequence stores and imparts genetic instructions, while RNA's sequence plays the role of a messenger and a regulator of gene expression. As biopolymers, nucleic acids also have exciting physicochemical properties, which can be rationally influenced by the base sequence in myriad ways. Consequently, in recent years nucleic acids have also become important building blocks for bottom-up nanotechnology: as molecules for the self-assembly of molecular nanostructures and also as a material for building machinelike nanodevices. In this Review we will cover the most important developments in this growing field of nucleic acid nanodevices. We also provide an overview of the biochemical and biophysical background of this field and the major "historical" influences that shaped its development. Particular emphasis is laid on DNA molecular motors, molecular robotics, molecular information processing, and applications of nucleic acid nanodevices in biology. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. The Influence of LINE-1 and SINE Retrotransposons on Mammalian Genomes.

    Science.gov (United States)

    Richardson, Sandra R; Doucet, Aurélien J; Kopera, Huira C; Moldovan, John B; Garcia-Perez, José Luis; Moran, John V

    2015-04-01

    Transposable elements have had a profound impact on the structure and function of mammalian genomes. The retrotransposon Long INterspersed Element-1 (LINE-1 or L1), by virtue of its replicative mobilization mechanism, comprises ∼17% of the human genome. Although the vast majority of human LINE-1 sequences are inactive molecular fossils, an estimated 80-100 copies per individual retain the ability to mobilize by a process termed retrotransposition. Indeed, LINE-1 is the only active, autonomous retrotransposon in humans and its retrotransposition continues to generate both intra-individual and inter-individual genetic diversity. Here, we briefly review the types of transposable elements that reside in mammalian genomes. We will focus our discussion on LINE-1 retrotransposons and the non-autonomous Short INterspersed Elements (SINEs) that rely on the proteins encoded by LINE-1 for their mobilization. We review cases where LINE-1-mediated retrotransposition events have resulted in genetic disease and discuss how the characterization of these mutagenic insertions led to the identification of retrotransposition-competent LINE-1s in the human and mouse genomes. We then discuss how the integration of molecular genetic, biochemical, and modern genomic technologies have yielded insight into the mechanism of LINE-1 retrotransposition, the impact of LINE-1-mediated retrotransposition events on mammalian genomes, and the host cellular mechanisms that protect the genome from unabated LINE-1-mediated retrotransposition events. Throughout this review, we highlight unanswered questions in LINE-1 biology that provide exciting opportunities for future research. Clearly, much has been learned about LINE-1 and SINE biology since the publication of Mobile DNA II thirteen years ago. Future studies should continue to yield exciting discoveries about how these retrotransposons contribute to genetic diversity in mammalian genomes.

  7. SVA retrotransposons: Evolution and genetic instability.

    Science.gov (United States)

    Hancks, Dustin C; Kazazian, Haig H

    2010-08-01

    SINE-VNTR-Alus (SVA) are non-autonomous hominid specific retrotransposons that are associated with disease in humans. SVAs are evolutionarily young and presumably mobilized by the LINE-1 reverse transcriptase in trans. SVAs are currently active and may impact the host through a variety of mechanisms including insertional mutagenesis, exon shuffling, alternative splicing, and the generation of differentially methylated regions (DMR). Here we review SVA biology, including SVA insertions associated with known diseases. Further, we discuss a model describing the initial formation of SVA and the mechanisms by which SVA may impact the host. Copyright © 2010 Elsevier Ltd. All rights reserved.

  8. Phylogenomic analysis of the L1 retrotransposons in Deuterostomia.

    Science.gov (United States)

    Kordis, Dusan; Lovsin, Nika; Gubensek, Franc

    2006-12-01

    L1 retrotransposons constitute the largest single component of mammalian genomes. In contrast to the single remaining lineage of L1 retrotransposons in mammalian genomes, some teleost fishes contain a highly diverse L1 retrotransposon repertoire. Major evolutionary changes in L1 retrotransposon repertoires have therefore taken place in the land vertebrates (Tetrapoda). The lack of sequence data for L1 retrotransposons in the basal living Tetrapoda lineages prompted an investigation of their distribution and evolution in the genomes of the key tetrapod lineages, amphibians and reptiles, and in lungfishes. In this study, we combined genome database searches with PCR analysis to demonstrate that L1 retrotransposons are present in the genomes of lungfishes, amphibians, and lepidosaurs. Phylogenomic analysis shows that the genomes of Deuterostomia possess three highly divergent groups of L1 retrotransposons, with distinct distribution patterns. The analysis of L1 diversity shows the presence of a very large number of diverse L1 families, each with very low copy numbers, at the time of the origin of tetrapods. During the evolution of synapsids, all but one L1 lineage have been lost. This study establishes that the loss of L1 diversity and explosion in copy numbers occurred in the synapsid ancestors of mammals, and was most probably caused by severe population bottlenecks.

  9. Distribution of Divo in Coffea genomes, a poorly described family of angiosperm LTR-Retrotransposons.

    Science.gov (United States)

    Dupeyron, Mathilde; de Souza, Rogerio Fernandes; Hamon, Perla; de Kochko, Alexandre; Crouzillat, Dominique; Couturon, Emmanuel; Domingues, Douglas Silva; Guyot, Romain

    2017-08-01

    Coffea arabica (the Arabica coffee) is an allotetraploid species originating from a recent hybridization between two diploid species: C. canephora and C. eugenioides. Transposable elements can drive structural and functional variation during the process of hybridization and allopolyploid formation in plants. To learn more about the evolution of the C. arabica genome, we characterized and studied a new Copia LTR-Retrotransposon (LTR-RT) family in diploid and allotetraploid Coffea genomes called Divo. It is a complete and relatively compact LTR-RT element (~5 kb), carrying typical Gag and Pol Copia type domains. Reverse Trancriptase (RT) domain-based phylogeny demonstrated that Divo is a new and well-supported family in the Bianca lineage, but strictly restricted to dicotyledonous species. In C. canephora, Divo is expressed and showed a genomic distribution along gene rich and gene poor regions. The copy number, the molecular estimation of insertion time and the analysis at orthologous locations of insertions in diploid and allotetraploid coffee genomes suggest that Divo underwent a different and recent transposition activity in C. arabica and C. canephora when compared to C. eugenioides. The analysis of this novel LTR-RT family represents an important step toward uncovering the genome structure and evolution of C. arabica allotetraploid genome.

  10. Retrotransposon expression and incorporation of cloned human and mouse retroelements in human spermatozoa.

    Science.gov (United States)

    Lazaros, Leandros; Kitsou, Chrysoula; Kostoulas, Charilaos; Bellou, Sofia; Hatzi, Elissavet; Ladias, Paris; Stefos, Theodoros; Markoula, Sofia; Galani, Vasiliki; Vartholomatos, Georgios; Tzavaras, Theodore; Georgiou, Ioannis

    2017-03-01

    To investigate the expression of long interspersed element (LINE) 1, human endogenous retrovirus (HERV) K10, and short interspersed element-VNTR-Alu element (SVA) retrotransposons in ejaculated human spermatozoa by means of reverse-transcription (RT) polymerase chain reaction (PCR) analysis as well as the potential incorporation of cloned human and mouse active retroelements in human sperm cell genome. Laboratory study. University research laboratories and academic hospital. Normozoospermic and oligozoospermic white men. RT-PCR analysis was performed to confirm the retrotransposon expression in human spermatozoa. Exogenous retroelements were tagged with a plasmid containing a green fluorescence (EGFP) retrotransposition cassette, and the de novo retrotransposition events were tested with the use of PCR, fluorescence-activated cell sorting analysis, and confocal microscopy. Retroelement expression in human spermatozoa, incorporation of cloned human and mouse active retroelements in human sperm genome, and de novo retrotransposition events in human spermatozoa. RT-PCR products of expressed human LINE-1, HERV-K10, and SVA retrotransposons were observed in ejaculated human sperm samples. The incubation of human spermatozoa with either retrotransposition-active human LINE-1 and HERV-K10 or mouse reverse transcriptase-deficient VL30 retrotransposons tagged with an EGFP-based retrotransposition cassette led to EGFP-positive spermatozo; 16.67% of the samples were positive for retrotransposition. The respective retrotransposition frequencies for the LINE-1, HERV-K10, and VL30 retrotransposons in the positive samples were 0.34 ± 0.13%, 0.37 ± 0.17%, and 0.30 ± 0.14% per sample of 10,000 spermatozoa. Our results show that: 1) LINE-1, HERV-K10, and SVA retrotransposons are transcriptionally expressed in human spermatozoa; 2) cloned active retroelements of human and mammalian origin can be incorporated in human sperm genome; 3) active reverse transcriptases exist in human

  11. Highly heterogeneous Ty3/Gypsy -like retrotransposon sequences ...

    African Journals Online (AJOL)

    like), sequences to be highly heterogeneous. Some Megyps clustered with other plants' Ty3/Gypsy-like retrotransposons, while some clustered with Gypsy of Drosophila melanogaster and Ty3-2 of Saccharomyces cerevisiae in the comparative ...

  12. SIRE1 RETROTRANSPOSONS IN BARLEY (Hordeum vulgare L.).

    Science.gov (United States)

    Cakmak, B; Marakli, S; Gozukirmizi, N

    2015-07-01

    Sireviruses are genera of copia LTR retrotransposons with a unique genome structure among retrotransposons. Barley (Hordeum vulgare L.) is an economically important plant. In this study, we used mature barley embryos, 10-day-old roots and 10-day-old leaves derived from the same barley plant to investigate SIRE) retrotransposon movements by Inter-Retrotransposon Amplified Polymorphism (IRAP) technique. We found polymorphism rates between 0-64% among embryos, roots and leaves. Polymorphism rates were detected to be 0-27% among embryos, 8-60% among roots, and 11-50% among leaves. Polymorphisms were observed not only among the parts of different individuals, but also on the parts of the same plant (23-64%). The internal domains of SIRE1 (GAG, ENV and RT) were also analyzed in the embryos, roots and leaves. Analysis of band profiles showed no polymorphism for GAG, however, different band patterns were observed among samples for RT and ENV. The sequencing of SIRE1 GAG, ENV and RT domains revealed 79% similarity for GAG, 96% for ENV and 83% for RT to copia retrotransposons. Comparison between barley retrotransposons and SIRE1 in barley indicated that SIRE1-GAG, ENV and RT might be diverge earlier from barley retrotransposons. SIRE1 sequences were compared with SIRE1 in barley, results showed the closest homologues were SIRE1-ENVand SIRE1-RTsequences, and SIRE1-GAG sequences was a sister group to sequences of Glycine max. This study is the first detailed investigation of SIRE1 in barley genome. The obtained findings are expected to contribute to the comprehension of SIRE1 retrotransposon and its role in barley genome.

  13. Two novel Ty1-copia retrotransposons isolated from coffee trees can effectively reveal evolutionary relationships in the Coffea genus (Rubiaceae).

    Science.gov (United States)

    Hamon, Perla; Duroy, Pierre-Olivier; Dubreuil-Tranchant, Christine; Mafra D'Almeida Costa, Paulo; Duret, Caroline; Razafinarivo, Norosoa J; Couturon, Emmanuel; Hamon, Serge; de Kochko, Alexandre; Poncet, Valérie; Guyot, Romain

    2011-06-01

    In the study, we developed new markers for phylogenetic relationships and intraspecies differentiation in Coffea. Nana and Divo, two novel Ty1-copia LTR-retrotransposon families, were isolated through C. canephora BAC clone sequencing. Nana- and Divo-based markers were used to test their: (1) ability to resolve recent phylogenetic relationships; (2) efficiency in detecting intra-species differentiation. Sequence-specific amplification polymorphism (SSAP), retrotransposon-microsatellite amplified polymorphism (REMAP) and retrotransposon-based insertion polymorphism (RBIP) approaches were applied to 182 accessions (31 Coffea species and one Psilanthus accession). Nana- and Divo-based markers revealed contrasted transpositional histories. At the BAC clone locus, RBIP results on C. canephora demonstrated that Nana insertion took place prior to C. canephora differentiation, while Divo insertion occurred after differentiation. Combined SSAP and REMAP data showed that Nana could resolve Coffea lineages, while Divo was efficient at a lower taxonomic level. The combined results indicated that the retrotransposon-based markers were useful in highlighting Coffea genetic diversity and the chronological pattern of speciation/differentiation events. Ongoing complete sequencing of the C. canephora genome will soon enable exhaustive identification of LTR-RTN families, as well as more precise in-depth analyses on contributions to genome size variation and Coffea evolution.

  14. LINE-1 retrotransposons and Let-7 miRNA: partners in the pathogenesis of cancer?

    Directory of Open Access Journals (Sweden)

    Stephen eOhms

    2014-10-01

    Full Text Available LINE-1 retrotransposons are insertional mutagens capable of altering the genomic landscape in many ways. Activation of the normally silent LINE-1 retrotransposon is associated with a high level of cancer-associated DNA damage and genomic instability. Studies of LINE-1 have so far focused mainly on changes in gene expression, and our knowledge of its impact on functional noncoding RNAs is in its infancy. However, current evidence suggests that a significant number of human miRNAs originate from retrotransposon sequences. Furthermore, LINE-1 is generally not expressed in normal tissues while its expression is widespread in epithelial cancers. Based on our recent studies, we demonstrate a functional link between aberrant LINE-1 expression and deregulation of let-7 miRNA expression. Since the expression of let-7 is modulated by LINE-1 activity, we discuss possible mechanisms for this effect and how the silencing of LINE-1 activation could provide new therapeutic options for cancer treatment. Based on the deep sequencing of small RNAs in parallel with gene expression profiling in breast cancer cells, we have identified potential pathways linking L1 activity to let-7 processing and maturation and ultimately to the control of stemness in

  15. Host factors that promote retrotransposon integration are similar in distantly related eukaryotes.

    Directory of Open Access Journals (Sweden)

    Sudhir Kumar Rai

    2017-12-01

    Full Text Available Retroviruses and Long Terminal Repeat (LTR-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements.

  16. Host factors that promote retrotransposon integration are similar in distantly related eukaryotes.

    Science.gov (United States)

    Rai, Sudhir Kumar; Sangesland, Maya; Lee, Michael; Esnault, Caroline; Cui, Yujin; Chatterjee, Atreyi Ghatak; Levin, Henry L

    2017-12-01

    Retroviruses and Long Terminal Repeat (LTR)-retrotransposons have distinct patterns of integration sites. The oncogenic potential of retrovirus-based vectors used in gene therapy is dependent on the selection of integration sites associated with promoters. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is studied as a model for oncogenic retroviruses because it integrates into the promoters of stress response genes. Although integrases (INs) encoded by retroviruses and LTR-retrotransposons are responsible for catalyzing the insertion of cDNA into the host genome, it is thought that distinct host factors are required for the efficiency and specificity of integration. We tested this hypothesis with a genome-wide screen of host factors that promote Tf1 integration. By combining an assay for transposition with a genetic assay that measures cDNA recombination we could identify factors that contribute differentially to integration. We utilized this assay to test a collection of 3,004 S. pombe strains with single gene deletions. Using these screens and immunoblot measures of Tf1 proteins, we identified a total of 61 genes that promote integration. The candidate integration factors participate in a range of processes including nuclear transport, transcription, mRNA processing, vesicle transport, chromatin structure and DNA repair. Two candidates, Rhp18 and the NineTeen complex were tested in two-hybrid assays and were found to interact with Tf1 IN. Surprisingly, a number of pathways we identified were found previously to promote integration of the LTR-retrotransposons Ty1 and Ty3 in Saccharomyces cerevisiae, indicating the contribution of host factors to integration are common in distantly related organisms. The DNA repair factors are of particular interest because they may identify the pathways that repair the single stranded gaps flanking the sites of strand transfer following integration of LTR retroelements.

  17. Different histories of two highly variable LTR retrotransposons in sunflower species.

    Science.gov (United States)

    Mascagni, Flavia; Cavallini, Andrea; Giordani, Tommaso; Natali, Lucia

    2017-11-15

    In the Helianthus genus, very large intra- and interspecific variability related to two specific retrotransposons of Helianthus annuus (Helicopia and SURE) exists. When comparing these two sequences to sunflower sequence databases recently produced by our lab, the Helicopia family was shown to belong to the Maximus/SIRE lineage of the Sirevirus genus of the Copia superfamily, whereas the SURE element (whose superfamily was not even previously identified) was classified as a Gypsy element of the Ogre/Tat lineage of the Metavirus genus. Bioinformatic analysis of the two retrotransposon families revealed their genomic abundance and relative proliferation timing. The genomic abundance of these families differed significantly among 12 Helianthus species. The ratio between the abundance of long terminal repeats and their reverse transcriptases suggested that the SURE family has relatively more solo long terminal repeats than does Helicopia. Pairwise comparisons of Illumina reads encoding the reverse transcriptase domain indicated that SURE amplification may have occurred more recently than that of Helicopia. Finally, the analysis of population structure based on the SURE and Helicopia polymorphisms of 32 Helianthus species evidenced two subpopulations, which roughly corresponded to species of the Helianthus and Divaricati/Ciliares sections. However, a number of species showed an admixed structure, confirming the importance of interspecific hybridisation in the evolution of this genus. In general, these two retrotransposon families differentially contributed to interspecific variability, emphasising the need to refer to specific families when studying genome evolution. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. A detailed linkage map of lettuce based on SSAP, AFLP and NBS markers

    NARCIS (Netherlands)

    Syed, H.; Sorensen, A.P.; Antonise, R.; van de Wiel, C.; van der Linden, C.G.; van 't Westende, W.; Hooftman, D.A.P.; den Nijs, J.C.M.; Flavell, A.J.

    2006-01-01

    Abstract Molecular markers based upon a novel lettuce LTR retrotransposon and the nucleotide binding site-leucine-rich repeat (NBS-LRR) family of disease resistance-associated genes have been combined with AFLP markers to generate a 458 locus genetic linkage map for lettuce. A total of 187

  19. A detailed linkage map of lettuce based on SSAP, AFLP and NBS markers

    NARCIS (Netherlands)

    Syed, N.; Sorensen, A.P.; Antonise, R.; Wiel, van de C.C.M.; Linden, van der C.G.; Westende, van 't W.P.C.; Hooftman, D.A.P.; Nijs, den H.C.M.; Flavell, A.

    2006-01-01

    Molecular markers based upon a novel lettuce LTR retrotransposon and the nucleotide binding site-leucine-rich repeat (NBS-LRR) family of disease resistance-associated genes have been combined with AFLP markers to generate a 458 locus genetic linkage map for lettuce. A total of 187

  20. Retrotransposons Mimic Germ Plasm Determinants to Promote Transgenerational Inheritance.

    Science.gov (United States)

    Tiwari, Bhavana; Kurtz, Paula; Jones, Amanda E; Wylie, Annika; Amatruda, James F; Boggupalli, Devi Prasad; Gonsalvez, Graydon B; Abrams, John M

    2017-10-09

    Retrotransposons are a pervasive class of mobile elements present in the genomes of virtually all forms of life [1, 2]. In metazoans, these are preferentially active in the germline, which, in turn, mounts defenses that restrain their activity [3, 4]. Here we report that certain classes of retrotransposons ensure transgenerational inheritance by invading presumptive germ cells before they are formed. Using sensitized Drosophila and zebrafish models, we found that diverse classes of retrotransposons migrate to the germ plasm, a specialized region of the oocyte that prefigures germ cells and specifies the germline of descendants in the fertilized egg. In Drosophila, we found evidence for a "stowaway" model, whereby Tahre retroelements traffic to the germ plasm by mimicking oskar RNAs and engaging the Staufen-dependent active transport machinery. Consistent with this, germ plasm determinants attracted retroelement RNAs even when these components were ectopically positioned in bipolar oocytes. Likewise, vertebrate retrotransposons similarly migrated to the germ plasm in zebrafish oocytes. Together, these results suggest that germ plasm targeting represents a fitness strategy adopted by some retrotransposons to ensure transgenerational propagation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Cassandra retrotransposons carry independently transcribed 5S RNA

    Science.gov (United States)

    Kalendar, Ruslan; Tanskanen, Jaakko; Chang, Wei; Antonius, Kristiina; Sela, Hanan; Peleg, Ofer; Schulman, Alan H.

    2008-01-01

    We report a group of TRIMs (terminal-repeat retrotransposons in miniature), which are small nonautonomous retrotransposons. These elements, named Cassandra, universally carry conserved 5S RNA sequences and associated RNA polymerase (pol) III promoters and terminators in their long terminal repeats (LTRs). They were found in all vascular plants investigated. Uniquely for LTR retrotransposons, Cassandra produces noncapped, polyadenylated transcripts from the 5S pol III promoter. Capped, read-through transcripts containing Cassandra sequences can also be detected in RNA and in EST databases. The predicted Cassandra RNA 5S secondary structures resemble those for cellular 5S rRNA, with high information content specifically in the pol III promoter region. Genic integration sites are common for Cassandra, an unusual feature for abundant retrotransposons. The 5S in each LTR produces a tandem 5S arrangement with an inter-5S spacing resembling that of cellular 5S. The distribution of 5S genes is very variable in flowering plants and may be partially explained by Cassandra activity. Cassandra thus appears both to have adapted a ubiquitous cellular gene for ribosomal RNA for use as a promoter and to parasitize an as-yet-unidentified group of retrotransposons for the proteins needed in its lifecycle. PMID:18408163

  2. CR1 clade of non-LTR retrotransposons from Maculinea butterflies (Lepidoptera: Lycaenidae: evidence for recent horizontal transmission

    Directory of Open Access Journals (Sweden)

    Blinov Alexander

    2007-06-01

    reasonable alternative explanation is horizontal transfer. In addition, phylogenetic markers for population analysis of Maculinea could be developed based on the described non-LTR retrotransposons.

  3. [Molecular bases of prion diseases].

    Science.gov (United States)

    Pokrovskiĭ, V I; Kiselev, O I

    1998-01-01

    The paper briefly analyzes the origin of priones and their association with the cellular gene and homologous protein of diseases in man and animals. There is evidence for a direct relationship of the agents that cause spongious encephalitis in the cattle and a new type of Creutzfeldt-Jacob disease in man. The molecular organization of priones and the conformational cellular protein changes underlying the infectious activation of the cell homologue of priones. Emphasis is first laid on the capacity of the cell homologue of priones and their infectiously active derivative to bind to DNA or RNA. In the context of concepts of the priones yeasts an attempt was made to explain the reproduction through the altered control of translation of mRNA that encodes the cellular homologue of priones, which accounts for the duration of the incubation period of the disease. The infections caused by priones are referred to as the so-called slow infections. But in the context of the proposed hypothesis, an infective process in the tissues did not really have some typical signs of infection and resembles accumulation diseases more without the replicative burst typical of infectious processes. The paper gives data on the vital cycle of priones in infected animals and changes in the accumulation of an infective agent. This assesses the currently available diagnostic methods and gives preference to the methods which will be based on the use of monoclonal antibodies that specifically recognize the conformationally altered form of an infectious prione or on the identification of primary oligomeric forms which manifest the onset of amyloidization of the damaged tissues. The main conclusion of the paper is that protein prionization is a common biological phenomenon and the diseases caused by these processes will increase in number in the near future, which makes it necessary to develop diagnostic methods and universal treatments of diseases, such as bacterial infections by using antibiotics.

  4. The Microprocessor controls the activity of mammalian retrotransposons

    DEFF Research Database (Denmark)

    Heras, Sara R.; Macias, Sara; Plass, Mireya

    2013-01-01

    More than half of the human genome is made of transposable elements whose ongoing mobilization is a driving force in genetic diversity; however, little is known about how the host regulates their activity. Here, we show that the Microprocessor (Drosha-DGCR8), which is required for microRNA biogen......More than half of the human genome is made of transposable elements whose ongoing mobilization is a driving force in genetic diversity; however, little is known about how the host regulates their activity. Here, we show that the Microprocessor (Drosha-DGCR8), which is required for micro......RNA biogenesis, also recognizes and binds RNAs derived from human long interspersed element 1 (LINE-1), Alu and SVA retrotransposons. Expression analyses demonstrate that cells lacking a functional Microprocessor accumulate LINE-1 mRNA and encoded proteins. Furthermore, we show that structured regions...... of the LINE-1 mRNA can be cleaved in vitro by Drosha. Additionally, we used a cell culture-based assay to show that the Microprocessor negatively regulates LINE-1 and Alu retrotransposition in vivo. Altogether, these data reveal a new role for the Microprocessor as a post-transcriptional repressor...

  5. Bases moleculares de las leucemias agudas

    Directory of Open Access Journals (Sweden)

    G. Martínez Antuña

    2006-04-01

    Full Text Available El gran desarrollo de la biología molecular en los últimos años ha contribuido a un importante avance en los conocimientos relacionados con las bases moleculares de las leucemias agudas (LA. Ademas de profundizar en la biología de estas enfermedades y conocer las bases moleculares, ha renido también gran impacto en mejorar el resultado de los tratamientos y disminuir la toxicidad de las terapias.

  6. LTR-retrotransposons in plants: Engines of evolution.

    Science.gov (United States)

    Galindo-González, Leonardo; Mhiri, Corinne; Deyholos, Michael K; Grandbastien, Marie-Angèle

    2017-08-30

    LTR retrotransposons are the most abundant group of transposable elements (TEs) in plants. These elements can fall inside or close to genes, and therefore influence their expression and evolution. This review aims to examine how LTR retrotransposons, especially Ty1-copia elements, mediate gene regulation and evolution. Various stimuli, including polyploidization and biotic and abiotic elicitors, result in the transcription and movement of these retrotransposons, and can facilitate adaptation. The presence of cis-regulatory motifs in the LTRs are central to their stress-mediated responses and are shared with host stress-responsive genes, showing a complex evolutionary history in which TEs provide new regulatory units to genes. The presence of retrotransposon remnants in genes that are necessary for normal gene function, demonstrates the importance of exaptation and co-option, and is also a consequence of the abundance of these elements in plant genomes. Furthermore, insertions of LTR retrotransposons in and around genes provide potential for alternative splicing, epigenetic control, transduction, duplication and recombination. These characteristics can become an active part of the evolution of gene families as in the case of resistance genes (R-genes). The character of TEs as exclusively selfish is now being re-evaluated. Since genome-wide reprogramming via TEs is a long evolutionary process, the changes we can examine are case-specific and their fitness advantage may not be evident until TE-derived motifs and domains have been completely co-opted and fixed. Nevertheless, the presence of LTR retrotransposons inside genes and as part of gene promoter regions is consistent with their roles as engines of plant genome evolution. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. GIN transposons: genetic elements linking retrotransposons and genes.

    Science.gov (United States)

    Marín, Ignacio

    2010-08-01

    In a previous work, we characterized a gene, called Gypsy Integrase 1 (GIN1), which encodes a protein very similar to the integrase domains present in Gypsy/Ty3 retrotransposons. I describe here a paralog of GIN1 and GIN2 and show that both genes are present in multiple vertebrates and that a likely homolog is found in urochordates. Surprisingly, phylogenetic and structural analyses support the counterintuitive idea that the GIN genes did not directly derive from retrotransposons but from a novel type of animal-specific DNA transposons, the GIN elements. These elements, described for the first time in this study, are characterized by containing a gene that encodes a protein that is also very similar to Gypsy/Ty3 integrases. It turns out that the sequences of the integrases encoded by GIN1 and GIN2 are more similar to those found in GIN elements than to those detected in retrotransposons. Moreover, several introns are in the same positions in the integrase-encoding genes of some GIN elements, GIN1 and GIN2. The simplest explanation for these results is that GIN elements appeared early in animal evolution by co-option of the integrase of a retrotransposon, they later expanded in multiple animal lineages, and, eventually, gave rise to the GIN genes. In summary, GIN transposons may be the "missing link" that explain how GIN genes evolved from retrotransposons. GIN1 and GIN2 may have contributed to control the expansion of GIN elements and Gypsy/Ty3 retrotransposons in chordates.

  8. Modeling the amplification dynamics of human alu retrotransposons.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available Retrotransposons have had a considerable impact on the overall architecture of the human genome. Currently, there are three lineages of retrotransposons (Alu, L1, and SVA that are believed to be actively replicating in humans. While estimates of their copy number, sequence diversity, and levels of insertion polymorphism can readily be obtained from existing genomic sequence data and population sampling, a detailed understanding of the temporal pattern of retrotransposon amplification remains elusive. Here we pose the question of whether, using genomic sequence and population frequency data from extant taxa, one can adequately reconstruct historical amplification patterns. To this end, we developed a computer simulation that incorporates several known aspects of primate Alu retrotransposon biology and accommodates sampling effects resulting from the methods by which mobile elements are typically discovered and characterized. By modeling a number of amplification scenarios and comparing simulation-generated expectations to empirical data gathered from existing Alu subfamilies, we were able to statistically reject a number of amplification scenarios for individual subfamilies, including that of a rapid expansion or explosion of Alu amplification at the time of human-chimpanzee divergence.

  9. Modeling the amplification dynamics of human Alu retrotransposons.

    Directory of Open Access Journals (Sweden)

    Dale J Hedges

    2005-09-01

    Full Text Available Retrotransposons have had a considerable impact on the overall architecture of the human genome. Currently, there are three lineages of retrotransposons (Alu, L1, and SVA that are believed to be actively replicating in humans. While estimates of their copy number, sequence diversity, and levels of insertion polymorphism can readily be obtained from existing genomic sequence data and population sampling, a detailed understanding of the temporal pattern of retrotransposon amplification remains elusive. Here we pose the question of whether, using genomic sequence and population frequency data from extant taxa, one can adequately reconstruct historical amplification patterns. To this end, we developed a computer simulation that incorporates several known aspects of primate Alu retrotransposon biology and accommodates sampling effects resulting from the methods by which mobile elements are typically discovered and characterized. By modeling a number of amplification scenarios and comparing simulation-generated expectations to empirical data gathered from existing Alu subfamilies, we were able to statistically reject a number of amplification scenarios for individual subfamilies, including that of a rapid expansion or explosion of Alu amplification at the time of human-chimpanzee divergence.

  10. BARE retrotransposons are translated and replicated via distinct RNA pools.

    Directory of Open Access Journals (Sweden)

    Wei Chang

    Full Text Available The replication of Long Terminal Repeat (LTR retrotransposons, which can constitute over 80% of higher plant genomes, resembles that of retroviruses. A major question for retrotransposons and retroviruses is how the two conflicting roles of their transcripts, in translation and reverse transcription, are balanced. Here, we show that the BARE retrotransposon, despite its organization into just one open reading frame, produces three distinct classes of transcripts. One is capped, polyadenylated, and translated, but cannot be copied into cDNA. The second is not capped or polyadenylated, but is destined for packaging and ultimate reverse transcription. The third class is capped, polyadenylated, and spliced to favor production of a subgenomic RNA encoding only Gag, the protein forming virus-like particles. Moreover, the BARE2 subfamily, which cannot synthesize Gag and is parasitic on BARE1, does not produce the spliced sub-genomic RNA for translation but does make the replication competent transcripts, which are packaged into BARE1 particles. To our knowledge, this is first demonstration of distinct RNA pools for translation and transcription for any retrotransposon.

  11. Polymerase chain reaction (PCR) based molecular characterization ...

    African Journals Online (AJOL)

    Polymerase chain reaction (PCR) based molecular characterization of popular wheat varieties of Khyber Pukhtunkhwa (KPK) region of Pakistan. ... Molecular markers used in this study show high rate of genetic diversity that can be used to assist a breeding program for the improvement of wheat in KPK-Pakistan. Key words: ...

  12. Coevolution between a family of parasite virulence effectors and a class of LINE-1 retrotransposons.

    Directory of Open Access Journals (Sweden)

    Soledad Sacristán

    2009-10-01

    Full Text Available Parasites are able to evolve rapidly and overcome host defense mechanisms, but the molecular basis of this adaptation is poorly understood. Powdery mildew fungi (Erysiphales, Ascomycota are obligate biotrophic parasites infecting nearly 10,000 plant genera. They obtain their nutrients from host plants through specialized feeding structures known as haustoria. We previously identified the AVR(k1 powdery mildew-specific gene family encoding effectors that contribute to the successful establishment of haustoria. Here, we report the extensive proliferation of the AVR(k1 gene family throughout the genome of B. graminis, with sequences diverging in formae speciales adapted to infect different hosts. Also, importantly, we have discovered that the effectors have coevolved with a particular family of LINE-1 retrotransposons, named TE1a. The coevolution of these two entities indicates a mutual benefit to the association, which could ultimately contribute to parasite adaptation and success. We propose that the association would benefit 1 the powdery mildew fungus, by providing a mechanism for amplifying and diversifying effectors and 2 the associated retrotransposons, by providing a basis for their maintenance through selection in the fungal genome.

  13. Mono-allelic retrotransposon insertion addresses epigenetic transcriptional repression in human genome

    Directory of Open Access Journals (Sweden)

    Byun Hyang-Min

    2012-02-01

    Full Text Available Abstract Background Retrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution. Their ability to move within genomes gives retrotransposons to affect genome instability. Methods we examined the polymorphic inserted AluYa5, evolutionary young Alu, in the progesterone receptor gene to determine the effects of Alu insertion on molecular environment. We used mono-allelic inserted cell lines which carry both Alu-present and Alu-absent alleles. To determine the epigenetic change and gene expression, we performed restriction enzyme digestion, Pyrosequencing, and Chromatin Immunoprecipitation. Results We observed that the polymorphic insertion of evolutionally young Alu causes increasing levels of DNA methylation in the surrounding genomic area and generates inactive histone tail modifications. Consequently the Alu insertion deleteriously inactivates the neighboring gene expression. Conclusion The mono-allelic Alu insertion cell line clearly showed that polymorphic inserted repetitive elements cause the inactivation of neighboring gene expression, bringing aberrant epigenetic changes.

  14. Revisiting plus-strand DNA synthesis in retroviruses and long terminal repeat retrotransposons: dynamics of enzyme: substrate interactions.

    Science.gov (United States)

    Fabris, Daniele; Marino, John P; Le Grice, Stuart F J

    2009-12-01

    Although polypurine tract (PPT)-primed initiation of plus-strand DNA synthesis in retroviruses and LTR-containing retrotransposons can be accurately duplicated, the molecular details underlying this concerted series of events remain largely unknown. Importantly, the PPT 3' terminus must be accommodated by ribonuclease H (RNase H) and DNA polymerase catalytic centers situated at either terminus of the cognate reverse transcriptase (RT), and in the case of the HIV-1 enzyme, ∼70Å apart. Communication between RT and the RNA/DNA hybrid therefore appears necessary to promote these events. The crystal structure of the HIV-1 RT/PPT complex, while informative, positions the RNase H active site several bases pairs from the PPT/U3 junction, and thus provides limited information on cleavage specificity. To fill the gap between biochemical and crystallographic approaches, we review a multidisciplinary approach combining chemical probing, mass spectrometry, NMR spectroscopy and single molecule spectroscopy. Our studies also indicate that nonnucleoside RT inhibitors affect enzyme orientation, suggesting initiation of plus-strand DNA synthesis as a potential therapeutic target.

  15. Revisiting Plus-Strand DNA Synthesis in Retroviruses and Long Terminal Repeat Retrotransposons: Dynamics of Enzyme: Substrate Interactions

    Directory of Open Access Journals (Sweden)

    Stuart F. J. Le Grice

    2009-11-01

    Full Text Available Although polypurine tract (PPT-primed initiation of plus-strand DNA synthesis in retroviruses and LTR-containing retrotransposons can be accurately duplicated, the molecular details underlying this concerted series of events remain largely unknown. Importantly, the PPT 3’ terminus must be accommodated by ribonuclease H (RNase H and DNA polymerase catalytic centers situated at either terminus of the cognate reverse transcriptase (RT, and in the case of the HIV-1 enzyme, ~70Å apart. Communication between RT and the RNA/DNA hybrid therefore appears necessary to promote these events. The crystal structure of the HIV-1 RT/PPT complex, while informative, positions the RNase H active site several bases pairs from the PPT/U3 junction, and thus provides limited information on cleavage specificity. To fill the gap between biochemical and crystallographic approaches, we review a multidisciplinary approach combining chemical probing, mass spectrometry, NMR spectroscopy and single molecule spectroscopy. Our studies also indicate that nonnucleoside RT inhibitors affect enzyme orientation, suggesting initiation of plus-strand DNA synthesis as a potential therapeutic target.

  16. Young, intact and nested retrotransposons are abundant in the onion and asparagus genomes

    Science.gov (United States)

    Vitte, C.; Estep, M. C.; Leebens-Mack, J.; Bennetzen, J. L.

    2013-01-01

    Background and Aims Although monocotyledonous plants comprise one of the two major groups of angiosperms and include >65 000 species, comprehensive genome analysis has been focused mainly on the Poaceae (grass) family. Due to this bias, most of the conclusions that have been drawn for monocot genome evolution are based on grasses. It is not known whether these conclusions apply to many other monocots. Methods To extend our understanding of genome evolution in the monocots, Asparagales genomic sequence data were acquired and the structural properties of asparagus and onion genomes were analysed. Specifically, several available onion and asparagus bacterial artificial chromosomes (BACs) with contig sizes >35 kb were annotated and analysed, with a particular focus on the characterization of long terminal repeat (LTR) retrotransposons. Key Results The results reveal that LTR retrotransposons are the major components of the onion and garden asparagus genomes. These elements are mostly intact (i.e. with two LTRs), have mainly inserted within the past 6 million years and are piled up into nested structures. Analysis of shotgun genomic sequence data and the observation of two copies for some transposable elements (TEs) in annotated BACs indicates that some families have become particularly abundant, as high as 4–5 % (asparagus) or 3–4 % (onion) of the genome for the most abundant families, as also seen in large grass genomes such as wheat and maize. Conclusions Although previous annotations of contiguous genomic sequences have suggested that LTR retrotransposons were highly fragmented in these two Asparagales genomes, the results presented here show that this was largely due to the methodology used. In contrast, this current work indicates an ensemble of genomic features similar to those observed in the Poaceae. PMID:23887091

  17. Helitrons and Retrotransposons Are Co-localized in Bos taurus Genomes.

    Science.gov (United States)

    Babii, A; Kovalchuk, S; Glazko, T; Kosovsky, G; Glazko, V

    2017-06-01

    DNA transposons helitrons are mobile genetic elements responsible for major movements of the genetic material within and across different genomes. This ability makes helitrons suitable candidate elements for the development of new approaches of multilocus genotyping of live-stock animals, along with the well-known microsatellite loci. We aimed to estimate the informativeness of helitron and microsatellite markers in assessing the consolidation and the "gene pool" standards of two commercial dairy cattle breeds (Ayrshire breed and holsteinized Black-and-White cattle) and one local breed of Kalmyk cattle, and to reveal any inter-breed difference in the organization of genomic regions flanked by helitrons in the studied cattle breeds. We used the combination of two highly-polymorphic genomic elements - helitrons and trinu-cleotide microsatellites (AGC)6G and (GAG)6C, respectively - for genome scanning of the sampled groups of cattle. Also, we pyrosequenced the genomic regions flanked by the inverted repeats of 3'-end of Heligloria family of helitron fragments. Generally, the both combinations of markers generated polymorphic spectra, based on which certain interbreed differentiation could be observed. The analysis of the identified interspersed repeats suggests that in factory and local cattle the genomic regions flanked by helitron fragments are shaped differently and contain different superfamilies of transposable elements, especially retrotransposons. Despite the well-known fact of retrotransposon-dependent microsatellite expansion, our data suggest that, in the cattle genome, the DNA transposons and microsatellites can also be found in close neighbourhood, and that helitrons and retrotransposons may form domains of increased variability - targets for factors of artificial selection.

  18. Epigenetic regulation of the rice retrotransposon Tos17.

    Science.gov (United States)

    Cheng, Chaoyang; Daigen, Masaaki; Hirochika, Hirohiko

    2006-10-01

    Transposable elements are major components of plant genomes. Their activity seems to be epigenetically regulated by gene silencing systems. Here we report epigenetic variation in the retrotransposon Tos17 activity in rice varieties. Of the two copies of Tos17 present in chromosome 7 (Tos17 (chr.7)) and chromosome 10 (Tos17 (chr.10)), Tos17 (chr.7) is strongly activated by tissue culture in most varieties including Nipponbare except for Moritawase, despite the identity of the DNA sequences in Moritawase and Nipponbare. Tos17 (chr.7) activity correlated with its methylation status, and Tos17 (chr.7 )in Moritawase was heavily methylated and activated by treatment of 5-azacytidine (5-azaC), a DNA methylation inhibitor. Although the original copies of Tos17 are methylated to some extent in all varieties examined, the transposed copies in calli mostly are not methylated. When plants were regenerated from calli, the degree of methylation of the Tos17 DNA increased gradually with the growth of plants, and a significant progress of DNA methylation occurred in the next generation after a completed reproductive cycle. With increasing DNA methylation, the transcription of transposed and original Tos17 copies driven by its own as well as by a flanking gene promoter were suppressed. We conclude that Tos17 DNA methylation controls the transpositional activity of Tos17, and modulates the activity of neighboring genes. Based on the analysis of the inactive Tos17 (chr.10), we propose that another mechanism, called transcriptional interference, is involved in the control of Tos17 activity.

  19. Infection-Induced Retrotransposon-Derived Noncoding RNAs Enhance Herpesviral Gene Expression via the NF-κB Pathway.

    Directory of Open Access Journals (Sweden)

    John Karijolich

    Full Text Available Short interspersed nuclear elements (SINEs are highly abundant, RNA polymerase III-transcribed noncoding retrotransposons that are silenced in somatic cells but activated during certain stresses including viral infection. How these induced SINE RNAs impact the host-pathogen interaction is unknown. Here we reveal that during murine gammaherpesvirus 68 (MHV68 infection, rapidly induced SINE RNAs activate the antiviral NF-κB signaling pathway through both mitochondrial antiviral-signaling protein (MAVS-dependent and independent mechanisms. However, SINE RNA-based signaling is hijacked by the virus to enhance viral gene expression and replication. B2 RNA expression stimulates IKKβ-dependent phosphorylation of the major viral lytic cycle transactivator protein RTA, thereby enhancing its activity and increasing progeny virion production. Collectively, these findings suggest that SINE RNAs participate in the innate pathogen response mechanism, but that herpesviruses have evolved to co-opt retrotransposon activation for viral benefit.

  20. Unique features of the rice blast resistance Pish locus revealed by large scale retrotransposon-tagging.

    Science.gov (United States)

    Takahashi, Akira; Hayashi, Nagao; Miyao, Akio; Hirochika, Hirohiko

    2010-08-13

    R gene-mediated resistance is one of the most effective mechanisms of immunity against pathogens in plants. To date some components that regulate the primary steps of plant immunity have been isolated, however, the molecular dissection of defense signaling downstream of the R proteins remains to be completed. In addition, R genes are known to be highly variable, however, the molecular mechanisms responsible for this variability remain obscure. To identify novel factors required for R gene-mediated resistance in rice, we used rice insertional mutant lines, induced by the endogenous retrotransposon Tos17, in a genetic screening involving the rice blast fungus Magnaporthe oryzae. We inoculated 41,119 mutant lines with the fungus using a high throughput procedure, and identified 86 mutant lines with diminished resistance. A genome analysis revealed that 72 of the 86 lines contained mutations in a gene encoding a nucleotide binding site (NBS) and leucine rich repeat (LRR) domain-containing (NBS-LRR) protein. A genetic complementation analysis and a pathogenesis assay demonstrated that this NBS-LRR gene encodes Pish, which confers resistance against races of M. oryzae containing avrPish. The other 14 lines have intact copies of the Pish gene, suggesting that they may contain mutations in the signaling components downstream of Pish. The genome analysis indicated that Pish and its neighboring three NBS-LRR genes are high similar to one another and are tandemly located. An in silico analysis of a Tos17 flanking sequence database revealed that this region is a "hot spot" for insertion. Intriguingly, the insertion sites are not distributed evenly among these four NBS-LRR genes, despite their similarity at the sequence and expression levels. In this work we isolated the R gene Pish, and identified several other mutants involved in the signal transduction required for Pish-mediated resistance. These results indicate that our genetic approach is efficient and useful for

  1. Unique features of the rice blast resistance Pish locus revealed by large scale retrotransposon-tagging

    Directory of Open Access Journals (Sweden)

    Takahashi Akira

    2010-08-01

    Full Text Available Abstract Background R gene-mediated resistance is one of the most effective mechanisms of immunity against pathogens in plants. To date some components that regulate the primary steps of plant immunity have been isolated, however, the molecular dissection of defense signaling downstream of the R proteins remains to be completed. In addition, R genes are known to be highly variable, however, the molecular mechanisms responsible for this variability remain obscure. Results To identify novel factors required for R gene-mediated resistance in rice, we used rice insertional mutant lines, induced by the endogenous retrotransposon Tos17, in a genetic screening involving the rice blast fungus Magnaporthe oryzae. We inoculated 41,119 mutant lines with the fungus using a high throughput procedure, and identified 86 mutant lines with diminished resistance. A genome analysis revealed that 72 of the 86 lines contained mutations in a gene encoding a nucleotide binding site (NBS and leucine rich repeat (LRR domain-containing (NBS-LRR protein. A genetic complementation analysis and a pathogenesis assay demonstrated that this NBS-LRR gene encodes Pish, which confers resistance against races of M. oryzae containing avrPish. The other 14 lines have intact copies of the Pish gene, suggesting that they may contain mutations in the signaling components downstream of Pish. The genome analysis indicated that Pish and its neighboring three NBS-LRR genes are high similar to one another and are tandemly located. An in silico analysis of a Tos17 flanking sequence database revealed that this region is a "hot spot" for insertion. Intriguingly, the insertion sites are not distributed evenly among these four NBS-LRR genes, despite their similarity at the sequence and expression levels. Conclusions In this work we isolated the R gene Pish, and identified several other mutants involved in the signal transduction required for Pish-mediated resistance. These results indicate that

  2. A Hadoop-based Molecular Docking System

    Science.gov (United States)

    Dong, Yueli; Guo, Quan; Sun, Bin

    2017-10-01

    Molecular docking always faces the challenge of managing tens of TB datasets. It is necessary to improve the efficiency of the storage and docking. We proposed the molecular docking platform based on Hadoop for virtual screening, it provides the preprocessing of ligand datasets and the analysis function of the docking results. A molecular cloud database that supports mass data management is constructed. Through this platform, the docking time is reduced, the data storage is efficient, and the management of the ligand datasets is convenient.

  3. Activation of an endogenous retrotransposon associated with epigenetic changes in Lotus japonicus

    DEFF Research Database (Denmark)

    Fukai, Eigo; Stougaard, Jens; Hayashi, Makoto

    2013-01-01

    Long terminal repeat retrotransposons occupy a large portion of genomes in flowering plants. In spite of their abundance, the majority are silenced and rarely transpose. One of the examples of a highly active retrotransposon is Lotus Retrotransposon 1(LORE1), of the model legume Lotus japonicus (...... significance of LORE1 as a member of chromovirus, a chromodomain containing clade of the Gypsy superfamily. Then we discuss possibilities and methodologies for using endogenous transposable elements as mutagens to generate gene tagging populations in plants...

  4. Condensin II subunit dCAP-D3 restricts retrotransposon mobilization in Drosophila somatic cells.

    Directory of Open Access Journals (Sweden)

    Andrew T Schuster

    2013-10-01

    Full Text Available Retrotransposon sequences are positioned throughout the genome of almost every eukaryote that has been sequenced. As mobilization of these elements can have detrimental effects on the transcriptional regulation and stability of an organism's genome, most organisms have evolved mechanisms to repress their movement. Here, we identify a novel role for the Drosophila melanogaster Condensin II subunit, dCAP-D3 in preventing the mobilization of retrotransposons located in somatic cell euchromatin. dCAP-D3 regulates transcription of euchromatic gene clusters which contain or are proximal to retrotransposon sequence. ChIP experiments demonstrate that dCAP-D3 binds to these loci and is important for maintaining a repressed chromatin structure within the boundaries of the retrotransposon and for repressing retrotransposon transcription. We show that dCAP-D3 prevents accumulation of double stranded DNA breaks within retrotransposon sequence, and decreased dCAP-D3 levels leads to a precise loss of retrotransposon sequence at some dCAP-D3 regulated gene clusters and a gain of sequence elsewhere in the genome. Homologous chromosomes exhibit high levels of pairing in Drosophila somatic cells, and our FISH analyses demonstrate that retrotransposon-containing euchromatic loci are regions which are actually less paired than euchromatic regions devoid of retrotransposon sequences. Decreased dCAP-D3 expression increases pairing of homologous retrotransposon-containing loci in tissue culture cells. We propose that the combined effects of dCAP-D3 deficiency on double strand break levels, chromatin structure, transcription and pairing at retrotransposon-containing loci may lead to 1 higher levels of homologous recombination between repeats flanking retrotransposons in dCAP-D3 deficient cells and 2 increased retrotransposition. These findings identify a novel role for the anti-pairing activities of dCAP-D3/Condensin II and uncover a new way in which dCAP-D3/Condensin

  5. Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals.

    Science.gov (United States)

    Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

    2015-01-01

    Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is "mammalian-specific genomic functions", a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of "mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons", based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes.

  6. Gas Sensors Based on Molecular Imprinting Technology.

    Science.gov (United States)

    Zhang, Yumin; Zhang, Jin; Liu, Qingju

    2017-07-04

    Molecular imprinting technology (MIT); often described as a method of designing a material to remember a target molecular structure (template); is a technique for the creation of molecularly imprinted polymers (MIPs) with custom-made binding sites complementary to the target molecules in shape; size and functional groups. MIT has been successfully applied to analyze; separate and detect macromolecular organic compounds. Furthermore; it has been increasingly applied in assays of biological macromolecules. Owing to its unique features of structure specificity; predictability; recognition and universal application; there has been exploration of the possible application of MIPs in the field of highly selective gas sensors. In this present study; we outline the recent advances in gas sensors based on MIT; classify and introduce the existing molecularly imprinted gas sensors; summarize their advantages and disadvantages; and analyze further research directions.

  7. DNA methylation and targeting of LINE retrotransposons in Entamoeba histolytica and Entamoeba invadens.

    Science.gov (United States)

    Harony, Hala; Bernes, Sabina; Siman-Tov, Rama; Ankri, Serge

    2006-05-01

    In this study, we have isolated by affinity chromatography, using anti-m5C antibody as a ligand, a DNA encoding reverse transcriptase of LINE retrotransposon (RT LINE) in both Entamoeba invadens and Entamoeba histolytica. RT LINE transcripts were detected in E. histolytica but were absent from E. invadens. The methylation status of genomic copies of E. invadens RT LINE was confirmed by bisulfite analysis. In contrast, all the genomic copies of the E. histolytica RT LINE analyzed in this study were not methylated. Many of these genomic copies diverge from the RT LINE isolated by m5C affinity chromatography by a number of mutations that includes conversion of C to T and G to A. These mutations are reminiscent of the conversion of C to T (and G to A on the complementary DNA strand) that occurred during primate evolution in Alu elements following accelerated deamination of methylated cytosines. E. invadens and E. histolytica RT LINEs isolated by affinity chromatography were cloned in a pEhAct Neo vector, amplified in E. coli GM2163 (dam-dcm) and transformed into E. histolytica. Bisulfite analysis of transfected amoeba showed the presence of m5C in E. invadens RT LINE replicated in E. histolytica, but not in E. histolytica RT LINE or in the neomycine phosphotransferase gene, which is also carried by the pEhAct Neo vector. These results suggest the existence of a specific mechanism based on DNA methylation that controls retrotransposons in these parasites.

  8. Large-scale transcriptome data reveals transcriptional activity of fission yeast LTR retrotransposons

    Directory of Open Access Journals (Sweden)

    Willerslev Eske

    2010-03-01

    Full Text Available Abstract Background Retrotransposons are transposable elements that proliferate within eukaryotic genomes through a process involving reverse transcription. The numbers of retrotransposons within genomes and differences between closely related species may yield insight into the evolutionary history of the elements. Less is known about the ongoing dynamics of retrotransposons, as analysis of genome sequences will only reveal insertions of retrotransposons that are fixed - or near fixation - in the population or strain from which genetic material has been extracted for sequencing. One pre-requisite for retrotransposition is transcription of the elements. Given their intrinsic sequence redundancy, transcriptome-level analyses of transposable elements are scarce. We have used recently published transcriptome data from the fission yeast Schizosaccharomyces pombe to assess the ability to detect and describe transcriptional activity from Long Terminal Repeat (LTR retrotransposons. LTR retrotransposons are normally flanked by two LTR sequences. However, the majority of LTR sequences in S. pombe exist as solitary LTRs, i.e. as single terminal repeat sequences not flanking a retrotransposon. Transcriptional activity was analysed for both full-length LTR retrotransposons and solitary LTRs. Results Two independent sets of transcriptome data reveal the presence of full-length, polyadenylated transcripts from LTR retrotransposons in S. pombe during growth phase in rich medium. The redundancy of retrotransposon sequences makes it difficult to assess which elements are transcriptionally active, but data strongly indicates that only a subset of the LTR retrotransposons contribute significantly to the detected transcription. A considerable level of reverse strand transcription is also detected. Equal levels of transcriptional activity are observed from both strands of solitary LTR sequences. Transcriptome data collected during meiosis suggests that transcription

  9. MASiVEdb: the Sirevirus Plant Retrotransposon Database

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    Bousios Alexandros

    2012-04-01

    Full Text Available Abstract Background Sireviruses are an ancient genus of the Copia superfamily of LTR retrotransposons, and the only one that has exclusively proliferated within plant genomes. Based on experimental data and phylogenetic analyses, Sireviruses have successfully infiltrated many branches of the plant kingdom, extensively colonizing the genomes of grass species. Notably, it was recently shown that they have been a major force in the make-up and evolution of the maize genome, where they currently occupy ~21% of the nuclear content and ~90% of the Copia population. It is highly likely, therefore, that their life dynamics have been fundamental in the genome composition and organization of a plethora of plant hosts. To assist studies into their impact on plant genome evolution and also facilitate accurate identification and annotation of transposable elements in sequencing projects, we developed MASiVEdb (Mapping and Analysis of SireVirus Elements Database, a collective and systematic resource of Sireviruses in plants. Description Taking advantage of the increasing availability of plant genomic sequences, and using an updated version of MASiVE, an algorithm specifically designed to identify Sireviruses based on their highly conserved genome structure, we populated MASiVEdb (http://bat.infspire.org/databases/masivedb/ with data on 16,243 intact Sireviruses (total length >158Mb discovered in 11 fully-sequenced plant genomes. MASiVEdb is unlike any other transposable element database, providing a multitude of highly curated and detailed information on a specific genus across its hosts, such as complete set of coordinates, insertion age, and an analytical breakdown of the structure and gene complement of each element. All data are readily available through basic and advanced query interfaces, batch retrieval, and downloadable files. A purpose-built system is also offered for detecting and visualizing similarity between user sequences and Sireviruses, as

  10. Environmental Phosphorus Recovery Based on Molecular Bioscavengers

    DEFF Research Database (Denmark)

    Gruber, Mathias Felix

    -scale quantum calculations to macro-scale fluid simulations, are employed to hint at the potential of a recovery technology based on molecular bioscavengers. As a first approach, data mining is used to obtain statistical information about how proteins in nature interact with phosphate groups, thereby revealing...

  11. Structural characterization of copia-type retrotransposons leads to insights into the marker development in a biofuel crop, Jatropha curcas L.

    Science.gov (United States)

    2013-01-01

    Background Recently, Jatropha curcas L. has attracted worldwide attention for its potential as a source of biodiesel. However, most DNA markers have demonstrated high levels of genetic similarity among and within jatropha populations around the globe. Despite promising features of copia-type retrotransposons as ideal genetic tools for gene tagging, mutagenesis, and marker-assisted selection, they have not been characterized in the jatropha genome yet. Here, we examined the diversity, evolution, and genome-wide organization of copia-type retrotransposons in the Asian, African, and Mesoamerican accessions of jatropha, then introduced a retrotransposon-based marker for this biofuel crop. Results In total, 157 PCR fragments that were amplified using the degenerate primers for the reverse transcriptase (RT) domain of copia-type retroelements were sequenced and aligned to construct the neighbor-joining tree. Phylogenetic analysis demonstrated that isolated copia RT sequences were classified into ten families, which were then grouped into three lineages. An in-depth study of the jatropha genome for the RT sequences of each family led to the characterization of full consensus sequences of the jatropha copia-type families. Estimated copy numbers of target sequences were largely different among families, as was presence of genes within 5 kb flanking regions for each family. Five copia-type families were as appealing candidates for the development of DNA marker systems. A candidate marker from family Jc7 was particularly capable of detecting genetic variation among different jatropha accessions. Fluorescence in situ hybridization (FISH) to metaphase chromosomes reveals that copia-type retrotransposons are scattered across chromosomes mainly located in the distal part regions. Conclusion This is the first report on genome-wide analysis and the cytogenetic mapping of copia-type retrotransposons of jatropha, leading to the discovery of families bearing high potential as DNA

  12. A nanoplasmonic switch based on molecular machines

    KAUST Repository

    Zheng, Yue Bing

    2009-06-01

    We aim to develop a molecular-machine-driven nanoplasmonic switch for its use in future nanophotonic integrated circuits (ICs) that have applications in optical communication, information processing, biological and chemical sensing. Experimental data show that an Au nanodisk array, coated with rotaxane molecular machines, switches its localized surface plasmon resonances (LSPR) reversibly when it is exposed to chemical oxidants and reductants. Conversely, bare Au nanodisks and disks coated with mechanically inert control compounds, do not display the same switching behavior. Along with calculations based on time-dependent density functional theory (TDDFT), these observations suggest that the nanoscale movements within surface-bound "molecular machines" can be used as the active components in plasmonic devices. ©2009 IEEE.

  13. An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons

    NARCIS (Netherlands)

    Jacobs, F.M.J.; Greenberg, D.; Nguyen, N.; Haeussler, M.; Ewing, A.D.; Katzman, S.; Paten, B.; Salama, S.R.; Haussler, D.

    2014-01-01

    Throughout evolution primate genomes have been modified by waves of retrotransposon insertions1, 2, 3. For each wave, the host eventually finds a way to repress retrotransposon transcription and prevent further insertions. In mouse embryonic stem cells, transcriptional silencing of retrotransposons

  14. Antisense Transcription of Retrotransposons in Drosophila: An Origin of Endogenous Small Interfering RNA Precursors.

    Science.gov (United States)

    Russo, Joseph; Harrington, Andrew W; Steiniger, Mindy

    2016-01-01

    Movement of transposons causes insertions, deletions, and chromosomal rearrangements potentially leading to premature lethality in Drosophila melanogaster. To repress these elements and combat genomic instability, eukaryotes have evolved several small RNA-mediated defense mechanisms. Specifically, in Drosophila somatic cells, endogenous small interfering (esi)RNAs suppress retrotransposon mobility. EsiRNAs are produced by Dicer-2 processing of double-stranded RNA precursors, yet the origins of these precursors are unknown. We show that most transposon families are transcribed in both the sense (S) and antisense (AS) direction in Dmel-2 cells. LTR retrotransposons Dm297, mdg1, and blood, and non-LTR retrotransposons juan and jockey transcripts, are generated from intraelement transcription start sites with canonical RNA polymerase II promoters. We also determined that retrotransposon antisense transcripts are less polyadenylated than sense. RNA-seq and small RNA-seq revealed that Dicer-2 RNA interference (RNAi) depletion causes a decrease in the number of esiRNAs mapping to retrotransposons and an increase in expression of both S and AS retrotransposon transcripts. These data support a model in which double-stranded RNA precursors are derived from convergent transcription and processed by Dicer-2 into esiRNAs that silence both sense and antisense retrotransposon transcripts. Reduction of sense retrotransposon transcripts potentially lowers element-specific protein levels to prevent transposition. This mechanism preserves genomic integrity and is especially important for Drosophila fitness because mobile genetic elements are highly active. Copyright © 2016 by the Genetics Society of America.

  15. sRNAs as possible regulators of retrotransposon activity in Cryptococcus gattii VGII.

    Science.gov (United States)

    Ferrareze, Patrícia Aline Gröhs; Streit, Rodrigo Silva Araujo; Dos Santos, Francine Melise; Schrank, Augusto; Kmetzsch, Livia; Vainstein, Marilene Henning; Staats, Charley Christian

    2017-04-12

    The absence of Argonaute genes in the fungal pathogen Cryptococcus gattii R265 and other VGII strains indicates that yeasts of this genotype cannot have a functional RNAi pathway, an evolutionarily conserved gene silencing mechanism performed by small RNAs. The success of the R265 strain as a pathogen that caused the Pacific Northwest and Vancouver Island outbreaks may imply that RNAi machinery loss could be beneficial under certain circumstances during evolution. As a result, a hypermutant phenotype would be created with high rates of genome retrotransposition, for instance. This study therefore aimed to evaluate in silicio the effect of retrotransposons and their control mechanisms by small RNAs on genomic stability and synteny loss of C. gattii R265 through retrotransposons sequence comparison and orthology analysis with other 16 C. gattii genomic sequences available. Retrotransposon mining identified a higher sequence count to VGI genotype compared to VGII, VGIII, and VGIV. However, despite the lower retrotransposon number, VGII exhibited increased synteny loss and genome rearrangement events. RNA-Seq analysis indicated highly expressed retrotransposons as well as sRNA production. Genome rearrangement and synteny loss may suggest a greater retrotransposon mobilization caused by RNAi pathway absence, but the effective presence of sRNAs that matches retrotransposon sequences means that an alternative retrotransposon silencing mechanism could be active in genomic integrity maintenance of C. gattii VGII strains.

  16. Regulating retrotransposon activity through the use of alternative transcription start sites

    DEFF Research Database (Denmark)

    Persson, Jenna; Steglich, Babett; Smialowska, Agata

    2016-01-01

    Retrotransposons, the ancestors of retroviruses, have the potential for gene disruption and genomic takeover if not kept in check. Paradoxically, although host cells repress these elements by multiple mechanisms, they are transcribed and are even activated under stress conditions. Here, we descri...... retrotransposon transcription from a nonproductive TSS allows for rapid stress-induced activation, while preventing uncontrolled transposon activity in the genome....

  17. Identification and characterization of a LTR retrotransposon from the genome of Cyprinus carpio var. Jian.

    Science.gov (United States)

    Cao, Liping; Yin, Guojun; Cao, Zheming; Bing, Xuwen; Ding, Weidong

    2016-06-01

    A Ty3/gypsy-retrotransposon-type transposon was found in the genome of the Jian carp (Cyprinus carpio var. Jian) in a previous study (unpublished), and was designated a JRE retrotransposon (Jian retrotransposon). The full-length JRE retrotransposon is 5126 bp, which includes two long terminal repeats of 470 bp at the 5' end and 453 bp at the 3' end, and two open reading frames between them: 4203 bp encoding the group-specific antigen (GAG) and polyprotein (POL). The pol gene has a typical Ty3/gypsy retrotransposon structure, and the gene order is protease, reverse transcriptase, RNase H, and integrase (PR-RT-RH-IN). A phylogenetic analysis of the pol gene showed that it has similarities of 40.7, 40, and 32.8 %, to retrotransposons of Azumapecten farreri, Mizuhopecten yessoensis, and Xiphophorus maculatus, respectively. Therefore, JRE might belong to the JULE retrotransposon family. The copy number of the JRE transposon in the genome of the Jian carp is 124, determined with real-time quantitative PCR. The mRNA of the JRE retrotransposon is expressed in five Jian carp tissues, the liver, kidney, blood, muscle, and gonad, and slightly higher in the kidney and liver than in the other tissues.

  18. Large-scale transcriptome data reveals transcriptional activity of fission yeast LTR retrotransposons

    DEFF Research Database (Denmark)

    Mourier, Tobias; Willerslev, Eske

    2010-01-01

    BACKGROUND: Retrotransposons are transposable elements that proliferate within eukaryotic genomes through a process involving reverse transcription. The numbers of retrotransposons within genomes and differences between closely related species may yield insight into the evolutionary history...... was analysed for both full-length LTR retrotransposons and solitary LTRs. RESULTS: Two independent sets of transcriptome data reveal the presence of full-length, polyadenylated transcripts from LTR retrotransposons in S. pombe during growth phase in rich medium. The redundancy of retrotransposon sequences...... of transcriptional activity are observed from both strands of solitary LTR sequences. Transcriptome data collected during meiosis suggests that transcription of solitary LTRs is correlated with the transcription of nearby protein-coding genes. CONCLUSIONS: Presumably, the host organism negatively regulates...

  19. LINE-1 Retrotransposons: Mediators of Somatic Variation in Neuronal Genomes?

    OpenAIRE

    Singer, Tatjana; McConnell, Michael J.; Marchetto, Maria C. N.; Coufal, Nicole G.; Gage, Fred H.

    2010-01-01

    LINE-1 (L1) elements are retrotransposons that insert extra copies of themselves throughout the genome using a “copy and paste” mechanism. L1s have contributed ~20% to total human genome content and are able to influence chromosome integrity and gene expression upon reinsertion. Recent studies show that L1 elements are active and “jumping” during neuronal differentiation. New somatic L1 insertions may generate “genomic plasticity” in neurons by causing variation in genomic DNA sequences and b...

  20. SVA elements are nonautonomous retrotransposons that cause disease in humans.

    Science.gov (United States)

    Ostertag, Eric M; Goodier, John L; Zhang, Yue; Kazazian, Haig H

    2003-12-01

    L1 elements are the only active autonomous retrotransposons in the human genome. The nonautonomous Alu elements, as well as processed pseudogenes, are retrotransposed by the L1 retrotransposition proteins working in trans. Here, we describe another repetitive sequence in the human genome, the SVA element. Our analysis reveals that SVA elements are currently active in the human genome. SVA elements, like Alus and L1s, occasionally insert into genes and cause disease. Furthermore, SVA elements are probably mobilized in trans by active L1 elements.

  1. Identification and characterization of REC66, a Ty1-copia-like retrotransposon in the genome of red flower of Mirabilis jalapa L.

    Directory of Open Access Journals (Sweden)

    Shunri Jiang

    2017-01-01

    Full Text Available Mirabilis jalapa Lis the most commonly grown ornamental species of Mirabilis and is available in a range of brilliant colors. However, genetic research on Mirabilis jalapa Lis limited. Using fluorescent differential display (FDD screening, we report the identification of a novel Ty1-copia-like retrotransposon in the genome of the red flower of Mirabilis jalapa L, and we named it REC66based on its sequence homology to the GAG protein from Ty1-copiaretrotransposon. Using degenerate primers based on the DNA sequence of REC66, a total of fourteen different variants in reverse transcriptase (RT sequence were recovered from the genomic DNA. These RT sequences show a high degree of heterogeneity characterized mainly by deletion mutation; they can be divided into three subfamilies, of which the majority encode defective RT. This is the first report of a Ty1-copiaretrotransposon in Mirabilis jalapa L. The finding could be helpful for the development of new molecular markers for genetic studies, particularly on the origin and evolutionary relationships of M. jalapa L, and the study of Ty1-copiaretrotransposons and plant genome evolution in the genus Mirabilisor family Nyctaginaceae.

  2. Acquisition of full-length viral helicase domains by insect retrotransposon-encoded polypeptides

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    Ekaterina eLazareva

    2015-12-01

    Full Text Available Recent metagenomic studies in insects identified many sequences unexpectedly closely related to plant virus genes. Here we describe a new example of this kind, insect R1 LINEs with an additional C-terminal domain in their open reading frame 2. This domain is similar to NTPase/helicase (SF1H domains, which are found in replicative proteins encoded by plant viruses of the genus Tobamovirus. We hypothesize that the SF1H domain could be acquired by LINEs, directly or indirectly, upon insect feeding on virus-infected plants. Possible functions of this domain in LINE transposition and involvement in LINEs counteraction the silencing-based cell defense against retrotransposons are discussed.

