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Sample records for secondary rearrangements mediated

  1. Mediator structure and rearrangements required for holoenzyme formation.

    Science.gov (United States)

    Tsai, Kuang-Lei; Yu, Xiaodi; Gopalan, Sneha; Chao, Ti-Chun; Zhang, Ying; Florens, Laurence; Washburn, Michael P; Murakami, Kenji; Conaway, Ronald C; Conaway, Joan W; Asturias, Francisco J

    2017-04-13

    The conserved Mediator co-activator complex has an essential role in the regulation of RNA polymerase II transcription in all eukaryotes. Understanding the structure and interactions of Mediator is crucial for determining how the complex influences transcription initiation and conveys regulatory information to the basal transcription machinery. Here we present a 4.4 Å resolution cryo-electron microscopy map of Schizosaccharomyces pombe Mediator in which conserved Mediator subunits are individually resolved. The essential Med14 subunit works as a central backbone that connects the Mediator head, middle and tail modules. Comparison with a 7.8 Å resolution cryo-electron microscopy map of a Mediator-RNA polymerase II holoenzyme reveals that changes in the structure of Med14 facilitate a large-scale Mediator rearrangement that is essential for holoenzyme formation. Our study suggests that access to different conformations and crosstalk between structural elements are essential for the Mediator regulation mechanism, and could explain the capacity of the complex to integrate multiple regulatory signals.

  2. The Globular State of the Single-Stranded RNA: Effect of the Secondary Structure Rearrangements

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    Grigoryan, Zareh A.; Karapetian, Armen T.

    2015-01-01

    The mutual influence of the slow rearrangements of secondary structure and fast collapse of the long single-stranded RNA (ssRNA) in approximation of coarse-grained model is studied with analytic calculations. It is assumed that the characteristic time of the secondary structure rearrangement is much longer than that for the formation of the tertiary structure. A nonequilibrium phase transition of the 2nd order has been observed. PMID:26345143

  3. The Globular State of the Single-Stranded RNA: Effect of the Secondary Structure Rearrangements

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    Zareh A. Grigoryan

    2015-01-01

    Full Text Available The mutual influence of the slow rearrangements of secondary structure and fast collapse of the long single-stranded RNA (ssRNA in approximation of coarse-grained model is studied with analytic calculations. It is assumed that the characteristic time of the secondary structure rearrangement is much longer than that for the formation of the tertiary structure. A nonequilibrium phase transition of the 2nd order has been observed.

  4. Subunit architecture and functional modular rearrangements of the transcriptional mediator complex.

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    Tsai, Kuang-Lei; Tomomori-Sato, Chieri; Sato, Shigeo; Conaway, Ronald C; Conaway, Joan W; Asturias, Francisco J

    2014-06-05

    The multisubunit Mediator, comprising ∼30 distinct proteins, plays an essential role in gene expression regulation by acting as a bridge between DNA-binding transcription factors and the RNA polymerase II (RNAPII) transcription machinery. Efforts to uncover the Mediator mechanism have been hindered by a poor understanding of its structure, subunit organization, and conformational rearrangements. By overcoming biochemical and image analysis hurdles, we obtained accurate EM structures of yeast and human Mediators. Subunit localization experiments, docking of partial X-ray structures, and biochemical analyses resulted in comprehensive mapping of yeast Mediator subunits and a complete reinterpretation of our previous Mediator organization model. Large-scale Mediator rearrangements depend on changes at the interfaces between previously described Mediator modules, which appear to be facilitated by factors conducive to transcription initiation. Conservation across eukaryotes of Mediator structure, subunit organization, and RNA polymerase II interaction suggest conservation of fundamental aspects of the Mediator mechanism. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Selenium-mediated synthesis of biaryls through rearrangement.

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    Shahzad, Sohail A; Vivant, Clotilde; Wirth, Thomas

    2010-03-19

    A new cyclization of beta-keto ester substituted stilbene derivatives using selenium electrophiles in the presence of Lewis acids is described. Substituted naphthols are obtained through cyclization and subsequent 1,2-rearrangement of aryl groups under very mild reaction conditions.

  6. Contribution of Large Genomic Rearrangements in Italian Lynch Syndrome Patients: Characterization of a Novel Alu-Mediated Deletion

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    Francesca Duraturo

    2013-01-01

    Full Text Available Lynch syndrome is associated with germ-line mutations in the DNA mismatch repair (MMR genes, mainly MLH1 and MSH2. Most of the mutations reported in these genes to date are point mutations, small deletions, and insertions. Large genomic rearrangements in the MMR genes predisposing to Lynch syndrome also occur, but the frequency varies depending on the population studied on average from 5 to 20%. The aim of this study was to examine the contribution of large rearrangements in the MLH1 and MSH2 genes in a well-characterised series of 63 unrelated Southern Italian Lynch syndrome patients who were negative for pathogenic point mutations in the MLH1, MSH2, and MSH6 genes. We identified a large novel deletion in the MSH2 gene, including exon 6 in one of the patients analysed (1.6% frequency. This deletion was confirmed and localised by long-range PCR. The breakpoints of this rearrangement were characterised by sequencing. Further analysis of the breakpoints revealed that this rearrangement was a product of Alu-mediated recombination. Our findings identified a novel Alu-mediated rearrangement within MSH2 gene and showed that large deletions or duplications in MLH1 and MSH2 genes are low-frequency mutational events in Southern Italian patients with an inherited predisposition to colon cancer.

  7. Genomic rearrangements by LINE-1 insertion-mediated deletion in the human and chimpanzee lineages.

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    Han, Kyudong; Sen, Shurjo K; Wang, Jianxin; Callinan, Pauline A; Lee, Jungnam; Cordaux, Richard; Liang, Ping; Batzer, Mark A

    2005-01-01

    Long INterspersed Elements (LINE-1s or L1s) are abundant non-LTR retrotransposons in mammalian genomes that are capable of insertional mutagenesis. They have been associated with target site deletions upon insertion in cell culture studies of retrotransposition. Here, we report 50 deletion events in the human and chimpanzee genomes directly linked to the insertion of L1 elements, resulting in the loss of approximately 18 kb of sequence from the human genome and approximately 15 kb from the chimpanzee genome. Our data suggest that during the primate radiation, L1 insertions may have deleted up to 7.5 Mb of target genomic sequences. While the results of our in vivo analysis differ from those of previous cell culture assays of L1 insertion-mediated deletions in terms of the size and rate of sequence deletion, evolutionary factors can reconcile the differences. We report a pattern of genomic deletion sizes similar to those created during the retrotransposition of Alu elements. Our study provides support for the existence of different mechanisms for small and large L1-mediated deletions, and we present a model for the correlation of L1 element size and the corresponding deletion size. In addition, we show that internal rearrangements can modify L1 structure during retrotransposition events associated with large deletions.

  8. A genomewide screen for suppressors of Alu-mediated rearrangements reveals a role for PIF1.

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    Karen M Chisholm

    Full Text Available Alu-mediated rearrangement of tumor suppressor genes occurs frequently during carcinogenesis. In breast cancer, this mechanism contributes to loss of the wild-type BRCA1 allele in inherited disease and to loss of heterozygosity in sporadic cancer. To identify genes required for suppression of Alu-mediated recombination we performed a genomewide screen of a collection of 4672 yeast gene deletion mutants using a direct repeat recombination assay. The primary screen and subsequent analysis identified 12 candidate genes including TSA, ELG1, and RRM3, which are known to play a significant role in maintaining genomic stability. Genetic analysis of the corresponding human homologs was performed in sporadic breast tumors and in inherited BRCA1-associated carcinomas. Sequencing of these genes in high risk breast cancer families revealed a potential role for the helicase PIF1 in cancer predisposition. PIF1 variant L319P was identified in three breast cancer families; importantly, this variant, which is predicted to be functionally damaging, was not identified in a large series of controls nor has it been reported in either dbSNP or the 1000 Genomes Project. In Schizosaccharomyces pombe, Pfh1 is required to maintain both mitochondrial and nuclear genomic integrity. Functional studies in yeast of human PIF1 L319P revealed that this variant cannot complement the essential functions of Pfh1 in either the nucleus or mitochondria. Our results provide a global view of nonessential genes involved in suppressing Alu-mediated recombination and implicate variation in PIF1 in breast cancer predisposition.

  9. ON THE PECULIARITIES OF THE RING CONTRACTION REACTIONS OF HOMODRIMANES VIA ACID MEDIATED EPOXIDE REARRANGEMENT

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    Veaceslav Kulciţki

    2011-06-01

    Full Text Available A selective rearrangement of a epoxy-homodrimanic substrate is described. Using fluorosulfonic acid at low temperature leads by ring contraction to a perhydrindanic structure. On the contrary, using boron trifluoride-diethyl ether at r.t. selectively brings about angular methyl migration.

  10. Secondary deuterium isotope effects and transition state structure in the aromatic claisen rearrangement

    International Nuclear Information System (INIS)

    McMichael, K.D.; Korver, G.L.

    1979-01-01

    Kinetic experiments were carried out simultaneously on separate methyl salicylate solutions of allyl phenyl ether and its deuterated phenyl analogues at 170 to 195 0 C. Gas chromatographic analysis for allyl phenyl ether using an internal standard (anisole) and mechanical integration produced concentration/time data which were fitted to the exponential form of the first-order rate equation by a standard and nonlinear least-square program. At least 15 points were obtained for each run, covering 10 to 85% reaction. The derived isotope effects show no temperature dependence. Averages for 6 runs with each compound are k/sub H//k/sub α-D 2 / = 1.18 and K/sub H//k/sub γ-D 2 / = 0.95. An equilibrium α effect of 1.30 and a γ effect of 0.87 may be calculated for both deuterium atoms at 185 0 C. These results show that the C--H vibration frequencies are approximately (1.18 - 1)/(1.27 - 1) or 57 to 77% of the way from those of allyl phenyl ether to those of the cyclohexadiene intermediate. The C--H frequencies of the γ carbon in the transition state are about (0.95 - 1)/(0.88 - 1) or 22 to 62% of the way to those of the intermediate. The structure of the transition state, as far as these bonding frequencies are concerned, is consistent with the Claisen rearrangement

  11. Flavin-mediated dual oxidation controls an enzymatic Favorskii-type rearrangement

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    Louie, Gordon; Noel, Joseph P.; Baran, Phil S.; Palfey, Bruce; Moore, Bradley S.

    2013-01-01

    Flavoproteins catalyze a diversity of fundamental redox reactions and are one of the most studied enzyme families1,2. As monooxygenases, they are universally thought to control oxygenation by means of a peroxyflavin species that transfers a single atom of molecular oxygen to an organic substrate1,3,4. Here we report that the bacterial flavoenzyme EncM5,6 catalyzes the peroxyflavin-independent oxygenation-dehydrogenation dual oxidation of a highly reactive poly(β-carbonyl). The crystal structure of EncM with bound substrate mimics coupled with isotope labeling studies reveal previously unknown flavin redox biochemistry. We show that EncM maintains an unanticipated stable flavin oxygenating species, proposed to be a flavin-N5-oxide, to promote substrate oxidation and trigger a rare Favorskii-type rearrangement that is central to the biosynthesis of the antibiotic enterocin. This work provides new insight into the fine-tuning of the flavin cofactor in offsetting the innate reactivity of a polyketide substrate to direct its efficient electrocyclization. PMID:24162851

  12. Divergence of RNA polymerase α subunits in angiosperm plastid genomes is mediated by genomic rearrangement.

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    Blazier, J Chris; Ruhlman, Tracey A; Weng, Mao-Lun; Rehman, Sumaiyah K; Sabir, Jamal S M; Jansen, Robert K

    2016-04-18

    Genes for the plastid-encoded RNA polymerase (PEP) persist in the plastid genomes of all photosynthetic angiosperms. However, three unrelated lineages (Annonaceae, Passifloraceae and Geraniaceae) have been identified with unusually divergent open reading frames (ORFs) in the conserved region of rpoA, the gene encoding the PEP α subunit. We used sequence-based approaches to evaluate whether these genes retain function. Both gene sequences and complete plastid genome sequences were assembled and analyzed from each of the three angiosperm families. Multiple lines of evidence indicated that the rpoA sequences are likely functional despite retaining as low as 30% nucleotide sequence identity with rpoA genes from outgroups in the same angiosperm order. The ratio of non-synonymous to synonymous substitutions indicated that these genes are under purifying selection, and bioinformatic prediction of conserved domains indicated that functional domains are preserved. One of the lineages (Pelargonium, Geraniaceae) contains species with multiple rpoA-like ORFs that show evidence of ongoing inter-paralog gene conversion. The plastid genomes containing these divergent rpoA genes have experienced extensive structural rearrangement, including large expansions of the inverted repeat. We propose that illegitimate recombination, not positive selection, has driven the divergence of rpoA.

  13. Dechlorination and chlorine rearrangement of 1,2,5,5,6,9,10-heptachlorodecane mediated by the whole pumpkin seedlings.

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    Li, Yanlin; Hou, Xingwang; Yu, Miao; Zhou, Qunfang; Liu, Jiyan; Schnoor, Jerald L; Jiang, Guibin

    2017-05-01

    Short chain chlorinated paraffins (SCCPs) are ubiquitously present as persistent organic pollutants in the environment. However, little information on the interaction of SCCPs with plants is currently available. In this work, young pumpkin plants (Cucurbita maxima × C. Moschata) were hydroponically exposed to the congener of chlorinated decane, 1,2,5,5,6,9,10-heptachlorodecane (1,2,5,5,6,9,10-HepCD), to investigate the uptake, translocation and transformation of chlorinated decanes in the intact plants. It was found that parent HepCD was taken up by the pumpkin roots, translocated from root to shoots, and phytovolatilized from pumpkin plants to air via the plant transpiration flux. Our data suggested that dechlorination of 1,2,5,5,6,9,10-HepCD to lower chlorinated decanes and rearrangement of chlorine atoms in the molecule were all mediated by the whole pumpkin seedlings. Chlorinated decanes were found in the shoots and roots of blank controls, indicating that chlorinated decanes in the air could be absorbed by leaves and translocated from shoots to roots. Lower chlorinated congeners (C 10 H 17 Cl 5 ) tended to detain in air compared to higher chlorinated congeners (C 10 H 16 Cl 6 and other C 10 H 15 Cl 7 ). Potential transformation pathway and behavior of 1,2,5,5,6,9,10-HepCD in pumpkin were proposed based on these experiments. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. NONO ubiquitination is mediated by FBW7 and GSK3 β via a degron lost upon chromosomal rearrangement in cancer.

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    Alfano, Luigi; Caporaso, Antonella; Altieri, Angela; Costa, Caterina; Forte, Iris M; Iannuzzi, Carmelina A; Barone, Daniela; Esposito, Luca; Giordano, Antonio; Pentimalli, Francesca

    2018-05-01

    NONO is an RNA-binding protein involved in transcription, mRNA splicing, DNA repair, and checkpoint activation in response to UV radiation. NONO expression has been found altered in several tumor types, including prostate, colon, breast, melanoma, and in papillary renal carcinoma, in which an X chromosome inversion generates a NONO-TFE3 fusion protein. Upon such rearrangement, NONO loses its C-terminal domain. Through bioinformatics analysis, we identified a putative degron motif, known to be recognized by the Skp1-Cul1-F-box-protein (SCF) complex. Here, we evaluated how this domain could affect NONO protein biology. We showed that NONO interacts with the nuclear FBW7α isoform and its ubiquitination is regulated following modulation of the GSK3β kinase. Mutation of T428A/T432A within the degron impaired polyubiquitination upon FBW7α and GSK3β overexpression. Overall, our data suggest that NONO is likely subjected to proteasome-mediated degradation and add NONO to the list of proteins targeted by FBW7, which is itself often deregulated in cancer. © 2017 Wiley Periodicals, Inc.

  15. Ku-mediated coupling of DNA cleavage and repair during programmed genome rearrangements in the ciliate Paramecium tetraurelia.

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    Antoine Marmignon

    2014-08-01

    Full Text Available During somatic differentiation, physiological DNA double-strand breaks (DSB can drive programmed genome rearrangements (PGR, during which DSB repair pathways are mobilized to safeguard genome integrity. Because of their unique nuclear dimorphism, ciliates are powerful unicellular eukaryotic models to study the mechanisms involved in PGR. At each sexual cycle, the germline nucleus is transmitted to the progeny, but the somatic nucleus, essential for gene expression, is destroyed and a new somatic nucleus differentiates from a copy of the germline nucleus. In Paramecium tetraurelia, the development of the somatic nucleus involves massive PGR, including the precise elimination of at least 45,000 germline sequences (Internal Eliminated Sequences, IES. IES excision proceeds through a cut-and-close mechanism: a domesticated transposase, PiggyMac, is essential for DNA cleavage, and DSB repair at excision sites involves the Ligase IV, a specific component of the non-homologous end-joining (NHEJ pathway. At the genome-wide level, a huge number of programmed DSBs must be repaired during this process to allow the assembly of functional somatic chromosomes. To understand how DNA cleavage and DSB repair are coordinated during PGR, we have focused on Ku, the earliest actor of NHEJ-mediated repair. Two Ku70 and three Ku80 paralogs are encoded in the genome of P. tetraurelia: Ku70a and Ku80c are produced during sexual processes and localize specifically in the developing new somatic nucleus. Using RNA interference, we show that the development-specific Ku70/Ku80c heterodimer is essential for the recovery of a functional somatic nucleus. Strikingly, at the molecular level, PiggyMac-dependent DNA cleavage is abolished at IES boundaries in cells depleted for Ku80c, resulting in IES retention in the somatic genome. PiggyMac and Ku70a/Ku80c co-purify as a complex when overproduced in a heterologous system. We conclude that Ku has been integrated in the Paramecium

  16. Detection of Side Chain Rearrangements Mediating the Motions of Transmembrane Helices in Molecular Dynamics Simulations of G Protein-Coupled Receptors

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    Zied Gaieb

    Full Text Available Structure and dynamics are essential elements of protein function. Protein structure is constantly fluctuating and undergoing conformational changes, which are captured by molecular dynamics (MD simulations. We introduce a computational framework that provides a compact representation of the dynamic conformational space of biomolecular simulations. This method presents a systematic approach designed to reduce the large MD simulation spatiotemporal datasets into a manageable set in order to guide our understanding of how protein mechanics emerge from side chain organization and dynamic reorganization. We focus on the detection of side chain interactions that undergo rearrangements mediating global domain motions and vice versa. Side chain rearrangements are extracted from side chain interactions that undergo well-defined abrupt and persistent changes in distance time series using Gaussian mixture models, whereas global domain motions are detected using dynamic cross-correlation. Both side chain rearrangements and global domain motions represent the dynamic components of the protein MD simulation, and are both mapped into a network where they are connected based on their degree of coupling. This method allows for the study of allosteric communication in proteins by mapping out the protein dynamics into an intramolecular network to reduce the large simulation data into a manageable set of communities composed of coupled side chain rearrangements and global domain motions. This computational framework is suitable for the study of tightly packed proteins, such as G protein-coupled receptors, and we present an application on a seven microseconds MD trajectory of CC chemokine receptor 7 (CCR7 bound to its ligand CCL21. Keywords: Molecular dynamics, Change-point detection, Side chain reorganization, Helical domain motion, Intramolecular network, Membrane proteins, GPCR, GPCR computational modeling, GPCR allostery

  17. Recent Developments in the Reformatsky-Claisen Rearrangement

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    Susumi Hatakeyama

    2012-11-01

    Full Text Available The rearrangement of allyl a-bromoacetates with Zn dust is known as the Reformatsky-Claisen rearrangement. Whereas the Ireland-Claisen rearrangement has been widely used in the synthesis of a diverse range of natural products, the Zn-mediated Reformatsky-Claisen rearrangement has not been utilized so often. In this article, we will provide an overview of recent advances in the Reformatsky-Claisen rearrangement field, including the In-mediated Reformatsky-Claisen rearrangement we have recently developed.

  18. Testing Mediation Using Multiple Regression and Structural Equation Modeling Analyses in Secondary Data

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    Li, Spencer D.

    2011-01-01

    Mediation analysis in child and adolescent development research is possible using large secondary data sets. This article provides an overview of two statistical methods commonly used to test mediated effects in secondary analysis: multiple regression and structural equation modeling (SEM). Two empirical studies are presented to illustrate the…

  19. A case with concurrent duplication, triplication, and uniparental isodisomy at 1q42.12-qter supporting microhomology-mediated break-induced replication model for replicative rearrangements.

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    Kohmoto, Tomohiro; Okamoto, Nana; Naruto, Takuya; Murata, Chie; Ouchi, Yuya; Fujita, Naoko; Inagaki, Hidehito; Satomura, Shigeko; Okamoto, Nobuhiko; Saito, Masako; Masuda, Kiyoshi; Kurahashi, Hiroki; Imoto, Issei

    2017-01-01

    Complex genomic rearrangements (CGRs) consisting of interstitial triplications in conjunction with uniparental isodisomy (isoUPD) have rarely been reported in patients with multiple congenital anomalies (MCA)/intellectual disability (ID). One-ended DNA break repair coupled with microhomology-mediated break-induced replication (MMBIR) has been recently proposed as a possible mechanism giving rise to interstitial copy number gains and distal isoUPD, although only a few cases providing supportive evidence in human congenital diseases with MCA have been documented. Here, we report on the chromosomal microarray (CMA)-based identification of the first known case with concurrent interstitial duplication at 1q42.12-q42.2 and triplication at 1q42.2-q43 followed by isoUPD for the remainder of chromosome 1q (at 1q43-qter). In distal 1q duplication/triplication overlapping with 1q42.12-q43, variable clinical features have been reported, and our 25-year-old patient with MCA/ID presented with some of these frequently described features. Further analyses including the precise mapping of breakpoint junctions within the CGR in a sequence level suggested that the CGR found in association with isoUPD in our case is a triplication with flanking duplications, characterized as a triplication with a particularly long duplication-inverted triplication-duplication (DUP-TRP/INV-DUP) structure. Because microhomology was observed in both junctions between the triplicated region and the flanking duplicated regions, our case provides supportive evidence for recently proposed replication-based mechanisms, such as MMBIR, underlying the formation of CGRs + isoUPD implicated in chromosomal disorders. To the best of our knowledge, this is the first case of CGRs + isoUPD observed in 1q and having DUP-TRP/INV-DUP structure with a long proximal duplication, which supports MMBIR-based model for genomic rearrangements. Molecular cytogenetic analyses using CMA containing single

  20. Rac1-mediated cytoskeleton rearrangements induced by intersectin-1s deficiency promotes lung cancer cell proliferation, migration and metastasis.

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    Jeganathan, Niranjan; Predescu, Dan; Zhang, Jin; Sha, Fei; Bardita, Cristina; Patel, Monal; Wood, Stephen; Borgia, Jeffrey A; Balk, Robert A; Predescu, Sanda

    2016-09-14

    The mechanisms involved in lung cancer (LC) progression are poorly understood making discovery of successful therapies difficult. Adaptor proteins play a crucial role in cancer as they link cell surface receptors to specific intracellular pathways. Intersectin-1s (ITSN-1s) is an important multidomain adaptor protein implicated in the pathophysiology of numerous pulmonary diseases. To date, the role of ITSN-1s in LC has not been studied. Human LC cells, human LC tissue and A549 LC cells stable transfected with myc-ITSN-1s construct (A549 + ITSN-1s) were used in correlation with biochemical, molecular biology and morphological studies. In addition scratch assay with time lapse microscopy and in vivo xenograft tumor and mouse metastasis assays were performed. ITSN-1s, a prevalent protein of lung tissue, is significantly downregulated in human LC cells and LC tissue. Restoring ITSN-1s protein level decreases LC cell proliferation and clonogenic potential. In vivo studies indicate that immunodeficient mice injected with A549 + ITSN-1s cells develop less and smaller metastatic tumors compared to mice injected with A549 cells. Our studies also show that restoring ITSN-1s protein level increases the interaction between Cbl E3 ubiquitin ligase and Eps8 resulting in enhanced ubiquitination of the Eps8 oncoprotein. Subsequently, downstream unproductive assembly of the Eps8-mSos1 complex leads to impaired activation of the small GTPase Rac1. Impaired Rac1 activation mediated by ITSN-1s reorganizes the cytoskeleton (increased thick actin bundles and focal adhesion (FA) complexes as well as collapse of the vimentin filament network) in favor of decreased LC cell migration and metastasis. ITSN-1s induced Eps8 ubiquitination and impaired Eps8-mSos1 complex formation, leading to impaired activation of Rac1, is a novel signaling mechanism crucial for abolishing the progression and metastatic potential of LC cells.

  1. Molecular rearrangements of superelectrophiles

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    Douglas A. Klumpp

    2011-03-01

    Full Text Available Superelectrophiles are multiply charged cationic species (dications, trications, etc. which are characterized by their reactions with weak nucleophiles. These reactive intermediates may also undergo a wide variety of rearrangement-type reactions. Superelectrophilic rearrangements are often driven by charge–charge repulsive effects, as these densely charged ions react so as to maximize the distances between charge centers. These rearrangements involve reaction steps similar to monocationic rearrangements, such as alkyl group shifts, Wagner–Meerwein shifts, hydride shifts, ring opening reactions, and other skeletal rearrangements. This review will describe these types of superelectrophilic reactions.

  2. Eosinophils mediate protective immunity against secondary nematode infection.

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    Huang, Lu; Gebreselassie, Nebiat G; Gagliardo, Lucille F; Ruyechan, Maura C; Luber, Kierstin L; Lee, Nancy A; Lee, James J; Appleton, Judith A

    2015-01-01

    Eosinophils are versatile cells that regulate innate and adaptive immunity, influence metabolism and tissue repair, and contribute to allergic lung disease. Within the context of immunity to parasitic worm infections, eosinophils are prominent yet highly varied in function. We have shown previously that when mice undergo primary infection with the parasitic nematode Trichinella spiralis, eosinophils play an important immune regulatory role that promotes larval growth and survival in skeletal muscle. In this study, we aimed to address the function of eosinophils in secondary infection with T. spiralis. By infecting eosinophil-ablated mice, we found that eosinophils are dispensable for immunity that clears adult worms or controls fecundity in secondary infection. In contrast, eosinophil ablation had a pronounced effect on secondary infection of skeletal muscle by migratory newborn larvae. Restoring eosinophils to previously infected, ablated mice caused them to limit muscle larvae burdens. Passive immunization of naive, ablated mice with sera or Ig from infected donors, together with transfer of eosinophils, served to limit the number of newborn larvae that migrated in tissue and colonized skeletal muscle. Results from these in vivo studies are consistent with earlier findings that eosinophils bind to larvae in the presence of Abs in vitro. Although our previous findings showed that eosinophils protect the parasite in primary infection, these new data show that eosinophils protect the host in secondary infection. Copyright © 2014 by The American Association of Immunologists, Inc.

  3. Degradations and Rearrangement Reactions

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    Zhang, Jianbo

    This section deals with recent reports concerning degradation and rearrangement reactions of free sugars as well as some glycosides. The transformations are classified in chemical and enzymatic ways. In addition, the Maillard reaction will be discussed as an example of degradation and rearrangement transformation and its application in current research in the fields of chemistry and biology.

  4. Ruphus-mediated Suzuki cross-coupling of secondary alkyl trifluoroborates

    NARCIS (Netherlands)

    Hoogenband, van den A.; Lange, J.H.M.; Terpstra, J.W.; Koch, M.; Visser, G.M.; Visser, de M.; Korstanje, T.J.; Jastrzebski, J.T.B.H.

    2008-01-01

    A Ruphos-mediated Suzuki cross-coupling between (hetero)aryl bromides and secondary alkyltrifluoroborates is described using palladium catalysis. The Ruphos ligand showed superior properties as compared to S-Phos in this type of reaction. This method constitutes a valuable extension to current

  5. Strengths and weaknesses of the school mediation from the perspective of students in secondary education

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    Laura García Raga

    2016-06-01

    Full Text Available In this paper we present a study to know the valuation of school mediation as an educational strategy taking into account the views of students in five schools in secondary Valencia, where the formal mediation process has been active for at least two years. It also seeks to identify the strengths and weaknesses identified.To achieve the objectives it has collected information from 593 students through an ad hoc difference between issues that all students must answer questionnaire; questions addressed only the students who have gone to mediation service; and finally issues to respond only the students who have acted as mediators.Through descriptive exploratory study conducted, is highlighted as a result the great general agreement exists on the part of students participating in valuing very positively to mediation, particularly their impact on conflict resolution and prevention of serious and violent situations. On the other hand, as for improvement, poor training in mediation and little relation to those benefits linked with faculty is detected, since mediation seems so positively influence the teaching faculty teaching in the classroom and in the relationships between students and faculty. In conclusion, the study shows that school mediation is considered advantageous for students and an opportunity that helps them manage their own conflicts, although there are aspects that should work towards the educational potential of school mediation in the improving coexistence and configuration of democratic citizenship.

  6. Rearrangements of Cycloalkenyl Aryl Ethers

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    Mercedesz Törincsi

    2016-04-01

    Full Text Available Rearrangement reactions of cycloalkenyl phenol and naphthyl ethers and the acid-catalyzed cyclization of the resulting product were investigated. Claisen rearrangement afforded 2-substituted phenol and naphthol derivatives. Combined Claisen and Cope rearrangement resulted in the formation of 4-substituted phenol and naphthol derivatives. In the case of cycloocthylphenyl ether the consecutive Claisen and Cope rearrangements were followed by an alkyl migration. The mechanism of this novel rearrangement reaction is also discussed.

  7. Charge Mediated Compaction and Rearrangement of Gas-Phase Proteins: A Case Study Considering Two Proteins at Opposing Ends of the Structure-Disorder Continuum

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    Jhingree, Jacquelyn R.; Bellina, Bruno; Pacholarz, Kamila J.; Barran, Perdita E.

    2017-07-01

    Charge reduction in the gas phase provides a direct means of manipulating protein charge state, and when coupled to ion mobility mass spectrometry (IM-MS), it is possible to monitor the effect of charge on protein conformation in the absence of solution. Use of the electron transfer reagent 1,3-dicyanobenzene, coupled with IM-MS, allows us to monitor the effect of charge reduction on the conformation of two proteins deliberately chosen from opposite sides of the order to disorder continuum: bovine pancreatic trypsin inhibitor (BPTI) and beta casein. The ordered BPTI presents compact conformers for each of three charge states accompanied by narrow collision cross-section distributions (TWCCSDN2→He). Upon reduction of BPTI, irrespective of precursor charge state, the TWCCSN2→He decreases to a similar distribution as found for the nESI generated ion of identical charge. The behavior of beta casein upon charge reduction is more complex. It presents over a wide charge state range (9-28), and intermediate charge states (13-18) have broad TWCCSDN2→He with multiple conformations, where both compaction and rearrangement are seen. Further, we see that the TWCCSDN2→He of the latter charge states are even affected by the presence of radical anions. Overall, we conclude that the flexible nature of some proteins result in broad conformational distributions comprised of many families, even for single charge states, and the barrier between different states can be easily overcome by an alteration of the net charge.

  8. RGM regulates BMP-mediated secondary axis formation in the sea anemone Nematostella vectensis.

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    Leclère, Lucas; Rentzsch, Fabian

    2014-12-11

    Patterning of the metazoan dorsoventral axis is mediated by a complex interplay of BMP signaling regulators. Repulsive guidance molecule (RGM) is a conserved BMP coreceptor that has not been implicated in axis specification. We show that NvRGM is a key positive regulator of BMP signaling during secondary axis establishment in the cnidarian Nematostella vectensis. NvRGM regulates first the generation and later the shape of a BMP-dependent Smad1/5/8 gradient with peak activity on the side opposite the NvBMP/NvRGM/NvChordin expression domain. Full knockdown of Smad1/5/8 signaling blocks the formation of endodermal structures, the mesenteries, and the establishment of bilateral symmetry, while altering the gradient through partial NvRGM or NvBMP knockdown shifts the boundaries of asymmetric gene expression and the positioning of the mesenteries along the secondary axis. These findings provide insight into the diversification of axis specification mechanisms and identify a previously unrecognized role for RGM in BMP-mediated axial patterning. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Rearrangements in ground and excited states

    CERN Document Server

    de Mayo, Paul

    1980-01-01

    Rearrangements in Ground and Excited States, Volume 3 presents essays on the chemical generation of excited states; the cis-trans isomerization of olefins; and the photochemical rearrangements in trienes. The book also includes essays on the zimmerman rearrangements; the photochemical rearrangements of enones; the photochemical rearrangements of conjugated cyclic dienones; and the rearrangements of the benzene ring. Essays on the photo rearrangements via biradicals of simple carbonyl compounds; the photochemical rearrangements involving three-membered rings or five-membered ring heterocycles;

  10. Rearrangements in ground and excited states

    CERN Document Server

    de Mayo, Paul

    1980-01-01

    Rearrangements in Ground and Excited States, Volume 2 covers essays on the theoretical approach of rearrangements; the rearrangements involving boron; and the molecular rearrangements of organosilicon compounds. The book also includes essays on the polytopal rearrangement at phosphorus; the rearrangement in coordination complexes; and the reversible thermal intramolecular rearrangements of metal carbonyls. Chemists and people involved in the study of rearrangements will find the book invaluable.

  11. Catalytic synthesis of amides via aldoximes rearrangement.

    Science.gov (United States)

    Crochet, Pascale; Cadierno, Victorio

    2015-02-14

    Amide bond formation reactions are among the most important transformations in organic chemistry because of the widespread occurrence of amides in pharmaceuticals, natural products and biologically active compounds. The Beckmann rearrangement is a well-known method to generate secondary amides from ketoximes. However, under the acidic conditions commonly employed, aldoximes RHC=NOH rarely rearrange into the corresponding primary amides RC(=O)NH2. In recent years, it was demonstrated that this atom-economical transformation can be carried out efficiently and selectively with the help of metal catalysts. Several homogeneous and heterogenous systems have been described. In addition, protocols offering the option to generate the aldoximes in situ from the corresponding aldehydes and hydroxylamine, or even from alcohols, have also been developed, as well as a series of tandem processes allowing the access to N-substituted amide products. In this Feature article a comprehensive overview of the advances achieved in this particular research area is presented.

  12. Fibrin accumulation secondary to loss of plasmin-mediated fibrinolysis drives inflammatory osteoporosis in mice.

    Science.gov (United States)

    Cole, Heather A; Ohba, Tetsuro; Nyman, Jeffry S; Hirotaka, Haro; Cates, Justin M M; Flick, Matthew J; Degen, Jay L; Schoenecker, Jonathan G

    2014-08-01

    Osteoporosis is a skeletal disorder characterized by low bone mass and increased bone fragility associated with aging, menopause, smoking, obesity, or diabetes. Persistent inflammation has been identified as an instigating factor in progressive bone loss. In addition to the role of fibrin in coagulation, inordinate fibrin deposition within a tissue matrix results in increased local inflammation. Given that fibrin accumulation is a hallmark of osteoporosis-related comorbidities, we undertook this study to test the hypothesis that persistent fibrin deposition causes inflammatory osteoporosis. Multiple imaging modalities, bone integrity metrics, and histologic analyses were employed to evaluate skeletal derangements in relation to fibrin deposition, circulating fibrinogen levels, and systemic markers of inflammation in mice that were plasminogen deficient and in plasminogen-deficient mice that were concomitantly either fibrinogen deficient or carrying a mutant form of fibrinogen lacking the αM β2 binding motif. Mice generated with a genetic deficit in the key fibrinolytic protease, plasmin, uniformly developed severe osteoporosis. Furthermore, the development of osteoporosis was fibrin(ogen) dependent, and the derangements in the bone remodeling unit were mechanistically tied to fibrin(ogen)-mediated activation of osteoclasts via activation of the leukocyte integrin receptor αM β2 on monocytes and secondary stimulation of osteoblasts by RANKL. Notably, the genetic elimination of fibrin(ogen) or the expression of a mutant form of fibrinogen retaining clotting function but lacking the αM β2 binding motif prevented the degenerative skeletal phenotypes, resulting in normal local and systemic cytokine levels. Taken together, these data reveal for the first time that fibrin promotes inflammation-driven systemic osteoporosis, which suggests a novel association between hemostasis, inflammation, and bone biology. Copyright © 2014 by the American College of Rheumatology.

  13. Claisen thermally rearranged (CTR) polymers

    Science.gov (United States)

    Tena, Alberto; Rangou, Sofia; Shishatskiy, Sergey; Filiz, Volkan; Abetz, Volker

    2016-01-01

    Thermally rearranged (TR) polymers, which are considered the next-generation of membrane materials because of their excellent transport properties and high thermal and chemical stability, are proven to have significant drawbacks because of the high temperature required for the rearrangement and low degree of conversion during this process. We demonstrate that using a [3,3]-sigmatropic rearrangement, the temperature required for the rearrangement of a solid glassy polymer was reduced by 200°C. Conversions of functionalized polyimide to polybenzoxazole of more than 97% were achieved. These highly mechanically stable polymers were almost five times more permeable and had more than two times higher degrees of conversion than the reference polymer treated under the same conditions. Properties of these second-generation TR polymers provide the possibility of preparing efficient polymer membranes in a form of, for example, thin-film composite membranes for various gas and liquid membrane separation applications. PMID:27482538

  14. Radical Smiles Rearrangement: An Update

    Directory of Open Access Journals (Sweden)

    Ingrid Allart-Simon

    2016-07-01

    Full Text Available Over the decades the Smiles rearrangement and its variants have become essential synthetic tools in modern synthetic organic chemistry. In this mini-review we summarized some very recent results of the radical version of these rearrangements. The selected examples illustrate the synthetic power of this approach, especially if it is incorporated into a domino process, for the preparation of polyfunctionalized complex molecules.

  15. Chiral auxiliary-mediated enantioenrichment of (+-)-ibuprofen, under Steglich conditions, with secondary alcohols derived from (R)-carvone

    Energy Technology Data Exchange (ETDEWEB)

    Amongero, Marcela; Visnovezky, Damian; Kaufman, Teodoro S., E-mail: kaufman@iquir-conicet.gov.a [Instituto de Quimica Rosario (IQUIR, CONICET-UNR) (Argentina); Universidad Nacional de Rosario (Argentina)

    2010-07-01

    The synthesis of a series of chiral secondary alcohols derived from (R)-carvone, and the stereochemical outcome of their reaction with (+-)-ibuprofen, is reported. The racemic drug was transformed into the corresponding diastereomeric esters mediated by DCC/DMAP, affording up to 5.7:1 diastereomeric ratios of the esters derived from either (S)- or (R)-ibuprofen, depending on the type of chiral auxiliary employed. (author)

  16. Chiral auxiliary-mediated enantioenrichment of (+-)-ibuprofen, under Steglich conditions, with secondary alcohols derived from (R)-carvone

    International Nuclear Information System (INIS)

    Amongero, Marcela; Visnovezky, Damian; Kaufman, Teodoro S.

    2010-01-01

    The synthesis of a series of chiral secondary alcohols derived from (R)-carvone, and the stereochemical outcome of their reaction with (±)-ibuprofen, is reported. The racemic drug was transformed into the corresponding diastereomeric esters mediated by DCC/DMAP, affording up to 5.7:1 diastereomeric ratios of the esters derived from either (S)- or (R)-ibuprofen, depending on the type of chiral auxiliary employed. (author)

  17. Chromosomal rearrangements in Tourette syndrome

    DEFF Research Database (Denmark)

    Bertelsen, Birgitte; Debes, Nanette Mol; Hjermind, Lena E

    2013-01-01

    , and identification of susceptibility genes through linkage and association studies has been complicated due to inherent difficulties such as no clear mode of inheritance, genetic heterogeneity, and apparently incomplete penetrance. Positional cloning through mapping of disease-related chromosome rearrangements has...... been an efficient tool for the cloning of disease genes in several Mendelian disorders and in a number of complex disorders. Through cytogenetic investigation of 205 TS patients, we identified three possibly disease-associated chromosome rearrangements rendering this approach relevant in chasing TS...

  18. Developing Leadership Capacity in English Secondary Schools and Universities: Global Positioning and Local Mediation

    Science.gov (United States)

    Wallace, Mike; Deem, Rosemary; O'Reilly, Dermot; Tomlinson, Michael

    2011-01-01

    Government responses to globalisation include developing educational leaders as reformers for workforce competitiveness in the knowledge economy. Qualitative research tracked interventions involving national leadership development bodies to acculturate leaders in secondary schools and universities. Acculturating leaders as reformers was mediated…

  19. Contribution of canonical nonhomologous end joining to chromosomal rearrangements is enhanced by ATM kinase deficiency.

    Science.gov (United States)

    Bhargava, Ragini; Carson, Caree R; Lee, Gabriella; Stark, Jeremy M

    2017-01-24

    A likely mechanism of chromosomal rearrangement formation involves joining the ends from two different chromosomal double-strand breaks (DSBs). These events could potentially be mediated by either of two end-joining (EJ) repair pathways [canonical nonhomologous end joining (C-NHEJ) or alternative end joining (ALT-EJ)], which cause distinct rearrangement junction patterns. The relative role of these EJ pathways during rearrangement formation has remained controversial. Along these lines, we have tested whether the DNA damage response mediated by the Ataxia Telangiectasia Mutated (ATM) kinase may affect the relative influence of C-NHEJ vs. ALT-EJ on rearrangement formation. We developed a reporter in mouse cells for a 0.4-Mbp deletion rearrangement that is formed by EJ between two DSBs induced by the Cas9 endonuclease. We found that disruption of the ATM kinase causes an increase in the frequency of the rearrangement as well as a shift toward rearrangement junctions that show hallmarks of C-NHEJ. Furthermore, ATM suppresses rearrangement formation in an experimental condition, in which C-NHEJ is the predominant EJ repair event (i.e., expression of the 3' exonuclease Trex2). Finally, several C-NHEJ factors are required for the increase in rearrangement frequency caused by inhibition of the ATM kinase. We also examined ATM effectors and found that H2AX shows a similar influence as ATM, whereas the influence of ATM on this rearrangement seems independent of 53BP1. We suggest that the contribution of the C-NHEJ pathway to the formation of a 0.4-Mbp deletion rearrangement is enhanced in ATM-deficient cells.

  20. Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1-Induced Parathyroid Cell Proliferation in Secondary Hyperparathyroidism.

    Science.gov (United States)

    Volovelsky, Oded; Cohen, Gili; Kenig, Ariel; Wasserman, Gilad; Dreazen, Avigail; Meyuhas, Oded; Silver, Justin; Naveh-Many, Tally

    2016-04-01

    Secondary hyperparathyroidism is characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation. However, the molecular pathways mediating the increased parathyroid cell proliferation remain undefined. Here, we found that the mTOR pathway was activated in the parathyroid of rats with secondary hyperparathyroidism induced by either chronic hypocalcemia or uremia, which was measured by increased phosphorylation of ribosomal protein S6 (rpS6), a downstream target of the mTOR pathway. This activation correlated with increased parathyroid cell proliferation. Inhibition of mTOR complex 1 by rapamycin decreased or prevented parathyroid cell proliferation in secondary hyperparathyroidism rats and in vitro in uremic rat parathyroid glands in organ culture. Knockin rpS6(p-/-) mice, in which rpS6 cannot be phosphorylated because of substitution of all five phosphorylatable serines with alanines, had impaired PTH secretion after experimental uremia- or folic acid-induced AKI. Uremic rpS6(p-/-) mice had no increase in parathyroid cell proliferation compared with a marked increase in uremic wild-type mice. These results underscore the importance of mTOR activation and rpS6 phosphorylation for the pathogenesis of secondary hyperparathyroidism and indicate that mTORC1 is a significant regulator of parathyroid cell proliferation through rpS6. Copyright © 2016 by the American Society of Nephrology.

  1. The hardness of train rearrangements

    NARCIS (Netherlands)

    Eggermont, C.E.J.; Hurkens, C.A.J.; Modelski, M.S.; Woeginger, G.J.

    2009-01-01

    We derive several results on the computational complexity of train rearrangement problems in railway optimization. Our main result states that arranging a departing train in a depot is NP-complete, even if each track in the depot contains only two cars.

  2. Translocation and gross deletion breakpoints in human inherited disease and cancer II: Potential involvement of repetitive sequence elements in secondary structure formation between DNA ends.

    Science.gov (United States)

    Chuzhanova, Nadia; Abeysinghe, Shaun S; Krawczak, Michael; Cooper, David N

    2003-09-01

    Translocations and gross deletions are responsible for a significant proportion of both cancer and inherited disease. Although such gene rearrangements are nonuniformly distributed in the human genome, the underlying mutational mechanisms remain unclear. We have studied the potential involvement of various types of repetitive sequence elements in the formation of secondary structure intermediates between the single-stranded DNA ends that recombine during rearrangements. Complexity analysis was used to assess the potential of these ends to form secondary structures, the maximum decrease in complexity consequent to a gross rearrangement being used as an indicator of the type of repeat and the specific DNA ends involved. A total of 175 pairs of deletion/translocation breakpoint junction sequences available from the Gross Rearrangement Breakpoint Database [GRaBD; www.uwcm.ac.uk/uwcm/mg/grabd/grabd.html] were analyzed. Potential secondary structure was noted between the 5' flanking sequence of the first breakpoint and the 3' flanking sequence of the second breakpoint in 49% of rearrangements and between the 5' flanking sequence of the second breakpoint and the 3' flanking sequence of the first breakpoint in 36% of rearrangements. Inverted repeats, inversions of inverted repeats, and symmetric elements were found in association with gross rearrangements at approximately the same frequency. However, inverted repeats and inversions of inverted repeats accounted for the vast majority (83%) of deletions plus small insertions, symmetric elements for one-half of all antigen receptor-mediated translocations, while direct repeats appear only to be involved in mediating simple deletions. These findings extend our understanding of illegitimate recombination by highlighting the importance of secondary structure formation between single-stranded DNA ends at breakpoint junctions. Copyright 2003 Wiley-Liss, Inc.

  3. Biotransformation and Rearrangement of Laromustine.

    Science.gov (United States)

    Nassar, Alaa-Eldin F; Wisnewski, Adam V; King, Ivan

    2016-08-01

    This review highlights the recent research into the biotransformations and rearrangement of the sulfonylhydrazine-alkylating agent laromustine. Incubation of [(14)C]laromustine with rat, dog, monkey, and human liver microsomes produced eight radioactive components (C-1 to C-8). There was little difference in the metabolite profile among the species examined, partly because NADPH was not required for the formation of most components, which instead involved decomposition and/or hydrolysis. The exception was C-7, a hydroxylated metabolite, largely formed by CYP2B6 and CYP3A4/5. Liquid chromatography-multistage mass spectrometry (LC-MS(n)) studies determined that collision-induced dissociation, and not biotransformation or enzyme catalysis, produced the unique mass spectral rearrangement. Accurate mass measurements performed with a Fourier-transform ion cyclotron resonance mass spectrometer (FTICR-MS) significantly aided determination of the elemental compositions of the fragments and in the case of laromustine revealed the possibility of rearrangement. Further, collision-induced dissociation produced the loss of nitrogen (N2) and methylsulfonyl and methyl isocyanate moieties. The rearrangement, metabolite/decomposition products, and conjugation reactions were analyzed utilizing hydrogen-deuterium exchange, exact mass, (13)C-labeled laromustine, nuclear magnetic resonance spectroscopy (NMR), and LC-MS(n) experiments to assist with the assignments of these fragments and possible mechanistic rearrangement. Such techniques produced valuable insights into these functions: 1) Cytochrome P450 is involved in C-7 formation but plays little or no role in the conversion of [(14)C]laromustine to C-1 through C-6 and C-8; 2) the relative abundance of individual degradation/metabolite products was not species-dependent; and 3) laromustine produces several reactive intermediates that may produce the toxicities seen in the clinical trials. Copyright © 2016 by The American Society for

  4. Representations as Mediation between Purposes as Junior Secondary Science Students Learn about the Human Body

    Science.gov (United States)

    Olander, Clas; Wickman, Per-Olof; Tytler, Russell; Ingerman, Åke

    2018-01-01

    The aim of this article is to investigate students' meaning-making processes of multiple representations during a teaching sequence about the human body in lower secondary school. Two main influences are brought together to accomplish the analysis: on the one hand, theories on signs and representations as scaffoldings for learning and, on the…

  5. Role of Cereal Secondary Metabolites Involved in Mediating the Outcome of Plant-Pathogen Interactions

    Directory of Open Access Journals (Sweden)

    Lauren A. Du Fall

    2011-12-01

    Full Text Available Cereal crops such as wheat, rice and barley underpin the staple diet for human consumption globally. A multitude of threats to stable and secure yields of these crops exist including from losses caused by pathogens, particularly fungal. Plants have evolved complex mechanisms to resist pathogens including programmed cell death responses, the release of pathogenicity-related proteins and oxidative bursts. Another such mechanism is the synthesis and release of secondary metabolites toxic to potential pathogens. Several classes of these compounds have been identified and their anti-fungal properties demonstrated. However the lack of suitable analytical techniques has hampered the progress of identifying and exploiting more of these novel metabolites. In this review, we summarise the role of the secondary metabolites in cereal crop diseases and briefly touch on the analytical techniques that hold the key to unlocking their potential in reducing yield losses.

  6. water stress mediated changes in growth, physiology and secondary metabolites of desi ajwain (trachyspermum ammi l.)

    International Nuclear Information System (INIS)

    Azhar, N.; Hussain, B.; Abbasi, K.Y.

    2011-01-01

    Biotic and abiotic stresses exert a considerable influence on the production of several secondary metabolites in plants; water stress is one of the most important abiotic stress factors. This study was carried out to elucidate the effect of drought stress on growth, physiology and secondary metabolite production in desi ajwain (Trachyspermum ammi L.). Plants were grown in pots and three drought levels (100%, 80% and 60%) of field capacity were created. The experiment was laid out in complete randomized design (CRD) with three replicates. Data on growth, physiological and biochemical parameters were recorded and analyzed statistically. Physiological parameters like transpiration rate and stomatal conductance decreased concentration increased. The photosynthetic rate showed significantly with increasing water stress levels, but internal CO/sub 2/ non-significant reduction from 100% field capacity to 80% field capacity but increased at 60% field capacity. Growth parameters including plant height, herb fresh and dry weights were reduced significantly with increasing stress levels, while total phenolic contents and chlorophyll contents increased under water stress conditions. These results suggest that cultivation of medicinal plants like desi ajwain under drought stress could enhance the production of secondary metabolites. (author)

  7. The Mediating Roles of Primary and Secondary Control in the Relationship between Body Satisfaction and Subjective Well-Being Among Middle-Aged and Older Women.