  3. Photoswitchable gel assembly based on molecular recognition

    Science.gov (United States)

    Yamaguchi, Hiroyasu; Kobayashi, Yuichiro; Kobayashi, Ryosuke; Takashima, Yoshinori; Hashidzume, Akihito; Harada, Akira

    2012-01-01

    The formation of effective and precise linkages in bottom-up or top-down processes is important for the development of self-assembled materials. Self-assembly through molecular recognition events is a powerful tool for producing functionalized materials. Photoresponsive molecular recognition systems can permit the creation of photoregulated self-assembled macroscopic objects. Here we demonstrate that macroscopic gel assembly can be highly regulated through photoisomerization of an azobenzene moiety that interacts differently with two host molecules. A photoregulated gel assembly system is developed using polyacrylamide-based hydrogels functionalized with azobenzene (guest) or cyclodextrin (host) moieties. Reversible adhesion and dissociation of the host gel from the guest gel may be controlled by photoirradiation. The differential affinities of α-cyclodextrin or β-cyclodextrin for the trans-azobenzene and cis-azobenzene are employed in the construction of a photoswitchable gel assembly system. PMID:22215078

  4. Retrotransposon silencing by DNA methylation can drive mammalian genomic imprinting.

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    Shunsuke Suzuki

    2007-04-01

    Full Text Available Among mammals, only eutherians and marsupials are viviparous and have genomic imprinting that leads to parent-of-origin-specific differential gene expression. We used comparative analysis to investigate the origin of genomic imprinting in mammals. PEG10 (paternally expressed 10 is a retrotransposon-derived imprinted gene that has an essential role for the formation of the placenta of the mouse. Here, we show that an orthologue of PEG10 exists in another therian mammal, the marsupial tammar wallaby (Macropus eugenii, but not in a prototherian mammal, the egg-laying platypus (Ornithorhynchus anatinus, suggesting its close relationship to the origin of placentation in therian mammals. We have discovered a hitherto missing link of the imprinting mechanism between eutherians and marsupials because tammar PEG10 is the first example of a differentially methylated region (DMR associated with genomic imprinting in marsupials. Surprisingly, the marsupial DMR was strictly limited to the 5' region of PEG10, unlike the eutherian DMR, which covers the promoter regions of both PEG10 and the adjacent imprinted gene SGCE. These results not only demonstrate a common origin of the DMR-associated imprinting mechanism in therian mammals but provide the first demonstration that DMR-associated genomic imprinting in eutherians can originate from the repression of exogenous DNA sequences and/or retrotransposons by DNA methylation.

  5. Retrotransposon-derived promoter of Mammalian Aebp2.

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    Hana Kim

    Full Text Available Variable DNA methylation in promoter regions has been implicated in altering transcriptional regulation. The current study analyzed the evolutionary origin and DNA methylation pattern of one of the promoters of Aebp2. According to the results, the first promoter of Aebp2 has been derived from retrotransposons independently in the primate and rodent lineages. DNA methylation analyses revealed that this promoter is unmethylated in sperm, methylated in mature oocytes, and partially methylated at embryonic day 10.5 (78.3% and 14.5 (58.3%. This promoter also shows variable levels of DNA methylation among adult organs, ranging from the highest in spleen (~80% to the lowest in tail (~50%. The results from the F1 hybrid of interspecific crossing further indicated that both alleles are equally methylated without any allele bias, also supported by its biallelic expression. Therefore, the partial methylation observed among somatic tissues is an outcome of the genome-wide resetting of DNA methylation during the implantation stage, but not of the inherited allelic methylation pattern preset during gametogenesis. Taken together, mammalian Aebp2 has adopted retrotransposons as its promoter, which displays partial DNA methylation pattern of allelic- or non-allelic origin during the different stages of development.

  6. Diversity, origin, and distribution of retrotransposons (gypsy and copia) in conifers.

    Science.gov (United States)

    Friesen, N; Brandes, A; Heslop-Harrison, J S

    2001-07-01

    We examined the diversity, evolution, and genomic organization of retroelements in a wide range of gymnosperms. In total, 165 fragments of the reverse transcriptase (RT) gene domain were sequenced from PCR products using newly designed primers for gypsy-like retrotransposons and well-known primers for copia-like retrotransposons; representatives of long interspersed nuclear element (LINE) retroposons were also found. Gypsy and copia-like retroelements are a major component of the gymnosperm genome, and in situ hybridization showed that individual element families were widespread across the chromosomes, consistent with dispersion and amplification via an RNA intermediate. Most of the retroelement families were widely distributed among the gymnosperms, including species with wide taxonomic separation from the Northern and Southern Hemispheres. When the gymnosperm sequences were analyzed together with retroelements from other species, the monophyletic origin of plant copia, gypsy, and LINE groups was well supported, with an additional clade including badnaviral and other, probably virus-related, plant sequences as well as animal and fungal gypsy elements. Plant retroelements showed high diversity within the phylogenetic trees of both copia and gypsy RT domains, with, for example, retroelement sequences from Arabidopsis thaliana being present in many supported groupings. No primary branches divided major taxonomic clades such as angiosperms, monocotyledons, gymnosperms, or conifers or (based on smaller samples) ferns, Gnetales, or Sphenopsida (Equisetum), suggesting that much of the existing diversity was present early in plant evolution, or perhaps that horizontal transfer of sequences has occurred. Within the phylogenetic trees for both gypsy and copia, two clearly monophyletic gymnosperm/conifer clades were revealed, providing evidence against recent horizontal transfer. The results put the evolution of the large and relatively conserved genome structure of

  7. Organic-based molecular switches for molecular electronics.

    Science.gov (United States)

    Fuentes, Noelia; Martín-Lasanta, Ana; Alvarez de Cienfuegos, Luis; Ribagorda, Maria; Parra, Andres; Cuerva, Juan M

    2011-10-05

    In a general sense, molecular electronics (ME) is the branch of nanotechnology which studies the application of molecular building blocks for the fabrication of electronic components. Among the different types of molecules, organic compounds have been revealed as promising candidates for ME, due to the easy access, great structural diversity and suitable electronic and mechanical properties. Thanks to these useful capabilities, organic molecules have been used to emulate electronic devices at the nanoscopic scale. In this feature article, we present the diverse strategies used to develop organic switches towards ME with special attention to non-volatile systems.

  8. Advanced molecular devices based on light-driven molecular motors

    NARCIS (Netherlands)

    Chen, Jiawen

    2015-01-01

    Nature has provided a large collection of molecular machines and devices that are among the most amazing nanostructures on this planet. These machines are able to operate complex biological processes which are of great importance in our organisms. Inspired by these natural devices, artificial

  9. SREBP controls oxygen-dependent mobilization of retrotransposons in fission yeast.

    Directory of Open Access Journals (Sweden)

    Alfica Sehgal

    2007-08-01

    Full Text Available Retrotransposons are mobile genetic elements that proliferate through an RNA intermediate. Transposons do not encode transcription factors and thus rely on host factors for mRNA expression and survival. Despite information regarding conditions under which elements are upregulated, much remains to be learned about the regulatory mechanisms or factors controlling retrotransposon expression. Here, we report that low oxygen activates the fission yeast Tf2 family of retrotransposons. Sre1, the yeast ortholog of the mammalian membrane-bound transcription factor sterol regulatory element binding protein (SREBP, directly induces the expression and mobilization of Tf2 retrotransposons under low oxygen. Sre1 binds to DNA sequences in the Tf2 long terminal repeat that functions as an oxygen-dependent promoter. We find that Tf2 solo long terminal repeats throughout the genome direct oxygen-dependent expression of adjacent coding and noncoding sequences, providing a potential mechanism for the generation of oxygen-dependent gene expression.

  10. Analysis of the repetitive component and retrotransposon population in the genome of a marine angiosperm, Posidonia oceanica (L.) Delile.

    Science.gov (United States)

    Barghini, Elena; Mascagni, Flavia; Natali, Lucia; Giordani, Tommaso; Cavallini, Andrea

    2015-12-01

    Posidonia oceanica is a monocotyledonous marine plant that plays a crucial role in maintaining the Mediterranean environment. Despite its ecological importance, basic knowledge of the functional and structural genomics of this species is still limited, as it is for the other seagrasses. Here, for the first time, we report data on the repetitive component of the genome of this seagrass using a low coverage of Illumina sequences and different assembly approaches. A dataset of 19,760 assembled sequences, mostly belonging to the repetitive fraction of the genome, was produced and annotated. Based on mapping Illumina reads onto this dataset, the genome structure of P. oceanica and its repetitive component was inferred. A very large proportion of the genome is represented by long-terminal-repeat (LTR) retrotransposons of both the Copia and Gypsy superfamilies. Posidonia LTR-retrotransposons were classified and their sequences analysed. Gypsy elements belong to three main lineages, while Copia ones belong to seven lineages. Gypsy elements were more represented than Copia ones in the set of assembled sequences and in the genome. Analysis of sequence variability indicated that Gypsy lineages have experienced amplification in more recent times compared to Copia ones. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals

    Science.gov (United States)

    KANEKO-ISHINO, Tomoko; ISHINO, Fumitoshi

    2015-01-01

    Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is “mammalian-specific genomic functions”, a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of “mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons”, based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes. PMID:26666304

  12. A Novel Terminal-Repeat Retrotransposon in Miniature (TRIM) Is Massively Expressed in Echinococcus multilocularis Stem Cells

    Science.gov (United States)

    Koziol, Uriel; Radio, Santiago; Smircich, Pablo; Zarowiecki, Magdalena; Fernández, Cecilia; Brehm, Klaus

    2015-01-01

    Taeniid cestodes (including the human parasites Echinococcus spp. and Taenia solium) have very few mobile genetic elements (MGEs) in their genome, despite lacking a canonical PIWI pathway. The MGEs of these parasites are virtually unexplored, and nothing is known about their expression and silencing. In this work, we report the discovery of a novel family of small nonautonomous long terminal repeat retrotransposons (also known as terminal-repeat retrotransposons in miniature, TRIMs) which we have named ta-TRIM (taeniid TRIM). ta-TRIMs are only the second family of TRIM elements discovered in animals, and are likely the result of convergent reductive evolution in different taxonomic groups. These elements originated at the base of the taeniid tree and have expanded during taeniid diversification, including after the divergence of closely related species such as Echinococcus multilocularis and Echinococcus granulosus. They are massively expressed in larval stages, from a small proportion of full-length copies and from isolated terminal repeats that show transcriptional read-through into downstream regions, generating novel noncoding RNAs and transcriptional fusions to coding genes. In E. multilocularis, ta-TRIMs are specifically expressed in the germinative cells (the somatic stem cells) during asexual reproduction of metacestode larvae. This would provide a developmental mechanism for insertion of ta-TRIMs into cells that will eventually generate the adult germ line. Future studies of active and inactive ta-TRIM elements could give the first clues on MGE silencing mechanisms in cestodes. PMID:26133390

  13. Molecularly Imprinted Polymer/Metal Organic Framework Based Chemical Sensors

    Directory of Open Access Journals (Sweden)

    Zhenzhong Guo

    2016-10-01

    Full Text Available The present review describes recent advances in the concept of molecular imprinting using metal organic frameworks (MOF for development of chemical sensors. Two main strategies regarding the fabrication, performance and applications of recent sensors based on molecularly imprinted polymers associated with MOF are presented: molecularly imprinted MOF films and molecularly imprinted core-shell nanoparticles using MOF as core. The associated transduction modes are also discussed. A brief conclusion and future expectations are described herein.

  14. Molecularly Imprinted Polymer/Metal Organic Framework Based Chemical Sensors

    OpenAIRE

    Zhenzhong Guo; Anca Florea; Mengjuan Jiang; Yong Mei; Weiying Zhang; Aidong Zhang; Robert Săndulescu; Nicole Jaffrezic-Renault

    2016-01-01

    International audience; The present review describes recent advances in the concept of molecular imprinting using metal organic frameworks (MOF) for development of chemical sensors. Two main strategies regarding the fabrication, performance and applications of recent sensors based on molecularly imprinted polymers associated with MOF are presented: molecularly imprinted MOF films and molecularly imprinted core-shell nanoparticles using MOF as core. The associated transduction modes are also d...

  15. Switching of dominant retrotransposon silencing strategies from posttranscriptional to transcriptional mechanisms during male germ-cell development in mice.

    Directory of Open Access Journals (Sweden)

    Kota Inoue

    2017-07-01

    Full Text Available Mammalian genomes harbor millions of retrotransposon copies, some of which are transpositionally active. In mouse prospermatogonia, PIWI-interacting small RNAs (piRNAs combat retrotransposon activity to maintain the genomic integrity. The piRNA system destroys retrotransposon-derived RNAs and guides de novo DNA methylation at some retrotransposon promoters. However, it remains unclear whether DNA methylation contributes to retrotransposon silencing in prospermatogonia. We have performed comprehensive studies of DNA methylation and polyA(+ RNAs (transcriptome in developing male germ cells from Pld6/Mitopld and Dnmt3l knockout mice, which are defective in piRNA biogenesis and de novo DNA methylation, respectively. The Dnmt3l mutation greatly reduced DNA methylation levels at most retrotransposons, but its impact on their RNA abundance was limited in prospermatogonia. In Pld6 mutant germ cells, although only a few retrotransposons exhibited reduced DNA methylation, many showed increased expression at the RNA level. More detailed analysis of RNA sequencing, nascent RNA quantification, profiling of cleaved RNA ends, and the results obtained from double knockout mice suggest that PLD6 works mainly at the posttranscriptional level. The increase in retrotransposon expression was larger in Pld6 mutants than it was in Dnmt3l mutants, suggesting that RNA degradation by the piRNA system plays a more important role than does DNA methylation in prospermatogonia. However, DNA methylation had a long-term effect: hypomethylation caused by the Pld6 or Dnmt3l mutation resulted in increased retrotransposon expression in meiotic spermatocytes. Thus, posttranscriptional silencing plays an important role in the early stage of germ cell development, then transcriptional silencing becomes important in later stages. In addition, intergenic and intronic retrotransposon sequences, in particular those containing the antisense L1 promoters, drove ectopic expression of nearby

  16. Inducible Transposition of a Heat-Activated Retrotransposon in Tissue Culture.

    Science.gov (United States)

    Masuta, Yukari; Nozawa, Kosuke; Takagi, Hiroki; Yaegashi, Hiroki; Tanaka, Keisuke; Ito, Tasuku; Saito, Hideyuki; Kobayashi, Hisato; Matsunaga, Wataru; Masuda, Seiji; Kato, Atsushi; Ito, Hidetaka

    2017-02-01

    A transposition of a heat-activated retrotransposon named ONSEN required compromise of a small RNA-mediated epigenetic regulation that includes RNA-directed DNA methylation (RdDM) machinery after heat treatment. In the current study, we analyzed the transcriptional and transpositional activation of ONSEN to better understand the underlying molecular mechanism involved in the maintenance and/or induction of transposon activation in plant tissue culture. We found the transposition of heat-primed ONSEN during tissue culture independently of RdDM mutation. The heat activation of ONSEN transcripts was not significantly up-regulated in tissue culture compared with that in heat-stressed seedlings, indicating that the transposition of ONSEN was regulated independently of the transcript level. RdDM-related genes were up-regulated by heat stress in both tissue culture and seedlings. The level of DNA methylation of ONSEN did not show any change in tissue culture, and the amount of ONSEN-derived small RNAs was not affected by heat stress. The results indicated that the transposition of ONSEN was regulated by an alternative mechanism in addition to the RdDM-mediated epigenetic regulation in tissue culture. We applied the tissue culture-induced transposition of ONSEN to Japanese radish, an important breeding species of the family Brassicaceae. Several new insertions were detected in a regenerated plant derived from heat-stressed tissues and its self-fertilized progeny, revealing the possibility of molecular breeding without genetic modification. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  17. LINE-1 retrotransposons: from 'parasite' sequences to functional elements.

    Science.gov (United States)

    Paço, Ana; Adega, Filomena; Chaves, Raquel

    2015-02-01

    Long interspersed nuclear elements-1 (LINE-1) are the most abundant and active retrotransposons in the mammalian genomes. Traditionally, the occurrence of LINE-1 sequences in the genome of mammals has been explained by the selfish DNA hypothesis. Nevertheless, recently, it has also been argued that these sequences could play important roles in these genomes, as in the regulation of gene expression, genome modelling and X-chromosome inactivation. The non-random chromosomal distribution is a striking feature of these retroelements that somehow reflects its functionality. In the present study, we have isolated and analysed a fraction of the open reading frame 2 (ORF2) LINE-1 sequence from three rodent species, Cricetus cricetus, Peromyscus eremicus and Praomys tullbergi. Physical mapping of the isolated sequences revealed an interspersed longitudinal AT pattern of distribution along all the chromosomes of the complement in the three genomes. A detailed analysis shows that these sequences are preferentially located in the euchromatic regions, although some signals could be detected in the heterochromatin. In addition, a coincidence between the location of imprinted gene regions (as Xist and Tsix gene regions) and the LINE-1 retroelements was also observed. According to these results, we propose an involvement of LINE-1 sequences in different genomic events as gene imprinting, X-chromosome inactivation and evolution of repetitive sequences located at the heterochromatic regions (e.g. satellite DNA sequences) of the rodents' genomes analysed.

  18. Identification of pathogenic retrotransposon insertions in cancer predisposition genes.

    Science.gov (United States)

    Qian, Yaping; Mancini-DiNardo, Debora; Judkins, Thaddeus; Cox, Hannah C; Brown, Krystal; Elias, Maria; Singh, Nanda; Daniels, Courtney; Holladay, Jayson; Coffee, Bradford; Bowles, Karla R; Roa, Benjamin B

    2017-10-01

    Cancer risks have been previously reported for some retrotransposon element (RE) insertions; however, detection of these insertions is technically challenging and very few oncogenic RE insertions have been reported. Here we evaluate RE insertions identified during hereditary cancer genetic testing using a comprehensive testing strategy. Individuals who had single-syndrome or pan-cancer hereditary cancer genetic testing from February 2004 to March 2017 were included. RE insertions were identified using Sanger sequencing, Next Generation Sequencing, or multiplex quantitative PCR, and further characterized using targeted PCR and sequencing analysis. Personal cancer history, ancestry, and haplotype were evaluated. A total of 37 unique RE insertions were identified in 10 genes, affecting 211 individuals. BRCA2 accounted for 45.9% (17/37) of all unique RE insertions. Several RE insertions were detected with high frequency in populations of conserved ancestry wherein up to 100% of carriers shared a high degree of haplotype conservation, suggesting founder effects. Our comprehensive testing strategy resulted in a substantial increase in the number of reported oncogenic RE insertions, several of which may have possible founder effects. Collectively, these data show that the detection of RE insertions is an important component of hereditary cancer genetic testing and may be more prevalent than previously reported. Copyright © 2017 Myriad Genetics, Inc. Published by Elsevier Inc. All rights reserved.

  19. Radiation of the Tnt1 retrotransposon superfamily in three Solanaceae genera

    Science.gov (United States)

    Manetti, Maria E; Rossi, Magdalena; Costa, Ana PP; Clausen, Andrea M; Van Sluys, Marie-Anne

    2007-01-01

    Background Tnt1 was the first active plant retrotransposon identified in tobacco after nitrate reductase gene disruption. The Tnt1 superfamily comprises elements from Nicotiana (Tnt1 and Tto1) and Lycopersicon (Retrolyc1 and Tlc1) species. The study presented here was conducted to characterise Tnt1-related sequences in 20 wild species of Solanum and five cultivars of Solanum tuberosum. Results Tnt1-related sequences were amplified from total genomic DNA using a PCR-based approach. Purified fragments were cloned and sequenced, and clustering analysis revealed three groups that differ in their U3 region. Using a network approach with a total of 453 non-redundant sequences isolated from Solanum (197), Nicotiana (140) and Lycopersicon (116) species, it is demonstrated that the Tnt1 superfamily can be treated as a population to resolve previous phylogenetic multifurcations. The resulting RNAseH network revealed that sequences group according to the Solanaceae genus, supporting a strong association with the host genome, whereas tracing the U3 region sequence association characterises the modular evolutionary pattern within the Tnt1 superfamily. Within each genus, and irrespective of species, nearly 20% of Tnt1 sequences analysed are identical, indicative of being part of an active copy. The network approach enabled the identification of putative "master" sequences and provided evidence that within a genus these master sequences are associated with distinct U3 regions. Conclusion The results presented here support the hypothesis that the Tnt1 superfamily was present early in the evolution of Solanaceae. The evidence also suggests that the RNAseH region of Tnt1 became fixed at the host genus level whereas, within each genus, propagation was ensured by the diversification of the U3 region. Different selection pressures seemed to have acted on the U3 and RNAseH modules of ancestral Tnt1 elements, probably due to the distinct functions of these regions in the retrotransposon

  20. Insertion of retrotransposons at chromosome ends: adaptive response to chromosome maintenance

    Directory of Open Access Journals (Sweden)

    Geraldine eServant

    2016-01-01

    Full Text Available The telomerase complex is a specialized reverse transcriptase that inserts tandem DNA arrays at the linear chromosome ends and contributes to the protection of the genetic information in eukaryotic genomes. Telomerases are phylogenetically related to retrotransposons, encoding also the reverse transcriptase activity required for the amplification of their sequences throughout the genome. Intriguingly the telomerase gene is lost from the drosophila genome and tandem retrotransposons replace telomeric sequences at the chromosome extremities. This observation suggests the versatility of reverse transcriptase activity in counteracting the chromosome shortening associated with genome replication and that retrotransposons can provide this activity in case of a dysfunctional telomerase. In this review paper, we describe the major classes of retroelements present in eukaryotic genomes in order to point out the differences and similarities with the telomerase complex. In a second part, we discuss the insertion of retroelements at the ends of chromosomes as an adaptive response for dysfunctional telomeres.

  1. Large distribution and high sequence identity of a Copia-type retrotransposon in angiosperm families.

    Science.gov (United States)

    Dias, Elaine Silva; Hatt, Clémence; Hamon, Serge; Hamon, Perla; Rigoreau, Michel; Crouzillat, Dominique; Carareto, Claudia Marcia Aparecida; de Kochko, Alexandre; Guyot, Romain

    2015-09-01

    Retrotransposons are the main component of plant genomes. Recent studies have revealed the complexity of their evolutionary dynamics. Here, we have identified Copia25 in Coffea canephora, a new plant retrotransposon belonging to the Ty1-Copia superfamily. In the Coffea genomes analyzed, Copia25 is present in relatively low copy numbers and transcribed. Similarity sequence searches and PCR analyses show that this retrotransposon with LTRs (Long Terminal Repeats) is widely distributed among the Rubiaceae family and that it is also present in other distantly related species belonging to Asterids, Rosids and monocots. A particular situation is the high sequence identity found between the Copia25 sequences of Musa, a monocot, and Ixora, a dicot species (Rubiaceae). Our results reveal the complexity of the evolutionary dynamics of the ancient element Copia25 in angiosperm, involving several processes including sequence conservation, rapid turnover, stochastic losses and horizontal transfer.

  2. Retrotransposons control fruit-specific, cold-dependent accumulation of anthocyanins in blood oranges.

    Science.gov (United States)

    Butelli, Eugenio; Licciardello, Concetta; Zhang, Yang; Liu, Jianjun; Mackay, Steve; Bailey, Paul; Reforgiato-Recupero, Giuseppe; Martin, Cathie

    2012-03-01

    Traditionally, Sicilian blood oranges (Citrus sinensis) have been associated with cardiovascular health, and consumption has been shown to prevent obesity in mice fed a high-fat diet. Despite increasing consumer interest in these health-promoting attributes, production of blood oranges remains unreliable due largely to a dependency on cold for full color formation. We show that Sicilian blood orange arose by insertion of a Copia-like retrotransposon adjacent to a gene encoding Ruby, a MYB transcriptional activator of anthocyanin production. The retrotransposon controls Ruby expression, and cold dependency reflects the induction of the retroelement by stress. A blood orange of Chinese origin results from an independent insertion of a similar retrotransposon, and color formation in its fruit is also cold dependent. Our results suggest that transposition and recombination of retroelements are likely important sources of variation in Citrus.

  3. [Department of the molecular bases of semiotics].

    Science.gov (United States)

    Ternovyĭ, K S

    1995-01-01

    Department of molecular basis of semiotics was organized in 1986. The main task of the department was to work out new approaches in estimation of the state of immune and blood system at the tissue, cell and molecular levels, using biochemical, biophysical and molecular biology techniques. There are several main directions of scientific investigations at the department. Most informational methods were collected in "immunological portrait" for differential diagnostic and complex investigation of the immune system of autoimmune patients. This group of techniques was used to study changes in the immune system of Kievites after the Chernobyl disaster. A decrease of complement and thymic serum activity was detected. Antibodies against nuclear components appeared in 20% of donors. And a higher of circulating immune complex of low molecular weight was observed. Low level of thymic serum activity in blood of autoimmune patients with rheumatoid arthritis, lupus erythematosus, diabetes, herpes and other depends on the appearance of zinc-independent timuline inhibitor less then 2000 D. Another kind of thymic hormone inhibitors was detected in thymectomized adult mice. Its effect disappears when zinc added in blood rather due to competition for lymphocyte surface receptors timuline and its inactive analogue than other mechanism. Therapeutic effect of UV irradiation of patients' blood was shown to be closely connected with the changes in thymic serum activity in respect to stabilization of thymic hormone/inhibitor ratio. The immunochemical techniques were used to detect and investigate tumor-associated chromatin antigens in human and animal tumor cells. Antigens not found in normal tissues were detected when using rabbit antibodies against chromatin of rat hepatocarcinoma and human colon and carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Molecular Bases of Cutaneous and Uveal Melanomas

    Directory of Open Access Journals (Sweden)

    Sudeep Gaudi

    2011-01-01

    Full Text Available Intensive research in recent years has begun to unlock the mysteries surrounding the molecular pathogenesis of melanoma, the deadliest of skin cancers. The high-penetrance, low-frequency susceptibility gene CDKN2A produces tumor suppressor proteins that function in concert with p53 and retinoblastoma protein to thwart melanomagenesis. Aberrant CDKN2A gene products have been implicated in a great many cases of familial cutaneous melanoma. Sporadic cases, on the other hand, often involve constitutive signal transduction along the mitogen-activated protein kinase (MAPK pathway, with particular focus falling upon mutated RAS and RAF protooncogenes. The proliferative effects of the MAPK pathway may be complemented by the antiapoptotic signals of the PI3K/AKT pathway. After skin, melanoma most commonly affects the eye. Data for the constitutive activation of the MAPK pathway in uveal melanoma exists as well, however, not through mutations of RAS and RAF. Rather, evidence implicates the proto-oncogene GNAQ. In the following discussion, we review the major molecular pathways implicated in both familial and sporadic cutaneous melanomagenesis, the former accounting for approximately 10% of cases. Additionally, we discuss the molecular pathways for which preliminary evidence suggests a role in uveal melanomagenesis.

  5. Human Retrotransposon Insertion Polymorphisms Are Associated with Health and Disease via Gene Regulatory Phenotypes

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2017-08-01

    Full Text Available The human genome hosts several active families of transposable elements (TEs, including the Alu, LINE-1, and SVA retrotransposons that are mobilized via reverse transcription of RNA intermediates. We evaluated how insertion polymorphisms generated by human retrotransposon activity may be related to common health and disease phenotypes that have been previously interrogated through genome-wide association studies (GWAS. To address this question, we performed a genome-wide screen for retrotransposon polymorphism disease associations that are linked to TE induced gene regulatory changes. Our screen first identified polymorphic retrotransposon insertions found in linkage disequilibrium (LD with single nucleotide polymorphisms that were previously associated with common complex diseases by GWAS. We further narrowed this set of candidate disease associated retrotransposon polymorphisms by identifying insertions that are located within tissue-specific enhancer elements. We then performed expression quantitative trait loci analysis on the remaining set of candidates in order to identify polymorphic retrotransposon insertions that are associated with gene expression changes in B-cells of the human immune system. This progressive and stringent screen yielded a list of six retrotransposon insertions as the strongest candidates for TE polymorphisms that lead to disease via enhancer-mediated changes in gene regulation. For example, we found an SVA insertion within a cell-type specific enhancer located in the second intron of the B4GALT1 gene. B4GALT1 encodes a glycosyltransferase that functions in the glycosylation of the Immunoglobulin G (IgG antibody in such a way as to convert its activity from pro- to anti-inflammatory. The disruption of the B4GALT1 enhancer by the SVA insertion is associated with down-regulation of the gene in B-cells, which would serve to keep the IgG molecule in a pro-inflammatory state. Consistent with this idea, the B4GALT1 enhancer

  6. Biomarkers of lead exposure and DNA methylation within retrotransposons.

    Science.gov (United States)

    Wright, Robert O; Schwartz, Joel; Wright, Rosalind J; Bollati, Valentina; Tarantini, Letizia; Park, Sung Kyun; Hu, Howard; Sparrow, David; Vokonas, Pantel; Baccarelli, Andrea

    2010-06-01

    DNA methylation is an epigenetic mark that regulates gene expression. Changes in DNA methylation within white blood cells may result from cumulative exposure to environmental metals such as lead. Bone lead, a marker of cumulative exposure, may therefore better predict DNA methylation than does blood lead. In this study we compared associations between lead biomarkers and DNA methylation. We measured global methylation in participants of the Normative Aging Study (all men) who had archived DNA samples. We measured patella and tibia lead levels by K-X-Ray fluorescence and blood lead by atomic absorption spectrophotometry. DNA samples from blood were used to determine global methylation averages within CpG islands of long interspersed nuclear elements-1 (LINE-1) and Alu retrotransposons. A mixed-effects model using repeated measures of Alu or LINE-1 as the dependent variable and blood/bone lead (tibia or patella in separate models) as the primary exposure marker was fit to the data. Overall mean global methylation (+/- SD) was 26.3 +/- 1.0 as measured by Alu and 76.8 +/- 1.9 as measured by LINE-1. In the mixed-effects model, patella lead levels were inversely associated with LINE-1 (beta = -0.25; p lead and blood lead did not predict global methylation for either Alu or LINE-1. Patella lead levels predicted reduced global DNA methylation within LINE-1 elements. The association between lead exposure and LINE-1 DNA methylation may have implications for the mechanisms of action of lead on health outcomes, and also suggests that changes in DNA methylation may represent a biomarker of past lead exposure.

  7. Guanidinium-based "molecular glues" for modulation of biomolecular functions.

    Science.gov (United States)

    Mogaki, Rina; Hashim, P K; Okuro, Kou; Aida, Takuzo

    2017-10-30

    Molecular adhesion based on multivalent interactions plays essential roles in various biological processes. Hence, "molecular glues" that can adhere to biomolecules may modulate biomolecular functions and therefore can be applied to therapeutics. This tutorial review describes design strategies for developing adhesive motifs for biomolecules based on multivalent interactions. We highlight a guanidinium ion-based salt-bridge as a key interaction for adhesion to biomolecules and discuss the application of molecular glues for manipulation of biomolecular assemblies, drug delivery systems, and modulation of biomolecular functions.

  8. Unidirectional light-driven molecular motors based on overcrowded alkenes.

    Science.gov (United States)

    Cnossen, Arjen; Browne, Wesley R; Feringa, Ben L

    2014-01-01

    Over the last two decades, interest in nanotechnology has led to the design and synthesis of a toolbox of nanoscale versions of macroscopic devices and components. In molecular nanotechnology, linear motors based on rotaxanes and rotary motors based on overcrowded alkenes are particularly promising for performing work at the nanoscale. In this chapter, progress on light-driven molecular motors based on overcrowded alkenes is reviewed. Both the so-called first and second generation molecular motors are discussed, as well as their potential applications.

  9. A path based approach to assessing molecular complexity.

    Science.gov (United States)

    Proudfoot, John R

    2017-05-01

    An atom environment, path based approach to calculating molecular complexity is described. Based on Shannon's equation, the method transforms the number and diversity of paths emanating from an atom to an atom-complexity from which a number of molecular complexity measures are derived. The method is independent of explicitly predefined features such as ring membership, bond types, chirality or symmetry. These path-based measures of complexity can distinguish subtle differences in molecular structure and an application to the visualization of marketed drugs, including a number of biologics, is presented. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Horizontal transfer of non-LTR retrotransposons from arthropods to flowering plants.

    Science.gov (United States)

    Gao, Dongying; Chu, Ye; Xia, Han; Xu, Chunming; Heyduk, Karolina; Abernathy, Brian; Ozias-Akins, Peggy; Leebens-Mack, James H; Jackson, Scott A

    2017-10-23

    Even though lateral movements of transposons across families and even phyla within multicellular eukaryotic kingdoms have been found, little is known about transposon transfer between the kingdoms Animalia and Plantae. We discovered a novel non-LTR retrotransposon, AdLINE3, in a wild peanut species. Sequence comparisons and phylogenetic analyses indicated that AdLINE3 is a member of the RTE clade, originally identified in a nematode and rarely reported in plants. We identified RTE elements in 82 plants, spanning angiosperms to algae, including recently active elements in some flowering plants. RTE elements in flowering plants were likely derived from a single family we refer to as An-RTE. Interestingly, An-RTEs show significant DNA sequence identity with non-LTR retroelements from 42 animals belonging to four phyla. Moreover, the sequence identity of RTEs between two arthropods and two plants was higher than that of homologous genes. Phylogenetic and evolutionary analyses of RTEs from both animals and plants suggest that the An-RTE family was likely transferred horizontally into angiosperms from an ancient aphid(s) or ancestral arthropod(s). Notably, some An-RTEs were recruited as coding sequences of functional genes participating in metabolic or other biochemical processes in plants. This is the first potential example of horizontal transfer of transposons between animals and flowering plants. Our findings help to understand exchanges of genetic material between the kingdom Animalia and Plantae and suggest arthropods likely impacted on plant genome evolution. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution 2017. This work is written by US Government employees and is in the public domain in the US.

  11. Molecular recognition in poly(epsilon-caprolactone)-based thermoplastic elastomers

    NARCIS (Netherlands)

    Wisse, Eva; Spiering, A. J. H.; van Leeuwen, Ellen N. M.; Renken, Raymond A. E.; Dankers, Patricia Y. W.; Brouwer, Linda A.; van Luyn, Marja J. A.; Harmsen, Martin C.; Sommerdijk, Nico A. J. M.; Meijer, E. W.

    2006-01-01

    The molecular recognition properties of the hydrogen bonding segments in biodegradable thermoplastic elastomers were explored, aiming at the further functionalization of these potentially interesting biomaterials. A poly(epsilon-caprolactone)-based poly(urea) 2 was synthesized and characterized in

  12. Rapid and Recent Evolution of LTR Retrotransposons Drives Rice Genome Evolution During the Speciation of AA-Genome Oryza Species.

    Science.gov (United States)

    Zhang, Qun-Jie; Gao, Li-Zhi

    2017-06-07

    The dynamics of long terminal repeat (LTR) retrotransposons and their contribution to genome evolution during plant speciation have remained largely unanswered. Here, we perform a genome-wide comparison of all eight Oryza AA-genome species, and identify 3911 intact LTR retrotransposons classified into 790 families. The top 44 most abundant LTR retrotransposon families show patterns of rapid and distinct diversification since the species split over the last ∼4.8 MY (million years). Phylogenetic and read depth analyses of 11 representative retrotransposon families further provide a comprehensive evolutionary landscape of these changes. Compared with Ty1-copia, independent bursts of Ty3-gypsy retrotransposon expansions have occurred with the three largest showing signatures of lineage-specific evolution. The estimated insertion times of 2213 complete retrotransposons from the top 23 most abundant families reveal divergent life histories marked by speedy accumulation, decline, and extinction that differed radically between species. We hypothesize that this rapid evolution of LTR retrotransposons not only divergently shaped the architecture of rice genomes but also contributed to the process of speciation and diversification of rice. Copyright © 2017 Zhang and Gao.

  13. Retrotransposon silencing and telomere integrity in somatic cells of Drosophila depends on the cytosine-5 methyltransferase DNMT2.

    Science.gov (United States)

    Phalke, Sameer; Nickel, Olaf; Walluscheck, Diana; Hortig, Frank; Onorati, Maria Cristina; Reuter, Gunter

    2009-06-01

    Here we show that the cytosine-5 methyltransferase DNMT2 controls retrotransposon silencing in Drosophila somatic cells. In Drosophila, significant DNMT2-dependent DNA methylation occurs during early embryogenesis. Suppression of white gene silencing by Mt2 (Dnmt2) null mutations in variegated P[w(+)] element insertions identified functional targets of DNMT2. The enzyme controls DNA methylation at retrotransposons in early embryos and initiates histone H4K20 trimethylation catalyzed by the SUV4-20 methyltransferase. In somatic cells, loss of DNMT2 eliminates H4K20 trimethylation at retrotransposons and impairs maintenance of retrotransposon silencing. In Dnmt2 and Suv4-20 null genotypes, retrotransposons are strongly overexpressed in somatic but not germline cells, where retrotransposon silencing depends on an RNAi mechanism. DNMT2 also controls integrity of chromosome 2R and 3R telomeres. In Dnmt2 null strains, we found stable loss of the subtelomeric clusters of defective Invader4 elements. Together, these results demonstrate a previously unappreciated role of DNA methylation in retrotransposon silencing and telomere integrity in Drosophila.

  14. An evolutionary arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons.

    Science.gov (United States)

    Jacobs, Frank M J; Greenberg, David; Nguyen, Ngan; Haeussler, Maximilian; Ewing, Adam D; Katzman, Sol; Paten, Benedict; Salama, Sofie R; Haussler, David

    2014-12-11

    Throughout evolution primate genomes have been modified by waves of retrotransposon insertions. For each wave, the host eventually finds a way to repress retrotransposon transcription and prevent further insertions. In mouse embryonic stem cells, transcriptional silencing of retrotransposons requires KAP1 (also known as TRIM28) and its repressive complex, which can be recruited to target sites by KRAB zinc-finger (KZNF) proteins such as murine-specific ZFP809 which binds to integrated murine leukaemia virus DNA elements and recruits KAP1 to repress them. KZNF genes are one of the fastest growing gene families in primates and this expansion is hypothesized to enable primates to respond to newly emerged retrotransposons. However, the identity of KZNF genes battling retrotransposons currently active in the human genome, such as SINE-VNTR-Alu (SVA) and long interspersed nuclear element 1 (L1), is unknown. Here we show that two primate-specific KZNF genes rapidly evolved to repress these two distinct retrotransposon families shortly after they began to spread in our ancestral genome. ZNF91 underwent a series of structural changes 8-12 million years ago that enabled it to repress SVA elements. ZNF93 evolved earlier to repress the primate L1 lineage until ∼12.5 million years ago when the L1PA3-subfamily of retrotransposons escaped ZNF93's restriction through the removal of the ZNF93-binding site. Our data support a model where KZNF gene expansion limits the activity of newly emerged retrotransposon classes, and this is followed by mutations in these retrotransposons to evade repression, a cycle of events that could explain the rapid expansion of lineage-specific KZNF genes.

  15. Controlling charge current through a DNA based molecular transistor

    Energy Technology Data Exchange (ETDEWEB)

    Behnia, S., E-mail: s.behnia@sci.uut.ac.ir; Fathizadeh, S.; Ziaei, J.

    2017-01-05

    Molecular electronics is complementary to silicon-based electronics and may induce electronic functions which are difficult to obtain with conventional technology. We have considered a DNA based molecular transistor and study its transport properties. The appropriate DNA sequence as a central chain in molecular transistor and the functional interval for applied voltages is obtained. I–V characteristic diagram shows the rectifier behavior as well as the negative differential resistance phenomenon of DNA transistor. We have observed the nearly periodic behavior in the current flowing through DNA. It is reported that there is a critical gate voltage for each applied bias which above it, the electrical current is always positive. - Highlights: • Modeling a DNA based molecular transistor and studying its transport properties. • Choosing the appropriate DNA sequence using the quantum chaos tools. • Choosing the functional interval for voltages via the inverse participation ratio tool. • Detecting the rectifier and negative differential resistance behavior of DNA.

  16. How a retrotransposon exploits the plant's heat stress response for its activation.

    Directory of Open Access Journals (Sweden)

    Vladimir V Cavrak

    2014-01-01

    Full Text Available Retrotransposons are major components of plant and animal genomes. They amplify by reverse transcription and reintegration into the host genome but their activity is usually epigenetically silenced. In plants, genomic copies of retrotransposons are typically associated with repressive chromatin modifications installed and maintained by RNA-directed DNA methylation. To escape this tight control, retrotransposons employ various strategies to avoid epigenetic silencing. Here we describe the mechanism developed by ONSEN, an LTR-copia type retrotransposon in Arabidopsis thaliana. ONSEN has acquired a heat-responsive element recognized by plant-derived heat stress defense factors, resulting in transcription and production of full length extrachromosomal DNA under elevated temperatures. Further, the ONSEN promoter is free of CG and CHG sites, and the reduction of DNA methylation at the CHH sites is not sufficient to activate the element. Since dividing cells have a more pronounced heat response, the extrachromosomal ONSEN DNA, capable of reintegrating into the genome, accumulates preferentially in the meristematic tissue of the shoot. The recruitment of a major plant heat shock transcription factor in periods of heat stress exploits the plant's heat stress response to achieve the transposon's activation, making it impossible for the host to respond appropriately to stress without losing control over the invader.

  17. Evolution of brain functions in mammals and LTR retrotransposon-derived genes.

    Science.gov (United States)

    Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

    2016-01-01

    In the human genome, there are approximately 30 LTR retrotransposon-derived genes, such as the sushi-ichi retrotransposon homologues (SIRH) and the paraneoplastic Ma antigen (PNMA) family genes. They are derivatives from the original LTR retrotransposons and each gene seems to have its own unique function. PEG10/SIRH1 as well as PEG11/RTL1/SIRH2 and SIRH7/LDOC1 play essential roles in placenta formation, maintenance of fetal capillaries and the differentiation/maturation of a variety of placental cells, respectively. All of this evidence provides strong support for their contribution to the evolution of viviparity in mammals via their eutherian-specific functions. SIRH11/ZCCHC16 is an X-linked gene that encodes a CCHC type of zinc-finger protein that exhibits high sequence identity to the LTR retrotransposon Gag protein and its deletion causes abnormal behavior related to cognition, including attention, impulsivity and working memory, possibly via the locus coeruleus noradrenaergic system in mice. Therefore, we have suggested that the acquisition of SIRH11/ZCCHC16 was involved in eutherian brain evolution. Interestingly, SIRH11/ZCCHC16 displays lineage-specific structural and putative species-specific functional variations in eutherians, suggesting that it contributed to the diversification of eutherians via increasing evolutionary fitness by these changes.

  18. How a retrotransposon exploits the plant's heat stress response for its activation.

    Science.gov (United States)

    Cavrak, Vladimir V; Lettner, Nicole; Jamge, Suraj; Kosarewicz, Agata; Bayer, Laura Maria; Mittelsten Scheid, Ortrun

    2014-01-01

    Retrotransposons are major components of plant and animal genomes. They amplify by reverse transcription and reintegration into the host genome but their activity is usually epigenetically silenced. In plants, genomic copies of retrotransposons are typically associated with repressive chromatin modifications installed and maintained by RNA-directed DNA methylation. To escape this tight control, retrotransposons employ various strategies to avoid epigenetic silencing. Here we describe the mechanism developed by ONSEN, an LTR-copia type retrotransposon in Arabidopsis thaliana. ONSEN has acquired a heat-responsive element recognized by plant-derived heat stress defense factors, resulting in transcription and production of full length extrachromosomal DNA under elevated temperatures. Further, the ONSEN promoter is free of CG and CHG sites, and the reduction of DNA methylation at the CHH sites is not sufficient to activate the element. Since dividing cells have a more pronounced heat response, the extrachromosomal ONSEN DNA, capable of reintegrating into the genome, accumulates preferentially in the meristematic tissue of the shoot. The recruitment of a major plant heat shock transcription factor in periods of heat stress exploits the plant's heat stress response to achieve the transposon's activation, making it impossible for the host to respond appropriately to stress without losing control over the invader.

  19. The Ty1 LTR-retrotransposon of budding yeast, Saccharomyces cerevisiae

    Science.gov (United States)

    Curcio, M. Joan; Lutz, Sheila; Lesage, Pascale

    2015-01-01

    Summary Long-terminal repeat (LTR)-retrotransposons generate a copy of their DNA (cDNA) by reverse transcription of their RNA genome in cytoplasmic nucleocapsids. They are widespread in the eukaryotic kingdom and are the evolutionary progenitors of retroviruses [1]. The Ty1 element of the budding yeast Saccharomyces cerevisiae was the first LTR-retrotransposon demonstrated to mobilize through an RNA intermediate, and not surprisingly, is the best studied. The depth of our knowledge of Ty1 biology stems not only from the predominance of active Ty1 elements in the S. cerevisiae genome but also the ease and breadth of genomic, biochemical and cell biology approaches available to study cellular processes in yeast. This review describes the basic structure of Ty1 and its gene products, the replication cycle, the rapidly expanding compendium of host co-factors known to influence retrotransposition and the nature of Ty1's elaborate symbiosis with its host. Our goal is to illuminate the value of Ty1 as a paradigm to explore the biology of LTR-retrotransposons in multicellular organisms, where the low frequency of retrotransposition events presents a formidable barrier to investigations of retrotransposon biology. PMID:25893143

  20. Insights into the DNA cleavage mechanism of human LINE-1 retrotransposon endonuclease

    NARCIS (Netherlands)

    Repanas, K.; Fuentes, G.; Cohen, S.; Bonvin, A.M.J.J.; Perrakis, A.

    2008-01-01

    The human LINE-1 endonuclease (L1-EN) contributes in defining the genomic integration sites of the abundant human L1 and Alu retrotransposons. LINEs have been considered as possible vehicles for gene delivery and understanding the mechanism of L1-EN could help engineering them as genetic tools. We

  1. An evaluation of a SVA retrotransposon in the FUS promoter as a transcriptional regulator and its association to ALS.

    Directory of Open Access Journals (Sweden)

    Abigail L Savage

    Full Text Available Genetic mutations of FUS have been linked to many diseases including Amyotrophic Lateral Sclerosis (ALS and Frontotemporal Lobar Degeneration. A primate specific and polymorphic retrotransposon of the SINE-VNTR-Alu (SVA family is present upstream of the FUS gene. Here we have demonstrated that this retrotransposon can act as a classical transcriptional regulatory domain in the context of a reporter gene construct both in vitro in the human SK-N-AS neuroblastoma cell line and in vivo in a chick embryo model. We have also demonstrated that the SVA is composed of multiple distinct regulatory domains, one of which is a variable number tandem repeat (VNTR. The ability of the SVA and its component parts to direct reporter gene expression supported a hypothesis that this region could direct differential FUS expression in vivo. The SVA may therefore contribute to the modulation of FUS expression exhibited in and associated with neurological disorders including ALS where FUS regulation may be an important parameter in progression of the disease. As VNTRs are often clinical associates for disease progression we determined the extent of polymorphism within the SVA. In total 2 variants of the SVA were identified based within a central VNTR. Preliminary analysis addressed the association of these SVA variants within a small sporadic ALS cohort but did not reach statistical significance, although we did not include other parameters such as SNPs within the SVA or an environmental factor in this analysis. The latter may be particularly important as the transcriptional and epigenetic properties of the SVA are likely to be directed by the environment of the cell.

  2. An evaluation of a SVA retrotransposon in the FUS promoter as a transcriptional regulator and its association to ALS.

    Science.gov (United States)

    Savage, Abigail L; Wilm, Thomas P; Khursheed, Kejhal; Shatunov, Aleksey; Morrison, Karen E; Shaw, Pamela J; Shaw, Christopher E; Smith, Bradley; Breen, Gerome; Al-Chalabi, Ammar; Moss, Diana; Bubb, Vivien J; Quinn, John P

    2014-01-01

    Genetic mutations of FUS have been linked to many diseases including Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration. A primate specific and polymorphic retrotransposon of the SINE-VNTR-Alu (SVA) family is present upstream of the FUS gene. Here we have demonstrated that this retrotransposon can act as a classical transcriptional regulatory domain in the context of a reporter gene construct both in vitro in the human SK-N-AS neuroblastoma cell line and in vivo in a chick embryo model. We have also demonstrated that the SVA is composed of multiple distinct regulatory domains, one of which is a variable number tandem repeat (VNTR). The ability of the SVA and its component parts to direct reporter gene expression supported a hypothesis that this region could direct differential FUS expression in vivo. The SVA may therefore contribute to the modulation of FUS expression exhibited in and associated with neurological disorders including ALS where FUS regulation may be an important parameter in progression of the disease. As VNTRs are often clinical associates for disease progression we determined the extent of polymorphism within the SVA. In total 2 variants of the SVA were identified based within a central VNTR. Preliminary analysis addressed the association of these SVA variants within a small sporadic ALS cohort but did not reach statistical significance, although we did not include other parameters such as SNPs within the SVA or an environmental factor in this analysis. The latter may be particularly important as the transcriptional and epigenetic properties of the SVA are likely to be directed by the environment of the cell.

  3. The RNAPII-CTD Maintains Genome Integrity through Inhibition of Retrotransposon Gene Expression and Transposition.

    Directory of Open Access Journals (Sweden)

    Maria J Aristizabal

    2015-10-01

    Full Text Available RNA polymerase II (RNAPII contains a unique C-terminal domain that is composed of heptapeptide repeats and which plays important regulatory roles during gene expression. RNAPII is responsible for the transcription of most protein-coding genes, a subset of non-coding genes, and retrotransposons. Retrotransposon transcription is the first step in their multiplication cycle, given that the RNA intermediate is required for the synthesis of cDNA, the material that is ultimately incorporated into a new genomic location. Retrotransposition can have grave consequences to genome integrity, as integration events can change the gene expression landscape or lead to alteration or loss of genetic information. Given that RNAPII transcribes retrotransposons, we sought to investigate if the RNAPII-CTD played a role in the regulation of retrotransposon gene expression. Importantly, we found that the RNAPII-CTD functioned to maintaining genome integrity through inhibition of retrotransposon gene expression, as reducing CTD length significantly increased expression and transposition rates of Ty1 elements. Mechanistically, the increased Ty1 mRNA levels in the rpb1-CTD11 mutant were partly due to Cdk8-dependent alterations to the RNAPII-CTD phosphorylation status. In addition, Cdk8 alone contributed to Ty1 gene expression regulation by altering the occupancy of the gene-specific transcription factor Ste12. Loss of STE12 and TEC1 suppressed growth phenotypes of the RNAPII-CTD truncation mutant. Collectively, our results implicate Ste12 and Tec1 as general and important contributors to the Cdk8, RNAPII-CTD regulatory circuitry as it relates to the maintenance of genome integrity.

  4. Bases moleculares de alfa-talasemia en la Argentina

    OpenAIRE

    Karen G Scheps; Liliana Francipane; Abigail Nash; Gloria E Cerrone; Silvia B Copelli; Viviana Varela

    2015-01-01

    La α-talasemia, es uno de los desórdenes hereditarios más frecuentes mundialmente. Al presente, el diagnóstico molecular es la única herramienta que permite el diagnóstico certero. El propósito de este trabajo fue caracterizar las bases moleculares de estos síndromes en nuestro medio, y establecer relaciones genotipo-fenotipo. Mediante la complementación de distintas técnicas de biología molecular e hibridación fluorescente in situ (FISH), se logró poner en evidencia la presencia de mutacione...

  5. Possibility of gas sensor based on C20 molecular devices

    Science.gov (United States)

    Zhao, Wenkai; Yang, Chuanlu; Zou, Dongqing; Sun, Zhaopeng; Ji, Guomin

    2017-06-01

    We theoretically investigate the possibility of diatomic gas detection (NO, CO, O2) by making use of the transport properties of the C20 molecular junctions. The calculations are performed by using nonequilibrium Green's function (NEGF) formalism in combination with density functional theory (DFT). In this work, we systematically study the most stable adsorption structural configurations, adsorption energy, and the transport properties on C20 molecular junctions with these diatomic gas molecules. It is found that NO and O2 gas molecule can be detected selectively. We suggest its possibility of nanosensors for highly sensitive and selective based on C20 molecular junction systems.

  6. The reverse transcriptase encoded by LINE-1 retrotransposons in the genesis, progression and therapy of cancer

    Directory of Open Access Journals (Sweden)

    Ilaria eSciamanna

    2016-02-01

    Full Text Available In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1 retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT, which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can sequester RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity.

  7. Identification of polymorphic SVA retrotransposons using a mobile element scanning method for SVA (ME-Scan-SVA)

    National Research Council Canada - National Science Library

    Ha, Hongseok; Loh, Jui Wan; Xing, Jinchuan

    2016-01-01

    Mobile element insertions are a major source of human genomic variation. SVA (SINE-R/VNTR/Alu) is the youngest retrotransposon family in the human genome and a number of diseases are known to be caused by SVA insertions...

  8. The impact of Ty3-gypsy group LTR retrotransposons Fatima on B-genome specificity of polyploid wheats

    National Research Council Canada - National Science Library

    Salina, Elena A; Sergeeva, Ekaterina M; Adonina, Irina G; Shcherban, Andrey B; Belcram, Harry; Huneau, Cecile; Chalhoub, Boulos

    2011-01-01

    .... Here, we investigated the impact of the well-represented family of gypsy LTR-retrotransposons, Fatima, on B-genome divergence of allopolyploid wheat using the fluorescent in situ hybridisation (FISH...

  9. Effects of As2O3 on DNA methylation, genomic instability, and LTR retrotransposon polymorphism in Zea mays.

    Science.gov (United States)

    Erturk, Filiz Aygun; Aydin, Murat; Sigmaz, Burcu; Taspinar, M Sinan; Arslan, Esra; Agar, Guleray; Yagci, Semra

    2015-12-01

    Arsenic is a well-known toxic substance on the living organisms. However, limited efforts have been made to study its DNA methylation, genomic instability, and long terminal repeat (LTR) retrotransposon polymorphism causing properties in different crops. In the present study, effects of As2O3 (arsenic trioxide) on LTR retrotransposon polymorphism and DNA methylation as well as DNA damage in Zea mays seedlings were investigated. The results showed that all of arsenic doses caused a decreasing genomic template stability (GTS) and an increasing Random Amplified Polymorphic DNAs (RAPDs) profile changes (DNA damage). In addition, increasing DNA methylation and LTR retrotransposon polymorphism characterized a model to explain the epigenetically changes in the gene expression were also found. The results of this experiment have clearly shown that arsenic has epigenetic effect as well as its genotoxic effect. Especially, the increasing of polymorphism of some LTR retrotransposon under arsenic stress may be a part of the defense system against the stress.

  10. Electronic transport properties of a quinone-based molecular switch

    Science.gov (United States)

    Zheng, Ya-Peng; Bian, Bao-An; Yuan, Pei-Pei

    2016-09-01

    In this paper, we carried out first-principles calculations based on density functional theory and non-equilibrium Green's function to investigate the electronic transport properties of a quinone-based molecule sandwiched between two Au electrodes. The molecular switch can be reversibly switched between the reduced hydroquinone (HQ) and oxidized quinone (Q) states via redox reactions. The switching behavior of two forms is analyzed through their I- V curves, transmission spectra and molecular projected self-consistent Hamiltonian at zero bias. Then we discuss the transmission spectra of the HQ and Q forms at different bias, and explain the oscillation of current according to the transmission eigenstates of LUMO energy level for Q form. The results suggest that this kind of a quinone-based molecule is usable as one of the good candidates for redox-controlled molecular switches.

  11. Progress in molecular-based management of differentiated thyroid cancer

    Science.gov (United States)

    Xing, Mingzhao; Haugen, Bryan R; Schlumberger, Martin

    2014-01-01

    Substantial developments have occurred in the past 5–10 years in clinical translational research of thyroid cancer. Diagnostic molecular markers, such as RET-PTC, RAS, and BRAFV600E mutations; galectin 3; and a new gene expression classifier, are outstanding examples that have improved diagnosis of thyroid nodules. BRAF mutation is a prognostic genetic marker that has improved risk stratification and hence tailored management of patients with thyroid cancer, including those with conventionally low risks. Novel molecular-targeted treatments hold great promise for radioiodine-refractory and surgically inoperable thyroid cancers as shown in clinical trials; such treatments are likely to become a component of the standard treatment regimen for patients with thyroid cancer in the near future. These novel molecular-based management strategies for thyroid nodules and thyroid cancer are the most exciting developments in this unprecedented era of molecular thyroid-cancer medicine. PMID:23668556

  12. An evolutionary arms race between KRAB zinc finger genes 91/93 and SVA/L1 retrotransposons

    Science.gov (United States)

    Jacobs, Frank MJ; Greenberg, David; Nguyen, Ngan; Haeussler, Maximilian; Ewing, Adam D; Katzman, Sol; Paten, Benedict; Salama, Sofie R; Haussler, David

    2014-01-01

    Summary Throughout evolution, primate genomes have been modified by waves of retrotransposon insertions1,2,3. For each wave, the host eventually finds a way to repress retrotransposon transcription and prevent further insertions. In mouse embryonic stem cells (mESCs), transcriptional silencing of retrotransposons requires TRIM28 (KAP1) and it’s repressive complex, which can be recruited to target sites by KRAB zinc finger proteins such as murine-specific ZFP809 which binds to integrated murine leukemia virus DNA elements and recruits KAP1 to repress them4,5. KZNF genes are one of the fastest growing gene families in primates and this expansion is hypothesized to enable primates to respond to newly emerged retrotransposons6,7. However, the identity of KZNF genes battling retrotransposons currently active in the human genome, such as SINE-VNTR-Alu (SVA)8 and Long Interspersed Nuclear Element-1 (L1)9, is unknown. We find that two primate-specific KZNF genes rapidly evolved to repress these two distinct retrotransposon families shortly after they began to spread in our ancestral genome. ZNF91 underwent a series of structural changes 8-12 MYA that enabled it to repress SVA elements. ZNF93 evolved earlier to repress the primate L1 lineage until ~12.5 MYA when the L1PA3-subfamily escaped ZNF93’s restriction through purge of the ZNF93 binding site. Our data support a model where KZNF gene expansion limits the activity of newly emerged retrotransposon classes, and this is followed by mutations in these retrotransposons to evade repression, a cycle of events that could explain the rapid expansion of lineage-specific KZNF genes. PMID:25274305

  13. Protein analysis based on molecular beacon probes and biofunctionalized nanoparticles

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    With the completion of the human genome-sequencing project, there has been a resulting change in the focus of studies from genomics to proteomics. By utilizing the inherent advantages of molecular beacon probes and biofunctionalized nanoparticles, a series of novel principles, methods and techniques have been exploited for bioanalytical and biomedical studies. This review mainly discusses the applications of molecular beacon probes and biofunctionalized nanoparticles-based technologies for realtime, in-situ, highly sensitive and highly selective protein analysis, including the nonspecific or specific protein detection and separation, protein/DNA interaction studies, cell surface protein recognition, and antigen-antibody binding process-based bacteria assays. The introduction of molecular beacon probes and biofunctionalized nanoparticles into the protein analysis area would necessarily advance the proteomics research.

  14. Pathogenic exon-trapping by SVA retrotransposon and rescue in Fukuyama muscular dystrophy.

    Science.gov (United States)

    Taniguchi-Ikeda, Mariko; Kobayashi, Kazuhiro; Kanagawa, Motoi; Yu, Chih-chieh; Mori, Kouhei; Oda, Tetsuya; Kuga, Atsushi; Kurahashi, Hiroki; Akman, Hasan O; DiMauro, Salvatore; Kaji, Ryuji; Yokota, Toshifumi; Takeda, Shin'ichi; Toda, Tatsushi

    2011-10-05

    Fukuyama muscular dystrophy (FCMD; MIM253800), one of the most common autosomal recessive disorders in Japan, was the first human disease found to result from ancestral insertion of a SINE-VNTR-Alu (SVA) retrotransposon into a causative gene. In FCMD, the SVA insertion occurs in the 3' untranslated region (UTR) of the fukutin gene. The pathogenic mechanism for FCMD is unknown, and no effective clinical treatments exist. Here we show that aberrant messenger RNA (mRNA) splicing, induced by SVA exon-trapping, underlies the molecular pathogenesis of FCMD. Quantitative mRNA analysis pinpointed a region that was missing from transcripts in patients with FCMD. This region spans part of the 3' end of the fukutin coding region, a proximal part of the 3' UTR and the SVA insertion. Correspondingly, fukutin mRNA transcripts in patients with FCMD and SVA knock-in model mice were shorter than the expected length. Sequence analysis revealed an abnormal splicing event, provoked by a strong acceptor site in SVA and a rare alternative donor site in fukutin exon 10. The resulting product truncates the fukutin carboxy (C) terminus and adds 129 amino acids encoded by the SVA. Introduction of antisense oligonucleotides (AONs) targeting the splice acceptor, the predicted exonic splicing enhancer and the intronic splicing enhancer prevented pathogenic exon-trapping by SVA in cells of patients with FCMD and model mice, rescuing normal fukutin mRNA expression and protein production. AON treatment also restored fukutin functions, including O-glycosylation of α-dystroglycan (α-DG) and laminin binding by α-DG. Moreover, we observe exon-trapping in other SVA insertions associated with disease (hypercholesterolemia, neutral lipid storage disease) and human-specific SVA insertion in a novel gene. Thus, although splicing into SVA is known, we have discovered in human disease a role for SVA-mediated exon-trapping and demonstrated the promise of splicing modulation therapy as the first radical

  15. Obtaining retrotransposon sequences, analysis of their genomic distribution and use of retrotransposon-derived genetic markers in lentil (Lens culinaris Medik.).

    Science.gov (United States)

    Rey-Baños, Rita; Sáenz de Miera, Luis E; García, Pedro; Pérez de la Vega, Marcelino

    2017-01-01

    Retrotransposons with long terminal repeats (LTR-RTs) are widespread mobile elements in eukaryotic genomes. We obtained a total of 81 partial LTR-RT sequences from lentil corresponding to internal retrotransposon components and LTRs. Sequences were obtained by PCR from genomic DNA. Approximately 37% of the LTR-RT internal sequences presented premature stop codons, pointing out that these elements must be non-autonomous. LTR sequences were obtained using the iPBS technique which amplifies sequences between LTR-RTs. A total of 193 retrotransposon-derived genetic markers, mainly iPBS, were used to obtain a genetic linkage map from 94 F7 inbred recombinant lines derived from the cross between the cultivar Lupa and the wild ancestor L. culinaris subsp. orientalis. The genetic map included 136 markers located in eight linkage groups. Clusters of tightly linked retrotransposon-derived markers were detected in linkage groups LG1, LG2, and LG6, hence denoting a non-random genomic distribution. Phylogenetic analyses identified the LTR-RT families in which internal and LTR sequences are included. Ty3-gypsy elements were more frequent than Ty1-copia, mainly due to the high Ogre element frequency in lentil, as also occurs in other species of the tribe Vicieae. LTR and internal sequences were used to analyze in silico their distribution among the contigs of the lentil draft genome. Up to 8.8% of the lentil contigs evidenced the presence of at least one LTR-RT similar sequence. A statistical analysis suggested a non-random distribution of these elements within of the lentil genome. In most cases (between 97% and 72%, depending on the LTR-RT type) none of the internal sequences flanked by the LTR sequence pair was detected, suggesting that defective and non-autonomous LTR-RTs are very frequent in lentil. Results support that LTR-RTs are abundant and widespread throughout of the lentil genome and that they are a suitable source of genetic markers useful to carry out further genetic

  16. Obtaining retrotransposon sequences, analysis of their genomic distribution and use of retrotransposon-derived genetic markers in lentil (Lens culinaris Medik..

    Directory of Open Access Journals (Sweden)

    Rita Rey-Baños

    Full Text Available Retrotransposons with long terminal repeats (LTR-RTs are widespread mobile elements in eukaryotic genomes. We obtained a total of 81 partial LTR-RT sequences from lentil corresponding to internal retrotransposon components and LTRs. Sequences were obtained by PCR from genomic DNA. Approximately 37% of the LTR-RT internal sequences presented premature stop codons, pointing out that these elements must be non-autonomous. LTR sequences were obtained using the iPBS technique which amplifies sequences between LTR-RTs. A total of 193 retrotransposon-derived genetic markers, mainly iPBS, were used to obtain a genetic linkage map from 94 F7 inbred recombinant lines derived from the cross between the cultivar Lupa and the wild ancestor L. culinaris subsp. orientalis. The genetic map included 136 markers located in eight linkage groups. Clusters of tightly linked retrotransposon-derived markers were detected in linkage groups LG1, LG2, and LG6, hence denoting a non-random genomic distribution. Phylogenetic analyses identified the LTR-RT families in which internal and LTR sequences are included. Ty3-gypsy elements were more frequent than Ty1-copia, mainly due to the high Ogre element frequency in lentil, as also occurs in other species of the tribe Vicieae. LTR and internal sequences were used to analyze in silico their distribution among the contigs of the lentil draft genome. Up to 8.8% of the lentil contigs evidenced the presence of at least one LTR-RT similar sequence. A statistical analysis suggested a non-random distribution of these elements within of the lentil genome. In most cases (between 97% and 72%, depending on the LTR-RT type none of the internal sequences flanked by the LTR sequence pair was detected, suggesting that defective and non-autonomous LTR-RTs are very frequent in lentil. Results support that LTR-RTs are abundant and widespread throughout of the lentil genome and that they are a suitable source of genetic markers useful to carry

  17. Next Generation Extended Lagrangian Quantum-based Molecular Dynamics

    Science.gov (United States)

    Negre, Christian

    2017-06-01

    A new framework for extended Lagrangian first-principles molecular dynamics simulations is presented, which overcomes shortcomings of regular, direct Born-Oppenheimer molecular dynamics, while maintaining important advantages of the unified extended Lagrangian formulation of density functional theory pioneered by Car and Parrinello three decades ago. The new framework allows, for the first time, energy conserving, linear-scaling Born-Oppenheimer molecular dynamics simulations, which is necessary to study larger and more realistic systems over longer simulation times than previously possible. Expensive, self-consinstent-field optimizations are avoided and normal integration time steps of regular, direct Born-Oppenheimer molecular dynamics can be used. Linear scaling electronic structure theory is presented using a graph-based approach that is ideal for parallel calculations on hybrid computer platforms. For the first time, quantum based Born-Oppenheimer molecular dynamics simulation is becoming a practically feasible approach in simulations of +100,000 atoms-representing a competitive alternative to classical polarizable force field methods. In collaboration with: Anders Niklasson, Los Alamos National Laboratory.

  18. Biodiversity of few Indian charophyte taxa based on molecular ...

    African Journals Online (AJOL)

    Biodiversity of few Indian charophyte taxa based on molecular characterization and construction of phylogenetic tree. ... such as band frequency, RAPD polymorphism, genetic identity index or similarity index, band sharing frequency and genetic distance within and in between Chara and Nitella were evaluated. With the ...

  19. Molecularly Imprinted Polymer-Carbon Nanotube based Cotinine sensor

    NARCIS (Netherlands)

    Abbas, Yawar; Bomer, Johan G.; Brusse-Keizer, M.G.J.; Movig, K; van der Valk, P.D.L.P.M.; Pieterse, Marcel E.; Segerink, Loes Irene; Olthuis, Wouter; van den Berg, Albert

    2016-01-01

    A cotinine sensor based on the dc resistance of a polymer composite films is presented. The composite film comprises a cotinine selective molecularly imprinted polymer and carbon nanotube particles. This polymer film is deposited over a gold interdigitated electrode array to measure its electrical

  20. Two-step regulation and continuous retrotransposition of the rice LINE-type retrotransposon Karma.

    Science.gov (United States)

    Komatsu, Mai; Shimamoto, Ko; Kyozuka, Junko

    2003-08-01

    Here, we report the identification of Karma, a LINE-type retrotransposon of plants for which continuous retrotransposition was observed in consecutive generations. The transcription of Karma is activated in cultured cells of rice upon DNA hypomethylation. However, transcription is insufficient for retrotransposition, because no increase in the copy number was observed in cultured cells or in the first generation of plants regenerated from them. Despite that finding, copy number increase was detected in the next generation of regenerated plants as well as in later generations, suggesting that the post-transcriptional regulation of Karma retrotransposition is development dependent. Our results indicate that two different mechanisms, one transcriptional and the other developmental, control the mobilization of KARMA: In addition, unlike other known active plant retrotransposons, Karma is not subject to de novo methylation, and retrotransposition persists through several generations.

  1. Functionally conserved RNA-binding and protein-protein interaction properties of LINE-ORF1p in an ancient clade of non-LTR retrotransposons of Entamoeba histolytica.

    Science.gov (United States)

    Gaurav, Amit Kumar; Kumar, Jitender; Agrahari, Mridula; Bhattacharya, Alok; Yadav, Vijay Pal; Bhattacharya, Sudha

    2017-01-01

    Retrotransposons are mobile genetic elements found in most organisms. Their origin and evolution is not very well understood. Retrotransposons that lack long terminal repeats (non-LTR) have been classified based on their reverse transcriptase (RT) and endonuclease sequences into groups, of which R2 is the most ancient. Its members contain a single open reading frame (ORF) while there are two ORFs in the other groups, of which ORF2 contains the RT and endonuclease sequences. It is thought that ORF1 was added later to the single-ORF-containing elements, and codes for a protein with nucleic acid binding activity. We have examined the non-LTR retrotransposons in Entamoeba histolytica, an early-branching parasitic protist, which belongs to the R2 group. However, unlike other members of R2, E. histolytica contains two ORFs. Here we show that EhLINE1-ORF1p is functionally related to the ORF1p found in the non-R2 groups. Its N-terminal region has RNA-binding activity and its C-terminal has a coiled coil domain which participates in protein-protein interaction. It lacks sequence-specificity of RNA-binding and binds to EhLINE1-RNA fragment and ribosomal RNA with comparable affinities. Our study suggests that ORF1p could have evolved independently to maintain functional conservation. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Intelligent DNA-based molecular diagnostics using linked genetic markers

    Energy Technology Data Exchange (ETDEWEB)

    Pathak, D.K.; Perlin, M.W.; Hoffman, E.P.

    1994-12-31

    This paper describes a knowledge-based system for molecular diagnostics, and its application to fully automated diagnosis of X-linked genetic disorders. Molecular diagnostic information is used in clinical practice for determining genetic risks, such as carrier determination and prenatal diagnosis. Initially, blood samples are obtained from related individuals, and PCR amplification is performed. Linkage-based molecular diagnosis then entails three data analysis steps. First, for every individual, the alleles (i.e., DNA composition) are determined at specified chromosomal locations. Second, the flow of genetic material among the individuals is established. Third, the probability that a given individual is either a carrier of the disease or affected by the disease is determined. The current practice is to perform each of these three steps manually, which is costly, time consuming, labor-intensive, and error-prone. As such, the knowledge-intensive data analysis and interpretation supersede the actual experimentation effort as the major bottleneck in molecular diagnostics. By examining the human problem solving for the task, we have designed and implemented a prototype knowledge-based system capable of fully automating linkage-based molecular diagnostics in X-linked genetic disorders, including Duchenne Muscular Dystrophy (DMD). Our system uses knowledge-based interpretation of gel electrophoresis images to determine individual DNA marker labels, a constraint satisfaction search for consistent genetic flow among individuals, and a blackboard-style problem solver for risk assessment. We describe the system`s successful diagnosis of DMD carrier and affected individuals from raw clinical data.

  3. LINE retrotransposon RNA is an essential structural and functional epigenetic component of a core neocentromeric chromatin.

    Directory of Open Access Journals (Sweden)

    Anderly C Chueh

    2009-01-01

    Full Text Available We have previously identified and characterized the phenomenon of ectopic human centromeres, known as neocentromeres. Human neocentromeres form epigenetically at euchromatic chromosomal sites and are structurally and functionally similar to normal human centromeres. Recent studies have indicated that neocentromere formation provides a major mechanism for centromere repositioning, karyotype evolution, and speciation. Using a marker chromosome mardel(10 containing a neocentromere formed at the normal chromosomal 10q25 region, we have previously mapped a 330-kb CENP-A-binding domain and described an increased prevalence of L1 retrotransposons in the underlying DNA sequences of the CENP-A-binding clusters. Here, we investigated the potential role of the L1 retrotransposons in the regulation of neocentromere activity. Determination of the transcriptional activity of a panel of full-length L1s (FL-L1s across a 6-Mb region spanning the 10q25 neocentromere chromatin identified one of the FL-L1 retrotransposons, designated FL-L1b and residing centrally within the CENP-A-binding clusters, to be transcriptionally active. We demonstrated the direct incorporation of the FL-L1b RNA transcripts into the CENP-A-associated chromatin. RNAi-mediated knockdown of the FL-L1b RNA transcripts led to a reduction in CENP-A binding and an impaired mitotic function of the 10q25 neocentromere. These results indicate that LINE retrotransposon RNA is a previously undescribed essential structural and functional component of the neocentromeric chromatin and that retrotransposable elements may serve as a critical epigenetic determinant in the chromatin remodelling events leading to neocentromere formation.

  4. Genome-wide analysis of LTR-retrotransposons in oil palm.

    Science.gov (United States)

    Beulé, Thierry; Agbessi, Mawussé Dt; Dussert, Stephane; Jaligot, Estelle; Guyot, Romain

    2015-10-15

    The oil palm (Elaeis guineensis Jacq.) is a major cultivated crop and the world's largest source of edible vegetable oil. The genus Elaeis comprises two species E. guineensis, the commercial African oil palm and E. oleifera, which is used in oil palm genetic breeding. The recent publication of both the African oil palm genome assembly and the first draft sequence of its Latin American relative now allows us to tackle the challenge of understanding the genome composition, structure and evolution of these palm genomes through the annotation of their repeated sequences. In this study, we identified, annotated and compared Transposable Elements (TE) from the African and Latin American oil palms. In a first step, Transposable Element databases were built through de novo detection in both genome sequences then the TE content of both genomes was estimated. Then putative full-length retrotransposons with Long Terminal Repeats (LTRs) were further identified in the E. guineensis genome for characterization of their structural diversity, copy number and chromosomal distribution. Finally, their relative expression in several tissues was determined through in silico analysis of publicly available transcriptome data. Our results reveal a congruence in the transpositional history of LTR retrotransposons between E. oleifera and E. guineensis, especially the Sto-4 family. Also, we have identified and described 583 full-length LTR-retrotransposons in the Elaeis guineensis genome. Our work shows that these elements are most likely no longer mobile and that no recent insertion event has occurred. Moreover, the analysis of chromosomal distribution suggests a preferential insertion of Copia elements in gene-rich regions, whereas Gypsy elements appear to be evenly distributed throughout the genome. Considering the high proportion of LTR retrotransposon in the oil palm genome, our work will contribute to a greater understanding of their impact on genome organization and evolution

  5. Cancer cells, on your histone marks, get SETDB1, silence retrotransposons, and go!

    Science.gov (United States)

    Robbez-Masson, Luisa; Tie, Christopher H C; Rowe, Helen M

    2017-11-06

    Cancer cells thrive on genetic and epigenetic changes that confer a selective advantage but also need strategies to avoid immune recognition. In this issue, Cuellar et al. (2017. J. Cell Biol https://doi.org/10.1083/jcb.201612160) find that the histone methyltransferase SETDB1 enables acute myeloid leukemia cells to evade sensing of retrotransposons by innate immune receptors. © 2017 Robbez-Masson et al.

  6. [Morphofunctional and molecular bases of pineal gland aging].

    Science.gov (United States)

    Khavinson, V Kh; Lin'kova, N S

    2012-01-01

    The review analyzed morphology, molecular and functional aspects of pineal gland aging and methods of it correction. The pineal gland is central organ, which regulates activity of neuroimmunoendocrine, antioxidant and other organisms systems. Functional activity of pineal gland is discreased at aging, which is the reason of melatonin level changing. The molecular and morphology research demonstrated, that pineal gland hadn't strongly pronounced atrophy at aging. Long-term experience showed, that peptides extract of pineal gland epithalamin and synthetic tetrapeptide on it base epithalon restored melatonin secretion in pineal gland and had strong regulatory activity at neuroimmunoendocrine and antioxidant organism systems.

  7. Restriction of Retrotransposon Mobilization in Schizosaccharomyces pombe by Transcriptional Silencing and Higher-Order Chromatin Organization

    Science.gov (United States)

    Murton, Heather E.; Grady, Patrick J. R.; Chan, Tsun Ho; Cam, Hugh P.; Whitehall, Simon K.

    2016-01-01

    Uncontrolled propagation of retrotransposons is potentially detrimental to host genome integrity. Therefore, cells have evolved surveillance mechanisms to restrict the mobility of these elements. In Schizosaccharomyces pombe the Tf2 LTR retrotransposons are transcriptionally silenced and are also clustered in the nucleus into structures termed Tf bodies. Here we describe the impact of silencing and clustering on the mobility of an endogenous Tf2 element. Deletion of genes such as set1+ (histone H3 lysine 4 methyltransferase) or abp1+ (CENP-B homolog) that both alleviate silencing and clustering, result in a corresponding increase in mobilization. Furthermore, expression of constitutively active Sre1, a transcriptional activator of Tf2 elements, also alleviates clustering and induces mobilization. In contrast, clustering is not disrupted by loss of the HIRA histone chaperone, despite high levels of expression, and in this background, mobilization frequency is only marginally increased. Thus, mutations that compromise transcriptional silencing but not Tf bodies are insufficient to drive mobilization. Furthermore, analyses of mutant alleles that separate the transcriptional repression and clustering functions of Set1 are consistent with control of Tf2 propagation via a combination of silencing and spatial organization. Our results indicate that host surveillance mechanisms operate at multiple levels to restrict Tf2 retrotransposon mobilization. PMID:27343236

  8. Transcriptional regulation of human-specific SVAF₁ retrotransposons by cis-regulatory MAST2 sequences.

    Science.gov (United States)

    Zabolotneva, Anastasia A; Bantysh, Olga; Suntsova, Maria V; Efimova, Nadezhda; Malakhova, Galina V; Schumann, Gerald G; Gayfullin, Nurshat M; Buzdin, Anton A

    2012-08-15

    SVA elements represent the youngest family of hominid non-LTR retrotransposons. Recently, a human-specific subfamily (termed SVA(F1), CpG-SVA, or MAST2-SVA) was discovered representing fusion of the CpG island-containing exon 1 of the MAST2 gene and a 5'-truncated SVA. SVA(F1) includes at least 84 members, which suggests exceptionally high retrotransposition level. We investigated if the acquirement of the MAST2 CpG-island might play a role in the success of the SVA(F1) subfamily. We observed that in 16 samples representing seven human tissues, MAST2 was cotranscribed with the members of the SVA(F1) subfamily, but not with other retrotransposons. We found that the methylation status of the MAST2-derived sequences of SVA(F1) elements reversely correlates with the transcriptional activity of MAST2. The MAST2 sequence at the 5' end of SVA(F1) acts as a positive transcriptional regulator in human germ cells. Finally, in various testicular tissue samples we uncovered a transcriptional correlation of MAST2 with the human L1, Alu and SVA retrotransposons. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Restriction of Retrotransposon Mobilization in Schizosaccharomyces pombe by Transcriptional Silencing and Higher-Order Chromatin Organization.

    Science.gov (United States)

    Murton, Heather E; Grady, Patrick J R; Chan, Tsun Ho; Cam, Hugh P; Whitehall, Simon K

    2016-08-01

    Uncontrolled propagation of retrotransposons is potentially detrimental to host genome integrity. Therefore, cells have evolved surveillance mechanisms to restrict the mobility of these elements. In Schizosaccharomyces pombe the Tf2 LTR retrotransposons are transcriptionally silenced and are also clustered in the nucleus into structures termed Tf bodies. Here we describe the impact of silencing and clustering on the mobility of an endogenous Tf2 element. Deletion of genes such as set1(+) (histone H3 lysine 4 methyltransferase) or abp1(+) (CENP-B homolog) that both alleviate silencing and clustering, result in a corresponding increase in mobilization. Furthermore, expression of constitutively active Sre1, a transcriptional activator of Tf2 elements, also alleviates clustering and induces mobilization. In contrast, clustering is not disrupted by loss of the HIRA histone chaperone, despite high levels of expression, and in this background, mobilization frequency is only marginally increased. Thus, mutations that compromise transcriptional silencing but not Tf bodies are insufficient to drive mobilization. Furthermore, analyses of mutant alleles that separate the transcriptional repression and clustering functions of Set1 are consistent with control of Tf2 propagation via a combination of silencing and spatial organization. Our results indicate that host surveillance mechanisms operate at multiple levels to restrict Tf2 retrotransposon mobilization. Copyright © 2016 Murton et al.

  10. Divergent non-LTR retrotransposon lineages from the genomes of scorpions (Arachnida: Scorpiones).

    Science.gov (United States)

    Glushkov, Sergei; Novikova, Olga; Blinov, Alexander; Fet, Victor

    2006-03-01

    We screened across the taxonomic diversity of order Scorpiones (22 species belonging to 21 genera and 10 families) for the presence of seven different clades of non-LTR retrotransposons in their genomes using PCR with newly designed clade-specific consensus-degenerate hybrid oligonucleotide primers. Scorpion genomes were found to contain four known non-LTR retrotransposon clades: R1, I, Jockey, and CR1. In total, 35 fragments of reverse transcriptase genes of new elements from 22 scorpion species were obtained and analyzed for three clades, Jockey, I, and CR1. Phylogenies of different clades of elements were built using amino acid sequences inferred from 33 non-LTR retrotransposon clones. Distinct evolutionary lineages, with several major groups of the non-LTR retroelements were identified, showing significant variation. Four lineages were revealed in Jockey clade. The phylogeny of I clade showed strong support for the monophyletic origin of such group of elements in scorpions. Three separate lineages can be distinguished in the phylogenetic tree of CR1 clade. The large fraction of the isolated elements appeared to be defective.

  11. The genomic organization of Ty3/gypsy-like retrotransposons in Helianthus (Asteraceae) homoploid hybrid species.

    Science.gov (United States)

    Staton, S Evan; Ungerer, Mark C; Moore, Richard C

    2009-09-01

    The origin of new diploid, or homoploid, hybrid species is associated with rapid genomic restructuring in the hybrid neospecies. This mode of speciation has been best characterized in wild sunflower species in the genus Helianthus, where three homoploid hybrid species (H. anomalus, H. deserticola, and H. paradoxus) have independently arisen via ancient hybridization events between the same two parental species (H. annuus and H. petiolaris). Most previous work examining genomic restructuring in these sunflower hybrid species has focused on chromosomal rearrangements. However, the origin of all three homoploid hybrid sunflower species also is associated with massive proliferation events of Ty3/gypsy-like retrotransposons in the hybrid species' genomes. We compared the genomic organization of these elements in the parent species and two of the homoploid hybrid species using fluorescence in situ hybridization (FISH). We found a significant expansion of Ty3/gypsy-like retrotransposons confined to the pericentromeric regions of two hybrid sunflower species, H. deserticola and H. paradoxus. In contrast, we detected no significant increase in the frequency or extent of dispersed retrotransposon populations in the hybrid species within the resolution limits of our assay. We discuss the potential role that transposable element proliferation and localization plays in the evolution of homoploid hybrid species.

  12. A deep-branching clade of retrovirus-like retrotransposons in bdelloid rotifers

    Science.gov (United States)

    Gladyshev, Eugene A.; Meselson, Matthew; Arkhipova, Irina R.

    2007-01-01

    Rotifers of class Bdelloidea, a group of aquatic invertebrates in which males and meiosis have never been documented, are also unusual in their lack of multicopy LINE-like and gypsy-like retrotransposons, groups inhabiting the genomes of nearly all other metazoans. Bdelloids do contain numerous DNA transposons, both intact and decayed, and domesticated Penelope-like retroelements Athena, concentrated at telomeric regions. Here we describe two LTR retrotransposons, each found at low copy number in a different bdelloid species, which define a clade different from previously known clades of LTR retrotransposons. Like bdelloid DNA transposons and Athena, these elements have been found preferentially in telomeric regions. Unlike bdelloid DNA transposons, many of which are decayed, the newly described elements, named Vesta and Juno, inhabiting the genomes of Philodina roseola and Adineta vaga, respectively, appear to be intact and to represent recent insertions, possibly from an exogenous source. We describe the retrovirus-like structure of the new elements, containing gag, pol, and env-like open reading frames, and discuss their possible origins, transmission, and behavior in bdelloid genomes. PMID:17129685

  13. Development and Characterisation of Irap Markers From Expressed Retrotransposon-like sequences in Pinus sylvestris L.

    Directory of Open Access Journals (Sweden)

    Voronova Angelika

    2014-07-01

    Full Text Available Conifer genomes are large and stably diploid, in contrast to angiosperms, which are more variable both in genome size and ploidy. Conifer genomes are characterised by multiple gene families and pseudogenes, contain large inter-gene regions and a considerable proportion of repetitive sequences. All members of plant retrotransposon orders have been identified in gymnosperm genomes, however active elements have not been described. Investigation of transposable elements in Scots pine (Pinus sylvestris L. could offer insights into transposon-mediated reorganisation under stress conditions in complex and ancient plant genomes. Nine Pinus sylvestris specific markers were developed to hypothetical long terminal repeats (LTRs from differentially expressed retrotransposon-like fragments after heat stress and insect damage. Genetic diversity of 150 trees from a naturally regenerated pine stand was investigated using the IRAP method. The developed markers revealed high levels of genetic diversity and were able to distinguish subpopulations growing in long-term differential environmental conditions. Somaclonal variation was also investigated using these markers and polymorphic fragments were identified between ramets of Scots pine clones growing in two different plantations, possibly indicating evidence of recent transposition events. Sequencing of the polymorphic fragments identified two groups of sequences containing LTR sequences of an unknown retrotransposon with homology to the LTRs of the Copia-17-PAb-I element.

  14. LTR-Retrotransposons from Bdelloid Rotifers Capture Additional ORFs Shared between Highly Diverse Retroelement Types.

    Science.gov (United States)

    Rodriguez, Fernando; Kenefick, Aubrey W; Arkhipova, Irina R

    2017-04-11

    Rotifers of the class Bdelloidea, microscopic freshwater invertebrates, possess a highlydiversified repertoire of transposon families, which, however, occupy less than 4% of genomic DNA in the sequenced representative Adineta vaga. We performed a comprehensive analysis of A. vaga retroelements, and found that bdelloid long terminal repeat (LTR)retrotransposons, in addition to conserved open reading frame (ORF) 1 and ORF2 corresponding to gag and pol genes, code for an unusually high variety of ORF3 sequences. Retrovirus-like LTR families in A. vaga belong to four major lineages, three of which are rotiferspecific and encode a dUTPase domain. However only one lineage contains a canonical envlike fusion glycoprotein acquired from paramyxoviruses (non-segmented negative-strand RNA viruses), although smaller ORFs with transmembrane domains may perform similar roles. A different ORF3 type encodes a GDSL esterase/lipase, which was previously identified as ORF1 in several clades of non-LTR retrotransposons, and implicated in membrane targeting. Yet another ORF3 type appears in unrelated LTR-retrotransposon lineages, and displays strong homology to DEDDy-type exonucleases involved in 3'-end processing of RNA and single-stranded DNA. Unexpectedly, each of the enzymatic ORF3s is also associated with different subsets of Penelope-like Athena retroelement families. The unusual association of the same ORF types with retroelements from different classes reflects their modular structure with a high degree of flexibility, and points to gene sharing between different groups of retroelements.

  15. Transcriptional Dynamics of LTR Retrotransposons in Early Generation and Ancient Sunflower Hybrids

    Science.gov (United States)

    Ungerer, Mark C.; Kawakami, Takeshi

    2013-01-01

    Hybridization and abiotic stress are natural agents hypothesized to influence activation and proliferation of transposable elements in wild populations. In this report, we examine the effects of these agents on expression dynamics of both quiescent and transcriptionally active sublineages of long terminal repeat (LTR) retrotransposons in wild sunflower species with a notable history of transposable element proliferation. For annual sunflower species Helianthus annuus and H. petiolaris, neither early generation hybridization nor abiotic stress, alone or in combination, induced transcriptional activation of quiescent sublineages of LTR retrotransposons. These treatments also failed to further induce expression of sublineages that are transcriptionally active; instead, expression of active sublineages in F1 and backcross hybrids was nondistinguishable from, or intermediate relative to, parental lines, and abiotic stress generally decreased normalized expression relative to controls. In contrast to findings for early generation hybridization between H. annuus and H. petiolaris, ancient sunflower hybrid species derived from these same two species and which have undergone massive proliferation events of LTR retrotransposons display 2× to 6× higher expression levels of transcriptionally active sublineages relative to parental sunflower species H. annuus and H. petiolaris. Implications and possible explanations for these findings are discussed. PMID:23335122

  16. Reverse Transcription in the Saccharomyces cerevisiae Long-Terminal Repeat Retrotransposon Ty3

    Directory of Open Access Journals (Sweden)

    Jason W. Rausch

    2017-03-01

    Full Text Available Converting the single-stranded retroviral RNA into integration-competent double-stranded DNA is achieved through a multi-step process mediated by the virus-coded reverse transcriptase (RT. With the exception that it is restricted to an intracellular life cycle, replication of the Saccharomyces cerevisiae long terminal repeat (LTR-retrotransposon Ty3 genome is guided by equivalent events that, while generally similar, show many unique and subtle differences relative to the retroviral counterparts. Until only recently, our knowledge of RT structure and function was guided by a vast body of literature on the human immunodeficiency virus (HIV enzyme. Although the recently-solved structure of Ty3 RT in the presence of an RNA/DNA hybrid adds little in terms of novelty to the mechanistic basis underlying DNA polymerase and ribonuclease H activity, it highlights quite remarkable topological differences between retroviral and LTR-retrotransposon RTs. The theme of overall similarity but distinct differences extends to the priming mechanisms used by Ty3 RT to initiate (− and (+ strand DNA synthesis. The unique structural organization of the retrotransposon enzyme and interaction with its nucleic acid substrates, with emphasis on polypurine tract (PPT-primed initiation of (+ strand synthesis, is the subject of this review.

  17. Bio-Mimetic Sensors Based on Molecularly Imprinted Membranes

    Directory of Open Access Journals (Sweden)

    Catia Algieri

    2014-07-01

    Full Text Available An important challenge for scientific research is the production of artificial systems able to mimic the recognition mechanisms occurring at the molecular level in living systems. A valid contribution in this direction resulted from the development of molecular imprinting. By means of this technology, selective molecular recognition sites are introduced in a polymer, thus conferring it bio-mimetic properties. The potential applications of these systems include affinity separations, medical diagnostics, drug delivery, catalysis, etc. Recently, bio-sensing systems using molecularly imprinted membranes, a special form of imprinted polymers, have received the attention of scientists in various fields. In these systems imprinted membranes are used as bio-mimetic recognition elements which are integrated with a transducer component. The direct and rapid determination of an interaction between the recognition element and the target analyte (template was an encouraging factor for the development of such systems as alternatives to traditional bio-assay methods. Due to their high stability, sensitivity and specificity, bio-mimetic sensors-based membranes are used for environmental, food, and clinical uses. This review deals with the development of molecularly imprinted polymers and their different preparation methods. Referring to the last decades, the application of these membranes as bio-mimetic sensor devices will be also reported.

  18. Bio-Mimetic Sensors Based on Molecularly Imprinted Membranes

    Science.gov (United States)

    Algieri, Catia; Drioli, Enrico; Guzzo, Laura; Donato, Laura

    2014-01-01

    An important challenge for scientific research is the production of artificial systems able to mimic the recognition mechanisms occurring at the molecular level in living systems. A valid contribution in this direction resulted from the development of molecular imprinting. By means of this technology, selective molecular recognition sites are introduced in a polymer, thus conferring it bio-mimetic properties. The potential applications of these systems include affinity separations, medical diagnostics, drug delivery, catalysis, etc. Recently, bio-sensing systems using molecularly imprinted membranes, a special form of imprinted polymers, have received the attention of scientists in various fields. In these systems imprinted membranes are used as bio-mimetic recognition elements which are integrated with a transducer component. The direct and rapid determination of an interaction between the recognition element and the target analyte (template) was an encouraging factor for the development of such systems as alternatives to traditional bio-assay methods. Due to their high stability, sensitivity and specificity, bio-mimetic sensors-based membranes are used for environmental, food, and clinical uses. This review deals with the development of molecularly imprinted polymers and their different preparation methods. Referring to the last decades, the application of these membranes as bio-mimetic sensor devices will be also reported. PMID:25196110

  19. AC-ELECTROKINETICS BASED TOOLS IN NANOENGINEERING AND MOLECULAR ELECTRONICS

    Directory of Open Access Journals (Sweden)

    R. Durán

    2005-08-01

    Full Text Available Slllcon-based mlcroeledronics has been following the integration prognosls of MOORE's Law durlng the past decades and posslbly will do so for another decade or two. Physlcal, technological and also flnancialllmlts In the foreseeable future will slow down the contlnued expansiOn of this branch of mlcroeledronlcs and instead wlll force a new technological approach based on molecular-scale eledronics (MOLETRONICS. New tools are needed to allow molecular devlce manufaduring and nanoscale engineering with hlgh precision and produdivlty. One group of methods with the potentlal for use In such a manufaduring process Is based on a.c. eledrokinetlcs effeds, which are descrlbed and discussed in this paper.

  20. Arthropod phylogeny based on eight molecular loci and morphology

    Science.gov (United States)

    Giribet, G.; Edgecombe, G. D.; Wheeler, W. C.

    2001-01-01

    The interrelationships of major clades within the Arthropoda remain one of the most contentious issues in systematics, which has traditionally been the domain of morphologists. A growing body of DNA sequences and other types of molecular data has revitalized study of arthropod phylogeny and has inspired new considerations of character evolution. Novel hypotheses such as a crustacean-hexapod affinity were based on analyses of single or few genes and limited taxon sampling, but have received recent support from mitochondrial gene order, and eye and brain ultrastructure and neurogenesis. Here we assess relationships within Arthropoda based on a synthesis of all well sampled molecular loci together with a comprehensive data set of morphological, developmental, ultrastructural and gene-order characters. The molecular data include sequences of three nuclear ribosomal genes, three nuclear protein-coding genes, and two mitochondrial genes (one protein coding, one ribosomal). We devised new optimization procedures and constructed a parallel computer cluster with 256 central processing units to analyse molecular data on a scale not previously possible. The optimal 'total evidence' cladogram supports the crustacean-hexapod clade, recognizes pycnogonids as sister to other euarthropods, and indicates monophyly of Myriapoda and Mandibulata.

  1. Graph-based interpretation of the molecular interstellar medium segmentation

    Science.gov (United States)

    Colombo, D.; Rosolowsky, E.; Ginsburg, A.; Duarte-Cabral, A.; Hughes, A.

    2015-12-01

    We present a generalization of the giant molecular cloud identification problem based on cluster analysis. The method we designed, SCIMES (Spectral Clustering for Interstellar Molecular Emission Segmentation) considers the dendrogram of emission in the broader framework of graph theory and utilizes spectral clustering to find discrete regions with similar emission properties. For Galactic molecular cloud structures, we show that the characteristic volume and/or integrated CO luminosity are useful criteria to define the clustering, yielding emission structures that closely reproduce `by-eye' identification results. SCIMES performs best on well-resolved, high-resolution data, making it complementary to other available algorithms. Using 12CO(1-0) data for the Orion-Monoceros complex, we demonstrate that SCIMES provides robust results against changes of the dendrogram-construction parameters, noise realizations and degraded resolution. By comparing SCIMES with other cloud decomposition approaches, we show that our method is able to identify all canonical clouds of the Orion-Monoceros region, avoiding the overdivision within high-resolution survey data that represents a common limitation of several decomposition algorithms. The Orion-Monoceros objects exhibit hierarchies and size-line width relationships typical to the turbulent gas in molecular clouds, although `the Scissors' region deviates from this common description. SCIMES represents a significant step forward in moving away from pixel-based cloud segmentation towards a more physical-oriented approach, where virtually all properties of the ISM can be used for the segmentation of discrete objects.

  2. LTR retrotransposon landscape in Medicago truncatula: more rapid removal than in rice

    Directory of Open Access Journals (Sweden)

    Liu Jin-Song

    2008-08-01

    Full Text Available Abstract Background Long terminal repeat retrotransposons (LTR elements are ubiquitous Eukaryotic TEs that transpose through RNA intermediates. Accounting for significant proportion of many plant genomes, LTR elements have been well established as one of the major forces underlying the evolution of plant genome size, structure and function. The accessibility of more than 40% of genomic sequences of the model legume Medicago truncatula (Mt has made the comprehensive study of its LTR elements possible. Results We use a newly developed tool LTR_FINDER to identify LTR retrotransposons in the Mt genome and detect 526 full-length elements as well as a great number of copies related to them. These elements constitute about 9.6% of currently available genomic sequences. They are classified into 85 families of which 64 are reported for the first time. The majority of the LTR retrotransposons belong to either Copia or Gypsy superfamily and the others are categorized as TRIMs or LARDs by their length. We find that the copy-number of Copia-like families is 3 times more than that of Gypsy-like ones but the latter contribute more to the genome. The analysis of PBS and protein-coding domain structure of the LTR families reveals that they tend to use only 4–5 types of tRNAs and many families have quite conservative ORFs besides known TE domains. For several important families, we describe in detail their abundance, conservation, insertion time and structure. We investigate the amplification-deletion pattern of the elements and find that the detectable full-length elements are relatively young and most of them were inserted within the last 0.52 MY. We also estimate that more than ten million bp of the Mt genomic sequences have been removed by the deletion of LTR elements and the removal of the full-length structures in Mt has been more rapid than in rice. Conclusion This report is the first comprehensive description and analysis of LTR retrotransposons in the

  3. Dendrimer-based contrast agents for molecular imaging.

    Science.gov (United States)

    Longmire, Michelle; Choyke, Peter L; Kobayashi, Hisataka

    2008-01-01

    The extensive adaptability of dendrimer-based contrast agents is ideal for the molecular imaging of organs and other target-specific locations. The ability of literally atom-by-atom modification on cores, interiors, and surface groups, permits the rational manipulation of dendrimer-based agents in order to optimize their physical characteristics, biodistribution, receptor-mediated targeting, and controlled release of the payload. Such modifications enable agents to localize preferentially to areas or organs of interest for facilitating target-specific imaging as well as assume excretion pathways that do not interfere with desired applications. Recent innovations in dendrimer research have increased agent directibility and new synthetic chemistry approaches have increased efficiency of production as well as led to the creation of novel dendrimer-based contrast agents. In addition, by taking advantage of the numerous attachment sites available on the surface of a single dendrimer molecule, new synthetic chemistry techniques have led to the development of multi-modality magnetic resonance, radionuclide, and fluorescence imaging agents for molecular imaging. Herein we discuss advances in dendrimer-based contrast agents for molecular imaging focusing mainly on the chemical design as applied to optical, magnetic resonance, computer tomography, radionuclide, and multi-modality imaging.

  4. Operation kinetics of a DNA-based molecular switch.

    Science.gov (United States)

    Simmel, Friedrich C; Yurke, Bernard; Sanyal, Rishi J

    2002-01-01

    The influence of temperature variation, salt concentration, and pH on the operation kinetics of a simple DNA-based molecular switch is investigated. The device shows robust behavior over a wide range of temperatures, pH, and salt concentrations. In particular, the device operates well under physiological conditions. The experimental data can be qualitatively understood in terms of the influence temperature, salt concentration, and pH have on DNA strand interactions.

  5. Molecularly Imprinted Polymer Based Sensor for the Detection of Theophylline

    Science.gov (United States)

    Braga, Guilherme S.; Paterno, Leonardo G.; Fonseca, Fernando J.; del Valle, Manel

    2011-11-01

    A molecularly imprinted polymer (MIP) impedance-based sensor was employed to detect theophylline in distilled water. To evaluate its sensibility, impedance measurements were carried out in a diluted solution of theophylline (1 mM) and distilled water using MIP and NIP (reference non-imprinted polymer) sensors. MIP showed higher sensitivity to theophylline than the NIP. This feature shows their suitability for developing an electronic tongue system for determination of methylxanthines.

  6. Tyl6, a novel Ty3/gypsy-like retrotransposon in the genome of the dimorphic fungus Yarrowia lipolytica.

    Science.gov (United States)

    Kovalchuk, Andriy; Senam, Senam; Mauersberger, Stephan; Barth, Gerold

    2005-09-01

    The novel LTR retrotransposon Tyl6 was detected in the genome of the dimorphic fungus Yarrowia lipolytica. Sequence analysis revealed that this element is related to the well-known Ty3 element of Saccharomyces cerevisiae and, especially, to the recently described Tse3 retrotransposon of Saccharomyces exiguus and to the del1-like plant retrotransposons. Tyl6 is 5108 bp long, is flanked by two identical long terminal repeats (LTR), each of 276 bp, and its ORFs are separated by a -1 frameshift. Both ORFs are intact and deduced translation products display a significant similarity with those of previously described Ty3/gypsy retrotransposons. Distribution of Tyl6 among Y. lipolytica strains of different origins was also analysed. A single copy of the novel retrotransposon is present in some commonly used laboratory strains, which are derivatives of the wild-type isolate YB423-12, whereas other strains of independent origin are devoid of Ty16. No solo LTR of Tyl6 was detected in the analysed strains. Copyright 2005 John Wiley & Sons, Ltd.

  7. Reverse transcriptase domain sequences from tree peony (Paeonia suffruticosa) long terminal repeat retrotransposons: sequence characterization and phylogenetic analysis.

    Science.gov (United States)

    Guo, Da-Long; Hou, Xiao-Gai; Jia, Tian

    2014-05-04

    Tree peony is an important horticultural plant worldwide of great ornamental and medicinal value. Long terminal repeat retrotransposons (LTR-retrotransposons) are the major components of most plant genomes and can substantially impact the genome in many ways. It is therefore crucial to understand their sequence characteristics, genetic distribution and transcriptional activity; however, no information about them is available in tree peony. Ty1-copia-like reverse transcriptase sequences were amplified from tree peony genomic DNA by polymerase chain reaction (PCR) with degenerate oligonucleotide primers corresponding to highly conserved domains of the Ty1-copia-like retrotransposons in this study. PCR fragments of roughly 270 bp were isolated and cloned, and 33 sequences were obtained. According to alignment and phylogenetic analysis, all sequences were divided into six families. The observed difference in the degree of nucleotide sequence similarity is an indication for high level of sequence heterogeneity among these clones. Most of these sequences have a frame shift, a stop codon, or both. Dot-blot analysis revealed distribution of these sequences in all the studied tree peony species. However, different hybridization signals were detected among them, which is in agreement with previous systematics studies. Reverse transcriptase PCR (RT-PCR) indicated that Ty1-copia retrotransposons in tree peony were transcriptionally inactive. The results provide basic genetic and evolutionary information of tree peony genome, and will provide valuable information for the further utilization of retrotransposons in tree peony.

  8. Quantum Fragment Based ab Initio Molecular Dynamics for Proteins.

    Science.gov (United States)

    Liu, Jinfeng; Zhu, Tong; Wang, Xianwei; He, Xiao; Zhang, John Z H

    2015-12-08

    Developing ab initio molecular dynamics (AIMD) methods for practical application in protein dynamics is of significant interest. Due to the large size of biomolecules, applying standard quantum chemical methods to compute energies for dynamic simulation is computationally prohibitive. In this work, a fragment based ab initio molecular dynamics approach is presented for practical application in protein dynamics study. In this approach, the energy and forces of the protein are calculated by a recently developed electrostatically embedded generalized molecular fractionation with conjugate caps (EE-GMFCC) method. For simulation in explicit solvent, mechanical embedding is introduced to treat protein interaction with explicit water molecules. This AIMD approach has been applied to MD simulations of a small benchmark protein Trpcage (with 20 residues and 304 atoms) in both the gas phase and in solution. Comparison to the simulation result using the AMBER force field shows that the AIMD gives a more stable protein structure in the simulation, indicating that quantum chemical energy is more reliable. Importantly, the present fragment-based AIMD simulation captures quantum effects including electrostatic polarization and charge transfer that are missing in standard classical MD simulations. The current approach is linear-scaling, trivially parallel, and applicable to performing the AIMD simulation of proteins with a large size.

  9. NEW MOLECULAR MEDICINE-BASED SCAR MANAGEMENT STRATEGIES

    Science.gov (United States)

    Arno, Anna I; Gauglitz, Gerd G; Barret, Juan P; Jeschke, Marc G

    2014-01-01

    Keloids and hypertrophic scar/span>s are prevalent disabling conditions with still suboptimal treatments. Basic science and molecular-based medicine research has contributed to unravel new bench-to-bedside scar therapies, and to dissect the complex signaling pathways involved. Peptides such as transforming growth factor beta (TGF-β) superfamily, with SMADs, Ski, SnoN, Fussels, endoglin, DS-Sily, Cav-1p, AZX100, thymosin-β4 and other related molecules may emerge as targets to prevent and treat keloids and hypertrophic scar/span>s. The aim of this review is to describe the basic complexity of these new molecular scar management strategies, and point out new fibrosis research lines. PMID:24438742

  10. Photomechanical Bending of Azobenzene-Based Photochromic Molecular Fibers

    Directory of Open Access Journals (Sweden)

    Riku Matsui

    2013-03-01

    Full Text Available Microfibers composed of azobenzene-based photochromic amorphous molecular materials, namely low molecular-mass photochromic materials with a glass-forming property, could be fabricated. These fibers were found to exhibit mechanical bending motion upon irradiation with a laser beam. In addition, the bending direction could be controlled by altering the polarization direction of the irradiated light without changing the position of the light source or the wavelength of the light. In-situ fluorescence observation of mass transport induced at the surface of the fiber doped with CdSe quantum dots suggested that the bending motions were related with the photoinduced mass transport taking place near the irradiated surface of the fiber.

  11. Accelerating convergence of molecular dynamics-based structural relaxation

    DEFF Research Database (Denmark)

    Christensen, Asbjørn

    2005-01-01

    We describe strategies to accelerate the terminal stage of molecular dynamics (MD)based relaxation algorithms, where a large fraction of the computational resources are used. First, we analyze the qualitative and quantitative behavior of the QuickMin family of MD relaxation algorithms and explore...... the influence of spectral properties and dimensionality of the molecular system on the algorithm efficiency. We test two algorithms, the MinMax and Lanczos, for spectral estimation from an MD trajectory, and use this to derive a practical scheme of time step adaptation in MD relaxation algorithms to improve...... efficiency. We also discuss the implementation aspects. Secondly, we explore the final state refinement acceleration by a combination with the conjugate gradient technique, where the key ingredient is an implicit corrector step. Finally, we test the feasibility of passive Hessian matrix accumulation from...

  12. Clustering the Orion B giant molecular cloud based on its molecular emission

    Science.gov (United States)

    Bron, Emeric; Daudon, Chloé; Pety, Jérôme; Levrier, François; Gerin, Maryvonne; Gratier, Pierre; Orkisz, Jan H.; Guzman, Viviana; Bardeau, Sébastien; Goicoechea, Javier R.; Liszt, Harvey; Öberg, Karin; Peretto, Nicolas; Sievers, Albrecht; Tremblin, Pascal

    2018-02-01

    Context. Previous attempts at segmenting molecular line maps of molecular clouds have focused on using position-position-velocity data cubes of a single molecular line to separate the spatial components of the cloud. In contrast, wide field spectral imaging over a large spectral bandwidth in the (sub)mm domain now allows one to combine multiple molecular tracers to understand the different physical and chemical phases that constitute giant molecular clouds (GMCs). Aims: We aim at using multiple tracers (sensitive to different physical processes and conditions) to segment a molecular cloud into physically/chemically similar regions (rather than spatially connected components), thus disentangling the different physical/chemical phases present in the cloud. Methods: We use a machine learning clustering method, namely the Meanshift algorithm, to cluster pixels with similar molecular emission, ignoring spatial information. Clusters are defined around each maximum of the multidimensional probability density function (PDF) of the line integrated intensities. Simple radiative transfer models were used to interpret the astrophysical information uncovered by the clustering analysis. Results: A clustering analysis based only on the J = 1-0 lines of three isotopologues of CO proves sufficient to reveal distinct density/column density regimes (nH 100 cm-3, 500 cm-3, and >1000 cm-3), closely related to the usual definitions of diffuse, translucent and high-column-density regions. Adding two UV-sensitive tracers, the J = 1-0 line of HCO+ and the N = 1-0 line of CN, allows us to distinguish two clearly distinct chemical regimes, characteristic of UV-illuminated and UV-shielded gas. The UV-illuminated regime shows overbright HCO+ and CN emission, which we relate to a photochemical enrichment effect. We also find a tail of high CN/HCO+ intensity ratio in UV-illuminated regions. Finer distinctions in density classes (nH 7 × 103 cm-3, 4 × 104 cm-3) for the densest regions are also

  13. Determinants of Genomic RNA Encapsidation in the Saccharomyces cerevisiae Long Terminal Repeat Retrotransposons Ty1 and Ty3

    Directory of Open Access Journals (Sweden)

    Katarzyna Pachulska-Wieczorek

    2016-07-01

    Full Text Available Long-terminal repeat (LTR retrotransposons are transposable genetic elements that replicate intracellularly, and can be considered progenitors of retroviruses. Ty1 and Ty3 are the most extensively characterized LTR retrotransposons whose RNA genomes provide the template for both protein translation and genomic RNA that is packaged into virus-like particles (VLPs and reverse transcribed. Genomic RNAs are not divided into separate pools of translated and packaged RNAs, therefore their trafficking and packaging into VLPs requires an equilibrium between competing events. In this review, we focus on Ty1 and Ty3 genomic RNA trafficking and packaging as essential steps of retrotransposon propagation. We summarize the existing knowledge on genomic RNA sequences and structures essential to these processes, the role of Gag proteins in repression of genomic RNA translation, delivery to VLP assembly sites, and encapsidation.

  14. Retrotransposons Control Fruit-Specific, Cold-Dependent Accumulation of Anthocyanins in Blood Oranges[W][OA

    Science.gov (United States)

    Butelli, Eugenio; Licciardello, Concetta; Zhang, Yang; Liu, Jianjun; Mackay, Steve; Bailey, Paul; Reforgiato-Recupero, Giuseppe; Martin, Cathie

    2012-01-01

    Traditionally, Sicilian blood oranges (Citrus sinensis) have been associated with cardiovascular health, and consumption has been shown to prevent obesity in mice fed a high-fat diet. Despite increasing consumer interest in these health-promoting attributes, production of blood oranges remains unreliable due largely to a dependency on cold for full color formation. We show that Sicilian blood orange arose by insertion of a Copia-like retrotransposon adjacent to a gene encoding Ruby, a MYB transcriptional activator of anthocyanin production. The retrotransposon controls Ruby expression, and cold dependency reflects the induction of the retroelement by stress. A blood orange of Chinese origin results from an independent insertion of a similar retrotransposon, and color formation in its fruit is also cold dependent. Our results suggest that transposition and recombination of retroelements are likely important sources of variation in Citrus. PMID:22427337

  15. Extension of Saccharomyces paradoxus chronological lifespan by retrotransposons in certain media conditions is associated with changes in reactive oxygen species.

    Science.gov (United States)

    VanHoute, David; Maxwell, Patrick H

    2014-10-01

    Retrotransposons are mobile DNA elements present throughout eukaryotic genomes that can cause mutations and genome rearrangements when they replicate through reverse transcription. Increased expression and/or mobility of retrotransposons has been correlated with aging in yeast, Caenorhabditis elegans, Drosophila melanogaster, and mammals. The many copies of retrotransposons in humans and various model organisms complicate further pursuit of this relationship. The Saccharomyces cerevisiae Ty1 retrotransposon was introduced into a strain of S. paradoxus that completely lacks retrotransposons to compare chronological lifespans (CLSs) of yeast strains with zero, low, or high Ty1 copy number. Yeast chronological lifespan reflects the progressive loss of cell viability in a nondividing state. Chronological lifespans for the strains were not different in rich medium, but were extended in high Ty1 copy-number strains in synthetic medium and in rich medium containing a low dose of hydroxyurea (HU), an agent that depletes deoxynucleoside triphosphates. Lifespan extension was not strongly correlated with Ty1 mobility or mutation rates for a representative gene. Buffering deoxynucleoside triphosphate levels with threonine supplementation did not substantially affect this lifespan extension, and no substantial differences in cell cycle arrest in the nondividing cells were observed. Lifespan extension was correlated with reduced reactive oxygen species during early stationary phase in high Ty1 copy strains, and antioxidant treatment allowed the zero Ty1 copy strain to live as long as high Ty1 copy-number strains in rich medium with hydroxyurea. This exceptional yeast system has identified an unexpected longevity-promoting role for retrotransposons that may yield novel insights into mechanisms regulating lifespan. Copyright © 2014 by the Genetics Society of America.

  16. Molecular Bases Underlying the Hepatoprotective Effects of Coffee.

    Science.gov (United States)

    Salomone, Federico; Galvano, Fabio; Li Volti, Giovanni

    2017-01-23

    Coffee is the most consumed beverage worldwide. Epidemiological studies with prospective cohorts showed that coffee intake is associated with reduced cardiovascular and all-cause mortality independently of caffeine content. Cohort and case-control studies reported an inverse association between coffee consumption and the degree of liver fibrosis as well as the development of liver cancer. Furthermore, the beneficial effects of coffee have been recently confirmed by large meta-analyses. In the last two decades, various in vitro and in vivo studies evaluated the molecular determinants for the hepatoprotective effects of coffee. In the present article, we aimed to critically review experimental evidence regarding the active components and the molecular bases underlying the beneficial role of coffee against chronic liver diseases. Almost all studies highlighted the beneficial effects of this beverage against liver fibrosis with the most solid results indicating a pivot role for both caffeine and chlorogenic acids. In particular, in experimental models of fibrosis, caffeine was shown to inhibit hepatic stellate cell activation by blocking adenosine receptors, and emerging evidence indicated that caffeine may also favorably impact angiogenesis and hepatic hemodynamics. On the other side, chlorogenic acids, potent phenolic antioxidants, suppress liver fibrogenesis and carcinogenesis by reducing oxidative stress and counteract steatogenesis through the modulation of glucose and lipid homeostasis in the liver. Overall, these molecular insights may have translational significance and suggest that coffee components need clinical evaluation.

  17. Molecular Bases Underlying the Hepatoprotective Effects of Coffee

    Directory of Open Access Journals (Sweden)

    Federico Salomone

    2017-01-01

    Full Text Available Coffee is the most consumed beverage worldwide. Epidemiological studies with prospective cohorts showed that coffee intake is associated with reduced cardiovascular and all-cause mortality independently of caffeine content. Cohort and case-control studies reported an inverse association between coffee consumption and the degree of liver fibrosis as well as the development of liver cancer. Furthermore, the beneficial effects of coffee have been recently confirmed by large meta-analyses. In the last two decades, various in vitro and in vivo studies evaluated the molecular determinants for the hepatoprotective effects of coffee. In the present article, we aimed to critically review experimental evidence regarding the active components and the molecular bases underlying the beneficial role of coffee against chronic liver diseases. Almost all studies highlighted the beneficial effects of this beverage against liver fibrosis with the most solid results indicating a pivot role for both caffeine and chlorogenic acids. In particular, in experimental models of fibrosis, caffeine was shown to inhibit hepatic stellate cell activation by blocking adenosine receptors, and emerging evidence indicated that caffeine may also favorably impact angiogenesis and hepatic hemodynamics. On the other side, chlorogenic acids, potent phenolic antioxidants, suppress liver fibrogenesis and carcinogenesis by reducing oxidative stress and counteract steatogenesis through the modulation of glucose and lipid homeostasis in the liver. Overall, these molecular insights may have translational significance and suggest that coffee components need clinical evaluation.

  18. Tunneling Nanoelectromechanical Switches Based on Compressible Molecular Thin Films.

    Science.gov (United States)

    Niroui, Farnaz; Wang, Annie I; Sletten, Ellen M; Song, Yi; Kong, Jing; Yablonovitch, Eli; Swager, Timothy M; Lang, Jeffrey H; Bulović, Vladimir

    2015-08-25

    Abrupt switching behavior and near-zero leakage current of nanoelectromechanical (NEM) switches are advantageous properties through which NEMs can outperform conventional semiconductor electrical switches. To date, however, typical NEMs structures require high actuation voltages and can prematurely fail through permanent adhesion (defined as stiction) of device components. To overcome these challenges, in the present work we propose a NEM switch, termed a "squitch," which is designed to electromechanically modulate the tunneling current through a nanometer-scale gap defined by an organic molecular film sandwiched between two electrodes. When voltage is applied across the electrodes, the generated electrostatic force compresses the sandwiched molecular layer, thereby reducing the tunneling gap and causing an exponential increase in the current through the device. The presence of the molecular layer avoids direct contact of the electrodes during the switching process. Furthermore, as the layer is compressed, the increasing surface adhesion forces are balanced by the elastic restoring force of the deformed molecules which can promote zero net stiction and recoverable switching. Through numerical analysis, we demonstrate the potential of optimizing squitch design to enable large on-off ratios beyond 6 orders of magnitude with operation in the sub-1 V regime and with nanoseconds switching times. Our preliminary experimental results based on metal-molecule-graphene devices suggest the feasibility of the proposed tunneling switching mechanism. With optimization of device design and material engineering, squitches can give rise to a broad range of low-power electronic applications.

  19. Molecular Docking and Structure-Based Drug Design Strategies

    Directory of Open Access Journals (Sweden)

    Leonardo G. Ferreira

    2015-07-01

    Full Text Available Pharmaceutical research has successfully incorporated a wealth of molecular modeling methods, within a variety of drug discovery programs, to study complex biological and chemical systems. The integration of computational and experimental strategies has been of great value in the identification and development of novel promising compounds. Broadly used in modern drug design, molecular docking methods explore the ligand conformations adopted within the binding sites of macromolecular targets. This approach also estimates the ligand-receptor binding free energy by evaluating critical phenomena involved in the intermolecular recognition process. Today, as a variety of docking algorithms are available, an understanding of the advantages and limitations of each method is of fundamental importance in the development of effective strategies and the generation of relevant results. The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods.

  20. Deep transcriptome profiling of mammalian stem cells supports a regulatory role for retrotransposons in pluripotency maintenance

    DEFF Research Database (Denmark)

    Fort, Alexandre; Hashimoto, Kosuke; Yamada, Daisuke

    2014-01-01

    The importance of microRNAs and long noncoding RNAs in the regulation of pluripotency has been documented; however, the noncoding components of stem cell gene networks remain largely unknown. Here we investigate the role of noncoding RNAs in the pluripotent state, with particular emphasis...... on nuclear and retrotransposon-derived transcripts. We have performed deep profiling of the nuclear and cytoplasmic transcriptomes of human and mouse stem cells, identifying a class of previously undetected stem cell-specific transcripts. We show that long terminal repeat (LTR)-derived transcripts contribute...

  1. The role of retrotransposons in gene family expansions: insights from the mouse Abp gene family.

    Science.gov (United States)

    Janoušek, Václav; Karn, Robert C; Laukaitis, Christina M

    2013-05-29

    Retrotransposons have been suggested to provide a substrate for non-allelic homologous recombination (NAHR) and thereby promote gene family expansion. Their precise role, however, is controversial. Here we ask whether retrotransposons contributed to the recent expansions of the Androgen-binding protein (Abp) gene families that occurred independently in the mouse and rat genomes. Using dot plot analysis, we found that the most recent duplication in the Abp region of the mouse genome is flanked by L1Md_T elements. Analysis of the sequence of these elements revealed breakpoints that are the relicts of the recombination that caused the duplication, confirming that the duplication arose as a result of NAHR using L1 elements as substrates. L1 and ERVII retrotransposons are considerably denser in the Abp regions than in one Mb flanking regions, while other repeat types are depleted in the Abp regions compared to flanking regions. L1 retrotransposons preferentially accumulated in the Abp gene regions after lineage separation and roughly followed the pattern of Abp gene expansion. By contrast, the proportion of shared vs. lineage-specific ERVII repeats in the Abp region resembles the rest of the genome. We confirmed the role of L1 repeats in Abp gene duplication with the identification of recombinant L1Md_T elements at the edges of the most recent mouse Abp gene duplication. High densities of L1 and ERVII repeats were found in the Abp gene region with abrupt transitions at the region boundaries, suggesting that their higher densities are tightly associated with Abp gene duplication. We observed that the major accumulation of L1 elements occurred after the split of the mouse and rat lineages and that there is a striking overlap between the timing of L1 accumulation and expansion of the Abp gene family in the mouse genome. Establishing a link between the accumulation of L1 elements and the expansion of the Abp gene family and identification of an NAHR-related breakpoint in

  2. Molecular imprinting sensor based on quantum weak measurement.

    Science.gov (United States)

    Li, Dongmei; He, Qinghua; He, Yonghong; Xin, Meiguo; Zhang, Yilong; Shen, Zhiyuan

    2017-08-15

    A new type of sensing protocol, based on a high precision metrology of quantum weak measurement, was first proposed for molecularly imprinted polymers (MIP) sensor. The feasibility, sensitivity and selectivity of weak measurement based MIP (WMMIP) sensor were experimentally demonstrated with bovine serum albumin (BSA). Weak measurement system exhibits high sensitivity to the optical phase shift corresponding to the refractive index change, which is induced by the specific capture of target protein molecules with its recognition sites. The recognition process can be finally characterized by the central wavelength shift of output spectra through weak value amplification. In our experiment, we prepared BSA@MIP with modified reversed-phase microemulsion method, and coated it on the internal surface of measuring channels assembled into the Mach-Zehnder (MZ) interferometer based optical weak measurement system. The design of this home-built optical system makes it possible to detect analyte in real time. The dynamic process of the specific adsorption and concentration response to BSA from 5×10-4 to 5×10-1μg/L was achieved with a limit of detection (LOD) of 8.01×10-12g/L. This WMMIP shows superiority in accuracy, fast response and low cost. Furthermore, real-time monitoring system can creatively promote the performance of MIP in molecular analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Aptamer-based molecular recognition for biosensor development.

    Science.gov (United States)

    Zhou, Jing; Battig, Mark R; Wang, Yong

    2010-11-01

    Nucleic acid aptamers are an emerging class of synthetic ligands and have recently attracted significant attention in numerous fields. One is in biosensor development. In principle, nucleic acid aptamers can be discovered to recognize any molecule of interest with high affinity and specificity. In addition, unlike most ligands evolved in nature, synthetic nucleic acid aptamers are usually tolerant of harsh chemical, physical, and biological conditions. These distinguished characteristics make aptamers attractive molecular recognition ligands for biosensing applications. This review first concisely introduces methods for aptamer discovery including upstream selection and downstream truncation, then discusses aptamer-based biosensor development from the viewpoint of signal production.

  4. Molecular Dipole Osmosis Based on Induced Charge Electro-Osmosis

    Science.gov (United States)

    Sugioka, Hideyuki

    2016-09-01

    We propose a novel mechanism of producing a large nonlinear electrokinetic vortex flow around a nonconductive polar molecule in an electrolyte. That is, a large nonlinear electrokinetic slip velocity is derived by considering a local giant permittivity due to a molecular electric dipole moment with induced-charge electro-osmosis (ICEO). Different from the conventional ICEO theory, our theory predicts that a nonconductive biomaterial, such as a base of a deoxyribonucleic acid (DNA) molecule, has a significantly high ICEO flow velocity because of its large local permittivity. We consider that our findings will contribute markedly to promising biomedical applications.

  5. Molecular tools for the construction of peptide-based materials.

    Science.gov (United States)

    Ramakers, B E I; van Hest, J C M; Löwik, D W P M

    2014-04-21

    Proteins and peptides are fundamental components of living systems where they play crucial roles at both functional and structural level. The versatile biological properties of these molecules make them interesting building blocks for the construction of bio-active and biocompatible materials. A variety of molecular tools can be used to fashion the peptides necessary for the assembly of these materials. In this tutorial review we shall describe five of the main techniques, namely solid phase peptide synthesis, native chemical ligation, Staudinger ligation, NCA polymerisation, and genetic engineering, that have been used to great effect for the construction of a host of peptide-based materials.

  6. Plasmon-Based Colorimetric Nanosensors for Ultrasensitive Molecular Diagnostics.

    Science.gov (United States)

    Tang, Longhua; Li, Jinghong

    2017-07-28

    Colorimetric detection of target analytes with high specificity and sensitivity is of fundamental importance to clinical and personalized point-of-care diagnostics. Because of their extraordinary optical properties, plasmonic nanomaterials have been introduced into colorimetric sensing systems, which provide significantly improved sensitivity in various biosensing applications. Here we review the recent progress on these plasmonic nanoparticles-based colorimetric nanosensors for ultrasensitive molecular diagnostics. According to their different colorimetric signal generation mechanisms, these plasmonic nanosensors are classified into two categories: (1) interparticle distance-dependent colorimetric assay based on target-induced forming cross-linking assembly/aggregate of plasmonic nanoparticles; and (2) size/morphology-dependent colorimetric assay by target-controlled growth/etching of the plasmonic nanoparticles. The sensing fundamentals and cutting-edge applications will be provided for each of them, particularly focusing on signal generation and/or amplification mechanisms that realize ultrasensitive molecular detection. Finally, we also discuss the challenge and give our future perspective in this emerging field.

  7. Mesoporous Silica Molecular Sieve based Nanocarriers: Transpiring Drug Dissolution Research.

    Science.gov (United States)

    Pattnaik, Satyanarayan; Pathak, Kamla

    2017-01-01

    Improvement of oral bioavailability through enhancement of dissolution for poorly soluble drugs has been a very promising approach. Recently, mesoporous silica based molecular sieves have demonstrated excellent properties to enhance the dissolution velocity of poorly water-soluble drugs. Current research in this area is focused on investigating the factors influencing the drug release from these carriers, the kinetics of drug release and manufacturing approaches to scale-up production for commercial manufacture. This comprehensive review provides an overview of different methods adopted for synthesis of mesoporous materials, influence of processing factors on properties of these materials and drug loading methods. The drug release kinetics from mesoporous silica systems, the manufacturability and stability of these formulations are reviewed. Finally, the safety and biocompatibility issues related to these silica based materials are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Retrotransposon-induced heterochromatin spreading in the mouse revealed by insertional polymorphisms.

    Directory of Open Access Journals (Sweden)

    Rita Rebollo

    2011-09-01

    Full Text Available The "arms race" relationship between transposable elements (TEs and their host has promoted a series of epigenetic silencing mechanisms directed against TEs. Retrotransposons, a class of TEs, are often located in repressed regions and are thought to induce heterochromatin formation and spreading. However, direct evidence for TE-induced local heterochromatin in mammals is surprisingly scarce. To examine this phenomenon, we chose two mouse embryonic stem (ES cell lines that possess insertionally polymorphic retrotransposons (IAP, ETn/MusD, and LINE elements at specific loci in one cell line but not the other. Employing ChIP-seq data for these cell lines, we show that IAP elements robustly induce H3K9me3 and H4K20me3 marks in flanking genomic DNA. In contrast, such heterochromatin is not induced by LINE copies and only by a minority of polymorphic ETn/MusD copies. DNA methylation is independent of the presence of IAP copies, since it is present in flanking regions of both full and empty sites. Finally, such spreading into genes appears to be rare, since the transcriptional start sites of very few genes are less than one Kb from an IAP. However, the B3galtl gene is subject to transcriptional silencing via IAP-induced heterochromatin. Hence, although rare, IAP-induced local heterochromatin spreading into nearby genes may influence expression and, in turn, host fitness.

  9. Tdd-3, a tRNA gene-associated poly(A) retrotransposon from Dictyostelium discoideum.

    Science.gov (United States)

    Winckler, T; Tschepke, C; de Hostos, E L; Jendretzke, A; Dingermann, T

    1998-04-01

    The full-length 5218-bp sequence of the mobile genetic element Tdd-3 from Dictyostelium discoideum is described. Tdd-3 encodes two overlapping open reading frames (ORFs) flanked by non-redundant, untranslated regions. The deduced amino acid sequence of ORF2 is homologous to reverse transcriptases (RTs) encoded by the class of poly(A) retrotransposons. ORF2 also encodes a putative protein domain related to the family of apurinic/apyrimidinic (AP) endonucleases, whose retroelement-encoded homologs have recently been proposed to represent the integrase function of poly(A) retrotransposons. Comparison of several genomic Tdd-3 copies revealed that element insertion is orientation specific and occurs about 100 bp downstream of tRNA genes in the D. discoideum genome. These properties of Tdd-3 suggest that the element is a tRNA gene-associated poly(A) retroelement present in the D. discoideum genome. Analysis of several cloned cDNAs derived from Tdd-3-specific plus strand RNAs indicate that the element is transcribed and polyadenylated during the growth of D. discoideum cells.

  10. Recent expansion of heat-activated retrotransposons in the coral symbiont Symbiodinium microadriaticum

    KAUST Repository

    Chen, Jit Ern

    2017-10-20

    Rising sea surface temperature is the main cause of global coral reef decline. Abnormally high temperatures trigger the breakdown of the symbiotic association between corals and their photosynthetic symbionts in the genus Symbiodinium. Higher genetic variation resulting from shorter generation times has previously been proposed to provide increased adaptability to Symbiodinium compared to the host. Retrotransposition is a significant source of genetic variation in eukaryotes and some transposable elements are specifically expressed under adverse environmental conditions. We present transcriptomic and phylogenetic evidence for the existence of heat stress-activated Ty1-copia-type LTR retrotransposons in the coral symbiont Symbiodinium microadriaticum. Genome-wide analyses of emergence patterns of these elements further indicate recent expansion events in the genome of S. microadriaticum. Our findings suggest that acute temperature increases can activate specific retrotransposons in the Symbiodinium genome with potential impacts on the rate of retrotransposition and the generation of genetic variation under heat stress.The ISME Journal advance online publication, 20 October 2017; doi:10.1038/ismej.2017.179.

  11. Insertional Polymorphism and Antiquity of PDR1 Retrotransposon Insertions in Pisum Species

    Science.gov (United States)

    Jing, Runchun; Knox, Maggie R.; Lee, Jennifer M.; Vershinin, Alexander V.; Ambrose, Michael; Ellis, T. H. Noel; Flavell, Andrew J.

    2005-01-01

    Sequences flanking 73 insertions of the retrotransposon PDR1 have been characterized, together with an additional 270 flanking regions from one side alone, from a diverse collection of Pisum germ plasm. Most of the identified flanking sequences are repetitious DNAs but more than expected (7%) lie within nuclear gene protein-coding regions. The approximate age of 52 of the PDR1 insertions has been determined by measuring sequence divergence among LTR pairs. These data show that PDR1 transpositions occurred within the last 5 MY, with a peak at 1–2.5 MYA. The insertional polymorphism of 68 insertions has been assessed across 47 selected Pisum accessions, representing the diversity of the genus. None of the insertions are fixed, showing that PDR1 insertions can persist in a polymorphic state for millions of years in Pisum. The insertional polymorphism data have been compared with the age estimations to ask what rules control the proliferation of PDR1 insertions in Pisum. Relatively recent insertions ( ∼2.5 MYA) are mostly found in small subsets of Pisum. Finally, the average age estimate for PDR1 insertions, together with an existing data set for PDR1 retrotransposon SSAP markers, has been used to derive an estimate of the effective population size for Pisum of ∼7.5 × 105. PMID:16085698

  12. TROMB, a new retrotransposon of the gypsy-Ty3 group from the fly Megaselia scalaris.

    Science.gov (United States)

    Suck, G; Traut, W

    2000-09-05

    We describe TROMB, a new LTR retrotransposon, from the phorid fly Megaselia scalaris. Three full-length copies (4226, 4160 and 4129bp) and a truncated one (319bp) have been isolated. The target site consensus is TATAT, with a 4bp target site duplication TATA. The LTRs are short (142bp) and contain a TATA-box and a polyadenylation signal. The isolated copies are degenerate to different degrees and presumably inactive. The polyprotein coding sequence contains scattered stop codons and deletions/insertions at non-homologous positions. The consensus sequence among the three full-length copies, however, has an uninterrupted open reading frame and, presumably, represents the original sequence of the active element. Southern hybridization experiments showed TROMB to be present at a low copy number in two wild-type strains of M. scalaris and absent in a related species, M. abdita. The order of domains in the polyprotein coding region, the target site specificity for AT-rich sequences, and the protein sequence similarity to blastopia, mdg3 and micropia place TROMB in the gypsy-Ty3 group of LTR retrotransposons.

  13. Molecular medicine of fragile X syndrome: based on known molecular mechanisms.

    Science.gov (United States)

    Luo, Shi-Yu; Wu, Ling-Qian; Duan, Ran-Hui

    2016-02-01

    Extensive research on fragile X mental retardation gene knockout mice and mutant Drosophila models has largely expanded our knowledge on mechanism-based treatment of fragile X syndrome (FXS). In light of these findings, several clinical trials are now underway for therapeutic translation to humans. Electronic literature searches were conducted using the PubMed database and ClinicalTrials.gov. The search terms included "fragile X syndrome", "FXS and medication", "FXS and therapeutics" and "FXS and treatment". Based on the publications identified in this search, we reviewed the neuroanatomical abnormalities in FXS patients and the potential pathogenic mechanisms to monitor the progress of FXS research, from basic studies to clinical trials. The pathological mechanisms of FXS were categorized on the basis of neuroanatomy, synaptic structure, synaptic transmission and fragile X mental retardation protein (FMRP) loss of function. The neuroanatomical abnormalities in FXS were described to motivate extensive research into the region-specific pathologies in the brain responsible for FXS behavioural manifestations. Mechanism-directed molecular medicines were classified according to their target pathological mechanisms, and the most recent progress in clinical trials was discussed. Current mechanism-based studies and clinical trials have greatly contributed to the development of FXS pharmacological therapeutics. Research examining the extent to which these treatments provided a rescue effect or FMRP compensation for the developmental impairments in FXS patients may help to improve the efficacy of treatments.