    Science.gov (United States)

    Watt, Ashli D; Konnert, Candace A; Speirs, Calandra E C

    2017-07-01

    This study examined primary and secondary control as mediators in the relationship between body satisfaction and subjective well-being (SWB) and explored age differences in the mediation model. Data from 362 women, aged 40-91 years, assessed (i) the relationships between body satisfaction, age, primary and secondary control strategies (body-specific social comparison, acceptance, and positive reappraisal), and three indices of SWB (positive affect, negative affect, and life satisfaction), (ii) the mediation effects of primary and secondary control on the relationship between body satisfaction and SWB, and (iii) whether mediational relationships were moderated by age. Body satisfaction was unrelated to age but positively related to positive affect and life satisfaction and negatively related to negative affect. Body satisfaction was also related to primary and secondary control strategies. There were significant indirect (mediated) effects of body satisfaction on all outcome variables through acceptance and positive reappraisal. These mediators were significant at all age levels, but exerted their strongest influence among younger women. This study provides new information about the mechanisms that influence the relationship between body satisfaction and SWB among a broad age range of women who are experiencing physical changes that are inconsistent with Western beauty standards. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Bacterial and iron oxide aggregates mediate secondary iron mineral formation: green rust versus magnetite.

    Science.gov (United States)

    Zegeye, A; Mustin, C; Jorand, F

    2010-06-01

    In the presence of methanoate as electron donor, Shewanella putrefaciens, a Gram-negative, facultative anaerobe, is able to transform lepidocrocite (gamma-FeOOH) to secondary Fe (II-III) minerals such as carbonated green rust (GR1) and magnetite. When bacterial cells were added to a gamma-FeOOH suspension, aggregates were produced consisting of both bacteria and gamma-FeOOH particles. Recently, we showed that the production of secondary minerals (GR1 vs. magnetite) was dependent on bacterial cell density and not only on iron reduction rates. Thus, gamma-FeOOH and S. putrefaciens aggregation pattern was suggested as the main mechanism driving mineralization. In this study, lepidocrocite bioreduction experiments, in the presence of anthraquinone disulfonate, were conducted by varying the [cell]/[lepidocrocite] ratio in order to determine whether different types of aggregate are formed, which may facilitate precipitation of GR1 as opposed to magnetite. Confocal laser scanning microscopy was used to analyze the relative cell surface area and lepidocrocite concentration within the aggregates and captured images were characterized by statistical methods for spatial data (i.e. variograms). These results suggest that the [cell]/[lepidocrocite] ratio influenced both the aggregate structure and the nature of the secondary iron mineral formed. Subsequently, a [cell]/[lepidocrocite] ratio above 1 x 10(7) cells mmol(-1) leads to densely packed aggregates and to the formation of GR1. Below this ratio, looser aggregates are formed and magnetite was systematically produced. The data presented in this study bring us closer to a more comprehensive understanding of the parameters governing the formation of minerals in dense bacterial suspensions and suggest that screening mineral-bacteria aggregate structure is critical to understanding (bio)mineralization pathways.

  9. RuO4-mediated oxidation of secondary amines 2. imines as main reaction intermediates

    Directory of Open Access Journals (Sweden)

    Florea Cristina A.

    2017-01-01

    Full Text Available Oxidation by RuO4 (generated in situ from RuO2 and NaIO4 of secondary amines such as Bn–NH–CH2R (1; R=H, Me gave complex reaction mixtures, but mainly amides. In the presence of cyanide, the leading products were α-aminonitriles. Comparison of the oxidation products of 1 with those from the corresponding imines PhCH=N–CH2R and Bn–N=CH–R showed that formation of the indicated imines is the first main step in the oxidation of 1. A detailed mechanism is proposed.

  10. Chlorovirus-mediated membrane depolarization of Chlorella alters secondary active transport of solutes.

    Science.gov (United States)

    Agarkova, Irina; Dunigan, David; Gurnon, James; Greiner, Timo; Barres, Julia; Thiel, Gerhard; Van Etten, James L

    2008-12-01

    Paramecium bursaria chlorella virus 1 (PBCV-1) is the prototype of a family of large, double-stranded DNA, plaque-forming viruses that infect certain eukaryotic chlorella-like green algae from the genus Chlorovirus. PBCV-1 infection results in rapid host membrane depolarization and potassium ion release. One interesting feature of certain chloroviruses is that they code for functional potassium ion-selective channel proteins (Kcv) that are considered responsible for the host membrane depolarization and, as a consequence, the efflux of potassium ions. This report examines the relationship between cellular depolarization and solute uptake. Annotation of the virus host Chlorella strain NC64A genome revealed 482 putative transporter-encoding genes; 224 are secondary active transporters. Solute uptake experiments using seven radioactive compounds revealed that virus infection alters the transport of all the solutes. However, the degree of inhibition varied depending on the solute. Experiments with nystatin, a drug known to depolarize cell membranes, produced changes in solute uptake that are similar but not identical to those that occurred during virus infection. Therefore, these studies indicate that chlorovirus infection causes a rapid and sustained depolarization of the host plasma membrane and that this depolarization leads to the inhibition of secondary active transporters that changes solute uptake.

  11. RuO4-mediated oxidation of secondary amines: Part 1. Are hydroxylamines main intermediates?

    Directory of Open Access Journals (Sweden)

    Florea Cristina A.

    2016-01-01

    Full Text Available The RuO4-catalyzed oxidation of secondary amines Bn-NH-CH2R (1a-b; R=H, Me gave mainly amides, but minute amounts of nitrones PhCH=N(O-CH2R (9a-b and traces of Bn-N(OH-CH2R (R=H, 4a were also detected. In the presence of cyanide, up to 22 reaction products were identified, but mainly α-aminonitriles. Comparison of the oxidation products of 1a-b with those of 4a-b, 9a-b, and Bn-N(O=CHR (10a-b showed that 4a-b cannot be main reaction intermediates formed from 1a-b.

  12. An RNA secondary structure bias for non-homologous reverse transcriptase-mediated deletions in vivo

    DEFF Research Database (Denmark)

    Duch, Mogens; Carrasco, Maria L; Jespersen, Thomas

    2004-01-01

    Murine leukemia viruses harboring an internal ribosome entry site (IRES)-directed translational cassette are able to replicate, but undergo loss of heterologous sequences upon continued passage. While complete loss of heterologous sequences is favored when these are flanked by a direct repeat......, deletion mutants with junction sites within the heterologous cassette may also be retrieved, in particular from vectors without flanking repeats. Such deletion mutants were here used to investigate determinants of reverse transcriptase-mediated non-homologous recombination. Based upon previous structural...... result from template switching during first-strand cDNA synthesis and that the choice of acceptor sites for non-homologous recombination are guided by non-paired regions. Our results may have implications for recombination events taking place within structured regions of retroviral RNA genomes...

  13. Dopamine agonist suppression of rapid-eye-movement sleep is secondary to sleep suppression mediated via limbic structures

    International Nuclear Information System (INIS)

    Miletich, R.S.

    1985-01-01

    The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and 3 H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by α-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period, phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S 2 episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. 3 H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system

  14. Mediational pathways connecting secondary education and age at marriage to maternal mortality: A comparison between developing and developed countries.

    Science.gov (United States)

    Hagues, Rachel Joy; Bae, DaYoung; Wickrama, Kandauda K A S

    2017-02-01

    While studies have shown that maternal mortality rates have been improving worldwide, rates are still high across developing nations. In general, poor health of women is associated with higher maternal mortality rates in developing countries. Understanding country-level risk factors can inform intervention and prevention efforts that could bring high maternal mortality rates down. Specifically, the authors were interested in investigating whether: (1) secondary education participation (SEP) or age at marriage (AM) of women were related to maternal mortality rates, and (2) adolescent birth rate and contraceptive use (CU) acted as mediators of this association. The authors add to the literature with this current article by showing the relation of SEP and AM to maternal mortality rates globally (both directly and indirectly through mediators) and then by comparing differences between developed and developing/least developed countries. Path analysis was used to test the hypothesized model using country level longitudinal data from 2000 to 2010 obtained from United Nations publications, World Health Organization materials, and World Bank development reports. Findings include a significant correlation between SEP and AM for developing countries; for developed countries the relation was not significant. As well, SEP in developing countries was associated with increased CU. Women in developing countries who finish school before marriage may have important social capital gains.

  15. Programmed Rearrangement in Ciliates: Paramecium.

    Science.gov (United States)

    Betermier, Mireille; Duharcourt, Sandra

    2014-12-01

    Programmed genome rearrangements in the ciliate Paramecium provide a nice illustration of the impact of transposons on genome evolution and plasticity. During the sexual cycle, development of the somatic macronucleus involves elimination of ∼30% of the germline genome, including repeated DNA (e.g., transposons) and ∼45,000 single-copy internal eliminated sequences (IES). IES excision is a precise cut-and-close process, in which double-stranded DNA cleavage at IES ends depends on PiggyMac, a domesticated piggyBac transposase. Genome-wide analysis has revealed that at least a fraction of IESs originate from Tc/mariner transposons unrelated to piggyBac. Moreover, genomic sequences with no transposon origin, such as gene promoters, can be excised reproducibly as IESs, indicating that genome rearrangements contribute to the control of gene expression. How the system has evolved to allow elimination of DNA sequences with no recognizable conserved motif has been the subject of extensive research during the past two decades. Increasing evidence has accumulated for the participation of noncoding RNAs in epigenetic control of elimination for a subset of IESs, and in trans-generational inheritance of alternative rearrangement patterns. This chapter summarizes our current knowledge of the structure of the germline and somatic genomes for the model species Paramecium tetraurelia, and describes the DNA cleavage and repair factors that constitute the IES excision machinery. We present an overview of the role of specialized RNA interference machineries and their associated noncoding RNAs in the control of DNA elimination. Finally, we discuss how RNA-dependent modification and/or remodeling of chromatin may guide PiggyMac to its cognate cleavage sites.

  16. Insomnia partially mediated the association between problematic Internet use and depression among secondary school students in China.

    Science.gov (United States)

    Li, Ji-Bin; Lau, Joseph T F; Mo, Phoenix K H; Su, Xue-Fen; Tang, Jie; Qin, Zu-Guo; Gross, Danielle L

    2017-12-01

    Background and aims This study aims to examine the mediating effects of insomnia on the associations between problematic Internet use, including Internet addiction (IA) and online social networking addiction (OSNA), and depression among adolescents. Methods A total of 1,015 secondary school students from Guangzhou in China participated in a cross-sectional survey. Levels of depression, insomnia, IA, and OSNA were assessed using the Center for Epidemiological Studies-Depression Scale, Pittsburgh Sleep Quality Index, Young's Diagnostic Questionnaire, and Online Social Networking Addiction Scale, respectively. Logistic regression models were fit to test the associations between IA, OSNA, insomnia, and depression. The mediation effects of insomnia were tested using Baron and Kenny's strategy. Results The prevalence of depression at moderate level or above (CES-D ≥ 21), insomnia, IA, and OSNA were 23.5%, 37.2%, 8.1%, and 25.5%, respectively. IA and OSNA were significantly associated with depression (IA: AOR = 2.79, 95% CI: 1.71, 4.55; OSNA: AOR = 3.27, 95% CI: 2.33, 4.59) and insomnia (IA: AOR = 2.83, 95% CI: 1.72, 4.65; OSNA: AOR = 2.19, 95% CI: 1.61, 2.96), after adjusting for significant background factors. Furthermore, insomnia partially mediated 60.6% of the effect of IA on depression (Sobel Z = 3.562, p high prevalence of IA and OSNA may be associated with increased risk of developing depression among adolescents, both through direct and indirect effects (via insomnia). Findings from this study indicated that it may be effective to develop and implement interventions that jointly consider the problematic Internet use, insomnia, and depression.

  17. Experimental data suggesting that inflammation mediated rat liver mitochondrial dysfunction results from secondary hypoxia rather than from direct effects of inflammatory mediators

    Directory of Open Access Journals (Sweden)

    Adelheid eWeidinger

    2013-06-01

    Full Text Available Systemic inflammatory response (SIR comprises direct effects of inflammatory mediators (IM and indirect effects, such as secondary circulatory failure which results in tissue hypoxia (HOX. These two key components, SIR and HOX, cause multiple organ failure (MOF. Since HOX and IM occur and interact simultaneously in vivo, it is difficult to clarify their individual pathological impact. To eliminate this interaction, precision cut liver slices (PCLS were used in this study aiming to dissect the effects of HOX and IM on mitochondrial function, integrity of cellular membrane and the expression of genes associated with inflammation. HOX was induced by incubating PCLS or rat liver mitochondria at pO2<1% followed by reoxygenation (HOX/ROX model. Inflammatory injury was stimulated by incubating PCLS with IM (IM model. We found upregulation of inducible nitric oxide synthase (iNOS expression only in the IM model, while heme oxygenase 1 (HO-1 expression was upregulated only in the HOX/ROX model. Elevated expression of interleukin 6 (IL-6 was found in both models reflecting converging pathways regulating the expression of this gene. Both models caused damage to hepatocytes resulting in the release of alanine aminotransferase (ALT. The leakage of aspartate aminotransferase (AST was observed only during the hypoxic phase in the HOX/ROX model. The reoxygenation phase of HOX, but not IM, drastically impaired mitochondrial electron supply via complex I and II. Additional experiments performed with isolated mitochondria showed that free iron, released during HOX, is likely a key prerequisite of mitochondrial dysfunction induced during the reoxygenation phase. Our data suggests that mitochondrial dysfunction, previously observed in in vivo SIR-models is the result of secondary circulatory failure inducing HOX rather than the result of a direct interaction of IM with liver cells.

  18. Thermal rearrangement of 7-methylbicyclo

    Science.gov (United States)

    Bender; Leber; Lirio; Smith

    2000-08-25

    The gas-phase thermal rearrangement of exo-7-methylbicyclo[3.2.0]hept-2-ene yields almost exclusively 5-methylnorbornene products. Inversion (i) of configuration dominates this [1,3] sigmatropic shift although some retention (r) is also observed. Because the [1,3] migration can only occur suprafacially (s) in this geometrically constrained system, the si/sr ratio of 7 observed for the migration of C7 in exo-7-methylbicyclo[3.2.0]hept-2-ene indicates that the orbital symmetry rules are somewhat permissive for the [1,3] sigmatropic migration of carbon.

  19. Representations as mediation between purposes as junior secondary science students learn about the human body

    Science.gov (United States)

    Olander, Clas; Wickman, Per-Olof; Tytler, Russell; Ingerman, Åke

    2018-01-01

    The aim of this article is to investigate students' meaning-making processes of multiple representations during a teaching sequence about the human body in lower secondary school. Two main influences are brought together to accomplish the analysis: on the one hand, theories on signs and representations as scaffoldings for learning and, on the other hand, pragmatist theories on how continuity between the purposes of different inquiry activities can be sustained. Data consist of 10 videotaped and transcribed lessons with 14-year-old students (N = 26) in Sweden. The analysis focused instances where meaning of representations was negotiated. Findings indicate that continuity is established in multiple ways, for example, as the use of metaphors articulated as an interlanguage expression that enables the students (and the teacher) to maintain the conversation and explain pressing issues in ways that support of the end-in-view of the immediate action. Continuity is also established between every day and scientific registers and between organisation levels as well as between the smaller parts and the whole system.

  20. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  1. Dopamine agonist suppression of rapid-eye-movement sleep is secondary to sleep suppression mediated via limbic structures

    Energy Technology Data Exchange (ETDEWEB)

    Miletich, R.S.

    1985-01-01

    The effects of pergolide, a direct dopamine receptor agonist, on sleep and wakefulness, motor behavior and /sup 3/H-spiperone specific binding in limbic structures and striatum in rats was studied. The results show that pergolide induced a biphasic dose effect, with high doses increasing wakefulness and suppressing sleep while low dose decreased wakefulness, but increased sleep. It was shown that pergolide-induced sleep suppression was blocked by ..cap alpha..-glupenthixol and pimozide, two dopamine receptor antagonists. It was further shown that pergolide merely delayed the rebound resulting from rapid-eye-movement (REM) sleep deprivation, that dopamine receptors stimulation had no direct effect on the period, phase or amplitude of the circadian rhythm of REM sleep propensity and that there was no alteration in the coupling of REM sleep episodes with S/sub 2/ episodes. Rapid-eye-movement sleep deprivation resulted in increased sensitivity to the pergolide-induced wakefulness stimulation and sleep suppression and pergolide-induced motor behaviors of locomotion and head bobbing. /sup 3/H-spiperone specific binding to dopamine receptors was shown to be altered by REM sleep deprivation in the subcortical limbic structures. It is concluded that the REM sleep suppressing action of dopamine receptor stimulation is secondary to sleep suppression per se and not secondary to a unique effect on the REM sleep. Further, it is suggested that the wakefulness stimulating action of dopamine receptor agonists is mediated by activation of the dopamine receptors in the terminal areas of the mesolimbocortical dopamine projection system.

  2. Rearrangements of organic peroxides and related processes

    Directory of Open Access Journals (Sweden)

    Ivan A. Yaremenko

    2016-08-01

    Full Text Available This review is the first to collate and summarize main data on named and unnamed rearrangement reactions of peroxides. It should be noted, that in the chemistry of peroxides two types of processes are considered under the term rearrangements. These are conventional rearrangements occurring with the retention of the molecular weight and transformations of one of the peroxide moieties after O–O-bond cleavage. Detailed information about the Baeyer−Villiger, Criegee, Hock, Kornblum−DeLaMare, Dakin, Elbs, Schenck, Smith, Wieland, and Story reactions is given. Unnamed rearrangements of organic peroxides and related processes are also analyzed. The rearrangements and related processes of important natural and synthetic peroxides are discussed separately.

  3. The mediating effects of coping strategies on the relationship between secondary traumatic stress and burnout in professional caregivers in the UAE.

    Science.gov (United States)

    Hamid, Abdalla A R M; Musa, Saif A

    2017-02-01

    Professional caregivers dealing with traumatized victims or mental health clients are at increased risk for developing the same symptoms as persons who are exposed directly to the trauma. This research was aimed at examining the relationship between secondary traumatic stress, burnout and coping strategies in 502 professional caregivers who work in schools, hospitals, charity institutes and welfare centers in the United Arab Emirates (UAE). A further aim was to test the mediating effect of coping on the relationship between burnout and secondary traumatic stress. Measures used in this study were the Professional Quality of Life Questionnaire (ProQOL), The General Health Questionnaire (GHQ-28), The Maslach Burnout Inventory: Human Services Survey (MBI-HSS) and Endler and Parker's Coping Inventory. Task-focused coping, personal accomplishment and compassion satisfaction were negatively associated with secondary traumatic stress. Burnout, emotion-focused and distraction coping were positively related to secondary traumatic stress. Coping partially mediated the relationship between burnout and secondary traumatic stress. There were also significant gender differences in depersonalization and distraction coping. Efforts need to focus on improvement of caregivers' work environments, enhancing their coping skills and professional development.

  4. Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms.

    Science.gov (United States)

    Kloosterman, Wigard P; Tavakoli-Yaraki, Masoumeh; van Roosmalen, Markus J; van Binsbergen, Ellen; Renkens, Ivo; Duran, Karen; Ballarati, Lucia; Vergult, Sarah; Giardino, Daniela; Hansson, Kerstin; Ruivenkamp, Claudia A L; Jager, Myrthe; van Haeringen, Arie; Ippel, Elly F; Haaf, Thomas; Passarge, Eberhard; Hochstenbach, Ron; Menten, Björn; Larizza, Lidia; Guryev, Victor; Poot, Martin; Cuppen, Edwin

    2012-06-28

    Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed unanticipated complexity resembling chromothripsis. We find that eight of them contain hallmarks of multiple clustered double-stranded DNA breaks (DSBs) on one or more chromosomes. In addition, nucleotide resolution analysis of 98 breakpoint junctions indicates that break repair involves nonhomologous or microhomology-mediated end joining. We observed that these eight rearrangements are balanced or contain sporadic deletions ranging in size between a few hundred base pairs and several megabases. The two remaining complex rearrangements did not display signs of DSBs and contain duplications, indicative of rearrangement processes involving template switching. Our work provides detailed insight into the characteristics of chromothripsis and supports a role for clustered DSBs driving some constitutional chromothripsis rearrangements. Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Sorting permutations by prefix and suffix rearrangements.

    Science.gov (United States)

    Lintzmayer, Carla Negri; Fertin, Guillaume; Dias, Zanoni

    2017-02-01

    Some interesting combinatorial problems have been motivated by genome rearrangements, which are mutations that affect large portions of a genome. When we represent genomes as permutations, the goal is to transform a given permutation into the identity permutation with the minimum number of rearrangements. When they affect segments from the beginning (respectively end) of the permutation, they are called prefix (respectively suffix) rearrangements. This paper presents results for rearrangement problems that involve prefix and suffix versions of reversals and transpositions considering unsigned and signed permutations. We give 2-approximation and ([Formula: see text])-approximation algorithms for these problems, where [Formula: see text] is a constant divided by the number of breakpoints (pairs of consecutive elements that should not be consecutive in the identity permutation) in the input permutation. We also give bounds for the diameters concerning these problems and provide ways of improving the practical results of our algorithms.

  6. Input-output rearrangement of isolated converters

    DEFF Research Database (Denmark)

    Madsen, Mickey Pierre; Kovacevic, Milovan; Mønster, Jakob Døllner

    2015-01-01

    This paper presents a new way of rearranging the input and output of isolated converters. The new arrangement posses several advantages, as increased voltage range, higher power handling capabilities, reduced voltage stress and improved efficiency, for applications where galvanic isolation...

  7. Functional rearrangement of the primary and secondary motor cortex in patients with primary tumors of the central nervous system located in the region of the central sulcus depending on the histopathological type and the size of tumor: Examination by means of functional magnetic resonance imaging

    International Nuclear Information System (INIS)

    Bryszewski, Bartosz; Pfajfer, Lucjan; Antosik-Biernacka, Aneta; Tybor, Krzysztof; Śmigielski, Janusz; Zawirski, Marek; Majos, Agata

    2012-01-01

    The aim of this study was to analyze the reorganization of the centers of the motor cortex in patients with primary neuroepithelial tumors of the central nervous system (CNS) located in the region of the central sulcus in relation to the histopathological type and the size of tumor, as determined by means of functional magnetic resonance imaging (fMRI). The fMRI was performed prior to the surgical treatment of patients with tumors located in the region of the central sulcus (WHO stage I and II, n=15; WHO stage III and IV, n=25). The analysis included a record of the activity in the areas of the primary motor cortex (M1) and the secondary motor cortex: the premotor cortex (PMA) and the accessory motor area (SMA). The results were correlated with the histopathological type of the tumor and its size expressed in cm 3 . The frequency of activation of the motor center was higher in the group of patients who had less aggressive tumors, such as low-grade glioma (LGG), as well as in tumors of lower volume, and this was true both for the hemisphere where the tumor was located and in the contralateral one. Mean values of t-statistics of activation intensity, mean numbers of activated clusters, and their ranges were lower in all analyzed motor areas of LGG tumors. The values of t-statistics and activation areas were higher in the case of small tumors located in ipsilateral centers, and in large tumors located in contralateral centers, aside from the SMA area where the values of t-statistics were equal for both groups. The contralateral SMA area was characterized by the highest stability of all examined centers of secondary motor cortex. No significant association (p>0.05) was observed between the absolute value of the mean registered activity (t-statistics) and the size of examined areas (number of clusters) when the groups were stratified with regards to the analyzed parameters. The presence of a neoplastic lesion, its histopathological type and finally its size modulate the

  8. A DFT exploration of the enantioselective rearrangement of cyclohexene oxide to cyclohexenol

    DEFF Research Database (Denmark)

    Brandt, Peter; Norrby, Per-Ola; Andersson, Pher G.

    2003-01-01

    In this paper, we present computational results for the (1S,3R,4R)-3-(pyrrolidinyl)-methyl-2-azabicyclo[2.2.1]heptane mediated rearrangement of cyclohexene oxide. The results nicely explain the differences in enantioselectivities between catalytic and stoichiometric mode between different ligands...

  9. Direct analysis by time-of-flight secondary ion mass spectrometry reveals action of bacterial laccase-mediator systems on both hardwood and softwood samples.

    Science.gov (United States)

    Goacher, Robyn E; Braham, Erick J; Michienzi, Courtney L; Flick, Robert M; Yakunin, Alexander F; Master, Emma R

    2017-12-29

    The modification and degradation of lignin play a vital role in carbon cycling as well as production of biofuels and bioproducts. The possibility of using bacterial laccases for the oxidation of lignin offers a route to utilize existing industrial protein expression techniques. However, bacterial laccases are most frequently studied on small model compounds that do not capture the complexity of lignocellulosic materials. This work studied the action of laccases from Bacillus subtilis and Salmonella typhimurium (EC 1.10.3.2) on ground wood samples from yellow birch (Betula alleghaniensis) and red spruce (Picea rubens). The ability of bacterial laccases to modify wood can be facilitated by small molecule mediators. Herein, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), gallic acid and sinapic acid mediators were tested. Direct analysis of the wood samples was achieved by time-of-flight secondary ion mass spectrometry (ToF-SIMS), a surface sensitive mass spectrometry technique that has characteristic peaks for H, G and S lignin. The action of the bacterial laccases on both wood samples was demonstrated and revealed a strong mediator influence. The ABTS mediator led to delignification, evident in an overall increase of polysaccharide peaks in the residual solid, along with equal loss of G and S-lignin peaks. The gallic acid mediator demonstrated minimal laccase activity. Meanwhile, the sinapic acid mediator altered the S/G peak ratio consistent with mediator attaching to the wood solids. The current investigation demonstrates the action of bacterial laccase-mediator systems directly on woody materials, and the potential of using ToF-SIMS to uncover the fundamental and applied role of bacterial enzymes in lignocellulose conversion. © 2017 Scandinavian Plant Physiology Society.

  10. The mediating role of secondary beliefs: enhancing the understanding of emotional responses and illness perceptions in arthritis.

    Science.gov (United States)

    McCracken, James; Lindner, Helen; Sciacchitano, Laura

    2008-01-01

    Chronic illnesses are a significant issue across many health professional domains, becoming an increasing burden on limited and costly resources. The current study investigated the relationship between secondary beliefs and emotional responses, beyond the relationship accounted for by illness perceptions, using the framework of Rational Emotive Behavior Therapy. Sixty-five adults with arthritis participated in the questionnaire-based study. Multivariate analysis found that different emotional representations of the illness were significantly predicted by the individual's secondary belief, above and beyond that predicted by the cognitive representation of their illness alone. The study found that individuals who utilized an achievement secondary belief experienced feelings of worry, whereas individuals who used an approval orientation to understand their arthritis experienced emotions such as depression, being upset, anger, anxiety, and fear. No significant pattern emerged for individuals who used a comfort secondary belief to understand their arthritis. These findings are in line with the theory of secondary beliefs, as articulated by Rational Emotive Behavior Therapy.

  11. Caryolene-forming carbocation rearrangements

    Directory of Open Access Journals (Sweden)

    Quynh Nhu N. Nguyen

    2013-02-01

    Full Text Available Density functional theory calculations on mechanisms of the formation of caryolene, a putative biosynthetic precursor to caryol-1(11-en-10-ol, reveal two mechanisms for caryolene formation: one involves a base-catalyzed deprotonation/reprotonation sequence and tertiary carbocation minimum, whereas the other (with a higher energy barrier involves intramolecular proton transfer and the generation of a secondary carbocation minimum and a hydrogen-bridged minimum. Both mechanisms are predicted to involve concerted suprafacial/suprafacial [2 + 2] cycloadditions, whose asynchronicity allows them to avoid the constraints of orbital symmetry.

  12. Rearrangement of cluster structure during fission processes

    DEFF Research Database (Denmark)

    Lyalin, Andrey G.; Obolensky, Oleg I.; Solov'yov, Andrey V.

    2004-01-01

    Results of molecular dynamics simulations of fission reactions $Na_10^2+ -->Na_7^++ Na_3^+ and Na_18^2+--> 2Na_9^+ are presented. The dependence of the fission barriers on the isomer structure of the parent cluster is analysed. It is demonstrated that the energy necessary for removing homothetic...... groups of atoms from the parent cluster is largely independent of the isomer form of the parent cluster. The importance of rearrangement of the cluster structure during the fission process is elucidated. This rearrangement may include transition to another isomer state of the parent cluster before actual...

  13. Relationship between mitochondrial gene rearrangements and stability of the origin of light strand replication

    Directory of Open Access Journals (Sweden)

    Miguel M. Fonseca

    2008-01-01

    Full Text Available Mitochondrial gene rearrangements are much more frequent in vertebrates than initially thought. It has been suggested that the origin of light strand replication could have an important role in the process of gene rearrangements, but this hypothesis has never been tested before. We used amphibians to test the correlation between light-strand replication origin thermodynamic stability and the occurrence of gene rearrangements. The two variables were correlated in a non-phylogenetic approach, but when tested in a phylogenetically based comparative method the correlation was not significant, although species with unstable light-strand replication origins were much more likely to have undergone gene rearrangements. This indicates that within amphibians there are stable and unstable phylogenetic groups regarding mitochondrial gene order. The species analyzed showed variability in the thermodynamic stability of the secondary structure, in the length of its stem and loop, and several species did not present the 5’-GCCGG-3’ motif reported to be necessary for efficient mitochondrial DNA replication. Future studies should focus on the role of the light-strand replication origin in mitochondrial DNA replication and gene rearrangements mechanisms.

  14. Transposon domestication versus mutualism in ciliate genome rearrangements.

    Directory of Open Access Journals (Sweden)

    Alexander Vogt

    Full Text Available Ciliated protists rearrange their genomes dramatically during nuclear development via chromosome fragmentation and DNA deletion to produce a trimmer and highly reorganized somatic genome. The deleted portion of the genome includes potentially active transposons or transposon-like sequences that reside in the germline. Three independent studies recently showed that transposase proteins of the DDE/DDD superfamily are indispensible for DNA processing in three distantly related ciliates. In the spirotrich Oxytricha trifallax, high copy-number germline-limited transposons mediate their own excision from the somatic genome but also contribute to programmed genome rearrangement through a remarkable transposon mutualism with the host. By contrast, the genomes of two oligohymenophorean ciliates, Tetrahymena thermophila and Paramecium tetraurelia, encode homologous PiggyBac-like transposases as single-copy genes in both their germline and somatic genomes. These domesticated transposases are essential for deletion of thousands of different internal sequences in these species. This review contrasts the events underlying somatic genome reduction in three different ciliates and considers their evolutionary origins and the relationships among their distinct mechanisms for genome remodeling.

  15. Genomic regulatory landscapes and chromosomal rearrangements

    DEFF Research Database (Denmark)

    Ladegaard, Elisabete L Engenheiro

    2008-01-01

    The main objectives of the PhD study are to identify and characterise chromosomal rearrangements within evolutionarily conserved regulatory landscapes around genes involved in the regulation of transcription and/or development (trans-dev genes). A frequent feature of trans-dev genes is that they ......The main objectives of the PhD study are to identify and characterise chromosomal rearrangements within evolutionarily conserved regulatory landscapes around genes involved in the regulation of transcription and/or development (trans-dev genes). A frequent feature of trans-dev genes...... the complex spatio-temporal expression of the associated trans-dev gene. Rare chromosomal breakpoints that disrupt the integrity of these regulatory landscapes may be used as a tool, not only to make genotype-phenotype associations, but also to link the associated phenotype with the position and tissue...... specificity of the individual CNEs. In this PhD study I have studied several chromosomal rearrangements with breakpoints in the vicinity of trans-dev genes. This included chromosomal rearrangements compatible with known phenotype-genotype associations (Rieger syndrome-PITX2, Mowat-Wilson syndrome-ZEB2...

  16. Generalization of the quark rearrangement model

    International Nuclear Information System (INIS)

    Fields, T.; Chen, C.K.

    1976-01-01

    An extension and generalization of the quark rearrangement model of baryon annihilation is described which can be applied to all annihilation reactions and which incorporates some of the features of the highly successful quark parton model. Some p anti-p interactions are discussed

  17. Dynamics of genome rearrangement in bacterial populations.

    Directory of Open Access Journals (Sweden)

    Aaron E Darling

    2008-07-01

    Full Text Available Genome structure variation has profound impacts on phenotype in organisms ranging from microbes to humans, yet little is known about how natural selection acts on genome arrangement. Pathogenic bacteria such as Yersinia pestis, which causes bubonic and pneumonic plague, often exhibit a high degree of genomic rearrangement. The recent availability of several Yersinia genomes offers an unprecedented opportunity to study the evolution of genome structure and arrangement. We introduce a set of statistical methods to study patterns of rearrangement in circular chromosomes and apply them to the Yersinia. We constructed a multiple alignment of eight Yersinia genomes using Mauve software to identify 78 conserved segments that are internally free from genome rearrangement. Based on the alignment, we applied Bayesian statistical methods to infer the phylogenetic inversion history of Yersinia. The sampling of genome arrangement reconstructions contains seven parsimonious tree topologies, each having different histories of 79 inversions. Topologies with a greater number of inversions also exist, but were sampled less frequently. The inversion phylogenies agree with results suggested by SNP patterns. We then analyzed reconstructed inversion histories to identify patterns of rearrangement. We confirm an over-representation of "symmetric inversions"-inversions with endpoints that are equally distant from the origin of chromosomal replication. Ancestral genome arrangements demonstrate moderate preference for replichore balance in Yersinia. We found that all inversions are shorter than expected under a neutral model, whereas inversions acting within a single replichore are much shorter than expected. We also found evidence for a canonical configuration of the origin and terminus of replication. Finally, breakpoint reuse analysis reveals that inversions with endpoints proximal to the origin of DNA replication are nearly three times more frequent. Our findings

  18. Rearrangement moves on rooted phylogenetic networks.

    Science.gov (United States)

    Gambette, Philippe; van Iersel, Leo; Jones, Mark; Lafond, Manuel; Pardi, Fabio; Scornavacca, Celine

    2017-08-01

    Phylogenetic tree reconstruction is usually done by local search heuristics that explore the space of the possible tree topologies via simple rearrangements of their structure. Tree rearrangement heuristics have been used in combination with practically all optimization criteria in use, from maximum likelihood and parsimony to distance-based principles, and in a Bayesian context. Their basic components are rearrangement moves that specify all possible ways of generating alternative phylogenies from a given one, and whose fundamental property is to be able to transform, by repeated application, any phylogeny into any other phylogeny. Despite their long tradition in tree-based phylogenetics, very little research has gone into studying similar rearrangement operations for phylogenetic network-that is, phylogenies explicitly representing scenarios that include reticulate events such as hybridization, horizontal gene transfer, population admixture, and recombination. To fill this gap, we propose "horizontal" moves that ensure that every network of a certain complexity can be reached from any other network of the same complexity, and "vertical" moves that ensure reachability between networks of different complexities. When applied to phylogenetic trees, our horizontal moves-named rNNI and rSPR-reduce to the best-known moves on rooted phylogenetic trees, nearest-neighbor interchange and rooted subtree pruning and regrafting. Besides a number of reachability results-separating the contributions of horizontal and vertical moves-we prove that rNNI moves are local versions of rSPR moves, and provide bounds on the sizes of the rNNI neighborhoods. The paper focuses on the most biologically meaningful versions of phylogenetic networks, where edges are oriented and reticulation events clearly identified. Moreover, our rearrangement moves are robust to the fact that networks with higher complexity usually allow a better fit with the data. Our goal is to provide a solid basis for

  19. Rearrangement moves on rooted phylogenetic networks.

    Directory of Open Access Journals (Sweden)

    Philippe Gambette

    2017-08-01

    Full Text Available Phylogenetic tree reconstruction is usually done by local search heuristics that explore the space of the possible tree topologies via simple rearrangements of their structure. Tree rearrangement heuristics have been used in combination with practically all optimization criteria in use, from maximum likelihood and parsimony to distance-based principles, and in a Bayesian context. Their basic components are rearrangement moves that specify all possible ways of generating alternative phylogenies from a given one, and whose fundamental property is to be able to transform, by repeated application, any phylogeny into any other phylogeny. Despite their long tradition in tree-based phylogenetics, very little research has gone into studying similar rearrangement operations for phylogenetic network-that is, phylogenies explicitly representing scenarios that include reticulate events such as hybridization, horizontal gene transfer, population admixture, and recombination. To fill this gap, we propose "horizontal" moves that ensure that every network of a certain complexity can be reached from any other network of the same complexity, and "vertical" moves that ensure reachability between networks of different complexities. When applied to phylogenetic trees, our horizontal moves-named rNNI and rSPR-reduce to the best-known moves on rooted phylogenetic trees, nearest-neighbor interchange and rooted subtree pruning and regrafting. Besides a number of reachability results-separating the contributions of horizontal and vertical moves-we prove that rNNI moves are local versions of rSPR moves, and provide bounds on the sizes of the rNNI neighborhoods. The paper focuses on the most biologically meaningful versions of phylogenetic networks, where edges are oriented and reticulation events clearly identified. Moreover, our rearrangement moves are robust to the fact that networks with higher complexity usually allow a better fit with the data. Our goal is to provide

  20. Self-beliefs mediate mathematical performance between primary and lower secondary school: A large scale longitudinal cohort study

    NARCIS (Netherlands)

    Reed, Helen; Kirschner, Paul A.; Jolles, Jelle

    2016-01-01

    It is often argued that enhancement of self-beliefs should be one of the key goals ofeducation. However, very little is known about the relation between self-beliefs and performance when students move from primary to secondary school in highly differentiated educational systems with early tracking.

  1. The Ultrafast Wolff Rearrangement in the Gas Phase

    Science.gov (United States)

    Steinbacher, Andreas; Roeding, Sebastian; Brixner, Tobias; Nuernberger, Patrick

    The Wolff rearrangement of gas-phase 5-diazo Meldrum's acid is disclosed with femtosecond ion spectroscopy. Distinct differences are found for 267 nm and 200 nm excitation, the latter leading to even two ultrafast rearrangement reactions.

  2. Triflic Anhydride-Mediated Beckmann Rearrangement Reaction of β ...

    Indian Academy of Sciences (India)

    aSchool of Chemistry and Materials Science, Heilongjiang University, Harbin 150080, China. bKey Laboratory of Synthetic Rubber, Changchun Institute of Applied Chemistry, ... which meanwhile releases quite a lot of acidic wastes.1,3.

  3. A Kinetics Investigation on the Nitro-Nitrite Rearrangement Mediated ...

    Indian Academy of Sciences (India)

    C/min) were used. This study indicated a four stage decomposition behaviour of DADNE, where ... As the method tracks the changes in Eα throughout the entire ..... Senum G I and Yang R T 1977 Rational approximations of the integral of the ...

  4. GGPP-Mediated Protein Geranylgeranylation in Oocyte Is Essential for the Establishment of Oocyte-Granulosa Cell Communication and Primary-Secondary Follicle Transition in Mouse Ovary.

    Directory of Open Access Journals (Sweden)

    Chen Jiang

    2017-01-01

    Full Text Available Folliculogenesis is a progressive and highly regulated process, which is essential to provide ova for later reproductive life, requires the bidirectional communication between the oocyte and granulosa cells. This physical connection-mediated communication conveys not only the signals from the oocyte to granulosa cells that regulate their proliferation but also metabolites from the granulosa cells to the oocyte for biosynthesis. However, the underlying mechanism of establishing this communication is largely unknown. Here, we report that oocyte geranylgeranyl diphosphate (GGPP, a metabolic intermediate involved in protein geranylgeranylation, is required to establish the oocyte-granulosa cell communication. GGPP and geranylgeranyl diphosphate synthase (Ggpps levels in oocytes increased during early follicular development. The selective depletion of GGPP in mouse oocytes impaired the proliferation of granulosa cells, primary-secondary follicle transition and female fertility. Mechanistically, GGPP depletion inhibited Rho GTPase geranylgeranylation and its GTPase activity, which was responsible for the accumulation of cell junction proteins in the oocyte cytoplasm and the failure to maintain physical connection between oocyte and granulosa cells. GGPP ablation also blocked Rab27a geranylgeranylation, which might account for the impaired secretion of oocyte materials such as Gdf9. Moreover, GGPP administration restored the defects in oocyte-granulosa cell contact, granulosa cell proliferation and primary-secondary follicle transition in Ggpps depletion mice. Our study provides the evidence that GGPP-mediated protein geranylgeranylation contributes to the establishment of oocyte-granulosa cell communication and then regulates the primary-secondary follicle transition, a key phase of folliculogenesis essential for female reproductive function.

  5. Chimeric Amino Acid Rearrangements as Immune Targets in Prostate Cancer

    Science.gov (United States)

    2016-05-01

    COVERED 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Chimeric Amino Acid Rearrangements as Immune Targets in Prostate Cancer 5b. GRANT NUMBER W81XWH...that result from gene rearrangements given their high frequency relative to somatic point mutations. Gene rearrangements can yield novel chimeric

  6. Concanavalin A-mediated in vitro activation of a secondary cytotoxic T-cell response in virus-primed splenocytes

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Jensen, B L

    1980-01-01

    In a recent report it was shown that what appeared to be secondary cytotoxic T cells could be obtained from lymphocytic choriomeningitis virus (LCMV)-primed splenocytes after stimulation in vitro with the non-specific T cell mitogen concanavalin A (Con A). The present experiments attempt to chara......In a recent report it was shown that what appeared to be secondary cytotoxic T cells could be obtained from lymphocytic choriomeningitis virus (LCMV)-primed splenocytes after stimulation in vitro with the non-specific T cell mitogen concanavalin A (Con A). The present experiments attempt...... to characterize further these effector cells and, in particular, to establish whether the Con A-activated cytotoxic effectors are qualitatively different from the secondary cytotoxic T cells induced by restimulation with the homologous antigen. It was found that: (1) in vitro activation with Con A could......, since no evidence was found to indicate a role for other cell types or soluble (cytotoxic or arming) factors; (4) cytotoxicity was specific with regard to both virus and 'self'. By comparison with previous data on LCMV-induced cytotoxic T cells, it is concluded that Con A induces the generation...

  7. System for the detection of chromosomal rearrangements using Sordaria macrospora

    Energy Technology Data Exchange (ETDEWEB)

    Arnaise, S.; Leblon, G.; Lares, L. (Paris-11 Univ., 91 - Orsay (France). Lab. de Biologie Cellulaire et Genetique)

    1984-01-01

    A system is described for the detection and diagnosis of induced chromosomal rearrangement using Sordaria macrospora. The system uses the property of the rearrangement to produce defective white ascospores as meiotic progeny from heterozygous crosses. Two reconstruction experiments have shown that this system is able to give reliable quantitative measures of rearrangement frequencies. Evidence for a photoreactivation process was obtained, suggesting that pyrimidine dimers may well be an important lesion in UV-induced chromosomal rearrangement. No evidence of induction of chromosomal rearrangement was obtained in experiments with the powerful chemical mutagen N-methyl-N'-nitro-N-nitrosoguanidine.

  8. The Wolff rearrangement in radical cations

    International Nuclear Information System (INIS)

    Ohashi, Mamoru; Tsujimoto, Kazuo; Shida, Yasuo; Yamada, Yasuji.

    1975-01-01

    The mass spectrometric behavior of 1-phenyl-4,5,6,7-tetrahydrobenzotriazole and its seven membered analog is described. The principal fragmentation process of the molecular ions is loss of nitrogen. It was concluded from the results of deuterium labeling and accurate mass measurements that the subsequent fragmentation of the M-N 2 ions proceeds via isomerization to the ring-contracted ketenimine ions by the Wolff rearrangement, in sharp contrast to the case of 1-phenylbenzotriazole. (auth.)

  9. Enantioselective catalytic fluorinative aza-semipinacol rearrangement.

    Science.gov (United States)

    Romanov-Michailidis, Fedor; Pupier, Marion; Besnard, Céline; Bürgi, Thomas; Alexakis, Alexandre

    2014-10-03

    An efficient and highly stereoselective fluorinative aza-semipinacol rearrangement is described. The catalytic reaction requires use of Selectfluor in combination with the chiral, enantiopure phosphate anion derived from acid L3. Under optimized conditions, cyclopropylamines A were transformed into β-fluoro cyclobutylimines B in good yields and high levels of diastereo- and enantiocontrol. Furthermore, the optically active cyclobutylimines were reduced diastereoselectively with L-Selectride in the corresponding fluorinated amines C, compounds of significant interest in the pharmacological industry.

  10. Occupancy statistics arising from weighted particle rearrangements

    International Nuclear Information System (INIS)

    Huillet, Thierry

    2007-01-01

    The box-occupancy distributions arising from weighted rearrangements of a particle system are investigated. In the grand-canonical ensemble, they are characterized by determinantal joint probability generating functions. For doubly non-negative weight matrices, fractional occupancy statistics, generalizing Fermi-Dirac and Bose-Einstein statistics, can be defined. A spatially extended version of these balls-in-boxes problems is investigated

  11. Comparing genomes with rearrangements and segmental duplications.

    Science.gov (United States)

    Shao, Mingfu; Moret, Bernard M E

    2015-06-15

    Large-scale evolutionary events such as genomic rearrange.ments and segmental duplications form an important part of the evolution of genomes and are widely studied from both biological and computational perspectives. A basic computational problem is to infer these events in the evolutionary history for given modern genomes, a task for which many algorithms have been proposed under various constraints. Algorithms that can handle both rearrangements and content-modifying events such as duplications and losses remain few and limited in their applicability. We study the comparison of two genomes under a model including general rearrangements (through double-cut-and-join) and segmental duplications. We formulate the comparison as an optimization problem and describe an exact algorithm to solve it by using an integer linear program. We also devise a sufficient condition and an efficient algorithm to identify optimal substructures, which can simplify the problem while preserving optimality. Using the optimal substructures with the integer linear program (ILP) formulation yields a practical and exact algorithm to solve the problem. We then apply our algorithm to assign in-paralogs and orthologs (a necessary step in handling duplications) and compare its performance with that of the state-of-the-art method MSOAR, using both simulations and real data. On simulated datasets, our method outperforms MSOAR by a significant margin, and on five well-annotated species, MSOAR achieves high accuracy, yet our method performs slightly better on each of the 10 pairwise comparisons. http://lcbb.epfl.ch/softwares/coser. © The Author 2015. Published by Oxford University Press.

  12. A general heuristic for genome rearrangement problems.

    Science.gov (United States)

    Dias, Ulisses; Galvão, Gustavo Rodrigues; Lintzmayer, Carla Négri; Dias, Zanoni

    2014-06-01

    In this paper, we present a general heuristic for several problems in the genome rearrangement field. Our heuristic does not solve any problem directly, it is rather used to improve the solutions provided by any non-optimal algorithm that solve them. Therefore, we have implemented several algorithms described in the literature and several algorithms developed by ourselves. As a whole, we implemented 23 algorithms for 9 well known problems in the genome rearrangement field. A total of 13 algorithms were implemented for problems that use the notions of prefix and suffix operations. In addition, we worked on 5 algorithms for the classic problem of sorting by transposition and we conclude the experiments by presenting results for 3 approximation algorithms for the sorting by reversals and transpositions problem and 2 approximation algorithms for the sorting by reversals problem. Another algorithm with better approximation ratio can be found for the last genome rearrangement problem, but it is purely theoretical with no practical implementation. The algorithms we implemented in addition to our heuristic lead to the best practical results in each case. In particular, we were able to improve results on the sorting by transpositions problem, which is a very special case because many efforts have been made to generate algorithms with good results in practice and some of these algorithms provide results that equal the optimum solutions in many cases. Our source codes and benchmarks are freely available upon request from the authors so that it will be easier to compare new approaches against our results.

  13. Zinc Finger Nuclease induced DNA double stranded breaks and rearrangements in MLL

    International Nuclear Information System (INIS)

    Do, To Uyen; Ho, Bay; Shih, Shyh-Jen; Vaughan, Andrew

    2012-01-01

    Highlights: ► A Zinc Finger Nuclease (ZFN) targeting a leukemogenic hot spot for rearrangement in MLL is created. ► The novel ZFN efficiently cleaves MLL exon 13. ► Despite MLL cleavage and evidence of mis-repair, no leukemogenic translocations were produced. ► MLL cleavage alone is insufficient to generate leukemogenic translocations. - Abstract: Radiation treatment or chemotherapy has been linked with a higher risk of secondary cancers such as therapy related Acute Myeloid Leukemia (tAML). Several of these cancers have been shown to be correlated to the introduction of double stranded breaks (DSB) and rearrangements within the Mixed Lineage Leukemia (MLL) gene. We used Zinc Finger Nucleases (ZFNs) to introduce precise cuts within MLL to examine how a single DNA DSB might lead to chromosomal rearrangements. A ZFN targeting exon 13 within the Breakpoint Cluster Region of MLL was transiently expressed in a human lymphoblast cell line originating from a CML patient. Although FISH analysis showed ZFN DSB at this region increased the rate of MLL fragmentation, we were unable to detect leukemogenic rearrangements or translocations via inverse PCR. Interestingly, gene fragmentation as well as small interstitial deletions, insertions and base substitutions increased with the inhibition of DNA-PK, suggesting repair of this particular DSB is linked to non-homologous end joining (NHEJ). Although mis-repair of DSBs may be necessary for the initiation of leukemogenic translocations, a MLL targeted DNA break alone is insufficient

  14. Zinc Finger Nuclease induced DNA double stranded breaks and rearrangements in MLL

    Energy Technology Data Exchange (ETDEWEB)

    Do, To Uyen [Graduate Group in Immunology, University of California Davis, Davis, CA 95616 (United States); Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States); Ho, Bay; Shih, Shyh-Jen [Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States); Vaughan, Andrew, E-mail: Andrew.vaughan@ucdmc.ucdavis.edu [Graduate Group in Immunology, University of California Davis, Davis, CA 95616 (United States); Department of Radiation Oncology, University of California Davis, Sacramento CA 95817 (United States)

    2012-12-15

    Highlights: ► A Zinc Finger Nuclease (ZFN) targeting a leukemogenic hot spot for rearrangement in MLL is created. ► The novel ZFN efficiently cleaves MLL exon 13. ► Despite MLL cleavage and evidence of mis-repair, no leukemogenic translocations were produced. ► MLL cleavage alone is insufficient to generate leukemogenic translocations. - Abstract: Radiation treatment or chemotherapy has been linked with a higher risk of secondary cancers such as therapy related Acute Myeloid Leukemia (tAML). Several of these cancers have been shown to be correlated to the introduction of double stranded breaks (DSB) and rearrangements within the Mixed Lineage Leukemia (MLL) gene. We used Zinc Finger Nucleases (ZFNs) to introduce precise cuts within MLL to examine how a single DNA DSB might lead to chromosomal rearrangements. A ZFN targeting exon 13 within the Breakpoint Cluster Region of MLL was transiently expressed in a human lymphoblast cell line originating from a CML patient. Although FISH analysis showed ZFN DSB at this region increased the rate of MLL fragmentation, we were unable to detect leukemogenic rearrangements or translocations via inverse PCR. Interestingly, gene fragmentation as well as small interstitial deletions, insertions and base substitutions increased with the inhibition of DNA-PK, suggesting repair of this particular DSB is linked to non-homologous end joining (NHEJ). Although mis-repair of DSBs may be necessary for the initiation of leukemogenic translocations, a MLL targeted DNA break alone is insufficient.