  14. Graphene-based nanomaterials as molecular imaging agents.

    Science.gov (United States)

    Garg, Bhaskar; Sung, Chu-Hsun; Ling, Yong-Chien

    2015-01-01

    Molecular imaging (MI) is a noninvasive, real-time visualization of biochemical events at the cellular and molecular level within tissues, living cells, and/or intact objects that can be advantageously applied in the areas of diagnostics, therapeutics, drug discovery, and development in understanding the nanoscale reactions including enzymatic conversions and protein-protein interactions. Consequently, over the years, great advancement has been made in the development of a variety of MI agents such as peptides, aptamers, antibodies, and various nanomaterials (NMs) including single-walled carbon nanotubes. Recently, graphene, a material popularized by Geim & Novoselov, has ignited considerable research efforts to rationally design and execute a wide range of graphene-based NMs making them an attractive platform for developing highly sensitive MI agents. Owing to their exceptional physicochemical and biological properties combined with desirable surface engineering, graphene-based NMs offer stable and tunable visible emission, small hydrodynamic size, low toxicity, and high biocompatibility and thus have been explored for in vitro and in vivo imaging applications as a promising alternative of traditional imaging agents. This review begins by describing the intrinsic properties of graphene and the key MI modalities. After which, we provide an overview on the recent advances in the design and development as well as physicochemical properties of the different classes of graphene-based NMs (graphene-dye conjugates, graphene-antibody conjugates, graphene-nanoparticle composites, and graphene quantum dots) being used as MI agents for potential applications including theranostics. Finally, the major challenges and future directions in the field will be discussed. © 2015 Wiley Periodicals, Inc.

  15. Molecular signatures-based prediction of enzyme promiscuity.

    Science.gov (United States)

    Carbonell, Pablo; Faulon, Jean-Loup

    2010-08-15

    Enzyme promiscuity, a property with practical applications in biotechnology and synthetic biology, has been related to the evolvability of enzymes. At the molecular level, several structural mechanisms have been linked to enzyme promiscuity in enzyme families. However, it is at present unclear to what extent these observations can be generalized. Here, we introduce for the first time a method for predicting catalytic and substrate promiscuity using a graph-based representation known as molecular signature. Our method, which has an accuracy of 85% for the non-redundant KEGG database, is also a powerful analytical tool for characterizing structural determinants of protein promiscuity. Namely, we found that signatures with higher contribution to the prediction of promiscuity are uniformly distributed in the protein structure of promiscuous enzymes. In contrast, those signatures that act as promiscuity determinants are significantly depleted around non-promiscuous catalytic sites. In addition, we present the study of the enolase and aminotransferase superfamilies as illustrative examples of characterization of promiscuous enzymes within a superfamily and achievement of enzyme promiscuity by protein reverse engineering. Recognizing the role of enzyme promiscuity in the process of natural evolution of enzymatic function can provide useful hints in the design of directed evolution experiments. We have developed a method with potential applications in the guided discovery and enhancement of latent catalytic capabilities surviving in modern enzymes. http://www.issb.genopole.fr~faulon.

  16. Advanced synchrotron-based and globar-sourced molecular (micro) spectroscopy contributions to advances in food and feed research on molecular structure, mycotoxin determination, and molecular nutrition.

    Science.gov (United States)

    Shi, Haitao; Yu, Peiqiang

    2017-04-17

    Mycotoxin contamination has been a worldwide problem for food and feeds production for a long time. There is an obviously increased focus of the food and feed industry toward the reduction of mycotoxin concentration in both the raw materials and finished products. Therefore, both effective qualitative and quantitative techniques for the determination of mycotoxins are required to minimize their harmful effects. Conventional wet chemical methods usually are time-consuming, expensive, and rely on complex extraction and cleanup pretreatments. Synchrotron-based and globar-based molecular spectroscopy have shown great potential to be developed as rapid and nondestructive tools for the determination of molecular structure, molecular nutrition and mycotoxins in feed and food. This article reviews the common types of mycotoxins in feed and food, their toxicity, as well as the conventional detection methods. The principle of advanced molecular spectroscopy techniques and their application prospects for mycotoxin detection are discussed. Recent progress in food and feed research with molecular spectroscopy techniques is highlighted. This review provides a potential and insight into how to determine the structure and mycotoxins of feed and food on a molecular basis with advanced Synchrotron-based and globar-based molecular (micro) spectroscopy.

  17. Bases moleculares de alfa-talasemia en la Argentina

    Directory of Open Access Journals (Sweden)

    Karen G Scheps

    2015-04-01

    Full Text Available La α-talasemia, es uno de los desórdenes hereditarios más frecuentes mundialmente. Al presente, el diagnóstico molecular es la única herramienta que permite el diagnóstico certero. El propósito de este trabajo fue caracterizar las bases moleculares de estos síndromes en nuestro medio, y establecer relaciones genotipo-fenotipo. Mediante la complementación de distintas técnicas de biología molecular e hibridación fluorescente in situ (FISH, se logró poner en evidencia la presencia de mutaciones α-talasémicas en 145 de 184 (78.8% pacientes estudiados con perfil hematológico compatible con α-talasemia. Dentro de este grupo, las deleciones correspondieron al defecto genético más frecuente, prevaleciendo la mutación -α3.7 en genotipos heterocigotas y homocigotas. Asimismo, en pacientes con fenotipo α0 las deleciones prevalentes fueron -MED y -CAL/CAMP. Este estudio permitió también describir una deleción de la región sub-telomérica en un paciente con α-talasemia y retraso mental. En el 7.6% de los pacientes caracterizados clínicamente como posibles α-talasémicos (microcitosis con valores de Hb A2 inferiores al 3.5%, se hallaron mutaciones β-talasémicas en estado heterocigota. Se lograron establecer perfiles hematológicos asociados a los genotipos α+ y α0 para pacientes adultos y niños. Esperamos que este trabajo pueda servir como guía para reconocer posibles portadores α-talasémicos. También permite destacar el trabajo en conjunto de médicos hematólogos, el laboratorio (bioquímico y de biología molecular y de los médicos genetistas, con el fin de proporcionar adecuado consejo genético.

  18. Identification of the Boudicca and Sinbad retrotransposons in the genome of the human blood fluke Schistosoma haematobium

    Directory of Open Access Journals (Sweden)

    Claudia S Copeland

    2006-08-01

    Full Text Available Schistosomes have a comparatively large genome, estimated for Schistosoma mansoni to be about 270 megabase pairs (haploid genome. Recent findings have shown that mobile genetic elements constitute significant proportions of the genomes of S. mansoni and S. japonicum. Much less information is available on the genome of the third major human schistosome, S. haematobium. In order to investigate the possible evolutionary origins of the S. mansoni long terminal repeat retrotransposons Boudicca and Sinbad, several genomes were searched by Southern blot for the presence of these retrotransposons. These included three species of schistosomes, S. mansoni, S. japonicum, and S. haematobium, and three related platyhelminth genomes, the liver flukes Fasciola hepatica and Fascioloides magna and the planarian, Dugesia dorotocephala. In addition, Homo sapiens and three snail host genomes, Biomphalaria glabrata, Oncomelania hupensis, and Bulinus truncatus, were examined for possible indications of a horizontal origin for these retrotransposons. Southern hybridization analysis indicated that both Boudicca and Sinbad were present in the genome of S. haematobium. Furthermore, low stringency Southern hybridization analyses suggested that a Boudicca-like retrotransposon was present in the genome of B. truncatus, the snail host of S. haematobium.

  19. Retrotransposon Proliferation Coincident with the Evolution of Dioecy in Asparagus

    OpenAIRE

    Alex Harkess; Francesco Mercati; Loredana Abbate; Michael McKain; J Chris Pires; Tea Sala; Francesco Sunseri; Agostino Falavigna; Jim Leebens-Mack

    2016-01-01

    Current phylogenetic sampling reveals that dioecy and an XY sex chromosome pair evolved once, or possibly twice, in the genus Asparagus. Although there appear to be some lineage-specific polyploidization events, the base chromosome number of 2n = 2× = 20 is relatively conserved across the Asparagus genus. Regardless, dioecious species tend to have larger genomes than hermaphroditic species. Here, we test whether this genome size expansion in dioecious species is related to a polyploidization ...

  20. Fullerene-based Anchoring Groups for Molecular Electronics

    DEFF Research Database (Denmark)

    Martin, Christian A.; Ding, Dapeng; Sørensen, Jakob Kryger

    2008-01-01

    We present results on a new fullerene-based anchoring group for molecular electronics. Using lithographic mechanically controllable break junctions in vacuum we have determined the conductance and stability of single-molecule junctions of 1,4-bis(fullero[c]pyrrolidin-1-yl)benzene. The compound can...... be self-assembled from solution and has a low-bias conductance of 3 × 10-4 G0. Compared to 1,4-benzenedithiol the fullerene-anchored molecule exhibits a considerably lower conductance spread. In addition, the signature of the new compound in histograms is more significant than that of 1,4-benzenediamine......, probably owing to a more stable adsorption motif. Statistical analyses of the breaking of the junctions confirm the stability of the fullerene-gold bond....

  1. Evolution of the EKA family of powdery mildew avirulence-effector genes from the ORF 1 of a LINE retrotransposon.

    Science.gov (United States)

    Amselem, Joelle; Vigouroux, Marielle; Oberhaensli, Simone; Brown, James K M; Bindschedler, Laurence V; Skamnioti, Pari; Wicker, Thomas; Spanu, Pietro D; Quesneville, Hadi; Sacristán, Soledad

    2015-11-10

    The Avrk1 and Avra10 avirulence (AVR) genes encode effectors that increase the pathogenicity of the fungus Blumeria graminis f.sp. hordei (Bgh), the powdery mildew pathogen, in susceptible barley plants. In resistant barley, MLK1 and MLA10 resistance proteins recognize the presence of AVRK1 and AVRA10, eliciting the hypersensitive response typical of gene for gene interactions. Avrk1 and Avra10 have more than 1350 homologues in Bgh genome, forming the EKA (Effectors homologous to Avr k 1 and Avr a 10) gene family. We tested the hypothesis that the EKA family originated from degenerate copies of Class I LINE retrotransposons by analysing the EKA family in the genome of Bgh isolate DH14 with bioinformatic tools specially developed for the analysis of Transposable Elements (TE) in genomes. The Class I LINE retrotransposon copies homologous to Avrk1 and Avra10 represent 6.5 % of the Bgh annotated genome and, among them, we identified 293 AVR/effector candidate genes. We also experimentally identified peptides that indicated the translation of several predicted proteins from EKA family members, which had higher relative abundance in haustoria than in hyphae. Our analyses indicate that Avrk1 and Avra10 have evolved from part of the ORF1 gene of Class I LINE retrotransposons. The co-option of Avra10 and Avrk1 as effectors from truncated copies of retrotransposons explains the huge number of homologues in Bgh genome that could act as dynamic reservoirs from which new effector genes may evolve. These data provide further evidence for recruitment of retrotransposons in the evolution of new biological functions.

  2. Chemically engineered graphene-based 2D organic molecular magnet.

    Science.gov (United States)

    Hong, Jeongmin; Bekyarova, Elena; de Heer, Walt A; Haddon, Robert C; Khizroev, Sakhrat

    2013-11-26

    Carbon-based magnetic materials and structures of mesoscopic dimensions may offer unique opportunities for future nanomagnetoelectronic/spintronic devices. To achieve their potential, carbon nanosystems must have controllable magnetic properties. We demonstrate that nitrophenyl functionalized graphene can act as a room-temperature 2D magnet. We report a comprehensive study of low-temperature magnetotransport, vibrating sample magnetometry (VSM), and superconducting quantum interference (SQUID) measurements before and after radical functionalization. Following nitrophenyl (NP) functionalization, epitaxially grown graphene systems can become organic molecular magnets with ferromagnetic and antiferromagnetic ordering that persists at temperatures above 400 K. The field-dependent, surface magnetoelectric properties were studied using scanning probe microscopy (SPM) techniques. The results indicate that the NP-functionalization orientation and degree of coverage directly affect the magnetic properties of the graphene surface. In addition, graphene-based organic magnetic nanostructures were found to demonstrate a pronounced magneto-optical Kerr effect (MOKE). The results were consistent across different characterization techniques and indicate room-temperature magnetic ordering along preferred graphene orientations in the NP-functionalized samples. Chemically isolated graphene nanoribbons (CINs) were observed along the preferred functionality directions. These results pave the way for future magnetoelectronic/spintronic applications based on promising concepts such as current-induced magnetization switching, magnetoelectricity, half-metallicity, and quantum tunneling of magnetization.

  3. FISH using a gag-like fragment probe reveals a common Ty3-gypsy-like retrotransposon in genome of Coffea species.

    Science.gov (United States)

    Yuyama, Priscila Mary; Pereira, Luiz Filipe Protasio; dos Santos, Tiago Benedito; Sera, Tumoru; Vilas-Boas, Laurival Antonio; Lopes, Fabrício Ramon; Carareto, Claudia Marcia Aparecida; Vanzela, André Luís Laforga

    2012-12-01

    The genus Coffea possesses about 100 species, and the most economically important are Coffea canephora and Coffea arabica. The latter is predominantly self-compatible with 2n = 4x = 44, while the others of the genus are diploid with 2n = 2x = 22 and mostly self-incompatible. Studies using molecular markers have been useful to detect differences between genomes in Coffea; however, molecular and cytogenetic studies have produced only limited information on the karyotypes organization. We used DOP-PCR to isolate repetitive elements from genome of Coffea arabica var. typica. The pCa06 clone, containing a fragment of 775 bp length, was characterized by sequencing and used as a probe in chromosomes of C. arabica and six other species: C. canephora, Coffea eugenioides, Coffea kapakata, Coffea liberica var. dewevrei, Coffea racemosa, and Coffea stenophylla. This insert shows similarities with a gag protein of the Ty3-gypsy-like super-family. Dot blot and FISH analyses demonstrated that pCa06 is differentially accumulated between species and chromosomes. Signals appeared scattered and clustered on the chromosomes and were also associated with heterochromatic regions. While the literature shows that there is a high karyotype similarity between Coffea species, our results point out differences in the accumulation and dispersion of this Ty3-gypsy-like retrotransposon during karyotype differentiation of Coffea.

  4. Assessing Plant Genetic Diversity by Molecular Tools

    Directory of Open Access Journals (Sweden)

    Linda Mondini

    2009-08-01

    Full Text Available This paper is an overview of the diverse, predominantly molecular techniques, used in assessing plant genetic diversity. In recent years, there has been a significant increase in the application of molecular genetic methods for assessing the conservation and use of plant genetic resources. Molecular techniques have been applied in the analysis of specific genes, as well as to increase understanding of gene action, generate genetic maps and assist in the development of gene transfer technologies. Molecular techniques have also had critical roles in studies of phylogeny and species evolution, and have been applied to increase our understanding of the distribution and extent of genetic variation within and between species. These techniques are well established and their advantages as well as limitations have been realized and described in this work. Recently, a new class of advanced techniques has emerged, primarily derived from a combination of earlier, more basic techniques. Advanced marker techniques tend to amalgamate advantageous features of several basic techniques, in order to increase the sensitivity and resolution to detect genetic discontinuity and distinctiveness. Some of the advanced marker techniques utilize newer classes of DNA elements, such as retrotransposons, mitochondrial and chloroplast based microsatellites, thereby revealing genetic variation through increased genome coverage. Techniques such as RAPD and AFLP are also being applied to cDNA-based templates to study patterns of gene expression and uncover the genetic basis of biological responses. The most important and recent advances made in molecular marker techniques are discussed in this review, along with their applications, advantages and limitations applied to plant sciences.

  5. POLYANA-A tool for the calculation of molecular radial distribution functions based on Molecular Dynamics trajectories

    Science.gov (United States)

    Dimitroulis, Christos; Raptis, Theophanes; Raptis, Vasilios

    2015-12-01

    We present an application for the calculation of radial distribution functions for molecular centres of mass, based on trajectories generated by molecular simulation methods (Molecular Dynamics, Monte Carlo). When designing this application, the emphasis was placed on ease of use as well as ease of further development. In its current version, the program can read trajectories generated by the well-known DL_POLY package, but it can be easily extended to handle other formats. It is also very easy to 'hack' the program so it can compute intermolecular radial distribution functions for groups of interaction sites rather than whole molecules.

  6. Molecular Diode Studies Based on a Highly Sensitive Molecular Measurement Technique.

    Science.gov (United States)

    Iwane, Madoka; Fujii, Shintaro; Kiguchi, Manabu

    2017-04-26

    In 1974, molecular electronics pioneers Mark Ratner and Arieh Aviram predicted that a single molecule could act as a diode, in which electronic current can be rectified. The electronic rectification property of the diode is one of basic functions of electronic components and since then, the molecular diode has been investigated as a first single-molecule device that would have a practical application. In this review, we first describe the experimental fabrication and electronic characterization techniques of molecular diodes consisting of a small number of molecules or a single molecule. Then, two main mechanisms of the rectification property of the molecular diode are discussed. Finally, representative results for the molecular diode are reviewed and a brief outlook on crucial issues that need to be addressed in future research is discussed.

  7. Molecular imaging based on metabolic glycoengineering and bioorthogonal click chemistry.

    Science.gov (United States)

    Yoon, Hong Yeol; Koo, Heebeom; Kim, Kwangmeyung; Kwon, Ick Chan

    2017-07-01

    Metabolic glycoengineering is a powerful technique that can introduce various chemical groups to cellular glycan by treatment of unnatural monosaccharide. Particularly, this technique has enabled many challenging trials for molecular imaging in combination with click chemistry, which provides fast and specific chemical conjugation reaction of imaging probes to metabolically-modified live cells. This review introduces recent progress in molecular imaging based on the combination of these two cutting-edge techniques. First, these techniques showed promising results in specific tumor cell imaging for cancer diagnosis and therapy. The related researches showed the surface of tumor cells could be labeled with bioorthogonal chemical groups by metabolic glycoengineering, which can be further conjugated with fluorescence dyes or nanoparticles with imaging probes by click chemistry, in vitro and in vivo. This method can be applied to heterogeneous tumor cells regardless of genetic properties of different tumor cells. Furthermore, the amount of targeting moieties on tumor cells can be freely controlled externally by treatment of unnatural monosaccharide. Second, this sequential use of metabolic glycoengineering and click chemistry is also useful in cell tracking to monitor the localization of the inoculated therapeutic cells including chondrocytes and stem cells. This therapeutic cell-labeling technique provided excellent viability of chondrocytes and stem cells during the whole process in vitro and in vivo. It can provide long-term and safe therapeutic cell imaging compared to traditional methods. These overall studies demonstrate the great potential of metabolic glycoengineering and click chemistry in live cell imaging. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. BASES MOLECULARES DA ABSORÇÃO DO FERRO

    Directory of Open Access Journals (Sweden)

    A. A. MACHADO

    2009-03-01

    Full Text Available

    O ferro é um elemento essencial a todos os organismos vivos e alterações em sua homeostase resultam em quadro de deficiência ou acúmulo, ambos com alta prevalência e relevância clínica. A última década foi marcada pela geração de conhecimentos importantes, que estão contribuindo para a elucidação dos mecanismos moleculares da homeostase do ferro. Foram identificadas proteínas, envolvidas na absorção intestinal do ferro não-heme, e progressos significativos foram feitos no entendimento da regulação da absorção intestinal do ferro, sendo identificadas várias moléculas candidatas. As bases moleculares da homeostase do ferro ainda não foram totalmente elucidadas, porém as informações já existentes sugerem que, em condições fisiológicas, a absorção, o transporte e o armazenamento sejam feitos por moléculas altamente especializadas e, em especial, a absorção, com mecanismos saturáveis em baixa concentração. No entanto, a absorção pode ocorrer por vias menos sujeitas ao controle, dependendo da sobrecarga e da natureza química do composto utilizado. Estas informações advogam a favor de uma revisão nas estratégias de combate à anemia ferropriva. PALAVRAS-CHAVE: Absorção do ferro; DMT-1; hepahestina; ceruloplasmina; ferroportina; hepcidina.

  9. Cell-based quantification of molecular biomarkers in histopathology specimens.

    Science.gov (United States)

    Al-Kofahi, Yousef; Lassoued, Wiem; Grama, Kedar; Nath, Sumit K; Zhu, Jianliang; Oueslati, Ridha; Feldman, Michael; Lee, William M F; Roysam, Badrinath

    2011-07-01

    To investigate the use of a computer-assisted technology for objective, cell-based quantification of molecular biomarkers in specified cell types in histopathology specimens, with the aim of advancing current visual estimation and pixel-level (rather than cell-based) quantification methods. Tissue specimens were multiplex-immunostained to reveal cell structures, cell type markers, and analytes, and imaged with multispectral microscopy. The image data were processed with novel software that automatically delineates and types each cell in the field, measures morphological features, and quantifies analytes in different subcellular compartments of specified cells.The methodology was validated with the use of cell blocks composed of differentially labelled cultured cells mixed in known proportions, and evaluated on human breast carcinoma specimens for quantifying human epidermal growth factor receptor 2, estrogen receptor, progesterone receptor, Ki67, phospho-extracellular signal-related kinase, and phospho-S6. Automated cell-level analyses closely matched human assessments, but, predictably, differed from pixel-level analyses of the same images. Our method reveals the type, distribution, morphology and biomarker state of each cell in the field, and allows multiple biomarkers to be quantified over specified cell types, regardless of their abundance. It is ideal for studying specimens from patients in clinical trials of targeted therapeutic agents, for investigating minority stromal cell subpopulations, and for phenotypic characterization to personalize therapy and prognosis. © 2011 Blackwell Publishing Limited.

  10. Magnetic and electronic properties of porphyrin-based molecular nanowires

    Directory of Open Access Journals (Sweden)

    Jia-Jia Zheng

    2016-01-01

    Full Text Available Using spin-polarized density functional theory calculations, we performed theoretical investigations on the electronic and magnetic properties of transition metal embedded porphyrin-based nanowires (TM-PNWs, TM = Cr, Mn, Co, Ni, Cu, and Zn. Our results indicate that Ni-PNW and Zn-PNW are nonmagnetic while the rest species are magnetic, and the magnetic moments in TM-PNWs and their corresponding isolated monomer structures are found to be the same. In addition, the spin coupling in the magnetic nanowires can be ignored leading to their degenerate AFM and FM states. These results can be ascribed to the weak intermetallic interactions because of the relatively large distances between neighbor TM atoms. Among all TM-PNW structures considered here, only Mn-PNW shows a half-metallic property while the others are predicted to be semiconducting. The present work paves a new way of obtaining ferromagnetic porphyrin-based nanowires with TM atoms distributed separately and orderly, which are expected to be good candidates for catalysts, energy storage and molecular spintronics.

  11. Magnetic and electronic properties of porphyrin-based molecular nanowires

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jia-Jia; Li, Qiao-Zhi; Dang, Jing-Shuang; Zhao, Xiang, E-mail: xzhao@mail.xjtu.edu.cn [Institute for Chemical Physics & Department of Chemistry, MOE Key Laboratory for Non-equilibrium Condensed Matter and Quantum Engineering, School of Science, Xi’an Jiaotong University, Xi’an 710049 (China); Wang, Wei-Wei [Research Center for Computational Science, Institute for Molecular Science, Okazaki, Aichi 444-8585 (Japan)

    2016-01-15

    Using spin-polarized density functional theory calculations, we performed theoretical investigations on the electronic and magnetic properties of transition metal embedded porphyrin-based nanowires (TM-PNWs, TM = Cr, Mn, Co, Ni, Cu, and Zn). Our results indicate that Ni-PNW and Zn-PNW are nonmagnetic while the rest species are magnetic, and the magnetic moments in TM-PNWs and their corresponding isolated monomer structures are found to be the same. In addition, the spin coupling in the magnetic nanowires can be ignored leading to their degenerate AFM and FM states. These results can be ascribed to the weak intermetallic interactions because of the relatively large distances between neighbor TM atoms. Among all TM-PNW structures considered here, only Mn-PNW shows a half-metallic property while the others are predicted to be semiconducting. The present work paves a new way of obtaining ferromagnetic porphyrin-based nanowires with TM atoms distributed separately and orderly, which are expected to be good candidates for catalysts, energy storage and molecular spintronics.

  12. Pathological Bases for a Robust Application of Cancer Molecular Classification

    Directory of Open Access Journals (Sweden)

    Salvador J. Diaz-Cano

    2015-04-01

    Full Text Available Any robust classification system depends on its purpose and must refer to accepted standards, its strength relying on predictive values and a careful consideration of known factors that can affect its reliability. In this context, a molecular classification of human cancer must refer to the current gold standard (histological classification and try to improve it with key prognosticators for metastatic potential, staging and grading. Although organ-specific examples have been published based on proteomics, transcriptomics and genomics evaluations, the most popular approach uses gene expression analysis as a direct correlate of cellular differentiation, which represents the key feature of the histological classification. RNA is a labile molecule that varies significantly according with the preservation protocol, its transcription reflect the adaptation of the tumor cells to the microenvironment, it can be passed through mechanisms of intercellular transference of genetic information (exosomes, and it is exposed to epigenetic modifications. More robust classifications should be based on stable molecules, at the genetic level represented by DNA to improve reliability, and its analysis must deal with the concept of intratumoral heterogeneity, which is at the origin of tumor progression and is the byproduct of the selection process during the clonal expansion and progression of neoplasms. The simultaneous analysis of multiple DNA targets and next generation sequencing offer the best practical approach for an analytical genomic classification of tumors.

  13. Molecular DNA-based detection of ionising radiation in meat.

    Science.gov (United States)

    Şakalar, Ergün

    2017-05-01

    Ionising radiation induces molecular alterations, such as formation of ions, free radicals, and new stable molecules, and cleavage of the chemical bonds of the molecules present in food. Irradiation-treated meat should be labelled to control the process and to ensure free consumer choice. Therefore, sensitive analytical methods are required to detect the irradiation dose. Meat samples were exposed to radiation doses of 0, 0.272, 0.497, 1.063, 3.64, 8.82 and 17.42 kGy in an industrial 60 Co gamma cell. Primers were designed to amplify 998, 498 and 250-base pair (bp) regions of the 18S rRNA gene of nuclear DNA from the irradiated samples. A new DNA-based method was developed to quantify the radiation exposed to the unstored meat and the meat stored at -20 °C for 3 and 6 months. The method was able to detect meat samples stored and unstored with dose limits of 1.063 and 3.64 kGy, respectively. The level of irradiation can be detected using primer pairs that target particularly different-sized sequences for DNA amplification by PCR. This method can be widely used for the analysis of not only meat samples, but also all biological materials containing DNA. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

  14. Numerous small hammerhead ribozyme variants associated with Penelope-like retrotransposons cleave RNA as dimers.

    Science.gov (United States)

    Lünse, Christina E; Weinberg, Zasha; Breaker, Ronald R

    2016-11-18

    Hammerhead ribozymes represent the most common of the nine natural classes of self-cleaving RNAs. The hammerhead catalytic core includes 11 highly-conserved nucleotides located largely within the unpaired regions of a junction formed by stems I, II and III. The vast majority of previously reported examples carry an additional pseudoknot or other tertiary interactions between nucleotides that precede stem I and nucleotides in the loop of stem II. These extra contacts are critical for high-speed RNA catalysis. Herein, we report the discovery of ∼150,000 additional variant hammerhead representatives that exhibit diminished stem III substructures. These variants are frequently associated with Penelope-like retrotransposons, which are a type of mobile genetic element. Kinetic analyses indicate that these RNAs form dimers to cleave RNA.

  15. Evolutionary dynamics in a novel L2 clade of non-LTR retrotransposons in Deuterostomia.

    Science.gov (United States)

    Lovsin, N; Gubensek, F; Kordi, D

    2001-12-01

    The evolution of the novel L2 clade of non-long terminal repeat (LTR) retrotransposons and their evolutionary dynamics in Deuterostomia has been examined. The short-term evolution of long interspersed nuclear element 2s (LINE2s) has been studied in 18 reptilian species by analysis of a PCR amplified 0.7-kb fragment encoding the palm/fingers subdomain of reverse transcriptase (RT). Most of the reptilian LINE2s examined are inactive since they contain multiple stop codons, indels, or frameshift mutations that disrupt the RT. Analysis of reptilian LINE2s has shown a high degree of sequence divergence and an unexpectedly large number of deletions. The evolutionary dynamics of LINE2s in reptiles has been found to be complex. LINE2s are shown to form a novel clade of non-LTR retrotransposons that is well separated from the CR1 clade. This novel L2 clade is more widely distributed than previously thought, and new representatives have been discovered in echinoderms, insects, teleost fishes, Xenopus, Squamata, and marsupials. There is an apparent absence of LINE2s from different vertebrate classes, such as cartilaginous fishes, Archosauria (birds and crocodiles), and turtles. Whereas the LINE2s are present in echinoderms and teleost fishes in a conserved form, in most tetrapods only highly degenerated pseudogenes can be found. The predominance of inactive LINE2s in Tetrapoda indicates that, in the host genomes, only inactive copies are still present. The present data indicate that the vertical inactivation of LINE2s might have begun at the time of Tetrapoda origin, 400 MYA. The evolutionary dynamics of the L2 clade in Deuterostomia can be described as a gradual vertical inactivation in Tetrapoda, stochastic loss in Archosauria and turtles, and strict vertical transmission in echinoderms and teleost fishes.

  16. Retrotransposons and tandem repeat sequences in the nuclear genomes of cryptomonad algae.

    Science.gov (United States)

    Khan, Hameed; Kozera, Catherine; Curtis, Bruce A; Bussey, Jillian Tarrant; Theophilou, Stan; Bowman, Sharen; Archibald, John M

    2007-02-01

    The cryptomonads are an enigmatic group of unicellular eukaryotic algae that possess two nuclear genomes, having acquired photosynthesis by the uptake and retention of a eukaryotic algal endosymbiont. The endosymbiont nuclear genome, or nucleomorph, of the cryptomonad Guillardia theta has been completely sequenced: at only 551 kilobases (kb) and with a gene density of approximately 1 gene/kb, it is a model of compaction. In contrast, very little is known about the structure and composition of the cryptomonad host nuclear genome. Here we present the results of two small-scale sequencing surveys of fosmid clone libraries from two distantly related cryptomonads, Rhodomonas salina CCMP1319 and Cryptomonas paramecium CCAP977/2A, corresponding to approximately 150 and approximately 235 kb of sequence, respectively. Very few of the random end sequences determined in this study show similarity to known genes in other eukaryotes, underscoring the considerable evolutionary distance between the cryptomonads and other eukaryotes whose nuclear genomes have been completely sequenced. Using a combination of fosmid clone end-sequencing, Southern hybridizations, and PCR, we demonstrate that Ty3-gypsy long-terminal repeat (LTR) retrotransposons and tandem repeat sequences are a prominent feature of the nuclear genomes of both organisms. The complete sequence of a 30.9-kb genomic fragment from R. salina was found to contain a full-length Ty3-gypsy element with near-identical LTRs and a chromodomain, a protein module suggested to mediate the site-specific integration of the retrotransposon. The discovery of chromodomain-containing retroelements in cryptomonads further expands the known distribution of the so-called chromoviruses across the tree of eukaryotes.

  17. Determinants of molecular marker based classification of rice (Oryza ...

    African Journals Online (AJOL)

    mr devi singh

    2015-01-07

    Jan 7, 2015 ... The genomic DNA of 44 rice varieties was isolated using CTAB method (Moller et al., 1992). 10. ISSR and 28 SSR molecular markers (Table 4) were used for genetic analysis. The ISSR-PCR technique (Zietkiewicz et al.,. 1994) was used to enhance the speed of sensitivity of detection of molecular markers.

  18. Molecular microenvironments: Solvent interactions with nucleic acid bases and ions

    Science.gov (United States)

    Macelroy, R. D.; Pohorille, A.

    1986-01-01

    The possibility of reconstructing plausible sequences of events in prebiotic molecular evolution is limited by the lack of fossil remains. However, with hindsight, one goal of molecular evolution was obvious: the development of molecular systems that became constituents of living systems. By understanding the interactions among molecules that are likely to have been present in the prebiotic environment, and that could have served as components in protobiotic molecular systems, plausible evolutionary sequences can be suggested. When stable aggregations of molecules form, a net decrease in free energy is observed in the system. Such changes occur when solvent molecules interact among themselves, as well as when they interact with organic species. A significant decrease in free energy, in systems of solvent and organic molecules, is due to entropy changes in the solvent. Entropy-driven interactioins played a major role in the organization of prebiotic systems, and understanding the energetics of them is essential to understanding molecular evolution.

  19. Sensitive determination of citrinin based on molecular imprinted electrochemical sensor

    Energy Technology Data Exchange (ETDEWEB)

    Atar, Necip [Department of Chemical Engineering, Faculty of Engineering, Pamukkale University, Denizli (Turkey); Yola, Mehmet Lütfi, E-mail: mehmetyola@gmail.com [Department of Metallurgical and Materials Engineering, Faculty of Engineering, Sinop University, Sinop (Turkey); Eren, Tanju [Department of Chemical Engineering, Faculty of Engineering, Pamukkale University, Denizli (Turkey)

    2016-01-30

    Graphical abstract: - Highlights: • Citrinin-imprinted electrochemical sensor is developed for the sensitive detection of citrinin. • The nanomaterial and citrinin-imprinted surfaces were characterized by several methods. • Citrinin-imprinted electrochemical sensor is sensitive and selective in analysis of food. • Citrinin-imprinted electrochemical sensor is preferred to the other methods. - Abstract: In this report, a novel molecular imprinted voltammetric sensor based on glassy carbon electrode (GCE) modified with platinum nanoparticles (PtNPs) involved in a polyoxometalate (H{sub 3}PW{sub 12}O{sub 40}, POM) functionalized reduced graphene oxide (rGO) was prepared for the determination of citrinin (CIT). The developed surfaces were characterized by using scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) method. CIT imprinted GCE was prepared via electropolymerization process of 80.0 mM pyrrole as monomer in the presence of phosphate buffer solution (pH 6.0) containing 20.0 mM CIT. The linearity range and the detection limit of the developed method were calculated as 1.0 × 10{sup −12}–1.0 × 10{sup −10} M and 2.0 × 10{sup −13} M, respectively. In addition, the voltammetric sensor was applied to rye samples. The stability and selectivity of the voltammetric sensor were also reported.

  20. Actin-based motility propelled by molecular motors

    Science.gov (United States)

    Upadyayula, Sai Pramod; Rangarajan, Murali

    2012-09-01

    Actin-based motility of Listeria monocytogenes propelled by filament end-tracking molecular motors has been simulated. Such systems may act as potential nanoscale actuators and shuttles useful in sorting and sensing biomolecules. Filaments are modeled as three-dimensional elastic springs distributed on one end of the capsule and persistently attached to the motile bacterial surface through an end-tracking motor complex. Filament distribution is random, and monomer concentration decreases linearly as a function of position on the bacterial surface. Filament growth rate increases with monomer concentration but decreases with the extent of compression. The growing filaments exert push-pull forces on the bacterial surface. In addition to forces, torques arise due to two factors—distribution of motors on the bacterial surface, and coupling of torsion upon growth due to the right-handed helicity of F-actin—causing the motile object to undergo simultaneous translation and rotation. The trajectory of the bacterium is simulated by performing a force and torque balance on the bacterium. All simulations use a fixed value of torsion. Simulations show strong alignment of the filaments and the long axis of the bacterium along the direction of motion. In the absence of torsion, the bacterial surface essentially moves along the direction of the long axis. When a small amount of the torsion is applied to the bacterial surface, the bacterium is seen to move in right-handed helical trajectories, consistent with experimental observations.

  1. A portable, integrated analyzer for microfluidic - based molecular analysis.

    Science.gov (United States)

    Qiu, Xianbo; Chen, Dafeng; Liu, Changchun; Mauk, Michael G; Kientz, Terry; Bau, Haim H

    2011-10-01

    A portable, fully automated analyzer that provides actuation and flow control to a disposable, self-contained, microfluidic cassette ("chip") for point-of-care, molecular testing is described. The analyzer provides mechanical actuation to compress pouches that pump liquids in the cassette, to open and close diaphragm valves for flow control, and to induce vibrations that enhance stirring. The analyzer also provides thermal actuation for the temperature cycling needed for polymerase chain reaction (PCR) amplification of nucleic acids and for various drying processes. To improve the temperature uniformity of the PCR chamber, the system utilizes a double-sided heating/cooling scheme with a custom feedforward, variable, structural proportional-integral-derivative (FVSPID) controller. The analyzer includes a programmable central processing unit that directs the sequence and timing of the various operations and that is interfaced with a computer. The disposable cassette receives a sample, and it carries out cell lysis, nucleic acid isolation, concentration, and purification, thermal cycling, and either real time or lateral flow (LF) based detection. The system's operation was demonstrated by processing saliva samples spiked with B. cereus cells. The amplicons were detected with a lateral flow assay using upconverting phosphor reporter particles. This system is particularly suited for use in regions lacking centralized laboratory facilities and skilled personnel.

  2. UPAR targeted molecular imaging of cancers with small molecule-based probes.

    Science.gov (United States)

    Ding, Feng; Chen, Seng; Zhang, Wanshu; Tu, Yufeng; Sun, Yao

    2017-10-15

    Molecular imaging can allow the non-invasive characterization and measurement of biological and biochemical processes at the molecular and cellular levels in living subjects. The imaging of specific molecular targets that are associated with cancers could allow for the earlier diagnosis and better treatment of diseases. Small molecule-based probes play prominent roles in biomedical research and have high clinical translation ability. Here, with an emphasis on small molecule-based probes, we review some recent developments in biomarkers, imaging techniques and multimodal imaging in molecular imaging and highlight the successful applications for molecular imaging of cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Symbol Synchronization for Diffusion-Based Molecular Communications.

    Science.gov (United States)

    Jamali, Vahid; Ahmadzadeh, Arman; Schober, Robert

    2017-12-01

    Symbol synchronization refers to the estimation of the start of a symbol interval and is needed for reliable detection. In this paper, we develop several symbol synchronization schemes for molecular communication (MC) systems where we consider some practical challenges, which have not been addressed in the literature yet. In particular, we take into account that in MC systems, the transmitter may not be equipped with an internal clock and may not be able to emit molecules with a fixed release frequency. Such restrictions hold for practical nanotransmitters, e.g., modified cells, where the lengths of the symbol intervals may vary due to the inherent randomness in the availability of food and energy for molecule generation, the process for molecule production, and the release process. To address this issue, we develop two synchronization-detection frameworks which both employ two types of molecule. In the first framework, one type of molecule is used for symbol synchronization and the other one is used for data detection, whereas in the second framework, both types of molecule are used for joint symbol synchronization and data detection. For both frameworks, we first derive the optimal maximum likelihood (ML) symbol synchronization schemes as performance upper bounds. Since ML synchronization entails high complexity, for each framework, we also propose three low-complexity suboptimal schemes, namely a linear filter-based scheme, a peak observation-based scheme, and a threshold-trigger scheme, which are suitable for MC systems with limited computational capabilities. Furthermore, we study the relative complexity and the constraints associated with the proposed schemes and the impact of the insertion and deletion errors that arise due to imperfect synchronization. Our simulation results reveal the effectiveness of the proposed synchronization schemes and suggest that the end-to-end performance of MC systems significantly depends on the accuracy of the symbol

  4. A CZT-based blood counter for quantitative molecular imaging.

    Science.gov (United States)

    Espagnet, Romain; Frezza, Andrea; Martin, Jean-Pierre; Hamel, Louis-André; Lechippey, Laëtitia; Beauregard, Jean-Mathieu; Després, Philippe

    2017-12-01

    Robust quantitative analysis in positron emission tomography (PET) and in single-photon emission computed tomography (SPECT) typically requires the time-activity curve as an input function for the pharmacokinetic modeling of tracer uptake. For this purpose, a new automated tool for the determination of blood activity as a function of time is presented. The device, compact enough to be used on the patient bed, relies on a peristaltic pump for continuous blood withdrawal at user-defined rates. Gamma detection is based on a 20 × 20 × 15 mm3 cadmium zinc telluride (CZT) detector, read by custom-made electronics and a field-programmable gate array-based signal processing unit. A graphical user interface (GUI) allows users to select parameters and easily perform acquisitions. This paper presents the overall design of the device as well as the results related to the detector performance in terms of stability, sensitivity and energy resolution. Results from a patient study are also reported. The device achieved a sensitivity of 7.1 cps/(kBq/mL) and a minimum detectable activity of 2.5 kBq/ml for 18F. The gamma counter also demonstrated an excellent stability with a deviation in count rates inferior to 0.05% over 6 h. An energy resolution of 8% was achieved at 662 keV. The patient study was conclusive and demonstrated that the compact gamma blood counter developed has the sensitivity and the stability required to conduct quantitative molecular imaging studies in PET and SPECT.

  5. A modular hierarchy-based theory of the chemical origins of life based on molecular complementarity.

    Science.gov (United States)

    Root-Bernstein, Robert

    2012-12-18

    Albert Szent-Gyorgyi once defined discovery as seeing what everyone else sees and thinking what no one else thinks. I often find that phenomena that are obvious to other people are not obvious to me. Molecular complementarity is one of these phenomena: while rare among any random set of compounds, it is ubiquitous in living systems. Because every molecule in a living system binds more or less specifically to several others, we now speak of "interactomes". What explains the ubiquity of molecular complementarity in living systems? What might such an explanation reveal about the chemical origins of life and the principles that have governed its evolution? Beyond this, what might complementarity tell us about the optimization of integrated systems in general? My research combines theoretical and experimental approaches to molecular complementarity relating to evolution from prebiotic chemical systems to superorganismal interactions. Experimentally, I have characterized complementarity involving specific binding between small molecules and explored how these small-molecule modules have been incorporated into macromolecular systems such as receptors and transporters. Several general principles have emerged from this research. Molecules that bind to each other almost always alter each other's physiological effects; and conversely, molecules that have antagonistic or synergistic physiological effects almost always bind to each other. This principle suggests a chemical link between biological structure and function. Secondly, modern biological systems contain an embedded molecular paleontology based on complementarity that can reveal their chemical origins. This molecular paleontology is often manifested through modules involving small, molecularly complementary subunits that are built into modern macromolecular structures such as receptors and transporters. A third principle is that complementary modules are conserved and repurposed at every stage of evolution. Molecular

  6. Discovery and partial characterization of a non-LTR retrotransposon that may be associated with abdominal segment deformity disease (ASDD) in the whiteleg shrimp Penaeus (Litopenaeus) vannamei

    Science.gov (United States)

    2013-01-01

    Background Abdominal segment deformity disease (ASDD) of cultivated whiteleg shrimp Penaeus (Litopenaeus) vannamei causes economic loss of approximately 10% in affected specimens because of the unsightliness of distorted abdominal muscles. It is associated with the presence of viral-like particles seen by electron microscopy in the ventral nerve cords of affected shrimp. Thus, shotgun cloning was carried out to seek viral-like sequences in affected shrimp. Results A new retrovirus-like element of 5052 bp (named abdominal segment deformity element or ASDE) was compiled by shotgun cloning and 3′ and 5′ RACE using RNA and DNA extracted from ventral nerve cords of ASDD shrimp. ASDE contained 7 putative open reading frames (ORF). One ORF (called the PENS sub-domain), had a deduced amino acid (aa) sequence homologous to the GIY-YIG endonuclease domain of penelope-like retrotransposons while two others were homologous to the reverse transcriptase (RT) and RNaseH domains of the pol gene of non-long terminal repeat (non-LTR) retrotransposons (called the NLRS sub-domain). No single amplicon of 5 kb containing both these elements was obtained by PCR or RT-PCR from ASDD shrimp. Subsequent analysis indicated that PENS and NLRS were not contiguous and that NLRS was a host genetic element. In situ hybridization using a dioxygenin-labeled NLRS probe revealed that NLRS gave positive reactions in abdominal-ganglion neurons of ASDD shrimp but not normal shrimp. Preliminary analysis indicated that long-term use of female broodstock after eyestalk ablation in the hatchery increased the intensity of RT-PCR amplicons for NLRS and also the prevalence of ASDD in mysis 3 offspring of the broodstock. The deformities persist upon further cultivation until shrimp harvest but do not increase in prevalence and do not affect growth or survival. Conclusions Our results suggested that NLRS is a shrimp genetic element associated with ASDD and that immediate preventative measures could include

  7. Elemental and Molecular Heritage: An Internet-based Display

    Directory of Open Access Journals (Sweden)

    Henry S. Rzepa

    1998-03-01

    Full Text Available The background to a Web page describing elemental and molecular heritage at Imperial College chemistry department is described. Photographs are shown of the original samples of elemental bromine and crystalline silicon, and molecular ferrocene and mauveine. 3D "Hyperactive" models of these systems are shown, together with a recently discovered heterocyclic systems scorpionine, which like mauveine is made by a deceptively simple chemical synthesis.

  8. Congenital neutropenia: diagnosis, molecular bases and patient management

    Science.gov (United States)

    2011-01-01

    The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe (Neutropenia can lead to life-threatening pyogenic infections, acute gingivostomatitis and chronic parodontal disease, and each successive infection may leave permanent sequelae. The risk of infection is roughly inversely proportional to the circulating polymorphonuclear neutrophil count and is particularly high at counts below 0.2 G/l. When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia) and congenital forms that may either be isolated or part of a complex genetic disease. Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant. About half the forms of congenital neutropenia with no extra-hematopoetic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE) mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia. Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency) and glycogen storage disease type Ib (associated with a glycogen storage syndrome). So far, the molecular bases of 12 neutropenic disorders have been identified. Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte-colony-stimulating factor (G-CSF). G-CSF has considerably improved these patients' outlook. It is usually well tolerated, but potential adverse effects

  9. Congenital neutropenia: diagnosis, molecular bases and patient management

    Directory of Open Access Journals (Sweden)

    Chantelot Christine

    2011-05-01

    Full Text Available Abstract The term congenital neutropenia encompasses a family of neutropenic disorders, both permanent and intermittent, severe ( When neutropenia is detected, an attempt should be made to establish the etiology, distinguishing between acquired forms (the most frequent, including post viral neutropenia and auto immune neutropenia and congenital forms that may either be isolated or part of a complex genetic disease. Except for ethnic neutropenia, which is a frequent but mild congenital form, probably with polygenic inheritance, all other forms of congenital neutropenia are extremely rare and have monogenic inheritance, which may be X-linked or autosomal, recessive or dominant. About half the forms of congenital neutropenia with no extra-hematopoetic manifestations and normal adaptive immunity are due to neutrophil elastase (ELANE mutations. Some patients have severe permanent neutropenia and frequent infections early in life, while others have mild intermittent neutropenia. Congenital neutropenia may also be associated with a wide range of organ dysfunctions, as for example in Shwachman-Diamond syndrome (associated with pancreatic insufficiency and glycogen storage disease type Ib (associated with a glycogen storage syndrome. So far, the molecular bases of 12 neutropenic disorders have been identified. Treatment of severe chronic neutropenia should focus on prevention of infections. It includes antimicrobial prophylaxis, generally with trimethoprim-sulfamethoxazole, and also granulocyte-colony-stimulating factor (G-CSF. G-CSF has considerably improved these patients' outlook. It is usually well tolerated, but potential adverse effects include thrombocytopenia, glomerulonephritis, vasculitis and osteoporosis. Long-term treatment with G-CSF, especially at high doses, augments the spontaneous risk of leukemia in patients with congenital neutropenia.

  10. Genome-wide survey and comparative analysis of LTR retrotransposons and their captured genes in rice and sorghum.

    Directory of Open Access Journals (Sweden)

    Shu-Ye Jiang

    Full Text Available Long terminal repeat (LTR retrotransposons are the major class I mobile elements in plants. They play crucial roles in gene expansion, diversification and evolution. However, their captured genes are yet to be genome-widely identified and characterized in most of plants although many genomes have been completely sequenced. In this study, we have identified 7,043 and 23,915 full-length LTR retrotransposons in the rice and sorghum genomes, respectively. High percentages of rice full-length LTR retrotransposons were distributed near centromeric region in each of the chromosomes. In contrast, sorghum full-length LTR retrotransposons were not enriched in centromere regions. This dissimilarity could be due to the discrepant retrotransposition during and after divergence from their common ancestor thus might be contributing to species divergence. A total of 672 and 1,343 genes have been captured by these elements in rice and sorghum, respectively. Gene Ontology (GO and gene set enrichment analysis (GSEA showed that no over-represented GO term was identified in LTR captured rice genes. For LTR captured sorghum genes, GO terms with functions in DNA/RNA metabolism and chromatin organization were over-represented. Only 36% of LTR captured rice genes were expressed and expression divergence was estimated as 11.9%. Higher percentage of LTR captured rice genes have evolved into pseudogenes under neutral selection. On the contrary, higher percentage of LTR captured sorghum genes were under purifying selection and 72.4% of them were expressed. Thus, higher percentage of LTR captured sorghum genes was functional. Small RNA analysis suggested that some of LTR captured genes in rice and sorghum might have been involved in negative regulation. On the other hand, positive selection has been observed in both rice and sorghum LTR captured genes and some of them were still expressed and functional. The data suggest that some of these LTR captured genes might have

  11. Linking maternal and somatic 5S rRNA types with different sequence-specific non-LTR retrotransposons.

    Science.gov (United States)

    Locati, Mauro D; Pagano, Johanna F B; Ensink, Wim A; van Olst, Marina; van Leeuwen, Selina; Nehrdich, Ulrike; Zhu, Kongju; Spaink, Herman P; Girard, Geneviève; Rauwerda, Han; Jonker, Martijs J; Dekker, Rob J; Breit, Timo M

    2017-04-01

    5S rRNA is a ribosomal core component, transcribed from many gene copies organized in genomic repeats. Some eukaryotic species have two 5S rRNA types defined by their predominant expression in oogenesis or adult tissue. Our next-generation sequencing study on zebrafish egg, embryo, and adult tissue identified maternal-type 5S rRNA that is exclusively accumulated during oogenesis, replaced throughout the embryogenesis by a somatic-type, and thus virtually absent in adult somatic tissue. The maternal-type 5S rDNA contains several thousands of gene copies on chromosome 4 in tandem repeats with small intergenic regions, whereas the somatic-type is present in only 12 gene copies on chromosome 18 with large intergenic regions. The nine-nucleotide variation between the two 5S rRNA types likely affects TFIII binding and riboprotein L5 binding, probably leading to storage of maternal-type rRNA. Remarkably, these sequence differences are located exactly at the sequence-specific target site for genome integration by the 5S rRNA-specific Mutsu retrotransposon family. Thus, we could define maternal- and somatic-type MutsuDr subfamilies. Furthermore, we identified four additional maternal-type and two new somatic-type MutsuDr subfamilies, each with their own target sequence. This target-site specificity, frequently intact maternal-type retrotransposon elements, plus specific presence of Mutsu retrotransposon RNA and piRNA in egg and adult tissue, suggest an involvement of retrotransposons in achieving the differential copy number of the two types of 5S rDNA loci. © 2017 Locati et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  12. Sol-gel-based molecularly imprinted xerogel for capillary microextraction.

    Science.gov (United States)

    Bagheri, Habib; Piri-Moghadam, Hamed

    2012-09-01

    A novel molecularly imprinted xerogel (MIX) based on organically modified silica (ORMOSIL) was successfully prepared for on-line capillary microextraction (CME) coupled with high-performance liquid chromatography (HPLC). The sol-gel-based xerogel was prepared using only one precursor and exhibited extensive selectivity towards triazines along with significant thermal and chemical stability. Atrazine was selected as a model template molecule and 3-(trimethoxysilyl)propylmethacrylate (TMSPMA) as a precursor in which the propylmethacrylate moiety was responsible for van der Waals, dipole-dipole, and hydrogen-bond interactions with the template. This moiety plays a key role in creation of selective sites while methoxysilyl groups in TMSPMA acted as crosslinkers between the template and the propylmethacrylate moiety. Moreover, a non-imprinted xerogel (NIX) was also prepared in the absence of the template for evaluating the extraction efficiency of the prepared MIX. Then, the prepared imprinted and non-imprinted xerogels were used for extraction of three selected analytes of triazines class including atrazine, ametryn, and terbutryn, which have rather similar structures. The extraction efficiency of the prepared xerogel for atrazine, the template molecule, was found to be ten times greater than the efficiency achieved by the non-imprinted one. In the meantime, the extraction efficiency ratio of MIX to NIX for ametryn and terbutryn was also rather significant (eight times). Moreover, other compounds from different classes including dicamba, mecoprop, and estriol were also analyzed to evaluate the selectivity of the prepared MIX towards triazines. The ratio of enrichment factors (EF) of MIX to NIX for atrazine, ametryn, terbutryn, dicamba, mecoprop, and estriol were about 10, 8, 8, 2, 2, and 3, respectively. The linearity for the analytes was in the range of 5-700 μg L(-1). Limit of detection was in the range of 1-5 μg L(-1) and the RSD% values (n = 5) were all below 6

  13. De novo genetic variation associated with retrotransposon activation, genomic rearrangements and trait variation in a recombinant inbred line population of Brassica napus derived from interspecific hybridization with Brassica rapa.

    Science.gov (United States)

    Zou, Jun; Fu, Donghui; Gong, Huihui; Qian, Wei; Xia, Wei; Pires, J Chris; Li, Ruiyuan; Long, Yan; Mason, Annaliese S; Yang, Tae-Jin; Lim, Yong P; Park, Beom S; Meng, Jinling

    2011-10-01

    Interspecific hybridization is a significant evolutionary force as well as a powerful method for crop breeding. Partial substitution of the AA subgenome in Brassica napus (A(n) A(n) C(n) C(n) ) with the Brassica rapa (A(r) A(r) ) genome by two rounds of interspecific hybridization resulted in a new introgressed type of B. napus (A(r) A(r) C(n) C(n) ). In this study, we construct a population of recombinant inbred lines of the new introgressed type of B. napus. Microsatellite, intron-based and retrotransposon markers were used to characterize this experimental population with genetic mapping, genetic map comparison and specific marker cloning analysis. Yield-related traits were also recorded for identification of quantitative trait loci (QTLs). A remarkable range of novel genomic alterations was observed in the population, including simple sequence repeat (SSR) mutations, chromosomal rearrangements and retrotransposon activations. Most of these changes occurred immediately after interspecific hybridization, in the early stages of genome stabilization and derivation of experimental lines. These novel genomic alterations affected yield-related traits in the introgressed B. napus to an even greater extent than the alleles alone that were introgressed from the A(r) subgenome of B. rapa, suggesting that genomic changes induced by interspecific hybridization are highly significant in both genome evolution and crop improvement. © 2011 The Authors. The Plant Journal © 2011 Blackwell Publishing Ltd.

  14. Ancient Origin of the U2 Small Nuclear RNA Gene-Targeting Non-LTR Retrotransposons Utopia.

    Directory of Open Access Journals (Sweden)

    Kenji K Kojima

    Full Text Available Most non-long terminal repeat (non-LTR retrotransposons encoding a restriction-like endonuclease show target-specific integration into repetitive sequences such as ribosomal RNA genes and microsatellites. However, only a few target-specific lineages of non-LTR retrotransposons are distributed widely and no lineage is found across the eukaryotic kingdoms. Here we report the most widely distributed lineage of target sequence-specific non-LTR retrotransposons, designated Utopia. Utopia is found in three supergroups of eukaryotes: Amoebozoa, SAR, and Opisthokonta. Utopia is inserted into a specific site of U2 small nuclear RNA genes with different strength of specificity for each family. Utopia families from oomycetes and wasps show strong target specificity while only a small number of Utopia copies from reptiles are flanked with U2 snRNA genes. Oomycete Utopia families contain an "archaeal" RNase H domain upstream of reverse transcriptase (RT, which likely originated from a plant RNase H gene. Analysis of Utopia from oomycetes indicates that multiple lineages of Utopia have been maintained inside of U2 genes with few copy numbers. Phylogenetic analysis of RT suggests the monophyly of Utopia, and it likely dates back to the early evolution of eukaryotes.

  15. Molecular materials and devices: developing new functional systems based on the coordination chemistry approach

    Directory of Open Access Journals (Sweden)

    Toma Henrique E.

    2003-01-01

    Full Text Available At the onset of the nanotechnology age, molecular designing of materials and single molecule studies are opening wide possibilities of using molecular systems in electronic and photonic devices, as well as in technological applications based on molecular switching or molecular recognition. In this sense, inorganic chemists are privileged by the possibility of using the basic strategies of coordination chemistry to build up functional supramolecular materials, conveying the remarkable chemical properties of the metal centers and the characteristics of the ancillary ligands. Coordination chemistry also provides effective self-assembly strategies based on specific metal-ligand affinity and stereochemistry. Several molecular based materials, derived from inorganic and metal-organic compounds are focused on this article, with emphasis on new supramolecular porphyrins and porphyrazines, metal-clusters and metal-polyimine complexes. Such systems are also discussed in terms of their applications in catalysis, sensors and molecular devices.

  16. Molecular Modelling of Peptide-Based Materials for Biomedical Applications.

    Science.gov (United States)

    Walsh, Tiffany R

    2017-01-01

    The molecular-level interactions between peptides and medically-relevant biomaterials, including nanoparticles, have the potential to advance technologies aimed at improving performance for medical applications including tissue implants and regenerative medicine. Peptides can possess materials-selective non-covalent adsorption properties, which in this instance can be exploited to enhance the biocompatibility and possible multi-functionality of medical implant materials. However, at present, their successful implementation in medical applications is largely on a trial-and-error basis, in part because a deep comprehension of general structure/function relationships at these interfaces is currently lacking. Molecular simulation approaches can complement experimental characterisation techniques and provide a wealth of relevant details at the atomic scale. In this Chapter, progress and prospects for advancing peptide-mediated medical implant surface treatments via molecular simulation is summarised for two of the most widely-found medical implant interfaces, titania and hydroxyapatite.

  17. Synthesis of Glucose Based Water Soluble Molecular Tweezers as Molecular Recognition Scaffolds

    Directory of Open Access Journals (Sweden)

    Lalit Sharma

    2011-01-01

    Full Text Available Dry heating of 4,4’-methylenedianiline and N,N’-dimethyl-4,4’-methylenedianiline with 5,6-anhydro-1,2-o-isopropylidene-α-D-glucofuranose afforded molecular tweezers having tertiary amino group linked to C-6 of the glucose moiety. These molecular tweezers on deprotection with dilute acid yielded water soluble analogs which were explored for the solubilization of neutral arenes viz. naphthalene, biphenyl, durene, fluorene, anthracene and phenanthrene in acidic aqueous medium. These solid liquid extraction studies revealed that 6,6’-(N,N’-dimethyl-4’’,4’’’-methylenedianilino bis (α-D-glucopyranose causes an approximate 31 fold increase in the solubility of biphenyl in aqueous medium and has best complementarity for naphthalene by forming 1:1 complex.

  18. Optical materials based on molecular nano/microcrystals and ...

    Indian Academy of Sciences (India)

    Wintec

    quantum confinement effect familiar in semiconductor nanocrystals (Wise 2000; Horn and Rieger 2001). Conside- ... 'break-down' approaches have been developed for the synthesis of molecular nanomaterials (Ozin and .... characterization of BCADQ and semiempirical quantum chemical computations on the molecule and ...

  19. Biodiversity of few Indian charophyte taxa based on molecular ...

    African Journals Online (AJOL)

    AJB SERVER

    2006-09-04

    Sep 4, 2006 ... Besides these, molecular characterization and isolation of Fe-hydrogenase was attempted in Chlorella fusca by Winkler et al. (2002) while Meneses (1996) used it to assess the population of Gracilaria. In Charophyta, Wood and Imahori (1965) either merged various independent species together or created ...

  20. Molecular phylogenetic implications in Brassica napus based on ...

    Indian Academy of Sciences (India)

    Brassica napus L. (canola, rapeseed) is one of the most important oil crops in many countries (Abdelmigid 2012;. Fayyaz et al. 2014), and thought to have originated from a cross where the maternal donor was closely related to two diploid species, B. oleracea (CC, 2n = 18) and B. rapa (AA, 2n = 20). Here, molecular ...

  1. Molecular characterization of Cymbidium kanran cultivars based on ...

    African Journals Online (AJOL)

    Fifty-four Cymbidium kanran cultivars from China, Japan and Korea were examined and analyzed by using the successive screening of 3'-end extended random primer amplified polymorphic DNA (ERAPD) markers to determine their molecular diversity and relationships. In ERAPD analyses, the strandspecific DNA ...

  2. Web Based Learning Support for Experimental Design in Molecular Biology.

    Science.gov (United States)

    Wilmsen, Tinri; Bisseling, Ton; Hartog, Rob

    An important learning goal of a molecular biology curriculum is a certain proficiency level in experimental design. Currently students are confronted with experimental approaches in textbooks, in lectures and in the laboratory. However, most students do not reach a satisfactory level of competence in the design of experimental approaches. This…

  3. Molecular phylogeny of Trametes and related genera based on ...

    African Journals Online (AJOL)

    use

    2011-12-12

    Dec 12, 2011 ... Key words: Trametes, internal transcribed spacer (ITS) sequences, nearly complete mitochondrial small subunit ribosomal DNA ... analysis. Unfortunately, the sequence length of these domains is short and they contain few informative sites, so they are not commonly used among molecular syst- ematists ...

  4. Diversity of the Ty-1 copia retrotransposon Tos17 in rice (Oryza sativa L.) and the AA genome of the Oryza genus.

    Science.gov (United States)

    Petit, Julie; Bourgeois, Emmanuelle; Stenger, Wilfried; Bès, Martine; Droc, Gaétan; Meynard, Donaldo; Courtois, Brigitte; Ghesquière, Alain; Sabot, François; Panaud, Olivier; Guiderdoni, Emmanuel

    2009-12-01

    Retrotransposons are mobile genetic elements, ubiquitous in Eukaryotic genomes, which have proven to be major genetic tools in determining phylogeny and structuring genetic diversity, notably in plants. We investigate here the diversity of the Ty1-copia retrotransposon Tos17 in the cultivated rice of Asian origin (Oryza sativa L.) and related AA genome species of the Oryza genus, to contribute understanding of the complex evolutionary history in this group of species through that of the element in the lineages. In that aim, we used a combination of Southern hybridization with a reverse transcriptase (RT) probe and an adapter-PCR mediated amplification, which allowed the sequencing of the genomic regions flanking Tos17 insertions. This analysis was carried out in a collection of 47 A-genome Oryza species accessions and 202 accessions of a core collection of Oryza sativa L. representative of the diversity of the species. Our Southern hybridization results show that Tos17 is present in all the accessions of the A-genome Oryza species, except for the South American species O. glumaepatula and the African species O. glaberrima and O. breviligulata. In O. sativa, the number of putative copies of Tos17 per accession ranged from 1 to 11 and multivariate analysis based on presence/absence of putative copies yielded a varietal clustering which is consistent with the isozyme classification of rice. Adapter PCR amplification and sequencing of flanking regions of Tos17 insertions in A-genome species other than O. sativa, followed by anchoring on the Nipponbare genome sequence, revealed 13 insertion sites of Tos17 in the surveyed O. rufipogon and O. longistaminata accessions, including one shared by both species. In O. sativa, the same approach revealed 25 insertions in the 6 varietal groups. Four insertion sites located on chromosomes 1, 2, 10, and 11 were found orthologous in O. rufipogon and O. sativa. The chromosome 1 insertion was also shared between O. rufipogon and O

  5. Osvaldo and Isis retrotransposons as markers of the Drosophila buzzatii colonisation in Australia

    Directory of Open Access Journals (Sweden)

    Fontdevila Antonio

    2011-04-01

    Full Text Available Abstract Background Transposable elements (TEs constitute an important source of genetic variability owing to their jumping and regulatory properties, and are considered to drive species evolution. Several factors that are able to induce TE transposition in genomes have been documented (for example environmental stress and inter- and intra-specific crosses but in many instances the reasons for TE mobilisation have yet to be elucidated. Colonising populations constitute an ideal model for studying TE behaviour and distribution as they are exposed to different environmental and new demographic conditions. In this study, the distribution of two TEs, Osvaldo and Isis, was examined in two colonising populations of D. buzzatii from Australia. Comparing Osvaldo copy numbers between Australian and Old World (reported in previous studies colonisations provides a valuable tool for elucidating the colonisation process and the effect of new conditions encountered by colonisers on TEs. Results The chromosomal distributions of Osvaldo and Isis retrotransposons in two colonising populations of D. buzzatii from Australia revealed sites of high insertion frequency (>10% and low frequency sites. Comparisons between Osvaldo insertion profiles in colonising populations from the Old World and Australia demonstrate a tendency towards a higher number of highly occupied sites with higher insertion frequency in the Old World than in Australian populations. Tests concerning selection against deleterious TE insertions indicate that Isis is more controlled by purifying selection than Osvaldo. The distribution of both elements on chromosomal arms follows a Poisson distribution and there are non-significant positive correlations between highly occupied sites and chromosomal inversions. Conclusions The occupancy profile of Osvaldo and Isis retrotransposons is characterised by the existence of high and low insertion frequency sites in the populations. These results demonstrate

  6. High-molecular-weight HPMA-based polymer drug carriers for delivery to tumor.

    Science.gov (United States)

    Kostka, L; Etrych, T

    2016-10-20

    In this work, design and synthesis of high-molecular-weight N-(2-hydroxypropyl)methacrylamide-based polymer drug delivery systems tailored for cancer therapy is summarized. Moreover, the influence of their architecture on tumor accumulation and in vivo anti-cancer efficacy is discussed. Mainly, the high-molecular-weight delivery systems, such as branched, grafted, multi-block, star-like or micellar systems, with molecular weights greater than the renal threshold are discussed and reviewed in detail.

  7. [Development of molecular pharmacognosy in China based on bibliometric analysis].

    Science.gov (United States)

    Liu, Yang; Wang, Jun-Wen; Tong, Yuan-Yuan; Yang, Ce; Huang, Man-Ting; Lei, Lei; Li, Hai-Yan

    2016-03-01

    The method of bibliometrics was used to analyze the literature about the application of molecular biotechnique to pharmacognosy which were searched and obtained from the CNKI database and Shanghai intellectual property information platform from the year 1995 to 2015.It was found that 22 462 articles were published and the 63% were funded, 50 core institutions and 888 authors, 18 core journals were engaged in this subject.496 items of patents were authorized and 90 kinds of Chinese Materia Medica were involved.In the view of the quantity and quality of published literature, the scale and influence of journals, institutions, and the extent of subject categories have made remarkable achievement. Molecular pharmacognosy has completed the germination stage of a new subject, and has been in a relatively mature and stable development status. Copyright© by the Chinese Pharmaceutical Association.

  8. Effect of molecular electrical doping on polyfuran based photovoltaic cells

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Shuwen; Opitz, Andreas; Salzmann, Ingo, E-mail: ingo.salzmann@physik.hu-berlin.de [Humboldt-Universität zu Berlin, Institut für Physik and IRIS Adlershof, Brook-Taylor Straße 6, 12489 Berlin (Germany); Frisch, Johannes [Helmholtz-Zentrum für Materialien und Energie GmbH, Bereich Solarenergieforschung, Albert-Einstein-Straße 15, 12489 Berlin (Germany); Cohen, Erez; Bendikov, Michael [Department of Organic Chemistry, Weizmann Institute of Science, 76100 Rehovot (Israel); Koch, Norbert [Humboldt-Universität zu Berlin, Institut für Physik and IRIS Adlershof, Brook-Taylor Straße 6, 12489 Berlin (Germany); Helmholtz-Zentrum für Materialien und Energie GmbH, Bereich Solarenergieforschung, Albert-Einstein-Straße 15, 12489 Berlin (Germany)

    2015-05-18

    The electronic, optical, and morphological properties of molecularly p-doped polyfuran (PF) films were investigated over a wide range of doping ratio in order to explore the impact of doping in photovoltaic applications. We find evidence for integer-charge transfer between PF and the prototypical molecular p-dopant tetrafluoro-tetracyanoquinodimethane (F4TCNQ) and employed the doped polymer in bilayer organic solar cells using fullerene as acceptor. The conductivity increase in the PF films at dopant loadings ≤2% significantly enhances the short-circuit current of photovoltaic devices. For higher doping ratios, however, F4TCNQ is found to precipitate at the heterojunction between the doped donor polymer and the fullerene acceptor. Ultraviolet photoelectron spectroscopy reveals that its presence acts beneficial to the energy-level alignment by doubling the open-circuit voltage of solar cells from 0.2 V to ca. 0.4 V, as compared to pristine PF.

  9. SYNTHESIS OF NOVEL BISPHENOL-BIPHENANTHROLINE-BASED MOLECULAR TWEEZERS

    Directory of Open Access Journals (Sweden)

    Said nadeem

    2015-11-01

    Full Text Available A molecular “dugdugi” 8 derived from 1,10-phenanthroline  was synthesized and characterized by using NMR, EIMS and UV studies. Bisphenol was alkylated with 1,3-dibromopropane and reacted with 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-ylphenol to obtain 8. 30 mmolL-1 solution of 8 was prepared in 10 % DMF in ethanol and was stirred for 30 min with 30 m L-1 ethanolic solutions of Co2+, Cr3+, Cu2+, Fe3+, Mn2+, Ni2+, Ag+, and Zn2+. Chemosensor 8 switched-on in the presence of Fe3+ by showing pink color while it remained turn-off in the presence of other metals. The UV spectra of the molecular “dugdugi” showed a peak at 279 nm which shifted to 290 nm after interacting with Fe3+. A new peak also appeared at 524 nm.

  10. Adsorbate-driven cooling of carbene-based molecular junctions

    Czech Academy of Sciences Publication Activity Database

    Foti, Giuseppe; Vázquez, Héctor

    2017-01-01

    Roč. 8, Oct (2017), s. 2060-2068 ISSN 2190-4286 R&D Projects: GA ČR GA15-19672S EU Projects: European Commission(XE) 702114 - HEATEXMOL Institutional support: RVO:68378271 Keywords : adsorbate * carbene * current-induced heating and cooling * molecular junction * vibrations Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 3.127, year: 2016

  11. Epidemiological bases and molecular mechanisms linking obesity, diabetes, and cancer.

    Science.gov (United States)

    Gutiérrez-Salmerón, María; Chocarro-Calvo, Ana; García-Martínez, José Manuel; de la Vieja, Antonio; García-Jiménez, Custodia

    2017-02-01

    The association between diabetes and cancer was hypothesized almost one century ago. Today, a vast number of epidemiological studies support that obese and diabetic populations are more likely to experience tissue-specific cancers, but the underlying molecular mechanisms remain unknown. Obesity, diabetes, and cancer share many hormonal, immune, and metabolic changes that may account for the relationship between diabetes and cancer. In addition, antidiabetic treatments may have an impact on the occurrence and course of some cancers. Moreover, some anticancer treatments may induce diabetes. These observations aroused a great controversy because of the ethical implications and the associated commercial interests. We report an epidemiological update from a mechanistic perspective that suggests the existence of many common and differential individual mechanisms linking obesity and type 1 and 2 diabetes mellitus to certain cancers. The challenge today is to identify the molecular links responsible for this association. Classification of cancers by their molecular signatures may facilitate future mechanistic and epidemiological studies. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. Molecular Dynamics Simulation of Carbon Nanotube Based Gears

    Science.gov (United States)

    Han, Jie; Globus, Al; Jaffe, Richard; Deardorff, Glenn; Chancellor, Marisa K. (Technical Monitor)

    1996-01-01

    We used molecular dynamics to investigate the properties and design space of molecular gears fashioned from carbon nanotubes with teeth added via a benzyne reaction known to occur with C60. A modified, parallelized version of Brenner's potential was used to model interatomic forces within each molecule. A Leonard-Jones 6-12 potential was used for forces between molecules. One gear was powered by forcing the atoms near the end of the buckytube to rotate, and a second gear was allowed.to rotate by keeping the atoms near the end of its buckytube on a cylinder. The meshing aromatic gear teeth transfer angular momentum from the powered gear to the driven gear. A number of gear and gear/shaft configurations were simulated. Cases in vacuum and with an inert atmosphere were examined. In an extension to molecular dynamics technology, some simulations used a thermostat on the atmosphere while the hydrocarbon gear's temperature was allowed to fluctuate. This models cooling the gears with an atmosphere. Results suggest that these gears can operate at up to 50-100 gigahertz in a vacuum or inert atmosphere at room temperature. The failure mode involves tooth slip, not bond breaking, so failed gears can be returned to operation by lowering temperature and/or rotation rate. Videos and atomic trajectory files in xyz format are presented.

  13. Identification and chromosomal distribution of copia-like retrotransposon sequences in the coffee (Coffea L. genome

    Directory of Open Access Journals (Sweden)

    Juan-Carlos Herrera

    2013-12-01

    Full Text Available The presence of copia-like transposable elements in seven coffee (Coffea sp. species, including the cultivated Coffea arabica, was investigated. The highly conserved domains of the reverse transcriptase (RT present in the copia retrotransposons were amplified by PCR using degenerated primers. Fragments of roughly 300 bp were obtained and the nucleotide sequence was determined for 36 clones, 19 of which showed good quality. The deduced amino acid sequences were compared by multiple alignment analysis. The data suggested two distinct coffee RT groups, designated as CRTG1 and CRTG2. The sequence identities among the groups ranged from 52 to 60% for CRTG1 and 74 to 85% for CRTG2. The multiple alignment analysis revealed that some of the clones in CRTG1 were closely related to the representative elements present in other plant species such as Brassica napus, Populus ciliata and Picea abis. Furthermore, the chromosomal localization of the RT domains in C. arabica and their putative ancestors was investigated by fluorescence in situ hybridization (FISH analysis. FISH signals were observed throughout the chromosomes following a similar dispersed pattern with some localized regions exhibiting higher concentrations of those elements, providing new evidence of their relative conservation and stability in the coffee genome

  14. Ablation of RNA interference and retrotransposons accompany acquisition and evolution of transposases to heterochromatin protein CENPB

    Science.gov (United States)

    Upadhyay, Udita; Srivastava, Suchita; Khatri, Indu; Nanda, Jagpreet Singh; Subramanian, Srikrishna; Arora, Amit; Singh, Jagmohan

    2017-01-01

    Inactivation of retrotransposons is accompanied by the emergence of centromere-binding protein-B (CENPB) in Schizosaccharomyces, as well as in metazoans. The RNA interference (RNAi)-induced transcriptional silencing (RITS) complex, comprising chromodomain protein-1 (Chp1), Tas3 (protein with unknown function), and Argonaute (Ago1), plays an important role in RNAi-mediated heterochromatinization. We find that whereas the Ago1 subunit of the RITS complex is highly conserved, Tas3 is lost and Chp1 is truncated in Schizosaccharomyces cryophilus and Schizosaccharomyces octosporus. We show that truncated Chp1 loses the property of heterochromatin localization and silencing when transformed in Schizosaccharomyces pombe. Furthermore, multiple copies of CENPB, related to Tc1/mariner and Tc5 transposons, occur in all Schizosaccharomyces species, as well as in humans, but with loss of transposase function (except Schizosaccharomyces japonicus). We propose that acquisition of Tc1/mariner and Tc5 elements by horizontal transfer in S. pombe (and humans) is accompanied by alteration of their function from a transposase/endonuclease to a heterochromatin protein, designed to suppress transposon expression and recombination. The resulting redundancy of RITS may have eased the selection pressure, resulting in progressive loss or truncation of tas3 and chp1 genes in S. octosporus and S. cryophilus and triggered similar evolutionary dynamics in the metazoan orthologues. PMID:28228545

  15. L1 retrotransposon antisense RNA within ASAR lncRNAs controls chromosome-wide replication timing.

    Science.gov (United States)

    Platt, Emily J; Smith, Leslie; Thayer, Mathew J

    2017-12-29

    Mammalian cells replicate their chromosomes via a temporal replication program. The ASAR6 and ASAR15 genes were identified as loci that when disrupted result in delayed replication and condensation of entire human chromosomes. ASAR6 and ASAR15 are monoallelically expressed long noncoding RNAs that remain associated with the chromosome from which they are transcribed. The chromosome-wide effects of ASAR6 map to the antisense strand of an L1 retrotransposon within ASAR6 RNA, deletion or inversion of which delayed replication of human chromosome 6. Furthermore, ectopic integration of ASAR6 or ASAR15 transgenes into mouse chromosomes resulted in delayed replication and condensation, an increase in H3K27me3, coating of the mouse chromosome with ASAR RNA, and a loss of mouse Cot-1 RNA expression in cis. Targeting the antisense strand of the L1 within ectopically expressed ASAR6 RNA restored normal replication timing. Our results provide direct evidence that L1 antisense RNA plays a functional role in chromosome-wide replication timing of mammalian chromosomes. © 2018 Platt et al.

  16. Drug Repositioning by Kernel-Based Integration of Molecular Structure, Molecular Activity, and Phenotype Data

    Science.gov (United States)

    Wang, Yongcui; Chen, Shilong; Deng, Naiyang; Wang, Yong

    2013-01-01

    Computational inference of novel therapeutic values for existing drugs, i.e., drug repositioning, offers the great prospect for faster and low-risk drug development. Previous researches have indicated that chemical structures, target proteins, and side-effects could provide rich information in drug similarity assessment and further disease similarity. However, each single data source is important in its own way and data integration holds the great promise to reposition drug more accurately. Here, we propose a new method for drug repositioning, PreDR (Predict Drug Repositioning), to integrate molecular structure, molecular activity, and phenotype data. Specifically, we characterize drug by profiling in chemical structure, target protein, and side-effects space, and define a kernel function to correlate drugs with diseases. Then we train a support vector machine (SVM) to computationally predict novel drug-disease interactions. PreDR is validated on a well-established drug-disease network with 1,933 interactions among 593 drugs and 313 diseases. By cross-validation, we find that chemical structure, drug target, and side-effects information are all predictive for drug-disease relationships. More experimentally observed drug-disease interactions can be revealed by integrating these three data sources. Comparison with existing methods demonstrates that PreDR is competitive both in accuracy and coverage. Follow-up database search and pathway analysis indicate that our new predictions are worthy of further experimental validation. Particularly several novel predictions are supported by clinical trials databases and this shows the significant prospects of PreDR in future drug treatment. In conclusion, our new method, PreDR, can serve as a useful tool in drug discovery to efficiently identify novel drug-disease interactions. In addition, our heterogeneous data integration framework can be applied to other problems. PMID:24244318

  17. Benchmarking ab initio binding energies of hydrogen-bonded molecular clusters based on FTIR spectroscopy

    DEFF Research Database (Denmark)

    Bork, Nicolai Christian; Du, Lin; Reiman, Heidi

    2014-01-01

    of the Gibbs free binding energies in molecular complexes and clusters based on gas phase FTIR spectroscopy. The acetonitrile-HCl molecular complex is identified via its redshifted H-Cl stretching vibrational mode. We determine the Gibbs free binding energy, ΔG°295 K, to between 4.8 and 7.9 kJ mol(-1...

  18. Molecular modeling of protonic acid doping of emeraldine base polyaniline for chemical sensors

    NARCIS (Netherlands)

    Chen, X.; Yuan, C.A.; Wong, C.K.Y.; Ye, H.; Leung, S.Y.Y.; Zhang, G.

    2012-01-01

    We proposed a molecular modeling methodology to study the protonic acid doping of emeraldine base polyaniline which can used in gas detection. The commercial forcefield COMPASS was used for the polymer and protonic acid molecules. The molecular model, which is capable of representing the polyaniline

  19. Molecular Imaging: A Useful Tool for the Development of Natural Killer Cell-Based Immunotherapies.

    Science.gov (United States)

    Gangadaran, Prakash; Ahn, Byeong-Cheol

    2017-01-01

    Molecular imaging is a relatively new discipline that allows visualization, characterization, and measurement of the biological processes in living subjects, including humans, at a cellular and molecular level. The interaction between cancer cells and natural killer (NK) cells is complex and incompletely understood. Despite our limited knowledge, progress in the search for immune cell therapies against cancer could be significantly improved by dynamic and non-invasive visualization and tracking of immune cells and by visualization of the response of cancer cells to therapies in preclinical and clinical studies. Molecular imaging is an essential tool for these studies, and a multimodal molecular imaging approach can be applied to monitor immune cells in vivo, for instance, to visualize therapeutic effects. In this review, we discuss the usefulness of NK cells in cancer therapies and the preclinical and clinical usefulness of molecular imaging in NK cell-based therapies. Furthermore, we discuss different molecular imaging modalities for use with NK cell-based therapies, and their preclinical and clinical applications in animal and human subjects. Molecular imaging has contributed to the development of NK cell-based therapies against cancers in animal models and to the refinement of current cell-based cancer immunotherapies. Developing sensitive and reproducible non-invasive molecular imaging technologies for in vivo NK cell monitoring and for real-time assessment of therapeutic effects will accelerate the development of NK cell therapies.

  20. Molecular Imaging: A Useful Tool for the Development of Natural Killer Cell-Based Immunotherapies

    Directory of Open Access Journals (Sweden)

    Prakash Gangadaran

    2017-09-01

    Full Text Available Molecular imaging is a relatively new discipline that allows visualization, characterization, and measurement of the biological processes in living subjects, including humans, at a cellular and molecular level. The interaction between cancer cells and natural killer (NK cells is complex and incompletely understood. Despite our limited knowledge, progress in the search for immune cell therapies against cancer could be significantly improved by dynamic and non-invasive visualization and tracking of immune cells and by visualization of the response of cancer cells to therapies in preclinical and clinical studies. Molecular imaging is an essential tool for these studies, and a multimodal molecular imaging approach can be applied to monitor immune cells in vivo, for instance, to visualize therapeutic effects. In this review, we discuss the usefulness of NK cells in cancer therapies and the preclinical and clinical usefulness of molecular imaging in NK cell-based therapies. Furthermore, we discuss different molecular imaging modalities for use with NK cell-based therapies, and their preclinical and clinical applications in animal and human subjects. Molecular imaging has contributed to the development of NK cell-based therapies against cancers in animal models and to the refinement of current cell-based cancer immunotherapies. Developing sensitive and reproducible non-invasive molecular imaging technologies for in vivo NK cell monitoring and for real-time assessment of therapeutic effects will accelerate the development of NK cell therapies.

  1. Choline metabolism-based molecular diagnosis of cancer: an update.

    Science.gov (United States)

    Glunde, Kristine; Penet, Marie-France; Jiang, Lu; Jacobs, Michael A; Bhujwalla, Zaver M

    2015-06-01

    Abnormal choline metabolism continues to be identified in multiple cancers. Molecular causes of abnormal choline metabolism are changes in choline kinase-α, ethanolamine kinase-α, phosphatidylcholine-specific phospholipase C and -D and glycerophosphocholine phosphodiesterases, as well as several choline transporters. The net outcome of these enzymatic changes is an increase in phosphocholine and total choline (tCho) and, in some cancers, a relative decrease of glycerophosphocholine. The increased tCho signal detected by (1)H magnetic resonance spectroscopy is being evaluated as a diagnostic marker in multiple cancers. Increased expression and activity of choline transporters and choline kinase-α have spurred the development of radiolabeled choline analogs as PET imaging tracers. Both tCho (1)H magnetic resonance spectroscopy and choline PET are being investigated to detect response to treatment. Enzymes mediating the abnormal choline metabolism are being explored as targets for cancer therapy. This review highlights recent molecular, therapeutic and clinical advances in choline metabolism in cancer.

  2. Fishing the molecular bases of Treacher Collins syndrome.

    Directory of Open Access Journals (Sweden)

    Andrea M J Weiner

    Full Text Available Treacher Collins syndrome (TCS is an autosomal dominant disorder of craniofacial development, and mutations in the TCOF1 gene are responsible for over 90% of TCS cases. The knowledge about the molecular mechanisms responsible for this syndrome is relatively scant, probably due to the difficulty of reproducing the pathology in experimental animals. Zebrafish is an emerging model for human disease studies, and we therefore assessed it as a model for studying TCS. We identified in silico the putative zebrafish TCOF1 ortholog and cloned the corresponding cDNA. The derived polypeptide shares the main structural domains found in mammals and amphibians. Tcof1 expression is restricted to the anterior-most regions of zebrafish developing embryos, similar to what happens in mouse embryos. Tcof1 loss-of-function resulted in fish showing phenotypes similar to those observed in TCS patients, and enabled a further characterization of the mechanisms underlying craniofacial malformation. Besides, we initiated the identification of potential molecular targets of treacle in zebrafish. We found that Tcof1 loss-of-function led to a decrease in the expression of cellular proliferation and craniofacial development. Together, results presented here strongly suggest that it is possible to achieve fish with TCS-like phenotype by knocking down the expression of the TCOF1 ortholog in zebrafish. This experimental condition may facilitate the study of the disease etiology during embryonic development.

  3. Fragment Molecular Orbital method-based Molecular Dynamics (FMO-MD) as a simulator for chemical reactions in explicit solvation.

    Science.gov (United States)

    Komeiji, Yuto; Ishikawa, Takeshi; Mochizuki, Yuji; Yamataka, Hiroshi; Nakano, Tatsuya

    2009-01-15

    Fragment Molecular Orbital based-Molecular Dynamics (FMO-MD, Komeiji et al., Chem Phys Lett 2003, 372, 342) is an ab initio MD method suitable for large molecular systems. Here, FMO-MD was implemented to conduct full quantum simulations of chemical reactions in explicit solvation. Several FMO-MD simulations were performed for a sphere of water to find a suitable simulation protocol. It was found that annealing of the initial configuration by a classical MD brought the subsequent FMO-MD trajectory to faster stabilization, and also that use of bond constraint in the FMO-MD heating stage effectively reduced the computation time. Then, the blue moon ensemble method (Sprik and Ciccotti, J Chem Phys 1998, 109, 7737) was implemented and was tested by calculating free energy profiles of the Menschutkin reaction (H3N + CH3Cl --> +H3NCH3 + Cl-) in the presence and absence of the solvent water via FMO-MD. The obtained free energy profiles were consistent with the Hammond postulate in that stabilization of the product by the solvent, namely hydration of Cl-, shifted the transition state to the reactant-side. Based on these FMO-MD results, plans for further improvement of the method are discussed. Copyright 2008 Wiley Periodicals, Inc.

  4. Non-invasive cancer detection using molecular device based on aromatic molecules

    Directory of Open Access Journals (Sweden)

    Rupan Preet Kaur

    2016-12-01

    Full Text Available Major advances in the molecular diagnostics of screening tissue and blood samples have fueled the search for biomarkers and diagnostic nanosensors that can detect abnormalities early in their development cycles. In this paper, we propose an aromatic molecular junction-based biomarker that can trace the concentration of lead in any live sample. A nanomolecular device based on an anthracenedithiol molecule was modeled. Its electrical transport attributes were computed using a semi-empirical extended Huckel theory combined with non-equilibrium Green’s function formalism. We observed that the current and conductance assay had prominent changes when the molecular junction device was exposed to variant concentrations of lead. Based on our results, we propose aromatic molecular junction-based biomarkers that can detect even minor adulterations of lead when plied at operating voltage range.

  5. Molecular basis of Acute Myelogenous Leukemia As bases moleculares da leucemia mielóide aguda

    Directory of Open Access Journals (Sweden)

    Eduardo M. Rego

    2002-01-01

    Full Text Available Acute Myelogenous Leukemia (AML is frequently associated with recurring chromosomal translocations, which lead to the fusion of two genes encoding transcription factors. As the moieties of these fusion proteins retain part of the functional domains of the wild-type proteins, they may interfere directly or indirectly with the transcriptional regulation of the leukemic cell, conferring survival advantage. The majority of the transcription factors commonly involved in recurring chromosomal translocations may be grouped in one of the following families: core binding factor (CBF, retinoic acid receptor alpha (RARalpha, homeobox (HOX family, and mixed lineage leukemia (MLL. In vivo analysis of the molecular basis of leukemogenesis through the generation of transgenic mouse models revealed that a common theme is the recruitment of transcriptional co-activators and co-repressors by these fusion proteins. However, the expression of the fusion protein is not sufficient to induce full blown leukemia, as evidenced in part by the long latencies required for disease development in the transgenic models of leukemia, and therefore, second mutagenic events may contribute to AML pathogenesis.A leucemia mielóide aguda (LMA está freqüentemente associada a translocações cromossômicas recorrentes. Em muitos casos, os genes presentes nos pontos de quebra cromossômica são conhecidos e, quase todos codificam para fatores de transcrição. O gene híbrido, resultante da justaposição de exons de genes distintos, codifica para proteínas de fusão. Como estas retêm a maior parte dos domínios funcionais das proteínas selvagens, elas interferem direta ou indiretamente com regulação da transcrição gênica, conferindo vantagem à sobrevivência das células leucêmicas. A maioria dos fatores de transcrição afetados pelas translocações cromossômicas associadas a LMA pode ser agrupada numa das seguintes famílias: dos core binding factors (CBF, do receptor

  6. Molecular Dynamics on FPGA Based Accelerated Processing Units

    Directory of Open Access Journals (Sweden)

    Maliţa Mihaela

    2017-01-01

    Full Text Available One of the main problems in providing the amount of computation requested by the Molecular Dynamic domain is to offer an appropriate architectural environment for solving all the aspects of the intense parts of the involved computation. Current solutions accelerate only partially the intense computation – forces com putation & position and speed updates, which represents around 75% from the total computational effort – thus limiting the help provided by the parallel computing resources involved. The aim of this paper is to introduce a parallel accelerator featured with functions able to add to the accelerated functions the neighbourhood list building, which represent around 25% from the total computation. Thus, accelerations higher than the current ~ 4× are expected. Our proposal, the MapReduce Accelerator, is evaluated using the Gromacs system. The Martini water example, running on a cycle accurate simulator, is used to evaluate the speed-up and the energy.

  7. Molecular bases of cellular senescence: Hayflick phenomenon 50 years later

    Directory of Open Access Journals (Sweden)

    Patrycja Sosińska

    2016-03-01

    Full Text Available Normal human somatic cells have strictly limited proliferative capacity and reach a state of senescence when it becomes exhausted. It is believed that senescence is a response to extensive and irreparable DNA injury, localized in telomeric and/or non-telomeric regions of the genome. Main cause of this damage is oxidative stress, increasing due to deteriorated function of mitochondria. Senescent cells accumulate in tissues during aging, which is causatively linked with the development of various pathologies in elderly individuals, including cancer. This paper, prepared exactly 50 years after Leonard Hayflick’s discovery of the relationship between cellular senescence and organismal aging is aimed at presenting the current knowledge about molecular determinants of senescence, with particular emphasis paid to the role of oxidative stress, effectors of senescence at the level of cell cycle, markers of this phenomenon, and the effect of senescent cells on the development of certain age-related diseases.

  8. ChemPreview: an augmented reality-based molecular interface.

    Science.gov (United States)

    Zheng, Min; Waller, Mark P

    2017-05-01

    Human computer interfaces make computational science more comprehensible and impactful. Complex 3D structures such as proteins or DNA are magnified by digital representations and displayed on two-dimensional monitors. Augmented reality has recently opened another door to access the virtual three-dimensional world. Herein, we present an augmented reality application called ChemPreview with the potential to manipulate bio-molecular structures at an atomistic level. ChemPreview is available at https://github.com/wallerlab/chem-preview/releases, and is built on top of the Meta 1 platform https://www.metavision.com/. ChemPreview can be used to interact with a protein in an intuitive way using natural hand gestures, thereby making it appealing to computational chemists or structural biologists. The ability to manipulate atoms in real world could eventually provide new and more efficient ways of extracting structural knowledge, or designing new molecules in silico. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Genetic diversity analysis of common beans based on molecular markers

    Directory of Open Access Journals (Sweden)

    Homar R. Gill-Langarica

    2011-01-01

    Full Text Available A core collection of the common bean (Phaseolus vulgaris L., representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each, as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP +3/+3 primer combinations and seven simple sequence repeats (SSR loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA and molecular variance (AMOVA analyses. AFLP analysis produced 530 bands (88.5% polymorphic while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus. AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  10. Uncovering Molecular Bases Underlying Bone Morphogenetic Protein Receptor Inhibitor Selectivity.

    Directory of Open Access Journals (Sweden)

    Abdelaziz Alsamarah

    Full Text Available Abnormal alteration of bone morphogenetic protein (BMP signaling is implicated in many types of diseases including cancer and heterotopic ossifications. Hence, small molecules targeting BMP type I receptors (BMPRI to interrupt BMP signaling are believed to be an effective approach to treat these diseases. However, lack of understanding of the molecular determinants responsible for the binding selectivity of current BMP inhibitors has been a big hindrance to the development of BMP inhibitors for clinical use. To address this issue, we carried out in silico experiments to test whether computational methods can reproduce and explain the high selectivity of a small molecule BMP inhibitor DMH1 on BMPRI kinase ALK2 vs. the closely related TGF-β type I receptor kinase ALK5 and vascular endothelial growth factor receptor type 2 (VEGFR2 tyrosine kinase. We found that, while the rigid docking method used here gave nearly identical binding affinity scores among the three kinases; free energy perturbation coupled with Hamiltonian replica-exchange molecular dynamics (FEP/H-REMD simulations reproduced the absolute binding free energies in excellent agreement with experimental data. Furthermore, the binding poses identified by FEP/H-REMD led to a quantitative analysis of physical/chemical determinants governing DMH1 selectivity. The current work illustrates that small changes in the binding site residue type (e.g. pre-hinge region in ALK2 vs. ALK5 or side chain orientation (e.g. Tyr219 in caALK2 vs. wtALK2, as well as a subtle structural modification on the ligand (e.g. DMH1 vs. LDN193189 will cause distinct binding profiles and selectivity among BMP inhibitors. Therefore, the current computational approach represents a new way of investigating BMP inhibitors. Our results provide critical information for designing exclusively selective BMP inhibitors for the development of effective pharmacotherapy for diseases caused by aberrant BMP signaling.

  11. Genetic diversity analysis of common beans based on molecular markers.

    Science.gov (United States)

    Gill-Langarica, Homar R; Muruaga-Martínez, José S; Vargas-Vázquez, M L Patricia; Rosales-Serna, Rigoberto; Mayek-Pérez, Netzahualcoyotl

    2011-10-01

    A core collection of the common bean (Phaseolus vulgaris L.), representing genetic diversity in the entire Mexican holding, is kept at the INIFAP (Instituto Nacional de Investigaciones Forestales, Agricolas y Pecuarias, Mexico) Germplasm Bank. After evaluation, the genetic structure of this collection (200 accessions) was compared with that of landraces from the states of Oaxaca, Chiapas and Veracruz (10 genotypes from each), as well as a further 10 cultivars, by means of four amplified fragment length polymorphisms (AFLP) +3/+3 primer combinations and seven simple sequence repeats (SSR) loci, in order to define genetic diversity, variability and mutual relationships. Data underwent cluster (UPGMA) and molecular variance (AMOVA) analyses. AFLP analysis produced 530 bands (88.5% polymorphic) while SSR primers amplified 174 alleles, all polymorphic (8.2 alleles per locus). AFLP indicated that the highest genetic diversity was to be found in ten commercial-seed classes from two major groups of accessions from Central Mexico and Chiapas, which seems to be an important center of diversity in the south. A third group included genotypes from Nueva Granada, Mesoamerica, Jalisco and Durango races. Here, SSR analysis indicated a reduced number of shared haplotypes among accessions, whereas the highest genetic components of AMOVA variation were found within accessions. Genetic diversity observed in the common-bean core collection represents an important sample of the total Phaseolus genetic variability at the main Germplasm Bank of INIFAP. Molecular marker strategies could contribute to a better understanding of the genetic structure of the core collection as well as to its improvement and validation.

  12. The Hairless Stem Phenotype of Cotton (Gossypium barbadense) Is Linked to a Copia-Like Retrotransposon Insertion in a Homeodomain-Leucine Zipper Gene (HD1).

    Science.gov (United States)

    Ding, Mingquan; Ye, Wuwei; Lin, Lifeng; He, Shae; Du, Xiongming; Chen, Aiqun; Cao, Yuefen; Qin, Yuan; Yang, Fen; Jiang, Yurong; Zhang, Hua; Wang, Xiyin; Paterson, Andrew H; Rong, Junkang

    2015-09-01

    Cotton (Gossypium) stem trichomes are mostly single cells that arise from stem epidermal cells. In this study, a homeodomain-leucine zipper gene (HD1) was found to cosegregate with the dominant trichome locus previously designated as T1 and mapped to chromosome 6. Characterization of HD1 orthologs revealed that the absence of stem trichomes in modern Gossypium barbadense varieties is linked to a large retrotransposon insertion in the ninth exon, 2565 bp downstream from the initial codon in the At subgenome HD1 gene (At-GbHD1). In both the At and Dt subgenomes, reduced transcription of GbHD1 genes is caused by this insertion. The disruption of At-HD1 further affects the expression of downstream GbMYB25 and GbHOX3 genes. Analyses of primitive cultivated accessions identified another retrotransposon insertion event in the sixth exon of At-GbHD1 that might predate the previously identified retrotransposon in modern varieties. Although both retrotransposon insertions results in similar phenotypic changes, the timing of these two retrotransposon insertion events fits well with our current understanding of the history of cotton speciation and dispersal. Taken together, the results of genetics mapping, gene expression and association analyses suggest that GbHD1 is an important component that controls stem trichome development and is a promising candidate gene for the T1 locus. The interspecific phenotypic difference in stem trichome traits also may be attributable to HD1 inactivation associated with retrotransposon insertion. Copyright © 2015 by the Genetics Society of America.

  13. Isolation and characterization of reverse transcriptase fragments of LTR retrotransposons from the genome of Chenopodium quinoa (Amaranthaceae).

    Science.gov (United States)

    Kolano, Bozena; Bednara, Edyta; Weiss-Schneeweiss, Hanna

    2013-10-01

    High heterogeneity was observed among conserved domains of reverse transcriptase ( rt ) isolated from quinoa. Only one Ty1- copia rt was highly amplified. Reverse transcriptase sequences were located predominantly in pericentromeric region of quinoa chromosomes. The heterogeneity, genomic abundance, and chromosomal distribution of reverse transcriptase (rt)-coding fragments of Ty1-copia and Ty3-gypsy long terminal repeat retrotransposons were analyzed in the Chenopodium quinoa genome. Conserved domains of the rt gene were amplified and characterized using degenerate oligonucleotide primer pairs. Sequence analyses indicated that half of Ty1-copia rt (51 %) and 39 % of Ty3-gypsy rt fragments contained intact reading frames. High heterogeneity among rt sequences was observed for both Ty1-copia and Ty3-gypsy rt amplicons, with Ty1-copia more heterogeneous than Ty3-gypsy. Most of the isolated rt fragments were present in quinoa genome in low copy numbers, with only one highly amplified Ty1-copia rt sequence family. The gypsy-like RNase H fragments co-amplified with Ty1-copia-degenerate primers were shown to be highly amplified in the quinoa genome indicating either higher abundance of some gypsy families of which rt domains could not be amplified, or independent evolution of this gypsy-region in quinoa. Both Ty1-copia and Ty3-gypsy retrotransposons were preferentially located in pericentromeric heterochromatin of quinoa chromosomes. Phylogenetic analyses of newly amplified rt fragments together with well-characterized retrotransposon families from other organisms allowed identification of major lineages of retroelements in the genome of quinoa and provided preliminary insight into their evolutionary dynamics.

  14. LTR-Retrotransposons in R. exoculata and Other Crustaceans: The Outstanding Success of GalEa-Like Copia Elements

    Science.gov (United States)

    Esnault, Caroline; Graça, Paula; Higuet, Dominique; Bonnivard, Eric

    2013-01-01

    Transposable elements are major constituents of eukaryote genomes and have a great impact on genome structure and stability. They can contribute to the genetic diversity and evolution of organisms. Knowledge of their distribution among several genomes is an essential condition to study their dynamics and to better understand their role in species evolution. LTR-retrotransposons have been reported in many diverse eukaryote species, describing a ubiquitous distribution. Given their abundance, diversity and their extended ranges in C-values, environment and life styles, crustaceans are a great taxon to investigate the genomic component of adaptation and its possible relationships with TEs. However, crustaceans have been greatly underrepresented in transposable element studies. Using both degenerate PCR and in silico approaches, we have identified 35 Copia and 46 Gypsy families in 15 and 18 crustacean species, respectively. In particular, we characterized several full-length elements from the shrimp Rimicaris exoculata that is listed as a model organism from hydrothermal vents. Phylogenic analyses show that Copia and Gypsy retrotransposons likely present two opposite dynamics within crustaceans. The Gypsy elements appear relatively frequent and diverse whereas Copia are much more homogeneous, as 29 of them belong to the single GalEa clade, and species- or lineage-dependent. Our results also support the hypothesis of the Copia retrotransposon scarcity in metazoans compared to Gypsy elements. In such a context, the GalEa-like elements present an outstanding wide distribution among eukaryotes, from fishes to red algae, and can be even highly predominant within a large taxon, such as Malacostraca. Their distribution among crustaceans suggests a dynamics that follows a “domino days spreading” branching process in which successive amplifications may interact positively. PMID:23469217

  15. LTR-retrotransposons in R. exoculata and other crustaceans: the outstanding success of GalEa-like copia elements.

    Directory of Open Access Journals (Sweden)

    Mathieu Piednoël

    Full Text Available Transposable elements are major constituents of eukaryote genomes and have a great impact on genome structure and stability. They can contribute to the genetic diversity and evolution of organisms. Knowledge of their distribution among several genomes is an essential condition to study their dynamics and to better understand their role in species evolution. LTR-retrotransposons have been reported in many diverse eukaryote species, describing a ubiquitous distribution. Given their abundance, diversity and their extended ranges in C-values, environment and life styles, crustaceans are a great taxon to investigate the genomic component of adaptation and its possible relationships with TEs. However, crustaceans have been greatly underrepresented in transposable element studies. Using both degenerate PCR and in silico approaches, we have identified 35 Copia and 46 Gypsy families in 15 and 18 crustacean species, respectively. In particular, we characterized several full-length elements from the shrimp Rimicaris exoculata that is listed as a model organism from hydrothermal vents. Phylogenic analyses show that Copia and Gypsy retrotransposons likely present two opposite dynamics within crustaceans. The Gypsy elements appear relatively frequent and diverse whereas Copia are much more homogeneous, as 29 of them belong to the single GalEa clade, and species- or lineage-dependent. Our results also support the hypothesis of the Copia retrotransposon scarcity in metazoans compared to Gypsy elements. In such a context, the GalEa-like elements present an outstanding wide distribution among eukaryotes, from fishes to red algae, and can be even highly predominant within a large taxon, such as Malacostraca. Their distribution among crustaceans suggests a dynamics that follows a "domino days spreading" branching process in which successive amplifications may interact positively.

  16. Molecular-based recursive partitioning analysis model for glioblastoma in the temozolomide era a correlative analysis based on nrg oncology RTOG 0525

    NARCIS (Netherlands)

    Bell, Erica Hlavin; Pugh, Stephanie L.; McElroy, Joseph P.; Gilbert, Mark R.; Mehta, Minesh; Klimowicz, Alexander C.; Magliocco, Anthony; Bredel, Markus; Robe, Pierre|info:eu-repo/dai/nl/413970957; Grosu, Anca L.; Stupp, Roger; Curran, Walter; Becker, Aline P.; Salavaggione, Andrea L.; Barnholtz-Sloan, Jill S.; Aldape, Kenneth; Blumenthal, Deborah T.; Brown, Paul D.; Glass, Jon; Souhami, Luis; Lee, R. Jeffrey; Brachman, David; Flickinger, John; Won, Minhee; Chakravarti, Arnab

    2017-01-01

    IMPORTANCE: There is a need for a more refined, molecularly based classification model for glioblastoma (GBM) in the temozolomide era. OBJECTIVE: To refine the existing clinically based recursive partitioning analysis (RPA) model by incorporating molecular variables. DESIGN, SETTING, AND

  17. Diagnostic use of computational retrotransposon detection: Successful definition of pathogenetic mechanism in a ciliopathy phenotype.

    Science.gov (United States)

    Takenouchi, Toshiki; Kuchikata, Tomu; Yoshihashi, Hiroshi; Fujiwara, Mineko; Uehara, Tomoko; Miyama, Sahoko; Yamada, Shiro; Kosaki, Kenjiro

    2017-05-01

    Among more than 5,000 human monogenic disorders with known causative genes, transposable element insertion of a Long Interspersed Nuclear Element 1 (LINE1, L1) is known as the mechanistic basis in only 13 genetic conditions. Meckel-Gruber syndrome is a rare ciliopathy characterized by occipital encephalocele and cystic kidney disease. Here, we document a boy with occipital encephalocele, post-axial polydactyly, and multicystic renal disease. A medical exome analysis detected a heterozygous frameshift mutation, c.4582_4583delCG p.(Arg1528Serfs*17) in CC2D2A in the maternally derived allele. The further use of a dedicated bioinformatics algorithm for detecting retrotransposon insertions led to the detection of an L1 insertion affecting exon 7 in the paternally derived allele. The complete sequencing and sequence homology analysis of the inserted L1 element showed that the L1 element was classified as L1HS (L1 human specific) and that the element had intact open reading frames in the two L1-encoded proteins. This observation ranks Meckel-Gruber syndrome as only the 14th disorder to be caused by an L1 insertion among more than 5,000 known human genetic disorders. Although a transposable element detection algorithm is not included in the current best-practice next-generation sequencing analysis, the present observation illustrates the utility of such an algorithm, which would require modest computational time and resources. Whether the seemingly infrequent recognition of L1 insertion in the pathogenesis of human genetic diseases might simply reflect a lack of appropriate detection methods remains to be seen. © 2017 Wiley Periodicals, Inc.

  18. Evolutionary dynamics of the Ty3/gypsy LTR retrotransposons in the genome of Anopheles gambiae.

    Directory of Open Access Journals (Sweden)

    Jose Manuel C Tubio

    Full Text Available Ty3/gypsy elements represent one of the most abundant and diverse LTR-retrotransposon (LTRr groups in the Anopheles gambiae genome, but their evolutionary dynamics have not been explored in detail. Here, we conduct an in silico analysis of the distribution and abundance of the full complement of 1045 copies in the updated AgamP3 assembly. Chromosomal distribution of Ty3/gypsy elements is inversely related to arm length, with densities being greatest on the X, and greater on the short versus long arms of both autosomes. Taking into account the different heterochromatic and euchromatic compartments of the genome, our data suggest that the relative abundance of Ty3/gypsy LTRrs along each chromosome arm is determined mainly by the different proportions of heterochromatin, particularly pericentric heterochromatin, relative to total arm length. Additionally, the breakpoint regions of chromosomal inversion 2La appears to be a haven for LTRrs. These elements are underrepresented more than 7-fold in euchromatin, where 33% of the Ty3/gypsy copies are associated with genes. The euchromatin on chromosome 3R shows a faster turnover rate of Ty3/gypsy elements, characterized by a deficit of proviral sequences and the lowest average sequence divergence of any autosomal region analyzed in this study. This probably reflects a principal role of purifying selection against insertion for the preservation of longer conserved syntenyc blocks with adaptive importance located in 3R. Although some Ty3/gypsy LTRrs show evidence of recent activity, an important fraction are inactive remnants of relatively ancient insertions apparently subject to genetic drift. Consistent with these computational predictions, an analysis of the occupancy rate of putatively older insertions in natural populations suggested that the degenerate copies have been fixed across the species range in this mosquito, and also are shared with the sibling species Anopheles arabiensis.

  19. 5′-Transducing SVA retrotransposon groups spread efficiently throughout the human genome

    Science.gov (United States)

    Damert, Annette; Raiz, Julija; Horn, Axel V.; Löwer, Johannes; Wang, Hui; Xing, Jinchuan; Batzer, Mark A.; Löwer, Roswitha; Schumann, Gerald G.

    2009-01-01

    SVA elements represent the youngest family of hominid non-LTR retrotransposons, which alter the human genome continuously. They stand out due to their organization as composite repetitive elements. To draw conclusions on the assembly process that led to the current organization of SVA elements and on their transcriptional regulation, we initiated our study by assessing differences in structures of the 116 SVA elements located on human chromosome 19. We classified SVA elements into seven structural variants, including novel variants like 3′-truncated elements and elements with 5′-flanking sequence transductions. We established a genome-wide inventory of 5′-transduced SVA elements encompassing ∼8% of all human SVA elements. The diversity of 5′ transduction events found indicates transcriptional control of their SVA source elements by a multitude of external cellular promoters in germ cells in the course of their evolution and suggests that SVA elements might be capable of acquiring 5′ promoter sequences. Our data indicate that SVA-mediated 5′ transduction events involve alternative RNA splicing at cryptic splice sites. We analyzed one remarkably successful human-specific SVA 5′ transduction group in detail because it includes at least 32% of all SVA subfamily F members. An ancient retrotransposition event brought an SVA insertion under transcriptional control of the MAST2 gene promoter, giving rise to the primal source element of this group. Members of this group are currently transcribed. Here we show that SVA-mediated 5′ transduction events lead to structural diversity of SVA elements and represent a novel source of genomic rearrangements contributing to genomic diversity. PMID:19652014

  20. 5'-Transducing SVA retrotransposon groups spread efficiently throughout the human genome.

    Science.gov (United States)

    Damert, Annette; Raiz, Julija; Horn, Axel V; Löwer, Johannes; Wang, Hui; Xing, Jinchuan; Batzer, Mark A; Löwer, Roswitha; Schumann, Gerald G

    2009-11-01

    SVA elements represent the youngest family of hominid non-LTR retrotransposons, which alter the human genome continuously. They stand out due to their organization as composite repetitive elements. To draw conclusions on the assembly process that led to the current organization of SVA elements and on their transcriptional regulation, we initiated our study by assessing differences in structures of the 116 SVA elements located on human chromosome 19. We classified SVA elements into seven structural variants, including novel variants like 3'-truncated elements and elements with 5'-flanking sequence transductions. We established a genome-wide inventory of 5'-transduced SVA elements encompassing approximately 8% of all human SVA elements. The diversity of 5' transduction events found indicates transcriptional control of their SVA source elements by a multitude of external cellular promoters in germ cells in the course of their evolution and suggests that SVA elements might be capable of acquiring 5' promoter sequences. Our data indicate that SVA-mediated 5' transduction events involve alternative RNA splicing at cryptic splice sites. We analyzed one remarkably successful human-specific SVA 5' transduction group in detail because it includes at least 32% of all SVA subfamily F members. An ancient retrotransposition event brought an SVA insertion under transcriptional control of the MAST2 gene promoter, giving rise to the primal source element of this group. Members of this group are currently transcribed. Here we show that SVA-mediated 5' transduction events lead to structural diversity of SVA elements and represent a novel source of genomic rearrangements contributing to genomic diversity.

  1. Characterisation of the potential function of SVA retrotransposons to modulate gene expression patterns.

    Science.gov (United States)

    Savage, Abigail L; Bubb, Vivien J; Breen, Gerome; Quinn, John P

    2013-05-21

    Retrotransposons are a major component of the human genome constituting as much as 45%. The hominid specific SINE-VNTR-Alus are the youngest of these elements constituting 0.13% of the genome; they are therefore a practical and amenable group for analysis of both their global integration, polymorphic variation and their potential contribution to modulation of genome regulation. Consistent with insertion into active chromatin we have determined that SVAs are more prevalent in genic regions compared to gene deserts. The consequence of which, is that their integration has greater potential to have affects on gene regulation. The sequences of SVAs show potential for the formation of secondary structure including G-quadruplex DNA. We have shown that the human specific SVA subtypes (E-F1) show the greatest potential for forming G-quadruplexes within the central tandem repeat component in addition to the 5' 'CCCTCT' hexamer. We undertook a detailed analysis of the PARK7 SVA D, located in the promoter of the PARK7 gene (also termed DJ-1), in a HapMap cohort where we identified 2 variable number tandem repeat domains and 1 tandem repeat within this SVA with the 5' CCCTCT element being one of the variable regions. Functionally we were able to demonstrate that this SVA contains multiple regulatory elements that support reporter gene expression in vitro and further show these elements exhibit orientation dependency. Our data supports the hypothesis that SVAs integrate preferentially in to open chromatin where they could modify the existing transcriptional regulatory domains or alter expression patterns by a variety of mechanisms.

  2. Stepwise evolution of two giant composite LTR-retrotransposon-like elements DA and Xiao

    Directory of Open Access Journals (Sweden)

    Li Xuanyang

    2009-06-01

    Full Text Available Abstract Background We recently discovered two composite long terminal repeat (LTR-retrotransposon-like elements which we named DA (~300 kb and Xiao (~30 kb, meaning big and small in Chinese respectively. Xiao and DA (three types of DA identified were found to have been derived from several donor sites and have spread to 30 loci in the human genome, totaling to 5 Mb. Our bioinformatics analyses with the released human, chimp, rhesus macaque, orangutan, and marmoset genomic sequences indicate that DA and Xiao emerged ~25 million years (Myr ago. Results To better understand the evolution of these two complex elements, we investigated various internal junctions of DA and Xiao as well as orthologous genomic sites of the 30 DA/Xiao loci in non-human primates including great apes, lesser apes, Old World monkeys, New World monkeys, and a prosimian. We found that Xiao and type I DA first emerged in the genome between 25 and 18 Myr ago, whereas type II and Type III DAs emerged between 14 and 7 Myr ago. Xiao and DA were most active in great apes, with their amplification peaking during 25-14 and 14-7 Myr ago, respectively. Neither DA nor Xiao seem to have been active in the human and chimp genomes during last 6 Myr. Conclusion The study has led to a more accurate age determination of the DA and Xiao elements than our previous bioinformatics analyses, and indicates that the amplification activity of the elements coincided with that of group I HERV-Es during evolution. It has also illustrated an evolutionary path with stepwise structural changes for the elements during past 25 Myr, and in doing so has shed more light on these two intriguing and complex elements that have reshaped our genome.

  3. Distinct influences of tandem repeats and retrotransposons on CENH3 nucleosome positioning

    Directory of Open Access Journals (Sweden)

    Gent Jonathan I

    2011-02-01

    Full Text Available Abstract Background Unique structural characteristics of centromere chromatin enable it to support assembly of the kinetochore and its associated tensions. The histone H3 variant CENH3 (centromeric histone H3 is viewed as the key element of centromere chromatin and its interaction with centromere DNA is epigenetic in that its localization to centromeres is not sequence-dependent. Results In order to investigate what influence the DNA sequence exerts on CENH3 chromatin structure, we examined CENH3 nucleosome footprints on maize centromere DNA. We found a predominant average nucleosome spacing pattern of roughly 190-bp intervals, which was also the dominant arrangement for nucleosomes genome-wide. For CENH3-containing nucleosomes, distinct modes of nucleosome positioning were evident within that general spacing constraint. Over arrays of the major ~156-bp centromeric satellite sequence (tandem repeat CentC, nucleosomes were not positioned in register with CentC monomers but in conformity with a striking ~10-bp periodicity of AA/TT dimers within the sequence. In contrast, nucleosomes on a class of centromeric retrotransposon (CRM2 lacked a detectable AA/TT periodicity but exhibited tightly phased positioning. Conclusions These data support a model in which general chromatin factors independent of both DNA sequence and CENH3 enforce roughly uniform centromeric nucleosome spacing while allowing flexibility in the mode in which nucleosomes are positioned. In the case of tandem repeat DNA, the natural bending effects related to AA/TT periodicity produce an energetically-favourable arrangement consistent with conformationally rigid nucleosomes and stable chromatin at centromeres.

  4. Retrotransposons Are the Major Contributors to the Expansion of the Drosophila ananassae Muller F Element

    Directory of Open Access Journals (Sweden)

    Wilson Leung

    2017-08-01

    Full Text Available The discordance between genome size and the complexity of eukaryotes can partly be attributed to differences in repeat density. The Muller F element (∼5.2 Mb is the smallest chromosome in Drosophila melanogaster, but it is substantially larger (>18.7 Mb in D. ananassae. To identify the major contributors to the expansion of the F element and to assess their impact, we improved the genome sequence and annotated the genes in a 1.4-Mb region of the D. ananassae F element, and a 1.7-Mb region from the D element for comparison. We find that transposons (particularly LTR and LINE retrotransposons are major contributors to this expansion (78.6%, while Wolbachia sequences integrated into the D. ananassae genome are minor contributors (0.02%. Both D. melanogaster and D. ananassae F-element genes exhibit distinct characteristics compared to D-element genes (e.g., larger coding spans, larger introns, more coding exons, and lower codon bias, but these differences are exaggerated in D. ananassae. Compared to D. melanogaster, the codon bias observed in D. ananassae F-element genes can primarily be attributed to mutational biases instead of selection. The 5′ ends of F-element genes in both species are enriched in dimethylation of lysine 4 on histone 3 (H3K4me2, while the coding spans are enriched in H3K9me2. Despite differences in repeat density and gene characteristics, D. ananassae F-element genes show a similar range of expression levels compared to genes in euchromatic domains. This study improves our understanding of how transposons can affect genome size and how genes can function within highly repetitive domains.

  5. Ablation of RNA interference and retrotransposons accompany acquisition and evolution of transposases to heterochromatin protein CENPB.

    Science.gov (United States)

    Upadhyay, Udita; Srivastava, Suchita; Khatri, Indu; Nanda, Jagpreet Singh; Subramanian, Srikrishna; Arora, Amit; Singh, Jagmohan

    2017-04-15

    Inactivation of retrotransposons is accompanied by the emergence of centromere-binding protein-B (CENPB) in Schizosaccharomyces, as well as in metazoans. The RNA interference (RNAi)-induced transcriptional silencing (RITS) complex, comprising chromodomain protein-1 (Chp1), Tas3 (protein with unknown function), and Argonaute (Ago1), plays an important role in RNAi-mediated heterochromatinization. We find that whereas the Ago1 subunit of the RITS complex is highly conserved, Tas3 is lost and Chp1 is truncated in Schizosaccharomyces cryophilus and Schizosaccharomyces octosporus We show that truncated Chp1 loses the property of heterochromatin localization and silencing when transformed in Schizosaccharomyces pombe Furthermore, multiple copies of CENPB, related to Tc1/mariner and Tc5 transposons, occur in all Schizosaccharomyces species, as well as in humans, but with loss of transposase function (except Schizosaccharomyces japonicus). We propose that acquisition of Tc1/mariner and Tc5 elements by horizontal transfer in S. pombe (and humans) is accompanied by alteration of their function from a transposase/endonuclease to a heterochromatin protein, designed to suppress transposon expression and recombination. The resulting redundancy of RITS may have eased the selection pressure, resulting in progressive loss or truncation of tas3 and chp1 genes in S. octosporus and S. cryophilus and triggered similar evolutionary dynamics in the metazoan orthologues. © 2017 Upadhyay et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  6. Compact microscope-based optical tweezers system for molecular manipulation

    Science.gov (United States)

    Sischka, Andy; Eckel, Rainer; Toensing, Katja; Ros, Robert; Anselmetti, Dario

    2003-11-01

    A compact single beam optical tweezers system for force measurements and manipulation of individual double-stranded deoxyribonucleic acid (DNA) molecules was integrated into a commercial inverted optical microscope. A maximal force of 150 pN combined with a force sensitivity of less than 0.5 pN allows measurements of elastic properties of single molecules which complements and overlaps the force regime accessible with atomic force microscopy (AFM). The manipulation and measurement performance of this system was tested with individual λ-DNA molecules and renders new aspects of dynamic forces phenomena with higher precision in contrast to AFM studies. An integrated liquid handling system with a fluid cell allows investigation of the force response of individual DNA molecules in the presence of DNA binding agents. Comparison of YOYO-1-, ethidium bromide intercalated DNA, and distamycin-A complexed DNA revealed accurate and reproducible differences in the force response to an external load. This opens the possibility to use it as a single molecule biosensor to investigate DNA binding agents and even to identify molecular binding mechanisms.

  7. Electrochemical sensors based on magnetic molecularly imprinted polymers: A review.

    Science.gov (United States)

    Yáñez-Sedeño, Paloma; Campuzano, Susana; Pingarrón, José M

    2017-04-01

    Participation of magnetic component in molecularly imprinted polymers (MIPs) has facilitated enormously the incorporation of these polymeric materials on electrode surfaces allowing the design of electrochemical sensors with very attractive analytical characteristics in terms of simplicity, reproducibility, low fabrication cost, high sensitivity and selectivity and rapid assay time. The magnetically susceptible resultant MIPs (MMIPs) allowed a simple and fast elution of the template molecules from MMIPs, are easily and faster collected without filtration, centrifugation or other complex operations and are also faster assembled and removed from the electrode surface by simply using an external magnetic field. A wide range of different (nano)materials such as gold nanoparticles (AuNPs), graphene oxide, single-walled and multi-walled carbon nanotubes (SWCNTs and MWCNTs) as well as different electrode modifiers (ionic liquids (ILs) and surfactants/dispersants) have been incorporated into the MMIPs to improve the analytical performance of the resulting electrochemical sensors which have demonstrated great promise for determination of relevant analytes in environmental, food and clinical analyses. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. [Williams syndrome: its clinical aspects and molecular bases].

    Science.gov (United States)

    Antonell, A; Del Campo, M; Flores, R; Campuzano, V; Perez-Jurado, L A

    2006-01-07

    Williams syndrome is a developmental disorder with an estimated prevalence of 1 in 7,500 newborns. Its phenotype is characterized by distinctive facial features, mild to moderate mental retardation and general cognitive deficits with a non-uniform profile, having problems in some areas (psychomotricity, visuospatial integration) and relative preservation of others (language, musicality), friendly personality, occasional hypercalcemia of infancy, and a vasculopathy with supravalvular aortic stenosis. Williams syndrome is caused by a submicroscopic deletion of 1.55 Mb in the chromosome band 7q11.23, which includes 26-28 genes. The mutational mechanism consists in a misalignment between regions of almost identical sequence and the subsequent unequal recombination. The reciprocal product of this rearrangement is the duplication of this region, causing a language specific disorder. Clinical-molecular correlations establishment through a good phenotypic characterization and the precise analysis of breakpoints in patients with atypical and typical deletions, altogether with the design of animal models and functional studies in vitro for the genes of the interval will be important to be able to determine the exact contribution of the genes to the phenotype, to know their pathogenesis and physiopathology, and to identify therapeutic methods.

  9. Descifrando las bases moleculares de la resistencia cuantitativa

    Directory of Open Access Journals (Sweden)

    Lopez Camilo

    2011-08-01

    Full Text Available Uno de los factores mas importantes que afectan los cultivos son las enfermedades ocasionadas por los patógenos. La resistencia vegetal ha sido clásicamente dividida en dos tipos: i competa, vertical o cualitativa que es gobernada por un solo gen y ii incompleta, horizontal o cuantitativa la cual es gobernada por varios genes. Aunque la resistencia cuantitativa provee resistencia de amplio espectro y es durable, los mecanismo moleculares subyacentes no han sido estudiados en detalle. En esta revisión se propone un modelo basado en la co-localización de genes similares a los clásicos genes de resistencia cualitativa con QTLs (Quantitative Trait Loci para explicar el mecanismo involucrado en el reconocimiento del patógeno durante la resistencia cuantitativa. Además se presenta información acerca del progreso obtenido en los últimos tres años para entender este tipo de resistencia, que culminó con la clonación de varios genes asociados a la resistencia cuantitativa. En conjunto, estos datos proveen nuevas luces sobre la naturaleza genética de este tipo de resistencia y de cómo puede ser empleada en programas de mejoramiento genético.

  10. Peptide-Based Molecular Hydrogels as Supramolecular Protein Mimics.

    Science.gov (United States)

    Singh, Nishant; Kumar, Mohit; Miravet, Juan F; Ulijn, Rein V; Escuder, Beatriu

    2017-01-23

    This Minireview concerns recent advances in the design, synthesis, and application of low molecular-weight peptidic hydrogelators. The sequence-specific combinations of amino acid side chain functionalities combined with hydrogen bonding of amide backbones and hydrophobic (aromatic) capping groups give these peptidic molecules the intrinsic tendency to self-assemble. The most prevalent designs include N-capped amino acid residues, bolamphiphilic peptides, and amphipathic peptides. Factors such as hydrophobic effects, the Hofmeister effect, and tunable ionization influence their aggregation properties. The self-assembly of simple bio-inspired building blocks into higher organized structures allows comparisons to be drawn with proteins and their complex functionalities, providing preliminary insights into complex biological functions and also enabling their application in a wide range of fields including catalysis, biomedical applications, and mimicry of natural dissipative systems. The Minireview is concluded by a short summary and outlook, highlighting the advances and steps required to bridge the gaps in the understanding of such systems. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Density functional theory based study of molecular interactions, recognition, engineering, and quantum transport in π molecular systems.

    Science.gov (United States)

    Cho, Yeonchoo; Cho, Woo Jong; Youn, Il Seung; Lee, Geunsik; Singh, N Jiten; Kim, Kwang S

    2014-11-18

    CONSPECTUS: In chemical and biological systems, various interactions that govern the chemical and physical properties of molecules, assembling phenomena, and electronic transport properties compete and control the microscopic structure of materials. The well-controlled manipulation of each component can allow researchers to design receptors or sensors, new molecular architectures, structures with novel morphology, and functional molecules or devices. In this Account, we describe the structures and electronic and spintronic properties of π-molecular systems that are important for controlling the architecture of a variety of carbon-based systems. Although DFT is an important tool for describing molecular interactions, the inability of DFT to accurately represent dispersion interactions has made it difficult to properly describe π-interactions. However, the recently developed dispersion corrections for DFT have allowed us to include these dispersion interactions cost-effectively. We have investigated noncovalent interactions of various π-systems including aromatic-π, aliphatic-π, and non-π systems based on dispersion-corrected DFT (DFT-D). In addition, we have addressed the validity of DFT-D compared with the complete basis set (CBS) limit values of coupled cluster theory with single, double, and perturbative triple excitations [CCSD(T)] and Møller-Plesset second order perturbation theory (MP2). The DFT-D methods are still unable to predict the correct ordering in binding energies within the benzene dimer and the cyclohexane dimer. Nevertheless, the overall DFT-D predicted binding energies are in reasonable agreement with the CCSD(T) results. In most cases, results using the B97-D3 method closely reproduce the CCSD(T) results with the optimized energy-fitting parameters. On the other hand, vdW-DF2 and PBE0-TS methods estimate the dispersion energies from the calculated electron density. In these approximations, the interaction energies around the equilibrium

  12. Oriented growth of porphyrin-based molecular wires on ionic crystals analysed by nc-AFM

    Science.gov (United States)

    Zimmerli, Lars; Kawai, Shigeki; Meyer, Ernst; Fendt, Leslie-Anne; Diederich, Francois

    2011-01-01

    Summary The growth of molecular assemblies at room temperature on insulating surfaces is one of the main goals in the field of molecular electronics. Recently, the directed growth of porphyrin-based molecular wires on KBr(001) was presented. The molecule–surface interaction associated with a strong dipole moment of the molecules was sufficient to bind them to the surface; while a stabilization of the molecular assemblies was reached due to the intermolecular interaction by π–π binding. Here, we show that the atomic structure of the substrate can control the direction of the wires and consequently, complex molecular assemblies can be formed. The electronic decoupling of the molecules by one or two monolayers of KBr from the Cu(111) substrate is found to be insufficient to enable comparable growth conditions to bulk ionic materials. PMID:21977413

  13. Gene expression-based diagnostics for molecular cancer classification of difficult to diagnose tumors.

    Science.gov (United States)

    Schnabel, Catherine A; Erlander, Mark G

    2012-09-01

    Standardized methods for accurate tumor classification are of critical importance for cancer diagnosis and treatment, particularly in diagnostically-challenging cases where site-directed therapies are an option. Molecular diagnostics for tumor classification, subclassification and site of origin determination based on advances in gene expression profiling have translated into clinical practice as complementary approaches to clinicopathological evaluations. In this review, the foundational science of gene expression-based cancer classification, technical and clinical considerations for clinical translation, and an overview of molecular signatures of tumor classification that are available for clinical use will be discussed. Proposed approaches will also be described for further integration of molecular tests for cancer classification into the diagnostic paradigm using a tissue-based strategy as a key component to direct evaluation. Increasing evidence of improved patient outcomes with the application of site and molecularly-targeted cancer therapy through use of molecular tools highlights the growing potential for these gene expression-based diagnostics to positively impact patient management. Looking forward, the availability of adequate tissue will be a significant issue and limiting factor as cancer diagnosis progresses; when the tumor specimen is limited, use of molecular classification may be a reasonable early step in the evaluation, particularly if the tumor is poorly-differentiated and has atypical features.

  14. The Influence of Single Nucleotide Polymorphism Microarray-Based Molecular Karyotype on Preimplantation Embryonic Development Potential.

    Science.gov (United States)

    Li, Gang; He, Nannan; Jin, Haixia; Liu, Yan; Guo, Yihong; Su, Yingchun; Sun, Yingpu

    2015-01-01

    In order to investigate the influence of the molecular karyotype based on single nucleotide polymorphism (SNP) microarray on embryonic development potential in preimplantation genetic diagnosis (PGD), we retrospectively analyzed the clinical data generated by PGD using embryos retrieved from parents with chromosome rearrangements in our center. In total, 929 embryos from 119 couples had exact diagnosis and development status. The blastocyst formation rate of balanced molecular karyotype embryos was 56.6% (276/488), which was significantly higher than that of genetic imbalanced embryos 24.5% (108/441) (P35 respectively. Blastocyst formation rates of male and female embryos were 44.5% (183/411) and 38.8% (201/518) respectively, with no significant difference between them (P>0.05). The rates of balanced molecular karyotype embryos vary from groups of embryos with different cell numbers at 68 hours after insemination. The blastocyst formation rate of embryos with 6-8 cells (48.1%) was significantly higher than that of embryos with 8 cells (42.9%) (Pabnormal molecular karyotypes in the subgroup of the arrest, morula and blastocyst. Thus, we conclude that embryos with balanced molecular karyotype have significant higher development potential than those with imbalanced molecular karyotype whilst maternal age, embryo gender and types of abnormal molecular karyotype have no significant influence on blastocyst formation. Compared with embryos with 8 cells, embryos with 6-8 blastomeres have higher rate of balanced molecular karyotype and blastocyst formation.

  15. Switchable Negative Differential Resistance Induced by Quantum Interference Effects in Porphyrin-based Molecular Junctions.

    Science.gov (United States)

    Nozaki, Daijiro; Lokamani; Santana-Bonilla, Alejandro; Dianat, Arezoo; Gutierrez, Rafael; Cuniberti, Gianaurelio

    2015-10-01

    Charge transport signatures of a carbon-based molecular switch consisting of different tautomers of metal-free porphyrin embedded between graphene nanoribbons is studied by combining electronic structure and nonequilibrium transport. Different low-energy and low-bias features are revealed, including negative differential resistance (NDR) and antiresonances, both mediated by subtle quantum interference effects. Moreover, the molecular junctions can display moderate rectifying or nonlinear behavior depending on the position of the hydrogen atoms within the porphyrin core. We rationalize the mechanism leading to NDR and antiresonances by providing a detailed analysis of transmission pathways and frontier molecular orbital distribution.

  16. Discrete Biogeography Based Optimization for Feature Selection in Molecular Signatures.

    Science.gov (United States)

    Liu, Bo; Tian, Meihong; Zhang, Chunhua; Li, Xiangtao

    2015-04-01

    Biomarker discovery from high-dimensional data is a complex task in the development of efficient cancer diagnoses and classification. However, these data are usually redundant and noisy, and only a subset of them present distinct profiles for different classes of samples. Thus, selecting high discriminative genes from gene expression data has become increasingly interesting in the field of bioinformatics. In this paper, a discrete biogeography based optimization is proposed to select the good subset of informative gene relevant to the classification. In the proposed algorithm, firstly, the fisher-markov selector is used to choose fixed number of gene data. Secondly, to make biogeography based optimization suitable for the feature selection problem; discrete migration model and discrete mutation model are proposed to balance the exploration and exploitation ability. Then, discrete biogeography based optimization, as we called DBBO, is proposed by integrating discrete migration model and discrete mutation model. Finally, the DBBO method is used for feature selection, and three classifiers are used as the classifier with the 10 fold cross-validation method. In order to show the effective and efficiency of the algorithm, the proposed algorithm is tested on four breast cancer dataset benchmarks. Comparison with genetic algorithm, particle swarm optimization, differential evolution algorithm and hybrid biogeography based optimization, experimental results demonstrate that the proposed method is better or at least comparable with previous method from literature when considering the quality of the solutions obtained. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Three decades of structure- and property-based molecular design

    DEFF Research Database (Denmark)

    Müller, Klaus

    2014-01-01

    -oriented medicinal chemistry. The exploration of oxetane is given as an example. For the sake of brevity, this account cannot detail all further developments that have taken place in each individual area of structure- and property-based drug discovery and it can only hint at important developments in other...

  18. Assessing ligand efficiencies using template-based molecular ...

    Indian Academy of Sciences (India)

    Statistical modelling using artificial neural network (ANN: 2 = 0.922) and multiple linear regression method (MLR: 2 = 0.851) showed good correlation between the biological activity, binding affinity, and different ligand efficiencies of the compounds, which suggest the robustness of the template-based binding ...

  19. Rapid Prototyping of Chemical Microsensors Based on Molecularly Imprinted Polymers Synthesized by Two-Photon Stereolithography.

    Science.gov (United States)

    Gomez, Laura Piedad Chia; Spangenberg, Arnaud; Ton, Xuan-Anh; Fuchs, Yannick; Bokeloh, Frank; Malval, Jean-Pierre; Tse Sum Bui, Bernadette; Thuau, Damien; Ayela, Cédric; Haupt, Karsten; Soppera, Olivier

    2016-07-01

    Two-photon stereolithography is used for rapid prototyping of submicrometre molecularly imprinted polymer-based 3D structures. The structures are evaluated as chemical sensing elements and their specific recognition properties for target molecules are confirmed. The 3D design capability is exploited and highlighted through the fabrication of an all-organic molecularly imprinted polymeric microelectromechanical sensor. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Virus-like attachment sites and plastic CpG islands:landmarks of diversity in plant Del retrotransposons.

    Directory of Open Access Journals (Sweden)

    Guilherme M Q Cruz

    Full Text Available Full-length Del elements from ten angiosperm genomes, 5 monocot and 5 dicot, were retrieved and putative attachment (att sites were identified. In the 2432 Del elements, two types of U5 att sites and a single conserved type of U3 att site were identified. Retroviral att sites confer specificity to the integration process, different att sites types therefore implies lineage specificity. While some features are common to all Del elements, CpG island patterns within the LTRs were particular to lineage specific clusters. All eudicot copies grouped into one single clade while the monocots harbour a more diverse collection of elements. Furthermore, full-length Del elements and truncated copies were unevenly distributed amongst chromosomes. Elements of Del lineage are organized in plants into three clusters and each cluster is composed of elements with distinct LTR features. Our results suggest that the Del lineage efficiently amplified in the monocots and that one branch is probably a newly emerging sub-lineage. Finally, sequences in all groups are under purifying selection. These results show the LTR region is dynamic and important in the evolution of LTR-retrotransposons, we speculate that it is a trigger for retrotransposon diversification.