  15. Pathway markers for pro-resolving lipid mediators in maternal and umbilical cord blood: A Secondary analysis of the Mothers, Omega-3, & Mental Health Study

    Directory of Open Access Journals (Sweden)

    Ellen L Mozurkewich

    2016-09-01

    Full Text Available The omega-3 fatty acids docosahexaenoic acid (DHA and eicosapentaenoic acid (EPA are precursors to immune regulatory and specialized pro-resolving mediators (SPM of inflammation termed resolvins, maresins, and protections. Evidence for lipid mediator formation in vivo can be gained through evaluation of their 5-lipoxygenase (LOX and 15-LOX metabolic pathway precursors and downstream metabolites: We performed a secondary blood sample analysis from 60 participants in the Mothers, Omega-3, and Mental Health study to determine whether SPM and SPM precursors are augmented by dietary EPA- and DHA-rich fish oil supplementation compared to soy oil placebo. We also aimed to study whether SPM and their precursors differ in early and late pregnancy or between maternal and umbilical cord blood. We found that compared to placebo supplementation, EPA- and DHA- rich fish oil supplementation increased SPM precursor 17-HDHA concentrations in maternal and umbilical cord blood (P=0.02 We found that the D-series resolvin pathway marker 17-HDHA increased significantly between enrollment and late pregnancy (P=0.049. Levels of both 14-HDHA, a maresin pathway marker, and 17-HDHA were significantly greater in umbilical cord blood than in maternal blood (P<0.001, both.

  16. Relationships between negative affect and academic achievement among secondary school students: the mediating effects of habituated exercise.

    Science.gov (United States)

    Hashim, Hairul A; Freddy, Golok; Rosmatunisah, Ali

    2012-09-01

    The current study was undertaken to examine the associations between self-determination, exercise habit, anxiety, depression, stress, and academic achievement among adolescents aged 13 and 14 years in eastern Malaysia. The sample consisted of 750 secondary school students (mean age = 13.4 years, SD = 0.49). Participants completed self-report measures of exercise behavioral regulation, negative affect, and exercise habit strength. Midyear exam results were used as an indicator of academic performance. Structural equation modeling was used to analyze the data. The results of structural equation modeling revealed a close model fit for the hypothesized model, which indicates that higher levels of self-determination were positively associated with habituated exercise behavior. In turn, exercise habit strength fostered academic achievement and buffered the debilitative effect of stress, depression, and anxiety on student academic performance. The analysis of model invariance revealed a nonsignificant difference between male and female subjects. The findings support the notion that habituated exercise fosters academic performance. In addition, we found that habituated exercise buffers the combined effects of stress, anxiety and depression on academic performance. The finding also supports the roles of self-determination in promoting exercise habituation.

  17. Adiabatic Rearrangement of Hollow PV Towers

    Directory of Open Access Journals (Sweden)

    Eric A Hendricks

    2010-10-01

    Full Text Available Diabatic heating from deep moist convection in the hurricane eyewall produces a towering annular structure of elevated potential vorticity (PV. This structure has been referred to as a hollow PV tower. The sign reversal of the radial gradient of PV satisfies the Charney-Stern necessary condition for combined barotropic-baroclinic instability. For thin enough annular structures, small perturbations grow exponentially, extract energy from the mean flow, and lead to hollow tower breakdown, with significant vortex structural and intensity change. The three-dimensional adiabatic rearrangements of two prototypical hurricane-like hollow PV towers (one thick and one thin are examined in an idealized framework. For both hollow towers, dynamic instability causes air parcels with high PV to be mixed into the eye preferentially at lower levels, where unstable PV wave growth rates are the largest. Little or no mixing is found to occur at upper levels. The mixing at lower and middle levels is most rapid for the breakdown of the thin hollow tower, consistent with previous barotropic results. For both hollow towers, this advective rearrangement of PV affects the tropical cyclone structure and intensity in a number of ways. First, the minimum central pressure and maximum azimuthal mean velocity simultaneously decrease, consistent with previous barotropic results. Secondly, isosurfaces of absolute angular momentum preferentially shift inward at low levels, implying an adiabatic mechanism by which hurricane eyewall tilt can form. Thirdly, a PV bridge, similar to that previously found in full-physics hurricane simulations, develops as a result of mixing at the isentropic levels where unstable PV waves grow most rapidly. Finally, the balanced mass field resulting from the PV rearrangement is warmer in the eye between 900 and 700 hPa. The location of this warming is consistent with observed warm anomalies in the eye, indicating that in certain instances the hurricane

  18. Gene activation by induced DNA rearrangements

    International Nuclear Information System (INIS)

    Schnipper, L.E.; Chan, V.; Sedivy, J.; Jat, P.; Sharp, P.A.

    1989-01-01

    A murine cell line (EN/NIH) containing the retroviral vector ZIPNeoSV(x)1 that was modified by deletion of the enhancer elements in the viral long terminal repeats has been used as an assay system to detect induced DNA rearrangements that result in activation of a transcriptionally silent reporter gene encoded by the viral genome. The spontaneous frequency of G418 resistance is less than 10(-7), whereas exposure to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or the combination of UV irradiation plus TPA resulted in the emergence of drug resistant cell lines at a frequency of 5 per 10(6) and 67 per 10(6) cells, respectively. In several of the cell lines that were analyzed a low level of amplification of one of the two parental retroviral integrants was observed, whereas in others no alteration in the region of the viral genome was detected. To determine the effect of the SV40 large T antigen on induced DNA rearrangements, EN/NIH cells were transfected with a temperature sensitive (ts) mutant of SV40 T. Transfectants were maintained at the permissive temperature (33 degrees C) for varying periods of time (1-5 days) in order to vary SV40 T antigen exposure, after which they were shifted to 39.5 degrees C for selection in G418. The frequency of emergence of drug resistant cell clones increased with duration of exposure to large T antigen (9-52 per 10(6) cells over 1-5 days, respectively), and all cell lines analyzed demonstrated DNA rearrangements in the region of the neo gene. A novel 18-kilobase pair XbaI fragment was cloned from one cell line which revealed the presence of a 2.0-kilobase pair EcoRI segment containing an inverted duplication which hybridized to neo sequences. It is likely that the observed rearrangement was initiated by the specific binding of large T antigen to the SV40 origin of replication encoded within the viral genome

  19. Habitat-mediated variation in the importance of ecosystem engineers for secondary cavity nesters in a nest web.

    Science.gov (United States)

    Robles, Hugo; Martin, Kathy

    2014-01-01

    Through physical state changes in biotic or abiotic materials, ecosystem engineers modulate resource availability to other organisms and are major drivers of evolutionary and ecological dynamics. Understanding whether and how ecosystem engineers are interchangeable for resource users in different habitats is a largely neglected topic in ecosystem engineering research that can improve our understanding of the structure of communities. We addressed this issue in a cavity-nest web (1999-2011). In aspen groves, the presence of mountain bluebird (Sialia currucoides) and tree swallow (Tachycineta bicolour) nests was positively related to the density of cavities supplied by northern flickers (Colaptes auratus), which provided the most abundant cavities (1.61 cavities/ha). Flickers in aspen groves provided numerous nesting cavities to bluebirds (66%) and swallows (46%), despite previous research showing that flicker cavities are avoided by swallows. In continuous mixed forests, however, the presence of nesting swallows was mainly related to cavity density of red-naped sapsuckers (Sphyrapicus nuchalis), which provided the most abundant cavities (0.52 cavities/ha), and to cavity density of hairy woodpeckers (Picoides villosus), which provided few (0.14 cavities/ha) but high-quality cavities. Overall, sapsuckers and hairy woodpeckers provided 86% of nesting cavities to swallows in continuous forests. In contrast, the presence of nesting bluebirds in continuous forests was associated with the density of cavities supplied by all the ecosystem engineers. These results suggest that (i) habitat type may mediate the associations between ecosystem engineers and resource users, and (ii) different ecosystem engineers may be interchangeable for resource users depending on the quantity and quality of resources that each engineer supplies in each habitat type. We, therefore, urge the incorporation of the variation in the quantity and quality of resources provided by ecosystem engineers

  20. Sterile DJH rearrangements reveal that distance between gene segments on the human Ig H chain locus influences their ability to rearrange

    DEFF Research Database (Denmark)

    Hansen, Tina Østergaard; Lange, Anders Blaabjerg; Barington, Torben

    2015-01-01

    Rearrangement of the Ig locus occurs in two steps. First, a JH gene is rearranged to a D gene followed by a VH gene rearranging to the DJH rearrangement. By next generation sequencing, we analyzed 9969 unique DJH rearrangements and 5919 unique VHDJH rearrangements obtained from peripheral blood B...... frequently than JH locus distal D genes, whereas VH locus proximal D genes were observed more frequently in nonproductive VHDJH rearrangements. We further demonstrate that the distance between VH, D, and JH gene segments influence their ability to rearrange within the human Ig locus....

  1. Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

    Directory of Open Access Journals (Sweden)

    Stephanie R. Hare

    2016-02-01

    Full Text Available This review describes unexpected dynamical behaviors of rearranging carbocations and the modern computational methods used to elucidate these aspects of reaction mechanisms. Unique potential energy surface topologies associated with these rearrangements have been discovered in recent years that are not only of fundamental interest, but also provide insight into the way Nature manipulates chemical space to accomplish specific chemical transformations. Cautions for analyzing both experimental and theoretical data on carbocation rearrangements are included throughout.

  2. Exceptional Complex Chromosomal Rearrangements in Three Generations

    Directory of Open Access Journals (Sweden)

    Hannie Kartapradja

    2015-01-01

    Full Text Available We report an exceptional complex chromosomal rearrangement (CCR found in three individuals in a family that involves 4 chromosomes with 5 breakpoints. The CCR was ascertained in a phenotypically abnormal newborn with additional chromosomal material on the short arm of chromosome 4. Maternal karyotyping indicated that the mother carried an apparently balanced CCR involving chromosomes 4, 6, 11, and 18. Maternal transmission of the derivative chromosome 4 resulted in partial trisomy for chromosomes 6q and 18q and a partial monosomy of chromosome 4p in the proband. Further family studies found that the maternal grandmother carried the same apparently balanced CCR as the proband’s mother, which was confirmed using the whole chromosome painting (WCP FISH. High resolution whole genome microarray analysis of DNA from the proband’s mother found no evidence for copy number imbalance in the vicinity of the CCR translocation breakpoints, or elsewhere in the genome, providing evidence that the mother’s and grandmother’s CCRs were balanced at a molecular level. This structural rearrangement can be categorized as an exceptional CCR due to its complexity and is a rare example of an exceptional CCR being transmitted in balanced and/or unbalanced form across three generations.

  3. A tandem cross-metathesis/semipinacol rearrangement reaction.

    Science.gov (United States)

    Plummer, Christopher W; Soheili, Arash; Leighton, James L

    2012-05-18

    An efficient and (E)-selective synthesis of a 6-alkylidenebicyclo[3.2.1]octan-8-one has been developed. The key step is a tandem cross-metathesis/semipinacol rearrangement reaction, wherein the Hoveyda-Grubbs II catalyst, or more likely a derivative thereof, serves as the Lewis acid for the rearrangement. Despite the fact that both the starting alkene and the cross-metathesis product are viable rearrangement substrates, only the latter rearranges, suggesting that the Lewis acidic species is generated only after the cross-metathesis reaction is complete.

  4. The importance of chemical analysis and quality-assurance for environmental mediation and acceptance in the use of secondary fuels in the cement plant Leube as an essential part of the ecological business strategy

    International Nuclear Information System (INIS)

    Mlekusch, T.

    2000-11-01

    In this paper I tried to combine the fields of environmental technology, environmental analysis, quality-management, environmental mediation and limiting values an the example of the use of secondary-fuels in the cement plant Leube in Gartenau (Austria). This project has proved to be very satisfying for the company and the adjoining owners. The first chapter deals with relations between environment and technology. A chronological description of the use of secondary fuels shows the development in this technology. The reactions of trace-elements in the burning process of cement clinker are described in the second chapter. Limiting values and the protection of human beings by the use of them are explained in the third chapter. The environmental mediation project of the use of secondary fuels in Gartenau is object of the fourth chapter. An essential part to acceptance is contributed by a good working quality-management and laboratory. (author)

  5. Genome-wide signatures of 'rearrangement hotspots' within segmental duplications in humans.

    Directory of Open Access Journals (Sweden)

    Mohammed Uddin

    Full Text Available The primary objective of this study was to create a genome-wide high resolution map (i.e., >100 bp of 'rearrangement hotspots' which can facilitate the identification of regions capable of mediating de novo deletions or duplications in humans. A hierarchical method was employed to fragment segmental duplications (SDs into multiple smaller SD units. Combining an end space free pairwise alignment algorithm with a 'seed and extend' approach, we have exhaustively searched 409 million alignments to detect complex structural rearrangements within the reference-guided assembly of the NA18507 human genome (18× coverage, including the previously identified novel 4.8 Mb sequence from de novo assembly within this genome. We have identified 1,963 rearrangement hotspots within SDs which encompass 166 genes and display an enrichment of duplicated gene nucleotide variants (DNVs. These regions are correlated with increased non-allelic homologous recombination (NAHR event frequency which presumably represents the origin of copy number variations (CNVs and pathogenic duplications/deletions. Analysis revealed that 20% of the detected hotspots are clustered within the proximal and distal SD breakpoints flanked by the pathogenic deletions/duplications that have been mapped for 24 NAHR-mediated genomic disorders. FISH Validation of selected complex regions revealed 94% concordance with in silico localization of the highly homologous derivatives. Other results from this study indicate that intra-chromosomal recombination is enhanced in genic compared with agenic duplicated regions, and that gene desert regions comprising SDs may represent reservoirs for creation of novel genes. The generation of genome-wide signatures of 'rearrangement hotspots', which likely serve as templates for NAHR, may provide a powerful approach towards understanding the underlying mutational mechanism(s for development of constitutional and acquired diseases.

  6. Bootstrapping phylogenies inferred from rearrangement data

    Directory of Open Access Journals (Sweden)

    Lin Yu

    2012-08-01

    Full Text Available Abstract Background Large-scale sequencing of genomes has enabled the inference of phylogenies based on the evolution of genomic architecture, under such events as rearrangements, duplications, and losses. Many evolutionary models and associated algorithms have been designed over the last few years and have found use in comparative genomics and phylogenetic inference. However, the assessment of phylogenies built from such data has not been properly addressed to date. The standard method used in sequence-based phylogenetic inference is the bootstrap, but it relies on a large number of homologous characters that can be resampled; yet in the case of rearrangements, the entire genome is a single character. Alternatives such as the jackknife suffer from the same problem, while likelihood tests cannot be applied in the absence of well established probabilistic models. Results We present a new approach to the assessment of distance-based phylogenetic inference from whole-genome data; our approach combines features of the jackknife and the bootstrap and remains nonparametric. For each feature of our method, we give an equivalent feature in the sequence-based framework; we also present the results of extensive experimental testing, in both sequence-based and genome-based frameworks. Through the feature-by-feature comparison and the experimental results, we show that our bootstrapping approach is on par with the classic phylogenetic bootstrap used in sequence-based reconstruction, and we establish the clear superiority of the classic bootstrap for sequence data and of our corresponding new approach for rearrangement data over proposed variants. Finally, we test our approach on a small dataset of mammalian genomes, verifying that the support values match current thinking about the respective branches. Conclusions Our method is the first to provide a standard of assessment to match that of the classic phylogenetic bootstrap for aligned sequences. Its

  7. Bootstrapping phylogenies inferred from rearrangement data.

    Science.gov (United States)

    Lin, Yu; Rajan, Vaibhav; Moret, Bernard Me

    2012-08-29

    Large-scale sequencing of genomes has enabled the inference of phylogenies based on the evolution of genomic architecture, under such events as rearrangements, duplications, and losses. Many evolutionary models and associated algorithms have been designed over the last few years and have found use in comparative genomics and phylogenetic inference. However, the assessment of phylogenies built from such data has not been properly addressed to date. The standard method used in sequence-based phylogenetic inference is the bootstrap, but it relies on a large number of homologous characters that can be resampled; yet in the case of rearrangements, the entire genome is a single character. Alternatives such as the jackknife suffer from the same problem, while likelihood tests cannot be applied in the absence of well established probabilistic models. We present a new approach to the assessment of distance-based phylogenetic inference from whole-genome data; our approach combines features of the jackknife and the bootstrap and remains nonparametric. For each feature of our method, we give an equivalent feature in the sequence-based framework; we also present the results of extensive experimental testing, in both sequence-based and genome-based frameworks. Through the feature-by-feature comparison and the experimental results, we show that our bootstrapping approach is on par with the classic phylogenetic bootstrap used in sequence-based reconstruction, and we establish the clear superiority of the classic bootstrap for sequence data and of our corresponding new approach for rearrangement data over proposed variants. Finally, we test our approach on a small dataset of mammalian genomes, verifying that the support values match current thinking about the respective branches. Our method is the first to provide a standard of assessment to match that of the classic phylogenetic bootstrap for aligned sequences. Its support values follow a similar scale and its receiver

  8. Mindful Self-Care and Secondary Traumatic Stress Mediate a Relationship Between Compassion Satisfaction and Burnout Risk Among Hospice Care Professionals.

    Science.gov (United States)

    Hotchkiss, Jason T

    2018-01-01

    Effective self-care in hospice is anecdotally proclaimed to reduce burnout risk. Yet, the topic has received little empirical attention. This study developed a model for predicting burnout risk from compassion satisfaction (CS), secondary traumatic stress (STS), and mindful self-care. Hospice care professionals (n = 324). Cross-sectional self-report survey. Mindful self-care was correlated with CS ( r = 0.497, p Burnout ( r = -0.726, p Burnout. Mindful self-care and STS mediated a relationship between CS and Burnout. Each self-care category was statistically significant protective factors against burnout risk ( p Burnout in order of strength were self-compassion and purpose (SC; r = -0.673), supportive structure (SS; r = -0.650), mindful self-awareness (MS; r = -0.642), mindful relaxation (MR; r = -0.531), supportive relationships (SR; r = -0.503), and physical care (PC; r = -0.435). However, for STS, only SS ( r = -0.407, p Burnout compared to published norms. Those who engaged in multiple and frequent self-care strategies experienced higher professional quality of life. Implications for hospice providers and suggestions for future research are discussed.

  9. SKI2 mediates degradation of RISC 5′-cleavage fragments and prevents secondary siRNA production from miRNA targets in Arabidopsis

    Science.gov (United States)

    Branscheid, Anja; Marchais, Antonin; Schott, Gregory; Lange, Heike; Gagliardi, Dominique; Andersen, Stig Uggerhøj; Voinnet, Olivier; Brodersen, Peter

    2015-01-01

    Small regulatory RNAs are fundamental in eukaryotic and prokaryotic gene regulation. In plants, an important element of post-transcriptional control is effected by 20–24 nt microRNAs (miRNAs) and short interfering RNAs (siRNAs) bound to the ARGONAUTE1 (AGO1) protein in an RNA induced silencing complex (RISC). AGO1 may cleave target mRNAs with small RNA complementarity, but the fate of the resulting cleavage fragments remains incompletely understood. Here, we show that SKI2, SKI3 and SKI8, subunits of a cytoplasmic cofactor of the RNA exosome, are required for degradation of RISC 5′, but not 3′-cleavage fragments in Arabidopsis. In the absence of SKI2 activity, many miRNA targets produce siRNAs via the RNA-dependent RNA polymerase 6 (RDR6) pathway. These siRNAs are low-abundant, and map close to the cleavage site. In most cases, siRNAs were produced 5′ to the cleavage site, but several examples of 3′-spreading were also identified. These observations suggest that siRNAs do not simply derive from RDR6 action on stable 5′-cleavage fragments and hence that SKI2 has a direct role in limiting secondary siRNA production in addition to its function in mediating degradation of 5′-cleavage fragments. PMID:26464441

  10. SKI2 mediates degradation of RISC 5'-cleavage fragments and prevents secondary siRNA production from miRNA targets in Arabidopsis.

    Science.gov (United States)

    Branscheid, Anja; Marchais, Antonin; Schott, Gregory; Lange, Heike; Gagliardi, Dominique; Andersen, Stig Uggerhøj; Voinnet, Olivier; Brodersen, Peter

    2015-12-15

    Small regulatory RNAs are fundamental in eukaryotic and prokaryotic gene regulation. In plants, an important element of post-transcriptional control is effected by 20-24 nt microRNAs (miRNAs) and short interfering RNAs (siRNAs) bound to the ARGONAUTE1 (AGO1) protein in an RNA induced silencing complex (RISC). AGO1 may cleave target mRNAs with small RNA complementarity, but the fate of the resulting cleavage fragments remains incompletely understood. Here, we show that SKI2, SKI3 and SKI8, subunits of a cytoplasmic cofactor of the RNA exosome, are required for degradation of RISC 5', but not 3'-cleavage fragments in Arabidopsis. In the absence of SKI2 activity, many miRNA targets produce siRNAs via the RNA-dependent RNA polymerase 6 (RDR6) pathway. These siRNAs are low-abundant, and map close to the cleavage site. In most cases, siRNAs were produced 5' to the cleavage site, but several examples of 3'-spreading were also identified. These observations suggest that siRNAs do not simply derive from RDR6 action on stable 5'-cleavage fragments and hence that SKI2 has a direct role in limiting secondary siRNA production in addition to its function in mediating degradation of 5'-cleavage fragments. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  11. Gestalt Theory Rearranged: Back to Wertheimer

    Directory of Open Access Journals (Sweden)

    Shelia Guberman

    2017-10-01

    Full Text Available Wertheimer's seminal paper of 1923 was of gerat influence in psychology and other sciences. Wertheimer also emphasized the weaknesses of the newborn Gestalt theory: too many basic laws, and the ambiguity of definitions. At the same time, the paper contained potential solutions to these problems, in the form of a number of very important ideas, some of which were presented implicitly: perception through imitation, communicative nature of linear drawings and writings, transfer from the visual domain to motor domain, linguistic interpretation of the Gestalt. In this paper it will be shown that based on these ideas the Gestalt theory can be rearranged so that the main notions can be well defined, and the general principle of Gestalt perception, which overarches all known laws and unifies different Gestalt phenomena (the imitation principle can be introduced. The presented model of Gestalt perception is supported by fundamental neurophysiological data—the mirror neurons phenomenon and simulation theory.

  12. Gestalt Theory Rearranged: Back to Wertheimer.

    Science.gov (United States)

    Guberman, Shelia

    2017-01-01

    Wertheimer's seminal paper of 1923 was of gerat influence in psychology and other sciences. Wertheimer also emphasized the weaknesses of the newborn Gestalt theory: too many basic laws, and the ambiguity of definitions. At the same time, the paper contained potential solutions to these problems, in the form of a number of very important ideas, some of which were presented implicitly: perception through imitation, communicative nature of linear drawings and writings, transfer from the visual domain to motor domain, linguistic interpretation of the Gestalt. In this paper it will be shown that based on these ideas the Gestalt theory can be rearranged so that the main notions can be well defined, and the general principle of Gestalt perception, which overarches all known laws and unifies different Gestalt phenomena (the imitation principle) can be introduced. The presented model of Gestalt perception is supported by fundamental neurophysiological data-the mirror neurons phenomenon and simulation theory.

  13. New progress in snake mitochondrial gene rearrangement.

    Science.gov (United States)

    Chen, Nian; Zhao, Shujin

    2009-08-01

    To further understand the evolution of snake mitochondrial genomes, the complete mitochondrial DNA (mtDNA) sequences were determined for representative species from two snake families: the Many-banded krait, the Banded krait, the Chinese cobra, the King cobra, the Hundred-pace viper, the Short-tailed mamushi, and the Chain viper. Thirteen protein-coding genes, 22-23 tRNA genes, 2 rRNA genes, and 2 control regions were identified in these mtDNAs. Duplication of the control region and translocation of the tRNAPro gene were two notable features of the snake mtDNAs. These results from the gene rearrangement comparisons confirm the correctness of traditional classification schemes and validate the utility of comparing complete mtDNA sequences for snake phylogeny reconstruction.

  14. Genome organization influences partner selection for chromosomal rearrangements

    NARCIS (Netherlands)

    Wijchers, P.J.; de Laat, W.

    2010-01-01

    Chromosomal rearrangements occur as a consequence of the erroneous repair of DNA double-stranded breaks, and often underlie disease. The recurrent detection of specific tumorigenic rearrangements suggests that there is a mechanism behind chromosomal partner selection involving the shape of the

  15. Constituent rearrangement model and large transverse momentum reactions

    International Nuclear Information System (INIS)

    Igarashi, Yuji; Imachi, Masahiro; Matsuoka, Takeo; Otsuki, Shoichiro; Sawada, Shoji.

    1978-01-01

    In this chapter, two models based on the constituent rearrangement picture for large p sub( t) phenomena are summarized. One is the quark-junction model, and the other is the correlating quark rearrangement model. Counting rules of the models apply to both two-body reactions and hadron productions. (author)

  16. Árni Magnússon's rearrangement of paper manuscripts

    DEFF Research Database (Denmark)

    Stegmann, Beeke

    Árni Magnússon’s rearrangement of paper manuscripts draws attention to the early history of Árni Magnússon’s (1663-1730) manuscript collection. The thesis examines Árni’s extensive rearrangement of paper manuscripts, showing that he repeatedly altered the physical composition of codices in his...

  17. Circumambulatory rearrangements of cyclopolyenes containing element-centred migrants

    International Nuclear Information System (INIS)

    Minkin, Vladimir I; Mikhailov, Igor E; Dushenko, Galina A; Zschunke, Adolf

    2003-01-01

    Data on circumambulatory rearrangements caused by rapid migrations of substituents formed by Group 13-17 elements around three- to nine-membered cyclopolyenes are generalised and systematised. Depending on the ring size, the nature of the migrating group, substituents in the ring and the medium, the rate constants of circumambulatory rearrangements vary over a wide range from 10 6 to 10 -8 s -1 at room temperature. Particular attention is given to analysis of the mechanisms of these rearrangements ([1, j]-, [2,3]- and [3,3]-sigmatropic shifts, haptotropic rearrangements and ionisation-recombination) and to the correlation of these mechanisms with the structural characteristics of the compounds that undergo rearrangements.

  18. ETV6-RUNX1 Rearrangement in Tunisian Pediatric B-Lineage Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Abir Gmidène

    2009-01-01

    Full Text Available In this study, Forty-one out of fifty-seven Tunisian children with B-lineage acute lymphoblastic leukemia (B-ALL, and without cytogenetically detectable recurrent abnormalities at the time of the diagnosis, were evaluated by fluorescence in situ hybridization (FISH for the t(12;21. This translocation leads ETV6-RUNX1 (previously TEL-AML1 fusion gene. 16 patients (28% had ETV6-RUNX1 rearrangement. In addition to this rearrangement, two cases showed a loss of the normal ETV6 allele, and three others showed an extra signal of the RUNX1 gene. Seven patients without ETV6-RUNX1 rearrangement showed extra signals of the RUNX1 gene. One out of the 7 patients was also associated with a t(3;12 identified by FISH. This is the first Tunisian study in which we report the incidence of t(12;21 among childhood B-lineage ALL and in which we have found multiple copies of RUNX1. Finally, our findings confirm that additional or secondary genetic changes are commonly encountered in pediatric B-lineage ALL with ETV6-RUNX1 gene fusion which is envisaged to play a pivotal role in disease progression.

  19. Nested Inversion Polymorphisms Predispose Chromosome 22q11.2 to Meiotic Rearrangements.

    Science.gov (United States)

    Demaerel, Wolfram; Hestand, Matthew S; Vergaelen, Elfi; Swillen, Ann; López-Sánchez, Marcos; Pérez-Jurado, Luis A; McDonald-McGinn, Donna M; Zackai, Elaine; Emanuel, Beverly S; Morrow, Bernice E; Breckpot, Jeroen; Devriendt, Koenraad; Vermeesch, Joris R

    2017-10-05

    Inversion polymorphisms between low-copy repeats (LCRs) might predispose chromosomes to meiotic non-allelic homologous recombination (NAHR) events and thus lead to genomic disorders. However, for the 22q11.2 deletion syndrome (22q11.2DS), the most common genomic disorder, no such inversions have been uncovered as of yet. Using fiber-FISH, we demonstrate that parents transmitting the de novo 3 Mb LCR22A-D 22q11.2 deletion, the reciprocal duplication, and the smaller 1.5 Mb LCR22A-B 22q11.2 deletion carry inversions of LCR22B-D or LCR22C-D. Hence, the inversions predispose chromosome 22q11.2 to meiotic rearrangements and increase the individual risk for transmitting rearrangements. Interestingly, the inversions are nested or flanking rather than coinciding with the deletion or duplication sizes. This finding raises the possibility that inversions are a prerequisite not only for 22q11.2 rearrangements but also for all NAHR-mediated genomic disorders. Copyright © 2017. Published by Elsevier Inc.

  20. Formation of Ketenimines via the Palladium-Catalyzed Decarboxylative π-Allylic Rearrangement of N-Alloc Ynamides.

    Science.gov (United States)

    Alexander, Juliana R; Cook, Matthew J

    2017-11-03

    A new approach for the formation of ketenimines via a decarboxylative allylic rearrangement pathway that does not require strong stabilizing or protecting groups has been developed. The products can be readily hydrolyzed into their corresponding secondary amides or reacted with sulfur ylides to perform an additional [2,3]-Wittig process. Mechanistic studies suggest an outer-sphere process in which reductive alkylation is rate-limiting.

  1. Complete nucleotide sequence and gene rearrangement of the ...

    Indian Academy of Sciences (India)

    3Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, People's Republic of China ... of these rearrangements involve tRNA genes, ND5 gene and ... ncbi.nlm.nih.gov/projects/Sequin/download/seq_win_download.

  2. Exohedral and skeletal rearrangements in the molecules of fullerene derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Ignat' eva, Daria V; Ioffe, I N; Troyanov, Sergey I; Sidorov, Lev N [Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow (Russian Federation)

    2011-07-31

    The data on the migration of monoatomic addends, perfluoroalkyl and more complex organic groups in the molecules of fullerene derivatives published mainly in the last decade are analyzed. Skeletal rearrangements of the carbon cage occurring during chemical reactions are considered.

  3. Triisobutylaluminium (TIBAL Promoted Rearrangement of C-glycosides

    Directory of Open Access Journals (Sweden)

    P. Sinay

    2005-08-01

    Full Text Available Triisobutylaluminium-promoted rearrangement of unsaturated glycosides containing electron-donating aglycons, such as C-aryl glycosides, provides direct access to highly functionalised cyclohexane derivatives.

  4. Combinatorial aspects of genome rearrangements and haplotype networks

    OpenAIRE

    Labarre , Anthony

    2008-01-01

    The dissertation covers two problems motivated by computational biology: genome rearrangements, and haplotype networks. Genome rearrangement problems are a particular case of edit distance problems, where one seeks to transform two given objects into one another using as few operations as possible, with the additional constraint that the set of allowed operations is fixed beforehand; we are also interested in computing the corresponding distances between those objects, i.e. merely computing t...

  5. Dehydrophenylnitrenes: matrix isolation and photochemical rearrangements.

    Science.gov (United States)

    Sander, Wolfram; Winkler, Michael; Cakir, Bayram; Grote, Dirk; Bettinger, Holger F

    2007-02-02

    The photochemistry of 3-iodo-2,4,5,6-tetrafluorophenyl azide 8 and 3,5-diiodo-2,4,6-trifluorophenyl azide 9 was studied by IR and EPR spectroscopy in cryogenic argon and neon matrices. Both compounds form the corresponding nitrenes as primary photoproducts in photostationary equilibria with their azirine and ketenimine isomers. In contrast to fluorinated phenylnitrenes, ring-opened products are obtained upon short-wavelength irradiation of the iodine-containing systems, indicative of C-I bond cleavage in the nitrenes or didehydroazepines under these conditions. Neither 3-dehydrophenylnitrene 6 nor 3,5-didehydrophenylnitrene 7 could be detected directly. The structures of the acyclic photoproducts were identified by extensive comparison with DFT calculated spectra. Mechanistic aspects of the rearrangements leading to the observed products and the electronic properties of the title intermediates are discussed on the basis of DFT as well as high-level ab initio calculations. The computations indicate strong through-bond coupling of the exocyclic orbital in the meta position with the singly occupied in-plane nitrene orbital in the monoradical nitrenes. In contrast to the ortho or para isomers, this interaction results in low-spin ground states for meta nitrene radicals and a weakening of the C1-C2 bond causing the kinetic instability of these species even under low-temperature conditions. 3,5-Didehydrophenylnitrenes, on the other hand, in which a strong C3-C5 interaction reduces coupling of the radical sites with the nitrene unit, might be accessible synthetic targets if the intermediate formation of labile monoradicals could be circumvented.

  6. Synthesis of rearranged unsaturated drimane derivatives

    Directory of Open Access Journals (Sweden)

    Miranda Domingos S. de

    2001-01-01

    Full Text Available A full account to the preparation and application of three appropriately substituted vinylcyclohexenes (2,2-dimethyl-3-vinylcyclohex-3-en-1-ol, 2,2-dimethyl-3-vinylcyclohex-3-en-1-one and 3,3-dimethyl-2-vinylcyclohexene in thermal Diels-Alder reactions with alpha,beta-unsaturated esters (methyl tiglate and methyl angelate is given. This approach delivered the racemic synthesis of ten octalin derivatives bearing a rearranged drimane skeleton (4 diastereomers of 1-methoxycarbonyl-6-hydroxy-1,2,5,5-tetramethyl-1,2,3,5,6,7, 8,8a-octahydronaphthalene; 1-methoxycarbonyl-6-oxo-1,2,5,5-tetramethyl-1,2,3,4,5,6,7,8-octahydronaphthalene; 2-methoxycarbonyl-6-oxo-1,2,5,5-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalene; 3 diastereomers of 1-methoxycarbonyl-1,2,5,5-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalene and 2-methoxycarbonyl-1,2,5,5-tetramethyl-1,2,3,5,6,7,8,8a-octahydronaphthalene . Central synthetic features included preparation of enoltriflates by Stang's protocol and the successful palladium-catalyzed cross-coupling reaction (Stille reaction of the triflate with the tri-n-butylvinylstannane. The octalins relative stereochemistry was unequivocally ascertained by spectroscopic methods and/or X-ray crystallography and these data now stand as useful tools to support the correct assignment of related natural products usually isolated in minute amounts.

  7. Theory of Mind as a mediator variable between neurocognition and functioning in young individuals in treatment with secondary services for non-psychotic disorders.

    Science.gov (United States)

    Francesconi, Marta; Minichino, Amedeo; Carrión, Ricardo E; Chiaie, Roberto Delle; Bevilacqua, Arturo; Parisi, Maurizio; Rullo, Santo; Bersani, Francesco Saverio; Biondi, Massimo; Cadenhead, Kristin

    2016-12-30

    A large body of studies provides evidence for a link between neurocognition, theory of mind (ToM) and functioning in psychotic spectrum disorders (PSDs), with ToM mediating the effect that neurocognition has on functioning. These three constructs and the related mediation effect may characterize different psychiatric syndromes other than PSDs. Structural equation modelling (SEM) was applied to baseline data from a longitudinal study of 138 young individuals with a recent-onset psychiatric disorder. Using SEM, we tested the hypothesis that ToM mediates the effect of neurocognition on functioning independent of the level of psychosis risk and the diagnostic category. In the mediation model the bootstrapping estimate revealed a significant indirect effect that was the association of social cognition with neurocognition and with functional outcome. ToM was significantly associated with neurocognition and the path from neurocognition to functioning was no longer significant as soon as the mediator (ToM) was entered into the mediation model consistent with a complete mediation effect through ToM. This mediation was independent of the psychosis-risk status and the psychiatric diagnoses. Our results provide useful information on a young psychiatric sample, in which specific therapeutic interventions have the potential to significantly limit functional disability. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. A plasma cell differentiation quality control ablates B cell clones with biallelic Ig rearrangements and truncated Ig production.

    Science.gov (United States)

    Srour, Nivine; Chemin, Guillaume; Tinguely, Aurélien; Ashi, Mohamad Omar; Oruc, Zéliha; Péron, Sophie; Sirac, Christophe; Cogné, Michel; Delpy, Laurent

    2016-01-11

    Aberrantly rearranged immunoglobulin (Ig) alleles are frequent. They are usually considered sterile and innocuous as a result of nonsense-mediated mRNA decay. However, alternative splicing can yield internally deleted proteins from such nonproductively V(D)J-rearranged loci. We show that nonsense codons from variable (V) Igκ exons promote exon-skipping and synthesis of V domain-less κ light chains (ΔV-κLCs). Unexpectedly, such ΔV-κLCs inhibit plasma cell (PC) differentiation. Accordingly, in wild-type mice, rearrangements encoding ΔV-κLCs are rare in PCs, but frequent in B cells. Likewise, enforcing expression of ΔV-κLCs impaired PC differentiation and antibody responses without disturbing germinal center reactions. In addition, PCs expressing ΔV-κLCs synthesize low levels of Ig and are mostly found among short-lived plasmablasts. ΔV-κLCs have intrinsic toxic effects in PCs unrelated to Ig assembly, but mediated by ER stress-associated apoptosis, making PCs producing ΔV-κLCs highly sensitive to proteasome inhibitors. Altogether, these findings demonstrate a quality control checkpoint blunting terminal PC differentiation by eliminating those cells expressing nonfunctionally rearranged Igκ alleles. This truncated Ig exclusion (TIE) checkpoint ablates PC clones with ΔV-κLCs production and exacerbated ER stress response. The TIE checkpoint thus mediates selection of long-lived PCs with limited ER stress supporting high Ig secretion, but with a cost in terms of antigen-independent narrowing of the repertoire. © 2016 Srour et al.

  9. Secondary Hypertension

    Science.gov (United States)

    Secondary hypertension Overview Secondary hypertension (secondary high blood pressure) is high blood pressure that's caused by another medical condition. Secondary hypertension can be caused by conditions that affect your kidneys, ...

  10. PMS2 inactivation by a complex rearrangement involving an HERV retroelement and the inverted 100-kb duplicon on 7p22.1.

    Science.gov (United States)

    Vogt, Julia; Wernstedt, Annekatrin; Ripperger, Tim; Pabst, Brigitte; Zschocke, Johannes; Kratz, Christian; Wimmer, Katharina

    2016-11-01

    Biallelic PMS2 mutations are responsible for more than half of all cases of constitutional mismatch repair deficiency (CMMRD), a recessively inherited childhood cancer predisposition syndrome. The mismatch repair gene PMS2 is partly embedded within one copy of an inverted 100-kb low-copy repeat (LCR) on 7p22.1. In an individual with CMMRD syndrome, PMS2 was found to be homozygously inactivated by a complex chromosomal rearrangement, which separates the 5'-part from the 3'-part of the gene. The rearrangement involves sequences of the inverted 100-kb LCR and a human endogenous retrovirus element and may be associated with an inversion that is indistinguishable from the known inversion polymorphism affecting the ~0.7-Mb sequence intervening the LCR. Its formation is best explained by a replication-based mechanism (RBM) such as fork stalling and template switching/microhomology-mediated break-induced replication (FoSTeS/MMBIR). This finding supports the hypothesis that the inverted LCR can not only facilitate the formation of the non-allelic homologous recombination-mediated inversion polymorphism but it also promotes the occurrence of more complex rearrangements that can be associated with a large inversion, as well, but are mediated by a RBM. This further suggests that among the inversion polymorphism on 7p22.1, more complex rearrangements might be hidden. Furthermore, as the locus is embedded in a common fragile site (CFS) region, this rearrangement also supports the recently raised hypothesis that CFS sequence motifs may facilitate replication-based rearrangement mechanisms.

  11. Quantum concept of the rearrangement of a crystal lattice

    International Nuclear Information System (INIS)

    Gureev, M.D.; Mednikov, S.I.

    1995-01-01

    Using quantum considerations based on the concept of lattice rearrangement waves, we carried out an analysis of processes of rearrangement of a crystal lattice occurring on a moving front (interface) of crystal rearrangement. For the introduction and quantization of these waves we use the method of acoustomechanical analogy and the Sommerfeld quantum conditions. We calculate the energies and the propagation velocities of the lattice rearrangement waves. Along with quanta having a certain momentum, quanta that have a certain angular momentum are introduced into consideration. On the basis of the concepts developed, we suggest a new expression for calculating the probability of thermofluctuational processes in a crystal. We perform a numerical analysis of the rate of growth of the γ-phase in iron in the process of α-γ-conversion. Satisfactory agreement with experiment is obtained. We discuss the limitations and prospects of further development of the concept suggested. For direct experimental verification of the concept we propose to investigate the diffraction of electrons and other particles on the lattice rearrangement waves, i.e., in the process of phase conversions or disintegration of crystals

  12. Genome rearrangements detected by SNP microarrays in individuals with intellectual disability referred with possible Williams syndrome.

    Directory of Open Access Journals (Sweden)

    Ariel M Pani

    2010-08-01

    Full Text Available Intellectual disability (ID affects 2-3% of the population and may occur with or without multiple congenital anomalies (MCA or other medical conditions. Established genetic syndromes and visible chromosome abnormalities account for a substantial percentage of ID diagnoses, although for approximately 50% the molecular etiology is unknown. Individuals with features suggestive of various syndromes but lacking their associated genetic anomalies pose a formidable clinical challenge. With the advent of microarray techniques, submicroscopic genome alterations not associated with known syndromes are emerging as a significant cause of ID and MCA.High-density SNP microarrays were used to determine genome wide copy number in 42 individuals: 7 with confirmed alterations in the WS region but atypical clinical phenotypes, 31 with ID and/or MCA, and 4 controls. One individual from the first group had the most telomeric gene in the WS critical region deleted along with 2 Mb of flanking sequence. A second person had the classic WS deletion and a rearrangement on chromosome 5p within the Cri du Chat syndrome (OMIM:123450 region. Six individuals from the ID/MCA group had large rearrangements (3 deletions, 3 duplications, one of whom had a large inversion associated with a deletion that was not detected by the SNP arrays.Combining SNP microarray analyses and qPCR allowed us to clone and sequence 21 deletion breakpoints in individuals with atypical deletions in the WS region and/or ID or MCA. Comparison of these breakpoints to databases of genomic variation revealed that 52% occurred in regions harboring structural variants in the general population. For two probands the genomic alterations were flanked by segmental duplications, which frequently mediate recurrent genome rearrangements; these may represent new genomic disorders. While SNP arrays and related technologies can identify potentially pathogenic deletions and duplications, obtaining sequence information

  13. Hominoid chromosomal rearrangements on 17q map to complex regions of segmental duplication.

    Science.gov (United States)

    Cardone, Maria Francesca; Jiang, Zhaoshi; D'Addabbo, Pietro; Archidiacono, Nicoletta; Rocchi, Mariano; Eichler, Evan E; Ventura, Mario

    2008-01-01

    Chromosomal rearrangements, such as translocations and inversions, are recurrent phenomena during evolution, and both of them are involved in reproductive isolation and speciation. To better understand the molecular basis of chromosome rearrangements and their part in karyotype evolution, we have investigated the history of human chromosome 17 by comparative fluorescence in situ hybridization (FISH) and sequence analysis. Human bacterial artificial chromosome/p1 artificial chromosome probes spanning the length of chromosome 17 were used in FISH experiments on great apes, Old World monkeys and New World monkeys to study the evolutionary history of this chromosome. We observed that the macaque marker order represents the ancestral organization. Human, chimpanzee and gorilla homologous chromosomes differ by a paracentric inversion that occurred specifically in the Homo sapiens/Pan troglodytes/Gorilla gorilla ancestor. Detailed analyses of the paracentric inversion revealed that the breakpoints mapped to two regions syntenic to human 17q12/21 and 17q23, both rich in segmental duplications. Sequence analyses of the human and macaque organization suggest that the duplication events occurred in the catarrhine ancestor with the duplication blocks continuing to duplicate or undergo gene conversion during evolution of the hominoid lineage. We propose that the presence of these duplicons has mediated the inversion in the H. sapiens/P. troglodytes/G. gorilla ancestor. Recently, the same duplication blocks have been shown to be polymorphic in the human population and to be involved in triggering microdeletion and duplication in human. These results further support a model where genomic architecture has a direct role in both rearrangement involved in karyotype evolution and genomic instability in human.

  14. Deletional rearrangement in the human T-cell receptor α-chain locus

    International Nuclear Information System (INIS)

    de Villartay, J.P.; Lewis, D.; Hockett, R.; Waldmann, T.A.; Korsmeyer, S.J.; Cohen, D.I.

    1987-01-01

    The antigen-specific receptor on the surface of mature T lymphocytes is a heterodimer consisting of polypeptides termed α and β. In the course of characterizing human T-cell tumors with an immature (CD4 - , CD8 - ) surface phenotype, the authors detected a 2-kilobase α-related transcript. Analysis of cDNA clones corresponding to this transcript established that a genetic element (which they call TEA, for T early α) located between the α-chain variable- and joining-region genes had been spliced to the α constant region. The TEA transcript is present early in thymocyte ontogeny, and its expression declines during T-cell maturation. More important, the TEA area functions as an active site for rearrangement within the α gene locus. Blot hybridization of restriction enzyme-digested DNA with a TEA probe revealed a narrowly limited pattern of rearrangement in polyclonal thymic DNA, surprisingly different from the pattern expected for the mature α gene with its complex diversity. These DNA blots also showed that TEA is generally present in the germ-line configuration in cells expressing the γδ heterodimeric receptor and is deleted from mature (αβ-expressing) T-lymphocyte tumors and lines. Moreover, the TEA transcript lacked a long open reading frame for protein but instead possessed multiple copies of a repetitive element resembling those utilized in the heavy-chain class switch of the immunoglobulin genes. The temporal nature of the rearrangements and expression detected by TEA suggests that this recombination could mediate a transition between immature (γδ-expressing) T cells and mature (αβ-expressing) T cells

  15. Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

    International Nuclear Information System (INIS)

    Huang, Xionggao; Wei, Yantao; Ma, Haizhi; Zhang, Shaochong

    2012-01-01

    Highlights: ► Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. ► Rac1 is activated in vitreous-transformed RPE cells. ► Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. ► Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. ► The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous-transformed human RPE cells undergo cytoskeletal rearrangements via Rac1 GTPase-dependent pathways that modulate LIMK1 and

  16. Vitreous-induced cytoskeletal rearrangements via the Rac1 GTPase-dependent signaling pathway in human retinal pigment epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Xionggao [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Department of Ophthalmology, Hainan Medical College, Haikou (China); Wei, Yantao; Ma, Haizhi [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China); Zhang, Shaochong, E-mail: zhshaochong@163.com [State Key Ophthalmic Laboratory, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou (China)

    2012-03-09

    Highlights: Black-Right-Pointing-Pointer Vitreous induces morphological changes and cytoskeletal rearrangements in RPE cells. Black-Right-Pointing-Pointer Rac1 is activated in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer Rac inhibition prevents morphological changes in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer Rac inhibition suppresses cytoskeletal rearrangements in vitreous-transformed RPE cells. Black-Right-Pointing-Pointer The vitreous-induced effects are mediated by a Rac1 GTPase/LIMK1/cofilin pathway. -- Abstract: Proliferative vitreoretinopathy (PVR) is mainly caused by retinal pigment epithelial (RPE) cell migration, invasion, proliferation and transformation into fibroblast-like cells that produce the extracellular matrix (ECM). The vitreous humor is known to play an important role in PVR. An epithelial-to-mesenchymal transdifferentiation (EMT) of human RPE cells induced by 25% vitreous treatment has been linked to stimulation of the mesenchymal phenotype, migration and invasion. Here, we characterized the effects of the vitreous on the cell morphology and cytoskeleton in human RPE cells. The signaling pathway that mediates these effects was investigated. Serum-starved RPE cells were incubated with 25% vitreous, and the morphological changes were examined by phase-contrast microscopy. Filamentous actin (F-actin) was examined by immunofluorescence and confocal microscopy. Protein phosphorylation of AKT, ERK1/2, Smad2/3, LIM kinase (LIMK) 1 and cofilin was analyzed by Western blot analysis. Vitreous treatment induced cytoskeletal rearrangements, activated Rac1 and enhanced the phosphorylation of AKT, ERK1/2 and Smad2/3. When the cells were treated with a Rac activation-specific inhibitor, the cytoskeletal rearrangements were prevented, and the phosphorylation of Smad2/3 was blocked. Vitreous treatment also enhanced the phosphorylation of LIMK1 and cofilin and the Rac inhibitor blocked this effect. We propose that vitreous

  17. Telomerase activation by genomic rearrangements in high-risk neuroblastoma

    Science.gov (United States)

    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L.; Sand, Frederik; Heuckmann, Johannes M.; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Glöckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R.; Savelyeva, Larissa; Watkins, Simon C.; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H.; Herrmann, Carl; O’Sullivan, Roderick J.; Westermann, Frank; Thomas, Roman K.; Fischer, Matthias

    2016-01-01

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system1. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive2–4. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type1,2,5. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours. PMID:26466568

  18. Frequency of USP6 rearrangements in myositis ossificans, brown tumor, and cherubism: molecular cytogenetic evidence that a subset of ''myositis ossificans-like lesions'' are the early phases in the formation of soft-tissue aneurysmal bone cyst

    International Nuclear Information System (INIS)

    Sukov, William R.; Erickson-Johnson, Michele; Unni, K.K.; Wang, Xiaoke; Oliveira, Andre M.; Franco, Marcello F.; Chou, Margaret M.; Wenger, Doris E.

    2008-01-01

    USP6 rearrangements with several partner genes have been identified recently in primary but not in secondary aneurysmal bone cysts (ABCs). Several lesions show histologic features that may overlap with ABC, including myositis ossificans (MO), brown tumor, and cherubism. The objective of this study was to assess whether these lesions harbored USP6 rearrangements. Twelve patients with classic radiologic and histologic features of MO, 6 with brown tumors, and 5 with cherubism diagnosed at our institution were studied for the presence of USP6 rearrangements using fluorescence in situ hybridization with probes flanking the USP6 locus on chromosome 17p13. In addition, conventional cytogenetic analysis was performed in 2 patients with cherubism. USP6 rearrangements were identified in 2 patients with radiologic and histologic features consistent with MO. None of the patients with brown tumor or cherubism demonstrated USP6 rearrangements. Cytogenetic analysis of the cherubism patients demonstrated normal karyotypes. These findings indicate that a subset of cases with apparent classic histologic and imaging features of MO are rather better classified as being soft-tissue ABC with clonal USP6 rearrangements. In contrast, no USP6 rearrangements were found in patients with cherubism or brown tumor, supporting the prevailing view that these lesions are distinct biologic entities. (orig.)

  19. Recurrent DNA inversion rearrangements in the human genome

    DEFF Research Database (Denmark)

    Flores, Margarita; Morales, Lucía; Gonzaga-Jauregui, Claudia

    2007-01-01

    Several lines of evidence suggest that reiterated sequences in the human genome are targets for nonallelic homologous recombination (NAHR), which facilitates genomic rearrangements. We have used a PCR-based approach to identify breakpoint regions of rearranged structures in the human genome...... to human genomic variation is discussed........ In particular, we have identified intrachromosomal identical repeats that are located in reverse orientation, which may lead to chromosomal inversions. A bioinformatic workflow pathway to select appropriate regions for analysis was developed. Three such regions overlapping with known human genes, located...

  20. Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci.

    Science.gov (United States)

    Rother, Magdalena B; Palstra, Robert-Jan; Jhunjhunwala, Suchit; van Kester, Kevin A M; van IJcken, Wilfred F J; Hendriks, Rudi W; van Dongen, Jacques J M; Murre, Cornelis; van Zelm, Menno C

    2016-01-08

    Progenitor-B cells recombine their immunoglobulin (Ig) loci to create unique antigen receptors. Despite a common recombination machinery, the Ig heavy and Ig light chain loci rearrange in a stepwise manner. We studied pre-pro-B cells and Rag(-/-) progenitor-B cells to determine whether Ig locus contraction or nuclear positioning is decisive for stepwise rearrangements. We found that both Ig loci were contracted in pro-B and pre-B cells. Igh relocated from the nuclear lamina to central domains only at the pro-B cell stage, whereas, Igκ remained sequestered at the lamina, and only at the pre-B cell stage located to central nuclear domains. Finally, in vitro induced re-positioning of Ig alleles away from the nuclear periphery increased germline transcription of Ig loci in pre-pro-B cells. Thus, Ig locus contraction juxtaposes genomically distant elements to mediate efficient recombination, however, sequential positioning of Ig loci away from the nuclear periphery determines stage-specific accessibility of Ig loci. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  1. Screening for subtle chromosomal rearrangements in an Egyptian ...

    African Journals Online (AJOL)

    A descriptive study was carried out to screen for subtle chromosomal rearrangements in a group of Egyptian children with idiopathic mental retardation (IMR) to estimate its frequency if detected. The study enrolled 30 patients with IMR, with the perquisite criteria of being <18 years at referral, their IQ <70, and manifesting at ...

  2. Screening for genomic rearrangements at BRCA1 locus in Iranian ...

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Home; Journals; Journal of Genetics; Volume 92; Issue 1. Screening for genomic rearrangements at BRCA1 locus in Iranian women with breast cancer using multiplex ligation-dependent probe amplification. Vahid R. Yassaee Babak Emamalizadeh Mir Davood Omrani. Research Note Volume 92 Issue 1 ...

  3. Conjugated polyaniline as a result of the benzidine rearrangement

    Czech Academy of Sciences Publication Activity Database

    Sapurina, Irina; Tenkovtsev, A. V.; Stejskal, Jaroslav

    2015-01-01

    Roč. 64, č. 4 (2015), s. 453-465 ISSN 0959-8103 R&D Projects: GA MŠk(CZ) LH14199; GA ČR(CZ) GA13-00270S Institutional support: RVO:61389013 Keywords : aniline * aniline oligomers * benzidine rearrangement Subject RIV: CD - Macromolecular Chemistry Impact factor: 2.414, year: 2015

  4. Frequent Chromatin Rearrangements in Myelodysplastic Syndromes - What Stands Behind?

    Czech Academy of Sciences Publication Activity Database

    Pagáčová, Eva; Falk, Martin; Falková, Iva; Lukášová, Emilie; Michalová, K.; Oltová, A.; Raška, I.; Kozubek, Stanislav

    2014-01-01

    Roč. 60, č. 2014 (2014), s. 1-7 ISSN 0015-5500 R&D Projects: GA ČR(CZ) GBP302/12/G157; GA MŠk(CZ) EE2.3.30.0030 Institutional support: RVO:68081707 Keywords : myelodysplastic syndromes * chromosomal rearrangements * chromosome 5 deletions Subject RIV: BO - Biophysics Impact factor: 1.000, year: 2014

  5. Genome rearrangements and phylogeny reconstruction in Yersinia pestis.

    Science.gov (United States)

    Bochkareva, Olga O; Dranenko, Natalia O; Ocheredko, Elena S; Kanevsky, German M; Lozinsky, Yaroslav N; Khalaycheva, Vera A; Artamonova, Irena I; Gelfand, Mikhail S

    2018-01-01

    Genome rearrangements have played an important role in the evolution of Yersinia pestis from its progenitor Yersinia pseudotuberculosis . Traditional phylogenetic trees for Y. pestis based on sequence comparison have short internal branches and low bootstrap supports as only a small number of nucleotide substitutions have occurred. On the other hand, even a small number of genome rearrangements may resolve topological ambiguities in a phylogenetic tree. We reconstructed phylogenetic trees based on genome rearrangements using several popular approaches such as Maximum likelihood for Gene Order and the Bayesian model of genome rearrangements by inversions. We also reconciled phylogenetic trees for each of the three CRISPR loci to obtain an integrated scenario of the CRISPR cassette evolution. Analysis of contradictions between the obtained evolutionary trees yielded numerous parallel inversions and gain/loss events. Our data indicate that an integrated analysis of sequence-based and inversion-based trees enhances the resolution of phylogenetic reconstruction. In contrast, reconstructions of strain relationships based on solely CRISPR loci may not be reliable, as the history is obscured by large deletions, obliterating the order of spacer gains. Similarly, numerous parallel gene losses preclude reconstruction of phylogeny based on gene content.

  6. Ring Expansion and Rearrangements of Rhodium(II) Azavinyl Carbenes

    Science.gov (United States)

    Selander, Nicklas; Worrell, Brady T.

    2013-01-01

    An efficient, regioselective and convergent method for the ring expansion and rearrangement of 1-sulfonyl-1,2,3-triazoles under rhodium(II)-catalyzed conditions is described. These denitrogenative reactions form substituted enaminone and olefin-based products, which in the former case can be further functionalized to unique products rendering the sulfonyl triazole traceless. PMID:23161725

  7. [Lung adenocarcinoma with concomitant EGFR mutation and ALK rearrangement].

    Science.gov (United States)

    Caliez, J; Monnet, I; Pujals, A; Rousseau-Bussac, G; Jabot, L; Boudjemaa, A; Leroy, K; Chouaid, C

    2017-05-01

    Among patients with non-small-cell lung cancer, coexistence of EGFR mutation and ALK rearrangement is rare. We describe the clinical features of two patients with this double anomaly. A 62-year-old Caucasian non-smoking woman was diagnosed with cT4N0M0 lung adenocarcinoma. Initial biopsy showed EGFR mutation and ALK rearrangement. She received cisplatin-gemcitabine, followed by 17 months of gemcitabine. Owing to progression, she received erlotinib for 14 months, then paclitaxel for 6 months and finally crizotinib. A partial response was achieved and maintained for 24 months. A 45-year-old Caucasian woman, light smoker, was diagnosed with cT2N3M0 lung adenocarcinoma. Only EGFR mutation was found on initial analysis. She underwent treatment with cisplatin-gemcitabine and thoracic radiotherapy. Progression occurred after 8 months and afatinbib was started. Eight months later, progression was observed with a neoplasic pleural effusion in which tumor cells expressing ALK rearrangement were found. A new FISH analysis was performed on the initial tumor but did not find this rearrangement. Despite a third line of crizotinib, the patient died one month later. The literature shows 45 other cases of these two abnormalities, observed either from the start or during follow-up. EGFR's TKI were almost always given before ALK's TKI. Therapeutic strategy needs to be clarified in cases of double alteration. With regard to the second patient, appearance of ALK rearrangement may constitute a resistance mechanism to EGFR's TKI. Copyright © 2016 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  8. Nuclear structure in cold rearrangement processes in fission and fusion

    Energy Technology Data Exchange (ETDEWEB)

    Armbruster, P.

    1998-11-01

    In fission and fusion of heavy nuclei large numbers of nucleons are rearranged at a scale of excitation energy very small compared to the binding energy of the nuclei. The energies involved are less than 40 MeV at nuclear temperatures below 1.5 MeV. The shapes of the configurations in the rearrangement of a binary system into a monosystem in fusion, or vice versa in fission, change their elongations by as much as 8 fm, the radius of the monosystem. The dynamics of the reactions macroscopically described by a potential energy surface, inertia parameters, dissipation, and a collision energy is strongly modified by the nuclear structure of the participating nuclei. Experiments showing nuclear structure effects in fusion and fission of the heaviest nuclei are reviewed. The reaction kinematics and the multitude of isotopes involved are investigated by detector techniques and by recoil spectrometers. The advancement of the latter allows to find very small reaction branches in the range of 10{sup -5} to 10{sup -10}. The experiments reveal nuclear structure effects in all stages of the rearrangement processes. These are discussed pointing to analogies in fusion and fission on the microscopic scale, notwithstanding that both processes macroscopically are irreversible. Heavy clusters, as 132Sn, 208Pb, nuclei with closed shell configurations N=82,126, Z=50,82 survive in large parts of the nuclear rearrangement. They determine the asymmetry in the mass distribution of low energy fission, and they allow to synthesise superheavy elements, until now up to element 112. Experiments on the cold rearrangement in fission and fusion are presented. Here, in the range of excitation energies below 12 MeV the phenomena are observed most convincingly. (orig.)

  9. Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms

    NARCIS (Netherlands)

    Kloosterman, Wigard P; Tavakoli-Yaraki, Masoumeh; van Roosmalen, Markus J; van Binsbergen, Ellen; Renkens, Ivo; Duran, Karen; Ballarati, Lucia; Vergult, Sarah; Giardino, Daniela; Hansson, Kerstin; Ruivenkamp, Claudia A L; Jager, Myrthe; van Haeringen, Arie; Ippel, Elly F; Haaf, Thomas; Passarge, Eberhard; Hochstenbach, Ron; Menten, Björn; Larizza, Lidia; Guryev, Victor; Poot, Martin; Cuppen, Edwin

    2012-01-01

    Chromothripsis represents a novel phenomenon in the structural variation landscape of cancer genomes. Here, we analyze the genomes of ten patients with congenital disease who were preselected to carry complex chromosomal rearrangements with more than two breakpoints. The rearrangements displayed

  10. Ligand flexibility and framework rearrangement in a new family of porous metal-organic frameworks

    DEFF Research Database (Denmark)

    Hawxwell, Samuel M; Espallargas, Guillermo Mínguez; Bradshaw, Darren

    2007-01-01

    Ligand flexibility permits framework rearrangement upon evacuation and gas uptake in a new family of porous MOFs.......Ligand flexibility permits framework rearrangement upon evacuation and gas uptake in a new family of porous MOFs....

  11. Claisen, Cope and Related Rearrangements in the Synthesis of Flavour and Fragrance Compounds

    Directory of Open Access Journals (Sweden)

    Janusz Nowicki

    2000-08-01

    Full Text Available A review of the use of the Claisen, Cope and related [3,3]-sigmatropic rearrangements, sequential ("tandem" sigmatropic rearrangements and the "ene" reaction in the syntheses of flavour and fragrance compounds is presented.

  12. Fine-tiling array CGH to improve diagnostics for alpha- and beta-thalassemia rearrangements

    NARCIS (Netherlands)

    Phylipsen, M.; Chaibunruang, A.; Vogelaar, I.P.; Balak, J.R.; Schaap, R.A.; Ariyurek, Y.; Fucharoen, S.; den Dunnen, J.T.; Giordano, P.C.; Bakker, E.; Harteveld, C.L.

    2012-01-01

    Implementation of multiplex ligation-dependent probe amplification (MLPA) for thalassemia causing deletions has lead to the detection of new rearrangements. Knowledge of the exact breakpoint sequences should give more insight into the molecular mechanisms underlying these rearrangements, and would

  13. Classic theory for chromosome rearrangements with spatially restricted volume for broken ends interaction

    International Nuclear Information System (INIS)

    Omel'yanchuk, L.V.

    1997-01-01

    D. Lea classic theory for chromosomal rearrangements formation was modified to account for local interaction of broken chromosome ends. This assumption makes it possible to drastically improve coincidence of the theory and experiment in the case of complex rearrangements

  14. Secondary mediation and regression analyses of the PTClinResNet database: determining causal relationships among the International Classification of Functioning, Disability and Health levels for four physical therapy intervention trials.

    Science.gov (United States)

    Mulroy, Sara J; Winstein, Carolee J; Kulig, Kornelia; Beneck, George J; Fowler, Eileen G; DeMuth, Sharon K; Sullivan, Katherine J; Brown, David A; Lane, Christianne J

    2011-12-01

    Each of the 4 randomized clinical trials (RCTs) hosted by the Physical Therapy Clinical Research Network (PTClinResNet) targeted a different disability group (low back disorder in the Muscle-Specific Strength Training Effectiveness After Lumbar Microdiskectomy [MUSSEL] trial, chronic spinal cord injury in the Strengthening and Optimal Movements for Painful Shoulders in Chronic Spinal Cord Injury [STOMPS] trial, adult stroke in the Strength Training Effectiveness Post-Stroke [STEPS] trial, and pediatric cerebral palsy in the Pediatric Endurance and Limb Strengthening [PEDALS] trial for children with spastic diplegic cerebral palsy) and tested the effectiveness of a muscle-specific or functional activity-based intervention on primary outcomes that captured pain (STOMPS, MUSSEL) or locomotor function (STEPS, PEDALS). The focus of these secondary analyses was to determine causal relationships among outcomes across levels of the International Classification of Functioning, Disability and Health (ICF) framework for the 4 RCTs. With the database from PTClinResNet, we used 2 separate secondary statistical approaches-mediation analysis for the MUSSEL and STOMPS trials and regression analysis for the STEPS and PEDALS trials-to test relationships among muscle performance, primary outcomes (pain related and locomotor related), activity and participation measures, and overall quality of life. Predictive models were stronger for the 2 studies with pain-related primary outcomes. Change in muscle performance mediated or predicted reductions in pain for the MUSSEL and STOMPS trials and, to some extent, walking speed for the STEPS trial. Changes in primary outcome variables were significantly related to changes in activity and participation variables for all 4 trials. Improvement in activity and participation outcomes mediated or predicted increases in overall quality of life for the 3 trials with adult populations. Variables included in the statistical models were limited to those

  15. Factors Predicting Burnout Among Chaplains: Compassion Satisfaction, Organizational Factors, and the Mediators of Mindful Self-Care and Secondary Traumatic Stress.

    Science.gov (United States)

    Hotchkiss, Jason T; Lesher, Ruth

    2018-06-01

    This study predicted Burnout from the self-care practices, compassion satisfaction, secondary traumatic stress, and organizational factors among chaplains who participated from all 50 states (N = 534). A hierarchical regression model indicated that the combined effect of compassion satisfaction, secondary traumatic stress, mindful self-care, demographic, and organizational factors explained 83.2% of the variance in Burnout. Chaplains serving in a hospital were slightly more at risk for Burnout than those in hospice or other settings. Organizational factors that most predicted Burnout were feeling bogged down by the "system" (25.7%) and an overwhelming caseload (19.9%). Each self-care category was a statistically significant protective factor against Burnout risk. The strongest protective factors against Burnout in order of strength were self-compassion and purpose, supportive structure, mindful self-awareness, mindful relaxation, supportive relationships, and physical care. For secondary traumatic stress, supportive structure, mindful self-awareness, and self-compassion and purpose were the strongest protective factors. Chaplains who engaged in multiple and frequent self-care strategies experienced higher professional quality of life and low Burnout risk. In the chaplain's journey toward wellness, a reflective practice of feeling good about doing good and mindful self-care are vital. The significance, implications, and limitations of the study were discussed.

  16. The mediating effect of sleep satisfaction on the relationship between stress and perceived health of adolescents suffering atopic disease: Secondary analysis of data from the 2013 9th Korea Youth Risk Behavior Web-based Survey.

    Science.gov (United States)

    Oh, Won Oak; Im, YeoJin; Suk, Min Hyun

    2016-11-01

    Difficulty in sleep is one disturbing symptom in adolescents with atopic diseases including asthma, allergic rhinitis, and atopic dermatitis. Assuming psychological stress can affect adolescents' health status, impaired sleep quality can be one mediator that negatively impacts the health status of adolescents with atopic disease. This study aimed to identify the mediating effect of sleep satisfaction on the relationship between stress and perceived health status in Korean adolescents with atopic disease and to examine the differences among three types of atopic disease. A cross-sectional descriptive study was completed based on secondary analysis of raw data from the 2013 9th Korea Youth Risk Behavior Web-based Survey. The 21,154 adolescents (29.2%) ever diagnosed and treated for at least one atopic disease regardless of the symptom presence in a recent year were extracted out of 72,435 survey participants. Then, the 13,216 individuals with exclusively single atopic diseases were included in analyzing the mediation model. Variables including demographics, stress, perceived health status, and sleep satisfaction were included. Pearson correlation, one-way ANOVA, path analysis to define direct/indirect effects with bootstrapping analysis, and multi-group variance analysis were conducted. High levels of stress in adolescents with atopic diseases had a significant and direct effect on their negative health status perception for all atopic disease groups. A significant negative mediating effect of sleep satisfaction was identified on the relationship between stress and perceived health status, irrespective of the type of atopic disease. Total effect and remaining direct effect on the path from stress and perceived health status via sleep satisfaction was high in adolescents with atopic dermatitis and allergic rhinitis compared to those with asthma. To improve sleep satisfaction for adolescents with atopic diseases, interventions are needed to enhance the adolescents

  17. Secondary Students' Writing Achievement Goals: Assessing the Mediating Effects of Mastery and Performance Goals on Writing Self-Efficacy, Affect, and Writing Achievement

    Directory of Open Access Journals (Sweden)

    Meryem Yilmaz Soylu

    2017-08-01

    Full Text Available The two studies reported here explored the factor structure of the newly constructed Writing Achievement Goal Scale (WAGS, and examined relationships among secondary students' writing achievement goals, writing self-efficacy, affect for writing, and writing achievement. In the first study, 697 middle school students completed the WAGS. A confirmatory factor analysis revealed a good fit for this data with a three-factor model that corresponds with mastery, performance approach, and performance avoidance goals. The results of Study 1 were an indication for the researchers to move forward with Study 2, which included 563 high school students. The secondary students completed the WAGS, as well as the Self-efficacy for Writing Scale, and the Liking Writing Scale. Students also self-reported grades for writing and for language arts courses. Approximately 6 weeks later, students completed a statewide writing assessment. We tested a theoretical model representing relationships among Study 2 variables using structural equation modeling including students' responses to the study scales and students' scores on the statewide assessment. Results from Study 2 revealed a good fit between a model depicting proposed relationships among the constructs and the data. Findings are discussed relative to achievement goal theory and writing.

  18. Secondary Students' Writing Achievement Goals: Assessing the Mediating Effects of Mastery and Performance Goals on Writing Self-Efficacy, Affect, and Writing Achievement

    Science.gov (United States)

    Yilmaz Soylu, Meryem; Zeleny, Mary G.; Zhao, Ruomeng; Bruning, Roger H.; Dempsey, Michael S.; Kauffman, Douglas F.

    2017-01-01

    The two studies reported here explored the factor structure of the newly constructed Writing Achievement Goal Scale (WAGS), and examined relationships among secondary students' writing achievement goals, writing self-efficacy, affect for writing, and writing achievement. In the first study, 697 middle school students completed the WAGS. A confirmatory factor analysis revealed a good fit for this data with a three-factor model that corresponds with mastery, performance approach, and performance avoidance goals. The results of Study 1 were an indication for the researchers to move forward with Study 2, which included 563 high school students. The secondary students completed the WAGS, as well as the Self-efficacy for Writing Scale, and the Liking Writing Scale. Students also self-reported grades for writing and for language arts courses. Approximately 6 weeks later, students completed a statewide writing assessment. We tested a theoretical model representing relationships among Study 2 variables using structural equation modeling including students' responses to the study scales and students' scores on the statewide assessment. Results from Study 2 revealed a good fit between a model depicting proposed relationships among the constructs and the data. Findings are discussed relative to achievement goal theory and writing. PMID:28878707

  19. Genomecmp: computer software to detect genomic rearrangements using markers

    Science.gov (United States)

    Kulawik, Maciej; Nowak, Robert M.

    2017-08-01

    Detection of genomics rearrangements is a tough task, because of the size of data to be processed. As genome sequences may consist of hundreds of millions symbols, it is not only practically impossible to compare them by hand, but it is also complex problem for computer software. The way to significantly accelerate the process is to use rearrangement detection algorithm based on unique short sequences called markers. The algorithm described in this paper develops markers using base genome and find the markers positions on other genome. The algorithm has been extended by support for ambiguity symbols. Web application with graphical user interface has been created using three-layer architecture, where users could run the task simultaneously. The accuracy and efficiency of proposed solution has been studied using generated and real data.

  20. Semiclassical asymptotic behavior and the rearrangement mechanisms for Coulomb particles

    International Nuclear Information System (INIS)

    Bogdanov, A.V.; Gevorkyan, A.S.; Dubrovskii, G.V.

    1986-01-01

    The semiclassical asymptotic behavior of the eikonal amplitude of the resonance rearrangement in a system of three Coulomb particles is studied. It is shown that the general formula for the amplitude correctly describes two classical mechanisms (pickup and knockout) and one nonclassical mechanism (stripping). The classical mechanisms predominate at high energies, while the stripping mechanism predominates at lower energies. In the region of medium energies the dominant mechanism is the pickup (or Thomas) mechanism, which is realized by nonclassical means. For such transitions the classical cross section diverges, and the amplitude must be computed on a complex trajectory. The physical reasons for introducing the approximate complex trajectories are discussed. The contributions of all the mechanisms to the rearrangement cross section are found in their analytic forms

  1. Ionization-induced rearrangement of defects in silicon

    International Nuclear Information System (INIS)

    Vinetskij, V.L.; Manojlo, M.A.; Matvijchuk, A.S.; Strikha, V.I.; Kholodar', G.A.

    1988-01-01

    Ionizing factor effect on defect rearrangement in silicon including centers with deep local electron levels in the p-n-transition region is considered. Deep center parameters were determined using non-steady-state capacity spectroscopy of deep levels (NCDLS) method. NCDLS spectrum measurement was performed using source p + -n - diodes and after their irradiation with 15 keV energy electrons or laser pulses. It is ascertained that in silicon samples containing point defect clusters defect rearrangement under ionizing factor effect takes place, i.e. deep level spectra are changed. This mechanism is efficient in case of silicon irradiation with subthreshold energy photons and electrons and can cause degradation of silicon semiconducting structures

  2. Incremental exposure facilitates adaptation to sensory rearrangement. [vestibular stimulation patterns

    Science.gov (United States)

    Lackner, J. R.; Lobovits, D. N.

    1978-01-01

    Visual-target pointing experiments were performed on 24 adult volunteers in order to compare the relative effectiveness of incremental (stepwise) and single-step exposure conditions on adaptation to visual rearrangement. The differences between the preexposure and postexposure scores served as an index of the adaptation elicited during the exposure period. It is found that both single-step and stepwise exposure to visual rearrangement elicit compensatory changes in sensorimotor coordination. However, stepwise exposure, when compared to single-step exposur in terms of the average magnitude of visual displacement over the exposure period, clearly enhances the rate of adaptation. It seems possible that the enhancement of adaptation to unusual patterns of sensory stimulation produced by incremental exposure reflects a general principle of sensorimotor function.

  3. Chromosome-specific staining to detect genetic rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Gray, Joe W.; Pinkel, Daniel; Tkachuk, Douglas; Westbrook, Carol

    2013-04-09

    Methods and compositions for staining based upon nucleic acid sequence that employ nucleic acid probes are provided. Said methods produce staining patterns that can be tailored for specific cytogenetic analyzes. Said probes are appropriate for in situ hybridization and stain both interphase and metaphase chromosomal material with reliable signals. The nucleic acid probes are typically of a complexity greater than 50 kb, the complexity depending upon the cytogenetic application. Methods and reagents are provided for the detection of genetic rearrangements. Probes and test kits are provided for use in detecting genetic rearrangements, particularly for use in tumor cytogenetics, in the detection of disease related loci, specifically cancer, such as chronic myelogenous leukemia (CML) and for biological dosimetry. Methods and reagents are described for cytogenetic research, for the differentiation of cytogenetically similar but genetically different diseases, and for many prognostic and diagnostic applications.

  4. A system for the detection of chromosomal rearrangements using Sordaria macrospora

    International Nuclear Information System (INIS)

    Arnaise, S.; Leblon, G.; Lares, L.

    1984-01-01

    A system is described for the detection and diagnosis of induced chromosomal rearrangement using Sordaria macrospora. The system uses the property of the rearrangement to produce defective white ascospores as meiotic progeny from heterozygous crosses. Two reconstruction experiments have shown that this system is able to give reliable quantitative measures of rearrangement frequencies. Evidence for a photoreactivation process was obtained, suggesting that pyrimidine dimers may well be an important lesion in UV-induced chromosomal rearrangement. No evidence of induction of chromosomal rearrangement was obtained in experiments with the powerful chemical mutagen N-methyl-N'-nitro-N-nitrosoguanidine. (orig.)

  5. A system for the detection of chromosomal rearrangements using Sordaria macrospora.

    Science.gov (United States)

    Arnaise, S; Leblon, G; Lares, L

    1984-01-01

    A system is described for the detection and diagnosis of induced chromosomal rearrangement using Sordaria macrospora. The system uses the property of the rearrangement to produce defective white ascospores as meiotic progeny from heterozygous crosses. Two reconstruction experiments have shown that this system is able to give reliable quantitative measures of rearrangement frequencies. Evidence for a photoreactivation process was obtained, suggesting that pyrimidine dimers may well be an important lesion in UV-induced chromosomal rearrangement. No evidence of induction of chromosomal rearrangement was obtained in experiments with the powerful chemical mutagen N-methyl-N'-nitro-N-nitrosoguanidine.

  6. Level rearrangement in exotic atoms and quantum dots

    International Nuclear Information System (INIS)

    Combescure, Monique; Khare, Avinash; Raina, Ashok; Richard Jean-Marc; Weydert, Carole

    2007-01-01

    A presentation and a generalisation are given of the phenomenon of level rearrangement, which occurs when an attractive long-range potential is supplemented by a short-range attractive potential of increasing strength. This problem has been discovered in condensate-matter physics and has also been studied in the physics of exotic atoms. A similar phenomenon occurs in a situation inspired by quantum dots, where a short-range interaction is added to an harmonic confinement. (authors)

  7. Detection of genomic rearrangements in cucumber using genomecmp software

    Science.gov (United States)

    Kulawik, Maciej; Pawełkowicz, Magdalena Ewa; Wojcieszek, Michał; PlÄ der, Wojciech; Nowak, Robert M.

    2017-08-01

    Comparative genomic by increasing information about the genomes sequences available in the databases is a rapidly evolving science. A simple comparison of the general features of genomes such as genome size, number of genes, and chromosome number presents an entry point into comparative genomic analysis. Here we present the utility of the new tool genomecmp for finding rearrangements across the compared sequences and applications in plant comparative genomics.

  8. Recent applications of ring-rearrangement metathesis in organic synthesis

    Directory of Open Access Journals (Sweden)

    Sambasivarao Kotha

    2015-10-01

    Full Text Available Ring-rearrangement metathesis (RRM involves multiple metathesis processes such as ring-opening metathesis (ROM/ring-closing metathesis (RCM in a one-pot operation to generate complex targets. RRM delivers complex frameworks that are difficult to assemble by conventional methods. The noteworthy point about this type of protocol is multi-bond formation and it is an atom economic process. In this review, we have covered literature that appeared during the last seven years (2008–2014.

  9. Quantifying stretching and rearrangement in epithelial sheet migration

    International Nuclear Information System (INIS)

    Lee, Rachel M; Nordstrom, Kerstin N; Losert, Wolfgang; Kelley, Douglas H; Ouellette, Nicholas T

    2013-01-01

    Although understanding the collective migration of cells, such as that seen in epithelial sheets, is essential for understanding diseases such as metastatic cancer, this motion is not yet as well characterized as individual cell migration. Here we adapt quantitative metrics used to characterize the flow and deformation of soft matter to contrast different types of motion within a migrating sheet of cells. Using a finite-time Lyapunov exponent (FTLE) analysis, we find that—in spite of large fluctuations—the flow field of an epithelial cell sheet is not chaotic. Stretching of a sheet of cells (i.e. positive FTLE) is localized at the leading edge of migration and increases when the cells are more highly stimulated. By decomposing the motion of the cells into affine and non-affine components using the metric D m in 2 , we quantify local plastic rearrangements and describe the motion of a group of cells in a novel way. We find an increase in plastic rearrangements with increasing cell densities, whereas inanimate systems tend to exhibit less non-affine rearrangements with increasing density. (paper)

  10. Elevated Rate of Genome Rearrangements in Radiation-Resistant Bacteria.

    Science.gov (United States)

    Repar, Jelena; Supek, Fran; Klanjscek, Tin; Warnecke, Tobias; Zahradka, Ksenija; Zahradka, Davor

    2017-04-01

    A number of bacterial, archaeal, and eukaryotic species are known for their resistance to ionizing radiation. One of the challenges these species face is a potent environmental source of DNA double-strand breaks, potential drivers of genome structure evolution. Efficient and accurate DNA double-strand break repair systems have been demonstrated in several unrelated radiation-resistant species and are putative adaptations to the DNA damaging environment. Such adaptations are expected to compensate for the genome-destabilizing effect of environmental DNA damage and may be expected to result in a more conserved gene order in radiation-resistant species. However, here we show that rates of genome rearrangements, measured as loss of gene order conservation with time, are higher in radiation-resistant species in multiple, phylogenetically independent groups of bacteria. Comparison of indicators of selection for genome organization between radiation-resistant and phylogenetically matched, nonresistant species argues against tolerance to disruption of genome structure as a strategy for radiation resistance. Interestingly, an important mechanism affecting genome rearrangements in prokaryotes, the symmetrical inversions around the origin of DNA replication, shapes genome structure of both radiation-resistant and nonresistant species. In conclusion, the opposing effects of environmental DNA damage and DNA repair result in elevated rates of genome rearrangements in radiation-resistant bacteria. Copyright © 2017 Repar et al.

  11. Highly variable rates of genome rearrangements between hemiascomycetous yeast lineages.

    Directory of Open Access Journals (Sweden)

    2006-03-01

    Full Text Available Hemiascomycete yeasts cover an evolutionary span comparable to that of the entire phylum of chordates. Since this group currently contains the largest number of complete genome sequences it presents unique opportunities to understand the evolution of genome organization in eukaryotes. We inferred rates of genome instability on all branches of a phylogenetic tree for 11 species and calculated species-specific rates of genome rearrangements. We characterized all inversion events that occurred within synteny blocks between six representatives of the different lineages. We show that the rates of macro- and microrearrangements of gene order are correlated within individual lineages but are highly variable across different lineages. The most unstable genomes correspond to the pathogenic yeasts Candida albicans and Candida glabrata. Chromosomal maps have been intensively shuffled by numerous interchromosomal rearrangements, even between species that have retained a very high physical fraction of their genomes within small synteny blocks. Despite this intensive reshuffling of gene positions, essential genes, which cluster in low recombination regions in the genome of Saccharomyces cerevisiae, tend to remain syntenic during evolution. This work reveals that the high plasticity of eukaryotic genomes results from rearrangement rates that vary between lineages but also at different evolutionary times of a given lineage.

  12. On colour rearrangement in hadronic W+W- events

    International Nuclear Information System (INIS)

    Sjoestrand, T.; Khoze, V.A.

    1994-01-01

    We discuss the possibility of colour rearrangement in e + e - →W + W - →q 1 anti q 2 q 3 anti q 4 events, i.e. that the original colour singlets q 1 anti q 2 and q 3 anti q 4 may be transmuted, for instance, into new singlets q 1 anti q 4 and q 3 anti q 2 . The effects on event properties could be quite large if such a rearrangement would occur instantaneously, so that gluon emission would be restricted to each of the new singlets separately. We argue that such a scenario is unlikely for two reasons. Firstly, the W + and W - usually decay at separate times after the W + W - production, which leads to large relative phases for energetic radiation off the two constituents of a rearranged system, and a corresponding dampening of the QCD cascades. Secondly, within the perturbative scenario the colour transmutation appears only in order α s 2 and is colour-suppressed. Colour reconnection at longer time scales is quite feasible, however, and may affect the fragmentation phase. If so, the nature of non-perturbative QCD can be probed in a new way. We formulate several alternative toy models and use these to estimate the colour reconnection probability as a function of the event kinematics. Possible consequences for LEP 2 events are illustrated, with special attention to systematic errors in W mass determinations. (orig.)

  13. DCJ-RNA - double cut and join for RNA secondary structures.

    Science.gov (United States)

    Badr, Ghada H; Al-Aqel, Haifa A

    2017-10-16

    Genome rearrangements are essential processes for evolution and are responsible for existing varieties of genome architectures. Many studies have been conducted to obtain an algorithm that identifies the minimum number of inversions that are necessary to transform one genome into another; this allows for genome sequence representation in polynomial time. Studies have not been conducted on the topic of rearranging a genome when it is represented as a secondary structure. Unlike sequences, the secondary structure preserves the functionality of the genome. Sequences can be different, but they all share the same structure and, therefore, the same functionality. This paper proposes a double cut and join for RNA secondary structures (DCJ-RNA) algorithm. This algorithm allows for the description of evolutionary scenarios that are based on secondary structures rather than sequences. The main aim of this paper is to suggest an efficient algorithm that can help researchers compare two ribonucleic acid (RNA) secondary structures based on rearrangement operations. The results, which are based on real datasets, show that the algorithm is able to count the minimum number of rearrangement operations, as well as to report an optimum scenario that can increase the similarity between the two structures. The algorithm calculates the distance between structures and reports a scenario based on the minimum rearrangement operations required to make the given structure similar to the other. DCJ-RNA can also be used to measure the distance between the two structures. This can help identify the common functionalities between different species.

  14. Novel tumorigenic rearrangement, Δrfp/ret, in a papillary thyroid carcinoma from externally irradiated patient

    International Nuclear Information System (INIS)

    Saenko, Vladimir; Rogounovitch, Tatiana; Shimizu-Yoshida, Yuki; Abrosimov, Aleksandr; Lushnikov, Eugeny; Roumiantsev, Pavel; Matsumoto, Naomichi; Nakashima, Masahiro; Meirmanov, Serik; Ohtsuru, Akira; Namba, Hiroyuki; Tsyb, Anatoly; Yamashita, Shunichi

    2003-01-01

    Molecular analysis of cDNA derived from a papillary thyroid carcinoma (PTC) (follicular variant of papillary thyroid carcinoma on histology) which developed in an externally irradiated patient 4 years after exposure identified a portion of the 5' region, exons 1-3, of the rfp gene juxtaposed upstream of the fragment encoding the tyrosine kinase (TK) domain of the ret gene. The fusion gene, termed Δrfp/ret, was the result of a balanced chromosomal translocation t(6;10) (p21.3;q11.2) confirmed by interphase FISH painting, with breakpoints occurring in introns 3 and 11 of the rfp and ret genes, respectively. Both Δrfp/ret and reciprocal ret/rfp chimeric introns had small deletions around breakpoints consistent with presumed misrepair of a radiation-induced double-strand DNA break underlying the rearrangement. No extensive sequence homology was found between the fragments flanking the breakpoints. The fusion protein retained the propensity to form oligomers likely to be mediated by a coiled-coil of the RFP polypeptide as assessed by a yeast two-hybrid system. NIH 3T3 fibroblasts stably transfected with a mammalian expression vector encoding full-length ΔRFP/RET readily gave rise to the tumors in athymic mice suggestive of high transforming potential of the fusion protein. Thus, the Δrfp/ret rearrangement may be causatively involved in cancerogenesis and provides additional evidence of the role of activated ret oncogene in the development of a subset of papillary thyroid carcinoma

  15. Novel tumorigenic rearrangement, {delta}rfp/ret, in a papillary thyroid carcinoma from externally irradiated patient

    Energy Technology Data Exchange (ETDEWEB)

    Saenko, Vladimir; Rogounovitch, Tatiana; Shimizu-Yoshida, Yuki; Abrosimov, Aleksandr; Lushnikov, Eugeny; Roumiantsev, Pavel; Matsumoto, Naomichi; Nakashima, Masahiro; Meirmanov, Serik; Ohtsuru, Akira; Namba, Hiroyuki; Tsyb, Anatoly; Yamashita, Shunichi

    2003-06-19

    Molecular analysis of cDNA derived from a papillary thyroid carcinoma (PTC) (follicular variant of papillary thyroid carcinoma on histology) which developed in an externally irradiated patient 4 years after exposure identified a portion of the 5' region, exons 1-3, of the rfp gene juxtaposed upstream of the fragment encoding the tyrosine kinase (TK) domain of the ret gene. The fusion gene, termed {delta}rfp/ret, was the result of a balanced chromosomal translocation t(6;10) (p21.3;q11.2) confirmed by interphase FISH painting, with breakpoints occurring in introns 3 and 11 of the rfp and ret genes, respectively. Both {delta}rfp/ret and reciprocal ret/rfp chimeric introns had small deletions around breakpoints consistent with presumed misrepair of a radiation-induced double-strand DNA break underlying the rearrangement. No extensive sequence homology was found between the fragments flanking the breakpoints. The fusion protein retained the propensity to form oligomers likely to be mediated by a coiled-coil of the RFP polypeptide as assessed by a yeast two-hybrid system. NIH 3T3 fibroblasts stably transfected with a mammalian expression vector encoding full-length {delta}RFP/RET readily gave rise to the tumors in athymic mice suggestive of high transforming potential of the fusion protein. Thus, the {delta}rfp/ret rearrangement may be causatively involved in cancerogenesis and provides additional evidence of the role of activated ret oncogene in the development of a subset of papillary thyroid carcinoma.

  16. SUMO E3 ligase Mms21 prevents spontaneous DNA damage induced genome rearrangements.

    Directory of Open Access Journals (Sweden)

    Jason Liang

    2018-03-01

    Full Text Available Mms21, a subunit of the Smc5/6 complex, possesses an E3 ligase activity for the Small Ubiquitin-like MOdifier (SUMO. Here we show that the mms21-CH mutation, which inactivates Mms21 ligase activity, causes increased accumulation of gross chromosomal rearrangements (GCRs selected in the dGCR assay. These dGCRs are formed by non-allelic homologous recombination between divergent DNA sequences mediated by Rad52-, Rrm3- and Pol32-dependent break-induced replication. Combining mms21-CH with sgs1Δ caused a synergistic increase in GCRs rates, indicating the distinct roles of Mms21 and Sgs1 in suppressing GCRs. The mms21-CH mutation also caused increased rates of accumulating uGCRs mediated by breakpoints in unique sequences as revealed by whole genome sequencing. Consistent with the accumulation of endogenous DNA lesions, mms21-CH mutants accumulate increased levels of spontaneous Rad52 and Ddc2 foci and had a hyper-activated DNA damage checkpoint. Together, these findings support that Mms21 prevents the accumulation of spontaneous DNA lesions that cause diverse GCRs.

  17. A route to hydroxylfluorenes: TsOH-mediated condensation reactions of 1,3-diketones with propargylic alcohols

    KAUST Repository

    Yao, Liangfeng; Tan, Davin; Miao, Xiaohe; Huang, Kuo-Wei

    2012-01-01

    An efficient method of preparing hydroxylfluorenes by TsOH-mediated tandem alkylation/rearrangements of propargylic alcohols with 1,3-diketones is described. These reactions are accomplished in moderate to good yields under mild conditions to offer

  18. Rac1 mediates cytokine-stimulated hemocyte spreading via prostaglandin biosynthesis in the beet armyworm, Spodoptera exigua

    Science.gov (United States)

    Cell spreading is an integral component of insect hemocytic immune reactions to infections and invasions. Cell spreading is accomplished by cytoskeleton rearrangement, which is activated by three major immune mediators, biogenic monoamines, plasmatocyte-spreading peptide (PSP), and eicosanoids, part...

  19. [Secondary hypertension].

    Science.gov (United States)

    Yoshida, Yuichi; Shibata, Hirotaka

    2015-11-01

    Hypertension is a common disease and a crucial predisposing factor of cardiovascular diseases. Approximately 10% of hypertensive patients are secondary hypertension, a pathogenetic factor of which can be identified. Secondary hypertension consists of endocrine, renal, and other diseases. Primary aldosteronism, Cushing's syndrome, pheochromocytoma, hyperthyroidism, and hypothyroidism result in endocrine hypertension. Renal parenchymal hypertension and renovascular hypertension result in renal hypertension. Other diseases such as obstructive sleep apnea syndrome are also very prevalent in secondary hypertension. It is very crucial to find and treat secondary hypertension at earlier stages since most secondary hypertension is curable or can be dramatically improved by specific treatment. One should keep in mind that screening of secondary hypertension should be done at least once in a daily clinical practice.

  20. Refining borders of genome-rearrangements including repetitions

    Directory of Open Access Journals (Sweden)

    JA Arjona-Medina

    2016-10-01

    Full Text Available Abstract Background DNA rearrangement events have been widely studied in comparative genomic for many years. The importance of these events resides not only in the study about relatedness among different species, but also to determine the mechanisms behind evolution. Although there are many methods to identify genome-rearrangements (GR, the refinement of their borders has become a huge challenge. Until now no accepted method exists to achieve accurate fine-tuning: i.e. the notion of breakpoint (BP is still an open issue, and despite repeated regions are vital to understand evolution they are not taken into account in most of the GR detection and refinement methods. Methods and results We propose a method to refine the borders of GR including repeated regions. Instead of removing these repetitions to facilitate computation, we take advantage of them using a consensus alignment sequence of the repeated region in between two blocks. Using the concept of identity vectors for Synteny Blocks (SB and repetitions, a Finite State Machine is designed to detect transition points in the difference between such vectors. The method does not force the BP to be a region or a point but depends on the alignment transitions within the SBs and repetitions. Conclusion The accurate definition of the borders of SB and repeated genomic regions and consequently the detection of BP might help to understand the evolutionary model of species. In this manuscript we present a new proposal for such a refinement. Features of the SBs borders and BPs are different and fit with what is expected. SBs with more diversity in annotations and BPs short and richer in DNA replication and stress response, which are strongly linked with rearrangements.

  1. Recurrence risk in de novo structural chromosomal rearrangements.

    Science.gov (United States)

    Röthlisberger, Benno; Kotzot, Dieter

    2007-08-01

    According to the textbook of Gardner and Sutherland [2004], the standard on genetic counseling for chromosome abnormalities, the recurrence risk of de novo structural or combined structural and numeric chromosome rearrangements is less than 0.5-2% and takes into account recurrence by chance, gonadal mosaicism, and somatic-gonadal mosaicism. However, these figures are roughly estimated and neither any systematic study nor exact or evidence-based risk calculations are available. To address this question, an extensive literature search was performed and surprisingly only 29 case reports of recurrence of de novo structural or combined structural and numeric chromosomal rearrangements were found. Thirteen of them were with a trisomy 21 due to an i(21q) replacing one normal chromosome 21. In eight of them low-level mosaicism in one of the parents was found either in fibroblasts or in blood or in both. As a consequence of the low number of cases and theoretical considerations (clinical consequences, mechanisms of formation, etc.), the recurrence risk should be reduced to less than 1% for a de novo i(21q) and to even less than 0.3% for all other de novo structural or combined structural and numeric chromosomal rearrangements. As the latter is lower than the commonly accepted risk of approximately 0.3% for indicating an invasive prenatal diagnosis and as the risk of abortion of a healthy fetus after chorionic villous sampling or amniocentesis is higher than approximately 0.5%, invasive prenatal investigation in most cases is not indicated and should only be performed if explicitly asked by the parents subsequent to appropriate genetic counseling. (c) 2007 Wiley-Liss, Inc.

  2. Precise detection of rearrangement breakpoints in mammalian chromosomes

    Directory of Open Access Journals (Sweden)

    Gautier Christian

    2008-06-01

    Full Text Available Abstract Background Genomes undergo large structural changes that alter their organisation. The chromosomal regions affected by these rearrangements are called breakpoints, while those which have not been rearranged are called synteny blocks. We developed a method to precisely delimit rearrangement breakpoints on a genome by comparison with the genome of a related species. Contrary to current methods which search for synteny blocks and simply return what remains in the genome as breakpoints, we propose to go further and to investigate the breakpoints themselves in order to refine them. Results Given some reliable and non overlapping synteny blocks, the core of the method consists in refining the regions that are not contained in them. By aligning each breakpoint sequence against its specific orthologous sequences in the other species, we can look for weak similarities inside the breakpoint, thus extending the synteny blocks and narrowing the breakpoints. The identification of the narrowed breakpoints relies on a segmentation algorithm and is statistically assessed. Since this method requires as input synteny blocks with some properties which, though they appear natural, are not verified by current methods for detecting such blocks, we further give a formal definition and provide an algorithm to compute them. The whole method is applied to delimit breakpoints on the human genome when compared to the mouse and dog genomes. Among the 355 human-mouse and 240 human-dog breakpoints, 168 and 146 respectively span less than 50 Kb. We compared the resulting breakpoints with some publicly available ones and show that we achieve a better resolution. Furthermore, we suggest that breakpoints are rarely reduced to a point, and instead consist in often large regions that can be distinguished from the sequences around in terms of segmental duplications, similarity with related species, and transposable elements. Conclusion Our method leads to smaller

  3. [Synthetic biology and rearrangements of microbial genetic material].

    Science.gov (United States)

    Liang, Quan-Feng; Wang, Qian; Qi, Qing-Sheng

    2011-10-01

    As an emerging discipline, synthetic biology has shown great scientific values and application prospects. Although there have been many reviews of various aspects on synthetic biology over the last years, this article, for the first time, attempted to discuss the relationship and difference between microbial genetics and synthetic biology. We summarized the recent development of synthetic biology in rearranging microbial genetic materials, including synthesis, design and reduction of genetic materials, standardization of genetic parts and modularization of genetic circuits. The relationship between synthetic biology and microbial genetic engineering was also discussed in the paper.

  4. Acid Rearrangement of Secoiridoids Related to Oleuropein and Secologanin

    DEFF Research Database (Denmark)

    Bianco, Armandodoriano; Jensen, Søren Rosendal; Olesen, Jens

    2003-01-01

    Acid treatment of an iridoid glycoside results in the cleavage of the acetal bond between the sugar unit and the monoterpenoid aglycon. Iridoids possessing non-conjugated enol ether systems, however, undergo the hydration of the iridoid enol ether functionality in acid medium, as well as the hydr...... as the hydrolysis of the bond. We examined the acid rearrangement of secoiridoids such as oleuropein (1) and secologanin (2) and their reduction products oleuropeinol (3) and secologaninol (4), to examine whether similar behaviour also occurs in this case....

  5. Evidence for compact cooperatively rearranging regions in a supercooled liquid

    International Nuclear Information System (INIS)

    Elenius, M; Dzugutov, M

    2009-01-01

    We examine structural relaxation in a supercooled glass-forming liquid simulated by constant-energy constant-volume (NVE) molecular dynamics. Time correlations of the total kinetic energy fluctuations are used as a comprehensive measure of the system's approach to the ergodic equilibrium. We find that, under cooling, the total structural relaxation becomes delayed as compared with the decay of the component of the intermediate scattering function corresponding to the main peak of the structure factor. This observation can be explained by collective movements of particles preserving many-body structural correlations within compact three-dimensional (3D) cooperatively rearranging regions.

  6. Secondary Evaluations.

    Science.gov (United States)

    Cook, Thomas D.

    Secondary evaluations, in which an investigator takes a body of evaluation data collected by a primary evaluation researcher and examines the data to see if the original conclusions about the program correspond with his own, are discussed. The different kinds of secondary evaluations and the advantages and disadvantages of each are pointed out,…

  7. A Prediction Model for ROS1-Rearranged Lung Adenocarcinomas based on Histologic Features

    OpenAIRE

    Zhou, Jianya; Zhao, Jing; Zheng, Jing; Kong, Mei; Sun, Ke; Wang, Bo; Chen, Xi; Ding, Wei; Zhou, Jianying

    2016-01-01

    Aims To identify the clinical and histological characteristics of ROS1-rearranged non-small-cell lung carcinomas (NSCLCs) and build a prediction model to prescreen suitable patients for molecular testing. Methods and Results We identified 27 cases of ROS1-rearranged lung adenocarcinomas in 1165 patients with NSCLCs confirmed by real-time PCR and FISH and performed univariate and multivariate analyses to identify predictive factors associated with ROS1 rearrangement and finally developed predi...

  8. A BAC clone fingerprinting approach to the detection of human genome rearrangements

    Science.gov (United States)

    Krzywinski, Martin; Bosdet, Ian; Mathewson, Carrie; Wye, Natasja; Brebner, Jay; Chiu, Readman; Corbett, Richard; Field, Matthew; Lee, Darlene; Pugh, Trevor; Volik, Stas; Siddiqui, Asim; Jones, Steven; Schein, Jacquie; Collins, Collin; Marra, Marco

    2007-01-01

    We present a method, called fingerprint profiling (FPP), that uses restriction digest fingerprints of bacterial artificial chromosome clones to detect and classify rearrangements in the human genome. The approach uses alignment of experimental fingerprint patterns to in silico digests of the sequence assembly and is capable of detecting micro-deletions (1-5 kb) and balanced rearrangements. Our method has compelling potential for use as a whole-genome method for the identification and characterization of human genome rearrangements. PMID:17953769

  9. Large Clinically Consequential Imbalances Detected at the Breakpoints of Apparently Balanced and Inherited Chromosome Rearrangements

    OpenAIRE

    South, Sarah T.; Rector, Lyndsey; Aston, Emily; Rowe, Leslie; Yang, Samuel P.

    2010-01-01

    When a chromosome abnormality is identified in a child with a developmental delay and/or multiple congenital anomalies and the chromosome rearrangement appears balanced, follow-up studies often examine both parents for this rearrangement. If either clinically unaffected parent has a chromosome abnormality with a banding pattern identical to the affected child's study, then it is assumed that the chromosome rearrangement is balanced and directly inherited from the normal carrier parent. It is ...