  1. The non-autonomous retrotransposon SVA is trans-mobilized by the human LINE-1 protein machinery.

    Science.gov (United States)

    Raiz, Julija; Damert, Annette; Chira, Sergiu; Held, Ulrike; Klawitter, Sabine; Hamdorf, Matthias; Löwer, Johannes; Strätling, Wolf H; Löwer, Roswitha; Schumann, Gerald G

    2012-02-01

    SINE-VNTR-Alu (SVA) elements are non-autonomous, hominid-specific non-LTR retrotransposons and distinguished by their organization as composite mobile elements. They represent the evolutionarily youngest, currently active family of human non-LTR retrotransposons, and sporadically generate disease-causing insertions. Since preexisting, genomic SVA sequences are characterized by structural hallmarks of Long Interspersed Elements 1 (LINE-1, L1)-mediated retrotransposition, it has been hypothesized for several years that SVA elements are mobilized by the L1 protein machinery in trans. To test this hypothesis, we developed an SVA retrotransposition reporter assay in cell culture using three different human-specific SVA reporter elements. We demonstrate that SVA elements are mobilized in HeLa cells only in the presence of both L1-encoded proteins, ORF1p and ORF2p. SVA trans-mobilization rates exceeded pseudogene formation frequencies by 12- to 300-fold in HeLa-HA cells, indicating that SVA elements represent a preferred substrate for L1 proteins. Acquisition of an AluSp element increased the trans-mobilization frequency of the SVA reporter element by ~25-fold. Deletion of (CCCTCT)(n) repeats and Alu-like region of a canonical SVA reporter element caused significant attenuation of the SVA trans-mobilization rate. SVA de novo insertions were predominantly full-length, occurred preferentially in G+C-rich regions, and displayed all features of L1-mediated retrotransposition which are also observed in preexisting genomic SVA insertions.

  2. Cognitive Function Related to the Sirh11/Zcchc16 Gene Acquired from an LTR Retrotransposon in Eutherians.

    Directory of Open Access Journals (Sweden)

    Masahito Irie

    2015-09-01

    Full Text Available Gene targeting of mouse Sushi-ichi-related retrotransposon homologue 11/Zinc finger CCHC domain-containing 16 (Sirh11/Zcchc16 causes abnormal behaviors related to cognition, including attention, impulsivity and working memory. Sirh11/Zcchc16 encodes a CCHC type of zinc-finger protein that exhibits high homology to an LTR retrotransposon Gag protein. Upon microdialysis analysis of the prefrontal cortex region, the recovery rate of noradrenaline (NA was reduced compared with dopamine (DA after perfusion of high potassium-containing artificial cerebrospinal fluid in knockout (KO mice. These data indicate that Sirh11/Zcchc16 is involved in cognitive function in the brain, possibly via the noradrenergic system, in the contemporary mouse developmental systems. Interestingly, it is highly conserved in three out of the four major groups of the eutherians, euarchontoglires, laurasiatheria and afrotheria, but is heavily mutated in xenarthran species such as the sloth and armadillo, suggesting that it has contributed to brain evolution in the three major eutherian lineages, including humans and mice. Sirh11/Zcchc16 is the first SIRH gene to be involved in brain function, instead of just the placenta, as seen in the case of Peg10, Peg11/Rtl1 and Sirh7/Ldoc1.

  3. Two-dimensional vibrational spectroscopy of rotaxane-based molecular machines.

    Science.gov (United States)

    Bodis, Pavol; Panman, Matthijs R; Bakker, Bert H; Mateo-Alonso, Aurelio; Prato, Maurizio; Buma, Wybren Jan; Brouwer, Albert M; Kay, Euan R; Leigh, David A; Woutersen, Sander

    2009-09-15

    It has recently become possible to synthesize mechanical devices the size of a single molecule. Although it is tempting to regard such molecular machines as nanoscale versions of their macroscopic analogs, many notions from macroscopic mechanics no longer apply at a molecular level. For instance, the concept of viscous friction is meaningless for a molecular machine because the size of the solvent molecules that cause the friction is comparable to that of the machine itself. Furthermore, in many cases, the interactions between a molecular machine and its surroundings are comparable to the force driving the machine. As a result, a certain amount of intrinsic randomness exists in the motion of molecular machines, and the details of their mechanics are largely unknown. For a detailed understanding of the mechanical behavior of molecular machines, experiments that probe their motion on an ultrafast time scale, such as two-dimensional (2D) vibrational spectroscopy, are essential. This method uses coupling between vibrational modes in a molecule to investigate the molecular conformation. The coupling shows up as off-diagonal peaks in a 2D graph of the vibrational response of the molecule, analogous to the spin coupling observed in multidimensional NMR spectroscopy. Both spin coupling and vibrational coupling are sensitive probes of the molecular conformation, but 2D vibrational spectroscopy shows orders of magnitude better time resolution than NMR. In this Account, we use 2D vibrational spectroscopy to study molecular machines based on rotaxanes. These devices consist of a linear thread and a macrocycle that is noncovalently locked onto the thread. In the rotaxanes we study, the macrocycle and the thread both contain CO and NH groups. By determining the coupling between the stretching modes of these goups from the cross peaks in the 2D spectrum, we directly and quantitatively probe the relative position and orientation of the macrocycle and the thread for both a small

  4. Lewis Acid-Base, Molecular Modeling, and Isotopic Labeling in a Sophomore Inorganic Chemistry Laboratory

    Science.gov (United States)

    Nataro, Chip; Ferguson, Michelle A.; Bocage, Katherine M.; Hess, Brian J.; Ross, Vincent J.; Swarr, Daniel T.

    2004-01-01

    An experiment to prepare a deuterium labeled adduct of a Lewis acid and Lewis base, to use computational methods allowing students to visualize the LUMO of Lewis acids, the HOMO of Lewis bases and the molecular orbitals of the adduct that is formed is developed. This allows students to see the interplay between calculated and experimental results.

  5. The formation of ZnO-based coatings from solutions containing high-molecular polyvinylpyrrolidone

    Science.gov (United States)

    Evstrop'ev, S. K.; Soshnikov, I. P.; Khrebtov, A. I.

    2016-05-01

    A method for deposition of transparent nanosize ZnO-based coatings on the glass surface from solutions containing high-molecular polyvinylpyrrolidone is described. The method can be used to form transparent homogeneous coatings based on ZnO with an increased energy gap width. It does not require any intricate technological equipment.

  6. Molecular monolayers for electrical passivation and functionalization of silicon-based solar energy devices

    NARCIS (Netherlands)

    Veerbeek, Janneke; Firet, Nienke J.; Vijselaar, Wouter; Elbersen, R.; Gardeniers, Han; Huskens, Jurriaan

    2017-01-01

    Silicon-based solar fuel devices require passivation for optimal performance yet at the same time need functionalization with (photo)catalysts for efficient solar fuel production. Here, we use molecular monolayers to enable electrical passivation and simultaneous functionalization of silicon-based

  7. Molecular spectroscopy and dynamics: a polyad-based perspective.

    Science.gov (United States)

    Herman, Michel; Perry, David S

    2013-07-07

    The efficiency and insight of global, polyad-based modeling in overtone spectroscopy and dynamics is demonstrated. Both vibration and vibration-rotation polyads are considered. The spectroscopic implications of polyad Hamiltonians derive from their ability to account for the detailed line positions and intensities of spectral features and their unique predictive power. The dynamical implications of polyad Hamiltonians include classical bifurcations that lead to the birth of new vibrational modes and intramolecular vibrational-rotational energy redistribution over multiple timescales. The literature is reviewed, with emphasis on acetylene results.

  8. Polarization conversion-based molecular sensing using anisotropic plasmonic metasurfaces.

    Science.gov (United States)

    Verre, R; Maccaferri, N; Fleischer, K; Svedendahl, M; Odebo Länk, N; Dmitriev, A; Vavassori, P; Shvets, I V; Käll, M

    2016-05-19

    Anisotropic media induce changes in the polarization state of transmitted and reflected light. Here we combine this effect with the refractive index sensitivity typical of plasmonic nanoparticles to experimentally demonstrate self-referenced single wavelength refractometric sensing based on polarization conversion. We fabricated anisotropic plasmonic metasurfaces composed of gold dimers and, as a proof of principle, measured the changes in the rotation of light polarization induced by biomolecular adsorption with a surface sensitivity of 0.2 ng cm(-2). We demonstrate the possibility of miniaturized sensing and we show that experimental results can be reproduced by analytical theory. Various ways to increase the sensitivity and applicability of the sensing scheme are discussed.

  9. Structure Controlled Long-Range Sequential Tunneling in Carbon-Based Molecular Junctions.

    Science.gov (United States)

    Morteza Najarian, Amin; McCreery, Richard L

    2017-04-25

    Carbon-based molecular junctions consisting of aromatic oligomers between conducting sp(2) hybridized carbon electrodes exhibit structure-dependent current densities (J) when the molecular layer thickness (d) exceeds ∼5 nm. All four of the molecular structures examined exhibit an unusual, nonlinear ln J vs bias voltage (V) dependence which is not expected for conventional coherent tunneling or activated hopping mechanisms. All molecules exhibit a weak temperature dependence, with J increasing typically by a factor of 2 over the range of 200-440 K. Fluorene and anthraquinone show linear plots of ln J vs d with nearly identical J values for the range d = 3-10 nm, despite significant differences in their free-molecule orbital energy levels. The observed current densities for anthraquinone, fluorene, nitroazobenzene, and bis-thienyl benzene for d = 7-10 nm show no correlation with occupied (HOMO) or unoccupied (LUMO) molecular orbital energies, contrary to expectations for transport mechanisms based on the offset between orbital energies and the electrode Fermi level. UV-vis absorption spectroscopy of molecular layers bonded to carbon electrodes revealed internal energy levels of the chemisorbed films and also indicated limited delocalization in the film interior. The observed current densities correlate well with the observed UV-vis absorption maxima for the molecular layers, implying a transport mechanism determined by the HOMO-LUMO energy gap. We conclude that transport in carbon-based aromatic molecular junctions is consistent with multistep tunneling through a barrier defined by the HOMO-LUMO gap, and not by charge transport at the electrode interfaces. In effect, interfacial "injection" at the molecule/electrode interfaces is not rate limiting due to relatively strong electronic coupling, and transport is controlled by the "bulk" properties of the molecular layer interior.

  10. Novel family of human transposable elements formed due to fusion of the first exon of gene MAST2 with retrotransposon SVA.

    Science.gov (United States)

    Bantysh, O B; Buzdin, A A

    2009-12-01

    We identified a novel human-specific family of transposable elements that consists of fused copies of the CpG-island containing the first exon of gene MAST2 and retrotransposon SVA. We propose a mechanism for the formation of this family termed CpG-SVA, comprising 5'-transduction by an SVA insert. After the divergence of human and chimpanzee ancestor lineages, retrotransposon SVA has inserted into the first intron of gene MAST2 in the sense orientation. Due to splicing of an aberrant RNA driven by MAST2 promoter, but terminally processed using SVA polyadenylation signal, the first exon of MAST2 has fused to a spliced 3'-terminal fragment of SVA retrotransposon. The above ancestor CpG-SVA element due to retrotranspositions of its own copies has formed a novel family represented in the human genome by 76 members. Recruitment of a MAST2 CpG island was most likely beneficial to the hybrid retrotransposons because it could significantly increase retrotransposition frequency. Also, we show that human L1 reverse transcriptase adds an extra cytosine residue to the 3' terminus of the nascent first strand of cDNA.

  11. A genome survey sequencing of the Java mouse deer (Tragulus javanicus) adds new aspects to the evolution of lineage specific retrotransposons in Ruminantia (Cetartiodactyla)

    DEFF Research Database (Denmark)

    Gallus, S; Kumar, V; Bertelsen, Mads Frost

    2015-01-01

    Ruminantia, the ruminating, hoofed mammals (cow, deer, giraffe and allies) are an unranked artiodactylan clade. Around 50-60 million years ago the BovB retrotransposon entered the ancestral ruminantian genome through horizontal gene transfer. A survey genome screen using 454-pyrosequencing...

  12. Singlet oxygen-based electrosensing by molecular photosensitizers

    Science.gov (United States)

    Trashin, Stanislav; Rahemi, Vanoushe; Ramji, Karpagavalli; Neven, Liselotte; Gorun, Sergiu M.; de Wael, Karolien

    2017-07-01

    Enzyme-based electrochemical biosensors are an inspiration for the development of (bio)analytical techniques. However, the instability and reproducibility of the reactivity of enzymes, combined with the need for chemical reagents for sensing remain challenges for the construction of useful devices. Here we present a sensing strategy inspired by the advantages of enzymes and photoelectrochemical sensing, namely the integration of aerobic photocatalysis and electrochemical analysis. The photosensitizer, a bioinspired perfluorinated Zn phthalocyanine, generates singlet-oxygen from air under visible light illumination and oxidizes analytes, yielding electrochemically-detectable products while resisting the oxidizing species it produces. Compared with enzymatic detection methods, the proposed strategy uses air instead of internally added reactive reagents, features intrinsic baseline correction via on/off light switching and shows C-F bonds-type enhanced stability. It also affords selectivity imparted by the catalytic process and nano-level detection, such as 20 nM amoxicillin in μl sample volumes.

  13. [Molecular identification in genus of Lilium based on DNA barcoding].

    Science.gov (United States)

    Zheng, Si-Hao; Li, Ya-Kang; Ren, Wei-Guang; Huang, Lin-Fang

    2014-12-01

    To establish a new method for identifying genus of Lilium by DNA barcoding technology, ITS, ITS2, psbA-trnH, matK and rbcL sequences were analyzed in term of variation of inter- and intra-species, barcoding gap, neighbor-joining tree to distinguish genus of Lilium based on 978 sequences from experimental and GenBank database, and identification efficiency was evaluated by Nearest distance and BLAST1 methods. The results showed that DNA barcoding could identify different species in genus of Lilium. ITS sequence performed higher identification efficiency, and had significant difference between intra- and inter-species. And NJ tree could also divide species into different clades. Results indicate that DNA barcoding can identify genus of Lilium accurately. ITS sequence can be the optimal barcode to identify species of Lilium.

  14. The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements

    Directory of Open Access Journals (Sweden)

    Morales Maria E

    2005-02-01

    Full Text Available Abstract Background Of the major families of long terminal repeat (LTR retrotransposons, the Pao/BEL family is probably the least well studied. It is becoming apparent that numerous LTR retrotransposons and other mobile genetic elements have colonized the genome of the human blood fluke, Schistosoma mansoni. Results A proviral form of Sinbad, a new LTR retrotransposon, was identified in the genome of S. mansoni. Phylogenetic analysis indicated that Sinbad belongs to one of five discreet subfamilies of Pao/BEL like elements. BLAST searches of whole genomes and EST databases indicated that members of this clade occurred in species of the Insecta, Nematoda, Echinodermata and Chordata, as well as Platyhelminthes, but were absent from all plants, fungi and lower eukaryotes examined. Among the deuterostomes examined, only aquatic species harbored these types of elements. All four species of nematode examined were positive for Sinbad sequences, although among insect and vertebrate genomes, some were positive and some negative. The full length, consensus Sinbad retrotransposon was 6,287 bp long and was flanked at its 5'- and 3'-ends by identical LTRs of 386 bp. Sinbad displayed a triple Cys-His RNA binding motif characteristic of Gag of Pao/BEL-like elements, followed by the enzymatic domains of protease, reverse transcriptase (RT, RNAseH, and integrase, in that order. A phylogenetic tree of deduced RT sequences from 26 elements revealed that Sinbad was most closely related to an unnamed element from the zebrafish Danio rerio and to Saci-1, also from S. mansoni. It was also closely related to Pao from Bombyx mori and to Ninja of Drosophila simulans. Sinbad was only distantly related to the other schistosome LTR retrotransposons Boudicca, Gulliver, Saci-2, Saci-3, and Fugitive, which are gypsy-like. Southern hybridization and bioinformatics analyses indicated that there were about 50 copies of Sinbad in the S. mansoni genome. The presence of ESTs

  15. Electrochemical control of quantum interference in anthraquinone-based molecular switches

    DEFF Research Database (Denmark)

    Markussen, Troels; Schiøtz, Jakob; Thygesen, Kristian Sommer

    2010-01-01

    Using first-principles calculations we analyze the electronic transport properties of a recently proposed anthraquinone-based electrochemical switch. Robust conductance on/off ratios of several orders of magnitude are observed due to destructive quantum interference present in the anthraquinone...... of hopping via the localized orbitals. The topology of the tight-binding model, which is dictated by the symmetries of the molecular orbitals, determines the amount of quantum interference....... but absent in the hydroquinone molecular bridge. A simple explanation of the interference effect is achieved by transforming the frontier molecular orbitals into localized molecular orbitals thereby obtaining a minimal tight-binding model describing the transport in the relevant energy range in terms...

  16. Open-Shell-Character-Based Molecular Design Principles: Applications to Nonlinear Optics and Singlet Fission.

    Science.gov (United States)

    Nakano, Masayoshi

    2017-01-01

    Open-shell character, e. g., diradical character, is a quantum chemically well-defined quantity in ground-state molecular systems, which is not an observable but can quantify the degree of effective bond weakness in the chemical sense or electron correlation strength in the physical sense. Because this quantity also correlates to specific excited states, physicochemical properties concerned with those states are expected to strongly correlate to the open-shell character. This feature enables us to open a new path to revealing the mechanism of these properties as well as to realizing new design principles for efficient functional molecular systems. This account explains the open-shell-character-based molecular design principles and introduces their applications to the rational design of highly efficient nonlinear optical and singlet fission molecular systems. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Detecting Molecular Properties by Various Laser-Based Techniques

    Energy Technology Data Exchange (ETDEWEB)

    Hsin, Tse-Ming [Iowa State Univ., Ames, IA (United States)

    2007-01-01

    Four different laser-based techniques were applied to study physical and chemical characteristics of biomolecules and dye molecules. These techniques are liole burning spectroscopy, single molecule spectroscopy, time-resolved coherent anti-Stokes Raman spectroscopy and laser-induced fluorescence microscopy. Results from hole burning and single molecule spectroscopy suggested that two antenna states (C708 & C714) of photosystem I from cyanobacterium Synechocystis PCC 6803 are connected by effective energy transfer and the corresponding energy transfer time is ~6 ps. In addition, results from hole burning spectroscopy indicated that the chlorophyll dimer of the C714 state has a large distribution of the dimer geometry. Direct observation of vibrational peaks and evolution of coumarin 153 in the electronic excited state was demonstrated by using the fs/ps CARS, a variation of time-resolved coherent anti-Stokes Raman spectroscopy. In three different solvents, methanol, acetonitrile, and butanol, a vibration peak related to the stretch of the carbonyl group exhibits different relaxation dynamics. Laser-induced fluorescence microscopy, along with the biomimetic containers-liposomes, allows the measurement of the enzymatic activity of individual alkaline phosphatase from bovine intestinal mucosa without potential interferences from glass surfaces. The result showed a wide distribution of the enzyme reactivity. Protein structural variation is one of the major reasons that are responsible for this highly heterogeneous behavior.

  18. Molecular Phylogenetic: Organism Taxonomy Method Based on Evolution History

    Directory of Open Access Journals (Sweden)

    N.L.P Indi Dharmayanti

    2011-03-01

    Full Text Available Phylogenetic is described as taxonomy classification of an organism based on its evolution history namely its phylogeny and as a part of systematic science that has objective to determine phylogeny of organism according to its characteristic. Phylogenetic analysis from amino acid and protein usually became important area in sequence analysis. Phylogenetic analysis can be used to follow the rapid change of a species such as virus. The phylogenetic evolution tree is a two dimensional of a species graphic that shows relationship among organisms or particularly among their gene sequences. The sequence separation are referred as taxa (singular taxon that is defined as phylogenetically distinct units on the tree. The tree consists of outer branches or leaves that represents taxa and nodes and branch represent correlation among taxa. When the nucleotide sequence from two different organism are similar, they were inferred to be descended from common ancestor. There were three methods which were used in phylogenetic, namely (1 Maximum parsimony, (2 Distance, and (3 Maximum likehoood. Those methods generally are applied to construct the evolutionary tree or the best tree for determine sequence variation in group. Every method is usually used for different analysis and data.

  19. Exploring viscosity, polarity and temperature sensitivity of BODIPY-based molecular rotors.

    Science.gov (United States)

    Vyšniauskas, Aurimas; López-Duarte, Ismael; Duchemin, Nicolas; Vu, Thanh-Truc; Wu, Yilei; Budynina, Ekaterina M; Volkova, Yulia A; Peña Cabrera, Eduardo; Ramírez-Ornelas, Diana E; Kuimova, Marina K

    2017-09-27

    Microviscosity is a key parameter controlling the rate of diffusion and reactions on the microscale. One of the most convenient tools for measuring microviscosity is by fluorescent viscosity sensors termed 'molecular rotors'. BODIPY-based molecular rotors in particular proved extremely useful in combination with fluorescence lifetime imaging microscopy, for providing quantitative viscosity maps of living cells as well as measuring dynamic changes in viscosity over time. In this work, we investigate several new BODIPY-based molecular rotors with the aim of improving on the current viscosity sensing capabilities and understanding how the structure of the fluorophore is related to its function. We demonstrate that due to subtle structural changes, BODIPY-based molecular rotors may become sensitive to temperature and polarity of their environment, as well as to viscosity, and provide a photophysical model explaining the nature of this sensitivity. Our data suggests that a thorough understanding of the photophysics of any new molecular rotor, in environments of different viscosity, temperature and polarity, is a must before moving on to applications in viscosity sensing.

  20. Comparison of molecular breeding values based on within- and across-breed training in beef cattle.

    Science.gov (United States)

    Kachman, Stephen D; Spangler, Matthew L; Bennett, Gary L; Hanford, Kathryn J; Kuehn, Larry A; Snelling, Warren M; Thallman, R Mark; Saatchi, Mahdi; Garrick, Dorian J; Schnabel, Robert D; Taylor, Jeremy F; Pollak, E John

    2013-08-16

    Although the efficacy of genomic predictors based on within-breed training looks promising, it is necessary to develop and evaluate across-breed predictors for the technology to be fully applied in the beef industry. The efficacies of genomic predictors trained in one breed and utilized to predict genetic merit in differing breeds based on simulation studies have been reported, as have the efficacies of predictors trained using data from multiple breeds to predict the genetic merit of purebreds. However, comparable studies using beef cattle field data have not been reported. Molecular breeding values for weaning and yearling weight were derived and evaluated using a database containing BovineSNP50 genotypes for 7294 animals from 13 breeds in the training set and 2277 animals from seven breeds (Angus, Red Angus, Hereford, Charolais, Gelbvieh, Limousin, and Simmental) in the evaluation set. Six single-breed and four across-breed genomic predictors were trained using pooled data from purebred animals. Molecular breeding values were evaluated using field data, including genotypes for 2227 animals and phenotypic records of animals born in 2008 or later. Accuracies of molecular breeding values were estimated based on the genetic correlation between the molecular breeding value and trait phenotype. With one exception, the estimated genetic correlations of within-breed molecular breeding values with trait phenotype were greater than 0.28 when evaluated in the breed used for training. Most estimated genetic correlations for the across-breed trained molecular breeding values were moderate (> 0.30). When molecular breeding values were evaluated in breeds that were not in the training set, estimated genetic correlations clustered around zero. Even for closely related breeds, within- or across-breed trained molecular breeding values have limited prediction accuracy for breeds that were not in the training set. For breeds in the training set, across- and within-breed trained

  1. Validation of risk stratification models in acute myeloid leukemia using sequencing-based molecular profiling.

    Science.gov (United States)

    Wang, M; Lindberg, J; Klevebring, D; Nilsson, C; Mer, A S; Rantalainen, M; Lehmann, S; Grönberg, H

    2017-10-01

    Risk stratification of acute myeloid leukemia (AML) patients needs improvement. Several AML risk classification models based on somatic mutations or gene-expression profiling have been proposed. However, systematic and independent validation of these models is required for future clinical implementation. We performed whole-transcriptome RNA-sequencing and panel-based deep DNA sequencing of 23 genes in 274 intensively treated AML patients (Clinseq-AML). We also utilized the The Cancer Genome Atlas (TCGA)-AML study (N=142) as a second validation cohort. We evaluated six previously proposed molecular-based models for AML risk stratification and two revised risk classification systems combining molecular- and clinical data. Risk groups stratified by five out of six models showed different overall survival in cytogenetic normal-AML patients in the Clinseq-AML cohort (P-value0.5). Risk classification systems integrating mutational or gene-expression data were found to add prognostic value to the current European Leukemia Net (ELN) risk classification. The prognostic value varied between models and across cohorts, highlighting the importance of independent validation to establish evidence of efficacy and general applicability. All but one model replicated in the Clinseq-AML cohort, indicating the potential for molecular-based AML risk models. Risk classification based on a combination of molecular and clinical data holds promise for improved AML patient stratification in the future.

  2. Fast parallel molecular algorithms for DNA-based computation: factoring integers.

    Science.gov (United States)

    Chang, Weng-Long; Guo, Minyi; Ho, Michael Shan-Hui

    2005-06-01

    The RSA public-key cryptosystem is an algorithm that converts input data to an unrecognizable encryption and converts the unrecognizable data back into its original decryption form. The security of the RSA public-key cryptosystem is based on the difficulty of factoring the product of two large prime numbers. This paper demonstrates to factor the product of two large prime numbers, and is a breakthrough in basic biological operations using a molecular computer. In order to achieve this, we propose three DNA-based algorithms for parallel subtractor, parallel comparator, and parallel modular arithmetic that formally verify our designed molecular solutions for factoring the product of two large prime numbers. Furthermore, this work indicates that the cryptosystems using public-key are perhaps insecure and also presents clear evidence of the ability of molecular computing to perform complicated mathematical operations.

  3. Lineage specific evolution of the VNTR composite retrotransposon central domain and its role in retrotransposition of gibbon LAVA elements.

    Science.gov (United States)

    Lupan, Iulia; Bulzu, Paul; Popescu, Octavian; Damert, Annette

    2015-05-16

    VNTR (Variable Number of Tandem Repeats) composite retrotransposons - SVA (SINE-R-VNTR-Alu), LAVA (LINE-1-Alu-VNTR-Alu), PVA (PTGR2-VNTR-Alu) and FVA (FRAM-VNTR-Alu) - are specific to hominoid primates. Their assembly, the evolution of their 5' and 3' domains, and the functional significance of the shared 5' Alu-like region are well understood. The central VNTR domain, by contrast, has long been assumed to represent a more or less random collection of 30-50 bp GC-rich repeats. It is only recently that it attracted attention in the context of regulation of SVA expression. Here we provide evidence that the organization of the VNTR is non-random, with conserved repeat unit (RU) arrays at both the 5' and 3' ends of the VNTRs of human, chimpanzee and orangutan SVA and gibbon LAVA. The younger SVA subfamilies harbour highly organized internal RU arrays. The composition of these arrays is specific to the human/chimpanzee and orangutan lineages, respectively. Tracing the development of the VNTR through evolution we show for the first time how tandem repeats evolve within the constraints set by a functional, non-autonomous non-LTR retrotransposon in two different families - LAVA and SVA - in different hominoid lineages. Our analysis revealed that a microhomology-driven mechanism mediates expansion/contraction of the VNTR domain at the DNA level. Elements of all four VNTR composite families have been shown to be mobilized by the autonomous LINE1 retrotransposon in trans. In case of SVA, key determinants of mobilization are found in the 5' hexameric repeat/Alu-like region. We now demonstrate that in LAVA, by contrast, the VNTR domain determines mobilization efficiency in the context of domain swaps between active and inactive elements. The central domain of VNTR composites evolves in a lineage-specific manner which gives rise to distinct structures in gibbon LAVA, orangutan SVA, and human/chimpanzee SVA. The differences observed between the families and lineages are likely to

  4. Prediction of Sliding Friction Coefficient Based on a Novel Hybrid Molecular-Mechanical Model.

    Science.gov (United States)

    Zhang, Xiaogang; Zhang, Yali; Wang, Jianmei; Sheng, Chenxing; Li, Zhixiong

    2018-08-01

    Sliding friction is a complex phenomenon which arises from the mechanical and molecular interactions of asperities when examined in a microscale. To reveal and further understand the effects of micro scaled mechanical and molecular components of friction coefficient on overall frictional behavior, a hybrid molecular-mechanical model is developed to investigate the effects of main factors, including different loads and surface roughness values, on the sliding friction coefficient in a boundary lubrication condition. Numerical modelling was conducted using a deterministic contact model and based on the molecular-mechanical theory of friction. In the contact model, with given external loads and surface topographies, the pressure distribution, real contact area, and elastic/plastic deformation of each single asperity contact were calculated. Then asperity friction coefficient was predicted by the sum of mechanical and molecular components of friction coefficient. The mechanical component was mainly determined by the contact width and elastic/plastic deformation, and the molecular component was estimated as a function of the contact area and interfacial shear stress. Numerical results were compared with experimental results and a good agreement was obtained. The model was then used to predict friction coefficients in different operating and surface conditions. Numerical results explain why applied load has a minimum effect on the friction coefficients. They also provide insight into the effect of surface roughness on the mechanical and molecular components of friction coefficients. It is revealed that the mechanical component dominates the friction coefficient when the surface roughness is large (Rq > 0.2 μm), while the friction coefficient is mainly determined by the molecular component when the surface is relatively smooth (Rq < 0.2 μm). Furthermore, optimal roughness values for minimizing the friction coefficient are recommended.

  5. Well-Defined Polyethylene-Based Random, Block, and Bilayered Molecular Cobrushes

    KAUST Repository

    Zhang, Hefeng

    2015-06-09

    Novel well-defined polyethylene-based random, block, and bilayered molecular cobrushes were synthesized through the macromonomer strategy. Two steps were involved in this approach: (i) synthesis of norbornyl-terminated macromonomers of polyethylene (PE), polycaprolactone (PCL), poly(ethylene oxide) (PEO), and polystyrene (PS), as well as polyethylene-b-polycaprolactone (PE-b-PCL), by esterification of the hydroxyl-terminated precursors (PE, PCL, PEO, PS, and PE-b-PCL) with 5-norbornene-2-carboxylic acid and (ii) ring-opening metathesis (co)polymerization of the resulting macromonomers to afford the PE-based molecular cobrushes. The PE-macromonomers were synthesized by polyhomologation of dimethylsulfoxonium methylide, while the others by anionic polymerization. Proton nuclear magnetic resonance spectroscopy (1H NMR) and high-temperature gel permeation chromatography (HT-GPC) were used to imprint the molecular characteristics of all macromonomers and molecular brushes and differential scanning calorimetry (DSC) for the thermal properties. The bilayered molecular cobrushes of P(PE-b-PCL) adopt a wormlike morphology on silica wafer as visualized by atomic force microscopy (AFM). © 2015 American Chemical Society.

  6. Molecularly imprinted fluorescent probe based on FRET for selective and sensitive detection of doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Zhifeng, E-mail: 897061147@qq.com [College of Chemistry and Materials Science, Hengyang Normal University, Key Laboratory of Functional Organometallic Materials of Hunan Province University, Hengyang 421008 (China); Deng, Peihong; Li, Junhua [College of Chemistry and Materials Science, Hengyang Normal University, Key Laboratory of Functional Organometallic Materials of Hunan Province University, Hengyang 421008 (China); Xu, Li [Department of Applied Chemistry, College of Materials and Energy, South China Agricultural University, Guangzhou 510642 (China); Tang, Siping [College of Chemistry and Materials Science, Hengyang Normal University, Key Laboratory of Functional Organometallic Materials of Hunan Province University, Hengyang 421008 (China)

    2017-04-15

    Highlights: • FRET-based molecularly imprinted probe for detection of doxorubicin was prepared. • The detection limit of the probe was 13.8 nM for doxorubicin. • The FRET-based probe had a higher selectivity for the template than ordinary MIMs. - Abstract: In this work, a new type of fluorescent probe for detection of doxorubicin has been constructed by the combined use of fluorescence resonance energy transfer (FRET) technology and molecular imprinting technique (MIT). Using doxorubicin as the template, the molecularly imprinted polymer thin layer was fabricated on the surfaces of carbon dot (CD) modified silica by sol-gel polymerization. The excitation energy of the fluorescent donor (CDs) could be transferred to the fluorescent acceptor (doxorubicin). The FRET based fluorescent probe demonstrated high sensitivity and selectivity for doxorubicin. The detection limit was 13.8 nM. The fluorescent probe was successfully applied for detecting doxorubicin in doxorubicin-spiked plasmas with a recovery of 96.8–103.8%, a relative standard deviation (RSD) of 1.3–2.8%. The strategy for construction of FRET-based molecularly imprinted materials developed in this work is very promising for analytical applications.

  7. Development of new candidate gene and EST-based molecular markers for Gossypium species

    Science.gov (United States)

    New source of molecular markers accelerates the efforts in improving cotton fiber traits and aid in developing high-density integrated genetic maps. We developed new markers based on candidate genes and G. arboreum expressed sequence tag (EST) sequences, and validated them through amplification, ge...

  8. Novel low-molecular-weight-gelator-based microcapsules with controllable morphology and temperature responsiveness.

    Science.gov (United States)

    Patel, Ashok R; Remijn, Caroline; Heussen, Patricia C M; den Adel, Ruud; Velikov, Krassimir P

    2013-02-04

    A new type of microcapsules with controllable morphology is presented. They are based on a low-molecular-weight gelator and can be switched from temperature-stable to temperature-responsive by simply modifying the preparation method. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Refinement of homology-based protein structures by molecular dynamics simulation techniques

    NARCIS (Netherlands)

    Fan, H; Mark, AE

    The use of classical molecular dynamics simulations, performed in explicit water, for the refinement of structural models of proteins generated ab initio or based on homology has been investigated. The study involved a test set of 15 proteins that were previously used by Baker and coworkers to

  10. Molecular modeling of the conductivity changes of the emeraldine base polyaniline due to protonic acid doping

    NARCIS (Netherlands)

    Chen, X.; Yuan, C.A.; Wong, C.K.Y.; Zhang, G.

    2012-01-01

    We propose a molecular modeling strategy, which is capable of predicting the conductivity change of emeraldine base polyaniline polymer due to different degree of protonic acid doping. The method is comprised of two key steps: (1) generating the amorphous unit cells with given number of polymer

  11. Encapsulation and solid state sequestration of gases by calix[6]arene-based molecular containers.

    Science.gov (United States)

    Lavendomme, Roy; Ajami, Daniela; Moerkerke, Steven; Wouters, Johan; Rissanen, Kari; Luhmer, Michel; Jabin, Ivan

    2017-06-13

    Two calix[6]arene-based molecular containers were synthesized in high yields. These containers can encapsulate small guests through a unique "rotating door" complexation process. The sequestration of greenhouse gases is clearly demonstrated. They can be stored in the solid state for long periods and released via dissolution of the inclusion complex.

  12. Molecular Docking of Enzyme Inhibitors: A Computational Tool for Structure-Based Drug Design

    Science.gov (United States)

    Rudnitskaya, Aleksandra; Torok, Bela; Torok, Marianna

    2010-01-01

    Molecular docking is a frequently used method in structure-based rational drug design. It is used for evaluating the complex formation of small ligands with large biomolecules, predicting the strength of the bonding forces and finding the best geometrical arrangements. The major goal of this advanced undergraduate biochemistry laboratory exercise…

  13. Redox regulation of a novel L1Md-A2 retrotransposon in vascular smooth muscle cells.

    Science.gov (United States)

    Lu, Kim P; Ramos, Kenneth S

    2003-07-25

    Activation and reintegration of retrotransposons into the genome is linked to several diseases in human and rodents, but mechanisms of gene activation remain largely unknown. Here we identify a novel gene of L1Md-A2 lineage in vascular smooth muscle cells and show that environmental hydrocarbons enhance gene expression and activate monomer-driven transcription via a redox-sensitive mechanism. Site-directed mutagenesis and progressive deletion analyses identified two antioxidant/electrophile response-like elements (5'-GTGACTCGAGC-3') within the A2/3 and A3 region. These elements mediated activation, with the A3 monomer playing an essential role in transactivation. This signaling pathway may contribute to gene instability during the course of atherogenesis.

  14. A tissue-specific promoter derived from a SINE retrotransposon drives biallelic expression of PLAGL1 in human lymphocytes.

    Directory of Open Access Journals (Sweden)

    Claire E L Smith

    Full Text Available The imprinted gene PLAGL1 is an important regulator of apoptosis and cell cycle arrest. Loss of its expression has been implicated in tumorigenesis in a range of different cancers, and overexpression during fetal development causes transient neonatal diabetes mellitus (TNDM. PLAGL1 lies within an imprinted region of chromosome 6q24, and monoallelic expression from the major, differentially methylated promoter (P1 occurs in most human tissues. However, in peripheral blood leukocytes, the active promoter (P2 is non-imprinted and drives biallelic transcription. We report here a novel PLAGL1 promoter (P5 derived from the insertion of a primate-specific, MIR3 SINE retrotransposon. P5 is highly utilized in lymphocytes, particularly in T cells, and like P2, directs biallelic transcription. Our results show that it is important to consider P5 in relation to PLAGL1 function in T cells when investigating the dysregulation of this gene.

  15. Towards a logic-based method to infer provenance-aware molecular networks

    OpenAIRE

    Aslaoui-Errafi, Zahira; Cohen-Boulakia, Sarah; Froidevaux, Christine; Gloaguen, Pauline; Poupon, Anne; Rougny, Adrien; Yahiaoui, Meriem

    2012-01-01

    International audience; Providing techniques to automatically infer molecular networks is particularly important to understand complex relationships between biological objects. We present a logic-based method to infer such networks and show how it allows inferring signalling networks from the design of a knowledge base. Provenance of inferred data has been carefully collected, allowing quality evaluation. More precisely, our method (i) takes into account various kinds of biological experiment...

  16. Isatin based thiosemicarbazone derivatives as potential bioactive agents: Anti-oxidant and molecular docking studies

    Science.gov (United States)

    Haribabu, J.; Subhashree, G. R.; Saranya, S.; Gomathi, K.; Karvembu, R.; Gayathri, D.

    2016-04-01

    A new series of isatin based thiosemicarbazones has been synthesized from benzylisatin and unsubstituted/substituted thiosemicarbazides (1-5). The synthesized compounds were characterized by elemental analyses, and UV-Visible, FT-IR, 1H &13C NMR and mass spectroscopic techniques. Three dimensional molecular structure of three compounds (1, 3 and 4) was determined by single crystal X-ray crystallography. Anti-oxidant activity of the thiosemicarbazone derivatives showed their excellent scavenging effect against free radicals. In addition, all the compounds showed good anti-haemolytic activity. In silico molecular docking studies were performed to screen the anti-inflammatory and anti-tuberculosis properties of thiosemicarbazone derivatives.

  17. pyPcazip: A PCA-based toolkit for compression and analysis of molecular simulation data

    Directory of Open Access Journals (Sweden)

    Ardita Shkurti

    2016-01-01

    Full Text Available The biomolecular simulation community is currently in need of novel and optimised software tools that can analyse and process, in reasonable timescales, the large generated amounts of molecular simulation data. In light of this, we have developed and present here pyPcazip: a suite of software tools for compression and analysis of molecular dynamics (MD simulation data. The software is compatible with trajectory file formats generated by most contemporary MD engines such as AMBER, CHARMM, GROMACS and NAMD, and is MPI parallelised to permit the efficient processing of very large datasets. pyPcazip is a Unix based open-source software (BSD licenced written in Python.

  18. An Evolvement-based Genetic Algorithm for Computer-aided Molecular Docking

    Science.gov (United States)

    Ling, Kang; Xiaoyu, Zhao; Xi, Chen; Xicheng, Wang

    2010-05-01

    Species dynamics model is introduced into the genetic algorithm to reflect the true state of evolution. An adaptive evolution algorithm is developed. In the algorithm, an adaptive strategy is used to overcome the difficulty of confirming the crossover and mutation probabilities. Small population strategy and optimal strategy ensure the diversity of the populations. Numerical results show that introducing species dynamics model can improve the efficiency of the algorithm. Based on the genetic algorithm, a new molecular docking program is developed. Docking result indicates that the algorithm can effectively solve the molecular docking problem.

  19. Chlorine Anion Encapsulation by Molecular Capsules Based on Cucurbit[5]uril and Decamethylcucurbit[5]uril

    OpenAIRE

    Zhu Tao; Sai-Feng Xue; Qian-Jiang Zhu; Yun-Qian Zhang

    2007-01-01

    Three barrel-shaped artificial molecular capsules 1-3, based on normal cucurbit[5]uril (Q[5]) and decamethylcucurbit[5]uril (Me10Q[5]), were synthesized and structurally characterized by single-crystal X-ray diffraction. Encapsulation of a chlorine anion in the cavity of a Q[5] or Me10Q[5] to form closed a molecular capsule with the coordinated metal ions or coordinated metal ions and water molecules in the crystal structures of these compounds is common. The three complexes [Pr2(C30H30N20O10...

  20. Toward molecular trait-based ecology through integration of biogeochemical, geographical and metagenomic data

    DEFF Research Database (Denmark)

    Raes, Jeroen; Letunic, Ivica; Yamada, Takuji

    2011-01-01

    Using metagenomic 'parts lists' to infer global patterns on microbial ecology remains a significant challenge. To deduce important ecological indicators such as environmental adaptation, molecular trait dispersal, diversity variation and primary production from the gene pool of an ecosystem, we...... integrated 25 ocean metagenomes with geographical, meteorological and geophysicochemical data. We find that climatic factors (temperature, sunlight) are the major determinants of the biomolecular repertoire of each sample and the main limiting factor on functional trait dispersal (absence of biogeographic...... composition derived from metagenomes is an important quantitative readout for molecular trait-based biogeography and ecology....

  1. Molecular biology-based methods for quantification of bacteria in mixed culture: perspectives and limitations.

    Science.gov (United States)

    Nagarajan, Karthiga; Loh, Kai-Chee

    2014-08-01

    Species-specific enumeration of mixed community is invaluable as it facilitates a better understanding of the significance of the individual strains, their interactions, and the underlying mechanisms of community dynamics. Mixed microbial community has been characterized by microbiological, biochemical, or molecular biology-based methods. While microbiological and biochemical techniques do not provide adequate quantitative information of the members of the consortia and require additional techniques for a more comprehensive analysis, molecular biology-based methods analyze the microbial consortium based on specific DNA sequences and do not require isolation and culturing of bacteria for quantitative analysis. These methods outshine conventional culture-based techniques in terms of better sensitivity, reproducibility, and reliability. Quantitative molecular biology methods have been classified as PCR-based and probe hybridization methods. The PCR-based methods includes quantitative real-time PCR and terminal restriction fragment length polymorphism, while fluorescent in situ hybridization and DNA microarrays fall under probe hybridization methods. The workflow, the quantification methods, and their potential applications are discussed in this review by highlighting their advantages and possible limitations.

  2. SCAR makers and multiplex PCR-based rapid molecular typing of Lentinula edodes strains.

    Science.gov (United States)

    Wu, Xueqian; Li, Haibo; Zhao, Weiwei; Fu, Lizhong; Peng, Huazheng; He, Liang; Cheng, Junwen; Wei, Hailong; Wu, Qingqi

    2010-11-01

    Lentinula edodes is the second most important cultivated mushroom worldwide, the most commercial strains have been identified only through traditional phenotypic analysis. In this study, a simple rapid PCR-based molecular method was developed for distinguishing commercial strains of L. edodes by developing specific sequence characterized amplified region (SCAR) markers and establishing multiplex PCR assays with the SCAR primers. Derived from the randomly amplified polymorphic DNA (RAPD) and sequence-related amplified polymorphism (SRAP) techniques, 10 informative SCAR markers were generated from 10 polymorphic RAPD and SRAP bands. The differences in SCAR phenotypes among different strains made these SCAR markers potentially useful to characterize 6 strains and identify them from other studied strains. Moreover, different SCAR phenotypes also made the other 17 studied strains to be divided into four distinguishable groups. The multiplex PCR assays were further established for the joint use of some SCAR markers efficiently. Compared with some identification methods reported previously, the special feature of this new molecular method is technically rapid and convenient in the practical use and suitable for analyzing large numbers of samples. Thus, the simple rapid PCR-based molecular method can be used as a helpful assistant tool for the lentinula industry. To our knowledge, this study is the first to describe a development of a new SCAR maker-based multiplex PCR assay for rapid molecular typing of edible mushroom.

  3. Gold-based hybrid nanomaterials for biosensing and molecular diagnostic applications.

    Science.gov (United States)

    Kim, Jung Eun; Choi, Ji Hye; Colas, Marion; Kim, Dong Ha; Lee, Hyukjin

    2016-06-15

    The properties of gold nanomaterials are particularly of interest to many researchers, since they show unique physiochemical properties such as optical adsorption of specific wavelength of light, high electrical conductance with rich surface electrons, and facile surface modification with sulfhydryl groups. These properties have facilitated the use of gold nanomaterials in the development of various hybrid systems for biosensors and molecular diagnostics. Combined with various synthetic materials such as fluorescence dyes, polymers, oligonucleotides, graphene oxides (GO), and quantum dots (QDs), the gold-based hybrid nanomaterials offer multi-functionalities in molecular detection with high specificity and sensitivity. These two aspects result in the increase of detection speed as well as the lower detection limits, having shown that this diagnosis method is more effective than other conventional ones. In this review, we have highlighted various examples of nanomaterials for biosensing and molecular diagnostics. The gold-based hybrid systems are categorized by three distinct detection approaches, in which include (1) optical, such as surface plasmon resonance (SPR), RAMAN, and surface-enhanced Raman scattering (SERS), (2) fluorescence, such as förster resonance energy transfer (FRET) and nanomaterial surface energy transfer (NSET), and (3) electrochemical, such as potentiometic, amperometric, and conductometric. Each example provides the detailed mechanism of molecular detection as well as the supporting experimental result with the limit of detection (LOD). Lastly, future perspective on novel development of gold-based hybrid nanomaterials is discussed as well as their challenges. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. ChemDes: an integrated web-based platform for molecular descriptor and fingerprint computation.

    Science.gov (United States)

    Dong, Jie; Cao, Dong-Sheng; Miao, Hong-Yu; Liu, Shao; Deng, Bai-Chuan; Yun, Yong-Huan; Wang, Ning-Ning; Lu, Ai-Ping; Zeng, Wen-Bin; Chen, Alex F

    2015-01-01

    Molecular descriptors and fingerprints have been routinely used in QSAR/SAR analysis, virtual drug screening, compound search/ranking, drug ADME/T prediction and other drug discovery processes. Since the calculation of such quantitative representations of molecules may require substantial computational skills and efforts, several tools have been previously developed to make an attempt to ease the process. However, there are still several hurdles for users to overcome to fully harness the power of these tools. First, most of the tools are distributed as standalone software or packages that require necessary configuration or programming efforts of users. Second, many of the tools can only calculate a subset of molecular descriptors, and the results from multiple tools need to be manually merged to generate a comprehensive set of descriptors. Third, some packages only provide application programming interfaces and are implemented in different computer languages, which pose additional challenges to the integration of these tools. A freely available web-based platform, named ChemDes, is developed in this study. It integrates multiple state-of-the-art packages (i.e., Pybel, CDK, RDKit, BlueDesc, Chemopy, PaDEL and jCompoundMapper) for computing molecular descriptors and fingerprints. ChemDes not only provides friendly web interfaces to relieve users from burdensome programming work, but also offers three useful and convenient auxiliary tools for format converting, MOPAC optimization and fingerprint similarity calculation. Currently, ChemDes has the capability of computing 3679 molecular descriptors and 59 types of molecular fingerprints. ChemDes provides users an integrated and friendly tool to calculate various molecular descriptors and fingerprints. It is freely available at http://www.scbdd.com/chemdes. The source code of the project is also available as a supplementary file. Graphical abstract:An overview of ChemDes. A platform for computing various molecular

  5. Possibility of gas sensor based on C{sub 20} molecular devices

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Wenkai [School of Physics and Optoelectronics Engineering, Ludong University, Yantai 264025 (China); Yang, Chuanlu, E-mail: yangchuanlu@126.com [School of Physics and Optoelectronics Engineering, Ludong University, Yantai 264025 (China); Zou, Dongqing [School of Physics, State Key Laboratory of Crystal Materials, Shandong University, Jinan 250100 (China); Sun, Zhaopeng [School of Physics and Optoelectronics Engineering, Ludong University, Yantai 264025 (China); Ji, Guomin [Electrical and Computer Engineering, The University of Oklahoma, Norman, Tulsa, OK 74078 (United States)

    2017-06-09

    We theoretically investigate the possibility of diatomic gas detection (NO, CO, O{sub 2}) by making use of the transport properties of the C{sub 20} molecular junctions. The calculations are performed by using nonequilibrium Green's function (NEGF) formalism in combination with density functional theory (DFT). In this work, we systematically study the most stable adsorption structural configurations, adsorption energy, and the transport properties on C{sub 20} molecular junctions with these diatomic gas molecules. It is found that NO and O{sub 2} gas molecule can be detected selectively. We suggest its possibility of nanosensors for highly sensitive and selective based on C{sub 20} molecular junction systems. - Highlights: • The most favorable adsorption site is investigated. • The mechanism of gas sensors is revealed. • NO and O{sub 2} gas molecules can be detected by C{sub 20} selectively.

  6. Comparison of five Calligonum species in Tarim Basin based on morphological and molecular data.

    Science.gov (United States)

    Abdurahman, Maryamgul; Sabirhazi, Gulnur; Liu, Bin; Yin, Linke; Pan, Borong

    2012-01-01

    Five Calligonum species endemic to the Tarim Basin - C. roborowskii , C. kuerlese , C. juoqiangense, C. yengisaricum , and C. taklimakanense - were compared using 14 morphological characteristics and nrDNA ITS and cpDNA trnL-F molecular data. Intraspecific and interspecific morphological variation was uncovered, with variation between species significant for most characteristics. Based on Euclidean distances, C. roborowskii and C. kuerlese were the most similar, and C. yengisaricum and C. kuerlese were the most divergent. There was very little variation in the molecular sequence data: although several variable sites were present in ITS and trnL-F regions, none of them were parsimony informative. Results of morphological and molecular analyses suggest that the various morphological characteristics of the studied Calligonum species are strongly shaped by environmental factors, with the observed intraspecific and interspecific morphological variation a product of the spatial isolation and extreme drought of the Tarim Basin.

  7. Mass Spectrometry Based Molecular 3D-Cartography of Plant Metabolites.

    Science.gov (United States)

    Floros, Dimitrios J; Petras, Daniel; Kapono, Clifford A; Melnik, Alexey V; Ling, Tie-Jun; Knight, Rob; Dorrestein, Pieter C

    2017-01-01

    Plants play an essential part in global carbon fixing through photosynthesis and are the primary food and energy source for humans. Understanding them thoroughly is therefore of highest interest for humanity. Advances in DNA and RNA sequencing and in protein and metabolite analysis allow the systematic description of plant composition at the molecular level. With imaging mass spectrometry, we can now add a spatial level, typically in the micrometer-to-centimeter range, to their compositions, essential for a detailed molecular understanding. Here we present an LC-MS based approach for 3D plant imaging, which is scalable and allows the analysis of entire plants. We applied this approach in a case study to pepper and tomato plants. Together with MS/MS spectra library matching and spectral networking, this non-targeted workflow provides the highest sensitivity and selectivity for the molecular annotations and imaging of plants, laying the foundation for studies of plant metabolism and plant-environment interactions.

  8. Molecular Dynamics Simulations of the First Reactions in Nitrate Ester-based Explosives

    Science.gov (United States)

    Cawkwell, Marc; Kober, Ed; Myers, Thomas; Manner, Virginia

    2017-06-01

    In order to better understand and manipulate explosive sensitivity, we have prepared and analyzed a series of pentaerythritol tetranitrate-based explosives with systematic changes to the molecular structure. Reactive, extended Lagrangian Born-Oppenheimer molecular dynamics simulations have been performed on this series of molecules in the condensed phase to understand how the reactivity changes with the molecular modifications. The net reactions occurring over the first few hundred picoseconds under conditions of static high temperature and shock compression have been identified by an innovative analysis of coordination geometry changes and reaction types rather than attempting to detail each individual reaction. The evolution of temperature and pressure owing to evolving chemistry in the shock compressed materials were also captured accurately. Changes in exothermicity and the populations of intermediate and product moieties are connected to the systematic changes in stoichiometry. The results of the simulations are compared to preliminary estimates of sensitivity derived from small scale impact tests on materials synthesized recently at LANL.

  9. A subtelomeric non-LTR retrotransposon Hebe in the bdelloid rotifer Adineta vaga is subject to inactivation by deletions but not 5' truncations

    Directory of Open Access Journals (Sweden)

    Gladyshev Eugene A

    2010-04-01

    Full Text Available Abstract Background Rotifers of the class Bdelloidea are microscopic freshwater invertebrates best known for: their capacity for anhydrobiosis; the lack of males and meiosis; and for the ability to capture genes from other non-metazoan species. Although genetic exchange between these animals might take place by non-canonical means, the overall lack of meiosis and syngamy should greatly impair the ability of transposable elements (TEs to spread in bdelloid populations. Previous studies demonstrated that bdelloid chromosome ends, in contrast to gene-rich regions, harbour various kinds of TEs, including specialized telomere-associated retroelements, as well as DNA TEs and retrovirus-like retrotransposons which are prone to horizontal transmission. Vertically-transmitted retrotransposons have not previously been reported in bdelloids and their identification and studies of the patterns of their distribution and evolution could help in the understanding of the high degree of TE compartmentalization within bdelloid genomes. Results We identified and characterized a non-long terminal repeat (LTR retrotransposon residing primarily in subtelomeric regions of the genome in the bdelloid rotifer Adineta vaga. Contrary to the currently prevailing views on the mode of proliferation of non-LTR retrotransposons, which results in frequent formation of 5'-truncated ('dead-on-arrival' copies due to the premature disengagement of the element-encoded reverse transcriptase from its template, this non-LTR element, Hebe, is represented only by non-5'-truncated copies. Most of these copies, however, were subject to internal deletions associated with microhomologies, a hallmark of non-homologous end-joining events. Conclusions The non-LTR retrotransposon Hebe from the bdelloid rotifer A. vaga was found to undergo frequent microhomology-associated deletions, rather than 5'-terminal truncations characteristic of this class of retrotransposons, and to exhibit preference for

  10. MOLECULAR COMPLEXES OF SULPHUR DIOXIDE WITH N,O-CONTAINING ORGANIC BASES (REVIEW

    Directory of Open Access Journals (Sweden)

    R. E. Khoma

    2016-10-01

    Full Text Available The literature data on the synthesis, stoichiometry, structure and relative stability of molecular  complexes of sulphur dioxide with N,O-containing organic bases have been systematized and  generalized. It was shown that the yield of the reaction product of sulfur dioxide with organic  bases (such as amines are strongly influenced by the conditions of synthesis: the nature of  the solvent (basicity, polarity, the temperature and SO2:L ratio in the reaction medium. The stoichiometry of SO2*nL molecular complexes depends on ligand denticity, as well as its  ability to H-bonding. The reaction of the sulfur oxide (IV with organic bases can give S←N and S←O complexes. With the increase of the value of base proton affinity the decrease ΔrSN values has been marked. Characteristic parameter Δr SN = r SN – a1(rS+ rN (where rSNis the S←N donor-acceptor bond length has been determined by microwave spectroscopy and X-ray analysis, rSand rNwere the tabulated values of the homopolar covalent radii of sulphur and nitrogen heteroatoms. The dependence of formation enthalpy of molecular complexes of basic amines and spectral characteristics has been noted; enthalpy-entropy compensation for S←N and S←O complex-es has been stated. Despite the limited experimental data on the thermodynamics of complex formation and the lengths of donor-acceptor bonds for the same compounds it has been found bond S←N strength in SO2 molecular complexes to depend on the intrinsic value of ΔrSN. The contribution of van der Waals forces and charge transfer forces to the formation of molecular complexes of sulphur dioxide has been stated.

  11. 3D-Lab: a collaborative web-based platform for molecular modeling.

    Science.gov (United States)

    Grebner, Christoph; Norrby, Magnus; Enström, Jonatan; Nilsson, Ingemar; Hogner, Anders; Henriksson, Jonas; Westin, Johan; Faramarzi, Farzad; Werner, Philip; Boström, Jonas

    2016-09-01

    The use of 3D information has shown impact in numerous applications in drug design. However, it is often under-utilized and traditionally limited to specialists. We want to change that, and present an approach making 3D information and molecular modeling accessible and easy-to-use 'for the people'. A user-friendly and collaborative web-based platform (3D-Lab) for 3D modeling, including a blazingly fast virtual screening capability, was developed. 3D-Lab provides an interface to automatic molecular modeling, like conformer generation, ligand alignments, molecular dockings and simple quantum chemistry protocols. 3D-Lab is designed to be modular, and to facilitate sharing of 3D-information to promote interactions between drug designers. Recent enhancements to our open-source virtual reality tool Molecular Rift are described. The integrated drug-design platform allows drug designers to instantaneously access 3D information and readily apply advanced and automated 3D molecular modeling tasks, with the aim to improve decision-making in drug design projects.

  12. Interference between concurrent resistance and endurance exercise: molecular bases and the role of individual training variables.

    Science.gov (United States)

    Fyfe, Jackson J; Bishop, David J; Stepto, Nigel K

    2014-06-01

    Concurrent training is defined as simultaneously incorporating both resistance and endurance exercise within a periodized training regime. Despite the potential additive benefits of combining these divergent exercise modes with regards to disease prevention and athletic performance, current evidence suggests that this approach may attenuate gains in muscle mass, strength, and power compared with undertaking resistance training alone. This has been variously described as the interference effect or concurrent training effect. In recent years, understanding of the molecular mechanisms mediating training adaptation in skeletal muscle has emerged and provided potential mechanistic insight into the concurrent training effect. Although it appears that various molecular signaling responses induced in skeletal muscle by endurance exercise can inhibit pathways regulating protein synthesis and stimulate protein breakdown, human studies to date have not observed such molecular 'interference' following acute concurrent exercise that might explain compromised muscle hypertrophy following concurrent training. However, given the multitude of potential concurrent training variables and the limitations of existing evidence, the potential roles of individual training variables in acute and chronic interference are not fully elucidated. The present review explores current evidence for the molecular basis of the specificity of training adaptation and the concurrent interference phenomenon. Additionally, insights provided by molecular and performance-based concurrent training studies regarding the role of individual training variables (i.e., within-session exercise order, between-mode recovery, endurance training volume, intensity, and modality) in the concurrent interference effect are discussed, along with the limitations of our current understanding of this complex paradigm.

  13. Simple and universal platform for logic gate operations based on molecular beacon probes.

    Science.gov (United States)

    Park, Ki Soo; Seo, Myung Wan; Jung, Cheulhee; Lee, Joon Young; Park, Hyun Gyu

    2012-07-23

    A new platform technology is herein described with which to construct molecular logic gates by employing the hairpin-structured molecular beacon probe as a basic work unit. In this logic gate operation system, single-stranded DNA is used as the input to induce a conformational change in a molecular beacon probe through a sequence-specific interaction. The fluorescent signal resulting from the opening of the molecular beacon probe is then used as the output readout. Importantly, because the logic gates are based on DNA, thus permitting input/output homogeneity to be preserved, their wiring into multi-level circuits can be achieved by combining separately operated logic gates or by designing the DNA output of one gate as the input to the other. With this novel strategy, a complete set of two-input logic gates is successfully constructed at the molecular level, including OR, AND, XOR, INHIBIT, NOR, NAND, XNOR, and IMPLICATION. The logic gates developed herein can be reversibly operated to perform the set-reset function by applying an additional input or a removal strand. Together, these results introduce a new platform technology for logic gate operation that enables the higher-order circuits required for complex communication between various computational elements. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Computing molecular fluctuations in biochemical reaction systems based on a mechanistic, statistical theory of irreversible processes.

    Science.gov (United States)

    Kulasiri, Don

    2011-01-01

    We discuss the quantification of molecular fluctuations in the biochemical reaction systems within the context of intracellular processes associated with gene expression. We take the molecular reactions pertaining to circadian rhythms to develop models of molecular fluctuations in this chapter. There are a significant number of studies on stochastic fluctuations in intracellular genetic regulatory networks based on single cell-level experiments. In order to understand the fluctuations associated with the gene expression in circadian rhythm networks, it is important to model the interactions of transcriptional factors with the E-boxes in the promoter regions of some of the genes. The pertinent aspects of a near-equilibrium theory that would integrate the thermodynamical and particle dynamic characteristics of intracellular molecular fluctuations would be discussed, and the theory is extended by using the theory of stochastic differential equations. We then model the fluctuations associated with the promoter regions using general mathematical settings. We implemented ubiquitous Gillespie's algorithms, which are used to simulate stochasticity in biochemical networks, for each of the motifs. Both the theory and the Gillespie's algorithms gave the same results in terms of the time evolution of means and variances of molecular numbers. As biochemical reactions occur far away from equilibrium-hence the use of the Gillespie algorithm-these results suggest that the near-equilibrium theory should be a good approximation for some of the biochemical reactions. © 2011 Elsevier Inc. All rights reserved.

  15. Molecular and cellular bases of adaptation to a changing environment in microorganisms.

    Science.gov (United States)

    Bleuven, Clara; Landry, Christian R

    2016-10-26

    Environmental heterogeneity constitutes an evolutionary challenge for organisms. While evolutionary dynamics under variable conditions has been explored for decades, we still know relatively little about the cellular and molecular mechanisms involved. It is of paramount importance to examine these molecular bases because they may play an important role in shaping the course of evolution. In this review, we examine the diversity of adaptive mechanisms in the face of environmental changes. We exploit the recent literature on microbial systems because those have benefited the most from the recent emergence of genetic engineering and experimental evolution followed by genome sequencing. We identify four emerging trends: (i) an adaptive molecular change in a pathway often results in fitness trade-off in alternative environments but the effects are dependent on a mutation's genetic background; (ii) adaptive changes often modify transcriptional and signalling pathways; (iii) several adaptive changes may occur within the same molecular pathway but be associated with pleiotropy of different signs across environments; (iv) because of their large associated costs, macromolecular changes such as gene amplification and aneuploidy may be a rapid mechanism of adaptation in the short-term only. The course of adaptation in a variable environment, therefore, depends on the complexity of the environment but also on the molecular relationships among the genes involved and between the genes and the phenotypes under selection. © 2016 The Author(s).

  16. A novel energy conversion based method for velocity correction in molecular dynamics simulations

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Hanhui [School of Aeronautics and Astronautics, Zhejiang University, Hangzhou 310027 (China); Collaborative Innovation Center of Advanced Aero-Engine, Hangzhou 310027 (China); Liu, Ningning [School of Aeronautics and Astronautics, Zhejiang University, Hangzhou 310027 (China); Ku, Xiaoke, E-mail: xiaokeku@zju.edu.cn [School of Aeronautics and Astronautics, Zhejiang University, Hangzhou 310027 (China); Fan, Jianren [State Key Laboratory of Clean Energy Utilization, Zhejiang University, Hangzhou 310027 (China)

    2017-05-01

    Molecular dynamics (MD) simulation has become an important tool for studying micro- or nano-scale dynamics and the statistical properties of fluids and solids. In MD simulations, there are mainly two approaches: equilibrium and non-equilibrium molecular dynamics (EMD and NEMD). In this paper, a new energy conversion based correction (ECBC) method for MD is developed. Unlike the traditional systematic correction based on macroscopic parameters, the ECBC method is developed strictly based on the physical interaction processes between the pair of molecules or atoms. The developed ECBC method can apply to EMD and NEMD directly. While using MD with this method, the difference between the EMD and NEMD is eliminated, and no macroscopic parameters such as external imposed potentials or coefficients are needed. With this method, many limits of using MD are lifted. The application scope of MD is greatly extended.

  17. A Formaldehyde Sensor Based on Molecularly-Imprinted Polymer on a TiO₂ Nanotube Array.

    Science.gov (United States)

    Tang, Xiaohui; Raskin, Jean-Pierre; Lahem, Driss; Krumpmann, Arnaud; Decroly, André; Debliquy, Marc

    2017-03-24

    Today, significant attention has been brought to the development of sensitive, specific, cheap, and reliable sensors for real-time monitoring. Molecular imprinting technology is a versatile and promising technology for practical applications in many areas, particularly chemical sensors. Here, we present a chemical sensor for detecting formaldehyde, a toxic common indoor pollutant gas. Polypyrrole-based molecularly-imprinted polymer (PPy-based MIP) is employed as the sensing recognition layer and synthesized on a titanium dioxide nanotube array (TiO₂-NTA) for increasing its surface-to-volume ratio, thereby improving the sensor performance. Our sensor selectively detects formaldehyde in the parts per million (ppm) range at room temperature. It also shows a long-term stability and small fluctuation to humidity variations. These are attributed to the thin fishnet-like structure of the PPy-based MIP on the highly-ordered and vertically-aligned TiO₂-NTA.

  18. Grid-based Continual Analysis of Molecular Interior for Drug Discovery, QSAR and QSPR.

    Science.gov (United States)

    Potemkin, Andrey V; Grishina, Maria A; Potemkin, Vladimir A

    2017-01-01

    In 1979, R.D.Cramer and M.Milne made a first realization of 3D comparison of molecules by aligning them in space and by mapping their molecular fields to a 3D grid. Further, this approach was developed as the DYLOMMS (Dynamic Lattice- Oriented Molecular Modelling System) approach. In 1984, H.Wold and S.Wold proposed the use of partial least squares (PLS) analysis, instead of principal component analysis, to correlate the field values with biological activities. Then, in 1988, the method which was called CoMFA (Comparative Molecular Field Analysis) was introduced and the appropriate software became commercially available. Since 1988, a lot of 3D QSAR methods, algorithms and their modifications are introduced for solving of virtual drug discovery problems (e.g., CoMSIA, CoMMA, HINT, HASL, GOLPE, GRID, PARM, Raptor, BiS, CiS, ConGO,). All the methods can be divided into two groups (classes):1. Methods studying the exterior of molecules; 2) Methods studying the interior of molecules. A series of grid-based computational technologies for Continual Molecular Interior analysis (CoMIn) are invented in the current paper. The grid-based analysis is fulfilled by means of a lattice construction analogously to many other grid-based methods. The further continual elucidation of molecular structure is performed in various ways. (i) In terms of intermolecular interactions potentials. This can be represented as a superposition of Coulomb, Van der Waals interactions and hydrogen bonds. All the potentials are well known continual functions and their values can be determined in all lattice points for a molecule. (ii) In the terms of quantum functions such as electron density distribution, Laplacian and Hamiltonian of electron density distribution, potential energy distribution, the highest occupied and the lowest unoccupied molecular orbitals distribution and their superposition. To reduce time of calculations using quantum methods based on the first principles, an original quantum

  19. Population structure and genotypic variation of Crataegus pontica inferred by molecular markers.

    Science.gov (United States)

    Rahmani, Mohammad-Shafie; Shabanian, Naghi; Khadivi-Khub, Abdollah; Woeste, Keith E; Badakhshan, Hedieh; Alikhani, Leila

    2015-11-01

    Information about the natural patterns of genetic variability and their evolutionary bases are of fundamental practical importance for sustainable forest management and conservation. In the present study, the genetic diversity of 164 individuals from fourteen natural populations of Crataegus pontica K.Koch was assessed for the first time using three genome-based molecular techniques; inter-retrotransposon amplified polymorphism (IRAP); inter-simple sequence repeats (ISSR) and start codon targeted (SCoT) polymorphism. IRAP, ISSR and SCoT analyses yielded 126, 254 and 199 scorable amplified bands, respectively, of which 90.48, 93.37 and 83.78% were polymorphic. ISSR revealed efficiency over IRAP and SCoT due to high effective multiplex ratio, marker index and resolving power. The dendrograms based on the markers used and combined data divided individuals into three major clusters. The correlation between the coefficient matrices for the IRAP, ISSR and SCoT data was significant. A higher level of genetic variation was observed within populations than among populations based on the markers used. The lower divergence levels depicted among the studied populations could be seen as evidence of gene flow. The promotion of gene exchange will be very beneficial to conserve and utilize the enormous genetic variability. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Genetic variability of hull-less barley accessions based on molecular and quantitative data

    Directory of Open Access Journals (Sweden)

    Ricardo Meneses Sayd

    2015-02-01

    Full Text Available The objective of this work was to characterize and quantify the genetic, molecular, and agronomic variability of hull-less barley genotypes, for the selection of parents and identification of genotypes adapted to the irrigated production system in the Brazilian Cerrado. Eighteen hull-less barley accessions were evaluated, and three covered barley accessions served as reference. The characterization was based on 157 RAPD molecular markers and ten agronomic traits. Genetic distance matrices were obtained based on molecular markers and quantitative traits. Graphic grouping and dispersion analyses were performed. Genetic, molecular, and agronomic variability was high among genotypes. Ethiopian accessions were genetically more similar, and the Brazilian ones were genetically more distant. For agronomic traits, two more consistent groupings were obtained, one with the most two-rowed materials, and the other with six-rowed materials. The more diverging materials were the two-rowed CI 13453, CN Cerrado 5, CN Cerrado 1, and CN Cerrado 2. The PI 356466, CN Cerrado 1, PI 370799, and CI 13453 genotypes show agronomic traits of interest and, as genetically different genotypes, they are indicated for crossing, in breeding programs.