  10. Insights into structural variations and genome rearrangements in prokaryotic genomes.

    Science.gov (United States)

    Periwal, Vinita; Scaria, Vinod

    2015-01-01

    Structural variations (SVs) are genomic rearrangements that affect fairly large fragments of DNA. Most of the SVs such as inversions, deletions and translocations have been largely studied in context of genetic diseases in eukaryotes. However, recent studies demonstrate that genome rearrangements can also have profound impact on prokaryotic genomes, leading to altered cell phenotype. In contrast to single-nucleotide variations, SVs provide a much deeper insight into organization of bacterial genomes at a much better resolution. SVs can confer change in gene copy number, creation of new genes, altered gene expression and many other functional consequences. High-throughput technologies have now made it possible to explore SVs at a much refined resolution in bacterial genomes. Through this review, we aim to highlight the importance of the less explored field of SVs in prokaryotic genomes and their impact. We also discuss its potential applicability in the emerging fields of synthetic biology and genome engineering where targeted SVs could serve to create sophisticated and accurate genome editing. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. FASEB Summer Research Conference. Genetic Recombination and Chromosome Rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Jinks-Robertson, Sue

    2002-02-01

    The 2001 meeting entitled ''Genetic Recombination and Genome Rearrangements'' was held July 21-26 in Snowmass, Colorado. The goal of the meeting was to bring together scientists using diverse approaches to study all aspects of genetic recombination. This goal was achieved by integrating talks covering the genetics, biochemistry and structural biology of homologous recombination, site-specific recombination, and nonhomologous recombination. The format of the meeting consisted of a keynote address on the opening evening, two formal plenary sessions on each of the four full meeting days, a single afternoon workshop consisting of short talks chosen from among submitted abstracts, and afternoon poster sessions on each of the four full meeting days. The eight plenary session were entitled: (1) Recombination Mechanisms, (2) Prokaryotic Recombination, (3) Repair and Recombination, (4) Site-specific Recombination and Transposition, (5) Eukaryotic Recombination I, (6) Genome Rearrangements, (7) Meiosis, and (8) Eukaryotic Recombination II. Each session included a mix of genetic, biochemical and structural talks; talks were limited to 20 minutes, followed by 10 minutes of very lively, general discussion. Much of the data presented in the plenary sessions was unpublished, thus providing attendees with the most up-to-date knowledge of this rapidly-moving field.

  12. Regioselective 1-N-Alkylation and Rearrangement of Adenosine Derivatives.

    Science.gov (United States)

    Oslovsky, Vladimir E; Drenichev, Mikhail S; Mikhailov, Sergey N

    2015-01-01

    Several methods for the preparation of some N(6)-substituted adenosines based on selective 1-N-alkylation with subsequent Dimroth rearrangement were developed. The proposed methods seem to be effective for the preparation of natural N(6)-isopentenyl- and N(6)-benzyladenosines, which are known to possess pronounced biological activities. Direct 1-N-alkylation of 2',3',5'-tri-O-acetyladenosine and 3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides in N,N-dimethylformamide (DMF) in the presence of BaCO3 and KI gave 1-N-substituted derivatives with quantitative yields, whereas 1-N-alkylation of adenosine was accompanied by significant O-alkylation. Moreover, the reaction of trimethylsilyl derivatives of N(6)-acetyl-2',3',5'-tri-O-acetyladenosine and N(6)-acetyl-3',5'-di-O-acetyl-2'-deoxyadenosine with alkyl halides leads to the formation of the stable 1-N-substituted adenosines. Dimroth rearrangement of 1-N-substituted adenosines in aqueous ammonia yields pure N(6)-substituted adenosines.

  13. Magnetic field re-arrangement after prominence eruption

    International Nuclear Information System (INIS)

    Kopp, R.A.; Poletto, G.

    1986-01-01

    It has long been known that magnetic reconnection plays a fundamental role in a variety of solar events. Although mainly invoked in flare problems, large-scale loops interconnecting active regions, evolving coronal hole boundaries, the solar magnetic cycle itself, provide different evidence of phenomena which involve magnetic reconnection. A further example might be given by the magnetic field rearrangement which occurs after the eruption of a prominence. Since most often a prominence reforms after its disappearance and may be observed at about the same position it occupied before erupting, the magnetic field has to undergo a temporary disruption to relax back, via reconnection, to a configuration similar to the previous one. The above sequence of events is best observable in the case of two-ribbon (2-R) flares but most probably is associated with all filament eruptions. Even if the explanation of the magnetic field rearrangement after 2-R flares in terms of reconnection is generally accepted, the lack of a three-dimensional model capable of describing the field reconfiguration, has prevented, up to now, a thorough analysis of its topology as traced by Hα/x-ray loops. The purpose of the present work is to present a numerical technique which enables one to predict and visualize the reconnected configuration, at any time t, and therefore allows one to make a significant comparison of observations and model predictions throughout the whole process. 5 refs., 3 figs

  14. Frequency of USP6 rearrangements in myositis ossificans, brown tumor, and cherubism: molecular cytogenetic evidence that a subset of ''myositis ossificans-like lesions'' are the early phases in the formation of soft-tissue aneurysmal bone cyst

    Energy Technology Data Exchange (ETDEWEB)

    Sukov, William R.; Erickson-Johnson, Michele; Unni, K.K.; Wang, Xiaoke; Oliveira, Andre M. [Mayo Clinic, Department of Laboratory Medicine and Pathology, Rochester, MN (United States); Franco, Marcello F. [Universidade Federal do Estado de Sao Paulo (UNEFESP), Departamento de Patologia, Sao Paulo (Brazil); Chou, Margaret M. [University of Pennsylvania School of Medicine, Philadelphia, PA (United States); Wenger, Doris E. [Mayo Clinic, Department of Radiology, Rochester, MN (United States)

    2008-04-15

    USP6 rearrangements with several partner genes have been identified recently in primary but not in secondary aneurysmal bone cysts (ABCs). Several lesions show histologic features that may overlap with ABC, including myositis ossificans (MO), brown tumor, and cherubism. The objective of this study was to assess whether these lesions harbored USP6 rearrangements. Twelve patients with classic radiologic and histologic features of MO, 6 with brown tumors, and 5 with cherubism diagnosed at our institution were studied for the presence of USP6 rearrangements using fluorescence in situ hybridization with probes flanking the USP6 locus on chromosome 17p13. In addition, conventional cytogenetic analysis was performed in 2 patients with cherubism. USP6 rearrangements were identified in 2 patients with radiologic and histologic features consistent with MO. None of the patients with brown tumor or cherubism demonstrated USP6 rearrangements. Cytogenetic analysis of the cherubism patients demonstrated normal karyotypes. These findings indicate that a subset of cases with apparent classic histologic and imaging features of MO are rather better classified as being soft-tissue ABC with clonal USP6 rearrangements. In contrast, no USP6 rearrangements were found in patients with cherubism or brown tumor, supporting the prevailing view that these lesions are distinct biologic entities. (orig.)

  15. Molecular screening of pituitary adenomas for gene mutations and rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Herman, V.; Drazin, N.Z.; Gonskey, R.; Melmed, S. (Cedars-Sinai Medical Center, Los Angeles, CA (United States))

    1993-07-01

    Although pituitary tumors arise as benign monoclonal neoplasms, genetic alterations have not readily been identified in these adenomas. The authors studied restriction fragment abnormalities involving the GH gene locus, and mutations in the p53 and H-, K-, and N-ras genes in 22 human GH cell adenomas. Twenty two nonsecretory adenomas were also examined for p53 and ras gene mutations. Seven prolactinoma DNA samples were tested for deletions in the multiple endocrine neoplasia-1 (MEN-1) locus, as well as for rearrangements in the hst gene, a member of the fibroblast growth factor family. In DNA from GH-cell adenomas, identical GH restriction patterns were detected in both pituitary and lymphocyte DNA in all patients and in one patient with a mixed GH-TSH cell adenoma. Using polymerase chain reaction (PCR)-single stranded conformation polymorphism analysis, no mutations were detected in exons 5, 6, 7 and 8 of the p53 gene in GH cell adenomas nor in 22 nonsecretory adenomas. Codons 12/13 and 61 of H-ras, K-ras, and N-ras genes were also intact on GH cell adenomas and in nonsecretory adenomas. Site-specific probes for chromosome 11q13 including, PYGM, D11S146, and INT2 were used in 7 sporadic PRL-secreting adenomas to detect deletions of the MEN-1 locus on chromosome 11. One patient was identified with a loss of 11p, and the remaining 6 patients did not demonstrate loss of heterozygosity in the pituitary 11q13 locus, compared to lymphocyte DNA. None of these patients demonstrated hst gene rearrangements which also maps to this locus. These results show that p53 and ras gene mutations are not common events in the pathogenesis of acromegaly and nonsecretory tumors. Although hst gene rearrangements and deletions of 11q13 are not associated with sporadic PRl-cell adenoma formation, a single patient was detected with a partial loss of chromosome 11, including the putative MEN-1 site. 31 refs., 5 figs., 2 tabs.

  16. Secondary Headaches

    Science.gov (United States)

    ... in the medical history or examination to suggest secondary headache. Headache can be caused by general medical conditions such as severe hypertension, or by conditions that affect the brain and ...

  17. Planar cell polarity signaling coordinates oriented cell division and cell rearrangement in clonally expanding growth plate cartilage.

    Science.gov (United States)

    Li, Yuwei; Li, Ang; Junge, Jason; Bronner, Marianne

    2017-10-10

    Both oriented cell divisions and cell rearrangements are critical for proper embryogenesis and organogenesis. However, little is known about how these two cellular events are integrated. Here we examine the linkage between these processes in chick limb cartilage. By combining retroviral-based multicolor clonal analysis with live imaging, the results show that single chondrocyte precursors can generate both single-column and multi-column clones through oriented division followed by cell rearrangements. Focusing on single column formation, we show that this stereotypical tissue architecture is established by a pivot-like process between sister cells. After mediolateral cell division, N-cadherin is enriched in the post-cleavage furrow; then one cell pivots around the other, resulting in stacking into a column. Perturbation analyses demonstrate that planar cell polarity signaling enables cells to pivot in the direction of limb elongation via this N-cadherin-mediated coupling. Our work provides new insights into the mechanisms generating appropriate tissue architecture of limb skeleton.

  18. SYNTHESIS OF ALLYL PHENYL ETHER AND CLAISEN REARRANGEMENT

    Directory of Open Access Journals (Sweden)

    Gagik Torosyan

    2011-12-01

    Full Text Available It has been established the possibility for phenol allylation on natural zeolites and them analogs. Here is demonstrated the synthesis of allyl phenol, which has wide industrial applications. The offered method in comparison with the traditional methods has more advantages – higher selectivity, smaller material and power resources consumption. It has been obtained the mixture of allylating phenols (30% in general with allyl phenyl ether (1 with 80% yields. At 600 K is obtained allylphenyl ether, at 700 K beginning the formation of allyl phenols, which is the result of direct C-allylation of the aromatic ring. It has been investigated the possibility of Claisen rearrangement in the same conditions. All of that are established by gas-liquid chromatography and liquid chromatography data.

  19. Highly rearranged mitochondrial genome in Nycteria parasites (Haemosporidia) from bats.

    Science.gov (United States)

    Karadjian, Gregory; Hassanin, Alexandre; Saintpierre, Benjamin; Gembu Tungaluna, Guy-Crispin; Ariey, Frederic; Ayala, Francisco J; Landau, Irene; Duval, Linda

    2016-08-30

    Haemosporidia parasites have mostly and abundantly been described using mitochondrial genes, and in particular cytochrome b (cytb). Failure to amplify the mitochondrial cytb gene of Nycteria parasites isolated from Nycteridae bats has been recently reported. Bats are hosts to a diverse and profuse array of Haemosporidia parasites that remain largely unstudied. There is a need to obtain more molecular data from chiropteran parasites. Such data would help to better understand the evolutionary history of Haemosporidia, which notably include the Plasmodium parasites, malaria's agents. We use next-generation sequencing to obtain the complete mitochondrial genome of Nycteria parasites from African Nycteris grandis (Nycteridae) and Rhinolophus alcyone (Rhinolophidae) and Asian Megaderma spasma (Megadermatidae). We report four complete mitochondrial genomes, including two rearranged mitochondrial genomes within Haemosporidia. Our results open outlooks into potentially undiscovered Haemosporidian diversity.

  20. New type of cells with multiple chromosome rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Aseeva, Elena A. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Snigiryova, Galina P. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Neverova, Anna L. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Bogomazova, Alexandra N.; Novitskaya, Natalia N.; Khazins, Eva D. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Domracheva, Elena V. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation)], E-mail: dom@blood.ru

    2010-04-15

    A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. The highest MAC frequency was observed in people exposed to {alpha}-radiation (Pu, Rn) and in cosmonauts. This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the fluorescence in situ hybridization (FISH) method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods are discussed.

  1. Multiple scattering in the nuclear rearrangement reactions at medium energy

    International Nuclear Information System (INIS)

    Tekou, A.

    1980-09-01

    It is shown that the multiple scattering mechanism is very important in the transfer of the large momenta involved in the nuclear rearrangement reactions at medium energy. In contrast to the usual belief, the reaction cross-section is not very sensitive to the high momenta components of the nuclear wave function. The multiple scattering mechanism is especially important in 4 He(p,d) 3 He reaction around 800 MeV. Here the collisions involving two nucleons of the target nucleus are dominant. The triple collisions contribution is also important. The four collision contribution is negligible in the forward direction and sizeable at large angles. Thus, using the K.M.T. approach in DWBA calculations, the second order term of the optical potential must be included. So, is it not well established that the second term of the K.M.T. optical potential is important for the proton elastic scattering on light nuclei. (author)

  2. New type of cells with multiple chromosome rearrangements

    International Nuclear Information System (INIS)

    Aseeva, E.A.; Domracheva, E.V.; Neverova, A.L; Bogomazova, A.N.; Snigiryova, G.P.; Novitskaya, N.N.; Khazins, E.D.

    2008-01-01

    Full text: A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. MAC were found in most of the examined groups and they were absent in the control population. A highest MAC frequency was observed in people exposed to alpha radiation (Pu, Ra). This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the FISH method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods is discussed

  3. Deep ancestry of programmed genome rearrangement in lampreys.

    Science.gov (United States)

    Timoshevskiy, Vladimir A; Lampman, Ralph T; Hess, Jon E; Porter, Laurie L; Smith, Jeramiah J

    2017-09-01

    In most multicellular organisms, the structure and content of the genome is rigorously maintained over the course of development. However some species have evolved genome biologies that permit, or require, developmentally regulated changes in the physical structure and content of the genome (programmed genome rearrangement: PGR). Relatively few vertebrates are known to undergo PGR, although all agnathans surveyed to date (several hagfish and one lamprey: Petromyzon marinus) show evidence of large scale PGR. To further resolve the ancestry of PGR within vertebrates, we developed probes that allow simultaneous tracking of nearly all sequences eliminated by PGR in P. marinus and a second lamprey species (Entosphenus tridentatus). These comparative analyses reveal conserved subcellular structures (lagging chromatin and micronuclei) associated with PGR and provide the first comparative embryological evidence in support of the idea that PGR represents an ancient and evolutionarily stable strategy for regulating inherent developmental/genetic conflicts between germline and soma. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Infrared divergence enforces a rearranged perturbation expansion II QED

    CERN Document Server

    Matsson, L

    1977-01-01

    For pt.I see ibid., vol.39A, p.604 (1977). Part I showed, for the case of scalar electrodynamics, that the ordinary perturbation expansion (OPE) must, except in certain cases, be rearranged in order to carry out uniquely the infrared (IR) exponentiation in a translation- and gauge-invariant way. The uniqueness of the exponent of order alpha follows from requiring exact order-by-order agreement with the OPE before summation and also from requiring that exponentiation of all factorizable parts must be done before integration. This technique is applied to ordinary spinor QED and a similar result is obtained without making the gamma -matrix algebra more complicated than in the OPE. This technique explicitly exhibits the structure of the remaining IR-regular part, which appears in terms of a correlation expansion with respect to photon momenta. (9 refs).

  5. Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

    Directory of Open Access Journals (Sweden)

    Sebastian Krüger

    2014-01-01

    Full Text Available This review summarizes the application of the divinylcyclopropane–cycloheptadiene rearrangement in synthetic organic chemistry. A brief overview of the new mechanistic insights concerning the title reaction is provided as well as a condensed account on the biological relevance of the topic. Heteroatom variants of this rearrangement are covered briefly.

  6. Hydrogen rearrangement to and from radical z fragments in electron capture dissociation of peptides

    DEFF Research Database (Denmark)

    Savitski, Mikhail M; Kjeldsen, Frank; Nielsen, Michael L

    2007-01-01

    Hydrogen rearrangement is an important process in radical chemistry. A high degree of H. rearrangement to and from z. ionic fragments (combined occurrence frequency 47% compared with that of z.) is confirmed in analysis of 15,000 tandem mass spectra of tryptic peptides obtained with electron...

  7. Initiation of MLL-rearranged AML is dependent on C/EBPα

    DEFF Research Database (Denmark)

    Ohlsson, Ewa; Hasemann, Marie Sigurd; Willer, Anton

    2014-01-01

    have compared gene expression profiles from human MLL-rearranged AML to normal progenitors and identified the myeloid tumor suppressor C/EBPα as a putative collaborator in MLL-rearranged AML. Interestingly, we find that deletion of Cebpa rendered murine hematopoietic progenitors completely resistant...

  8. Heterogeneity of BCR-ABL rearrangement in patients with chronic myeloid leukemia in Pakistan.

    Science.gov (United States)

    Tabassum, Najia; Saboor, Mohammad; Ghani, Rubina; Moinuddin, Moinuddin

    2014-07-01

    Breakpoint cluster region-Abelson (BCR-ABL) rearrangement or Philadelphia (Ph) chromosome in Chronic Myeloid Leukemia (CML) is derived from a reciprocal chromosomal translocation between ABL gene on chromosome 9 and BCR gene on chromosome 22. This chimeric protein has various sizes and therefore different clinical behaviour. The purpose of this study was to determine the heterogeneity of BCR-ABL rearrangement in patients with Ph(+)CML in Pakistan. The study was conducted at Civil Hospital and Baqai Institute of Hematology (BIH) Karachi. Blood samples from 25 patients with CML were collected. Multiplex reverse transcription polymerase chain reaction (RT-PCR) was performed to identify various BCR-ABL transcripts. All 25 samples showed BCR-ABL rearrangements. Out of these, 24 (96%) patients expressed p210 BCR-ABL rearrangements i.e. 60% (n=15) had b3a2 and 32% (n=8) had b2a2 rearrangements. Co-expression of b3a2 /b2a2 rearrangement and p190 (e1a3) rearrangement was also identified in two patients. It is apparent that majority of the patients had p210 BCR-ABL rearrangements. Frequency of co-expression and rare fusion transcripts was very low.

  9. Kraft lignin chain extension chemistry via propargylation, oxidative coupling, and Claisen rearrangement.

    Science.gov (United States)

    Sen, Sanghamitra; Sadeghifar, Hasan; Argyropoulos, Dimitris S

    2013-10-14

    Despite its aromatic and polymeric nature, the heterogeneous, stochastic, and reactive characteristics of softwood kraft lignin seriously limit its potential for thermoplastic applications. Our continuing efforts toward creating thermoplastic lignin polymers are now focused at exploring propargylation derivatization chemistry and its potential as a versatile novel route for the eventual utilization of technical lignins with a significant amount of molecular control. To do this, we initially report the systematic propargylation of softwood kraft lignin. The synthesized derivatives were extensively characterized with thermal methods (DSC, TGA), (1)H, (13)C, and quantitative (31)P NMR and IR spectroscopies. Further on, we explore the versatile nature of the lignin pendant propargyl groups by demonstrating two distinct chain extension chemistries; the solution-based, copper-mediated, oxidative coupling and the thermally induced, solid-state, Claissen rearrangement polymerization chemistries. Overall, we show that it is possible to modulate the reactivity of softwood kraft lignin via a combination of methylation and chain extension providing a rational means for the creation of higher molecular weight polymers with the potential for thermoplastic materials and carbon fibers with the desired control of structure-property relations.

  10. Heterogeneous fates and dynamic rearrangement of regenerative epidermis-derived cells during zebrafish fin regeneration.

    Science.gov (United States)

    Shibata, Eri; Ando, Kazunori; Murase, Emiko; Kawakami, Atsushi

    2018-04-13

    The regenerative epidermis (RE) is a specialized tissue that plays an essential role in tissue regeneration. However, the fate of the RE during and after regeneration is unknown. In this study, we performed Cre- loxP -mediated cell fate tracking and revealed the fates of a major population of the RE cells that express fibronectin 1b ( fn1b ) during zebrafish fin regeneration. Our study showed that these RE cells are mainly recruited from the inter-ray epidermis, and that they follow heterogeneous cell fates. Early recruited cells contribute to initial wound healing and soon disappear by apoptosis, while the later recruited cells contribute to the regenerated epidermis. Intriguingly, many of these cells are also expelled from the regenerated tissue by a dynamic caudal movement of the epidermis over time, and in turn the loss of epidermal cells is replenished by a global self-replication of basal and suprabasal cells in fin. De-differentiation of non-basal epidermal cells into the basal epidermal cells did not occur during regeneration. Overall, our study reveals the heterogeneous fates of RE cells and a dynamic rearrangement of the epidermis during and after regeneration. © 2018. Published by The Company of Biologists Ltd.

  11. ECM-dependent HIF induction directs trophoblast stem cell fate via LIMK1-mediated cytoskeletal rearrangement.

    Directory of Open Access Journals (Sweden)

    Hwa J Choi

    Full Text Available The Hypoxia-inducible Factor (HIF family of transcriptional regulators coordinates the expression of dozens of genes in response to oxygen deprivation. Mammalian development occurs in a hypoxic environment and HIF-null mice therefore die in utero due to multiple embryonic and placental defects. Mouse embryonic stem cells do not differentiate into placental cells; therefore, trophoblast stem cells (TSCs are used to study mouse placental development. Consistent with a requirement for HIF activity during placental development in utero, TSCs derived from HIF-null mice exhibit severe differentiation defects and fail to form trophoblast giant cells (TGCs in vitro. Interestingly, differentiating TSCs induce HIF activity independent of oxygen tension via unclear mechanisms. Here, we show that altering the extracellular matrix (ECM composition upon which TSCs are cultured changes their differentiation potential from TGCs to multinucleated syncytiotropholasts (SynTs and blocks oxygen-independent HIF induction. We further find that modulation of Mitogen Activated Protein Kinase Kinase-1/2 (MAP2K1/2, MEK-1/2 signaling by ECM composition is responsible for this effect. In the absence of ECM-dependent cues, hypoxia-signaling pathways activate this MAPK cascade to drive HIF induction and redirect TSC fate along the TGC lineage. In addition, we show that integrity of the microtubule and actin cytoskeleton is critical for TGC fate determination. HIF-2α ensures TSC cytoskeletal integrity and promotes invasive TGC formation by interacting with c-MYC to induce non-canonical expression of Lim domain kinase 1-an enzyme that regulates microtubule and actin stability, as well as cell invasion. Thus, we find that HIF can integrate positional and metabolic cues from within the TSC niche to regulate placental development by modulating the cellular cytoskeleton via non-canonical gene expression.

  12. Divergence of RNA polymerase ? subunits in angiosperm plastid genomes is mediated by genomic rearrangement

    OpenAIRE

    Blazier, J. Chris; Ruhlman, Tracey A.; Weng, Mao-Lun; Rehman, Sumaiyah K.; Sabir, Jamal S. M.; Jansen, Robert K.

    2016-01-01

    Genes for the plastid-encoded RNA polymerase (PEP) persist in the plastid genomes of all photosynthetic angiosperms. However, three unrelated lineages (Annonaceae, Passifloraceae and Geraniaceae) have been identified with unusually divergent open reading frames (ORFs) in the conserved region of rpoA, the gene encoding the PEP ? subunit. We used sequence-based approaches to evaluate whether these genes retain function. Both gene sequences and complete plastid genome sequences were assembled an...

  13. Correlating Structural Order with Structural Rearrangement in Dusty Plasma Liquids: Can Structural Rearrangement be Predicted by Static Structural Information?

    Science.gov (United States)

    Su, Yen-Shuo; Liu, Yu-Hsuan; I, Lin

    2012-11-01

    Whether the static microstructural order information is strongly correlated with the subsequent structural rearrangement (SR) and their predicting power for SR are investigated experimentally in the quenched dusty plasma liquid with microheterogeneities. The poor local structural order is found to be a good alarm to identify the soft spot and predict the short term SR. For the site with good structural order, the persistent time for sustaining the structural memory until SR has a large mean value but a broad distribution. The deviation of the local structural order from that averaged over nearest neighbors serves as a good second alarm to further sort out the short time SR sites. It has the similar sorting power to that using the temporal fluctuation of the local structural order over a small time interval.

  14. Dienone-phenol Rearrangement of C-9 Oxygenated Decalinic Dienone and Analogs through B-Ring Cleavage

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Dehydrogenation of 9-hydroxy decalinic enones and analogs with DDQ resulted in a formal dienone-phenol type rearrangement via B-ring cleavage, while the corresponding dienone acetates underwent base-catalyzed formal dienone-phenol type rearrangement analogously.

  15. Rearrangements under confinement lead to increased binding energy of Synaptotagmin-1 with anionic membranes in Mg2+ and Ca2.

    Science.gov (United States)

    Gruget, Clémence; Coleman, Jeff; Bello, Oscar; Krishnakumar, Shyam S; Perez, Eric; Rothman, James E; Pincet, Frederic; Donaldson, Stephen H

    2018-05-01

    Synaptotagmin-1 (Syt1) is the primary calcium sensor (Ca 2+ ) that mediates neurotransmitter release at the synapse. The tandem C2 domains (C2A and C2B) of Syt1 exhibit functionally critical, Ca 2+ -dependent interactions with the plasma membrane. With the surface forces apparatus, we directly measure the binding energy of membrane-anchored Syt1 to an anionic membrane and find that Syt1 binds with ~6 k B T in EGTA, ~10 k B T in Mg 2+ and ~18 k B T in Ca 2+ . Molecular rearrangements measured during confinement are more prevalent in Ca 2+ and Mg 2+ and suggest that Syt1 initially binds through C2B, then reorients the C2 domains into the preferred binding configuration. These results provide energetic and mechanistic details of the Syt1 Ca 2+ -activation process in synaptic transmission. © 2018 Federation of European Biochemical Societies.

  16. Protein kinase FgSch9 serves as a mediator of the target of rapamycin and high osmolarity glycerol pathways and regulates multiple stress responses and secondary metabolism in Fusarium graminearum.

    Science.gov (United States)

    Gu, Qin; Zhang, Chengqi; Yu, Fangwei; Yin, Yanni; Shim, Won-Bo; Ma, Zhonghua

    2015-08-01

    Saccharomyces cerevisiae protein kinase Sch9 is one of the downstream effectors of the target of rapamycin (TOR) complex 1 and plays multiple roles in stress resistance, longevity and nutrient sensing. However, the functions of Sch9 orthologs in filamentous fungi, particularly in pathogenic species, have not been characterized to date. Here, we investigated biological and genetic functions of FgSch9 in Fusarium graminearum. The FgSCH9 deletion mutant (ΔFgSch9) was defective in aerial hyphal growth, hyphal branching and conidial germination. The mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell wall-damaging agents, and to rapamycin, while showing increased thermal tolerance. We identified FgMaf1 as one of the FgSch9-interacting proteins that plays an important role in regulating mycotoxin biosynthesis and virulence of F. graminearum. Co-immunoprecipitation and affinity capture-mass spectrometry assays showed that FgSch9 also interacts with FgTor and FgHog1. More importantly, both ΔFgSch9 and FgHog1 null mutant (ΔFgHog1) exhibited increased sensitivity to osmotic and oxidative stresses. This defect was more severe in the FgSch9/FgHog1 double mutant. Taken together, we propose that FgSch9 serves as a mediator of the TOR and high osmolarity glycerol pathways, and regulates vegetative differentiation, multiple stress responses and secondary metabolism in F. graminearum. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  17. Synthesis of (±)-amathaspiramide F and discovery of an unusual stereocontrolling element for the [2,3]-Stevens rearrangement.

    Science.gov (United States)

    Soheili, Arash; Tambar, Uttam K

    2013-10-04

    A formal total synthesis of (±)-amathaspiramide F through a tandem palladium-catalyzed allylic amination/[2,3]-Stevens rearrangement is reported. The unexpected diastereoselectivity of the [2,3]-Stevens rearrangement was controlled by the substitution patterns of an aromatic ring. This discovery represents a new stereocontrolling element for [2,3]-sigmatropic rearrangements in complex molecular settings.

  18. Human heavy-chain variable region gene family nonrandomly rearranged in familial chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Shen, A.; Humphries, C.; Tucker, P.; Blattner, F.

    1987-01-01

    The authors have identified a family of human immunoglobulin heavy-chain variable-region (V/sub H/) genes, one member of which is rearranged in two affected members of a family in which the father and four of five siblings developed chronic lymphocytic leukemia. Cloning and sequencing of the rearranged V/sub H/ genes from leukemic lymphocytes of three affected siblings showed that two siblings had rearranged V/sub H/ genes (V/sub H/TS1 and V/sub H/WS1) that were 90% homologous. The corresponding germ-line gene, V/sub H/251, was found to part of a small (four gene) V/sub H/ gene family, which they term V/sub H/V. The DNA sequence homology to V/sub H/WS1 (95%) and V/sub H/TS1 (88%) and identical restriction sites on the 5' side of V/sub H/ confirm that rearrangement of V/sub H/251 followed by somatic mutation produced the identical V/sub H/ gene rearrangements in the two siblings. V/sub H/TS1 is not a functional V/sub H/ gene; a functional V/sub H/ rearrangement was found on the other chromosome of this patient. The other two siblings had different V/sub H/ gene rearrangements. All used different diversity genes. Mechanisms proposed for nonrandom selection of a single V/sub H/ gene include developmental regulation of this V/sub H/ gene rearrangement or selection of a subpopulation of B cells in which this V/sub H/ has been rearranged

  19. Atomic rearrangements in ordered fcc alloys during neutron irradiation

    International Nuclear Information System (INIS)

    Kirk, M.A.; Blewitt, T.H.

    1978-01-01

    Three sets of experiments performed at Argonne National Laboratory over the past few years are described. These experiments deal with atomic rearrangements in the ordered alloys Ni 3 Mn and Cu 3 Au during fast and thermal neutron bombardment. The unique magnetic properties of ordered Ni 3 Mn are utilized to investigate radiation damage production mechanisms at low temperature (5 K) where defect migration is not possible and only disordering is observed. In the case of thermal neutron bombardment, the average recoil energy is about 450 eV and significant disordering due to [110] replacement collision sequences is observed. For fast neutron bombardment where typical recoil energies are 20 keV, significant random disordering is observed but no evidence for sizable replacement sequences is found. The bombardment of ordered Cu 3 Au by fast and thermal neutrons at higher temperature (approx. 150 0 C) is studied by electrical resistance techniques. Both ordering and disordering are observed and related to the number of migrating vacancies escaping from the high energy collision cascade

  20. Ferrier rearrangement promoted by an electrochemically generated zirconium catalyst.

    Science.gov (United States)

    Stevanović, Dragana; Pejović, Anka; Damljanović, Ivan; Minić, Aleksandra; Bogdanović, Goran A; Vukićević, Mirjana; Radulović, Niko S; Vukićević, Rastko D

    2015-04-30

    In situ generated zirconium catalyst from a sacrificial zirconium anode was successfully applied to promote Ferrier rearrangement of 3,4,5-tri-O-acetyl-D-glucal and 6-deoxy-3,4-di-O-acetyl-L-glucal (3,4-di-O-acetyl-L-rhamnal) in the presence of three thiols and eleven thiophenols as nucleophiles. A simple constant current electrolysis (20 mA, 0.4 F mol(-1)) of an acetonitrile solution of lithium perchlorate (0.1 M) containing the corresponding glycal and S-nucleophiles, using a zirconium anode and a platinum cathode resulted in the successful synthesis of the corresponding 2,3-unsaturated peracetylated thioglycosides (with an average anomer ratio α/β=4.129 in the case of peracetylated D-glucal and 8.740 in the case of L-rhamnal). The same procedure proved to be appropriate in synthesizing dihydropyran derivatives ('C-glycosides') using allyltrimethylsilane as the nucleophile (only 'α-anomers' were obtained). All new compounds were fully characterized by spectral data, whereas single-crystal X-ray analysis was performed for two thioglycosides. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Heavy cluster in cold nuclear rearrangements in fusion and fission

    International Nuclear Information System (INIS)

    Armbruster, P.

    1997-01-01

    The experimental evidence for the appearance of cluster aspects in the dynamics of large rearrangements processes, as fusion and fission, is presented. Clusters in the sense as used in the following are strongly bound, doubly magic neutron rich nuclei as 48 Ca 28 , 78 Ni 50 , 132 Sn 82 , and 208 Pb 126 , the spherical nuclei Z=114 - 126 and N=184, and nuclei with closed shells N=28, 50, 82, and 126, and Z=28, 50, and 82. As with increasing nucleon numbers, the absolute shell corrections to the binding energies increase, the strongest effects are to be observed for the higher shells. The 132 cluster manifests itself in low energy fission (Faissner, H. and Wildermuth, K. Nucl. Phys., 58 (1964) 177). The 208 Pb cluster gave the new radioactivity (Rose, M.J. and Jones G.A., Nature, 307 (1984) 245) and the first superheavy elements (SHE) (Armbruster P., Ann. Rev. Nucl. Part. Sci., 35 (1985) 135-94; Munzenberg, G. Rep. Progr. Phys., 51 (1988) 57). The paper discuss experiments concerning the stability of clusters to intrinsic excitation energy in fusion and fission (Armbruster, P. Lect. Notes Phys., 158 (1982) 1). and the manifestation of clusters in the fusion entrance channel (Armbruster, P., J. Phys. Soc. Jpn., 58 (1989) 232). The importance of compactness of the clustering system seems to be equally decisive in fission and fusion. Finally, it s covered the importance of clusters for the production of SHEs)

  2. Stress-induced rearrangement of Fusarium retrotransposon sequences.

    Science.gov (United States)

    Anaya, N; Roncero, M I

    1996-11-27

    Rearrangement of fusarium oxysporum retrotransposon skippy was induced by growth in the presence of potassium chlorate. Three fungal strains, one sensitive to chlorate (Co60) and two resistant to chlorate and deficient for nitrate reductase (Co65 and Co94), were studied by Southern analysis of their genomic DNA. Polymorphism was detected in their hybridization banding pattern, relative to the wild type grown in the absence of chlorate, using various enzymes with or without restriction sites within the retrotransposon. Results were consistent with the assumption that three different events had occurred in strain Co60: genomic amplification of skippy yielding tandem arrays of the element, generation of new skippy sequences, and deletion of skippy sequences. Amplification of Co60 genomic DNA using the polymerase chain reaction and divergent primers derived from the retrotransposon generated a new band, corresponding to one long terminal repeat plus flanking sequences, that was not present in the wild-type strain. Molecular analysis of nitrate reductase-deficient mutants showed that generation and deletion of skippy sequences, but not genomic amplification in tandem repeats, had occurred in their genomes.

  3. Complex genomic rearrangement in CCS-LacZ transgenic mice.

    Science.gov (United States)

    Stroud, Dina Myers; Darrow, Bruce J; Kim, Sang Do; Zhang, Jie; Jongbloed, Monique R M; Rentschler, Stacey; Moskowitz, Ivan P G; Seidman, Jonathan; Fishman, Glenn I

    2007-02-01

    The cardiac conduction system (CCS)-lacZ insertional mouse mutant strain genetically labels the developing and mature CCS. This pattern of expression is presumed to reflect the site of transgene integration rather than regulatory elements within the transgene proper. We sought to characterize the genomic structure of the integration locus and identify nearby gene(s) that might potentially confer the observed CCS-specific transcription. We found rearrangement of chromosome 7 between regions D1 and E1 with altered transcription of multiple genes in the D1 region. Several lines of evidence suggested that regulatory elements from at least one gene, Slco3A1, influenced CCS-restricted reporter gene expression. In embryonic hearts, Slco3A1 was expressed in a spatial pattern similar to the CCS-lacZ transgene and was similarly neuregulin-responsive. At later stages, however, expression patterns of the transgene and Slco3A1 diverged, suggesting that the Slco3A1 locus may be necessary, but not sufficient to confer CCS-specific transgene expression in the CCS-lacZ line. (c) 2007 Wiley-Liss, Inc.

  4. Nicotine affects protein complex rearrangement in Caenorhabditis elegans cells.

    Science.gov (United States)

    Sobkowiak, Robert; Zielezinski, Andrzej; Karlowski, Wojciech M; Lesicki, Andrzej

    2017-10-01

    Nicotine may affect cell function by rearranging protein complexes. We aimed to determine nicotine-induced alterations of protein complexes in Caenorhabditis elegans (C. elegans) cells, thereby revealing links between nicotine exposure and protein complex modulation. We compared the proteomic alterations induced by low and high nicotine concentrations (0.01 mM and 1 mM) with the control (no nicotine) in vivo by using mass spectrometry (MS)-based techniques, specifically the cetyltrimethylammonium bromide (CTAB) discontinuous gel electrophoresis coupled with liquid chromatography (LC)-MS/MS and spectral counting. As a result, we identified dozens of C. elegans proteins that are present exclusively or in higher abundance in either nicotine-treated or untreated worms. Based on these results, we report a possible network that captures the key protein components of nicotine-induced protein complexes and speculate how the different protein modules relate to their distinct physiological roles. Using functional annotation of detected proteins, we hypothesize that the identified complexes can modulate the energy metabolism and level of oxidative stress. These proteins can also be involved in modulation of gene expression and may be crucial in Alzheimer's disease. The findings reported in our study reveal putative intracellular interactions of many proteins with the cytoskeleton and may contribute to the understanding of the mechanisms of nicotinic acetylcholine receptor (nAChR) signaling and trafficking in cells.

  5. Impact of local electrostatic field rearrangement on field ionization

    Science.gov (United States)

    Katnagallu, Shyam; Dagan, Michal; Parviainen, Stefan; Nematollahi, Ali; Grabowski, Blazej; Bagot, Paul A. J.; Rolland, Nicolas; Neugebauer, Jörg; Raabe, Dierk; Vurpillot, François; Moody, Michael P.; Gault, Baptiste

    2018-03-01

    Field ion microscopy allows for direct imaging of surfaces with true atomic resolution. The high charge density distribution on the surface generates an intense electric field that can induce ionization of gas atoms. We investigate the dynamic nature of the charge and the consequent electrostatic field redistribution following the departure of atoms initially constituting the surface in the form of an ion, a process known as field evaporation. We report on a new algorithm for image processing and tracking of individual atoms on the specimen surface enabling quantitative assessment of shifts in the imaged atomic positions. By combining experimental investigations with molecular dynamics simulations, which include the full electric charge, we confirm that change is directly associated with the rearrangement of the electrostatic field that modifies the imaging gas ionization zone. We derive important considerations for future developments of data reconstruction in 3D field ion microscopy, in particular for precise quantification of lattice strains and characterization of crystalline defects at the atomic scale.

  6. Ultrastructural analysis of radiation induced chromosome breaks and rearrangements

    International Nuclear Information System (INIS)

    Fernandez, J.L.; Goyanes, V.J.; Campos, A.; Cajigal, D.

    1990-01-01

    Chinese Hamster chromosomes R-banded in vitro were gamma-irradiated and chromatid breaks and rearrangements examined by electron microscopy employing whole-mounting technique. Breaks were preferentially located at the point of transition between G- and R-bands where the chromosome showed an average diameter 71.65 % of the wide condensed R-bands. This result was similar to the average diameter of narrow G-bands. Three chromosomes which were thin sectioned presented their broken terminal end organized as a coil constituted by two 23 nm wide chromatin fibers coiling together. Coils diameter was 43.70 % of the mean chromatid diameter. The border of damage-breakage was analyzed in whole-mounted chromosomes where breaks were photoinduced in BrdU-substituted DNA. Measurements of the angle of the sharp border of damage with respect to the chromatid axis showed a tendency to be more perpendicular as condensation progressed. These results clearly correlate with the several levels of chromatin fiber organization of the metaphase chromosome. (author)

  7. A Distinct Class of Genome Rearrangements Driven by Heterologous Recombination.

    Science.gov (United States)

    León-Ortiz, Ana María; Panier, Stephanie; Sarek, Grzegorz; Vannier, Jean-Baptiste; Patel, Harshil; Campbell, Peter J; Boulton, Simon J

    2018-01-18

    Erroneous DNA repair by heterologous recombination (Ht-REC) is a potential threat to genome stability, but evidence supporting its prevalence is lacking. Here we demonstrate that recombination is possible between heterologous sequences and that it is a source of chromosomal alterations in mitotic and meiotic cells. Mechanistically, we find that the RTEL1 and HIM-6/BLM helicases and the BRCA1 homolog BRC-1 counteract Ht-REC in Caenorhabditis elegans, whereas mismatch repair does not. Instead, MSH-2/6 drives Ht-REC events in rtel-1 and brc-1 mutants and excessive crossovers in rtel-1 mutant meioses. Loss of vertebrate Rtel1 also causes a variety of unusually large and complex structural variations, including chromothripsis, breakage-fusion-bridge events, and tandem duplications with distant intra-chromosomal insertions, whose structure are consistent with a role for RTEL1 in preventing Ht-REC during break-induced replication. Our data establish Ht-REC as an unappreciated source of genome instability that underpins a novel class of complex genome rearrangements that likely arise during replication stress. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Structural rearrangements of chromosomes in the domestic chicken: experimental production by X-irradiation of spermatozoa

    International Nuclear Information System (INIS)

    Wooster, W.E.; Fechheimer, N.S.; Jaap, R.G.

    1977-01-01

    In order to produce chicks heterozygous for structural aberrations of chromosomes, 67 hens were inseminated with semen that had been exposed to 1200 R of X-rays. A sample of 204 chicks was hatched and survived. Among these, 18 (8.9%) contained rearrangements comprising 19 translocations and one pericentric inversion. All 10 males and eight females heterozygous for rearrangements were fertile and transmitted these rearrangements to approximately half their hatched progeny. Each of the major chromosomes of the chicken karyotype, except number 6, was involved in one or more of the translocations. The pericentric inversion was of a segment of chromosome number 2. (author)

  9. Analysis of chromosome rearrangements on the basis of synaptonemal complexes in the offspring of mice exposed to γ-rays

    International Nuclear Information System (INIS)

    Kalikinskaya, E.I.; Bogdanov, Yu.F.; Kolomiets, O.L.; Shevchenko, V.A.

    1986-01-01

    Electron-microscopic analysis of synaptonemic complexes (SC), spread on the hypophase surface, was conducted to investigate chromosome rearrangements in sterile and semisterile F 1 malemause offsprings, exposed to 5 Gy γ-rays Paralelly Chromosome rearrangement account in diakinesis-metaphase 1 was conducted using light microscope, in the same animals. During SC analysis in pachytene chromosome rearrangements were found in 63% of spermatocytes. Under chromosome analysis in diakinesis-metaphase 1 in the same animals chromosome rearrangements were found only in 32% of cells. SC analysis allows one to reveal chromosome rearrangements, which can not be revealed in diakinesis-metaphase 1

  10. Unusual reactions of diazocarbonyl compounds with α,β-unsaturated δ-amino esters: Rh(II-catalyzed Wolff rearrangement and oxidative cleavage of N–H-insertion products

    Directory of Open Access Journals (Sweden)

    Valerij A. Nikolaev

    2016-08-01

    Full Text Available Rh(II-сatalyzed reactions of aroyldiazomethanes, diazoketoesters and diazodiketones with α,β-unsaturated δ-aminoesters, in contrast to reactions of diazomalonates and other diazoesters, give rise to the Wolff rearrangement and/or oxidative cleavage of the initially formed N–H-insertion products. These oxidation processes are mediated by Rh(II catalysts possessing perfluorinated ligands. The formation of pyrrolidine structures, characteristic for catalytic reactions of diazoesters, was not observed in these processes at all.

  11. Evaluation of NGS and RT-PCR methods for ALK rearrangement in European NSCLC patients

    DEFF Research Database (Denmark)

    Letovanec, Igor; Finn, Stephen; Zygoura, Panagiota

    2018-01-01

    INTRODUCTION: The reported prevalence of ALK rearrangement in NSCLC ranges from 2%-7%. The primary standard diagnostic method is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has also proven to be a reproducible and sensitive technique. Reverse transcriptase...

  12. Rearrangement of 5-trimethylsilylthebaine on treatment with L-selectride: an efficient synthesis of (+)-bractazonine.

    Science.gov (United States)

    Chen, Weibin; Wu, Huifang; Bernard, Denzil; Metcalf, Matthew D; Deschamps, Jeffrey R; Flippen-Anderson, Judith L; MacKerell, Alexander D; Coop, Andrew

    2003-03-07

    Treatment of 5-trimethylsilylthebaine with L-Selectride gave rise to a rearrangement to 10-trimethylsilylbractazonine through migration of the phenyl group, whereas treatment of thebaine with strong Lewis acids is known to lead to a similar rearrangement through migration of the alkyl bridge to give, after reduction, (+)-neodihydrothebaine. It is suggested that the rearrangement of the alkyl group of thebaine is favored due to the formation of a tertiary benzylic cation. However, for 5-trimethylsilylthebaine, the lithium ion of L-Selectride acts as the Lewis acid and the beta-silyl effect dominates in the stabilization of any positive charge. This rearrangement provides a clear example of the greater relative migratory aptitude of phenyl groups over alkyl groups, and provides an efficient synthesis of (+)-bractazonine from thebaine.

  13. Recurrent reciprocal genomic rearrangements of 17q12 are associated with renal disease, diabetes, and epilepsy

    DEFF Research Database (Denmark)

    Mefford, Heather C; Clauin, Severine; Sharp, Andrew J

    2007-01-01

    predisposed to recurrent rearrangement, by array-based comparative genomic hybridization. We found that 6% of fetal material showed evidence of microdeletion or microduplication, including three independent events that likely resulted from unequal crossing-over between segmental duplications. One...

  14. Low frequency of large genomic rearrangements of BRCA1 and BRCA2 in western Denmark

    DEFF Research Database (Denmark)

    Thomassen, Mads; Gerdes, Anne-Marie; Cruger, Dorthe

    2006-01-01

    Germline mutations in BRCA1 and BRCA2 predispose female carriers to breast and ovarian cancer. The majority of mutations identified are small deletions or insertions or are nonsense mutations. Large genomic rearrangements in BRCA1 are found with varying frequencies in different populations......, but BRCA2 rearrangements have not been investigated thoroughly. The objective in this study was to determine the frequency of large genomic rearrangements in BRCA1 and BRCA2 in a large group of Danish families with increased risk of breast and ovarian cancer. A total of 617 families previously tested...... negative for mutations involving few bases were screened with multiplex ligation-dependent probe amplification (MLPA). Two deletions in BRCA1 were identified in three families; no large rearrangements were detected in BRCA2. The large deletions constitute 3.8% of the BRCA1 mutations identified, which...

  15. Transformation of follicular lymphoma to plasmablastic lymphoma with c-myc gene rearrangement.

    Science.gov (United States)

    Ouansafi, Ihsane; He, Bing; Fraser, Cory; Nie, Kui; Mathew, Susan; Bhanji, Rumina; Hoda, Rana; Arabadjief, Melissa; Knowles, Daniel; Cerutti, Andrea; Orazi, Attilio; Tam, Wayne

    2010-12-01

    Follicular lymphoma (FL) is an indolent lymphoma that transforms to high-grade lymphoma, mostly diffuse large B-cell lymphoma, in about a third of patients. We present the first report of a case of FL that transformed to plasmablastic lymphoma (PBL). Clonal transformation of the FL to PBL was evidenced by identical IGH/BCL2 gene rearrangements and VDJ gene usage in rearranged IGH genes. IGH/ BCL2 translocation was retained in the PBL, which also acquired c-myc gene rearrangement. Genealogic analysis based on somatic hypermutation of the rearranged IGH genes of both FL and PBL suggests that transformation of the FL to PBL occurred most likely by divergent evolution from a common progenitor cell rather than direct evolution from the FL clone. Our study of this unusual case expands the histologic spectrum of FL transformation and increases our understanding of the pathogenetic mechanisms of transformation of indolent lymphomas to aggressive lymphomas.

  16. Synthesis of fused tricyclic systems by thermal Cope rearrangement of furan-substituted vinyl cyclopropanes.

    Science.gov (United States)

    Klaus, Verena; Wittmann, Stéphane; Senn, Hans M; Clark, J Stephen

    2018-05-15

    A novel method for the stereoselective construction of hexahydroazuleno[4,5-b]furans from simple precursors has been developed. The route involves the use of our recently developed Brønsted acid catalysed cyclisation reaction of acyclic ynenones to prepare fused 1-furanyl-2-alkenylcyclopropanes that undergo highly stereoselective thermal Cope rearrangement to produce fused tricyclic products. Substrates possessing an E-alkene undergo smooth Cope rearrangement at 40 °C, whereas the corresponding Z-isomers do not react at this temperature. Computational studies have been performed to explain the difference in behaviour of the E- and Z-isomers in the Cope rearrangement reaction. The hexahydroazuleno[4,5-b]furans produced by Cope rearrangement have potential as advanced intermediates for the synthesis of members of the guaianolide family of natural products.

  17. Total synthesis of broussonetine F: the orthoamide Overman rearrangement of an allylic diol.

    Science.gov (United States)

    Hama, Naoto; Aoki, Toshihiro; Miwa, Shohei; Yamazaki, Miki; Sato, Takaaki; Chida, Noritaka

    2011-02-18

    A first total synthesis of broussonetine F from diethyl L-tartrate was achieved. The cornerstone of our synthesis was an orthoamide Overman rearrangement, which provided an allylic amino alcohol with complete diastereoselectivity.

  18. Secondary osteoporosis.

    Science.gov (United States)

    Gennari, C; Martini, G; Nuti, R

    1998-06-01

    Generalized osteoporosis currently represents a heterogeneous group of conditions with many different causes and pathogenetic mechanisms, that often are variably associated. The term "secondary" is applied to all patients with osteoporosis in whom the identifiable causal factors are other than menopause and aging. In this heterogeneous group of conditions, produced by many different pathogenetic mechanisms, a negative bone balance may be variably associated with low, normal or increased bone remodeling states. A consistent group of secondary osteoporosis is related to endocrinological or iatrogenic causes. Exogenous hypercortisolism may be considered an important risk factor for secondary osteoporosis in the community, and probably glucocorticoid-induced osteoporosis is the most common type of secondary osteoporosis. Supraphysiological doses of corticosteroids cause two abnormalities in bone metabolism: a relative increase in bone resorption, and a relative reduction in bone formation. Bone loss, mostly of trabecular bone, with its resultant fractures is the most incapacitating consequence of osteoporosis. The estimated incidence of fractures in patients prescribed corticosteroid is 30% to 50%. Osteoporosis is considered one of the potentially serious side effects of heparin therapy. The occurrence of heparin-induced osteoporosis appeared to be strictly related to the length of treatment (over 4-5 months), and the dosage (15,000 U or more daily), but the pathogenesis is poorly understood. It has been suggested that heparin could cause an increase in bone resorption by increasing the number of differentiated osteoclasts, and by enhancing the activity of individual osteoclasts. Hyperthyroidism is frequently associated with loss of trabecular and cortical bone; the enhanced bone turnover that develops in thyrotoxicosis is characterized by an increase in the number of osteoclasts and resorption sites, and an increase in the ratio of resorptive to formative bone

  19. Microwave-radiation-induced molecular structural rearrangement of hen egg-white lysozyme

    Science.gov (United States)

    Singh, Anang K.; Burada, P. S.; Bhattacharya, Susmita; Bag, Sudipta; Bhattacharya, Amitabha; Dasgupta, Swagata; Roy, Anushree

    2018-05-01

    We have investigated the nonthermal effect of 10 GHz/22 dBm microwave radiation on hen egg-white lysozyme (HEWL) over different irradiation times, ranging from 2 min to 1 h. To ensure a control over the radiation parameters, a pair of microwave rectangular waveguides is used to irradiate the samples. Optical spectroscopic measurements, which include UV-visible absorption spectroscopy, Raman spectroscopy, and far UV CD spectroscopy, reveal the exposure of the buried tryptophan (Trp) residues of the native molecule between 15 and 30 min of radiation. The higher duration of the perturbation leads to a compact structure of the protein and Trp residues are buried again. Interestingly, we do not find any change in the secondary structure of the protein even for 1 h duration of radiation. The relaxation dynamics of the irradiated molecules also has been discussed. We have shown that the molecules relax to their native configuration in 7-8 h after the radiation field is turned off. The structural rearrangement over the above timescale has further been probed by a model calculation, based on a modified Langevin equation. Our coarse-grained simulation approach utilizes the mean of atomic positions and net atomic charge of each amino acid of native HEWL to mimic the initial conformation of the molecule. The modified positions of the residues are then calculated for the given force fields. The simulation results reveal the nonmonotonous change in overall size of the molecule, as observed experimentally. The radiation parameters used in our experiments are very similar to those of some of the electronic devices we often come across. Thus, we believe that the results of our studies on a simple protein structure may help us in understanding the effect of radiation on complex biological systems as well.

  20. Secondary osteoporosis.

    Science.gov (United States)

    Boyle, I T

    1993-10-01

    Osteoporosis with attendant increased fracture risk is a common complication of many other diseases. Indeed, almost all chronic diseases make some impact on life-style, usually by restricting physical activity and hence reducing the anabolic effect of exercise and gravitational strains on the skeleton. Restricted appetite and modified gastrointestinal tract function is another commonplace finding that has an impact on bone nutrition and synthesis, as on other systems. Sex hormone status is of particular importance for the maintenance of the normal skeleton, and the postmenopausal woman is at particular risk for most causes of secondary osteoporosis. In dealing with secondary osteoporosis in the hypo-oestrogenic woman, the question of giving hormone replacement therapy in addition to other disease-specific therapy should always be considered, as, for example, in a young amenorrhoeic woman with Crohn's disease. Similarly, in hypogonadal men the administration of testosterone is useful for bone conservation. The wider availability of bone densitometry ought to make us more aware of the presence of osteoporosis in the many disease states discussed above. This is particularly important as the life span of such patients is now increased by improved management of the underlying disease process in many instances. Even in steroid-induced osteoporosis--one of the commonest and most severe forms of osteoporosis--we now have some effective therapy in the form of the bisphosphonates and other anti-bone-resorbing drug classes. The possibility of prophylaxis against secondary osteoporosis has therefore become a possibility, although the very long-term effects of such drug regimens are still unknown. In some situations, such as thyrotoxicosis, Cushing's syndrome and immobilization, spontaneous resolution of at least part of the osteoporosis is possible after cure of the underlying problem. The shorter the existence of the basic problem, the more successful the restoration of the

  1. Cytological evidence of chromosomal rearrangement in the second meiotic division after exposure to X-rays

    Energy Technology Data Exchange (ETDEWEB)

    Szemere, G. (Orvostudomanyi Egyetem, Szeged (Hungary). Orvosbiologiai Intezet)

    1982-01-01

    Metaphase II cells with unequal dyad-arms and obvious X/autosomal rearrangements were found after an exposure to X-rays (2 Gy) of male mice at different stages of meiosis (pachytene, diplotene and diakinesis) with a frequency of 0.2, 1.26 and 0.6%, respectively, giving a direct cytological evidence of structural chromosomal rearrangements in metaphase II cells, partly with autosomal and partly with X/autosomal partners.

  2. Isotopic labelling studies for a gold-catalysed skeletal rearrangement of alkynyl aziridines

    Directory of Open Access Journals (Sweden)

    Neil Spencer

    2011-06-01

    Full Text Available Isotopic labelling studies were performed to probe a proposed 1,2-aryl shift in the gold-catalysed cycloisomerisation of alkynyl aziridines into 2,4-disubstituted pyrroles. Two isotopomers of the expected skeletal rearrangement product were identified using 13C-labelling and led to a revised mechanism featuring two distinct skeletal rearrangements. The mechanistic proposal has been rationalised against the reaction of a range of 13C- and deuterium-labelled substrates.

  3. Brueckner Rearrangement Effects in $^5_\\Lambda$He and $^6_{\\Lambda\\Lambda}$He

    OpenAIRE

    Kohno, M.; Fujiwara, Y.; Akaishi, Y.

    2003-01-01

    Rearrangement effects in light hypernuclei are investigated in the framework of the Brueckner theory. We can estimate without detailed numerical calculations that the energy of the $\\alpha$-core is reduced by more than 2.5 MeV when the $\\Lambda$ adheres to $^4$He to form $^5_\\Lambda$He. Similar assessment of rearrangement contributions is essential to deduce the strength of $\\Lambda\\Lambda$ interaction from experimentally observed $\\Delta B_{\\Lambda\\Lambda}$. The recently observed experimenta...

  4. Cytological evidence of chromosomal rearrangement in the second meiotic division after exposure to X-rays

    International Nuclear Information System (INIS)

    Szemere, G.

    1982-01-01

    Metaphase II cells with unequal dyad-arms and obvious X/autosomal rearrangements were found after an exposure to X-rays (2 Gy) of male mice at different stages of meiosis (pachytene, diplotene and diakinesis) with a frequency of 0.2, 1.26 and 0.6%, respectively, giving a direct cytological evidence of structural chromosomal rearrangements in metaphase II cells, partly with autosomal and partly with X/autosomal partners. (author)

  5. Deciphering the Code of the Cancer Genome: Mechanisms of Chromosome Rearrangement

    OpenAIRE

    Willis, Nicholas A.; Rass, Emilie; Scully, Ralph

    2015-01-01

    Chromosome rearrangement plays a causal role in tumorigenesis by contributing to the inactivation of tumor suppressor genes, the dysregulated expression or amplification of oncogenes and the generation of novel gene fusions. Chromosome breaks are important intermediates in this process. How, when and where these breaks arise and the specific mechanisms engaged in their repair strongly influence the resulting patterns of chromosome rearrangement. Here, we review recent progress in understandin...

  6. MAML2 rearrangement in primary pulmonary mucoepidermoid carcinoma and the correlation with FLT1 expression.

    Directory of Open Access Journals (Sweden)

    Fen Zhu

    Full Text Available INTRODUCTION: Primary pulmonary mucoepidermoid carcinoma (PMEC is an uncommon neoplasm with remarkable resemblance to mucoepidermoid carcinoma of the salivary glands. The latter has been shown to harbor t(11,19 resulting in MECT1-MAML2 fusion, which may be of diagnostic and prognostic values. However, the importance of such feature in PMEC has not been well studied. METHODS: We detected MAML2 rearrangement using fluorescence in situ hybridization (FISH in tissue samples from 42 cases of PMEC and 40 of adenosquamous carcinoma (ASC, and the expression of potential downstream targets of MECT1-MAML2, including HES1, FLT1 and NR4A2 with immunohistochemistry (IHC. The findings were then examined regarding the clinicopathological parameters and patient outcomes. RESULTS: FISH analysis revealed MAML2 rearrangement in 50% of the PMEC cases, and such property was prominent in considerable younger patients (33 versus 60 years; p = 0.001 and restricted to cases of low and intermediate grades. IHC analysis showed that FLT1 and HES1 were expressed at lower level in MAML2 rearranged group than MAML2 non-rearranged group (p<0.001 and p = 0.023, respectively. Survival analysis showed significant correlation between MAML2 rearrangement and overall survival (p = 0.023 or disease-free survival (p = 0.027 as well as correlation between FLT1 and overall survival (p = 0.009. CONCLUSIONS: MAML2 rearrangement appears frequent in PMEC and specific with this tumor. Both the presence of MAML2 rearrangement and absence of FLT1 tend to confer a favorable clinical outcome. These findings suggest that molecular detection of MAML2 rearrangement combined with FLT1 may be of important clinical value for PMEC.

  7. DNA rearrangements from γ-irradiated normal human fibroblasts preferentially occur in transcribed regions of the genome

    International Nuclear Information System (INIS)

    Forrester, H.B.; Radford, I.R.

    2003-01-01

    Full text: DNA rearrangement events leading to chromosomal aberrations are central to ionizing radiation-induced cell death. Although DNA double-strand breaks are probably the lesion that initiates formation of chromosomal aberrations, little is understood about the molecular mechanisms that generate and modulate DNA rearrangement. Examination of the sequences that flank sites of DNA rearrangement may provide information regarding the processes and enzymes involved in rearrangement events. Accordingly, we developed a method using inverse PCR that allows the detection and sequencing of putative radiation-induced DNA rearrangements in defined regions of the human genome. The method can detect single copies of a rearrangement event that has occurred in a particular region of the genome and, therefore, DNA rearrangement detection does not require survival and continued multiplication of the affected cell. Ionizing radiation-induced DNA rearrangements were detected in several different regions of the genome of human fibroblast cells that were exposed to 30 Gy of γ-irradiation and then incubated for 24 hours at 37 deg C. There was a 3- to 5-fold increase in the number of products amplified from irradiated as compared with control cells in the target regions 5' to the C-MYC, CDKN1A, RB1, and FGFR2 genes. Sequences were examined from 121 DNA rearrangements. Approximately half of the PCR products were derived from possible inter-chromosomal rearrangements and the remainder were from intra-chromosomal events. A high proportion of the sequences that rearranged with target regions were located in genes, suggesting that rearrangements may occur preferentially in transcribed regions. Eighty-four percent of the sequences examined by reverse transcriptase PCR were from transcribed sequences in IMR-90 cells. The distribution of DNA rearrangements within the target regions is non-random and homology occurs between the sequences involved in rearrangements in some cases but is not

  8. A route to hydroxylfluorenes: TsOH-mediated condensation reactions of 1,3-diketones with propargylic alcohols

    KAUST Repository

    Yao, Liangfeng

    2012-01-01

    An efficient method of preparing hydroxylfluorenes by TsOH-mediated tandem alkylation/rearrangements of propargylic alcohols with 1,3-diketones is described. These reactions are accomplished in moderate to good yields under mild conditions to offer a straightforward and convenient one step synthetic route to hydroxylfluorene derivatives through a plausible mechanism involving a sequence of dehydration, addition, rearrangement and aromatization. This journal is © The Royal Society of Chemistry 2012.

  9. Palindromic nucleotide analysis in human T cell receptor rearrangements.

    Directory of Open Access Journals (Sweden)

    Santosh K Srivastava

    Full Text Available Diversity of T cell receptor (TCR genes is primarily generated by nucleotide insertions upon rearrangement from their germ line-encoded V, D and J segments. Nucleotide insertions at V-D and D-J junctions are random, but some small subsets of these insertions are exceptional, in that one to three base pairs inversely repeat the sequence of the germline DNA. These short complementary palindromic sequences are called P nucleotides. We apply the ImmunoSeq deep-sequencing assay to the third complementarity determining region (CDR3 of the β chain of T cell receptors, and use the resulting data to study P nucleotides in the repertoire of naïve and memory CD8(+ and CD4(+ T cells. We estimate P nucleotide distributions in a cross section of healthy adults and different T cell subtypes. We show that P nucleotide frequency in all T cell subtypes ranges from 1% to 2%, and that the distribution is highly biased with respect to the coding end of the gene segment. Classification of observed palindromic sequences into P nucleotides using a maximum conditional probability model shows that single base P nucleotides are very rare in VDJ recombination; P nucleotides are primarily two bases long. To explore the role of P nucleotides in thymic selection, we compare P nucleotides in productive and non-productive sequences of CD8(+ naïve T cells. The naïve CD8(+ T cell clones with P nucleotides are more highly expanded.

  10. Delineating Rearrangements in Single Yeast Artificial Chromosomes by Quantitative DNA Fiber Mapping

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich G.; Greulich-Bode, Karin M.; Wu, Jenny; Duell, Thomas

    2009-09-18

    Cloning of large chunks of human genomic DNA in recombinant systems such as yeast or bacterial artificial chromosomes has greatly facilitated the construction of physical maps, the positional cloning of disease genes or the preparation of patient-specific DNA probes for diagnostic purposes. For this process to work efficiently, the DNA cloning process and subsequent clone propagation need to maintain stable inserts that are neither deleted nor otherwise rearranged. Some regions of the human genome; however, appear to have a higher propensity than others to rearrange in any host system. Thus, techniques to detect and accurately characterize such rearrangements need to be developed. We developed a technique termed 'Quantitative DNA Fiber Mapping (QDFM)' that allows accurate tagging of sequence elements of interest with near kilobase accuracy and optimized it for delineation of rearrangements in recombinant DNA clones. This paper demonstrates the power of this microscopic approach by investigating YAC rearrangements. In our examples, high-resolution physical maps for regions within the immunoglobulin lambda variant gene cluster were constructed for three different YAC clones carrying deletions of 95 kb and more. Rearrangements within YACs could be demonstrated unambiguously by pairwise mapping of cosmids along YAC DNA molecules. When coverage by YAC clones was not available, distances between cosmid clones were estimated by hybridization of cosmids onto DNA fibers prepared from human genomic DNA. In addition, the QDFM technology provides essential information about clone stability facilitating closure of the maps of the human genome as well as those of model organisms.

  11. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  12. Lack of nonfunctional B-cell receptor rearrangements in a patient with normal B cell numbers despite partial RAG1 deficiency and atypical SCID/Omenn syndrome

    DEFF Research Database (Denmark)

    Ohm-Laursen, Line; Nielsen, Christian; Fisker, Niels

    2008-01-01

    rearrangements to those of age-matched controls, cord blood, and adults revealed an almost total lack of nonproductive rearrangements (2.7% versus 14.7%, 27.6%, and 19.8% in the controls, respectively) indicating failure to correct out-of-frame rearrangements by a second rearrangement on the homologous...

  13. Antibody repertoire development in fetal and neonatal piglets. XXII. Lambda rearrangement precedes kappa rearrangement during B-cell lymphogenesis in swine

    Science.gov (United States)

    PCR was used to detect VDJ and VJ rearrangement, expression of RAG-1, TdT and VpreB and the presence of signal joint circles (SJC) in an effort to identify sites of B cell lymphogenesis in tissue lysates and sorted leukocytes of fetal and newborn piglets. VDJ, VlambdaJlambda but not VkappaJkappa re...

  14. Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer.

    Science.gov (United States)

    Pailler, Emma; Adam, Julien; Barthélémy, Amélie; Oulhen, Marianne; Auger, Nathalie; Valent, Alexander; Borget, Isabelle; Planchard, David; Taylor, Melissa; André, Fabrice; Soria, Jean Charles; Vielh, Philippe; Besse, Benjamin; Farace, Françoise

    2013-06-20

    The diagnostic test for ALK rearrangement in non-small-cell lung cancer (NSCLC) for crizotinib treatment is currently done on tumor biopsies or fine-needle aspirations. We evaluated whether ALK rearrangement diagnosis could be performed by using circulating tumor cells (CTCs). The presence of an ALK rearrangement was examined in CTCs of 18 ALK-positive and 14 ALK-negative patients by using a filtration enrichment technique and filter-adapted fluorescent in situ hybridization (FA-FISH), a FISH method optimized for filters. ALK-rearrangement patterns were determined in CTCs and compared with those present in tumor biopsies. ALK-rearranged CTCs and tumor specimens were characterized for epithelial (cytokeratins, E-cadherin) and mesenchymal (vimentin, N-cadherin) marker expression. ALK-rearranged CTCs were monitored in five patients treated with crizotinib. All ALK-positive patients had four or more ALK-rearranged CTCs per 1 mL of blood (median, nine CTCs per 1 mL; range, four to 34 CTCs per 1 mL). No or only one ALK-rearranged CTC (median, one per 1 mL; range, zero to one per 1 mL) was detected in ALK-negative patients. ALK-rearranged CTCs harbored a unique (3'5') split pattern, and heterogeneous patterns (3'5', only 3') of splits were present in tumors. ALK-rearranged CTCs expressed a mesenchymal phenotype contrasting with heterogeneous epithelial and mesenchymal marker expressions in tumors. Variations in ALK-rearranged CTC levels were detected in patients being treated with crizotinib. ALK rearrangement can be detected in CTCs of patients with ALK-positive NSCLC by using a filtration technique and FA-FISH, enabling both diagnostic testing and monitoring of crizotinib treatment. Our results suggest that CTCs harboring a unique ALK rearrangement and mesenchymal phenotype may arise from clonal selection of tumor cells that have acquired the potential to drive metastatic progression of ALK-positive NSCLC.

  15. Detection of Gene Rearrangements in Circulating Tumor Cells: Examples of ALK-, ROS1-, RET-Rearrangements in Non-Small-Cell Lung Cancer and ERG-Rearrangements in Prostate Cancer.

    Science.gov (United States)

    Catelain, Cyril; Pailler, Emma; Oulhen, Marianne; Faugeroux, Vincent; Pommier, Anne-Laure; Farace, Françoise

    2017-01-01

    Circulating tumor cells (CTCs) hold promise as biomarkers to aid in patient treatment stratification and disease monitoring. Because the number of cells is a critical parameter for exploiting CTCs for predictive biomarker's detection, we developed a FISH (fluorescent in situ hybridization) method for CTCs enriched on filters (filter-adapted FISH [FA-FISH]) that was optimized for high cell recovery. To increase the feasibility and reliability of the analyses, we combined fluorescent staining and FA-FISH and developed a semi-automated microscopy method for optimal FISH signal identification in filtration-enriched CTCs . Here we present these methods and their use for the detection and characterization of ALK-, ROS1-, RET-rearrangement in CTCs from non-small-cell lung cancer and ERG-rearrangements in CTCs from prostate cancer patients.

  16. Rearrangements of MYC gene facilitate risk stratification in diffuse large B-cell lymphoma patients treated with rituximab-CHOP

    DEFF Research Database (Denmark)

    Tzankov, Alexandar; Xu-Monette, Zijun Y; Gerhard, Marc

    2014-01-01

    In order to address the debatable prognostic role of MYC rearrangements in diffuse large B-cell lymphoma patients treated with rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone, we evaluated MYC rearrangements by fluorescence in situ hybridization in 563 cases using...... with the dual-fusion probes, 15 detectable only with the break-apart probes and 20 detectable with both dual-fusion probes and break-apart probes. MYC rearrangements correlated with germinal center B-cell origin (P=0.02), MYC protein expression (P=0.032), and larger tumor mass size (P=0.0003). Patients with MYC...... was prognostically additive. Radiotherapy seemed to diminish the prognostic effects of MYC rearrangements in diffuse large B-cell lymphoma patients since only 2/10 irradiated patients with MYC rearrangements died of/with disease, compared with 16/28 non-irradiated patients with MYC rearrangements. We conclude...

  17. Dysregulation of the DNA Damage Response and KMT2A Rearrangement in Fetal Liver Hematopoietic Cells.

    Directory of Open Access Journals (Sweden)

    Mai Nanya

    Full Text Available Etoposide, a topoisomerase 2 (TOP2 inhibitor, is associated with the development of KMT2A (MLL-rearranged infant leukemia. An epidemiological study suggested that in utero exposure to TOP2 inhibitors may be involved in generation of KMT2A (MLL rearrangement. The present study examined the mechanism underlying the development of KMT2A (MLL-rearranged infant leukemia in response to in utero exposure to etoposide in a mouse model. Fetal liver hematopoietic stem cells were more susceptible to etoposide than maternal bone marrow mononuclear cells. Etoposide-induced Kmt2a breakage was detected in fetal liver hematopoietic stem cells using a newly developed chromatin immunoprecipitation (ChIP assay. Assessment of etoposide-induced chromosomal translocation by next-generation RNA sequencing (RNA-seq identified several chimeric fusion messenger RNAs that were generated by etoposide treatment. However, Kmt2a (Mll-rearranged fusion mRNA was detected in Atm-knockout mice, which are defective in the DNA damage response, but not in wild-type mice. The present findings suggest that in utero exposure to TOP2 inhibitors induces Kmt2a rearrangement when the DNA damage response is defective.

  18. Processes of fungal proteome evolution and gain of function: gene duplication and domain rearrangement

    International Nuclear Information System (INIS)

    Cohen-Gihon, Inbar; Nussinov, Ruth; Sharan, Roded

    2011-01-01

    During evolution, organisms have gained functional complexity mainly by modifying and improving existing functioning systems rather than creating new ones ab initio. Here we explore the interplay between two processes which during evolution have had major roles in the acquisition of new functions: gene duplication and protein domain rearrangements. We consider four possible evolutionary scenarios: gene families that have undergone none of these event types; only gene duplication; only domain rearrangement, or both events. We characterize each of the four evolutionary scenarios by functional attributes. Our analysis of ten fungal genomes indicates that at least for the fungi clade, species significantly appear to gain complexity by gene duplication accompanied by the expansion of existing domain architectures via rearrangements. We show that paralogs gaining new domain architectures via duplication tend to adopt new functions compared to paralogs that preserve their domain architectures. We conclude that evolution of protein families through gene duplication and domain rearrangement is correlated with their functional properties. We suggest that in general, new functions are acquired via the integration of gene duplication and domain rearrangements rather than each process acting independently

  19. Hexose rearrangements upon fragmentation of N-glycopeptides and reductively aminated N-glycans.

    Science.gov (United States)

    Wuhrer, Manfred; Koeleman, Carolien A M; Deelder, André M

    2009-06-01

    Tandem mass spectrometry of glycans and glycoconjugates in protonated form is known to result in rearrangement reactions leading to internal residue loss. Here we studied the occurrence of hexose rearrangements in tandem mass spectrometry of N-glycopeptides and reductively aminated N-glycans by MALDI-TOF/TOF-MS/MS and ESI-ion trap-MS/MS. Fragmentation of proton adducts of oligomannosidic N-glycans of ribonuclease B that were labeled with 2-aminobenzamide and 2-aminobenzoic acid resulted in transfer of one to five hexose residues to the fluorescently tagged innermost N-acetylglucosamine. Glycopeptides from various biological sources with oligomannosidic glycans were likewise shown to undergo hexose rearrangement reactions, resulting in chitobiose cleavage products that have acquired one or two hexose moieties. Tryptic immunoglobulin G Fc-glycopeptides with biantennary N-glycans likewise showed hexose rearrangements resulting in hexose transfer to the peptide moiety retaining the innermost N-acetylglucosamine. Thus, as a general phenomenon, tandem mass spectrometry of reductively aminated glycans as well as glycopeptides may result in hexose rearrangements. This characteristic of glycopeptide MS/MS has to be considered when developing tools for de novo glycopeptide structural analysis.

  20. Characterization of apparently balanced chromosomal rearrangements from the developmental genome anatomy project.

    Science.gov (United States)

    Higgins, Anne W; Alkuraya, Fowzan S; Bosco, Amy F; Brown, Kerry K; Bruns, Gail A P; Donovan, Diana J; Eisenman, Robert; Fan, Yanli; Farra, Chantal G; Ferguson, Heather L; Gusella, James F; Harris, David J; Herrick, Steven R; Kelly, Chantal; Kim, Hyung-Goo; Kishikawa, Shotaro; Korf, Bruce R; Kulkarni, Shashikant; Lally, Eric; Leach, Natalia T; Lemyre, Emma; Lewis, Janine; Ligon, Azra H; Lu, Weining; Maas, Richard L; MacDonald, Marcy E; Moore, Steven D P; Peters, Roxanna E; Quade, Bradley J; Quintero-Rivera, Fabiola; Saadi, Irfan; Shen, Yiping; Shendure, Jay; Williamson, Robin E; Morton, Cynthia C

    2008-03-01

    Apparently balanced chromosomal rearrangements in individuals with major congenital anomalies represent natural experiments of gene disruption and dysregulation. These individuals can be studied to identify novel genes critical in human development and to annotate further the function of known genes. Identification and characterization of these genes is the goal of the Developmental Genome Anatomy Project (DGAP). DGAP is a multidisciplinary effort that leverages the recent advances resulting from the Human Genome Project to increase our understanding of birth defects and the process of human development. Clinically significant phenotypes of individuals enrolled in DGAP are varied and, in most cases, involve multiple organ systems. Study of these individuals' chromosomal rearrangements has resulted in the mapping of 77 breakpoints from 40 chromosomal rearrangements by FISH with BACs and fosmids, array CGH, Southern-blot hybridization, MLPA, RT-PCR, and suppression PCR. Eighteen chromosomal breakpoints have been cloned and sequenced. Unsuspected genomic imbalances and cryptic rearrangements were detected, but less frequently than has been reported previously. Chromosomal rearrangements, both balanced and unbalanced, in individuals with multiple congenital anomalies continue to be a valuable resource for gene discovery and annotation.

  1. Quantitative and Qualitative Changes in V-J α Rearrangements During Mouse Thymocytes Differentiation

    Science.gov (United States)

    Pasqual, Nicolas; Gallagher, Maighréad; Aude-Garcia, Catherine; Loiodice, Mélanie; Thuderoz, Florence; Demongeot, Jacques; Ceredig, Rod; Marche, Patrice Noël; Jouvin-Marche, Evelyne

    2002-01-01

    Knowledge of the complete nucleotide sequence of the mouse TCRAD locus allows an accurate determination V-J rearrangement status. Using multiplex genomic PCR assays and real time PCR analysis, we report a comprehensive and systematic analysis of the V-J recombination of TCR α chain in normal mouse thymocytes during development. These respective qualitative and quantitative approaches give rise to four major points describing the control of gene rearrangements. (a) The V-J recombination pattern is not random during ontogeny and generates a limited TCR α repertoire; (b) V-J rearrangement control is intrinsic to the thymus; (c) each V gene rearranges to a set of contiguous J segments with a gaussian-like frequency; (d) there are more rearrangements involving V genes at the 3′ side than 5′ end of V region. Taken together, this reflects a preferential association of V and J gene segments according to their respective positions in the locus, indicating that accessibility of both V and J regions is coordinately regulated, but in different ways. These results provide a new insight into TCR α repertoire size and suggest a scenario for V usage during differentiation. PMID:12417627

  2. Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  3. Teachers as mediators

    DEFF Research Database (Denmark)

    Dorf, Hans; Kelly, Peter; Hohmann, Ulrike

    2012-01-01

    Within the context of lower secondary English teaching in South West England, this study identifies in broad terms the competing goals between which English teachers mediate and the explicit and hidden tensions that result. To understand the interactions of competing goals, teachers’ goal...... and cultural influences on practice. Yet the teachers observed moved smoothly between goal-oriented behaviours in a continuous and comfortable style, easily and without reflecting any tensions between them. Thus, this article elaborates an account of situated English teaching....

  4. The He+H¯→He p¯+e+ rearrangement

    Science.gov (United States)

    Todd, Allan C.; Armour, Edward A. G.

    2006-06-01

    In this paper, we present a summary of our work in progress on calculating cross sections for the He+H¯→He p¯+e+ rearrangement process in He H¯ scattering. This has involved a study of the system He p¯ within the Born-Oppenheimer (BO) approximation using the Rayleigh-Ritz variational method. This work has been reported in [A.C. Todd, E.A.G. Armour, J. Phys. B 38 (2005) 3367] and is summarised here. Similar calculations are in progress for the He+H¯ entrance channel. We intend to use the entrance channel and rearrangement channel wave functions to obtain the cross sections for the rearrangement using the distorted wave Born approximation T-matrix method described elsewhere in these proceedings [E.A.G. Armour, S. Jonsell, Y. Liu, A.C. Todd, these Proceedings, doi:10.1016/j.nimb.2006.01.049].

  5. The He+H-bar → Hep-bar +e+ rearrangement

    International Nuclear Information System (INIS)

    Todd, Allan C.; Armour, Edward A.G.

    2006-01-01

    In this paper, we present a summary of our work in progress on calculating cross sections for the He+H-bar ->Hep-bar +e + rearrangement process in HeH-bar scattering. This has involved a study of the system Hep-bar within the Born-Oppenheimer (BO) approximation using the Rayleigh-Ritz variational method. This work has been reported in [A.C. Todd, E.A.G. Armour, J. Phys. B 38 (2005) 3367] and is summarised here. Similar calculations are in progress for the He+H-bar entrance channel. We intend to use the entrance channel and rearrangement channel wave functions to obtain the cross sections for the rearrangement using the distorted wave Born approximation T-matrix method described elsewhere in these proceedings [E.A.G. Armour, S. Jonsell, Y. Liu, A.C. Todd, these Proceedings, doi:10.1016/j.nimb.2006.01.049

  6. Marfan syndrome with a complex chromosomal rearrangement including deletion of the FBN1 gene

    Directory of Open Access Journals (Sweden)

    Colovati Mileny ES

    2012-01-01

    Full Text Available Abstract Background The majority of Marfan syndrome (MFS cases is caused by mutations in the fibrillin-1 gene (FBN1, mapped to chromosome 15q21.1. Only few reports on deletions including the whole FBN1 gene, detected by molecular cytogenetic techniques, were found in literature. Results We report here on a female patient with clinical symptoms of the MFS spectrum plus craniostenosis, hypothyroidism and intellectual deficiency who presents a 1.9 Mb deletion, including the FBN1 gene and a complex rearrangement with eight breakpoints involving chromosomes 6, 12 and 15. Discussion This is the first report of MFS with a complex chromosome rearrangement involving a deletion of FBN1 and contiguous genes. In addition to the typical clinical findings of the Marfan syndrome due to FBN1 gene haploinsufficiency, the patient presents features which may be due to the other gene deletions and possibly to the complex chromosome rearrangement.

  7. Mutations and Rearrangements in the Genome of Sulfolobus solfataricus P2

    DEFF Research Database (Denmark)

    Redder, P.; Garrett, R. A.

    2006-01-01

    The genome of Sulfolobus solfataricus P2 carries a larger number of transposable elements than any other sequenced genome from an archaeon or bacterium and, as a consequence, may be particularly susceptible to rearrangement and change. In order to gain more insight into the natures and frequencies...... of different types of mutation and possible rearrangements that can occur in the genome, the pyrEF locus was examined for mutations that were isolated after selection with 5-fluoroorotic acid. About two-thirds of the 130 mutations resulted from insertions of mobile elements, including insertion sequence (IS...... deletions, insertions, and a duplication, were observed, and about one-fifth of the mutations occurred elsewhere in the genome, possibly in an orotate transporter gene. One mutant exhibited a 5-kb genomic rearrangement at the pyrEF locus involving a two-step IS element-dependent reaction, and its boundaries...

  8. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

    International Nuclear Information System (INIS)

    Pasquinelli, C.; Garreau, F.; Bougueleret, L.; Cariani, E.; Thiers, V.; Croissant, O.; Hadchouel, M.; Tiollais, P.; Brechot, C.; Grzeschik, K.H.

    1988-01-01

    Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration

  9. Clinical and CT characteristics of surgically resected lung adenocarcinomas harboring ALK rearrangements or EGFR mutations

    International Nuclear Information System (INIS)

    Wang, Hua; Schabath, Matthew B.; Liu, Ying; Han, Ying; Li, Qi; Gillies, Robert J.; Ye, Zhaoxiang

    2016-01-01

    Purpose: To determine if clinical and CT characteristics of surgically resected lung adenocarcinomas can distinguish those harboring ALK rearrangements from EGFR mutations. Materials and methods: Patients who had surgical resection and histologically confirmed lung adenocarcinoma were enrolled, including 41 patients with ALK rearrangements and 66 patients with EGFR mutations. Eighteen categorical and six quantitative CT characteristics were used to evaluate the tumors. Differences in clinical and CT characteristics between the two groups were investigated. Results: Age (P = 0.003), histological subtypes (P < 0.001), pathological stage (P = 0.007), and five CT characteristics, including size (P < 0.001), GGO (P = 0.001), bubble-like lucency (P = 0.048), lymphadenopathy (P = 0.001), and tumor shadow disappearance rate (P = 0.005) were significantly different between patients harboring ALK rearrangements compared to patients with EGFR mutations. When we compared histologic components, a solid pattern was more common (P = 0.009) in tumors with ALK rearrangements, and lepidic and acinar patterns were more common (P < 0.001 and P = 0.040, respectively) in those with EGFR mutations. Backward elimination analyses revealed that age (OR = 0.93; 95% CI 0.89–0.98), GGO (OR = 0.14; 95% CI 0.03–0.67), and lymphadenopathy (OR = 4.15; 95% CI 1.49–11.60) were significantly associated with ALK rearrangement status. Conclusion: Our analyses revealed that clinical and CT characteristics of lung adenocarcinomas harboring ALK rearrangements were significantly different, compared with those with EGFR mutations. These differences may be related to the molecular pathology of these diseases.

  10. Clinical and CT characteristics of surgically resected lung adenocarcinomas harboring ALK rearrangements or EGFR mutations

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hua [Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Schabath, Matthew B. [Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Liu, Ying [Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Han, Ying [Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Li, Qi [Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China); Gillies, Robert J. [Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Department of Radiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (United States); Ye, Zhaoxiang, E-mail: yezhaoxiang@163.com [Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin (China)

    2016-11-15

    Purpose: To determine if clinical and CT characteristics of surgically resected lung adenocarcinomas can distinguish those harboring ALK rearrangements from EGFR mutations. Materials and methods: Patients who had surgical resection and histologically confirmed lung adenocarcinoma were enrolled, including 41 patients with ALK rearrangements and 66 patients with EGFR mutations. Eighteen categorical and six quantitative CT characteristics were used to evaluate the tumors. Differences in clinical and CT characteristics between the two groups were investigated. Results: Age (P = 0.003), histological subtypes (P < 0.001), pathological stage (P = 0.007), and five CT characteristics, including size (P < 0.001), GGO (P = 0.001), bubble-like lucency (P = 0.048), lymphadenopathy (P = 0.001), and tumor shadow disappearance rate (P = 0.005) were significantly different between patients harboring ALK rearrangements compared to patients with EGFR mutations. When we compared histologic components, a solid pattern was more common (P = 0.009) in tumors with ALK rearrangements, and lepidic and acinar patterns were more common (P < 0.001 and P = 0.040, respectively) in those with EGFR mutations. Backward elimination analyses revealed that age (OR = 0.93; 95% CI 0.89–0.98), GGO (OR = 0.14; 95% CI 0.03–0.67), and lymphadenopathy (OR = 4.15; 95% CI 1.49–11.60) were significantly associated with ALK rearrangement status. Conclusion: Our analyses revealed that clinical and CT characteristics of lung adenocarcinomas harboring ALK rearrangements were significantly different, compared with those with EGFR mutations. These differences may be related to the molecular pathology of these diseases.

  11. Chromosomal Rainbows detect Oncogenic Rearrangements of Signaling Molecules in Thyroid Tumors

    Energy Technology Data Exchange (ETDEWEB)

    O' Brien, Benjamin; Jossart, Gregg H.; Ito, Yuko; Greulich-Bode, Karin M.; Weier, Jingly F.; Munne, Santiago; Clark, Orlo H.; Weier, Heinz-Ulrich G.

    2010-08-19

    Altered signal transduction can be considered a hallmark of many solid tumors. In thyroid cancers the receptor tyrosine kinase (rtk) genes NTRK1 (Online Mendelian Inheritance in Man = OMIM *191315, also known as 'TRKA'), RET ('Rearranged during Transfection protooncogene', OMIM *164761) and MET (OMIM *164860) have been reported as activated, rearranged or overexpressed. In many cases, a combination of cytogenetic and molecular techniques allows elucidation of cellular changes that initiate tumor development and progression. While the mechanisms leading to overexpression of the rtk MET gene remain largely unknown, a variety of chromosomal rearrangements of the RET or NTKR1 gene could be demonstrated in thyroid cancer. Abnormal expressions in these tumors seem to follow a similar pattern: the rearrangement translocates the 3'-end of the rtk gene including the entire catalytic domain to an expressed gene leading to a chimeric RNA and protein with kinase activity. Our research was prompted by an increasing number of reports describing translocations involving ret and previously unknown translocation partners. We developed a high resolution technique based on fluorescence in situ hybridization (FISH) to allow rapid screening for cytogenetic rearrangements which complements conventional chromosome banding analysis. Our technique applies simultaneous hybridization of numerous probes labeled with different reporter molecules which are distributed along the target chromosome allowing the detection of cytogenetic changes at near megabase-pair (Mbp) resolution. Here, we report our results using a probe set specific for human chromosome 10, which is altered in a significant portion of human thyroid cancers (TC's). While rendering accurate information about the cytogenetic location of rearranged elements, our multi-locus, multi-color analysis was developed primarily to overcome limitations of whole chromosome painting (WCP) and chromosome banding

  12. Free energy landscape and cooperatively rearranging region in a hard sphere glass

    Science.gov (United States)

    Yoshidome, Takashi; Yoshimori, Akira; Odagaki, Takashi

    2007-08-01

    Exploiting the density functional theory, we calculate the free energy landscape (FEL) of the hard sphere glass in three dimensions. From the FEL, we estimate the number of the particles in the cooperatively rearranging region (CRR). We find that the density dependence of the number of the particles in the CRR is expressed as a power law function of the density. Analyzing the relaxation process in the CRR, we also find that the string motion is the elementary process for the structural relaxation, which leads to the natural definition of the simultaneously rearranging region as the particles displaced in the string motion.

  13. Tandem catalytic allylic amination and [2,3]-Stevens rearrangement of tertiary amines.

    Science.gov (United States)

    Soheili, Arash; Tambar, Uttam K

    2011-08-24

    We have developed a catalytic allylic amination involving tertiary aminoesters and allylcarbonates, which is the first example of the use of tertiary amines as intermolecular nucleophiles in metal-catalyzed allylic substitution chemistry. This process is employed in a tandem ammonium ylide generation/[2,3]-rearrangement reaction, which formally represents a palladium-catalyzed Stevens rearrangement. Low catalyst loadings and mild reaction conditions are compatible with an unprecedented substrate scope for the ammonium ylide functionality, and products are generated in high yields and diastereoselectivities. Mechanistic studies suggested the reversible formation of an ammonium intermediate.

  14. Unexpected rearrangements in the synthesis of an unsymmetrical tridentate dianionic N-heterocyclic carbene

    KAUST Repository

    Despagnet-Ayoub, Emmanuelle; Miqueu, Karinne; Sotiropoulos, Jean-Marc; Henling, Lawrence M.; Day, Michael W.; Labinger, Jay A.; Bercaw, John E.

    2013-01-01

    Starting from the same ethylenediamine species, three valuable carbene precursors were synthesized under differing conditions: a tridentate dianionic N-heterocyclic carbene bearing an aniline, a phenol and a central dihydroimidazolium salt, its benzimidazolium isomer by intramolecular rearrangement and a dicationic benzimidazolium-benzoxazolium salt by changing the Brønsted acid from HCl to HBF4. A DFT study was performed to understand the rearrangement pathway. The structure of a bis[(NCO)carbene] zirconium complex was determined. © 2013 The Royal Society of Chemistry.

  15. The rearrangement process in a two-stage broadcast switching network

    DEFF Research Database (Denmark)

    Jacobsen, Søren B.

    1988-01-01

    The rearrangement process in the two-stage broadcast switching network presented by F.K. Hwang and G.W. Richards (ibid., vol.COM-33, no.10, p.1025-1035, Oct. 1985) is considered. By defining a certain function it is possible to calculate an upper bound on the number of connections to be moved...... during a rearrangement. When each inlet channel appears twice, the maximum number of connections to be moved is found. For a special class of inlet assignment patterns in the case of which each inlet channel appears three times, the maximum number of connections to be moved is also found. In the general...

  16. Triazole–Au(I complex as chemoselective catalyst in promoting propargyl ester rearrangements

    Directory of Open Access Journals (Sweden)

    Dawei Wang

    2011-07-01

    Full Text Available Triazole–Au (TA–Au catalysts were employed in several transformations involving propargyl ester rearrangement. Good chemoselectivity was observed, which allowed the effective activation of the alkyne without affecting the reactivity of the allene ester intermediates. These results led to the investigation of the preparation of allene ester intermediates with TA–Au catalysts under anhydrous conditions. As expected, the desired 3,3-rearrangement products were obtained in excellent yields (generally >90% yields with 1% loading. Besides the typical ester migrating groups, carbonates and carbamates were also found to be suitable for this transformation, which provided a highly efficient, practical method for the preparation of substituted allenes.

  17. Deciphering the Code of the Cancer Genome: Mechanisms of Chromosome Rearrangement

    Science.gov (United States)

    Willis, Nicholas A.; Rass, Emilie; Scully, Ralph

    2015-01-01

    Chromosome rearrangement plays a causal role in tumorigenesis by contributing to the inactivation of tumor suppressor genes, the dysregulated expression or amplification of oncogenes and the generation of novel gene fusions. Chromosome breaks are important intermediates in this process. How, when and where these breaks arise and the specific mechanisms engaged in their repair strongly influence the resulting patterns of chromosome rearrangement. Here, we review recent progress in understanding how certain distinctive features of the cancer genome, including clustered mutagenesis, tandem segmental duplications, complex breakpoints, chromothripsis, chromoplexy and chromoanasynthesis may arise. PMID:26726318

  18. Mechanistic and kinetic insights into the thermally induced rearrangement of alpha-pinene.

    Science.gov (United States)

    Stolle, Achim; Ondruschka, Bernd; Findeisen, Matthias

    2008-11-07

    The thermal rearrangement of alpha-pinene (1) is interesting from mechanistic as well as kinetic point of view. Carrier gas pyrolyses with 1 and its acyclic isomers ocimene (2) and alloocimene (3) were performed to investigate the thermal network of these hydrocarbons. Kinetic analysis of the major reaction steps allows for a deeper insight in the reaction mechanism. Thus it was possible to explain the racemization of 1, the formation of racemic limonene (4), and the absence of the primary pyrolysis product 2 in the reaction mixture resulting from thermal rearrangement of 1. Results supported the conclusion that the reactions starting with 1 involve biradical transition states.

  19. Polyarene mediators for mediated redox flow battery

    Science.gov (United States)

    Delnick, Frank M.; Ingersoll, David; Liang, Chengdu

    2018-01-02

    The fundamental charge storage mechanisms in a number of currently studied high energy redox couples are based on intercalation, conversion, or displacement reactions. With exception to certain metal-air chemistries, most often the active redox materials are stored physically in the electrochemical cell stack thereby lowering the practical gravimetric and volumetric energy density as a tradeoff to achieve reasonable power density. In a general embodiment, a mediated redox flow battery includes a series of secondary organic molecules that form highly reduced anionic radicals as reaction mediator pairs for the reduction and oxidation of primary high capacity redox species ex situ from the electrochemical cell stack. Arenes are reduced to stable anionic radicals that in turn reduce a primary anode to the charged state. The primary anode is then discharged using a second lower potential (more positive) arene. Compatible separators and solvents are also disclosed herein.

  20. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer.

    Science.gov (United States)

    Pailler, E; Auger, N; Lindsay, C R; Vielh, P; Islas-Morris-Hernandez, A; Borget, I; Ngo-Camus, M; Planchard, D; Soria, J-C; Besse, B; Farace, F

    2015-07-01

    Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24-55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7-11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged patients show considerable heterogeneity of ROS1-gene

  1. Thermal evolution of the spin ordering at the concomitant spin–orbital rearrangement temperature in RVO{sub 3} (R=Lu, Yb and Tm)

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, Tapati, E-mail: tapati.sarkar@angstrom.uu.se [Department of Engineering Sciences, Uppsala University, Box 534, SE-75121 Uppsala (Sweden); Ivanov, Sergey A. [Department of Engineering Sciences, Uppsala University, Box 534, SE-75121 Uppsala (Sweden); Center of Materials Science, Karpov Institute of Physical Chemistry, 105064 Moscow K-64 (Russian Federation); Bazuev, G.V. [Institute of Solid State Chemistry, Ural Branch of the Russian Academy of Science, 620999 Ekaterinburg GSP-145 (Russian Federation); Nordblad, Per; Mathieu, Roland [Department of Engineering Sciences, Uppsala University, Box 534, SE-75121 Uppsala (Sweden)

    2016-07-01

    Synthesis, crystal structure and magnetization measurements of phase pure polycrystalline RVO{sub 3} (R=Lu, Yb and Tm) are reported. The compounds were stabilized in the orthorhombic structure by thermal treatment of the respective precursors (RVO{sub 4}) in a reducing atmosphere. Special pressure treatment was carried out during the synthesis to ensure phase pure samples without secondary phases. Magnetization measurements reveal the presence of two spin ordering temperatures in the samples. Interestingly, at the lower spin ordering temperature, T{sub SO2}, the uncompensated excess moment of the antiferromagnetic spin structure has different field dependences above and below T{sub SO2}, causing a jump in the thermal evolution of the magnetization that changes sign with increasing field strength. This jump is associated with the reported magnetic and orbital rearrangement in the samples, and the different spin configurations in the C- and G-type antiferromagnetic structures. - Highlights: • Magnetization measurements of polycrystalline RVO{sub 3} (R=Lu, Yb, Tm) are reported. • The samples have two spin ordering temperatures, T{sub SO1} and T{sub SO2} (T{sub SO1}>T{sub SO2}). • A magnetic field dependent jump of the excess magnetization, ΔM is observed at T{sub SO2.} • The jump in ΔM is associated with magnetic and orbital rearrangement in the samples. • ΔM is probably affected by possible phase coexistence in the samples.

  2. Pull-push mechanism for the 1,2-hydrogen rearrangement of carbenes. Substituent and deuterium isotope effects for thermal decomposition of 1-phenyl-2-diazopropanes

    International Nuclear Information System (INIS)

    Su, D.T.T.; Thornton, E.R.

    1978-01-01

    Intramolecular and intermolecular deuterium isotope effects have been measured for the thermal carbene H rearrangements of three substituted 1-phenyl-2-diazopropanes-1-d in hexane at 25 0 C. The isotope effects, k/sub H//k/sub D/, vary from ca. 1.2 to 1.5, increasing with electron-withdrawing substituents, for the formation of both cis- and trans-β-methylstyrenes. Product ratios were determined for these compounds as well as the corresponding undeuterated ones, permitting calculation of intermolecular primary and secondary isotope effects. In addition, the competition among the cis and trans products and the product of H migration from the terminal methyl group permitted determination of Hammett rho values of ca. -1 for the competition between benzylic and terminal migration. The results strongly indicate a ''pull-push'' mechanism, which can be pictured roughly as electrophilic attack on the C--H bond by the phantom p orbital of the carbene along with backside nucleophilic attack by the carbene unshared electron pair to push the H away and form the π bond. The data are believed to be consistent only with a nonzero barrier for the carbene hydrogen rearrangement

  3. Mediation Analysis with Multiple Mediators

    OpenAIRE

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  4. Mitochondrial genome of the Komodo dragon: efficient sequencing method with reptile-oriented primers and novel gene rearrangements.

    Science.gov (United States)

    Kumazawa, Yoshinori; Endo, Hideki

    2004-04-30

    The mitochondrial genome of the Komodo dragon (Varanus komodoensis) was nearly completely sequenced, except for two highly repetitive noncoding regions. An efficient sequencing method for squamate mitochondrial genomes was established by combining the long polymerase chain reaction (PCR) technology and a set of reptile-oriented primers designed for nested PCR amplifications. It was found that the mitochondrial genome had novel gene arrangements in which genes from NADH dehydrogenase subunit 6 to proline tRNA were extensively shuffled with duplicate control regions. These control regions had 99% sequence similarity over 700 bp. Although snake mitochondrial genomes are also known to possess duplicate control regions with nearly identical sequences, the location of the second control region suggested independent occurrence of the duplication on lineages leading to snakes and the Komodo dragon. Another feature of the mitochondrial genome of the Komodo dragon was the considerable number of tandem repeats, including sequences with a strong secondary structure, as a possible site for the slipped-strand mispairing in replication. These observations are consistent with hypotheses that tandem duplications via the slipped-strand mispairing may induce mitochondrial gene rearrangements and may serve to maintain similar copies of the control region.

  5. Rearrangement of crystallographic domains driven by magnetic field in ferromagnetic Ni2MnGa and antiferromagnetic CoO

    International Nuclear Information System (INIS)

    Terai, Tomoyuki; Yasui, Motoyoshi; Yamamoto, Masataka; Kakeshita, Tomoyuki

    2009-01-01

    We have investigated the rearrangement of crystallographic domains (martensite variants) in Ni 2 MnGa ferromagnetic shape memory alloy and CoO antiferromagnetic oxide by applying magnetic field up to 8.0 MA/m. From the result of optical microscope observation of Ni 2 MnGa single crystal, when a magnetic field is applied along [001] p (p represents a parent phase), the rearrangement of crystallographic domains occurs and the single domain state is obtained below T Ms = 202 K. The same rearrangement occurs but partially when a magnetic field is applied along [110] p . On the other hand, when a magnetic field is applied along [111] p , the rearrangement does not occur. In case of the CoO single crystal, when a magnetic field is applied along [001] p below T Ms = 293 K, the rearrangement occurs at 170 K ≤ T ≤ 293 K, but does not occur at T p and [111] p , the rearrangement does not occur below T Ms . In order to explain the rearrangement in the alloy and the oxide, we have evaluated the magnetic shear stress, τ mag , which is derived from the difference in magnetic energy among crystallographic domains and have compared it with the shear stress required for the twinning plane movement, τ req . As a result, we have found that the rearrangement occurs when the value of τ mag is larger than or equal to the value of τ req for the present alloy and oxide.