  1. Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Byeong-Cheol Ahn

    2016-01-01

    Full Text Available Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term “theranostics” was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging.

  2. Modulation of the sensitive temperature range of fluorescent molecular thermometers based on thermoresponsive polymers.

    Science.gov (United States)

    Uchiyama, Seiichi; Matsumura, Yuriko; de Silva, A Prasanna; Iwai, Kaoru

    2004-03-15

    Fluorescent molecular thermometers based on polymers showing a temperature-induced phase transition and labeled with polarity-sensitive fluorescent benzofurazans are the most sensitive known. Here we show a simple and effective method for modulating the sensitive temperature ranges of fluorescent molecular thermometers based on such temperature-responsive polymers. 4-N-(2-acryloyloxyethyl)-N-methylamino-7-N,N-dimethylaminosulfonyl-2,1,3-benzoxadiazole was adopted as a polarity-sensitive fluorescent benzofurazan, and nine copolymers of two kinds of acrylamide derivative (N-n-propylacrylamide, N-isopropylacrylamide, and/or N-isopropylmethacrylamide) with a small amount of DBD-AE were obtained. The fluorescence intensities of these copolymers in aqueous solution sharply increased with increasing temperature over a small range (6-7 degrees C). In contrast, these fluorescent molecular thermometers differed from one another in the sensitive temperature range (between 20 and 49 degrees C). Moreover, the sensitive temperature ranges were well related to the acrylamide ratios in feed. In addition, the responses from these fluorescent molecular thermometers to the change in temperature were reversible and exactly repeatable during 10 cycles of heating and cooling (relative standard deviation of the fluorescence intensity, 0.44-1.0%).

  3. Pre-examination factors affecting molecular diagnostic test results and interpretation: A case-based approach.

    Science.gov (United States)

    Payne, Deborah A; Baluchova, Katarina; Peoc'h, Katell H; van Schaik, Ron H N; Chan, K C Allen; Maekawa, Masato; Mamotte, Cyril; Russomando, Graciela; Rousseau, François; Ahmad-Nejad, Parviz

    2017-04-01

    Multiple organizations produce guidance documents that provide opportunities to harmonize quality practices for diagnostic testing. The International Organization for Standardization ISO 15189 standard addresses requirements for quality in management and technical aspects of the clinical laboratory. One technical aspect addresses the complexities of the pre-examination phase prior to diagnostic testing. The Committee for Molecular Diagnostics of the International Federation for Clinical Chemistry and Laboratory Medicine (also known as, IFCC C-MD) conducted a survey of international molecular laboratories and determined ISO 15189 to be the most referenced guidance document. In this review, the IFCC C-MD provides case-based examples illustrating the value of select pre-examination processes as these processes relate to molecular diagnostic testing. Case-based examples in infectious disease, oncology, inherited disease and pharmacogenomics address the utility of: 1) providing information to patients and users, 2) designing requisition forms, 3) obtaining informed consent and 4) maintaining sample integrity prior to testing. The pre-examination phase requires extensive and consistent communication between the laboratory, the healthcare provider and the end user. The clinical vignettes presented in this paper illustrate the value of applying select ISO 15189 recommendations for general laboratory to the more specialized area of Molecular Diagnostics. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Molecular dynamics based enhanced sampling of collective variables with very large time steps.

    Science.gov (United States)

    Chen, Pei-Yang; Tuckerman, Mark E

    2018-01-14

    Enhanced sampling techniques that target a set of collective variables and that use molecular dynamics as the driving engine have seen widespread application in the computational molecular sciences as a means to explore the free-energy landscapes of complex systems. The use of molecular dynamics as the fundamental driver of the sampling requires the introduction of a time step whose magnitude is limited by the fastest motions in a system. While standard multiple time-stepping methods allow larger time steps to be employed for the slower and computationally more expensive forces, the maximum achievable increase in time step is limited by resonance phenomena, which inextricably couple fast and slow motions. Recently, we introduced deterministic and stochastic resonance-free multiple time step algorithms for molecular dynamics that solve this resonance problem and allow ten- to twenty-fold gains in the large time step compared to standard multiple time step algorithms [P. Minary et al., Phys. Rev. Lett. 93, 150201 (2004); B. Leimkuhler et al., Mol. Phys. 111, 3579-3594 (2013)]. These methods are based on the imposition of isokinetic constraints that couple the physical system to Nosé-Hoover chains or Nosé-Hoover Langevin schemes. In this paper, we show how to adapt these methods for collective variable-based enhanced sampling techniques, specifically adiabatic free-energy dynamics/temperature-accelerated molecular dynamics, unified free-energy dynamics, and by extension, metadynamics, thus allowing simulations employing these methods to employ similarly very large time steps. The combination of resonance-free multiple time step integrators with free-energy-based enhanced sampling significantly improves the efficiency of conformational exploration.

  5. Molecular dynamics based enhanced sampling of collective variables with very large time steps

    Science.gov (United States)

    Chen, Pei-Yang; Tuckerman, Mark E.

    2018-01-01

    Enhanced sampling techniques that target a set of collective variables and that use molecular dynamics as the driving engine have seen widespread application in the computational molecular sciences as a means to explore the free-energy landscapes of complex systems. The use of molecular dynamics as the fundamental driver of the sampling requires the introduction of a time step whose magnitude is limited by the fastest motions in a system. While standard multiple time-stepping methods allow larger time steps to be employed for the slower and computationally more expensive forces, the maximum achievable increase in time step is limited by resonance phenomena, which inextricably couple fast and slow motions. Recently, we introduced deterministic and stochastic resonance-free multiple time step algorithms for molecular dynamics that solve this resonance problem and allow ten- to twenty-fold gains in the large time step compared to standard multiple time step algorithms [P. Minary et al., Phys. Rev. Lett. 93, 150201 (2004); B. Leimkuhler et al., Mol. Phys. 111, 3579-3594 (2013)]. These methods are based on the imposition of isokinetic constraints that couple the physical system to Nosé-Hoover chains or Nosé-Hoover Langevin schemes. In this paper, we show how to adapt these methods for collective variable-based enhanced sampling techniques, specifically adiabatic free-energy dynamics/temperature-accelerated molecular dynamics, unified free-energy dynamics, and by extension, metadynamics, thus allowing simulations employing these methods to employ similarly very large time steps. The combination of resonance-free multiple time step integrators with free-energy-based enhanced sampling significantly improves the efficiency of conformational exploration.

  6. Contemporary nucleic acid-based molecular techniques for detection, identification, and characterization of Bifidobacterium.

    Science.gov (United States)

    Mianzhi, Yao; Shah, Nagendra P

    2017-03-24

    Bifidobacteria are one of the most important bacterial groups found in the gastrointestinal tract of humans. Medical and food industry researchers have focused on bifidobacteria because of their health-promoting properties. Researchers have historically relied on classic phenotypic approaches (culture and biochemical tests) for detection and identification of bifidobacteria. Those approaches still have values for the identification and detection of some bifidobacterial species, but they are often labor-intensive and time-consuming and can be problematic in differentiating closely related species. Rapid, accurate, and reliable methods for detection, identification, and characterization of bifidobacteria in a mixed bacterial population have become a major challenge. The advent of nucleic acid-based molecular techniques has significantly advanced isolation and detection of bifidobacteria. Diverse nucleic acid-based molecular techniques have been employed, including hybridization, target amplification, and fingerprinting. Certain techniques enable the detection, characterization, and identification at genus-, species-, and strains-levels, whereas others allow typing of species or strains of bifidobacteria. In this review, an overview of methodological principle, technique complexity, and application of various nucleic acid-based molecular techniques for detection, identification, and characterization of bifidobacteria is presented. Advantages and limitations of each technique are discussed, and significant findings based on particular techniques are also highlighted.

  7. An efficient DNA-fueled molecular machine for the discrimination of single-base changes.

    Science.gov (United States)

    Song, Tingjie; Xiao, Shiyan; Yao, Dongbao; Huang, Fujian; Hu, Maobin; Liang, Haojun

    2014-09-17

    A new strategy for single-base polymorphism (SNP) detection based on the assembly of DNA-AuNPs (gold nanoparticles) driven by a DNA-fueled molecular machine, is established and optimized. It is highly efficient, works at room temperature, and is easy to handle. A single-base change on an oligonucleotide strand is unambiguously discriminated for either SNPs or insertions and deletions (indels). The strategy is demonstrated to detect a mutation in the breast cancer gene BRCA1 in homogeneous solution at room temperature. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Molecular electronic devices based on single-walled carbon nanotube electrodes.

    Science.gov (United States)

    Feldman, Alina K; Steigerwald, Michael L; Guo, Xuefeng; Nuckolls, Colin

    2008-12-01

    As the top-down fabrication techniques for silicon-based electronic materials have reached the scale of molecular lengths, researchers have been investigating nanostructured materials to build electronics from individual molecules. Researchers have directed extensive experimental and theoretical efforts toward building functional optoelectronic devices using individual organic molecules and fabricating metal-molecule junctions. Although this method has many advantages, its limitations lead to large disagreement between experimental and theoretical results. This Account describes a new method to create molecular electronic devices, covalently bridging a gap in a single-walled carbon nanotube (SWNT) with an electrically functional molecule. First, we introduce a molecular-scale gap into a nanotube by precise oxidative cutting through a lithographic mask. Now functionalized with carboxylic acids, the ends of the cleaved carbon nanotubes are reconnected with conjugated diamines to give robust diamides. The molecular electronic devices prepared in this fashion can withstand and respond to large environmental changes based on the functional groups in the molecules. For example, with oligoanilines as the molecular bridge, the conductance of the device is sensitive to pH. Similarly, using diarylethylenes as the bridge provides devices that can reversibly switch between conjugated and nonconjugated states. The molecular bridge can perform the dual task of carrying electrical current and sensing/recognition through biological events such as protein/substrate binding and DNA hybridization. The devices based on DNA can measure the difference in electrical properties of complementary and mismatched strands. A well-matched duplex DNA 15-mer in the gap exhibits a 300-fold lower resistance than a duplex with a GT or CA mismatch. This system provides an ultrasensitive way to detect single-nucleotide polymorphisms at the individual molecule level. Restriction enzymes can cleave

  9. 3D-QSAR, molecular docking, and molecular dynamic simulations for prediction of new Hsp90 inhibitors based on isoxazole scaffold.

    Science.gov (United States)

    Abbasi, Maryam; Sadeghi-Aliabadi, Hojjat; Amanlou, Massoud

    2017-05-24

    Heat shock protein 90(Hsp90), as a molecular chaperone, play a crucial role in folding and proper function of many proteins. Hsp90 inhibitors containing isoxazole scaffold are currently being used in the treatment of cancer as tumor suppressers. Here in the present studies, new compounds based on isoxazole scaffold were predicted using a combination of molecular modeling techniques including three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamic (MD) simulations. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were also done. The steric and electrostatic contour map of CoMFA and CoMSIA were created. Hydrophobic, hydrogen bond donor and acceptor of CoMSIA model also were generated, and new compounds were predicted by CoMFA and CoMSIA contour maps. To investigate the binding modes of the predicted compounds in the active site of Hsp90, a molecular docking simulation was carried out. MD simulations were also conducted to evaluate the obtained results on the best predicted compound and the best reported Hsp90 inhibitors in the 3D-QSAR model. Findings indicate that the predicted ligands were stable in the active site of Hsp90.

  10. Development of new molecular markers for the Colletotrichum genus using RetroCl1 sequences.

    Science.gov (United States)

    Dos Santos, Leandro Vieira; de Queiroz, Marisa Vieira; Santana, Mateus Ferreira; Soares, Marcos Antônio; de Barros, Everaldo Gonçalves; de Araújo, Elza Fernandes; Langin, Thierry

    2012-03-01

    A nonautonomous element of 624 bp, called RetroCl1 (Retroelement Colletotrichum lindemuthianum 1), was identified in the plant pathogenic fungus Colletotrichum lindemuthianum. RetroCl1 contains terminal direct repeats (223 bp) that are surrounded by CTAGT sequences. It has a short internal domain of 178 bp and shows characteristics of terminal-repeat retrotransposon in miniature (TRIM) family. We used RetroCl1 sequence to develop molecular markers for the Colletotrichum genus. IRAP (Inter-Retrotransposon Amplified Polymorphism) and REMAP (Retrotransposon-Microsatellite Amplified Polymorphism) markers were used to analyze the genetic diversity of C. lindemuthianum. Fifty-four isolates belonging to different races were used. A total of 45 loci were amplified. The Nei index showed significant differences among the populations divided according to race, indicating that they are structured according to pathotype. No clear correlation between IRAP and REMAP markers with pathogenic characterization was found. C. lindemuthianum has high genetic diversity, and the analysis of molecular variance showed that 51% of variability is found among the populations of different races. The markers were also tested in different Colletotrichum species. In every case, multiple bands were amplified, indicating that these markers can be successfully used in different species belonging to the Colletotrichum genus.

  11. Sputum-Based Molecular Biomarkers for the Early Detection of Lung Cancer: Limitations and Promise

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Connie E. [Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine. 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Tchou-Wong, Kam-Meng; Rom, William N., E-mail: william.rom@nyumc.org [Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine. 462 First Avenue, NBV 7N24, New York, NY 10016 (United States); Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987 (United States)

    2011-07-19

    Lung cancer is the leading cause of cancer deaths, with an overall survival of 15% at five years. Biomarkers that can sensitively and specifically detect lung cancer at early stage are crucial for improving this poor survival rate. Sputum has been the target for the discovery of non-invasive biomarkers for lung cancer because it contains airway epithelial cells, and molecular alterations identified in sputum are most likely to reflect tumor-associated changes or field cancerization caused by smoking in the lung. Sputum-based molecular biomarkers include morphology, allelic imbalance, promoter hypermethylation, gene mutations and, recently, differential miRNA expression. To improve the sensitivity and reproducibility of sputum-based biomarkers, we recommend standardization of processing protocols, bronchial epithelial cell enrichment, and identification of field cancerization biomarkers.

  12. Modeling the relationship between body weight and energy intake: a molecular diffusion-based approach.

    Science.gov (United States)

    Gong, Zhejun; Gong, Zhefeng

    2012-06-29

    Body weight is at least partly controlled by the choices made by a human in response to external stimuli. Changes in body weight are mainly caused by energy intake. By analyzing the mechanisms involved in food intake, we considered that molecular diffusion plays an important role in body weight changes. We propose a model based on Fick's second law of diffusion to simulate the relationship between energy intake and body weight. This model was applied to food intake and body weight data recorded in humans; the model showed a good fit to the experimental data. This model was also effective in predicting future body weight. In conclusion, this model based on molecular diffusion provides a new insight into the body weight mechanisms. This article was reviewed by Dr. Cabral Balreira (nominated by Dr. Peter Olofsson), Prof. Yang Kuang and Dr. Chao Chen.

  13. Sputum-Based Molecular Biomarkers for the Early Detection of Lung Cancer: Limitations and Promise

    Directory of Open Access Journals (Sweden)

    William N. Rom

    2011-07-01

    Full Text Available Lung cancer is the leading cause of cancer deaths, with an overall survival of 15% at five years. Biomarkers that can sensitively and specifically detect lung cancer at early stage are crucial for improving this poor survival rate. Sputum has been the target for the discovery of non-invasive biomarkers for lung cancer because it contains airway epithelial cells, and molecular alterations identified in sputum are most likely to reflect tumor-associated changes or field cancerization caused by smoking in the lung. Sputum-based molecular biomarkers include morphology, allelic imbalance, promoter hypermethylation, gene mutations and, recently, differential miRNA expression. To improve the sensitivity and reproducibility of sputum-based biomarkers, we recommend standardization of processing protocols, bronchial epithelial cell enrichment, and identification of field cancerization biomarkers.

  14. Development of a molecularly imprinted polymer based surface plasmon resonance sensor for theophylline monitoring

    Science.gov (United States)

    Zheng, Rui; Cameron, Brent D.

    2011-03-01

    Molecularly imprinted polymer (MIP) thin films and surface plasmon resonance (SPR) sensing technologies were combined to develop a novel sensing platform for monitoring real-time theophylline concentration, which is a compound of interest in environmental monitoring and a molecular probe for phenotyping certain cytochrome P450 enzymes. The MIPs hydrogel is easy to synthesize and provides shape-selective recognition with high affinity to specific target molecules. Different polymerization formulas were tested and optimized. The influence of the monomer sensitive factors were addressed by SPR. SPR is an evanescent wave optics based sensing technique that is suitable for real-time and label free sensing purposes. Gold nanorods (Au NRs) were uniformly immobilized onto a SPR sensing surface for the construction of a fiber optics based prism-free localized SPR (LSPR) measurement. This technique can be also applied to assess the activities of other small organic molecules by adjusting the polymerization formula, thus, this approach also has many other potential applications.

  15. Extending rule-based methods to model molecular geometry and 3D model resolution.

    Science.gov (United States)

    Hoard, Brittany; Jacobson, Bruna; Manavi, Kasra; Tapia, Lydia

    2016-08-01

    Computational modeling is an important tool for the study of complex biochemical processes associated with cell signaling networks. However, it is challenging to simulate processes that involve hundreds of large molecules due to the high computational cost of such simulations. Rule-based modeling is a method that can be used to simulate these processes with reasonably low computational cost, but traditional rule-based modeling approaches do not include details of molecular geometry. The incorporation of geometry into biochemical models can more accurately capture details of these processes, and may lead to insights into how geometry affects the products that form. Furthermore, geometric rule-based modeling can be used to complement other computational methods that explicitly represent molecular geometry in order to quantify binding site accessibility and steric effects. We propose a novel implementation of rule-based modeling that encodes details of molecular geometry into the rules and binding rates. We demonstrate how rules are constructed according to the molecular curvature. We then perform a study of antigen-antibody aggregation using our proposed method. We simulate the binding of antibody complexes to binding regions of the shrimp allergen Pen a 1 using a previously developed 3D rigid-body Monte Carlo simulation, and we analyze the aggregate sizes. Then, using our novel approach, we optimize a rule-based model according to the geometry of the Pen a 1 molecule and the data from the Monte Carlo simulation. We use the distances between the binding regions of Pen a 1 to optimize the rules and binding rates. We perform this procedure for multiple conformations of Pen a 1 and analyze the impact of conformation and resolution on the optimal rule-based model. We find that the optimized rule-based models provide information about the average steric hindrance between binding regions and the probability that antibodies will bind to these regions. These optimized models

  16. Molecular and Supramolecular Engineering of Thiophene Based Materials for Application in Organic Electronics and Bioimaging

    OpenAIRE

    Di Maria, Francesca Giulia

    2016-01-01

    Thiophene based oligomers and polymers are of great current interest from a scientific and technological point of view for their numerous properties: they are electroactive, fluorescent, chemically stable and allow a great diversity in molecular structures and a fine tuning of functional characteristics. They display ‘plasticity’ in adapting their geometry to the environment in the solid state and in creating supramolecular architectures by self-organization. Moreover, they have the capabilit...

  17. Modeling of Car-Following Required Safe Distance Based on Molecular Dynamics

    OpenAIRE

    Dayi Qu; Xiufeng Chen; Wansan Yang; Xiaohua Bian

    2014-01-01

    In car-following procedure, some distances are reserved between the vehicles, through which drivers can avoid collisions with vehicles before and after them in the same lane and keep a reasonable clearance with lateral vehicles. This paper investigates characters of vehicle operating safety in car following state based on required safe distance. To tackle this problem, we probe into required safe distance and car-following model using molecular dynamics, covering longitudinal and lateral safe...

  18. Analysis of gas-surface scattering models based on computational molecular dynamics

    Science.gov (United States)

    Yakunchikov, A. N.; Kovalev, V. L.; Utyuzhnikov, S. V.

    2012-12-01

    The paper is devoted to the comparison of different scattering models for molecular hydrogen interacting with a graphite surface. Such problems occur in many applications related to gas-solid problems in high-altitude-vehicle thermodynamics and nanotechnologies. The scattering kernels by Maxwell, Epstein and Cercignani-Lampis are analyzed for different conditions. A new analytical scattering kernel based on the combination of Epstein and Cercignani-Lampis models is proposed for better agreement with the trajectory computational results.

  19. The Hairless Stem Phenotype of Cotton (Gossypium barbadense) Is Linked to a Copia-Like Retrotransposon Insertion in a Homeodomain-Leucine Zipper Gene (HD1)

    OpenAIRE

    Ding, Mingquan; Ye, Wuwei; Lin, Lifeng; He, Shae; Du, Xiongming; Chen, Aiqun; Cao, Yuefen; Qin, Yuan; Yang, Fen; Jiang, Yurong; Zhang, Hua; Wang, Xiyin; Paterson, Andrew H.; Rong, Junkang

    2015-01-01

    Cotton (Gossypium) stem trichomes are mostly single cells that arise from stem epidermal cells. In this study, a homeodomain-leucine zipper gene (HD1) was found to cosegregate with the dominant trichome locus previously designated as T1 and mapped to chromosome 6. Characterization of HD1 orthologs revealed that the absence of stem trichomes in modern Gossypium barbadense varieties is linked to a large retrotransposon insertion in the ninth exon, 2565 bp downstream from the initial codon in th...

  20. Phthalocyanine dimerization-based molecular beacons using near-IR fluorescence

    Science.gov (United States)

    Nesterova, Irina V.; Erdem, S. Sibel; Pakhomov, Serhii; Hammer, Robert P.; Soper, Steven A.

    2009-01-01

    Herein we demonstrate the use of a novel dimerization-based molecular beacon (MB) probe consisting of two metallo-phthalocyanine (Pc) fluorophores that use near-IR fluorescence, appropriate for highly specific and sensitive in-vivo and/or in-vitro DNA/RNA detection. Pc’s possess a propensity to form non-fluorescent H-dimers that is utilized as the molecular “off” switch in the closed MB conformation. The “on” switch, which is generated when the solution target binds to the loop of the MB forming the open form, also provides two fluorophores for transduction resulting in a doubling of the extinction coefficient and improving the resulting fluorescence yield compared to a classical single-fluorophore/quencher MB system. In addition, the Pc-based MBs possess high thermal, photo and chemical stabilities that are essential for many highly sensitive applications, such as molecular imaging. The dimer-based MBs were obtained using a simple single-step synthesis procedure and demonstrated excellent quenching efficiencies (98%) as well as a high signal-to-background ratio (~60) exceeding the performance characteristics of many conventionally-available MB probes. PMID:19191492

  1. Feasibility study of molecular memory device based on DNA using methylation to store information

    Science.gov (United States)

    Jiang, Liming; Qiu, Wanzhi; Al-Dirini, Feras; Hossain, Faruque M.; Evans, Robin; Skafidas, Efstratios

    2016-07-01

    DNA, because of its robustness and dense information storage capability, has been proposed as a potential candidate for next-generation storage media. However, encoding information into the DNA sequence requires molecular synthesis technology, which to date is costly and prone to synthesis errors. Reading the DNA strand information is also complex. Ideally, DNA storage will provide methods for modifying stored information. Here, we conduct a feasibility study investigating the use of the DNA 5-methylcytosine (5mC) methylation state as a molecular memory to store information. We propose a new 1-bit memory device and study, based on the density functional theory and non-equilibrium Green's function method, the feasibility of electrically reading the information. Our results show that changes to methylation states lead to changes in the peak of negative differential resistance which can be used to interrogate memory state. Our work demonstrates a new memory concept based on methylation state which can be beneficial in the design of next generation DNA based molecular electronic memory devices.

  2. Molecular phylogeny of Toxoplasmatinae: comparison between inferences based on mitochondrial and apicoplast genetic sequences

    Directory of Open Access Journals (Sweden)

    Michelle Klein Sercundes

    2016-03-01

    Full Text Available Abstract Phylogenies within Toxoplasmatinae have been widely investigated with different molecular markers. Here, we studied molecular phylogenies of the Toxoplasmatinae subfamily based on apicoplast and mitochondrial genes. Partial sequences of apicoplast genes coding for caseinolytic protease (clpC and beta subunit of RNA polymerase (rpoB, and mitochondrial gene coding for cytochrome B (cytB were analyzed. Laboratory-adapted strains of the closely related parasites Sarcocystis falcatula and Sarcocystis neurona were investigated, along with Neospora caninum, Neospora hughesi, Toxoplasma gondii (strains RH, CTG and PTG, Besnoitia akodoni, Hammondia hammondiand two genetically divergent lineages of Hammondia heydorni. The molecular analysis based on organellar genes did not clearly differentiate between N. caninum and N. hughesi, but the two lineages of H. heydorni were confirmed. Slight differences between the strains of S. falcatula and S. neurona were encountered in all markers. In conclusion, congruent phylogenies were inferred from the three different genes and they might be used for screening undescribed sarcocystid parasites in order to ascertain their phylogenetic relationships with organisms of the family Sarcocystidae. The evolutionary studies based on organelar genes confirm that the genusHammondia is paraphyletic. The primers used for amplification of clpC and rpoB were able to amplify genetic sequences of organisms of the genus Sarcocystisand organisms of the subfamily Toxoplasmatinae as well.

  3. Molecular-based screening for perinatal group B streptococcal infection: implications for prevention and therapy.

    Science.gov (United States)

    Emonet, Stéphane; Schrenzel, Jacques; Martinez de Tejada, Begoña

    2013-12-01

    Group B streptococci (GBS) are a leading cause of infectious neonatal morbidity and mortality. Timely and accurate identification of colonized pregnant women is imperative to implement intrapartum antibioprophylaxis (IAP) to reduce the risk of early neonatal sepsis. Current guidelines recommend screening for GBS carriage with vaginal-rectal cultures. However, cultures require 24-72 h, thus precluding their use for intrapartum screening and these are only performed at 35-37 weeks gestation. New rapid molecular-based tests can detect GBS within hours. They have the potential to be used intrapartum and to allow for selective IAP in women carrying GBS. An advantage is that they can sometimes be performed by non-laboratory staff in the labor suite, thus avoiding delays in sample transfers to the microbiology laboratory. Another possible use of molecular-based assays is for the diagnosis of neonatal sepsis, where tests with a short turnaround time and high sensitivity and specificity are crucial. In this situation, the detection of microorganisms once antibiotic therapy has already been started is important, as treatment is started immediately once sepsis is suspected without waiting for microbiological confirmation. In this article, we discuss the state-of-the-art molecular-based tests available for GBS screening during pregnancy, as well as their implications for IAP for the diagnosis and prevention of neonatal sepsis.

  4. Enrichment of low molecular weight serum proteins using acetonitrile precipitation for mass spectrometry based proteomic analysis.

    Science.gov (United States)

    Kay, Richard; Barton, Chris; Ratcliffe, Lucy; Matharoo-Ball, Balwir; Brown, Pamela; Roberts, Jane; Teale, Phil; Creaser, Colin

    2008-10-01

    A rapid acetonitrile (ACN)-based extraction method has been developed that reproducibly depletes high abundance and high molecular weight proteins from serum prior to mass spectrometric analysis. A nanoflow liquid chromatography/tandem mass spectrometry (nano-LC/MS/MS) multiple reaction monitoring (MRM) method for 57 high to medium abundance serum proteins was used to characterise the ACN-depleted fraction after tryptic digestion. Of the 57 targeted proteins 29 were detected and albumin, the most abundant protein in serum and plasma, was identified as the 20th most abundant protein in the extract. The combination of ACN depletion and one-dimensional nano-LC/MS/MS enabled the detection of the low abundance serum protein, insulin-like growth factor-I (IGF-I), which has a serum concentration in the region of 100 ng/mL. One-dimensional sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS-PAGE) analysis of the depleted serum showed no bands corresponding to proteins of molecular mass over 75 kDa after extraction, demonstrating the efficiency of the method for the depletion of high molecular weight proteins. Total protein analysis of the ACN extracts showed that approximately 99.6% of all protein is removed from the serum. The ACN-depletion strategy offers a viable alternative to the immunochemistry-based protein-depletion techniques commonly used for removing high abundance proteins from serum prior to MS-based proteomic analyses.

  5. Feasibility study of molecular memory device based on DNA using methylation to store information

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Liming; Al-Dirini, Feras [Department of Electrical and Electronic Engineering, The University of Melbourne, Parkville 3010 (Australia); Center for Neural Engineering (CfNE), The University of Melbourne, Carlton 3053 (Australia); National ICT Australia, The University of Melbourne, Parkville 3010 (Australia); Qiu, Wanzhi; Skafidas, Efstratios, E-mail: sskaf@unimelb.edu.au [Department of Electrical and Electronic Engineering, The University of Melbourne, Parkville 3010 (Australia); Center for Neural Engineering (CfNE), The University of Melbourne, Carlton 3053 (Australia); Hossain, Faruque M. [Center for Neural Engineering (CfNE), The University of Melbourne, Carlton 3053 (Australia); Evans, Robin [Department of Electrical and Electronic Engineering, The University of Melbourne, Parkville 3010 (Australia)

    2016-07-14

    DNA, because of its robustness and dense information storage capability, has been proposed as a potential candidate for next-generation storage media. However, encoding information into the DNA sequence requires molecular synthesis technology, which to date is costly and prone to synthesis errors. Reading the DNA strand information is also complex. Ideally, DNA storage will provide methods for modifying stored information. Here, we conduct a feasibility study investigating the use of the DNA 5-methylcytosine (5mC) methylation state as a molecular memory to store information. We propose a new 1-bit memory device and study, based on the density functional theory and non-equilibrium Green's function method, the feasibility of electrically reading the information. Our results show that changes to methylation states lead to changes in the peak of negative differential resistance which can be used to interrogate memory state. Our work demonstrates a new memory concept based on methylation state which can be beneficial in the design of next generation DNA based molecular electronic memory devices.

  6. A molecular receptor targeted, hydroxyapatite nanocrystal based multi-modal contrast agent.

    Science.gov (United States)

    Ashokan, Anusha; Menon, Deepthy; Nair, Shantikumar; Koyakutty, Manzoor

    2010-03-01

    Multi-modal molecular imaging can significantly improve the potential of non-invasive medical diagnosis by combining basic anatomical descriptions with in-depth phenotypic characteristics of disease. Contrast agents with multifunctional properties that can sense and enhance the signature of specific molecular markers, together with high biocompatibility are essential for combinatorial molecular imaging approaches. Here, we report a multi-modal contrast agent based on hydroxyapatite nanocrystals (nHAp), which is engineered to show simultaneous contrast enhancement for three major molecular imaging techniques such as magnetic resonance imaging (MRI), X-ray imaging and near-infrared (NIR) fluorescence imaging. Monodispersed nHAp crystals of average size approximately 30 nm and hexagonal crystal structure were in situ doped with multiple rare-earth impurities by a surfactant-free, aqueous wet-chemical method at 100 degrees C. Doping of nHAp with Eu(3+) (3 at%) resulted bright near-infrared fluorescence (700 nm) due to efficient (5)D(0)-(7)F(4) electronic transition and co-doping with Gd(3+) resulted enhanced paramagnetic longitudinal relaxivity (r(1) approximately 12 mM(-1) s(-1)) suitable for T(1) weighted MR imaging together with approximately 80% X-ray attenuation suitable for X-ray contrast imaging. Capability of MF-nHAp to specifically target and enhance the signature of molecular receptors (folate) in cancer cells was realized by carbodiimide grafting of cell-membrane receptor ligand folic acid (FA) on MF-nHAp surface aminized with dendrigraft polymer, polyethyleneimine (PEI). The FA-PEI-MF-nHAp conjugates showed specific aggregation on FR(+ve) cells while leaving the negative control cells untouched. Nanotoxicity evaluation of this multifunctional nHAp carried out on primary human endothelial cells (HUVEC), normal mouse lung fibroblast cell line (L929), human nasopharyngeal carcinoma (KB) and human lung cancer cell line (A549) revealed no apparent toxicity even

  7. Synchrotron based mass spectrometry to investigate the molecular properties of mineral-organic associations

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Suet Yi; Kleber, Markus; Takahashi, Lynelle K.; Nico, Peter; Keiluweit, Marco; Ahmed, Musahid

    2013-04-01

    Soil organic matter (OM) is important because its decay drives life processes in the biosphere. Analysis of organic compounds in geological systems is difficult because of their intimate association with mineral surfaces. To date there is no procedure capable of quantitatively separating organic from mineral phases without creating artifacts or mass loss. Therefore, analytical techniques that can (a) generate information about both organic and mineral phases simultaneously and (b) allow the examination of predetermined high-interest regions of the sample as opposed to conventional bulk analytical techniques are valuable. Laser Desorption Synchrotron Postionization (synchrotron-LDPI) mass spectrometry is introduced as a novel analytical tool to characterize the molecular properties of organic compounds in mineral-organic samples from terrestrial systems, and it is demonstrated that when combined with Secondary Ion Mass Spectrometry (SIMS), can provide complementary information on mineral composition. Mass spectrometry along a decomposition gradient in density fractions, verifies the consistency of our results with bulk analytical techniques. We further demonstrate that by changing laser and photoionization energies, variations in molecular stability of organic compounds associated with mineral surfaces can be determined. The combination of synchrotron-LDPI and SIMS shows that the energetic conditions involved in desorption and ionization of organic matter may be a greater determinant of mass spectral signatures than the inherent molecular structure of the organic compounds investigated. The latter has implications for molecular models of natural organic matter that are based on mass spectrometric information.

  8. Logic integration of mRNA signals by an RNAi-based molecular computer.

    Science.gov (United States)

    Xie, Zhen; Liu, Siyuan John; Bleris, Leonidas; Benenson, Yaakov

    2010-05-01

    Synthetic in vivo molecular 'computers' could rewire biological processes by establishing programmable, non-native pathways between molecular signals and biological responses. Multiple molecular computer prototypes have been shown to work in simple buffered solutions. Many of those prototypes were made of DNA strands and performed computations using cycles of annealing-digestion or strand displacement. We have previously introduced RNA interference (RNAi)-based computing as a way of implementing complex molecular logic in vivo. Because it also relies on nucleic acids for its operation, RNAi computing could benefit from the tools developed for DNA systems. However, these tools must be harnessed to produce bioactive components and be adapted for harsh operating environments that reflect in vivo conditions. In a step toward this goal, we report the construction and implementation of biosensors that 'transduce' mRNA levels into bioactive, small interfering RNA molecules via RNA strand exchange in a cell-free Drosophila embryo lysate, a step beyond simple buffered environments. We further integrate the sensors with our RNAi 'computational' module to evaluate two-input logic functions on mRNA concentrations. Our results show how RNA strand exchange can expand the utility of RNAi computing and point toward the possibility of using strand exchange in a native biological setting.

  9. A Combined Experimental and Molecular Dynamics Study of Iodide-Based Ionic Liquid and Water Mixtures.

    Science.gov (United States)

    Nickerson, Stella D; Nofen, Elizabeth M; Chen, Haobo; Ngan, Miranda; Shindel, Benjamin; Yu, Hongyu; Dai, Lenore L

    2015-07-16

    Iodide-based ionic liquids have been widely employed as iodide sources in electrolytes for applications utilizing the triiodide/iodide redox couple. While adding a low-viscosity solvent such as water to ionic liquids can greatly enhance their usefulness, mixtures of highly viscous iodide-containing ILs with water have never been studied. This paper investigates, for the first time, mixtures of water and the ionic liquid 1-butyl-3-methylimidazolium iodide ([BMIM][I]) through a combined experimental and molecular dynamics study. The density, melting point, viscosity, and conductivity of these mixtures were measured by experiment. The composition region below 50% water by mole was found to differ dramatically from the region above 50% water, with trends in density and melting point differing before and after that point. Water was found to have a profound effect on viscosity and conductivity of the IL, and the effect of hydrogen bonding was discussed. Molecular dynamics simulations representing the same mixture compositions were performed. Molecular ordering was observed, as were changes in this ordering corresponding to water content. Molecular ordering was related to the experimentally measured mixture properties, providing a possible explanation for the two distinct composition regions identified by experiment.

  10. Genetic Diversity of Some Sweet Cherry Cultivars Based on Molecular Markers

    Directory of Open Access Journals (Sweden)

    Ioana Virginia Berindean

    2016-11-01

    Full Text Available Sweet cherry (Prunus avium L., originated around the Caspian and Black Sea, is an important fruit tree species of economic interest, and hence, breeding and conservation are requested (. Genetic analysis at the molecular level can be used effectively to study molecular polymorphism existing between intraspecific and interspecific tree species and phylogenetic relationships between them and their hybrids. The purpose of this study was to characterize and determine genetic relationships among the sweet cherry native genotypes belonging to Fruit Research & Development Station Bistrita, Romania, using RAPD markers. To eliminate the existence of possible synonyms from national romanian collection, we collect four Van cultivars, from four different national collection. For molecular analysis of the 16 varieties of sweet cherry were considered 13 RAPD primers selected from the literature. They were later used to determine the genetic variability at the molecular level using PAST program, and the dendrogram was generated based on Jaccard’s genetic distance. The dendrogram constructed by PAST software. The quantity and quality of the DNA obtained was suitable to achieve PCR amplification step. Only seven out of the 13 RAPD primers have generate polymorphic bands. The rest of seven were monomorphics. The most polymorphic primer was OPB10 which generated 11 bands from which 100% were polymorphic.Seven RAPD primers generated a high level of polymorphism which allowed to divide these cherry varieties into two groups according to their genetic geographical origin and the pedigree.

  11. Genetic variability among elite popcorn lines based on molecular and morphoagronomic characteristics.

    Science.gov (United States)

    Dos Santos, J F; Mangolin, C A; Machado, M F P S; Scapim, C A; Giordani, W; Gonçalves, L S A

    2017-06-29

    Knowledge of genetic diversity among genotypes and relationships among elite lines is of great importance for the development of breeding programs. Therefore, the objective of this study was to evaluate genetic variability based on the morphoagronomic and molecular characterization of 18 elite popcorn (Zea mays var. everta) lines to be used by Universidade Estadual de Maringá breeding programs. We used 31 microsatellite primers (widely distributed in the genome), and 16 morphological descriptors (including the resistance to maize white spot, common rust, polysora rust of maize, cercospora and leaf blights). The molecular data revealed variability among the lines, which were divided into four groups that were partially concordant with unweighted pair group method with arithmetic mean (UPMGA) and Bayesian clusters. The lines G3, G4, G11, and G13 exhibited favorable morphological characters and low disease incidence rates. The four groups were confirmed using the Gower distance in the UPGMA cluster; however, there was no association with the dissimilarity patterns obtained using the molecular data. The absence of a correlation suggests that both characterizations (morphoagronomic and molecular) are important for discriminating among elite popcorn lines.

  12. The preferred nucleotide contexts of the AID/APOBEC cytidine deaminases have differential effects when mutating retrotransposon and virus sequences compared to host genes.

    Directory of Open Access Journals (Sweden)

    Jeffrey Chen

    2017-03-01

    Full Text Available The AID / APOBEC genes are a family of cytidine deaminases that have evolved in vertebrates, and particularly mammals, to mutate RNA and DNA at distinct preferred nucleotide contexts (or "hotspots" on foreign genomes such as viruses and retrotransposons. These enzymes play a pivotal role in intrinsic immunity defense mechanisms, often deleteriously mutating invading retroviruses or retrotransposons and, in the case of AID, changing antibody sequences to drive affinity maturation. We investigate the strength of various hotspots on their known biological targets by evaluating the potential impact of mutations on the DNA coding sequences of these targets, and compare these results to hypothetical hotspots that did not evolve. We find that the existing AID / APOBEC hotspots have a large impact on retrotransposons and non-mammalian viruses while having a much smaller effect on vital mammalian genes, suggesting co-evolution with AID / APOBECs may have had an impact on the genomes of the viruses we analyzed. We determine that GC content appears to be a significant, but not sole, factor in resistance to deaminase activity. We discuss possible mechanisms AID and APOBEC viral targets have adopted to escape the impacts of deamination activity, including changing the GC content of the genome.

  13. Digital logic circuit based on two component molecular systems of BSA and salen

    Science.gov (United States)

    Hai-Bin, Lin; Feng, Chen; Hong-Xu, Guo

    2018-02-01

    A new fluorescent molecular probe 1 was designed and constructed by combining bovine serum albumin (BSA) and N,N‧-bis(salicylidene)ethylenediamine (salen). Stimulated by Zn2 +, tris, or EDTAH2Na2, the distance between BSA and salen was regulated, which was accompanied by an obvious change in the fluorescence intensity at 350 or 445 nm based on Förster resonance energy transfer. Moreover, based on the encoding binary digits in these inputs and outputs applying positive logic conventions, a monomolecular circuit integrating one OR, three NOT, and three YES gates, was successfully achieved.

  14. Fast screening of ketamine in biological samples based on molecularly imprinted photonic hydrogels

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Liang [Department of Forensic Science, People' s Public Security University of China, Beijing (China); Meng, Pinjia, E-mail: mengpinjia@163.com [Department of Forensic Science, People' s Public Security University of China, Beijing (China); Zhang, Qingqing; Wang, Yanji [Department of Forensic Science, People' s Public Security University of China, Beijing (China)

    2013-04-10

    Graphical abstract: A novel label-free colorimetric chemosensor: with the increase in the concentration of ketamine, the Bragg diffraction peak of MIPHs gradually shifted to the longer wavelength region. Accompanying the peak shift, the color change of MIPHs was also observed obviously: from green to red. Highlights: ► We developed the label-free colorimetric MIPHs for handy and fast screening of ketamine. ► The obvious color change of MIPHs was observed upon ketamine. ► The MIPHs exhibited good sensing abilities in an aqueous environment. ► The sensing mechanisms of the water-compatible MIPHs were investigated. ► The MIPHs were employed to screening ketamine in real biological samples. -- Abstract: A novel label-free colorimetric chemosensor was developed for handy and fast screening of ketamine with high sensitivity and specificity based on molecularly imprinted photonic hydrogels (MIPHs) that combined the colloidal-crystal with molecular imprinting technique. The unique inverse opal arrays with a thin polymer wall in which the imprinted nanocavities of ketamine moleculars distributed allowed high sensitive, quick responsive, specific detection of the target analyte, and good regenerating ability in an aqueous environment. Due to the hierarchical inverse opal structural characteristics, the specific ketamine molecular recognition process can induce obvious swelling of the MIPHs to be directly transferred into visually perceptible optical signal (change in color) which can be detected by the naked eye through Bragg diffractive shifts of ordered macroporous arrays. In order to enhance the recognition ability in aqueous environments, the MIPHs were designed as water-compatible and synthesized in a water–methanol system. The molecular recognition mechanisms were investigated. The proposed MIPHs were successfully employed to screen trace level ketamine in human urine and saliva samples, exhibiting high sensitivity, rapid response, and specificity in the

  15. Development and Integration of an SSR-Based Molecular Identity Database into Sugarcane Breeding Program

    Directory of Open Access Journals (Sweden)

    Yong-Bao Pan

    2016-04-01

    Full Text Available Sugarcane breeding is very difficult and it takes 12 to 14 years to develop a new cultivar for commercial production. This is because sugarcane varieties are highly polyploid, inter-specific hybrids with 100 to 130 chromosomes that may vary across geographical areas. Other obstacles/constraints include the small size of flowers that may not synchronize but may self-pollinate, difficulty in distinguishing hybrids from self progenies, extreme (G × E interactive effect, and potential variety mis-identification during vegetative propagation and varietal exchange. To help cane breeders circumvent these constraints, a simple sequence repeats (SSR-based molecular identity database has been developed at the United States Department of Agriculture-Agricultural Research Service, Sugarcane Research Unit in Houma, LA. Since 2005, approximately 2000 molecular identities have been constructed for clones of sugarcane and related Saccharum species that cover geographical areas including Argentina, Australia, Bangladesh, China, Colombia, India, Mexico, Pakistan, South Africa, Thailand, USA (Louisiana, Florida, Texas, and Hawaii, and Venezuela. The molecular identity database is updated annually and has been utilized to: (1 provide molecular descriptors to newly registered cultivars; (2 identify in a timely fashion any mislabeled or unidentifiable clones from cross parents and field evaluation plots; (3 develop de novo clones of energy cane with S. spontaneum cytoplasm; (4 provide clone-specific fingerprint information for assessing cross quality and paternity of polycross; (5 determine genetic relatedness of parental clones; (6 select F1 hybrids from (elite × wild or (wild × elite crosses; and (7 investigate the inheritance of SSR markers in sugarcane. The integration of the molecular identity database into the sugarcane breeding program may improve the overall efficacy of cultivar development and commercialization.

  16. Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies.

    Science.gov (United States)

    Islam, Md Ataul; Pillay, Tahir S

    2017-08-01

    In this study, we searched for potential DNA GyrB inhibitors using pharmacophore-based virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors was collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptors and hydrophobicity regions were critical for inhibition of DNA GyrB. Good statistical results of the pharmacophore model indicated that the model was robust in nature. Virtual screening of molecular databases revealed three molecules as potential antimycobacterial agents. The final screened promising compounds were evaluated in molecular docking and molecular dynamics simulation studies. In the molecular dynamics studies, RMSD and RMSF values undoubtedly explained that the screened compounds formed stable complexes with DNA GyrB. Therefore, it can be concluded that the compounds identified may have potential for the treatment of TB. © 2017 John Wiley & Sons A/S.

  17. Initiating heavy-atom-based phasing by multi-dimensional molecular replacement.

    Science.gov (United States)

    Pedersen, Bjørn Panyella; Gourdon, Pontus; Liu, Xiangyu; Karlsen, Jesper Lykkegaard; Nissen, Poul

    2016-03-01

    To obtain an electron-density map from a macromolecular crystal the phase problem needs to be solved, which often involves the use of heavy-atom derivative crystals and concomitant heavy-atom substructure determination. This is typically performed by dual-space methods, direct methods or Patterson-based approaches, which however may fail when only poorly diffracting derivative crystals are available. This is often the case for, for example, membrane proteins. Here, an approach for heavy-atom site identification based on a molecular-replacement parameter matrix (MRPM) is presented. It involves an n-dimensional search to test a wide spectrum of molecular-replacement parameters, such as different data sets and search models with different conformations. Results are scored by the ability to identify heavy-atom positions from anomalous difference Fourier maps. The strategy was successfully applied in the determination of a membrane-protein structure, the copper-transporting P-type ATPase CopA, when other methods had failed to determine the heavy-atom substructure. MRPM is well suited to proteins undergoing large conformational changes where multiple search models should be considered, and it enables the identification of weak but correct molecular-replacement solutions with maximum contrast to prime experimental phasing efforts.

  18. Electron induced conformational changes of an imine-based molecular switch on a Au(111) surface

    Energy Technology Data Exchange (ETDEWEB)

    Lotze, Christian; Henningsen, Nils; Franke, Katharina; Schulze, Gunnar; Pascual, Jose Ignacio [Inst. f. Experimentalphysik, Freie Universitaet Berlin (Germany); Luo, Ying; Haag, Rainer [Inst. f. Organische Chemie, Freie Universitaet Berlin (Germany)

    2009-07-01

    Azobenzene-based molecules exhibit a cis-trans configurational photoisomerisation in solution. Recently, the adsorption properties of azobenzene derivatives have been investigated on different metal surfaces in order to explore the possible changes in the film properties induced by external stimuli. In azobenzene, the diazo-bridge is a key group for the isomerization process. Its interaction with a metal surface is dominated through the N lone-pair electrons, which reduces the efficiency of the conformational change. In order to reduce the molecule-surface interaction, we explore an alternative molecular architecture by substituting the diazo-bridge (-N=N-) of azobenzene by an imine-group (-N=CH-). We have investigated the imine-based compound para-carboxyl-di-benzene-imine (PCI) adsorbed on a Au(111) surface. The carboxylic terminations mediates the formation of strongly bonded molecular dimers, which align in ordered rows preferentially following the fcc regions of the Au(111) herringbone reconstruction. Low temperature scanning tunneling microscopy was used to induce conformational changes between trans and cis state of individual molecules in a molecular monolayer.

  19. Characterization of nanoparticle-based contrast agents for molecular magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Shan, Liang, E-mail: shanli@mail.nih.gov; Chopra, Arvind; Leung, Kam; Eckelman, William C. [National Institutes of Health, Molecular Imaging and Contrast Agent Database, National Center for Biotechnology Information, National Library of Medicine (United States); Menkens, Anne E. [National Institutes of Health, National Cancer Institute (United States)

    2012-09-15

    The development of molecular imaging agents is currently undergoing a dramatic expansion. As of October 2011, {approx}4,800 newly developed agents have been synthesized and characterized in vitro and in animal models of human disease. Despite this rapid progress, the transfer of these agents to clinical practice is rather slow. To address this issue, the National Institutes of Health launched the Molecular Imaging and Contrast Agents Database (MICAD) in 2005 to provide freely accessible online information regarding molecular imaging probes and contrast agents for the imaging community. While compiling information regarding imaging agents published in peer-reviewed journals, the MICAD editors have observed that some important information regarding the characterization of a contrast agent is not consistently reported. This makes it difficult for investigators to evaluate and meta-analyze data generated from different studies of imaging agents, especially for the agents based on nanoparticles. This article is intended to serve as a guideline for new investigators for the characterization of preclinical studies performed with nanoparticle-based MRI contrast agents. The common characterization parameters are summarized into seven categories: contrast agent designation, physicochemical properties, magnetic properties, in vitro studies, animal studies, MRI studies, and toxicity. Although no single set of parameters is suitable to define the properties of the various types of contrast agents, it is essential to ensure that these agents meet certain quality control parameters at the preclinical stage, so that they can be used without delay for clinical studies.

  20. Molecular junctions based on SAMs of cruciform oligo(phenylene ethynylene)s

    DEFF Research Database (Denmark)

    Wei, Zhongming; Li, Tao; Jennum, Karsten Stein

    2012-01-01

    Cruciform oligo(phenylene ethynylene)s (OPEs) with an extended tetrathiafulvalene (TTF) donor moiety (OPE5-TTF and OPE3-TTF) and their simple analogues (OPE5-S and OPE3) without conjugated substituents were used to form high quality self-assembled monolayers (SAMs) on ultra-flat gold substrates....... Molecular junctions based on these SAMs were investigated using conducting-probe atomic force microscopy (CP-AFM). The TTF substituent changes the molecular orbital energy levels and decreases the HOMO-LUMO energy gap, resulting in a nine-fold increase in conductance for both TTF cruciform OPEs compared...... to the unsubstituted analogues. The difference in electrical transport properties of the SAMs was reproduced by the theoretical transport calculations for the single molecules....

  1. Photoinduced Pedalo-Type Motion in an Azodicarboxamide-Based Molecular Switch.

    Science.gov (United States)

    Amirjalayer, Saeed; Martinez-Cuezva, Alberto; Berna, Jose; Woutersen, Sander; Buma, Wybren Jan

    2017-11-15

    Well-defined structural changes of molecular units that can be triggered by light are crucial for the development of photoactive functional materials. Herein, we report on a novel switch that has azodicarboxamide as its photo-triggerable element. Time-resolved UV-pump/IR probe spectroscopy in combination with quantum-chemical calculations shows that the azodicarboxamide functionality, in contrast to other azo-based chromophores, does not undergo trans-cis photoisomerization. Instead, a photoinduced pedalo-type motion occurs, which because of its volume-conserving properties enables the design of functional molecular systems with controllable motion in a confined space. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

  2. Sequence-Specific β-Peptide Synthesis by a Rotaxane-Based Molecular Machine.

    Science.gov (United States)

    De Bo, Guillaume; Gall, Malcolm A Y; Kitching, Matthew O; Kuschel, Sonja; Leigh, David A; Tetlow, Daniel J; Ward, John W

    2017-08-09

    We report on the synthesis and operation of a three-barrier, rotaxane-based, artificial molecular machine capable of sequence-specific β-homo (β 3 ) peptide synthesis. The machine utilizes nonproteinogenic β 3 -amino acids, a class of amino acids not generally accepted by the ribosome, particularly consecutively. Successful operation of the machine via native chemical ligation (NCL) demonstrates that even challenging 15- and 19-membered ligation transition states are suitable for information translation using this artificial molecular machine. The peptide-bond-forming catalyst region can be removed from the transcribed peptide by peptidases, artificial and biomachines working in concert to generate a product that cannot be made by either machine alone.

  3. Molecular characterisation of lumpy skin disease virus and sheeppox virus based on P32 gene

    Directory of Open Access Journals (Sweden)

    P.M.A.Rashid

    2017-06-01

    Full Text Available Lumpy skin disease virus (LSDV and sheeppox virus (SPV have a considerable economic impact on the cattle and small ruminant industry. They are listed in group A of contagious disease by the World Organization for Animal Health (OIE. This study addressed molecular characterisation of first LSDV outbreak and an endemic SPV in Kurdistan region of Iraq based on P32 gene. The results indicated that P32 gene can be successfully used for diagnosis of LSDV. The phylogenic and molecular analysis showed that there may be a new LSDV isolate circulating in Kurdistan which uniquely shared the same characteristic amino acid sequence with SPV and GPV, leucine at amino acid position 51 in P32 gene as well as few genetically distinct SPV causing pox disease in Kurdistan sheep. This study provided sequence information of P32 gene for several LSDV isolates, which positively affects the epidemiological study of Capripoxvirus

  4. Self-consistent field theory based molecular dynamics with linear system-size scaling

    Energy Technology Data Exchange (ETDEWEB)

    Richters, Dorothee [Institute of Mathematics and Center for Computational Sciences, Johannes Gutenberg University Mainz, Staudinger Weg 9, D-55128 Mainz (Germany); Kühne, Thomas D., E-mail: kuehne@uni-mainz.de [Institute of Physical Chemistry and Center for Computational Sciences, Johannes Gutenberg University Mainz, Staudinger Weg 7, D-55128 Mainz (Germany); Technical and Macromolecular Chemistry, University of Paderborn, Warburger Str. 100, D-33098 Paderborn (Germany)

    2014-04-07

    We present an improved field-theoretic approach to the grand-canonical potential suitable for linear scaling molecular dynamics simulations using forces from self-consistent electronic structure calculations. It is based on an exact decomposition of the grand canonical potential for independent fermions and does neither rely on the ability to localize the orbitals nor that the Hamilton operator is well-conditioned. Hence, this scheme enables highly accurate all-electron linear scaling calculations even for metallic systems. The inherent energy drift of Born-Oppenheimer molecular dynamics simulations, arising from an incomplete convergence of the self-consistent field cycle, is circumvented by means of a properly modified Langevin equation. The predictive power of the present approach is illustrated using the example of liquid methane under extreme conditions.

  5. Recent Advances of Activatable Molecular Probes Based on Semiconducting Polymer Nanoparticles in Sensing and Imaging

    Science.gov (United States)

    Lyu, Yan

    2017-01-01

    Molecular probes that change their signals in response to the target of interest have a critical role in fundamental biology and medicine. Semiconducting polymer nanoparticles (SPNs) have recently emerged as a new generation of purely organic photonic nanoagents with desirable properties for biological applications. In particular, tunable optical properties of SPNs allow them to be developed into photoluminescence, chemiluminescence, and photoacoustic probes, wherein SPNs usually serve as the energy donor and internal reference for luminescence and photoacoustic probes, respectively. Moreover, facile surface modification and intraparticle engineering provide the versatility to make them responsive to various biologically and pathologically important substances and indexes including small‐molecule mediators, proteins, pH and temperature. This article focuses on recent advances in the development of SPN‐based activatable molecular probes for sensing and imaging. The designs and applications of these probes are discussed in details, and the present challenges to further advance them into life science are also analyzed. PMID:28638783

  6. Friction in carborane-based molecular rotors driven by gas flow or electric field: classical molecular dynamics.

    Science.gov (United States)

    Prokop, Alexandr; Vacek, Jaroslav; Michl, Josef

    2012-03-27

    Friction in molecular rotors is examined by classical molecular dynamics simulations for grid-mounted azimuthal dipolar molecular rotors, whose rotation is either allowed to decay freely or is driven at GHz frequencies by a flow of rare gas or by a rotating electric field. The rotating parts (rotators) are propeller-shaped. Their two to six blades consist of condensed aromatic rings and are attached to a deltahedral carborane hub, whose antipodal carbons carry [n]staffane axles mounted on a square molecular grid. The dynamic friction constant η has been derived in several independent ways with similar results. Analysis of free rotation decay yields η as a continuous exponentially decreasing function of rotor frequency. The calculated dependence of friction torque on frequency resembles the classical macroscopic Stribeck curve. Its relation to rotational potential energy barriers and the key role of the rate of intramolecular vibrational redistribution (IVR) of energy and angular momentum from rotator rotation to other modes are considered in two limiting regimes. (i) In the strongly overdamped regime, rotation is much slower than IVR, and effective friction can be expressed through potential barriers to rotation. (ii) In the strongly underdamped regime, rotation is much faster than IVR, whose rate then determines friction. © 2012 American Chemical Society

  7. Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

    Science.gov (United States)

    Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

    2017-06-01

    Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. NONLINEAR OPTICAL MOLECULAR CRYSTAL BASED ON 2,6-DIAMINOPYRIDINE: SYNTHESIS AND CHARACTERIZATION

    Directory of Open Access Journals (Sweden)

    I. M. Pavlovetc

    2014-05-01

    Full Text Available The paper deals with investigation of a new nonlinear optical material based on nonlinear optical chromophore (4-Nitrophenol and aminopyridine (2,6-Diaminopyridine. Calculation results are presented for molecular packing in the crystalline compound, based on the given components. According to these results the finite material must have a noncentrosymmetric lattice, which determines the presence of the second order nonlinear optical response. Investigations carried out in this work confirm these calculations. Results of experiments are given describing the co-crystallization of these components and the following re-crystallization of the obtained material. In order to get a monocrystal form, the optimal conditions for the synthesis of molecular crystals based on these components are determined. Sufficiently large homogeneous crystals are obtained, that gave the possibility to record their spectra in the visible and near infrared parts of the spectrum, to determine their nonlinear optical properties and the level of homogeneity. Their optical (optical transmission and optical laser damage threshold and nonlinear optical properties are presented. For observation and measurement of the nonlinear optical properties an installation was built which implements the comparative method for measurements of nonlinear optical properties. A potassium titanyl oxide phosphate crystal was used as a sample for comparison. Results are given for the conversion efficiency of the primary laser radiation in the second optical harmonic relative to the signal obtained on the potassium titanyl oxide phosphate crystal. Obtained results show that the molecular co-crystal based on 2,6-Diaminopyridine is a promising nonlinear optical material for generating the second optical harmonic on the Nd: YAG laser (532 nm.

  9. Structural and molecular docking studies of biologically active mercaptopyrimidine Schiff bases

    Science.gov (United States)

    Kirubavathy, S. Jone; Velmurugan, R.; Karvembu, R.; Bhuvanesh, N. S. P.; Enoch, Israel V. M. V.; Selvakumar, P. Mosae; Premnath, D.; Chitra, S.

    2017-01-01

    Novel Schiff bases derived from the treatment of mercapto-diamino pyrimidine with two different aldehydes are characterized using elemental analysis, single crystal X-ray diffraction and 1H NMR spectroscopy. The pharmacological action of the synthesized compounds viz., antimicrobial, anticancer and antitubercular activities is studied. The Schiff bases show a very good activity against various test pathogens. DNA and β-CD binding interactions of the compounds are studied using UV-Visible absorption and fluorescence spectral measurements. The binding constants of the compounds towards β-CD are in the order of 103 to 104. Molecular docking is done using MOE program on the 3D structure of the enzymes, viz., human thymidylate synthase complexed with dump and raltitrex, candida albicans N-myristoyltransferasepeptidic inhibitor, catalytic domain of protein kinase pKnb from mycobacterium tuberculosis in complex with mitoxantrone, pare, topoisomerase atpase inhibitor, E. coli and lactobacillus casdihydrofolatereductase. The MIC/IC50 values of the Schiff bases are compared with the glide scores from the molecular docking studies. The number of hydrogen bonding interactions between the Schiff bases and amino acid residues are also reported.

  10. High performance computing for three-dimensional agent-based molecular models.

    Science.gov (United States)

    Pérez-Rodríguez, G; Pérez-Pérez, M; Fdez-Riverola, F; Lourenço, A

    2016-07-01

    Agent-based simulations are increasingly popular in exploring and understanding cellular systems, but the natural complexity of these systems and the desire to grasp different modelling levels demand cost-effective simulation strategies and tools. In this context, the present paper introduces novel sequential and distributed approaches for the three-dimensional agent-based simulation of individual molecules in cellular events. These approaches are able to describe the dimensions and position of the molecules with high accuracy and thus, study the critical effect of spatial distribution on cellular events. Moreover, two of the approaches allow multi-thread high performance simulations, distributing the three-dimensional model in a platform independent and computationally efficient way. Evaluation addressed the reproduction of molecular scenarios and different scalability aspects of agent creation and agent interaction. The three approaches simulate common biophysical and biochemical laws faithfully. The distributed approaches show improved performance when dealing with large agent populations while the sequential approach is better suited for small to medium size agent populations. Overall, the main new contribution of the approaches is the ability to simulate three-dimensional agent-based models at the molecular level with reduced implementation effort and moderate-level computational capacity. Since these approaches have a generic design, they have the major potential of being used in any event-driven agent-based tool. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. A novel approach for differentiating pathogenic and non-pathogenic Leptospira based on molecular fingerprinting.

    Science.gov (United States)

    Xiao, Di; Zhang, Cuicai; Zhang, Huifang; Li, Xiuwen; Jiang, Xiugao; Zhang, Jianzhong

    2015-04-24

    Leptospirosis is a worldwide, deadly zoonotic disease. Pathogenic Leptospira causes leptospirosis. The rapid and accurate identification of pathogenic and non-pathogenic Leptospira strains is essential for appropriate therapeutic management and timely intervention for infection control. The molecular fingerprint is a simple and rapid alternative tool for microorganisms identification, which is based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In this study, molecular fingerprint was performed to identify pathogenic strains of Leptospira. Phylogenetic analysis based on 16S rRNA gene sequences was used as the reference method. In addition, a label-free technique was used to reveal the different proteins of pathogenic or non-pathogenic Leptospira. A reference database was constructed using 30 Leptospira strains, including 16 pathogenic strains and 14 non-pathogenic strains. Two super reference spectra that were associated with pathogenicity were established. Overall, 33 Leptospira strains were used for validation, and 32 of 33 Leptospira strains could be identified on the species level and all the 33 could be classified as pathogenic or non-pathogenic. The super reference spectra and the major spectra projection (MSP) dendrogram correctly categorized the Leptospira strains into pathogenic and non-pathogenic groups, which was consistent with the 16S rRNA reference methods. Between the pathogenic and non-pathogenic strains, 108 proteins were differentially expressed. molecular fingerprint is an alternative to conventional molecular identification and can rapidly distinguish between pathogenic and non-pathogenic Leptospira strains. Therefore, molecular fingerprint may play an important role in the clinical diagnosis, treatment, surveillance, and tracking of epidemic outbreaks of leptospirosis. Leptospirosis is a worldwide zoonosis that is caused by spirochetes of the genus Leptospira. Leptospirosis is a serious zoonotic

  12. Potent Human Telomerase Inhibitors: Molecular Dynamic Simulations, Multiple Pharmacophore-Based Virtual Screening, and Biochemical Assays.

    Science.gov (United States)

    Shirgahi Talari, Faezeh; Bagherzadeh, Kowsar; Golestanian, Sahand; Jarstfer, Michael; Amanlou, Massoud

    2015-12-28

    Telomere maintenance is a universal cancer hallmark, and small molecules that disrupt telomere maintenance generally have anticancer properties. Since the vast majority of cancer cells utilize telomerase activity for telomere maintenance, the enzyme has been considered as an anticancer drug target. Recently, rational design of telomerase inhibitors was made possible by the determination of high resolution structures of the catalytic telomerase subunit from a beetle and subsequent molecular modeling of the human telomerase complex. A hybrid strategy including docking, pharmacophore-based virtual screening, and molecular dynamics simulations (MDS) were used to identify new human telomerase inhibitors. Docking methodology was applied to investigate the ssDNA telomeric sequence and two well-known human telomerase inhibitors' (BIBR1532 and MST-312) modes of interactions with hTERT TEN domain. Subsequently molecular dynamic simulations were performed to monitor and compare hTERT TEN domain, TEN-ssDNA, TEN-BIBR1532, TEN-MST-312, and TEN-ssDNA-BIBR1532 behavior in a dynamic environment. Pharmacophore models were generated considering the inhibitors manner in the TEN domain anchor site. These exploratory studies identified several new potent inhibitors whose IC50 values were generated experimentally in a low micromolar range with the aid of biochemical assays, including both the direct telomerase and the telomeric repeat amplification protocol (TRAP) assays. The results suggest that the current models of human telomerase are useful templates for rational inhibitor design.

  13. Systematic studies of Australian stipoid grasses (Austrostipa based on micro-morphological and molecular characteristics

    Directory of Open Access Journals (Sweden)

    BETTY MAULIYA BUSTAM

    2010-01-01

    Full Text Available Bustam BM (2010 Systematic studies of Australian stipoid grasses (Austrostipa based on micro-morphological and molecular characteristics. Biodiversitas 11: 9-14. This research is one of many studies on stipoid grasses organized by the International Stipeae Working Group (ISWG. This research tested the subgeneric classification of Austrostipa proposed by Jacobs and Everett (1996 and tested how informative the micro morphological characters used. Data were collected from herbarium specimens of 36 species (33 species of Austrostipa, two species of Hesperostipa and one species of Anemanthele at Royal Botanic Gardens, Sydney. Twenty eight micro morphological characters were used. The data were collected from both adaxial and abaxial surfaces of leaves, and from the lemma epidermis using a scanning electron microscope (SEM. ISWG provided the molecular data. Parsimony analysis and a distance method (Unweighteic Pair Group with Arithmatic Mean: UPGMA were used to analyze mico morphological and molecular data separately. Only UPGMA analysis was used to analyze the combined data. The results support the monophyly of Austrostipa. However, there is a little support for the subgeneric classification of Austrostipa proposed by Jacobs and Everett (1996, other than for the consistent recognition of Falcatae. The characters for comparisons between genera are too homoplasious at this level and do not contain enough information for analyses at subgeneric level, a problem apparently shared with the DNA sequences.