  6. Region-Specific Involvement of Actin Rearrangement-Related Synaptic Structure Alterations in Conditioned Taste Aversion Memory

    Science.gov (United States)

    Bi, Ai-Ling; Wang, Yue; Li, Bo-Qin; Wang, Qian-Qian; Ma, Ling; Yu, Hui; Zhao, Ling; Chen, Zhe-Yu

    2010-01-01

    Actin rearrangement plays an essential role in learning and memory; however, the spatial and temporal regulation of actin dynamics in different phases of associative memory has not been fully understood. Here, using the conditioned taste aversion (CTA) paradigm, we investigated the region-specific involvement of actin rearrangement-related…

  7. Carbocyclization cascades of allyl ketenimines via aza-Claisen rearrangements of N-phosphoryl-N-allyl-ynamides.

    Science.gov (United States)

    DeKorver, Kyle A; Wang, Xiao-Na; Walton, Mary C; Hsung, Richard P

    2012-04-06

    A series of carbocyclization cascades of allyl ketenimines initiated through a thermal aza-Claisen rearrangement of N-phosphoryl-N-allyl ynamides is described. Interceptions of the cationic intermediate via Meerwein-Wagner rearrangements and polyene-type cyclizations en route to fused bi- and tricyclic frameworks are featured.

  8. An Efficient Synthesis of de novo Imidates via Aza-Claisen Rearrangements of N-Allyl Ynamides

    Science.gov (United States)

    DeKorver, Kyle A.; North, Troy D.; Hsung, Richard P.

    2010-01-01

    A novel thermal 3-aza-Claisen rearrangement of N-allyl ynamides for the synthesis of α-allyl imidates is described. Also, a sequential aza-Claisen, Pd-catalyzed Overman rearrangement is described for the synthesis of azapine-2-ones. PMID:21278848

  9. Large BRCA1 and BRCA2 genomic rearrangements in Danish high risk breast-ovarian cancer families

    DEFF Research Database (Denmark)

    Hansen, Thomas v O; Jønson, Lars; Albrechtsen, Anders

    2009-01-01

    BRCA1 and BRCA2 germ-line mutations predispose to breast and ovarian cancer. Large genomic rearrangements of BRCA1 account for 0-36% of all disease causing mutations in various populations, while large genomic rearrangements in BRCA2 are more rare. We examined 642 East Danish breast and/or ovaria...

  10. Reaction of hypochlorite with amino acids and peptides : EPR evidence for rapid rearrangement and fragmentation of nitrogen-centred radicals

    International Nuclear Information System (INIS)

    Hawkins, C.L.; Davies, M.J.

    1998-01-01

    Various amino acid side chains have been shown to be particularly susceptible to attack and modification by hypochlorite (HOCl). It is known that tyrosine is readily chlorinated by HOCl to give 3-chlorotyrosine and this product has been employed as a marker of HOCl-mediated damage to proteins. Cysteine and methionine react rapidly with HOCl to give oxy acids and cystine (from cysteine) and sulphoxides (from methionine). Lysine and amino acids which lack the above functional groups also react with HOCl via the free amino group which results in the generation of unstable chloramine intermediates; subsequent decomposition of these species gives NH 3 , CO 2 and aldehydes. While the products of reaction of HOCl with amino acids and peptides are reasonably well characterised, the mechanism(s) by which these products arise is less well understood. Electron paramagnetic resonance (EPR) spectroscopy with spin trapping and UV/visible spectroscopy has been employed to examine the reaction of HOCl with amino acids and some small peptides. Reaction of HOCl with N-acetyl amino acids or small peptides gives radicals predominantly at α-carbon sites via reaction at N-terminal free amino groups or amide (peptide) bonds. It is proposed that these carbon-centred radicals are produced as a result of the rearrangement of initial nitrogen-centred radicals formed on cleavage of the N-CI bond of the chloramine/chloramide species by a 1,2-shift reaction

  11. Synthesis of N-protected Galactosamine Building Blocks from D-Tagatose via the Heyns Rearrangement

    DEFF Research Database (Denmark)

    Wrodnigg, Tanja M.; Lundt, Inge; Stütz, Arnold E.

    2006-01-01

    N-Acetyl-D-galactosamine (11), a very important naturally occurring building block of oligosaccharides, is easily accessible via the Heyns rearrangement of D-tagatose (3) with benzylamine. The short and efficient synthesis of various differently N-protected D-galactosamine derivatives is reported....

  12. Conversion and non-conversion approach to preimplantation diagnosis for chromosomal rearrangements in 475 cycles.

    Science.gov (United States)

    Kuliev, Anver; Janzen, Jeanine Cieslak; Zlatopolsky, Zev; Kirillova, Irina; Ilkevitch, Yury; Verlinsky, Yury

    2010-07-01

    Due to the limitations of preimplantation genetic diagnosis (PGD) for chromosomal rearrangements by interphase fluorescent in-situ hybridization (FISH) analysis, a method for obtaining chromosomes from single blastomeres was introduced by their fusion with enucleated or intact mouse zygotes, followed by FISH analysis of the resulting heterokaryons. Although this allowed a significant improvement in the accuracy of testing of both maternally and paternally derived translocations, it is still labour intensive and requires the availability of fertilized mouse oocytes, also creating ethical issues related to the formation of interspecies heterokaryons. This method was modified with a chemical conversion procedure that has now been clinically applied for the first time on 877 embryos from PGD cycles for chromosomal rearrangements and has become the method of choice for performing PGD for structural rearrangements. This is presented within the context of overall experience of 475 PGD cycles for translocations with pre-selection and transfer of balanced or normal embryos in 342 (72%) of these cycles, which resulted in 131 clinical pregnancies (38%), with healthy deliveries of 113 unaffected children. The spontaneous abortion rate in these cycles was as low as 17%, which confirms an almost five-fold reduction of spontaneous abortion rate following PGD for chromosomal rearrangements. 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  13. A single oncogenic enhancer rearrangement causes concomitant EVI1 and GATA2 deregulation in leukemia

    NARCIS (Netherlands)

    Gröschel, Stefan; Sanders, Mathijs A; Hoogenboezem, Remco; de Wit, Elzo; Bouwman, Britta A M; Erpelinck, Claudia; van der Velden, Vincent H J; Havermans, Marije; Avellino, Roberto; van Lom, Kirsten; Rombouts, Elwin J; van Duin, Mark; Döhner, Konstanze; Beverloo, H Berna; Bradner, James E; Döhner, Hartmut; Löwenberg, Bob; Valk, Peter J M; Bindels, Eric M J; de Laat, Wouter; Delwel, Ruud

    2014-01-01

    Chromosomal rearrangements without gene fusions have been implicated in leukemogenesis by causing deregulation of proto-oncogenes via relocation of cryptic regulatory DNA elements. AML with inv(3)/t(3;3) is associated with aberrant expression of the stem-cell regulator EVI1. Applying functional

  14. Thermally rearranged (TR) bismaleimide-based network polymers for gas separation membranes.

    Science.gov (United States)

    Do, Yu Seong; Lee, Won Hee; Seong, Jong Geun; Kim, Ju Sung; Wang, Ho Hyun; Doherty, Cara M; Hill, Anita J; Lee, Young Moo

    2016-11-15

    Highly permeable, thermally rearranged polymer membranes based on bismaleimide derivatives that exhibit excellent CO 2 permeability up to 5440 Barrer with a high BET surface area (1130 m 2 g -1 ) are reported for the first time. In addition, the membranes can be easily used to form semi-interpenetrating networks with other polymers endowing them with superior gas transport properties.

  15. Electron beam-induced Fries rearrangement of arylsulfonamides and arylsulfonates in the crystalline state

    International Nuclear Information System (INIS)

    Kato, Jun; Yuasa, Kanako; Yamashita, Takashi; Maekawa, Yasunari; Yoshida, Masaru

    2003-01-01

    Electron beam (EB)-induced reactions of organic crystals containing a carbonyl or a sulfonyl group have been investigated. The EB irradiation of benzenesulfonanilide (BSA) in the crystalline state induced the Fries rearrangement to yield o- and p-aminodiphenylsulfones as the major and minor products, respectively. Several BSA derivatives also had the same reactivity, while benzanilide as the corresponding carbonyl compound did not rearrange under the same conditions. These results showed that the S-N bond could be cleaved selectively by EB irradiation but the C-N bond couldn't, which could take place only by the use of EB. The EB irradiation of phenyl p-toluenesulfonate (PTS) crystals gave not only Fries-type products but also the oxidation product. By comparing with the reactivity of liquid phenyl benzenesulfonate, the EB-induced Fries rearrangement was suggested to proceed under crystalline lattice restrictions. The G-values of arylsulfonamides and arylsulfonates were in the range of ca. 1-2 molecules per 100 eV of absorbed energy. This is the first Fries rearrangement via direct excitation by EB irradiation. (author)

  16. Molecular Mechanisms and Diagnosis of Chromosome 22q11.2 Rearrangements

    Science.gov (United States)

    Emanuel, Beverly S.

    2008-01-01

    Several recurrent, constitutional genomic disorders are present on chromosome 22q. These include the translocations and deletions associated with DiGeorge and velocardiofacial syndrome and the translocations that give rise to the recurrent t(11;22) supernumerary der(22) syndrome (Emanuel syndrome). The rearrangement breakpoints on 22q cluster…

  17. Beckmann rearrangement of aldoximes catalyzed by transition metal salts: mechanical aspects

    NARCIS (Netherlands)

    Leusink, A.J.; Meerbeek, T.G.; Noltes, J.G.

    1977-01-01

    The Beckmann rearrangement of aldoximes catalyzed by transition metal salts like palladium and nickel acetylacetonates is shown to be a dehydration‐hydration reaction in which the anti‐oxime is converted into nitrile and the nitrile is converted into amide.

  18. Condensed tannins. Base-catalysed reactions of polymeric procyanidins with phloroglucinol: Intramolecular rearrangements

    Science.gov (United States)

    Peter E. Laks; Richard W. Hemingway; Anthony H. Conner

    1987-01-01

    Reactions of polymeric procyanidins with phloroglucinol at pH 12.0 and temperatures of 23 or 50°C gave epicatechin-(4β)-phloroglucinol (7), by cleavage of the interflavanoid bond between procyanidin units with subsequent addition of phloroglucinol, and (+)-catechin from the terminal unit. The phloroglucinol adduct (7) rearranged to an enolic form of 8-(3,4-...

  19. Iridium-Catalyzed Dynamic Kinetic Isomerization: Expedient Synthesis of Carbohydrates from Achmatowicz Rearrangement Products.

    Science.gov (United States)

    Wang, Hao-Yuan; Yang, Ka; Bennett, Scott R; Guo, Sheng-rong; Tang, Weiping

    2015-07-20

    A highly stereoselective dynamic kinetic isomerization of Achmatowicz rearrangement products was discovered. This new internal redox isomerization provided ready access to key intermediates for the enantio- and diastereoselective synthesis of a series of naturally occurring sugars. The nature of the de novo synthesis also enables the preparation of both enantiomers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Single Particle Potential of a Σ Hyperon in Nuclear Matter. II Rearrangement Effects

    International Nuclear Information System (INIS)

    Dabrowski, J.

    2000-01-01

    The rearrangement contribution to the real part of the single particle potential of a Σ hyperon in nuclear matter, U Σ , is investigated. The isospin and spin dependent parts of U Σ are considered. Results obtained for four models of the Nijmegen baryon-baryon interaction are presented and discussed. (author)

  1. Intergenomic rearrangements after polyploidization of Kengyilia thoroldiana (Poaceae: Triticeae) affected by environmental factors.

    Science.gov (United States)

    Wang, Qiuxia; Liu, Huitao; Gao, Ainong; Yang, Xinming; Liu, Weihua; Li, Xiuquan; Li, Lihui

    2012-01-01

    Polyploidization is a major evolutionary process. Approximately 70-75% species of Triticeae (Poaceae) are polyploids, involving 23 genomes. To investigate intergenomic rearrangements after polyploidization of Triticeae species and to determine the effects of environmental factors on them, nine populations of a typical polyploid Triticeae species, Kengyilia thoroldiana (Keng) J.L.Yang et al. (2n = 6x = 42, StStPPYY), collected from different environments, were studied using genome in situ hybridization (GISH). We found that intergenomic rearrangements occurred between the relatively large P genome and the small genomes, St (8.15%) and Y (22.22%), in polyploid species via various types of translocations compared to their diploid progenitors. However, no translocation was found between the relatively small St and Y chromosomes. Environmental factors may affect rearrangements among the three genomes. Chromosome translocations were significantly more frequent in populations from cold alpine and grassland environments than in populations from valley and lake-basin habitats (P<0.05). The relationship between types of chromosome translocations and altitude was significant (r = 0.809, P<0.01). Intergenomic rearrangements associated with environmental factors and genetic differentiation of a single basic genome should be considered as equally important genetic processes during species' ecotype evolution.

  2. Density, viscosity and surface tension of liquid phase Beckmann rearrangement mixtures

    NARCIS (Netherlands)

    Zuidhof, K.T.; Croon, de M.H.J.M.; Schouten, J.C.; Tinge, J.T.

    2015-01-01

    We have determined the density, dynamic viscosity, and surface tension of liquid phase Beckmann rearrangement mixtures, consisting of e-caprolactam and fuming oleum. These important properties have been measured in wide ranges of both temperature and molar ratios of acid and e-caprolactam, covering

  3. DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution

    NARCIS (Netherlands)

    Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M.

    DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it

  4. Aberrant immunoglobulin and c-myc gene rearrangements in patients with nonmalignant monoclonal cryoglobulinemia

    International Nuclear Information System (INIS)

    Perl, A.; Wang, N.; Williams, J.M.; Hunt, M.J.; Rosenfeld, S.I.; Condemi, J.J.; Packman, C.H.; Abraham, G.N.

    1987-01-01

    The status of the immunoglobulin (Ig) genes was investigated in patients with idiopathic nonmalignant monoclonal IgG cryoglobulinemia (NCG). In NCG, monoclonal antibodies are synthesized at an accelerated rate by nonmalignant B lymphocytes. In order to determine whether this high production rate is related to a clonal B cell expansion, the rearrangement of the Ig genes was investigated by Southern blot analysis of genomic, 32 P-labelled, DNA extracted from the peripheral blood lymphocytes of four NCG patients. In three of four (VI, BR, and CH) clonal expansion of B cells was detected using probes specific for the genes. BamHI digestion of DNA from VI and BR produced three rearranged fragments which cohybridized with two of the probes. This finding suggested the presence of additional nonsecretory B cell clones and/or disruption of the gene segments spanned by and detected with the probes. In addition, the possibility of aberrant gene rearrangements was supported by noting the alteration of the c-myc gene locus in genomic DNA from peripheral blood leukocytes of VI and CH. Northern blot analysis of RNA isolated from peripheral blood B cells of VI and CH demonstrated aberrant transcripts of the c-myc gene, showing an active role of the altered c-myc locus. Detection of c-myc rearrangement in NCG patients clearly shows that this event may not be a final step in malignant B cell transformation

  5. Interphase FISH detection of BCL2 rearrangement in follicular lymphoma using breakpoint-flanking probes

    NARCIS (Netherlands)

    Vaandrager, J W; Schuuring, E; Raap, T; Philippo, K; Kleiverda, K; Kluin, P

    Rearrangement of the BCL2 gene is an important parameter for the differential diagnosis of non-Hodgkin lymphomas. Although a relatively large proportion of breakpoints is clustered, many are missed by standard PCR. A FISH assay is therefore desired. Up to now, a lack of probes flanking the BCL2 gene

  6. Effects of structural rearrangements on the rheology of rennet-induced casein particle gels

    NARCIS (Netherlands)

    Mellema, M.; Walstra, P.; Opheusden, van J.H.J.; Vliet, van T.

    2002-01-01

    During ageing of casein or skim milk gels, structural changes take place that affect gel parameters, such as pore size and storage modulus. These changes can be explained in terms of rearrangements of the gel network at various length scales. In this paper, rheological experiments on rennet-induced

  7. Myeloid neoplasm with prominent eosinophilia and PDGFRA rearrangement treated with imatinib mesylate

    DEFF Research Database (Denmark)

    Rathe, Mathias; Kielsgaard Kristensen, Thomas; Møller, Michael Boe

    2010-01-01

    of FIP1L1-PDGFRA positive disease has been reported. We report a 2-year-old female with a myeloid neoplasm associated with eosinophilia and rearrangement of PDGFRA. Treatment with imatinib resulted in complete and durable clinical, hematological, and molecular remission within 3 months after starting...

  8. Intergenomic rearrangements after polyploidization of Kengyilia thoroldiana (Poaceae: Triticeae affected by environmental factors.

    Directory of Open Access Journals (Sweden)

    Qiuxia Wang

    Full Text Available Polyploidization is a major evolutionary process. Approximately 70-75% species of Triticeae (Poaceae are polyploids, involving 23 genomes. To investigate intergenomic rearrangements after polyploidization of Triticeae species and to determine the effects of environmental factors on them, nine populations of a typical polyploid Triticeae species, Kengyilia thoroldiana (Keng J.L.Yang et al. (2n = 6x = 42, StStPPYY, collected from different environments, were studied using genome in situ hybridization (GISH. We found that intergenomic rearrangements occurred between the relatively large P genome and the small genomes, St (8.15% and Y (22.22%, in polyploid species via various types of translocations compared to their diploid progenitors. However, no translocation was found between the relatively small St and Y chromosomes. Environmental factors may affect rearrangements among the three genomes. Chromosome translocations were significantly more frequent in populations from cold alpine and grassland environments than in populations from valley and lake-basin habitats (P<0.05. The relationship between types of chromosome translocations and altitude was significant (r = 0.809, P<0.01. Intergenomic rearrangements associated with environmental factors and genetic differentiation of a single basic genome should be considered as equally important genetic processes during species' ecotype evolution.

  9. Comparative analysis of clinicoradiologic characteristics of lung adenocarcinomas with ALK rearrangements or EGFR mutations

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, J.Y.; Zheng, J.; Chen, X.; Zhou, J.Y. [Zhejiang University, Department of Respiratory Disease, Thoracic Disease Center, First Affiliated Hospital, College of Medicine, Hangzhou (China); Yu, Z.F.; Xiao, W.B.; Jiang, L.N. [Zhejiang University, Department of Radiology, First Affiliated Hospital, College of Medicine, Hangzhou (China); Zhao, J.; Sun, K.; Wang, B.; Ding, W. [Zhejiang University, Department of Pathology, First Affiliated Hospital, College of Medicine, Hangzhou (China)

    2015-05-01

    To compare the clinicoradiologic features of tumours with echinoderm anaplastic lymphoma kinase (ALK) rearrangements, epidermal growth factor receptor (EGFR) mutations, or wild type (WT) for both genes in a cohort of patients with lung adenocarcinoma to identify useful characteristics of different gene statuses. In 346 lung adenocarcinoma patients, ALK rearrangements were confirmed with fluorescence in situ hybridisation, and EGFR mutations were determined by pyrosequencing assay. Patients were divided into three groups: ALK rearrangement (ALK+ group, n = 48), EGFR mutation (EGFR+ group, n = 166), and WT for both genes (WT group, n = 132). Chest computed tomography (CT) examinations were performed in all patients. The percentages of ground-glass opacity volume (pGGO) and tumour shadow disappearance rate (TDR) were measured using semi-automated nodule assessment software. The pGGO was significantly lower in the ALK+ group (25.1 % ± 24.3) than in the EGFR+ group (37.2 % ± 25.7, p < 0.001) and the WT group (36.1 % ± 24.6, p = 0.001). The TDR in the ALK+ group (17.3 % ± 25.1) was significantly lower than in the EGFR+ group (26.8 % ± 24.9, p = 0.002) and the WT group (25.7 % ± 24.6, p = 0.003). Solid pattern with lower incidence of lobulated border, finely spiculated margins, pleural retraction, and bubble-like lucency on CT imaging are the main characteristics of ALK rearrangement tumours. (orig.)

  10. Synthesis and Rearrangement of Dewar Benzenes Into Biaryls: Experimental Evidence for Conrotatory Ring Opening

    Czech Academy of Sciences Publication Activity Database

    Janková, Š.; Dračínský, Martin; Císařová, I.; Kotora, Martin

    -, č. 1 (2008), s. 47-51 ISSN 1434-193X R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : Dewar benzene * biaryls * alkynes * Hammett * rearrangement Subject RIV: CC - Organic Chemistry Impact factor: 3.016, year: 2008

  11. Mapping of 5q35 chromosomal rearrangements within a genomically unstable region

    DEFF Research Database (Denmark)

    Buysse, Karen; Crepel, An; Menten, Björn

    2008-01-01

    these rearrangements. METHODS: We analysed a series of patients with breakpoints clustering within chromosome band 5q35. Using high density arrays and subsequent quantitative polymerase chain reaction (qPCR), we characterised the breakpoints of four interstitial deletions (including one associated with an unbalanced...

  12. A proposal for calculating the importance of exchange effects in rearrangement collisions

    International Nuclear Information System (INIS)

    Mihailovic, M.V.; Nagarajan, M.A.

    1980-02-01

    A formalism based on the generator co-ordinate method (GCM) for reactions is derived to test approximations in the most commonly used methods for calculating the rearrangement amplitudes: namely the distorted wave Born approximation (DWBA), the coupled channel Born approximation (CCBA) and the coupled reaction channel (CRC). (author)

  13. Replication stalling by catalytically impaired Twinkle induces mitochondrial DNA rearrangements in cultured cells

    NARCIS (Netherlands)

    Pohjoismaki, J.L.; Goffart, S.; Spelbrink, J.N.

    2011-01-01

    Pathological mitochondrial DNA (mtDNA) rearrangements have been proposed to result from repair of double-strand breaks caused by blockage of mitochondrial DNA (mtDNA) replication. As mtDNA deletions are seen only in post-mitotic tissues, it has been suggested that they are selected out in actively

  14. Qualitative and quantitative ultrastructural analysis of the membrane rearrangements induced by coronavirus

    NARCIS (Netherlands)

    Ulasli, M.; Verheije, M.H.; de Haan, C.A.M.; Reggiori, F.M.

    2011-01-01

    Coronaviruses (CoV) are enveloped positive-strand RNA viruses that induce different membrane rearrangements in infected cells in order to efficiently replicate and assemble. The origin, the protein composition and the function of these structures are not well established. To shed further light on

  15. Configurational rearrangements of bistable centers in covalent semiconductors - phase transitions of the second type

    International Nuclear Information System (INIS)

    Ivanyukovich, V.A.; Karas', V.I.; Lomako, V.M.

    1989-01-01

    A new radiation configurational-bistable defect diffring from the known similar defects by the fact that it possessestemperature inversion of states is detected in gallium arsenide. Configurational-bistable rearrangements are shown to be considered as phase transitions of the second type

  16. HOXA9 is required for survival in human MLL-rearranged acute leukemias

    NARCIS (Netherlands)

    J. Faber (Joerg); A.V. Krivtsov (Andrei); M.C. Stubbs (Matthew); R. Wright (Renee); T.N. Davis (Tina); M.M. van den Heuvel-Eibrink (Marry); C.M. Zwaan (Christian Michel); A.L. Kung (Andrew); S.A. Armstrong (Scott)

    2009-01-01

    textabstractLeukemias that harbor translocations involving the mixed lineage leukemia gene (MLL) possess unique biologic characteristics and often have an unfavorable prognosis. Gene expression analyses demonstrate a distinct profile for MLL-rearranged leukemias with consistent high-level expression

  17. Aminocyclopentanols as sugar mimics. Synthesis from unsaturated bicyclic lactones by Overman rearrangement

    DEFF Research Database (Denmark)

    Bøjstrup, Marie; Fanefjord, Mette; Lundt, Inge

    2007-01-01

    Bicyclic cyclopentane lactones, prepared from bromodeoxyaldonolactones, were transformed into aminocyclopentanols with an Overman rearrangement as the key step. Two of the compounds prepared, 7 and 19, were found to be good inhibitors of jack bean alpha-mannosidase and beta-D-N-acetylglucosaminid...

  18. Multi-step rearrangement mechanism for acetyl cedrene to the hydrocarbon follower

    DEFF Research Database (Denmark)

    Paknikar, Shashikumar Keshav; Kamounah, Fadhil S.; Hansen, Poul Erik

    2017-01-01

    Conversion of acetyl cedrene (2) to its follower (3) using acetic anhydride and polyphosphoric acid involves a multi-step cationic molecular rearrangement, which is consistent with deuteriation and 1-13C labeling studies of acetyl cedrene. The key step involves cyclopropylcarbinyl cation-cyclopro...

  19. Aniridia-associated cytogenetic rearrangements suggest that a position effect may cause the mutant phenotype

    NARCIS (Netherlands)

    Fantes, J.; Redeker, B.; Breen, M.; Boyle, S.; Brown, J.; Fletcher, J.; Jones, S.; Bickmore, W.; Fukushima, Y.; Mannens, M.

    1995-01-01

    Current evidence suggests that aniridia (absence of iris) is caused by loss of function of one copy of the PAX6 gene, which maps to 11p13. We present the further characterisation of two aniridia pedigrees in which the disease segregates with chromosomal rearrangements which involve 11p13 but do not

  20. Phylogenetic signal from rearrangements in 18 Anopheles species by joint scaffolding extant and ancestral genomes.

    Science.gov (United States)

    Anselmetti, Yoann; Duchemin, Wandrille; Tannier, Eric; Chauve, Cedric; Bérard, Sèverine

    2018-05-09

    Genomes rearrangements carry valuable information for phylogenetic inference or the elucidation of molecular mechanisms of adaptation. However, the detection of genome rearrangements is often hampered by current deficiencies in data and methods: Genomes obtained from short sequence reads have generally very fragmented assemblies, and comparing multiple gene orders generally leads to computationally intractable algorithmic questions. We present a computational method, ADSEQ, which, by combining ancestral gene order reconstruction, comparative scaffolding and de novo scaffolding methods, overcomes these two caveats. ADSEQ provides simultaneously improved assemblies and ancestral genomes, with statistical supports on all local features. Compared to previous comparative methods, it runs in polynomial time, it samples solutions in a probabilistic space, and it can handle a significantly larger gene complement from the considered extant genomes, with complex histories including gene duplications and losses. We use ADSEQ to provide improved assemblies and a genome history made of duplications, losses, gene translocations, rearrangements, of 18 complete Anopheles genomes, including several important malaria vectors. We also provide additional support for a differentiated mode of evolution of the sex chromosome and of the autosomes in these mosquito genomes. We demonstrate the method's ability to improve extant assemblies accurately through a procedure simulating realistic assembly fragmentation. We study a debated issue regarding the phylogeny of the Gambiae complex group of Anopheles genomes in the light of the evolution of chromosomal rearrangements, suggesting that the phylogenetic signal they carry can differ from the phylogenetic signal carried by gene sequences, more prone to introgression.

  1. The diverse effects of complex chromosome rearrangements and chromothripsis in cancer development

    NARCIS (Netherlands)

    De Pagter, Mirjam S.; Kloosterman, Wigard P.

    2015-01-01

    In recent years, enormous progress has been made with respect to the identification of somatic mutations that contribute to cancer development. Mutation types range from small substitutions to large structural genomic rearrangements, including complex reshuffling of the genome. Sets of mutations in

  2. Radiation-induced genomic instability driven by de novo chromosomal rearrangement hot spots

    International Nuclear Information System (INIS)

    Grosovsky, A.J.; Allen, R.N.; Moore, S.R.

    2003-01-01

    Genomic instability has become generally recognized as a critical contributor to tumor progression by generating the necessary number of genetic alterations required for expression of a clinically significant malignancy. Our study of chromosomal instability investigates the hypothesis that chromosomal rearrangements can generate novel breakage-prone sites, resulting in instability acting predominantly in cis. Here we present an analysis of the karyotypic distribution of instability associated chromosomal rearrangements in TK6 and derivative human lymphoblasts. Karyotypic analysis performed on a total of 455 independent clones included 183 rearrangements distributed among 100 separate unstable clones. The results demonstrate that the breakpoints of chromosomal rearrangements in unstable clones are non-randomly distributed throughout the genome. This pattern is statistically significant, and incompatible with expectations for random breakage associated with loss or alteration of a trans-acting factor. Furthermore, specific chromosomal breakage hot spots associated with instability have been identified; these occur in several independent unstable clones and are often repeatedly broken and rejoined during the outgrowth of an individual clone. In complimentary studies, genomic instability was generated without any exposure to a DNA-damaging agent, but rather by transfection with alpha heterochromatin DNA. In a prospective analysis, human-hamster hybrid AL cells containing a single human chromosome 11 were transfected with heterochromatic alpha DNA repeats and clones were analyzed by chromosome 11 painting. Transfection with alpha DNA was associated with karyotypic heterogeneity in 40% of clones examined; control transfections with plasmid alone did not lead to karyotypic heterogeneity

  3. Unique mosaicism of structural chromosomal rearrangement: is chromosome 18 preferentially involved?

    NARCIS (Netherlands)

    Pater, J.M. de; Smeets, D.F.C.M.; Scheres, J.M.J.C.

    2003-01-01

    The mentally normal mother of a 4-year-old boy with del(18)(q21.3) syndrome was tested cytogenetically to study the possibility of an inherited structural rearrangement of chromosome 18. She was found to carry an unusual mosaicism involving chromosomes 18 and 21. Two unbalanced cell lines were seen

  4. Identification of a structural chromosomal rearrangement in the karyotype of a root vole from Chernobyl

    International Nuclear Information System (INIS)

    Nadzhafova, R.S.; Bulatova, N.Sh.; Kozlovskii, A.I.; Ryabov, I.N.

    1994-01-01

    Karyological studies of rodents within a 30-km radius of the Chernobyl nuclear power plant revealed one female root vole (Microtus oeconomus) with an abnormal karyotype. The use of C, G, and AgNOR banding methods allowed determination that morphological changes in two nonhomologous autosomes, which were accompanied by rearrangements in distribution of G bands, heterochromatin, and NOR, are the result of a reciprocal translocation. Chromosomal aberrations were probably inherited or appeared in embryogenesis, since none of the analyzed cells of the studied vole had a normal karyotype. It is important to note that this rearrangement was detected five years after the meltdown. Both breaks and reunions of the chromosomes that participate in this rearrangement are probably located in regions that are not important for functioning of these chromosomes. Thus, it can be supposed that the detected rearrangement did not influence the viability of the vole. This karyotype was compared to a standard karyotype of a root vole from another area of the species range. The heteromorphism of the first pair of chromosomes in both voles, which was detected for the first time, is probably normal for the karyotype of M. oeconomus and is not linked with any radiation-induced intrachromosomal aberrations

  5. Nuclear positioning rather than contraction controls ordered rearrangements of immunoglobulin loci

    NARCIS (Netherlands)

    M.B. Rother (Magdalena); R.-J.T.S. Palstra (Robert-Jan); S. Jhunjhunwala (Suchit); K.A.M. Van Kester (Kevin A. M.); W.F.J. van IJcken (Wilfred); R.W. Hendriks (Rudi); J.J.M. van Dongen (Jacques); C. Murre (Cornelis); M.C. van Zelm (Menno)

    2016-01-01

    textabstractProgenitor-B cells recombine their immunoglobulin (Ig) loci to create unique antigen receptors. Despite a common recombination machinery, the Ig heavy and Ig light chain loci rearrange in a stepwise manner. We studied pre-pro-B cells and Rag-/- progenitor-B cells to determine whether Ig

  6. Distribution of the various radiation-induced chromosomal rearrangements in relation to the dose and sampling time

    International Nuclear Information System (INIS)

    Dutrillaux, B.; Viegas-Pequignot, E.; Prod'homme, M.; Sportes, M.

    1985-01-01

    The quantitative analysis of the chromosome rearrangements detected in 2128 R-banded metaphases, obtained from γ-irradiated human lymphocytes after 48 to 96 h in culture is reported. Depending on the culture time, and possibly on the dose of radiation (from 1 to 3 Gy), the most frequent type of rearrangement was either dicentrics or reciprocal translocations. In first generation mitoses, the frequency of cells without rearrangement ranged from 0.66 to 0.18, and the mean number of rearranged chromosomes per cell from 0.79 to 3.28. The dose-response curve follows a quadratic function for dicentric aberration yields, but not for other rearrangements. (Auth.)

  7. Radical Rearrangement Chemistry in Ultraviolet Photodissociation of Iodotyrosine Systems: Insights from Metastable Dissociation, Infrared Ion Spectroscopy, and Reaction Pathway Calculations.

    Science.gov (United States)

    Ranka, Karnamohit; Zhao, Ning; Yu, Long; Stanton, John F; Polfer, Nicolas C

    2018-05-29

    We report on the ultraviolet photodissociation (UVPD) chemistry of protonated tyrosine, iodotyrosine, and diiodotyrosine. Distonic loss of the iodine creates a high-energy radical at the aromatic ring that engages in hydrogen/proton rearrangement chemistry. Based on UVPD kinetics measurements, the appearance of this radical is coincident with the UV irradiation pulse (8 ns). Conversely, sequential UVPD product ions exhibit metastable decay on ca. 100 ns timescales. Infrared ion spectroscopy is capable of confirming putative structures of the rearrangement products as proton transfers from the imine and β-carbon hydrogens. Potential energy surfaces for the various reaction pathways indicate that the rearrangement chemistry is highly complex, compatible with a cascade of rearrangements, and that there is no preferred rearrangement pathway even in small molecular systems like these. Graphical Abstract.

  8. 17β-Estradiol-Induced Synaptic Rearrangements Are Accompanied by Altered Ectonucleotidase Activities in Male Rat Hippocampal Synaptosomes.

    Science.gov (United States)

    Mitrović, Nataša; Zarić, Marina; Drakulić, Dunja; Martinović, Jelena; Sévigny, Jean; Stanojlović, Miloš; Nedeljković, Nadežda; Grković, Ivana

    2017-03-01

    17β-Estradiol (E2) rapidly, by binding to membrane estrogen receptors, activates cell signaling cascades which induce formation of new dendritic spines in the hippocampus of males as in females, but the interaction with other metabolic processes, such as extracellular adenine nucleotides metabolism, are currently unknown. Extracellular adenine nucleotides play significant roles, controlling excitatory glutamatergic synapses and development of neural circuits and synaptic plasticity. Their precise regulation in the synaptic cleft is tightly controlled by ecto-nucleoside triphosphate diphosphohydrolase (NTPDase)/ecto-5'-nucleotidase (eN) enzyme chain. Therefore, we sought to clarify whether a single systemic injection of E2 in male rats is accompanied by changes in the expression of the pre- and postsynaptic proteins and downstream kinases linked to E2-induced synaptic rearrangement as well as alterations in NTPDase/eN pathway in the hippocampal synaptosomes. Obtained data showed activation of mammalian target of rapamycin and upregulation of key synaptic proteins necessary for spine formation, 24 h after systemic E2 administration. In E2-mediated conditions, we found downregulation of NTPDase1 and NTPDase2 and attenuation of adenine nucleotide hydrolysis by NTPDase/eN enzyme chain, without changes in NTPDase3 properties and augmentation of synaptic tissue-nonspecific alkaline phosphatase (TNAP) activity. Despite reduced NTPDase activities, increased TNAP activity probably prevents toxic accumulation of ATP in the extracellular milieu and also hydrolyzes accumulated ADP due to unchanged NTPDase3 activity. Thus, our initial evaluation supports idea of specific roles of different ectonucleotidases and their coordinated actions in E2-mediated spine remodeling and maintenance.

  9. Internal flow inside droplets within a concentrated emulsion during droplet rearrangement

    Science.gov (United States)

    Leong, Chia Min; Gai, Ya; Tang, Sindy K. Y.

    2018-03-01

    Droplet microfluidics, in which each droplet serves as a micro-reactor, has found widespread use in high-throughput biochemical screening applications. These droplets are often concentrated at various steps to form a concentrated emulsion. As part of a serial interrogation and sorting process, such concentrated emulsions are typically injected into a tapered channel leading to a constriction that fits one drop at a time for the probing of droplet content in a serial manner. The flow physics inside the droplets under these flow conditions are not well understood but are critical for predicting and controlling the mixing of reagents inside the droplets as reactors. Here we investigate the flow field inside droplets of a concentrated emulsion flowing through a tapered microchannel using micro-particle image velocimetry. The confining geometry of the channel forces the number of rows of drops to reduce by one at specific and uniformly spaced streamwise locations, which are referred to as droplet rearrangement zones. Within each rearrangement zone, the phase-averaged velocity results show that the motion of the droplets involved in the rearrangement process, also known as a T1 event, creates vortical structures inside themselves and their adjacent droplets. These flow structures increase the circulation inside droplets up to 2.5 times the circulation in droplets at the constriction. The structures weaken outside of the rearrangement zones suggesting that the flow patterns created by the T1 process are transient. The time scale of circulation is approximately the same as the time scale of a T1 event. Outside of the rearrangement zones, flow patterns in the droplets are determined by the relative velocity between the continuous and disperse phases.

  10. Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

    Energy Technology Data Exchange (ETDEWEB)

    Nishino, Mizuki, E-mail: Mizuki_Nishino@DFCI.HARVARD.EDU [Department of Radiology, Brigham and Women’s Hospital, 450 Brookline Ave., Boston MA, 02215 (United States); Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave., Boston MA, 02215 (United States); Sacher, Adrian G.; Gandhi, Leena; Chen, Zhao; Akbay, Esra [Department of Medical Oncology and Department of Medicine Dana-Farber Cancer Institute and Brigham and Women’s Hospital 450 Brookline Ave., Boston MA, 02215 (United States); Fedorov, Andriy; Westin, Carl F.; Hatabu, Hiroto [Department of Radiology, Brigham and Women’s Hospital, 450 Brookline Ave., Boston MA, 02215 (United States); Johnson, Bruce E.; Hammerman, Peter; Wong, Kwok-kin [Department of Medical Oncology and Department of Medicine Dana-Farber Cancer Institute and Brigham and Women’s Hospital 450 Brookline Ave., Boston MA, 02215 (United States)

    2017-03-15

    Highlights: • Role of co-clinical studies in precision cancer medicine is increasingly recognized. • This study compared tumor volume in co-clinical trials of ALK-rearranged NSCLC. • Similarities and differences of tumor volume changes in mice and humans were noted. • The study provides insights to optimize murine co-clinical trial designs. - Abstract: Purpose: To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC). Methods: Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans. Results: The median tumor volume decrease (%) at the maximal response was −40.4% (range: −79.5%–+11.7%) in mice, and −72.9% (range: −100%–+72%) in humans (Wilcoxon p = 0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months. Conclusion: The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.

  11. Clinical significance of productive immunoglobulin heavy chain gene rearrangements in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Katsibardi, Katerina; Braoudaki, Maria; Papathanasiou, Chrissa; Karamolegou, Kalliopi; Tzortzatou-Stathopoulou, Fotini

    2011-09-01

    We analyzed the CDR3 region of 80 children with B-cell acute lymphoblastic leukemia (B-ALL) using the ImMunoGeneTics Information System and JOINSOLVER. In total, 108 IGH@ rearrangements were analyzed. Most of them (75.3%) were non-productive. IGHV@ segments proximal to IGHD-IGHJ@ were preferentially rearranged (45.3%). Increased utilization of IGHV3 segments IGHV3-13 (11.3%) and IGHV3-15 (9.3%), IGHD3 (30.5%), and IGHJ4 (34%) was noted. In pro-B ALL more frequent were IGHV3-11 (33.3%) and IGHV6-1 (33.3%), IGHD2-21 (50%), IGHJ4 (50%), and IGHJ6 (50%) segments. Shorter CDR3 length was observed in IGHV@6, IGHD7, and IGHJ1 segments, whereas increased CDR3 length was related to IGHV3, IGHD2, and IGHJ4 segments. Increased risk of relapse was found in patients with productive sequences. Specifically, the relapse-free survival rate at 5 years in patients with productive sequences at diagnosis was 75% (standard error [SE] ±9%), whereas in patients with non-productive sequences it was 97% (SE ±1.92%) (p-value =0.0264). Monoclonality and oligoclonality were identified in 81.2% and 18.75% cases at diagnosis, respectively. Sequence analysis revealed IGHV@ to IGHDJ joining only in 6.6% cases with oligoclonality. The majority (75%) of relapsed patients had monoclonal IGH@ rearrangements. The preferential utilization of IGHV@ segments proximal to IGHDJ depended on their location on the IGHV@ locus. Molecular mechanisms occurring during IGH@ rearrangement might play an essential role in childhood ALL prognosis. In our study, the productivity of the rearranged sequences at diagnosis proved to be a significant prognostic factor.

  12. Micellar dipolar rearrangement is sensitive to hydrophobic chain length: Implication for structural switchover of piroxicam.

    Science.gov (United States)

    Sethy, Dasaratha; Chakraborty, Hirak

    2016-10-01

    The interfacial properties of the membrane are exceptionally vital in drug-membrane interaction. They not only select out a particular prototropic form of the drug molecule for incorporation, but are also potent enough to induce structural switchover of these drugs in several cases. In this work, we quantitatively monitored the change in dipolar rearrangement of the micellar interface (as a simplified membrane mimic) by measuring the dielectric constant and dipole potential with the micellization of SDS at pH 3.6. The dielectric constant and dipole potential were measured utilizing the fluorescence of polarity sensitive probe, pyrene and potential-sensitive probe, di-8-ANEPPS, respectively. Our study demonstrates that the change in dipolar rearrangement directly influences the switchover equilibrium between the anionic and neutral from of piroxicam. We have further extended our work to evaluate the effect of hydrophobic chain length of the surfactants on the dipolar rearrangement and its effect on the structural switchover of piroxicam. It is interesting that the extent of switchover of piroxicam is directly correlated with the dipolar rearrangement induced bythe varying hydrophobic chain length of the surfactants. To the best of our knowledge, our results constitute the first report to show the dependence of dipole potential on the hydrophobic chain length of the surfactant and demonstrate that the dipolar rearrangement directly tunes the extent of structural switchover of piroxicam, which was so far only intuitive. We consider that this new finding would have promising implication in drug distribution and drug efficacy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Antibody-Based Detection of ERG Rearrangement-Positive Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Kyung Park

    2010-07-01

    Full Text Available TMPRSS2-ERG gene fusions occur in 50% of prostate cancers and result in the overexpression of a chimeric fusion transcript that encodes a truncated ERG product. Previous attempts to detect truncated ERG products have been hindered by a lack of specific antibodies. Here, we characterize a rabbit anti-ERG monoclonal antibody (clone EPR 3864; Epitomics, Burlingame, CA using immunoblot analysis on prostate cancer cell lines, synthetic TMPRSS2-ERG constructs, chromatin immunoprecipitation, and immunofluorescence. We correlated ERG protein expression with the presence of ERG gene rearrangements in prostate cancertissues using a combined immunohistochemistry(IHC and fluorescence in situ hybridization (FISH analysis. We independently evaluated two patient cohorts and observed ERG expression confined to prostate cancer cells and high-grade prostatic intraepithelial reoplasia associated with ERG-positive cancer, as well as vessels and lymphocytes (where ERG has a known biologic role. Image analysis of 131 cases demonstrated nearly 100% sensitivity for detecting ERG rearrangement prostate cancer, with only 2 (1.5% of 131 cases demonstrating strong ERG protein expression without any known ERG gene fusion. The combired pathology evaluation of 207 patient tumors for ERG protein expression had 95.7% sensitivity and 96.5% specificity for determining ERG rearrangement prostate cancer. Ir conclusion, this study qualifies a specific anti-ERG antibody and demonstrates exquisite association between ERG gene rearrangement and truncated ERG protein product expression. Giver the ease of performing IHC versus FISH, ERG protein expression may be useful for molecularly subtypirg prostate cancer based or ERG rearrangement status and suggests clinical utility it prostate needle biopsy evaluation.

  14. Spatially Rearranged Object Parts Can Facilitate Perception of Intact Whole Objects

    Directory of Open Access Journals (Sweden)

    Laura eCacciamani

    2014-05-01

    Full Text Available The familiarity of an object depends on the spatial arrangement of its parts; when the parts are spatially rearranged, they form a novel, unrecognizable configuration. Yet the same collection of parts comprises both the familiar and novel configuration. Is it possible that the collection of familiar parts activates a representation of the intact familiar configuration even when they are spatially rearranged? We presented novel configurations as primes before test displays that assayed effects on figure-ground perception from memories of intact familiar objects. In our test displays, two equal-area regions shared a central border; one region depicted a portion of a familiar object. Previous research with such displays has shown that participants are more likely to perceive the region depicting a familiar object as the figure and the abutting region as its ground when the familiar object is depicted in its upright orientation rather than upside down. The novel primes comprised either the same or a different collection of parts as the familiar object in the test display (part-rearranged and control primes, respectively. We found that participants were more likely to perceive the familiar region as figure in upright vs. inverted displays following part-rearranged primes but not control primes. Thus, priming with a novel configuration comprising the same familiar parts as the upcoming figure-ground display facilitated orientation-dependent effects of object memories on figure assignment. Similar results were obtained when the spatially rearranged collection of parts was suggested on the groundside of the prime’s border, suggesting that familiar parts in novel configurations access the representation of their corresponding intact whole object before figure assignment. These data demonstrate that familiar parts access memories of familiar objects even when they are arranged in a novel configuration.

  15. Spatially rearranged object parts can facilitate perception of intact whole objects.

    Science.gov (United States)

    Cacciamani, Laura; Ayars, Alisabeth A; Peterson, Mary A

    2014-01-01

    The familiarity of an object depends on the spatial arrangement of its parts; when the parts are spatially rearranged, they form a novel, unrecognizable configuration. Yet the same collection of parts comprises both the familiar and novel configuration. Is it possible that the collection of familiar parts activates a representation of the intact familiar configuration even when they are spatially rearranged? We presented novel configurations as primes before test displays that assayed effects on figure-ground perception from memories of intact familiar objects. In our test displays, two equal-area regions shared a central border; one region depicted a portion of a familiar object. Previous research with such displays has shown that participants are more likely to perceive the region depicting a familiar object as the figure and the abutting region as its ground when the familiar object is depicted in its upright orientation rather than upside down. The novel primes comprised either the same or a different collection of parts as the familiar object in the test display (part-rearranged and control primes, respectively). We found that participants were more likely to perceive the familiar region as figure in upright vs. inverted displays following part-rearranged primes but not control primes. Thus, priming with a novel configuration comprising the same familiar parts as the upcoming figure-ground display facilitated orientation-dependent effects of object memories on figure assignment. Similar results were obtained when the spatially rearranged collection of parts was suggested on the groundside of the prime's border, suggesting that familiar parts in novel configurations access the representation of their corresponding intact whole object before figure assignment. These data demonstrate that familiar parts access memories of familiar objects even when they are arranged in a novel configuration.

  16. Chromosomal instability can be induced by the formation of breakage-prone chromosome rearrangement junctions

    International Nuclear Information System (INIS)

    Allen, R.N.; Ritter, L.; Moore, S.R.; Grosovsky, A.J.

    2003-01-01

    Full text: Studies in our lab have led to the hypothesis that chromosomal rearrangements can generate novel breakage-prone sites, resulting in chromosomal instability acting predominantly in cis. For example, specific breakage of large blocks of centromeric region heterochromatin on chromosome 16q by treatment with 2,6-diaminopurine (DAP) is associated with repeated rearrangement of chromosome 16q during outgrowth of DAP-treated clones, thereby establishing a link between the initial site of damage and the occurrence of persistent chromosomal instability. Similarly, karyotypic analysis of gamma ray induced instability demonstrated that chromosomal rearrangements in sub-clones were significantly clustered near the site of previously identified chromosomal rearrangement junctions in unstable parental clones. This study investigates the hypothesis that integration of transfected sequences into host chromosomes could create breakage-prone junction regions and persistent genomic instability without exposure to DNA-damage agents. These junctions may mimic the unstable chromosomal rearrangements induced by DAP or radiation, and thus provide a test of the broader hypothesis that instability can to some extent be attributed to the formation of novel chromosomal breakage hot spots. These experiments were performed using human-hamster hybrid AL cells containing a single human chromosome 11, which was used to monitor instability in a chromosomal painting assay. AL cells were transfected with a 2.5 Kb fragment containing multiple copies of the 180 bp human alpha heterochromatic repeat, which resulted in chromosomal instability in 41% of the transfected clones. Parallel exposure to gamma-radiation resulted in a similar level of chromosomal instability, although control transfections with plasmid alone did not lead to karyotypic instability. Chromosomal instability induced by integration of alpha heterochromatic repeats was also frequently associated with delayed reproductive

  17. Co-clinical quantitative tumor volume imaging in ALK-rearranged NSCLC treated with crizotinib

    International Nuclear Information System (INIS)

    Nishino, Mizuki; Sacher, Adrian G.; Gandhi, Leena; Chen, Zhao; Akbay, Esra; Fedorov, Andriy; Westin, Carl F.; Hatabu, Hiroto; Johnson, Bruce E.; Hammerman, Peter; Wong, Kwok-kin

    2017-01-01

    Highlights: • Role of co-clinical studies in precision cancer medicine is increasingly recognized. • This study compared tumor volume in co-clinical trials of ALK-rearranged NSCLC. • Similarities and differences of tumor volume changes in mice and humans were noted. • The study provides insights to optimize murine co-clinical trial designs. - Abstract: Purpose: To evaluate and compare the volumetric tumor burden changes during crizotinib therapy in mice and human cohorts with ALK-rearranged non-small-cell lung cancer (NSCLC). Methods: Volumetric tumor burden was quantified on serial imaging studies in 8 bitransgenic mice with ALK-rearranged adenocarcinoma treated with crizotinib, and in 33 human subjects with ALK-rearranged NSCLC treated with crizotinib. The volumetric tumor burden changes and the time to maximal response were compared between mice and humans. Results: The median tumor volume decrease (%) at the maximal response was −40.4% (range: −79.5%–+11.7%) in mice, and −72.9% (range: −100%–+72%) in humans (Wilcoxon p = 0.03). The median time from the initiation of therapy to maximal response was 6 weeks in mice, and 15.7 weeks in humans. Overall volumetric response rate was 50% in mice and 97% in humans. Spider plots of tumor volume changes during therapy demonstrated durable responses in the human cohort, with a median time on therapy of 13.1 months. Conclusion: The present study described an initial attempt to evaluate quantitative tumor burden changes in co-clinical imaging studies of genomically-matched mice and human cohorts with ALK-rearranged NSCLC treated with crizotinib. Differences are noted in the degree of maximal volume response between the two cohorts in this well-established paradigm of targeted therapy, indicating a need for further studies to optimize co-clinical trial design and interpretation.

  18. The photochemical reaction of 1,1-dicyano-3-phenylbut-1-ene. Simultaneous occurrence of p-methane and di-p-methane rearrangements

    Directory of Open Access Journals (Sweden)

    Silva Francisco A. da

    1999-01-01

    Full Text Available The direct photolysis of 1,1-dicyano-3-phenylbut-1-ene (3-MDCN was investigated at room temperature in solvents of different polarities (hexane, dichloromethane and acetonitrile. Cyclopropanes arising from both the di-pi-methane and pi-methane (1,2-H migration processes were obtained as photoproducts. The structures of the products were elucidated by ¹H-NMR, GC/MS, IR and chromatography. Relative quantum yield determination and GC analysis of sequential irradiations gave evidence that: i no secondary reactions occur, even at high conversions; ii the di-pi-methane rearrangement is significantly more affected by the solvent variation than the pi-methane reaction. Photosensitization with acetophenone or acetone did not yield any observable products. The existence of the simultaneous mechanisms and the observed effects were considered as evidence of a possible differentiation between localized and delocalized excitation on the excited state surface.