  14. Effect of molecular conformation on the mechanofluorochromic properties based on DDIF

    Science.gov (United States)

    Mai, Runsheng; Peng, Huojun; Meng, Yuying; Chang, Xinyue; Jiang, Yue; Gao, Jinwei; Zhou, Guofu; Liu, Jun-ming

    2017-07-01

    Mechanofluorochromic (MFC) materials are smart materials in that their absorption and/or emission can respond to mechanical stimuli. They have received much attention recently. Although there have been several new material systems designed, little work has been done regarding the influence of molecular conformation on MFC properties. Herein, to disclose the relationship between molecular conformation and MFC properties, two molecules based on a 6, 12-Dihydro-6, 12-diaza-indeno[1,2-b]fluorine (DDIF) building block with thienyl linker, BDDIF-Th and BDDIF-BTh, have been designed and synthesized. Optical and electrochemical properties have been studied by UV-vis spectrometer and cyclic voltammetry measurements. Weak aggregation-induced emission (AIE) phenomena were obtained in the tetrahydrofuran (THF)/water solution. MFC behaviors suggest that BDDIF-Th is more sensible to the external mechanical forces than BDDIF-BTh. The color change could be attributed to the appearance of new emission peak instead of a bathochromic or hypsochromic effect. Theoretical calculations reveal that MFC performance is highly related to the molecular conformation, meaning that the BDDIF-BTh with perpendicular conformation is more difficult to flatten than the comparatively planar BDDIF-Th.

  15. Electrochemical cholesterol sensor based on carbon nanotube@molecularly imprinted polymer modified ceramic carbon electrode.

    Science.gov (United States)

    Tong, Yuejin; Li, Haidong; Guan, Huaimin; Zhao, Jianming; Majeed, Saadat; Anjum, Saima; Liang, Feng; Xu, Guobao

    2013-09-15

    A monolithic molecular imprinting sensor based on ceramic carbon electrode (CCE) has been reported. The sensor can be renewed simply by smoothing. It was fabricated by thoroughly mixing multiwalled carbon nanotube@molecularly imprinted polymer (MWCNT@MIP), graphite powder, and silicon alkoxide, and then packing the resulting complex mixture of components firmly into the electrode cavity of a Teflon sleeve. The incorporated MWCNT@MIP in CCEs functioned as a recognition element for cholesterol determination. The MWCNT@MIP-CCEs were tested in the presence or absence of cholesterol by cyclic voltammetry and linear sweep voltammetry. The cholesterol sensor has excellent sensitivity with a linear range of 10-300nM and a detection limit of 1nM (S/N=3). The monolithic molecular imprinting sensor exhibits good stability, high sensitivity, and user-friendly reusability for cholesterol determination. This study shows that CCE is a promising matrix for MIP sensors. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Mass-spectrometry-based molecular characterization of extracellular vesicles: lipidomics and proteomics.

    Science.gov (United States)

    Kreimer, Simion; Belov, Arseniy M; Ghiran, Ionita; Murthy, Shashi K; Frank, David A; Ivanov, Alexander R

    2015-06-05

    This review discusses extracellular vesicles (EVs), which are submicron-scale, anuclear, phospholipid bilayer membrane enclosed vesicles that contain lipids, metabolites, proteins, and RNA (micro and messenger). They are shed from many, if not all, cell types and are present in biological fluids and conditioned cell culture media. The term EV, as coined by the International Society of Extracellular Vesicles (ISEV), encompasses exosomes (30-100 nm in diameter), microparticles (100-1000 nm), apoptotic blebs, and other EV subsets. EVs have been implicated in cell-cell communication, coagulation, inflammation, immune response modulation, and disease progression. Multiple studies report that EV secretion from disease-affected cells contributes to disease progression, e.g., tumor niche formation and cancer metastasis. EVs are attractive sources of biomarkers due to their biological relevance and relatively noninvasive accessibility from a range of physiological fluids. This review is focused on the molecular profiling of the protein and lipid constituents of EVs, with emphasis on mass-spectrometry-based "omic" analytical techniques. The challenges in the purification and molecular characterization of EVs, including contamination of isolates and limitations in sample quantities, are discussed along with possible solutions. Finally, the review discusses the limited but growing investigation of post-translational modifications of EV proteins and potential strategies for future in-depth molecular characterization of EVs.

  17. Molecular polypyridine-based metal complexes as catalysts for the reduction of CO2.

    Science.gov (United States)

    Elgrishi, Noémie; Chambers, Matthew B; Wang, Xia; Fontecave, Marc

    2017-02-06

    Polypyridyl transition metal complexes represent one of the more thoroughly studied classes of molecular catalysts towards CO2 reduction to date. Initial reports in the 1980s began with an emphasis on 2nd and 3rd row late transition metals, but more recently the focus has shifted towards earlier metals and base metals. Polypyridyl platforms have proven quite versatile and amenable to studying various parameters that govern product distribution for CO2 reduction. However, open questions remain regarding the key mechanistic steps that govern product selectivity and efficiency. Polypyridyl complexes have also been immobilized through a variety of methods to afford active catalytic materials for CO2 reductions. While still an emerging field, materials incorporating molecular catalysts represent a promising strategy for electrochemical and photoelectrochemical devices capable of CO2 reduction. In general, this class of compounds remains the most promising for the continued development of molecular systems for CO2 reduction and an inspiration for the design of related non-polypyridyl catalysts.

  18. Computational prediction and experimental selectivity coefficients for hydroxyzine and cetirizine molecularly imprinted polymer based potentiometric sensors

    Energy Technology Data Exchange (ETDEWEB)

    Azimi, Abolfazl; Javanbakht, Mehran, E-mail: mehranjavanbakht@gmail.com

    2014-02-17

    Graphical abstract: -- Highlights: •Possible configurations template/monomer complexes were designed and optimized. •Effect of the electrostatic force on the selectivity of MIPs was investigated. •A correlation between selectivity of sensors and a charge distribution was obtained. -- Abstract: In spite of the increasing usages number of molecularly imprinted polymers (MIPs) in many scientific applications, the theoretical aspects of participating intra molecular forces are not fully understood. This work investigates effects of the electrostatic force, the Mulliken charge and the role of cavity's backbone atoms on the selectivity of MIPs. Moreover, charge distribution, which is a computational parameter, was proposed for the prediction of the selectivity coefficients of MIP-based sensors. In the computational approaches and experimental study, methacrylic acid (MAA) was chosen as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the cross linker for hydroxyzine and cetirizine imprinted polymers. Ab initio, DFT B3LYP method was carried out on molecular optimization. With regard to results obtained from molecules optimization and hydrogen bonding properties, possible configurations of 1:n (n ≤ 5) template/monomer complexes were designed and optimized. The binding energy for each complex in gas phase was calculated. Depending on the most stable configuration, hydroxyzine and cetirizine imprinted polymer models were designed. The calculations including the porogen were also investigated. The theoretical charge distributions for the template and some potential interfering molecules were calculated. The results showed a correlation between the selectivity coefficients and the theoretical charge distributions. The results surprisingly show that charge distribution based model was able to predict the selectivity coefficients of MIP based potentiometric sensors.

  19. Comparison of molecular and extract-based allergy diagnostics with multiplex and singleplex analysis.

    Science.gov (United States)

    Huss-Marp, Johannes; Gutermuth, Jan; Schäffner, Ina; Darsow, Ulf; Pfab, Florian; Brockow, Knut; Ring, Johannes; Behrendt, Heidrun; Jakob, Thilo; Ahlgrim, Christoph

    ImmunoCAP ISAC 112, is a commercially available molecular allergy IgE multiplex test. Data on the comparison of this rather novel test with extract-based as well as molecular ImmunoCAP singleplex IgE tests is missing. To perform a comparison between the ISAC multiplex IgE assay and the ImmunoCAP singleplex test results. Serum samples of 101 adults with grass pollen allergy were analysed for sIgE to 112 allergenic molecules represented on the ISAC test as well as to common atopy-related extract-based allergy tests with the ImmunoCAP System (house dust mite [d1], cat [e1], dog [e5], cow's milk [f2], hen's egg [f1], hazelnut [f17], celery [f85], Alternaria alternate [m6], as well as pollen from birch [t3], hazel [t4], mugwort [w6], and ragweed [w1]). Subsequently statistical analysis was performed with the Spearman rank correlation test and the Clopper-Pearson method in order to compare the ISAC multiplex results with the sIgE singleplex results. The positive percent agreements (PPA) and negative percent agreement (NPA) of corresponding allergens between the ISAC sIgE test and the extract-based singleplex ImmunoCAP results at cutoff 0.1 kUA/l varied between 60-100 % for PPA and 78-97 % for NPA. When taking into account corresponding allergens molecular testing with the ISAC multiplex test correlates well with ImmunoCAP singleplex results.

  20. Analysis of molecular expression patterns and integration with other knowledge bases using probabilistic Bayesian network models

    Energy Technology Data Exchange (ETDEWEB)

    Moler, Edward J.; Mian, I.S.

    2000-03-01

    How can molecular expression experiments be interpreted with greater than ten to the fourth measurements per chip? How can one get the most quantitative information possible from the experimental data with good confidence? These are important questions whose solutions require an interdisciplinary combination of molecular and cellular biology, computer science, statistics, and complex systems analysis. The explosion of data from microarray techniques present the problem of interpreting the experiments. The availability of large-scale knowledge bases provide the opportunity to maximize the information extracted from these experiments. We have developed new methods of discovering biological function, metabolic pathways, and regulatory networks from these data and knowledge bases. These techniques are applicable to analyses for biomedical engineering, clinical, and fundamental cell and molecular biology studies. Our approach uses probabilistic, computational methods that give quantitative interpretations of data in a biological context. We have selected Bayesian statistical models with graphical network representations as a framework for our methods. As a first step, we use a nave Bayesian classifier to identify statistically significant patterns in gene expression data. We have developed methods which allow us to (a) characterize which genes or experiments distinguish each class from the others, (b) cross-index the resulting classes with other databases to assess biological meaning of the classes, and (c) display a gross overview of cellular dynamics. We have developed a number of visualization tools to convey the results. We report here our methods of classification and our first attempts at integrating the data and other knowledge bases together with new visualization tools. We demonstrate the utility of these methods and tools by analysis of a series of yeast cDNA microarray data and to a set of cancerous/normal sample data from colon cancer patients. We discuss

  1. Hybridogenesis and a potential case of R2 non-LTR retrotransposon horizontal transmission in Bacillus stick insects (Insecta Phasmida).

    Science.gov (United States)

    Scavariello, Claudia; Luchetti, Andrea; Martoni, Francesco; Bonandin, Livia; Mantovani, Barbara

    2017-02-06

    Horizontal transfer (HT) is an event in which the genetic material is transferred from one species to another, even if distantly related, and it has been demonstrated as a possible essential part of the lifecycle of transposable elements (TEs). However, previous studies on the non-LTR R2 retrotransposon, a metazoan-wide distributed element, indicated its vertical transmission since the Radiata-Bilateria split. Here we present the first possible instances of R2 HT in stick insects of the genus Bacillus (Phasmida). Six R2 elements were characterized in the strictly bisexual subspecies B. grandii grandii, B. grandii benazzii and B. grandii maretimi and in the obligatory parthenogenetic taxon B. atticus. These elements were compared with those previously retrieved in the facultative parthenogenetic species B. rossius. Phylogenetic inconsistencies between element and host taxa, and age versus divergence analyses agree and support at least two HT events. These HT events can be explained by taking into consideration the complex Bacillus reproductive biology, which includes also hybridogenesis, gynogenesis and androgenesis. Through these non-canonical reproductive modes, R2 elements may have been transferred between Bacillus genomes. Our data suggest, therefore, a possible role of hybridization for TEs survival and the consequent reshaping of involved genomes.

  2. Mutation in a primate-conserved retrotransposon reveals a noncoding RNA as a mediator of infantile encephalopathy

    Science.gov (United States)

    Cartault, François; Munier, Patrick; Benko, Edgar; Desguerre, Isabelle; Hanein, Sylvain; Boddaert, Nathalie; Bandiera, Simonetta; Vellayoudom, Jeanine; Krejbich-Trotot, Pascale; Bintner, Marc; Hoarau, Jean-Jacques; Girard, Muriel; Génin, Emmanuelle; de Lonlay, Pascale; Fourmaintraux, Alain; Naville, Magali; Rodriguez, Diana; Feingold, Josué; Renouil, Michel; Munnich, Arnold; Westhof, Eric; Fähling, Michael; Lyonnet, Stanislas; Henrion-Caude, Alexandra

    2012-01-01

    The human genome is densely populated with transposons and transposon-like repetitive elements. Although the impact of these transposons and elements on human genome evolution is recognized, the significance of subtle variations in their sequence remains mostly unexplored. Here we report homozygosity mapping of an infantile neurodegenerative disease locus in a genetic isolate. Complete DNA sequencing of the 400-kb linkage locus revealed a point mutation in a primate-specific retrotransposon that was transcribed as part of a unique noncoding RNA, which was expressed in the brain. In vitro knockdown of this RNA increased neuronal apoptosis, consistent with the inappropriate dosage of this RNA in vivo and with the phenotype. Moreover, structural analysis of the sequence revealed a small RNA-like hairpin that was consistent with the putative gain of a functional site when mutated. We show here that a mutation in a unique transposable element-containing RNA is associated with lethal encephalopathy, and we suggest that RNAs that harbor evolutionarily recent repetitive elements may play important roles in human brain development. PMID:22411793

  3. Insertion of an SVA-E retrotransposon into the CASP8 gene is associated with protection against prostate cancer.

    Science.gov (United States)

    Stacey, Simon N; Kehr, Birte; Gudmundsson, Julius; Zink, Florian; Jonasdottir, Aslaug; Gudjonsson, Sigurjon A; Sigurdsson, Asgeir; Halldorsson, Bjarni V; Agnarsson, Bjarni A; Benediktsdottir, Kristrun R; Aben, Katja K H; Vermeulen, Sita H; Cremers, Ruben G; Panadero, Angeles; Helfand, Brian T; Cooper, Phillip R; Donovan, Jenny L; Hamdy, Freddie C; Jinga, Viorel; Okamoto, Ichiro; Jonasson, Jon G; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M; Masson, Gisli; Magnusson, Olafur T; Iordache, Paul D; Helgason, Agnar; Helgason, Hannes; Sulem, Patrick; Gudbjartsson, Daniel F; Kong, Augustine; Jonsson, Eirikur; Barkardottir, Rosa B; Einarsson, Gudmundur V; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Mates, Ioan N; Neal, David E; Catalona, William J; Mayordomo, José I; Kiemeney, Lambertus A; Thorleifsson, Gudmar; Stefansson, Kari

    2016-03-01

    Transcriptional and splicing anomalies have been observed in intron 8 of the CASP8 gene (encoding procaspase-8) in association with cutaneous basal-cell carcinoma (BCC) and linked to a germline SNP rs700635. Here, we show that the rs700635[C] allele, which is associated with increased risk of BCC and breast cancer, is protective against prostate cancer [odds ratio (OR) = 0.91, P = 1.0 × 10(-6)]. rs700635[C] is also associated with failures to correctly splice out CASP8 intron 8 in breast and prostate tumours and in corresponding normal tissues. Investigation of rs700635[C] carriers revealed that they have a human-specific short interspersed element-variable number of tandem repeat-Alu (SINE-VNTR-Alu), subfamily-E retrotransposon (SVA-E) inserted into CASP8 intron 8. The SVA-E shows evidence of prior activity, because it has transduced some CASP8 sequences during subsequent retrotransposition events. Whole-genome sequence (WGS) data were used to tag the SVA-E with a surrogate SNP rs1035142[T] (r(2) = 0.999), which showed associations with both the splicing anomalies (P = 6.5 × 10(-32)) and with protection against prostate cancer (OR = 0.91, P = 3.8 × 10(-7)). © The Author 2016. Published by Oxford University Press.

  4. A 5-methylcytosine DNA glycosylase/lyase demethylates the retrotransposon Tos17 and promotes its transposition in rice

    KAUST Repository

    La, Honggui

    2011-09-06

    DNA 5-methylcytosine (5-meC) is an important epigenetic mark for transcriptional gene silencing in many eukaryotes. In Arabidopsis, 5-meC DNA glycosylase/lyases actively remove 5-meC to counter-act transcriptional gene silencing in a locus-specific manner, and have been suggested to maintain the expression of transposons. However, it is unclear whether plant DNA demethylases can promote the transposition of transposons. Here we report the functional characterization of the DNA glycosylase/lyase DNG701 in rice. DNG701 encodes a large (1,812 amino acid residues) DNA glycosylase domain protein. Recombinant DNG701 protein showed 5-meC DNA glycosylase and lyase activities in vitro. Knockout or knockdown of DNG701 in rice plants led to DNA hypermethylation and reduced expression of the retrotransposon Tos17. Tos17 showed less transposition in calli derived from dng701 knockout mutant seeds compared with that in wild-type calli. Overexpression of DNG701 in both rice calli and transgenic plants substantially reduced DNA methylation levels of Tos17 and enhanced its expression. The overexpression also led to more frequent transposition of Tos17 in calli. Our results demonstrate that rice DNG701 is a 5-meC DNA glycosylase/lyase responsible for the demethylation of Tos17 and this DNA demethylase plays a critical role in promoting Tos17 transposition in rice calli.

  5. A retrotransposon in an HKT1 family sodium transporter causes variation of leaf Na+ exclusion and salt tolerance in maize.

    Science.gov (United States)

    Zhang, Ming; Cao, Yibo; Wang, Zhiping; Wang, Zhi-Qiang; Shi, Junpeng; Liang, Xiaoyan; Song, Weibin; Chen, Qijun; Lai, Jinsheng; Jiang, Caifu

    2017-11-15

    Soil salinity is one of several major abiotic stresses that constrain maize productivity worldwide. An improved understanding of salt-tolerance mechanisms will thus enhance the breeding of salt-tolerant maize and boost productivity. Previous studies have indicated that the maintenance of leaf Na+ concentration is essential for maize salt tolerance, and the difference in leaf Na+ exclusion has previously been associated with variation in salt tolerance between maize varieties. Here, we report the identification and functional characterization of a maize salt-tolerance quantitative trait locus (QTL), Zea mays Na+ Content1 (ZmNC1), which encodes an HKT-type transporter (designated as ZmHKT1). We show that a natural ZmHKT1 loss-of-function allele containing a retrotransposon insertion confers increased accumulation of Na+ in leaves, and salt hypersensitivity. We next show that ZmHKT1 encodes a plasma membrane-localized Na+ -selective transporter, and is preferentially expressed in root stele (including the parenchyma cells surrounding the xylem vessels). We also show that loss of ZmHKT1 function increases xylem sap Na+ concentration and causes increased root-to-shoot Na+ delivery, indicating that ZmHKT1 promotes leaf Na+ exclusion and salt tolerance by withdrawing Na+ from the xylem sap. We conclude that ZmHKT1 is a major salt-tolerance QTL and identifies an important new gene target in breeding for improved maize salt tolerance. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  6. Efficient L1 regularization-based reconstruction for fluorescent molecular tomography using restarted nonlinear conjugate gradient.

    Science.gov (United States)

    Shi, Junwei; Zhang, Bin; Liu, Fei; Luo, Jianwen; Bai, Jing

    2013-09-15

    For the ill-posed fluorescent molecular tomography (FMT) inverse problem, the L1 regularization can protect the high-frequency information like edges while effectively reduce the image noise. However, the state-of-the-art L1 regularization-based algorithms for FMT reconstruction are expensive in memory, especially for large-scale problems. An efficient L1 regularization-based reconstruction algorithm based on nonlinear conjugate gradient with restarted strategy is proposed to increase the computational speed with low memory consumption. The reconstruction results from phantom experiments demonstrate that the proposed algorithm can obtain high spatial resolution and high signal-to-noise ratio, as well as high localization accuracy for fluorescence targets.

  7. Film-based Sensors with Piezoresistive Molecular Conductors as Active Components Strain Damage and Thermal Regeneration

    Directory of Open Access Journals (Sweden)

    Elena Laukhina

    2011-02-01

    Full Text Available The article is addressed to the development of flexible all-organic bi layer (BL film-based sensors being capable of measuring strain as a well-defined electrical signal in a wide range of elongations and temperature. The purpose was achieved by covering polycarbonate films with the polycrystalline layer of a high piezoresistive organic molecular conductor. To determine restrictions for sensor applications, the effect of monoaxial strain on the resistance and texture of the sensing layers of BL films was studied. The experiments have shown that the maximum strain before fracture is about 1 %. A thermal regeneration of the sensing layer of the BL film-based sensors that were damaged by cyclic load is also described. These sensors are able to take the place of conventional metal-based strain and pressure gages in low cost innovative controlling and monitoring technologies.

  8. Cell adhesion monitoring of human induced pluripotent stem cell based on intrinsic molecular charges

    Science.gov (United States)

    Sugimoto, Haruyo; Sakata, Toshiya

    2014-01-01

    We have shown a simple way for real-time, quantitative, non-invasive, and non-label monitoring of human induced pluripotent stem (iPS) cell adhesion by use of a biologically coupled-gate field effect transistor (bio-FET), which is based on detection of molecular charges at cell membrane. The electrical behavior revealed quantitatively the electrical contacts of integrin-receptor at the cell membrane with RGDS peptide immobilized at the gate sensing surface, because that binding site was based on cationic α chain of integrin. The platform based on the bio-FET would provide substantial information to evaluate cell/material bio-interface and elucidate biding mechanism of adhesion molecules, which could not be interpreted by microscopic observation.

  9. Sinocurculigo, a new genus of Hypoxidaceae from China based on molecular and morphological evidence.

    Directory of Open Access Journals (Sweden)

    Ke-Wei Liu

    Full Text Available BACKGROUND: The monocot family Hypoxidaceae consists of nine genera with nearly 200 species. They occur mostly in the Southern Hemisphere with only a few species in the Northern Hemisphere, of which three genera, Hypoxis, Molineria, and Curculigo, with eight species are distributed in China. Recently, we have found a hypoxid-like plant in China that is quite different in floral structure from any of the three genera and even of the known taxa in Hypoxidaceae. METHODOLOGY/PRINCIPAL FINDINGS: In addition to morphological analysis, we performed maximum parsimony, maximum likelihood, and Bayesian inference analyses based on fragments of the chloroplast matK and rbcL genes of 60 taxa in 12 families representing all major clades of the Hypoxidaceae alliance. Results showed that Hypoxidaceae is monophyletic and and that the new plant belongs to it, forming a distinct clade within the family Hypoxidaceae as a sister of Molineria. Phylogeny of the Hypoxidaceae family was constructed based on a combined matrix of the chloroplast rbcL, trnS-G, and trnL-F regions of 59 taxa in Hypoxidaceae and its alliance. Findings of the molecular investigation is consistent with those of the morphological analysis. CONCLUSIONS/SIGNIFICANCE: Based on the results of our molecular and morphological analyses in the present study, we propose a new genus, Sinocurculigo.

  10. Mass Spectrometry-based Approaches to Understand the Molecular Basis of Memory

    Directory of Open Access Journals (Sweden)

    Arthur Henriques Pontes

    2016-10-01

    Full Text Available The central nervous system is responsible for an array of cognitive functions such as memory, learning, language and attention. These processes tend to take place in distinct brain regions; yet, they need to be integrated to give rise to adaptive or meaningful behavior. Since cognitive processes result from underlying cellular and molecular changes, genomics and transcriptomics assays have been applied to human and animal models to understand such events. Nevertheless, genes and RNAs are not the end products of most biological functions. In order to gain further insights toward the understanding of brain processes, the field of proteomics has been of increasing importance in the past years. Advancements in liquid chromatography-tandem mass spectrometry (LC-MS/MS have enable the identification and quantification of thousand of proteins with high accuracy and sensitivity, fostering a revolution in the neurosciences. Herein, we review the molecular bases of explicit memory in the hippocampus. We outline the principles of mass spectrometry (MS-based proteomics, highlighting the use of this analytical tool to study memory formation. In addition, we discuss MS-based targeted approaches as the future of protein analysis.

  11. Mass Spectrometry-based Approaches to Understand the Molecular Basis of Memory

    Science.gov (United States)

    Pontes, Arthur; de Sousa, Marcelo

    2016-10-01

    The central nervous system is responsible for an array of cognitive functions such as memory, learning, language and attention. These processes tend to take place in distinct brain regions; yet, they need to be integrated to give rise to adaptive or meaningful behavior. Since cognitive processes result from underlying cellular and molecular changes, genomics and transcriptomics assays have been applied to human and animal models to understand such events. Nevertheless, genes and RNAs are not the end products of most biological functions. In order to gain further insights toward the understanding of brain processes, the field of proteomics has been of increasing importance in the past years. Advancements in liquid chromatography-tandem mass spectrometry (LC-MS/MS) have enable the identification and quantification of thousand of proteins with high accuracy and sensitivity, fostering a revolution in the neurosciences. Herein, we review the molecular bases of explicit memory in the hippocampus. We outline the principles of mass spectrometry (MS)-based proteomics, highlighting the use of this analytical tool to study memory formation. In addition, we discuss MS-based targeted approaches as the future of protein analysis.

  12. Liposome Formulation of Fullerene-Based Molecular Diagnostic and Therapeutic Agents

    Science.gov (United States)

    Zhou, Zhiguo

    2013-01-01

    Fullerene medicine is a new but rapidly growing research subject. Fullerene has a number of desired structural, physical and chemical properties to be adapted for biological use including antioxidants, anti-aging, anti-inflammation, photodynamic therapy, drug delivery, and magnetic resonance imaging contrast agents. Chemical functionalization of fullerenes has led to several interesting compounds with very promising preclinical efficacy, pharmacokinetic and safety data. However, there is no clinical evaluation or human use except in fullerene-based cosmetic products for human skincare. This article summarizes recent advances in liposome formulation of fullerenes for the use in therapeutics and molecular imaging. PMID:24300561

  13. Molecular Solid EOS based on Quasi-Harmonic Oscillator approximation for phonons

    Energy Technology Data Exchange (ETDEWEB)

    Menikoff, Ralph [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2014-09-02

    A complete equation of state (EOS) for a molecular solid is derived utilizing a Helmholtz free energy. Assuming that the solid is nonconducting, phonon excitations dominate the specific heat. Phonons are approximated as independent quasi-harmonic oscillators with vibrational frequencies depending on the specific volume. The model is suitable for calibrating an EOS based on isothermal compression data and infrared/Raman spectroscopy data from high pressure measurements utilizing a diamond anvil cell. In contrast to a Mie-Gruneisen EOS developed for an atomic solid, the specific heat and Gruneisen coefficient depend on both density and temperature.

  14. Reconstruction for limited-projection fluorescence molecular tomography based on projected restarted conjugate gradient normal residual.

    Science.gov (United States)

    Cao, Xu; Zhang, Bin; Liu, Fei; Wang, Xin; Bai, Jing

    2011-12-01

    Limited-projection fluorescence molecular tomography (FMT) can greatly reduce the acquisition time, which is suitable for resolving fast biology processes in vivo but suffers from severe ill-posedness because of the reconstruction using only limited projections. To overcome the severe ill-posedness, we report a reconstruction method based on the projected restarted conjugate gradient normal residual. The reconstruction results of two phantom experiments demonstrate that the proposed method is feasible for limited-projection FMT. © 2011 Optical Society of America

  15. Glucose optical fibre sensor based on a luminescent molecularly imprinted polymer

    Science.gov (United States)

    Elosua, C.; Wren, S. P.; Sun, T.; Arregui, F. J.; Grattan, Kenneth T. V.

    2015-09-01

    An optrode able to detect glucose dissolved in water has been implemented. The device is based on the luminescence emission of a Molecularly Imprinted Polymer synthesized specifically for glucose detection, therefore its intensity changes in presence of glucose. This sensing material is attached onto a cleaved ended polymer-clad optical fibre and it is excited by light via 1x2 fibre coupler. The reflected fluorescence signal increases when it is immersed into glucose solutions and recovers to the baseline when it is dipped in ultrapure water. This reversible behaviour indicates the measurement repeatability of using such a glucose sensor.

  16. A facile molecularly imprinted polymer-based fluorometric assay for detection of histamine

    DEFF Research Database (Denmark)

    Feng, Xiaotong; Ashley, Jon; Zhou, Tongchang

    2018-01-01

    Histamine is a biogenic amine naturally present in many body cells. It is also a contaminant that is mostly found in spoiled food. The consumption of foods containing high levels of histamine may lead to an allergy-like food poisoning. Analytical methods that can routinely screen histamine are thus...... urgently needed. In this paper, we developed a facile and cost-effective molecularly imprinted polymer (MIP)-based fluorometric assay to directly quantify histamine. Histamine-specific MIP nanoparticles (nanoMIPs) were synthesized using a modified solid-phase synthesis method. They were then immobilized...

  17. Bases moleculares das hemoglobinas variantes e talassemias no Rio Grande do Sul

    OpenAIRE

    Sandrine Comparsi Wagner

    2010-01-01

    Hemoglobinopatias são alterações nos genes das globinas que determinam hemoglobinas variantes e/ou talassemias, com manifestações clínicas variáveis em seus portadores. Estudos realizados no Brasil mostram alta prevalência de heterozigotos para Hb S e Hb C, além das talassemias α e β. Considerando-se essa alta frequência populacional e a constituição étnica do sul do país, este trabalho teve como objetivo determinar as bases moleculares das hemoglobinas variantes e talassemias no Rio Grande d...

  18. NaviCell: a web-based environment for navigation, curation and maintenance of large molecular interaction maps.

    Science.gov (United States)

    Kuperstein, Inna; Cohen, David P A; Pook, Stuart; Viara, Eric; Calzone, Laurence; Barillot, Emmanuel; Zinovyev, Andrei

    2013-10-07

    Molecular biology knowledge can be formalized and systematically represented in a computer-readable form as a comprehensive map of molecular interactions. There exist an increasing number of maps of molecular interactions containing detailed and step-wise description of various cell mechanisms. It is difficult to explore these large maps, to organize discussion of their content and to maintain them. Several efforts were recently made to combine these capabilities together in one environment, and NaviCell is one of them. NaviCell is a web-based environment for exploiting large maps of molecular interactions, created in CellDesigner, allowing their easy exploration, curation and maintenance. It is characterized by a combination of three essential features: (1) efficient map browsing based on Google Maps; (2) semantic zooming for viewing different levels of details or of abstraction of the map and (3) integrated web-based blog for collecting community feedback. NaviCell can be easily used by experts in the field of molecular biology for studying molecular entities of interest in the context of signaling pathways and crosstalk between pathways within a global signaling network. NaviCell allows both exploration of detailed molecular mechanisms represented on the map and a more abstract view of the map up to a top-level modular representation. NaviCell greatly facilitates curation, maintenance and updating the comprehensive maps of molecular interactions in an interactive and user-friendly fashion due to an imbedded blogging system. NaviCell provides user-friendly exploration of large-scale maps of molecular interactions, thanks to Google Maps and WordPress interfaces, with which many users are already familiar. Semantic zooming which is used for navigating geographical maps is adopted for molecular maps in NaviCell, making any level of visualization readable. In addition, NaviCell provides a framework for community-based curation of maps.

  19. Synthesis, molecular docking and biological evaluation of bis-pyrimidine Schiff base derivatives.

    Science.gov (United States)

    Kumar, Sanjiv; Lim, Siong Meng; Ramasamy, Kalavathy; Vasudevan, Mani; Shah, Syed Adnan Ali; Selvaraj, Manikandan; Narasimhan, Balasubramanian

    2017-09-18

    Heterocyclic pyrimidine nucleus, which is an essential base component of the genetic material of deoxyribonucleic acid, demonstrated various biological activities. A series of bis-pyrimidine Schiff bases were synthesized and screened for its antimicrobial and anticancer potentials. The molecular docking study was carried to find the interaction between active molecules with receptor. The structures of synthesized bis-pyrimidine Schiff bases were confirmed by spectral studies. The synthesized bis-pyrimidine derivatives were evaluated for their antimicrobial activity (MIC = µmol/mL) against selected Gram positive; Gram negative bacterial and fungal strains by tube dilution method. The anticancer activity (IC50 = µmol/mL) of the synthesized compounds was determined against human colorectal carcinoma (HCT116) cancer cell line by Sulforhodamine B (SRB) assay. Molecular docking studies provided information regarding the binding mode of active bis-pyrimidine Schiff bases with the cyclin-dependent kinase 8 (CDK8) receptor. The antimicrobial screening results indicated that compounds, q1 (MICbs = 0.83 µmol/mL), q16 (MICan = 1.54 µmol/mL and MICec = 0.77 µmol/mL), q1 and q19 (MICca = 0.41 µmol/mL) and q20 (MIC = 0.36 µmol/mL) are the most active ones. Compounds q1 (IC50 = 0.18 µmol/mL) have emerged as potent anticancer molecule against human colorectal carcinoma cancer cell line than the reference drug, 5-fluorouracil. Molecular docking studies indicated that compound q1 (the most active molecule) has the maximum hydrogen bond interaction (four) and π-π stacking (three) network among the bis-pyrimidine Schiff bases. Graphical abstract Graphical illustration of predicted binding mode of bis-pyrimidine Schiff bases in the active site of CDK8. a. Compound 1 (magenta color), b. Compound 5 (green color), c. Compound 8 (red color), d. Compound 13 (split pea color).

  20. Hybrid Materials Based on Magnetic Layered Double Hydroxides: A Molecular Perspective.

    Science.gov (United States)

    Abellán, Gonzalo; Martí-Gastaldo, Carlos; Ribera, Antonio; Coronado, Eugenio

    2015-06-16

    Design of functional hybrids lies at the very core of synthetic chemistry as it has enabled the development of an unlimited number of solids displaying unprecedented or even improved properties built upon the association at the molecular level of quite disparate components by chemical design. Multifunctional hybrids are a particularly appealing case among hybrid organic/inorganic materials. Here, chemical knowledge is used to deploy molecular components bearing different functionalities within a single solid so that these properties can coexist or event interact leading to unprecedented phenomena. From a molecular perspective, this can be done either by controlled assembly of organic/inorganic molecular tectons into an extended architecture of hybrid nature or by intercalation of organic moieties within the empty channels or interlamellar space offered by inorganic solids with three-dimensional (MOFs, zeolites, and mesoporous hosts) or layered structures (phosphates, silicates, metal dichalcogenides, or anionic clays). This Account specifically illustrates the use of layered double hydroxides (LDHs) in the preparation of magnetic hybrids, in line with the development of soft inorganic chemistry processes (also called "Chimie Douce"), which has significantly contributed to boost the preparation hybrid materials based on solid-state hosts and subsequent development of applications. Several features sustain the importance of LDHs in this context. Their magnetism can be manipulated at a molecular level by adequate choice of constituting metals and interlayer separation for tuning the nature and extent of magnetic interactions across and between planes. They display unparalleled versatility in accommodating a broad range of anionic species in their interlamellar space that encompasses not only simple anions but chemical systems of increasing dimensionality and functionalities. Their swelling characteristics allow for their exfoliation in organic solvents with high

  1. Taxonomic position and phylogeny of the genus Vargasiella (Orchidaceae, Vandoideae) based on molecular and morphological evidence.

    Science.gov (United States)

    Szlachetko, Dariusz L; Górniak, Marcin; Kolanowska, Marta; Mytnik-Ejsmont, Joanna; Kowalkowska, Agnieszka K; Rutkowski, Piotr; Koliński, Tomasz

    2014-01-01

    Since the description of the Neotropical genus Vargasiella in 1952, its taxonomic position has remained unclear, mainly due to a lack of sufficient data. In this study, the taxonomic position of Vargasiella was revised based on the outcomes of macro- and micromorphological studies, analyses of selected molecular markers and ecological methods of niche distribution modeling. The phylogenetic relationships were inferred using three DNA markers: matK, trnL-F and ITS sequences. The morphological studies included the analysis of macromorphological features of herbarium specimens as well as micromorphological examination of preserved flowers. The ecological niche modeling was applied to identify the distribution of the suitable niches of the studied taxa. The relationships between Vargasiella and most similar taxa remain unresolved based on the molecular analysis. The outcomes from the morphological studies indicated significant differences between Vargasiella, Warrea and Warreopsis. Moreover, a niche shift in response to changing climate after the last glacial maximum is observed in Vargasiella, while no substantial changes in the occupied habitats were identified in the other related taxa. The clocktree of the Zygopetaleae estimated from the matK gene indicated that the most recent common ancestors of Vargasiella, Warrea and Warreopsis originated in the Miocene, while the divergence time for Vargasiella and Warrea was assessed at approximately 5.4 Ma ago. Vargasiella seems to be an outshoot of the main branch of evolution of the Zygopetaleae. It is noteworthy that the Vargasiella-Warrea dichotomy could have taken place later than the divergence of Warreopsis from the mutual lineage. The molecular analysis and morphological data suggest that Vargasiella and Warrea could have evolved from a common ancestor. Accumulation of morphological differences and acceleration of the evolution of Vargasiella were more intensive than in other Warreinae and this could probably be

  2. Molecular bases of cytoskeleton plasticity during the Trypanosoma brucei parasite cycle.

    Science.gov (United States)

    Rotureau, Brice; Subota, Ines; Bastin, Philippe

    2011-05-01

    African trypanosomes are flagellated protozoan parasites responsible for sleeping sickness and transmitted by tsetse flies. The accomplishment of their parasite cycle requires adaptation to highly diverse environments. These transitions take place in a strictly defined order and are accompanied by spectacular morphological modifications in cell size, shape and positioning of organelles. To understand the molecular bases of these processes, parasites isolated from different tissues of the tsetse fly were analysed by immunofluorescence with markers for specific cytoskeleton components and by a new immunofluorescence-based assay for evaluation of the cell volume. The data revealed striking differences between proliferative stages found in the midgut or in the salivary glands and the differentiating stage occurring in the proventriculus. Cell proliferation was characterized by a significant increase in cell volume, by a pronounced cell elongation marked by microtubule extension at the posterior end, and by the production of a new flagellum similar to the existing one. In contrast, the differentiating stage found in the proventriculus does not display any increase in cell volume neither in cell length, but is marked by a profound remodelling of the posterior part of the cytoskeleton and by changes in molecular composition and/or organization of the flagellum attachment zone. © 2011 Blackwell Publishing Ltd.

  3. Molecular systematics of Dendrobium (Orchidaceae, Dendrobieae) from mainland Asia based on plastid and nuclear sequences.

    Science.gov (United States)

    Xiang, Xiao-Guo; Schuiteman, André; Li, De-Zhu; Huang, Wei-Chang; Chung, Shih-Wen; Li, Jian-Wu; Zhou, Hai-Lang; Jin, Wei-Tao; Lai, Yang-Jun; Li, Zhen-Yu; Jin, Xiao-Hua

    2013-12-01

    Dendrobium is one of the three largest genera and presents some of the most intricate taxonomic problems in the family Orchidaceae. Based on five DNA markers and a broad sampling of Dendrobium and its relatives from mainland Asia (109 species), our results indicate that mainland Asia Dendrobium is divided into eight clades (with two unplaced species) that form polytomies along the spine of the cladogram. Both Dendrobium and Epigeneium are well supported as monophyletic, whereas sect. Dendrobium, sect. Densiflora, sect. Breviflores, sect. Holochrysa, are paraphyletic/polyphyletic. Many ignored phylogenetic relationships, such as the one of major clades formed by D. jenkinsii and D. lindleyi (two members of sect. Densiflora), the Aphyllum group, the Devonianum group, the Catenatum group, the Crepidatum group, and the Dendrobium moniliforme complex are well supported by both molecular and morphological evidence. Based on our data, we propose to broaden sect. Dendrobium to include sect. Stuposa, sect. Breviflores, and sect. Holochrysa and to establish a new section to accommodate D. jenkinsii and D. lindleyi. Our results indicated that it is preferable to use a broad generic concept of Dendrobium and to pursue an improved infrageneric classification at sectional level, taking into account both morphology and current molecular findings. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Development of molecularly imprinted polymer-based field effect transistor for sugar chain sensing

    Science.gov (United States)

    Nishitani, Shoichi; Kajisa, Taira; Sakata, Toshiya

    2017-04-01

    In this study, we developed a molecularly imprinted polymer-based field-effect transistor (MIP-gate FET) for selectively detecting sugar chains in aqueous media, focusing on 3‧-sialyllactose (3SLac) and 6‧-sialyllactose (6SLac). The FET biosensor enables the detection of small molecules as long as they have intrinsic charges. Additionally, the MIP gels include the template for the target molecule, which is selectively trapped without requiring enzyme-target molecule reaction. The MIP gels were synthesized on the gate surface of the FET device, including phenylboronic acid (PBA), which enables binding to sugar chains. Firstly, the 3SLac-MIP-gate FET quantitatively detected 3SLac at µM levels. This is because the FET device recognized the change in molecular charges on the basis of PBA-3SLac binding in the MIP gel. Moreover, 3SLac was selectively detected using the 3SLac- and 6SLac-MIP-gate FETs to some extent, where the detecting signal from the competent was suppressed by 40% at maximum. Therefore, a platform based on the MIP-coupled FET biosensor is suitable for a selective biosensing system in an enzyme-free manner, which can be applied widely in medical fields. However, we need to further improve the selectivity of MIP-gate FETs to discriminate more clearly between similar structures of sugar chains such as 3SLac and 6SLac.

  5. Genetic aberrations and molecular biology of skull base chordoma and chondrosarcoma.

    Science.gov (United States)

    Kitamura, Yohei; Sasaki, Hikaru; Yoshida, Kazunari

    2017-04-01

    Chordomas and chondrosarcomas are two major malignant bone neoplasms located at the skull base. These tumors are rarely metastatic, but can be locally invasive and resistant to conventional chemotherapies and radiotherapies. Accordingly, therapeutic approaches for the treatment of these tumors can be difficult. Additionally, their location at the skull base makes them problematic. Although accurate diagnosis of these tumors is important because of their distinct prognoses, distinguishing between these tumor types is difficult due to overlapping radiological and histopathological findings. However, recent accumulation of molecular and genetic studies, including extracranial location analysis, has provided us clues for accurate diagnosis. In this report, we review the genetic aberrations and molecular biology of these two tumor types. Among the abundant genetic features of these tumors, brachyury immunohistochemistry and direct sequencing of IDH1/2 are simple and useful techniques that can be used to distinguish between these tumors. Although it is still unclear why these tumors, which have such distinct genetic backgrounds, show similar histopathological findings, comparison of their genetic backgrounds could provide essential information.

  6. Network analysis of genes regulated in renal diseases: implications for a molecular-based classification

    Directory of Open Access Journals (Sweden)

    Jagadish HV

    2009-09-01

    Full Text Available Abstract Background Chronic renal diseases are currently classified based on morphological similarities such as whether they produce predominantly inflammatory or non-inflammatory responses. However, such classifications do not reliably predict the course of the disease and its response to therapy. In contrast, recent studies in diseases such as breast cancer suggest that a classification which includes molecular information could lead to more accurate diagnoses and prediction of treatment response. This article describes how we extracted gene expression profiles from biopsies of patients with chronic renal diseases, and used network visualizations and associated quantitative measures to rapidly analyze similarities and differences between the diseases. Results The analysis revealed three main regularities: (1 Many genes associated with a single disease, and fewer genes associated with many diseases. (2 Unexpected combinations of renal diseases that share relatively large numbers of genes. (3 Uniform concordance in the regulation of all genes in the network. Conclusion The overall results suggest the need to define a molecular-based classification of renal diseases, in addition to hypotheses for the unexpected patterns of shared genes and the uniformity in gene concordance. Furthermore, the results demonstrate the utility of network analyses to rapidly understand complex relationships between diseases and regulated genes.

  7. Bases moleculares de la enfermedad de Alzheimer. Perspectivas de nuevos enfoques terapéuticos

    Directory of Open Access Journals (Sweden)

    Jorge A. Huete-Pérez

    2007-12-01

    Full Text Available L ESTUDIO DE LA ENFERMEDAD DE ALZHEIMER HA AVANZADO mucho en los últimos años gracias al descubrimiento de los genes implicados, sus mutaciones y variantes. Este cúmulo de conocimientos se ha ido organizando en diferentes hipótesis que dan mayor importancia a uno u otro factor genético. Con el progreso acelerado de la fármaco-genómica, se han identificado nuevos factores genéticos de los procesos patogénicos, lo cual debería conllevar a nuevas formas de tratamiento. En este artículo de revisión abordamos las bases moleculares y genéticas del mal de Alzheimer y discutimos las posibles nuevas terapias. The study of Alzheimer’s Disease (AD has advanced much in the last few years, thanks to the discovery of associated genes and their variants and mutations. This accumulation of knowledge has led to the creation of various hypotheses concerning AD which give greater relevance to one or other genetic factor. With the accelerated pace of development in the area of pharmaceutical genomics, new genetic factors involved in the pathogenic process have been identified, which should lead to new avenues for treatment. In this review article we discuss the molecular and genetic bases for AD as well as potential new therapies.

  8. Development of New Candidate Gene and EST-Based Molecular Markers for Gossypium Species.

    Science.gov (United States)

    Buyyarapu, Ramesh; Kantety, Ramesh V; Yu, John Z; Saha, Sukumar; Sharma, Govind C

    2011-01-01

    New source of molecular markers accelerate the efforts in improving cotton fiber traits and aid in developing high-density integrated genetic maps. We developed new markers based on candidate genes and G. arboreum EST sequences that were used for polymorphism detection followed by genetic and physical mapping. Nineteen gene-based markers were surveyed for polymorphism detection in 26 Gossypium species. Cluster analysis generated a phylogenetic tree with four major sub-clusters for 23 species while three species branched out individually. CAP method enhanced the rate of polymorphism of candidate gene-based markers between G. hirsutum and G. barbadense. Two hundred A-genome based SSR markers were designed after datamining of G. arboreum EST sequences (Mississippi Gossypium arboreum  EST-SSR: MGAES). Over 70% of MGAES markers successfully produced amplicons while 65 of them demonstrated polymorphism between the parents of G. hirsutum and G. barbadense RIL population and formed 14 linkage groups. Chromosomal localization of both candidate gene-based and MGAES markers was assisted by euploid and hypoaneuploid CS-B analysis. Gene-based and MGAES markers were highly informative as they were designed from candidate genes and fiber transcriptome with a potential to be integrated into the existing cotton genetic and physical maps.

  9. Molecular cancer classification using a meta-sample-based regularized robust coding method.

    Science.gov (United States)

    Wang, Shu-Lin; Sun, Liuchao; Fang, Jianwen

    2014-01-01

    Previous studies have demonstrated that machine learning based molecular cancer classification using gene expression profiling (GEP) data is promising for the clinic diagnosis and treatment of cancer. Novel classification methods with high efficiency and prediction accuracy are still needed to deal with high dimensionality and small sample size of typical GEP data. Recently the sparse representation (SR) method has been successfully applied to the cancer classification. Nevertheless, its efficiency needs to be improved when analyzing large-scale GEP data. In this paper we present the meta-sample-based regularized robust coding classification (MRRCC), a novel effective cancer classification technique that combines the idea of meta-sample-based cluster method with regularized robust coding (RRC) method. It assumes that the coding residual and the coding coefficient are respectively independent and identically distributed. Similar to meta-sample-based SR classification (MSRC), MRRCC extracts a set of meta-samples from the training samples, and then encodes a testing sample as the sparse linear combination of these meta-samples. The representation fidelity is measured by the l2-norm or l1-norm of the coding residual. Extensive experiments on publicly available GEP datasets demonstrate that the proposed method is more efficient while its prediction accuracy is equivalent to existing MSRC-based methods and better than other state-of-the-art dimension reduction based methods.

  10. MDWeb and MDMoby: an integrated web-based platform for molecular dynamics simulations.

    Science.gov (United States)

    Hospital, Adam; Andrio, Pau; Fenollosa, Carles; Cicin-Sain, Damjan; Orozco, Modesto; Gelpí, Josep Lluís

    2012-05-01

    MDWeb and MDMoby constitute a web-based platform to help access to molecular dynamics (MD) in the standard and high-throughput regime. The platform provides tools to prepare systems from PDB structures mimicking the procedures followed by human experts. It provides inputs and can send simulations for three of the most popular MD packages (Amber, NAMD and Gromacs). Tools for analysis of trajectories, either provided by the user or retrieved from our MoDEL database (http://mmb.pcb.ub.es/MoDEL) are also incorporated. The platform has two ways of access, a set of web-services based on the BioMoby framework (MDMoby), programmatically accessible and a web portal (MDWeb). http://mmb.irbbarcelona.org/MDWeb; additional information and methodology details can be found at the web site ( http://mmb.irbbarcelona.org/MDWeb/help.php)

  11. Functionality in Electrospun Nanofibrous Membranes Based on Fiber’s Size, Surface Area, and Molecular Orientation

    Directory of Open Access Journals (Sweden)

    Akihiko Tanioka

    2011-08-01

    Full Text Available Electrospinning is a versatile method for forming continuous thin fibers based on an electrohydrodynamic process. This method has the following advantages: (i the ability to produce thin fibers with diameters in the micrometer and nanometer ranges; (ii one-step forming of the two- or three-dimensional nanofiber network assemblies (nanofibrous membranes; and (iii applicability for a broad spectrum of molecules, such as synthetic and biological polymers and polymerless sol-gel systems. Electrospun nanofibrous membranes have received significant attention in terms of their practical applications. The major advantages of nanofibers or nanofibrous membranes are the functionalities based on their nanoscaled-size, highly specific surface area, and highly molecular orientation. These functionalities of the nanofibrous membranes can be controlled by their fiber diameter, surface chemistry and topology, and internal structure of the nanofibers. This report focuses on our studies and describes fundamental aspects and applications of electrospun nanofibrous membranes.

  12. Mesh-based Monte Carlo method in time-domain widefield fluorescence molecular tomography

    Science.gov (United States)

    Chen, Jin; Fang, Qianqian; Intes, Xavier

    2012-10-01

    We evaluated the potential of mesh-based Monte Carlo (MC) method for widefield time-gated fluorescence molecular tomography, aiming to improve accuracy in both shape discretization and photon transport modeling in preclinical settings. An optimized software platform was developed utilizing multithreading and distributed parallel computing to achieve efficient calculation. We validated the proposed algorithm and software by both simulations and in vivo studies. The results establish that the optimized mesh-based Monte Carlo (mMC) method is a computationally efficient solution for optical tomography studies in terms of both calculation time and memory utilization. The open source code, as part of a new release of mMC, is publicly available at http://mcx.sourceforge.net/mmc/.

  13. Molecular Assembly of Polysaccharide-Based Microcapsules and Their Biomedical Applications.

    Science.gov (United States)

    Feng, Xiyun; Du, Cuiling; Li, Junbai

    2016-08-01

    Advanced multifunctional microcapsules have revealed great potential in biomedical applications owing to their tunable size, shape, surface properties, and stimuli responsiveness. Polysaccharides are one of the most acceptable biomaterials for biomedical applications because of their outstanding virtues such as biocompatibility, biodegradability, and low toxicity. Many efforts have been devoted to investigating novel molecular design and efficient building blocks for polysaccharide-based microcapsules. In this Personal Account, we first summarize the common features of polysaccharides and the main principles of the design and fabrication of polysaccharide-based microcapsules, and further discuss their applications in biomedical areas and perspectives for future research. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. [A molecular phylogeny of Shennongjia white bear based on mitochondrial cytochrome b gene sequence].

    Science.gov (United States)

    Wang, Hui-Juan; Zhang, Zhi-Min; Liu, Zhong-Lai; Xiong, Guo-Mei

    2006-10-01

    The phylogenetic relationship of Shennongjia white bear has been an open question. Total DNA was extracted and sequenced from hair and feces of Shennongjia white bear. Based on the partial Cyt b gene sequence obtained from the samples, the authors aligned them using the Clustal W software program. The MEGA software was used to analyze the divergences and base substitutions of the partial Cyt b gene among the 11 species: Shennongjia white bear, Selenarctos thibetanus, Euarctos americanus, Helarctos malayanus, Ursus arctos, Thalarctos maritimus, Melursus ursinus, Procyon lotor, Ailuropoda melanoleuca, Ailurus fulgens and Tremarctos ornatus. The phylogenetic trees constructed by multiple methods (NJ and MP) supported nearly the same topology. Our molecular results show that the sequence divergence between Shennongjia white bear and Asiatic black bear (Selenarctos thibetanus) is lower than that between other species.

  15. Fuzzy method of recognition of high molecular substances in evidence-based biology

    Science.gov (United States)

    Olevskyi, V. I.; Smetanin, V. T.; Olevska, Yu. B.

    2017-10-01

    Nowadays modern requirements to achieving reliable results along with high quality of researches put mathematical analysis methods of results at the forefront. Because of this, evidence-based methods of processing experimental data have become increasingly popular in the biological sciences and medicine. Their basis is meta-analysis, a method of quantitative generalization of a large number of randomized trails contributing to a same special problem, which are often contradictory and performed by different authors. It allows identifying the most important trends and quantitative indicators of the data, verification of advanced hypotheses and discovering new effects in the population genotype. The existing methods of recognizing high molecular substances by gel electrophoresis of proteins under denaturing conditions are based on approximate methods for comparing the contrast of electrophoregrams with a standard solution of known substances. We propose a fuzzy method for modeling experimental data to increase the accuracy and validity of the findings of the detection of new proteins.

  16. Protein crystallization and biosensor applications of hydrogel-based molecularly imprinted polymers.

    Science.gov (United States)

    Reddy, Subrayal M; Phan, Quan T; El-Sharif, Hazim; Govada, Lata; Stevenson, Derek; Chayen, Naomi E

    2012-12-10

    We have characterized the imprinting capability of a family of acrylamide polymer-based molecularly imprinted polymers (MIPs) for bovine hemoglobin (BHb) and trypsin (Tryp) using spectrophotometric and quartz crystal microbalance (QCM) sensor techniques. Bulk gel characterization on acrylamide (AA), N-hydroxymethylacrylamide (NHMA), and N-isopropylacrylamide (NiPAM) gave varied selectivities when compared with nonimprinted polymers. We have also harnessed the ability of the MIPs to facilitate protein crystallization as a means of evaluating their selectivity for cognate and noncognate proteins. Crystallization trials indicated improved crystal formation in the order NiPAMprotein loading. Equivalent results for acrylamide MIPs suggested that the cavities were equally selective for both proteins, while N-isopropylacrylamide MIPs were not selective for either cognate BHb or noncognate BSA. All BHb MIP-QCM sensors based on AA, NHMA, or NiPAM were essentially nonresponsive to smaller, noncognate proteins. Protein crystallization studies validated the hydrophilic efficacy of MIPS indicated in the QCM studies.

  17. Acid-Base Interactions at the Molecular Level: Adhesion and Friction Studies with Interfacial Force Microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Burns, A.R.; Carpick, R.W.; Houston, J.E.; Michalske, T.A.

    1998-12-09

    To examine the forces of acid-base adhesive interactions at the molecular level, we utilize the scanning probe Interracial Force Microscope (IFM). Unlike cantilever-based atomic force microscopes, the EM is a non-compliant, mechanically stable probe that provides a complete adhesive profile without jump-to-contact. In this way, we are able to quantitatively measure the work of adhesion and bond energies at well-defined, nanometer-scale single asperity contacts. In particular, we will discuss the displacement-controlled adhesive forces between self-assembled monolayer of functionalized alkanethiols strongly bound to a gold substrate and a similarly functionalized tip. We also discuss a method utilizing decoupled lateral and normal force sensors to simultaneously observe the onset of both friction and chemical bond formation. Measurements show that friction can be directly attributed to bond formation and rupture well before repulsive contact.

  18. Remote stabilization of copper paddlewheel based molecular building blocks in metal-organic frameworks

    KAUST Repository

    Gao, Wenyang

    2015-03-24

    Copper paddlewheel based molecular building blocks (MBBs) are ubiquitous and have been widely employed for the construction of highly porous metal-organic frameworks (MOFs). However, most copper paddlewheel based MOFs fail to retain their structural integrity in the presence of water. This instability is directly correlated to the plausible displacement of coordinating carboxylates in the copper paddlewheel MBB, [Cu2(O2C-)4], by the strongly coordinating water molecules. In this comprehensive study, we illustrate the chemical stability control in the rht-MOF platform via strengthening the coordinating bonds within the triangular inorganic MBB, [Cu3O(N4-x(CH)xC-)3] (x = 0, 1, or 2). Remotely, the chemical stabilization propagated into the paddlewheel MBB to afford isoreticular rht-MOFs with remarkably enhanced water/chemical stabilities compared to the prototypal rht-MOF-1. © 2015 American Chemical Society.

  19. Molecular phylogeny of Anopheles hyrcanus group (Diptera: Culicidae) based on mtDNA COI.

    Science.gov (United States)

    Fang, Yuan; Shi, Wen-Qi; Zhang, Yi

    2017-05-08

    The Anopheles hyrcanus group, which includes at least 25 species, is widely distributed in the Oriental and Palearctic regions. Some group members have been incriminated as vectors of malaria and other mosquito-borne diseases. It is difficult to identify Hyrcanus Group members by morphological features. Thus, molecular phylogeny has been proposed as an important complementary method to traditional morphological taxonomy. Based on the GenBank database and our original study data, we used 466 mitochondrial DNA COI sequences belonging to 18 species to reconstruct the molecular phylogeny of the Hyrcanus Group across its worldwide geographic range. The results are as follows. 1) The average conspecific K2P divergence was 0.008 (range 0.002-0.017), whereas sequence divergence between congroup species averaged 0.064 (range 0.026-0.108). 2) The topology of COI tree of the Hyrcanus Group was generally consistent with classical morphological taxonomy in terms of species classification, but disagreed in subgroup division. In the COI tree, the group was divided into at least three main clusters. The first cluster contained An. nimpe; the second was composed of the Nigerrimus Subgroup and An. argyropus; and the third cluster was comprised of the Lesteri Subgroup and other unassociated species. 3) Phylogenetic analysis of COI indicated that ancient hybridizations probably occurred among the three closely related species, An. sinensis, An. belenrae, and An. kleini. 4) The results supported An. paraliae as a probable synonym of An. lesteri, and it was possible that An. pseudopictus and An. hyrcanus were the same species, as evident from their extremely low interspecific genetic divergence (0.020 and 0.007, respectively) and their phylogenetic positions. In summary, we reconstructed the molecular phylogeny and analysed genetic divergence of the Hyrcanus Group using mitochondrial COI sequences. Our results suggest that in the future of malaria surveillance, we should not only pay

  20. Novel Modification of HistoGel-Based Cell Block Preparation Method: Improved Sufficiency for Molecular Studies.

    Science.gov (United States)

    Rekhtman, Natasha; Buonocore, Darren J; Rudomina, Dorota; Friedlander, Maria; Dsouza, Crisbane; Aggarwal, Gitika; Arcila, Maria; Edelweiss, Marcia; Lin, Oscar

    2017-11-02

    - Cell block preparation methods vary substantially across institutions and are frequently suboptimal. The growing importance of biomarker testing in the era of targeted therapies makes optimization of cell block preparation critically important. - To develop an improved cell block preparation method. - Ex vivo fine-needle aspirates and scrapes from surgically resected tumors were used to develop an improved HistoGel (Thermo Fisher Scientific, Waltham, Massachusetts)-based cell block preparation method. Cellularity yield with the new versus the standard method was assessed in ex vivo split samples and in consecutive clinical fine-needle aspirates processed before (n = 100) and after (n = 100) the new method was implemented in our laboratory. Sufficiency of cell block material for potential molecular studies was estimated by manual cell quantitation. - The key modification in the new method was pretreatment of the pelleted cells with 95% ethanol before the addition of HistoGel (HistoGel + ethanol method). In addition, we optimized the melting conditions of HistoGel and added a dark, inorganic marker to the cell pellets to highlight the desired level of sectioning during microtomy. Cell blocks from ex vivo split samples showed that the HistoGel + ethanol method yielded, on average, an 8.3-fold (range, 1-20) greater cellularity compared with the standard HistoGel-only method. After the switch from the standard HistoGel method to the modified method in our clinical practice, sufficiency of positive fine-needle aspirates for some molecular studies increased from 72% to 97% (P = .002). - We describe a simple and readily adoptable modification of the HistoGel method, which results in substantial improvement in cell capture in cell blocks, leading to significant increase in sufficiency for potential molecular and other ancillary studies.

  1. Cyndi: a multi-objective evolution algorithm based method for bioactive molecular conformational generation

    Directory of Open Access Journals (Sweden)

    Li Honglin

    2009-03-01

    Full Text Available Abstract Background Conformation generation is a ubiquitous problem in molecule modelling. Many applications require sampling the broad molecular conformational space or perceiving the bioactive conformers to ensure success. Numerous in silico methods have been proposed in an attempt to resolve the problem, ranging from deterministic to non-deterministic and systemic to stochastic ones. In this work, we described an efficient conformation sampling method named Cyndi, which is based on multi-objective evolution algorithm. Results The conformational perturbation is subjected to evolutionary operation on the genome encoded with dihedral torsions. Various objectives are designated to render the generated Pareto optimal conformers to be energy-favoured as well as evenly scattered across the conformational space. An optional objective concerning the degree of molecular extension is added to achieve geometrically extended or compact conformations which have been observed to impact the molecular bioactivity (J Comput -Aided Mol Des 2002, 16: 105–112. Testing the performance of Cyndi against a test set consisting of 329 small molecules reveals an average minimum RMSD of 0.864 Å to corresponding bioactive conformations, indicating Cyndi is highly competitive against other conformation generation methods. Meanwhile, the high-speed performance (0.49 ± 0.18 seconds per molecule renders Cyndi to be a practical toolkit for conformational database preparation and facilitates subsequent pharmacophore mapping or rigid docking. The copy of precompiled executable of Cyndi and the test set molecules in mol2 format are accessible in Additional file 1. Conclusion On the basis of MOEA algorithm, we present a new, highly efficient conformation generation method, Cyndi, and report the results of validation and performance studies comparing with other four methods. The results reveal that Cyndi is capable of generating geometrically diverse conformers and outperforms

  2. Systematics of the blindsnakes (Serpentes: Scolecophidia: Typhlopoidea) based on molecular and morphological evidence.

    Science.gov (United States)

    Pyron, Robert Alexander; Wallach, Van

    2014-07-08

    The blindsnake superfamily Typhlopoidea (Gerrhopilidae, Typhlopidae, and Xenotyphlopidae) is a diverse, widespread part of the global snake fauna. A recent systematic revision based on molecular phylogenetic analyses and some morphological evidence presented a preliminary solution to the non-monophyly of many previously recognized genera, but additional clarification is needed regarding the recognition of some species and genera. We rectify these problems here with a new molecular phylogenetic analysis including 95 of the 275 currently recognized, extant typhlopoids, incorporating both nuclear and mitochondrial loci. We supplement this with data on the external, visceral, and hemipenial morphology of nearly all species to generate a revised classification for Typhlopoidea. Based on morphological data, we re-assign Cathetorhinus from Typhlopidae to Gerrhopilidae. Xenotyphlopidae maintains its current contents (Xenotyphlops). In Typhlopidae, one monotypic genus is synonymized with its larger sister-group as it cannot be unambiguously diagnosed morphologically (Sundatyphlops with Anilios), and two genera are synonymizedwith Typhlops (Antillotyphlops and Cubatyphlops), as they are not reciprocally monophyletic. The genus Asiatyphylops is renamed Argyrophis, the senior synonym for the group. We erect one new genus (Lemuriatyphlops) for a phylogenetically distinct species-group in Asiatyphlopinae. Fourteen of eighteen recognized typhlopid genera are maintained in four subfamilies: Afrotyphlopinae (Afrotyphlops, Grypotyphlops [re-assigned from Asiatyphlopinae], Letheobia, and Rhinotyphlops), Asiatyphlopinae (Acutotyphlops, Anilios, Cyclotyphlops, Indotyphlops, Malayotyphlops, Ramphotyphlops, and Xerotyphlops), Madatyphlopinae (Madatyphlops), and Typhlopinae (Amerotyphlops and Typhlops), some with altered contents. Diagnoses based on morphology are provided for all 19 typhlopoid genera, accounting for all 275 species. This taxonomy provides a robust platform for future

  3. Cell Line Data Base: structure and recent improvements towards molecular authentication of human cell lines

    Science.gov (United States)

    Romano, Paolo; Manniello, Assunta; Aresu, Ottavia; Armento, Massimiliano; Cesaro, Michela; Parodi, Barbara

    2009-01-01

    The Cell Line Data Base (CLDB) is a well-known reference information source on human and animal cell lines including information on more than 6000 cell lines. Main biological features are coded according to controlled vocabularies derived from international lists and taxonomies. HyperCLDB (http://bioinformatics.istge.it/hypercldb/) is a hypertext version of CLDB that improves data accessibility by also allowing information retrieval through web spiders. Access to HyperCLDB is provided through indexes of biological characteristics and navigation in the hypertext is granted by many internal links. HyperCLDB also includes links to external resources. Recently, an interest was raised for a reference nomenclature for cell lines and CLDB was seen as an authoritative system. Furthermore, to overcome the cell line misidentification problem, molecular authentication methods, such as fingerprinting, single-locus short tandem repeat (STR) profile and single nucleotide polymorphisms validation, were proposed. Since this data is distributed, a reference portal on authentication of human cell lines is needed. We present here the architecture and contents of CLDB, its recent enhancements and perspectives. We also present a new related database, the Cell Line Integrated Molecular Authentication (CLIMA) database (http://bioinformatics.istge.it/clima/), that allows to link authentication data to actual cell lines. PMID:18927105

  4. ParaDockS: a framework for molecular docking with population-based metaheuristics.

    Science.gov (United States)

    Meier, René; Pippel, Martin; Brandt, Frank; Sippl, Wolfgang; Baldauf, Carsten

    2010-05-24

    Molecular docking is a simulation technique that aims to predict the binding pose between a ligand and a receptor. The resulting multidimensional continuous optimization problem is practically unsolvable in an exact way. One possible approach is the combination of an optimization algorithm and an objective function that describes the interaction. The software ParaDockS is designed to hold different optimization algorithms and objective functions. At the current stage, an adapted particle-swarm optimizer (PSO) is implemented. Available objective functions are (i) the empirical objective function p-Score and (ii) an adapted version of the knowledge-based potential PMF04. We tested the docking accuracy in terms of reproducing known crystal structures from the PDBbind core set. For 73% of the test instances the native binding mode was found with an rmsd below 2 A. The virtual screening efficiency was tested with a subset of 13 targets and the respective ligands and decoys from the directory of useful decoys (DUD). ParaDockS with PMF04 shows a superior early enrichment. The here presented approach can be employed for molecular docking experiments and virtual screenings of large compound libraries in academia as well as in industrial research and development. The performance in terms of accuracy and enrichment is close to the results of commercial software solutions.

  5. Inquiry-Based Learning: Inflammation as a Model to Teach Molecular Techniques for Assessing Gene Expression

    Directory of Open Access Journals (Sweden)

    Kathryn E. Gunn

    2013-08-01

    Full Text Available This laboratory module simulates the process used by working scientists to ask and answer a question of biological interest. Instructors facilitate acquisition of knowledge using a comprehensive, inquiry-based approach in which students learn theory, hypothesis development, experimental design, and data interpretation and presentation. Using inflammation in macrophages as a model system, students perform a series of molecular biology techniques to address the biological question: “Does stimulus ‘X’ induce inflammation?” To ask this question, macrophage cells are treated with putative inflammatory mediators and then assayed for evidence of inflammatory response. Students become familiar with their assigned mediator and the relationship between their mediator and inflammation by conducting literature searches, then using this information to generate hypotheses which address the effect of their mediator on induction of inflammation. The cellular and molecular approaches used to test their hypo