  19. Biochemical and secondary metabolites changes under moisture ...

    African Journals Online (AJOL)

    The study showed the importance of carbohydrate and nitrogen cycle related metabolites in mediating tolerance in cassava by affecting their phenotypic expression in the plant. Keywords: Hydrothermal stress, bio-chemicals, pigments, secondary metabolites, cassava. African Journal of Biotechnology, Vol 13(31) 3173-3186 ...

  20. Secondary Leukemia Associated with the Anti-Cancer Agent, Etoposide, a Topoisomerase II Inhibitor

    OpenAIRE

    Sachiko Ezoe

    2012-01-01

    Etoposide is an anticancer agent, which is successfully and extensively used in treatments for various types of cancers in children and adults. However, due to the increases in survival and overall cure rate of cancer patients, interest has arisen on the potential risk of this agent for therapy-related secondary leukemia. Topoisomerase II inhibitors, including etoposide and teniposide, frequently cause rearrangements involving the mixed lineage leukemia (MLL<...

  1. Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

    Directory of Open Access Journals (Sweden)

    Hyun-Kyoung Kim

    Full Text Available BACKGROUND: The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs, which are abundant in solid tumors, can be utilized for identification of rearranged ends. METHOD: As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP microarray method entailing CNB-region refinement by competitor DNA. RESULT: Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9% were identified, and two polymerase chain reaction (PCR-amplifiable rearrangements were obtained in six cases (66.7%. And significantly, TNGS-CNB, with its high positive identification rate (82.6% of PCR-amplifiable rearrangements at candidate sites (19/23, just from filtering of aligned sequences, requires little effort for validation. CONCLUSION: Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

  2. Targeted next-generation sequencing at copy-number breakpoints for personalized analysis of rearranged ends in solid tumors.

    Science.gov (United States)

    Kim, Hyun-Kyoung; Park, Won Cheol; Lee, Kwang Man; Hwang, Hai-Li; Park, Seong-Yeol; Sorn, Sungbin; Chandra, Vishal; Kim, Kwang Gi; Yoon, Woong-Bae; Bae, Joon Seol; Shin, Hyoung Doo; Shin, Jong-Yeon; Seoh, Ju-Young; Kim, Jong-Il; Hong, Kyeong-Man

    2014-01-01

    The concept of the utilization of rearranged ends for development of personalized biomarkers has attracted much attention owing to its clinical applicability. Although targeted next-generation sequencing (NGS) for recurrent rearrangements has been successful in hematologic malignancies, its application to solid tumors is problematic due to the paucity of recurrent translocations. However, copy-number breakpoints (CNBs), which are abundant in solid tumors, can be utilized for identification of rearranged ends. As a proof of concept, we performed targeted next-generation sequencing at copy-number breakpoints (TNGS-CNB) in nine colon cancer cases including seven primary cancers and two cell lines, COLO205 and SW620. For deduction of CNBs, we developed a novel competitive single-nucleotide polymorphism (cSNP) microarray method entailing CNB-region refinement by competitor DNA. Using TNGS-CNB, 19 specific rearrangements out of 91 CNBs (20.9%) were identified, and two polymerase chain reaction (PCR)-amplifiable rearrangements were obtained in six cases (66.7%). And significantly, TNGS-CNB, with its high positive identification rate (82.6%) of PCR-amplifiable rearrangements at candidate sites (19/23), just from filtering of aligned sequences, requires little effort for validation. Our results indicate that TNGS-CNB, with its utility for identification of rearrangements in solid tumors, can be successfully applied in the clinical laboratory for cancer-relapse and therapy-response monitoring.

  3. Chromosomal Rearrangements in Post-Chernobyl Papillary Thyroid Carcinomas: Evaluation by Spectral Karyotyping and Automated Interphase FISH

    Directory of Open Access Journals (Sweden)

    Ludwig Hieber

    2011-01-01

    Full Text Available Structural genomic rearrangements are frequent findings in human cancers. Therefore, papillary thyroid carcinomas (PTCs were investigated for chromosomal aberrations and rearrangements of the RET proto-oncogene. For this purpose, primary cultures from 23 PTC have been established and metaphase preparations were analysed by spectral karyotyping (SKY. In addition, interphase cell preparations of the same cases were investigated by fluorescence in situ hybridisation (FISH for the presence of RET/PTC rearrangements using RET-specific DNA probes. SKY analysis of PTC revealed structural aberrations of chromosome 11 and several numerical aberrations with frequent loss of chromosomes 20, 21, and 22. FISH analysis for RET/PTC rearrangements showed prevalence of this rearrangement in 72% (16 out of 22 of cases. However, only subpopulations of tumour cells exhibited this rearrangement indicating genetic heterogeneity. The comparison of visual and automated scoring of FISH signals revealed concordant results in 19 out of 22 cases (87% indicating reliable scoring results using the optimised scoring parameter for RET/PTC with the automated Metafer4 system. It can be concluded from this study that genomic rearrangements are frequent in PTC and therefore important events in thyroid carcinogenesis.

  4. REARRANGEMENT IN THE B-GENOME FROM DIPLOID PROGENITOR TO WHEAT ALLOPOLYPOLID

    Directory of Open Access Journals (Sweden)

    Salina E.A.

    2012-08-01

    Full Text Available Three key periods that were accompanied by considerable rearrangements in the B genome of wheat and its progenitor can be considered. The first period covers the period from the divergence of diploid Triticum and Aegilops species from their common progenitor (2.5–6 million years ago to formation of the tetraploid T. diccocoides (about 500 thousand years ago. Significant genomic rearrangements in the diploid progenitor of the B genome, Ae. speltoides (SS genome, involved a considerable amplification of repeated DNA sequences, which led to an increase in the number of heterochromatin blocks on chromosomes relative to other diploid Aegilops and Triticum species. Our analysis has demonstrated that during this period the Spelt1 repeats intensively amplified as well as several mobile elements proliferated, in particular, the genome-specific gypsy LTR-retrotransposon Fatima and CACTA DNA-transposon Caspar. The second period in the B-genome evolution was associated with the emergence of tetraploid (BBAA genome and its subsequent evolution. The third most important event leading to the next rearrangement of the B genome took place relatively recently, 7000–9500 years ago, being associated with the emergence of hexaploid wheat with the genomic formula BBAADD. The evolution of the B/S genome involved intergenomic and intragenomic translocations and chromosome inversions. So far, five rearrangements in the B-genome chromosomes of polyploid wheats has been observed and described; the majority of them took place during the formation and evolution of tetraploid species. The mapping of the S-genome chromosomes and comparison with the B-genome chromosome maps have demonstrated that individual rearrangements pre-existed in Ae. speltoides; moreover, Ae. speltoides is polymorphic for these rearrangements.Chromosome 5B is nearly 870 Mbp (5BL = 580 Mbp and 5BS = 290 Mbp and is known to carry important genes controlling the key aspects of wheat biology, in

  5. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  6. Quantum control of the photoinduced Wolff rearrangement of diazonaphthoquinone in the condensed phase

    Energy Technology Data Exchange (ETDEWEB)

    Wolpert, Daniel; Gerber, Gustav; Brixner, Tobias [Physikalisches Institut, Universitaet Wuerzburg, Am Hubland, 97074 Wuerzburg (Germany); Schade, Marco; Langhojer, Florian [Institut fuer Physikalische Chemie, Universitaet Wuerzburg, Am Hubland, 97074 Wuerzburg (Germany)], E-mail: brixner@phys-chemie.uni-wuerzburg.de

    2008-04-14

    A shaped UV pump-MIR probe setup is employed for quantum control of the photoinduced Wolff rearrangement reaction of diazonaphthoquinone (DNQ) dissolved in methanol, yielding a ketene photoproduct. Time-resolved vibrational spectroscopy is a well-suited tool to monitor a photoreaction in the liquid phase as the narrow vibrational lines allow the observation of structural changes. Especially in the mid-infrared region, marker modes originating from different photoproducts can be identified unambiguously providing suitable feedback signals for open-loop or closed-loop control schemes. We report an experiment where the initiation of a complicated structural change of a molecule, involving bond cleavage and rearrangement, in the liquid phase can be controlled and mechanistic insight is obtained. Single-parameter scans show that the molecule is sensitive to intrapulse dumping during the excitation. Adaptive optimizations lead to pulse structures which can be understood consistently with this dumping mechanism.

  7. TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemia

    DEFF Research Database (Denmark)

    Willer, Anton; Jakobsen, Janus Schou; Ohlsson, E

    2015-01-01

    orchestrates a transcriptional program required for the maintenance of MLL-rearranged acute myeloid leukemia (AML). TGIF1/TGIF2 are relatively uncharacterized TALE transcription factors, which, in contrast to the remaining family, have been shown to act as transcriptional repressors. Given the general......Members of the TALE (three-amino-acid loop extension) family of atypical homeodomain-containing transcription factors are important downstream effectors of oncogenic fusion proteins involving the mixed lineage leukemia (MLL) gene. A well-characterized member of this protein family is MEIS1, which...... influence the clinical outcome. Collectively, these findings demonstrate that TALE family members can act both positively and negatively on transcriptional programs responsible for leukemic maintenance and provide novel insights into the regulatory gene expression circuitries in MLL-rearranged AML.Leukemia...

  8. Aza Cope Rearrangement of Propargyl Enammonium Cations Catalyzed By a Self-Assembled `Nanozyme

    Energy Technology Data Exchange (ETDEWEB)

    Hastings, Courntey J.; Fiedler, Dorothea; Bergman, Robert G.; Raymond, Kenneth N.

    2008-02-27

    The tetrahedral [Ga{sub 4}L{sub 6}]{sup 12-} assembly (L = N,N-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene) encapsulates a variety of cations, including propargyl enammonium cations capable of undergoing the aza Cope rearrangement. For propargyl enammonium substrates that are encapsulated in the [Ga{sub 4}L{sub 6}]{sup 12-} assembly, rate accelerations of up to 184 are observed when compared to the background reaction. After rearrangement, the product iminium ion is released into solution and hydrolyzed allowing for catalytic turnover. The activation parameters for the catalyzed and uncatalyzed reaction were determined, revealing that a lowered entropy of activation is responsible for the observed rate enhancements. The catalyzed reaction exhibits saturation kinetics; the rate data obey the Michaelis-Menten model of enzyme kinetics, and competitive inhibition using a non-reactive guest has been demonstrated.

  9. Alignment-free microbial phylogenomics under scenarios of sequence divergence, genome rearrangement and lateral genetic transfer.

    Science.gov (United States)

    Bernard, Guillaume; Chan, Cheong Xin; Ragan, Mark A

    2016-07-01

    Alignment-free (AF) approaches have recently been highlighted as alternatives to methods based on multiple sequence alignment in phylogenetic inference. However, the sensitivity of AF methods to genome-scale evolutionary scenarios is little known. Here, using simulated microbial genome data we systematically assess the sensitivity of nine AF methods to three important evolutionary scenarios: sequence divergence, lateral genetic transfer (LGT) and genome rearrangement. Among these, AF methods are most sensitive to the extent of sequence divergence, less sensitive to low and moderate frequencies of LGT, and most robust against genome rearrangement. We describe the application of AF methods to three well-studied empirical genome datasets, and introduce a new application of the jackknife to assess node support. Our results demonstrate that AF phylogenomics is computationally scalable to multi-genome data and can generate biologically meaningful phylogenies and insights into microbial evolution.

  10. T-cell receptor gene rearrangement in Epstein-Barr virus infectious mononucleosis.

    Science.gov (United States)

    Marbello, L; Riva, M; Veronese, S; Nosari, A M; Ravano, E; Colosimo, A; Paris, L; Morra, E

    2012-09-01

    This report describes the case of a previously healthy young man who presented with fever, pharyngitis, cervical lymphadenopathy, lymphocytosis, and severe thrombocytopenia. Serological tests for Epstein-Barr virus were diagnostic of a primary Epstein-Barr virus infectious mononucleosis but severe thrombocytopenia aroused the suspicion of a lymphoproliferative disease. T-cell receptor gene analysis performed on peripheral and bone marrow blood revealed a T-cell receptor γ-chain rearrangement without the evidence of malignancy using standard histologic and immunophenotype studies. Signs and symptoms of the infectious disease, blood count, and T-cell receptor gene rearrangement resolved with observation without the evidence of emergence of a lymphoproliferative disease. In the contest of a suspected lymphoproliferative disease, molecular results should be integrated with all available data for an appropriate diagnosis.

  11. Transverse momentum in the multiple production processes and urbaryon rearrangement model

    International Nuclear Information System (INIS)

    Igarashi, Yuji; Matsuoka, Takeo; Sawada, Shoji

    1977-01-01

    Several characteristic features of p sub(T) distribution are studied on the basis of the multibody amplitude of urbaryon rearrangement model which is a generalization of the all-angle formula for two-body hadronic reactions at high energies. Several characteristic structures of amplitudes of the model are compared with other models. The seagull behaviour observed in the longitudinal momentum dependence of the average p sub(T) of pion is explained as a result of long range correlation among the hadrons linked with each other by rearranged urbaryons. It is also shown that the increase of average p sub(T) with particle mass and the dependence on unitary spins such as strangeness and charm are well reproduced by the model amplitudes. (auth.)

  12. The role of hydrogen bonding on kinetics of rearrangement of heterocyclic aldoximes in perchloric acide

    International Nuclear Information System (INIS)

    Azzouz, A.S.; Abdullah, K.A.; Al-Niemi, I.

    1995-01-01

    Four paris of syn and anti aromatic heterocyclic aldoximes as 2-thiophenealdoxime, 2- furfuraladoxime, 2-pyridinealdoxime and 2-pyrrolealdoxime are prepared. The strcutures of these geometrical isomers are confirmed by the meaasurements of their U.V. I, R and melting points. Experiments show the existence of these aldoximers in an intramolecular hy-drogen bonding with variable strength depending on the hetero ztoms in the aldoximes. The first order rate constants of the rearrangement of syn aldoximes follow the order of hetero S>O>N, while the anti aldoximes show irregular order, Factors governing the aniti constants of the rearrangement of syn and anti aldoximes are analysed. Activation parameters are estimated and discussed on the basis of isokinetic relation-ship. The differences in physical and spectroscpic behavior of aldoximes lead to an important suggestion regarding the configuration of oxime. (author). 27 refs., 2 figs., 2 tabs

  13. The Role of SPINK1 in ETS Rearrangement Negative Prostate Cancers

    Science.gov (United States)

    Tomlins, Scott A.; Rhodes, Daniel R.; Yu, Jianjun; Varambally, Sooryanarayana; Mehra, Rohit; Perner, Sven; Demichelis, Francesca; Helgeson, Beth E.; Laxman, Bharathi; Morris, David S.; Cao, Qi; Cao, Xuhong; Andrén, Ove; Fall, Katja; Johnson, Laura; Wei, John T.; Shah, Rajal B.; Al-Ahmadie, Hikmat; Eastham, James A.; Eggener, Scott E.; Fine, Samson W.; Hotakainen, Kristina; Stenman, Ulf-Håkan; Tsodikov, Alex; Gerald, William L.; Lilja, Hans; Reuter, Victor E.; Kantoff, Phillip W.; Scardino, Peter T.; Rubin, Mark A.; Bjartell, Anders S.; Chinnaiyan, Arul M.

    2009-01-01

    Summary ETS gene fusions have been characterized in a majority of prostate cancers, however the key molecular alterations in ETS negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier-expression exclusively in a subset of ETS rearrangement negative cancers (~10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier-expression can be detected non-invasively in urine and observed that SPINK1 outlier-expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier-expression model, and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement negative prostate cancers. PMID:18538735

  14. TQ-bifurcations in discrete dynamical systems: Analysis of qualitative rearrangements of the oscillation mode

    Energy Technology Data Exchange (ETDEWEB)

    Makarenko, A. V., E-mail: avm.science@mail.ru [Constructive Cybernetics Research Group (Russian Federation)

    2016-10-15

    A new class of bifurcations is defined in discrete dynamical systems, and methods for their diagnostics and the analysis of their properties are presented. The TQ-bifurcations considered are implemented in discrete mappings and are related to the qualitative rearrangement of the shape of trajectories in an extended space of states. Within the demonstration of the main capabilities of the toolkit, an analysis is carried out of a logistic mapping in a domain to the right of the period-doubling limit point. Five critical values of the parameter are found for which the geometric structure of the trajectories of the mapping experiences a qualitative rearrangement. In addition, an analysis is carried out of the so-called “trace map,” which arises in the problems of quantum-mechanical description of various properties of discrete crystalline and quasicrystalline lattices.

  15. Theoretical Studies of [2,3]-Sigmatropic Rearrangements of Allylic Selenoxides and Selenimides

    Directory of Open Access Journals (Sweden)

    Sonia Antony

    2009-08-01

    Full Text Available Density-functional theory is used to model the endo and exo transition states for [2,3]-sigmatropic rearrangement of allylic aryl-selenoxides and -selenimides. The endo transition state is generally preferred for selenoxides if there is no substitution at the 2 position of the allyl group. Based upon the relative energies of the endo and exo transition states, enantioselectivity of rearrangements is expected to be greatest for molecules with substitutions at the 1- or (E-3- position of the allyl group. Ortho substitution of a nitro group on the ancillary selenoxide phenyl ring reduces the activation barriers, increases the difference between the endo and exo activation barriers and shifts the equilibrium toward products.

  16. A Wittig-olefination-Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis.

    Science.gov (United States)

    Kulkarni, Mukund G; Desai, Mayur P; Birhade, Deekshaputra R; Shaikh, Yunus B; Dhatrak, Ajit N; Gannimani, Ramesh

    2012-01-01

    Efficient syntheses are described for the synthetically important 3-methylquinoline-4-carbaldehydes 6a-h from o-nitrobenzaldehydes 1a-h employing a Wittig-olefination-Claisen-rearrangement protocol. The Wittig reaction of o-nitrobenzaldehydes with crotyloxymethylene triphenylphosphorane afforded crotyl vinyl ethers 2a-h, which on heating under reflux in xylene underwent Claisen rearrangement to give 4-pentenals 3a-h. Protection of the aldehyde group of the 4-pentenals as acetals 4a-h and subsequent oxidative cleavage of the terminal olefin furnished nitroaldehydes 5a-h. Reductive cyclization of these nitroaldehydes yielded the required 3-methylquinoline-4-carbaldehydes 6a-h in excellent yields. Therefore, an efficient method was developed for the preparation of 3-methylquinoline-4-carbaldehydes from o-nitrobenzaldehydes in a simple five-step procedure.

  17. A Wittig-olefination–Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis

    Directory of Open Access Journals (Sweden)

    Mukund G. Kulkarni

    2012-10-01

    Full Text Available Efficient syntheses are described for the synthetically important 3-methylquinoline-4-carbaldehydes 6a–h from o-nitrobenzaldehydes 1a–h employing a Wittig-olefination–Claisen-rearrangement protocol. The Wittig reaction of o-nitrobenzaldehydes with crotyloxymethylene triphenylphosphorane afforded crotyl vinyl ethers 2a–h, which on heating under reflux in xylene underwent Claisen rearrangement to give 4-pentenals 3a–h. Protection of the aldehyde group of the 4-pentenals as acetals 4a–h and subsequent oxidative cleavage of the terminal olefin furnished nitroaldehydes 5a–h. Reductive cyclization of these nitroaldehydes yielded the required 3-methylquinoline-4-carbaldehydes 6a–h in excellent yields. Therefore, an efficient method was developed for the preparation of 3-methylquinoline-4-carbaldehydes from o-nitrobenzaldehydes in a simple five-step procedure.

  18. A Wittig-olefination–Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis

    Science.gov (United States)

    Desai, Mayur P; Birhade, Deekshaputra R; Shaikh, Yunus B; Dhatrak, Ajit N; Gannimani, Ramesh

    2012-01-01

    Summary Efficient syntheses are described for the synthetically important 3-methylquinoline-4-carbaldehydes 6a–h from o-nitrobenzaldehydes 1a–h employing a Wittig-olefination–Claisen-rearrangement protocol. The Wittig reaction of o-nitrobenzaldehydes with crotyloxymethylene triphenylphosphorane afforded crotyl vinyl ethers 2a–h, which on heating under reflux in xylene underwent Claisen rearrangement to give 4-pentenals 3a–h. Protection of the aldehyde group of the 4-pentenals as acetals 4a–h and subsequent oxidative cleavage of the terminal olefin furnished nitroaldehydes 5a–h. Reductive cyclization of these nitroaldehydes yielded the required 3-methylquinoline-4-carbaldehydes 6a–h in excellent yields. Therefore, an efficient method was developed for the preparation of 3-methylquinoline-4-carbaldehydes from o-nitrobenzaldehydes in a simple five-step procedure. PMID:23209506

  19. Fries rearrangement of naphthyl benzoates; Ansoku kosan naphthyl no fries ten`i

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, J.; Haraguchi, Y.; Iwaki, T.; Yamana, Sasaki, H. [Tottori University, Tottori (Japan). Faculty of Engineering

    1996-10-10

    When 1-naphthyl benzoate (1{alpha}) was boiled with anhydrous aluminum chloride (AlCl3) in chlorobenzene, 2-benzoyl-l-naphthol(2) and 4-benzoyl-l-naphthol(3) were obtained as the rearrangement products. A product 1-benzoyl-2-naphthol (4) was given from 2-naphthyl benzoate (1{beta}) under the same reaction conditions. It seems that 2 and 3 are formed via intramolecular pathway from 1{alpha}. Other ester 1{beta} may proceed via both inter- and intramolecular pathways to give 4. Retro-Fries rearrangement of 2 and 3 to 1{alpha} took place in the presence of AlCl3 in boiling chlorobenzene. The compound 4 `however` was almost recovered the reaction of 4 with AlCl3 in chlorobenzene at refluxed temperature. 25 refs., 3 figs., 1 tab.

  20. Chromosomal instability mediated by non-B DNA: cruciform conformation and not DNA sequence is responsible for recurrent translocation in humans.

    Science.gov (United States)

    Inagaki, Hidehito; Ohye, Tamae; Kogo, Hiroshi; Kato, Takema; Bolor, Hasbaira; Taniguchi, Mariko; Shaikh, Tamim H; Emanuel, Beverly S; Kurahashi, Hiroki

    2009-02-01

    Chromosomal aberrations have been thought to be random events. However, recent findings introduce a new paradigm in which certain DNA segments have the potential to adopt unusual conformations that lead to genomic instability and nonrandom chromosomal rearrangement. One of the best-studied examples is the palindromic AT-rich repeat (PATRR), which induces recurrent constitutional translocations in humans. Here, we established a plasmid-based model that promotes frequent intermolecular rearrangements between two PATRRs in HEK293 cells. In this model system, the proportion of PATRR plasmid that extrudes a cruciform structure correlates to the levels of rearrangement. Our data suggest that PATRR-mediated translocations are attributable to unusual DNA conformations that confer a common pathway for chromosomal rearrangements in humans.

  1. Migration of the phosphoryl group in the photochemical and thermal Wolff rearrangement

    International Nuclear Information System (INIS)

    Polozov, A.M.; Pavlov, V.A.; Polezhaeva, N.A.; Liorber, B.G.; Tarzivolova, T.A.; Arbuzov, B.A.

    1986-01-01

    For the study of the rearrangement the authors prepared methyl 2-diazo-3-(diisopropoxyphosphinyl)-3-oxopropinoate by the diazo-transfer method. By the same method they prepared methyl 2-diazo-3-(diethoxyphosphinyl)-3-oxopropioinate. Unlike its carbonyl analog, the first compound proved to be extremely unstable. In vacuum distillation or chromatography on silica gel it decomposes. The structure of the ester was proved by elemental analysis and methods of 1 H and 31 P NMR spectroscopy

  2. Guidelines for the rearrangement of Auschwitz Museum based on web pictures analysis

    OpenAIRE

    Mantyka, M. (Marta); Stachura, E. (Ewa)

    2016-01-01

    This paper attempts to answer the question whether the exhibition of the Auschwitz Museum communicates its message properly to the audience or it should be modernised/ rearranged. The aim of the study is so to investigate the way visitors currently look at Auschwitz via the filter of social media. Between November 2014 until January 2015 the number of Instagram pictures with hashtag “Auschwitz” posted on-line nearly doubled to astonishing 80.000 images. In August 2016 the numbe...

  3. Hadronic J/psi and charmed particle production and correlating quark rearrangement model

    International Nuclear Information System (INIS)

    Nishitani, Tadashi

    1979-01-01

    On the basis of the correlating quark rearrangement model, the exclusive and inclusive production cross sections of J/psi and charmed particles in hadron collisions are calculated. It is shown that the inclusive production cross section of charmed particles is several tens of μb at p sub( l) -- 100 GeV/c in hadron collisions. The OZI rule is discussed in connection with the production mechanism of J/psi particles. (author)

  4. The effect of substrate size in the Beckmann rearrangement: MOFs vs. zeolites

    Czech Academy of Sciences Publication Activity Database

    Opanasenko, Maksym; Shamzhy, Mariya; Lamač, Martin; Čejka, Jiří

    2013-01-01

    Roč. 204, APR 2013 (2013), s. 94-100 ISSN 0920-5861 R&D Projects: GA ČR GBP106/12/G015 Grant - others:European Commission(XE) FP7/2007-2013, contract 228862 Institutional support: RVO:61388955 Keywords : Beckmann rearrangement * oximes * CuBTC Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.309, year: 2013

  5. Meiotic Recombination Analyses in Pigs Carrying Different Balanced Structural Chromosomal Rearrangements.

    Directory of Open Access Journals (Sweden)

    Nicolas Mary

    Full Text Available Correct pairing, synapsis and recombination between homologous chromosomes are essential for normal meiosis. All these events are strongly regulated, and our knowledge of the mechanisms involved in this regulation is increasing rapidly. Chromosomal rearrangements are known to disturb these processes. In the present paper, synapsis and recombination (number and distribution of MLH1 foci were studied in three boars (Sus scrofa domestica carrying different chromosomal rearrangements. One (T34he was heterozygote for the t(3;4(p1.3;q1.5 reciprocal translocation, one (T34ho was homozygote for that translocation, while the third (T34Inv was heterozygote for both the translocation and a pericentric inversion inv(4(p1.4;q2.3. All three boars were normal for synapsis and sperm production. This particular situation allowed us to rigorously study the impact of rearrangements on recombination. Overall, the rearrangements induced only minor modifications of the number of MLH1 foci (per spermatocyte or per chromosome and of the length of synaptonemal complexes for chromosomes 3 and 4. The distribution of MLH1 foci in T34he was comparable to that of the controls. Conversely, the distributions of MLH1 foci on chromosome 4 were strongly modified in boar T34Inv (lack of crossover in the heterosynaptic region of the quadrivalent, and crossover displaced to the chromosome extremities, and also in boar T34ho (two recombination peaks on the q-arms compared with one of higher magnitude in the controls. Analyses of boars T34he and T34Inv showed that the interference was propagated through the breakpoints. A different result was obtained for boar T34ho, in which the breakpoints (transition between SSC3 and SSC4 chromatin on the bivalents seemed to alter the transmission of the interference signal. Our results suggest that the number of crossovers and crossover interference could be regulated by partially different mechanisms.

  6. DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution

    OpenAIRE

    Falconer, Ester; Hills, Mark; Naumann, Ulrike; Poon, Steven S. S.; Chavez, Elizabeth A.; Sanders, Ashley D.; Zhao, Yongjun; Hirst, Martin; Lansdorp, Peter M.

    2012-01-01

    DNA rearrangements such as sister chromatid exchanges (SCEs) are sensitive indicators of genomic stress and instability, but they are typically masked by single-cell sequencing techniques. We developed Strand-seq to independently sequence parental DNA template strands from single cells, making it possible to map SCEs at orders-of-magnitude greater resolution than was previously possible. On average, murine embryonic stem (mES) cells exhibit eight SCEs, which are detected at a resolution of up...

  7. Immunoglobulin gene expression and regulation of rearrangement in kappa transgenic mice

    International Nuclear Information System (INIS)

    Ritchie, K.A.

    1986-01-01

    Transgenic mice were produced by microinjection of the functionally rearranged immunoglobulin kappa gene from the myeloma MOPC-21 into the male pronucleus of fertilized mouse eggs, and implantation of the microinjected embryos into foster mothers. Mice that integrated the injected gene were detected by hybridizing tail DNA dots with radioactively labelled pBR322 plasmid DNA, which detects pBR322 sequences left as a tag on the microinjected DNA. Mice that integrated the injected gene (six males) were mated and the DNA, RNA and serum kappa chains of their offspring were analyzed. A rabbit anti-mouse kappa chain antiserum was also produced for use in detection of mouse kappa chains on protein blots. Hybridomas were produced from the spleen cells of these kappa transgenic mice to immortalize representative B cells and to investigate expression of the transgenic kappa gene, its effect on allelic exclusion, and its effect on the control of light chain gene rearrangement and expression. The results show that the microinjected DNA is integrated as concatamers in unique single or, rarely, two separate sites in the genome. The concatamers are composed of several copies (16 to 64) of injected DNA arranged in a head to tail fashion. The transgene is expressed into protein normally and in a tissue specific fashion. For the first time in these transgenic mice, all tissues contain a functionally rearranged and potentially expressible immunoglobulin gene. The transgene is expressed only in B cells and not in hepatocytes, for example. This indicates that rearrangement of immunoglobulin genes is necessary but not sufficient for the tissue specific expression of these genes by B cells

  8. The role of chromosomal rearrangements in the evolution of Silene latifolia sex chromosomes

    Czech Academy of Sciences Publication Activity Database

    Hobza, Roman; Kejnovský, Eduard; Vyskot, Boris; Widmer, A.

    2007-01-01

    Roč. 278, č. 6 (2007), s. 633-638 ISSN 1617-4615 R&D Projects: GA ČR(CZ) GA204/05/2097; GA ČR(CZ) GA521/06/0056 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : chromosomal rearrangements * sex chromosomes * FISH Subject RIV: BO - Biophysics Impact factor: 2.978, year: 2007

  9. Cinteny: flexible analysis and visualization of synteny and genome rearrangements in multiple organisms

    Directory of Open Access Journals (Sweden)

    Meller Jaroslaw

    2007-03-01

    Full Text Available Abstract Background Identifying syntenic regions, i.e., blocks of genes or other markers with evolutionary conserved order, and quantifying evolutionary relatedness between genomes in terms of chromosomal rearrangements is one of the central goals in comparative genomics. However, the analysis of synteny and the resulting assessment of genome rearrangements are sensitive to the choice of a number of arbitrary parameters that affect the detection of synteny blocks. In particular, the choice of a set of markers and the effect of different aggregation strategies, which enable coarse graining of synteny blocks and exclusion of micro-rearrangements, need to be assessed. Therefore, existing tools and resources that facilitate identification, visualization and analysis of synteny need to be further improved to provide a flexible platform for such analysis, especially in the context of multiple genomes. Results We present a new tool, Cinteny, for fast identification and analysis of synteny with different sets of markers and various levels of coarse graining of syntenic blocks. Using Hannenhalli-Pevzner approach and its extensions, Cinteny also enables interactive determination of evolutionary relationships between genomes in terms of the number of rearrangements (the reversal distance. In particular, Cinteny provides: i integration of synteny browsing with assessment of evolutionary distances for multiple genomes; ii flexibility to adjust the parameters and re-compute the results on-the-fly; iii ability to work with user provided data, such as orthologous genes, sequence tags or other conserved markers. In addition, Cinteny provides many annotated mammalian, invertebrate and fungal genomes that are pre-loaded and available for analysis at http://cinteny.cchmc.org. Conclusion Cinteny allows one to automatically compare multiple genomes and perform sensitivity analysis for synteny block detection and for the subsequent computation of reversal distances

  10. Rearranging the lenslet array of the compact passive interference imaging system with high resolution

    Science.gov (United States)

    Liu, Gang; Wen, Desheng; Song, Zongxi

    2017-10-01

    With the development of aeronautics and astronautics, higher resolution requirement of the telescope was necessary. However, the increase in resolution of conventional telescope required larger apertures, whose size, weight and power consumption could be prohibitively expensive. This limited the further development of the telescope. This paper introduced a new imaging technology using interference—Compact Passive Interference Imaging Technology with High Resolution, and proposed a rearranging method for the arrangement of the lenslet array to obtain continuously object spatial frequency.

  11. Exploiting the CNC side chain in heterocyclic rearrangements: synthesis of 4(5)-acylamino-imidazoles.

    Science.gov (United States)

    Piccionello, Antonio Palumbo; Buscemi, Silvestre; Vivona, Nicolò; Pace, Andrea

    2010-08-06

    A new variation on the Boulton-Katritzky reaction is reported, namely, involving use of a CNC side chain. A novel Montmorillonite-K10 catalyzed nonreductive transamination of a 3-benzoyl-1,2,4-oxadiazole afforded a 3-(alpha-aminobenzyl)-1,2,4-oxadiazole, which was condensed with benzaldehydes to afford the corresponding imines. In the presence of strong base, these imines underwent Boulton-Katritzky-type rearrangement to afford novel 4(5)-acylaminoimidazoles.

  12. Recurrent Reciprocal Genomic Rearrangements of 17q12 Are Associated with Renal Disease, Diabetes, and Epilepsy

    OpenAIRE

    Mefford, Heather C. ; Clauin, Séverine ; Sharp, Andrew J. ; Moller, Rikke S. ; Ullmann, Reinhard ; Kapur, Raj ; Pinkel, Dan ; Cooper, Gregory M. ; Ventura, Mario ; Ropers, H. Hilger ; Tommerup, Niels ; Eichler, Evan E. ; Bellanne-Chantelot, Christine 

    2007-01-01

    Most studies of genomic disorders have focused on patients with cognitive disability and/or peripheral nervous system defects. In an effort to broaden the phenotypic spectrum of this disease model, we assessed 155 autopsy samples from fetuses with well-defined developmental pathologies in regions predisposed to recurrent rearrangement, by array-based comparative genomic hybridization. We found that 6% of fetal material showed evidence of microdeletion or microduplication, including three inde...

  13. Automation of ALK gene rearrangement testing with fluorescence in situ hybridization (FISH): a feasibility study.

    Science.gov (United States)

    Zwaenepoel, Karen; Merkle, Dennis; Cabillic, Florian; Berg, Erica; Belaud-Rotureau, Marc-Antoine; Grazioli, Vittorio; Herelle, Olga; Hummel, Michael; Le Calve, Michele; Lenze, Dido; Mende, Stefanie; Pauwels, Patrick; Quilichini, Benoit; Repetti, Elena

    2015-02-01

    In the past several years we have observed a significant increase in our understanding of molecular mechanisms that drive lung cancer. Specifically in the non-small cell lung cancer sub-types, ALK gene rearrangements represent a sub-group of tumors that are targetable by the tyrosine kinase inhibitor Crizotinib, resulting in significant reductions in tumor burden. Phase II and III clinical trials were performed using an ALK break-apart FISH probe kit, making FISH the gold standard for identifying ALK rearrangements in patients. FISH is often considered a labor and cost intensive molecular technique, and in this study we aimed to demonstrate feasibility for automation of ALK FISH testing, to improve laboratory workflow and ease of testing. This involved automation of the pre-treatment steps of the ALK assay using various protocols on the VP 2000 instrument, and facilitating automated scanning of the fluorescent FISH specimens for simplified enumeration on various backend scanning and analysis systems. The results indicated that ALK FISH can be automated. Significantly, both the Ikoniscope and BioView system of automated FISH scanning and analysis systems provided a robust analysis algorithm to define ALK rearrangements. In addition, the BioView system facilitated consultation of difficult cases via the internet. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Low rate of interchromosomal rearrangements during old radiation of gekkotan lizards (Squamata: Gekkota).

    Science.gov (United States)

    Johnson Pokorná, Martina; Trifonov, Vladimir A; Rens, Willem; Ferguson-Smith, Malcolm A; Kratochvíl, Lukáš

    2015-06-01

    Gekkotan lizards are a highly specious (∼1600 described species) clade of squamate lizards with nearly cosmopolitan distribution in warmer areas. The clade is primarily nocturnal and forms an ecologically dominant part of the world nocturnal herpetofauna. However, molecular cytogenetic methods to study the evolution of karyotypes have not been widely applied in geckos. Our aim here was to uncover the extent of chromosomal rearrangements across the whole group Gekkota and to search for putative synapomorphies supporting the newly proposed phylogenetic relationships within this clade. We applied cross-species chromosome painting with the recently derived whole-chromosomal probes from the gekkonid species Gekko japonicus to members of the major gekkotan lineages. We included members of the families Diplodactylidae, Carphodactylidae, Pygopodidae, Eublepharidae, Phyllodactylidae and Gekkonidae. Our study demonstrates relatively high chromosome conservatism across the ancient group of gekkotan lizards. We documented that many changes in chromosomal shape across geckos can be attributed to intrachromosomal rearrangements. The documented rearrangements are not totally in agreement with the recently newly erected family Phyllodactylidae. The results also pointed to homoplasy, particularly in the reuse of chromosome breakpoints, in the evolution of gecko karyotypes.

  15. Conditional genomic rearrangement by designed meiotic recombination using VDE (PI-SceI) in yeast.

    Science.gov (United States)

    Fukuda, Tomoyuki; Ohya, Yoshikazu; Ohta, Kunihiro

    2007-10-01

    Meiotic recombination plays critical roles in the acquisition of genetic diversity and has been utilized for conventional breeding of livestock and crops. The frequency of meiotic recombination is normally low, and is extremely low in regions called "recombination cold domains". Here, we describe a new and highly efficient method to modulate yeast meiotic gene rearrangements using VDE (PI-SceI), an intein-encoded endonuclease that causes an efficient unidirectional meiotic gene conversion at its recognition sequence (VRS). We designed universal targeting vectors, by use of which the strain that inserts the VRS at a desired site is acquired. Meiotic induction of the strains provided unidirectional gene conversions and frequent genetic rearrangements of flanking genes with little impact on cell viability. This system thus opens the way for the designed modulation of meiotic gene rearrangements, regardless of recombinational activity of chromosomal domains. Finally, the VDE-VRS system enabled us to conduct meiosis-specific conditional knockout of genes where VDE-initiated gene conversion disrupts the target gene during meiosis, serving as a novel approach to examine the functions of genes during germination of resultant spores.

  16. Symmetry Breaking in NMR Spectroscopy: The Elucidation of Hidden Molecular Rearrangement Processes

    Directory of Open Access Journals (Sweden)

    Michael J. McGlinchey

    2014-08-01

    Full Text Available Variable-temperature NMR spectroscopy is probably the most convenient and sensitive technique to monitor changes in molecular structure in solution. Rearrangements that are rapid on the NMR time-scale exhibit simplified spectra, whereby non-equivalent nuclear environments yield time-averaged resonances. At lower temperatures, when the rate of exchange is sufficiently reduced, these degeneracies are split and the underlying “static” molecular symmetry, as seen by X-ray crystallography, becomes apparent. Frequently, however, such rearrangement processes are hidden, even when they become slow on the NMR time-scale, because the molecular point group remains unchanged. Judicious symmetry breaking, such as by substitution of a molecular fragment by a similar, but not identical moiety, or by the incorporation of potentially diastereotopic (chemically non-equivalent nuclei, allows the elucidation of the kinetics and energetics of such processes. Examples are chosen that include a wide range of rotations, migrations and other rearrangements in organic, inorganic and organometallic chemistry.

  17. Bond rearrangement caused by sudden single and multiple ionization of water molecules

    International Nuclear Information System (INIS)

    Ben-Itzhak, I.; Sayler, A. Max; Leonard, M.; Maseberg, J.W.; Hathiramani, D.; Wells, E.; Smith, M.A.; Xia, Jiangfan; Wang, Pengqian; Carnes, K.D.; Esry, B.D.

    2005-01-01

    Bond rearrangement, namely the dissociation of water into H 2 + +O q+ following ionization by fast proton and highly charged ion impact, was investigated. Single ionization by fast proton impact exhibits a strong isotopic effect, the dissociation of H 2 O + ->H 2 + +O being about twice as likely as D 2 O + ->D 2 + +O, with HDO + ->HD + +O in between. This suggests that the bond rearrangement does not happen during the slow dissociation, but rather during the very fast ionization, and thus H 2 + should also be produced when the water molecule is multiply ionized. We observed that the H 2 + +O + and H 2 + +O 2+ production in 1MeV/amu F 7+ +H 2 O collisions are 0.209+/-0.006% and 0.0665+/-0.003%, respectively, of the main double-ionization dissociation product, H 2 O 2+ ->H + +OH + . This ratio is similar to the triple to double ionization ratio in similar collisions with atomic targets thus suggesting that the bond-rearrangement fraction out of each ionization level is approximately constant. Similar dissociation channels in the heavier water isotopes, which are expected to be smaller, are under study. Finally, the fragmentation of HDO exhibits very strong isotopic preference for breaking the OH bond over the OD bond

  18. The formation and recovery of two-break chromosome rearrangements from irradiated spermatozoa of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Leigh, B.

    1978-01-01

    Chromosome and chromatid-type rearrangements can be induced by exposure of spermatozoa of Drosophila to ionising radiation. A model, proposed to explain the formation and recovery of compound autosomes, has been extended to account for the induction of centric fragments capped by a duplication of paternal chromosome material. Three basic assumptions have been used; (1) that the sperm nucleus contains a haploid set of unreplicated chromosomes, (2) that the broken chromosome ends can be joined together before or after replication, and (3) that one of the first two cleavage nuclei may be lost and an adult organism derived from the other. The present paper reports a theoretical application of this combination of aasumptions to the general case of the formation and recovery of two-break rearrangements. This has led to an elucidation of the relation between repeats, compounds, fragments, and deficiencies on the one hand and inversions and translocations on the other hand. Dicentric chromosomes and segmental aneuploidy can be simply explained. A selective screen is formed by the segregation of chromatid rearrangements and the aneuploidy tolerance levels of the early cleavage nuclei. Thus there is an alternative way of explaining observations which might indicate preferential breakage or joining

  19. Measurement of correlations between low-frequency vibrational modes and particle rearrangements in quasi-two-dimensional colloidal glasses

    NARCIS (Netherlands)

    Chen, K.; Manning, M.L.; Yunker, P.J.; Ellenbroek, W.G.; Zhang, Zexin; Liu, Andrea J.; Yodh, A.G.

    2011-01-01

    We investigate correlations between low-frequency vibrational modes and rearrangements in two-dimensional colloidal glasses composed of thermosensitive microgel particles, which readily permit variation of the sample packing fraction. At each packing fraction, the particle displacement covariance

  20. Measurement of correlations between low-frequency vibrational modes and particle rearrangements in quasi-two-dimensional colloidal glasses.

    Science.gov (United States)

    Chen, Ke; Manning, M L; Yunker, Peter J; Ellenbroek, Wouter G; Zhang, Zexin; Liu, Andrea J; Yodh, A G

    2011-09-02

    We investigate correlations between low-frequency vibrational modes and rearrangements in two-dimensional colloidal glasses composed of thermosensitive microgel particles, which readily permit variation of the sample packing fraction. At each packing fraction, the particle displacement covariance matrix is measured and used to extract the vibrational spectrum of the "shadow" colloidal glass (i.e., the particle network with the same geometry and interactions as the sample colloid but absent damping). Rearrangements are induced by successive, small reductions in the packing fraction. The experimental results suggest that low-frequency quasilocalized phonon modes in colloidal glasses, i.e., modes that present low energy barriers for system rearrangements, are spatially correlated with rearrangements in this thermal system.

  1. Putative interchromosomal rearrangements in the hexaploid wheat (Triticum aestivum L.) genotype 'Chinese Spring' revealed by gene locations on homoeologous chromosomes

    Czech Academy of Sciences Publication Activity Database

    Ma, J.; Stiller, J.; Zheng, Z.; Wei, Y.M.; Zheng, Y.L.; Yan, G.J.; Doležel, Jaroslav; Liu, C.

    2015-01-01

    Roč. 15, MAR 11 2015 (2015) ISSN 1471-2148 Institutional support: RVO:61389030 Keywords : Interchromosomal rearrangements * Wheat genome * Translocation Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.406, year: 2015

  2. Appearance and evolution of the specific chromosomal rearrangements associated with malignant transformation of mouse m5S cells

    International Nuclear Information System (INIS)

    Kodama, S.; Okumura, Y.; Komatsu, K.; Sasaki, M.S.

    1991-01-01

    Chromosomal alterations were studied during the acquisition of malignant phenotypes in two karyotypically distinct cells isolated from transformed foci induced by x-irradiation in mouse m5S cells. Because the transformants, despite foci origin, showed low ability to grow in agar, they were cultured in vitro with serial transfer schedules to allow further cell generations and assayed for anchorage independence (AI) at each passage level. The AI frequency increased with the cell doubling numbers. Chromosome analysis showed that a focus was one cell origin, but the transformants showed karyotypic instability during cell proliferation, giving rise to the rearrangements clustered in the distal region of the specific chromosomes. These rearrangements appeared to be directed toward the acquisition of malignant phenotypes. Analysis of the types and sites of rearrangements indicated that a mechanism exists that induces frequent rearrangements of the specific region of a chromosome during the process of transformation into the malignant state

  3. The effects of chromosome rearrangements on the expression of heterochromatic genes in chromosome 2L of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Wakimoto, B.T.; Hearn, M.G.

    1990-01-01

    The light (lt) gene of Drosophila melanogaster is located at the base of the left arm of chromosome 2, within or very near centromeric heterochromatin (2Lh). Chromosome rearrangements that move the lt + gene from its normal proximal position and place the gene in distal euchromatin result in mosaic or variegated expression of the gene. The cytogenetic and genetic properties of 17 lt-variegated rearrangements induced by X radiation are described in this report. The authors show that five of the heterochromatic genes adjacent to lt are subject to inactivation by these rearrangements and that the euchromatic loci in proximal 2L are not detectably affected. The properties of the rearrangements suggest that proximity to heterochromatin is an important regulatory requirement for at least six 2Lh genes. They discuss how the properties of the position effects on heterochromatic genes relate to other proximity-dependent phenomena such as transvection

  4. A stereoselective synthesis of (+)-physoperuvine using a tandem aza-Claisen rearrangement and ring closing metathesis reaction.

    Science.gov (United States)

    Zaed, Ahmed M; Swift, Michael D; Sutherland, Andrew

    2009-07-07

    A stereoselective synthesis of (+)-physoperuvine, a tropane alkaloid from Physalis peruviana Linne has been developed using a one-pot tandem aza-Claisen rearrangement and ring closing metathesis reaction to form the key amino-substituted cycloheptene ring.

  5. The complete mitochondrial genome sequence of the spider habronattus oregonensis reveals rearranged and extremely truncated tRNAs

    International Nuclear Information System (INIS)

    Masta, Susan E.; Boore, Jeffrey L.

    2004-01-01

    We sequenced the entire mitochondrial genome of the jumping spider Habronattus oregonensis of the arachnid order Araneae (Arthropoda: Chelicerata). A number of unusual features distinguish this genome from other chelicerate and arthropod mitochondrial genomes. Most of the transfer RNA gene sequences are greatly reduced in size and cannot be folded into typical cloverleaf-shaped secondary structures. At least nine of the tRNA sequences lack the potential to form TYC arm stem pairings, and instead are inferred to have TV-replacement loops. Furthermore, sequences that could encode the 3' aminoacyl acceptor stems in at least 10 tRNAs appear to be lacking, because fully paired acceptor stems are not possible and because the downstream sequences instead encode adjacent genes. Hence, these appear to be among the smallest known tRNA genes. We postulate that an RNA editing mechanism must exist to restore the 3' aminoacyl acceptor stems in order to allow the tRNAs to function. At least seven tRN As are rearranged with respect to the chelicerate Limulus polyphemus, although the arrangement of the protein-coding genes is identical. Most mitochondrial protein-coding genes of H. oregonensis have ATN as initiation codons, as commonly found in arthropod mtDNAs, but cytochrome oxidase subunit 2 and 3 genes apparently use UUG as an initiation codon. Finally, many of the gene sequences overlap one another and are truncated. This 14,381 bp genome, the first mitochondrial genome of a spider yet sequenced, is one of the smallest arthropod mitochondrial genomes known. We suggest that post transcriptional RNA editing can likely maintain function of the tRNAs while permitting the accumulation of mutations that would otherwise be deleterious. Such mechanisms may have allowed for the minimization of the spider mitochondrial genome

  6. Karyotype in secondary hematologic disorders after treatment for Hodgkin's disease. A study of 19 patients

    International Nuclear Information System (INIS)

    Iurlo, A.; Mecucci, C.; Van Orshoven, A.; Michaux, J.L.; Boogaerts, M.; Van den Berghe, H.

    1988-01-01

    In 19 cases of secondary hematologic disorders in patients previously treated for Hodgkin's disease, chromosome aberrations were analyzed in relation to the type of previous chemo- and/or radiotherapy, age of the patients, histopathologic features of the Hodgkin's disease at diagnosis, time interval between the treatment and the occurrence of the secondary disorder, and survival. The karyotype was of significant prognostic value when three cytogenetic groups were considered: patients with normal karyotypes; patients with aberrations of chromosome 7 as the sole anomaly; and patients with complex rearrangements and translocations. The last group showed the lowest rate of survival. Bone marrow transplantation was successful in two patients with a normal karyotype

  7. Gold-catalyzed intermolecular coupling of sulfonylacetylene with allyl ethers: [3,3]- and [1,3]-rearrangements

    Directory of Open Access Journals (Sweden)

    Jungho Jun

    2013-08-01

    Full Text Available Gold-catalyzed intermolecular couplings of sulfonylacetylenes with allyl ethers are reported. A cooperative polarization of alkynes both by a gold catalyst and a sulfonyl substituent resulted in an efficient intermolecular tandem carboalkoxylation. Reactions of linear allyl ethers are consistent with the [3,3]-sigmatropic rearrangement mechanism, while those of branched allyl ethers provided [3,3]- and [1,3]-rearrangement products through the formation of a tight ion–dipole pair.

  8. Rearrangement and convergence improvement of the Born series in scattering theory on the basis of orthogonal projections

    International Nuclear Information System (INIS)

    Kukulin, V.I.; Pomerantsev, V.N.

    1976-01-01

    Method of rearrangement of the Born series in scattering theory is proposed which uses the corthogonal projecting pseudopotentials (OPP) proposed recently. It is proved vigorously that the rearranged Born series will converge for all negative and small positive energy value seven in the presence of bound states. Method of correct introduction of scattering operators in orthogonal subspaces is displayed. Comparison of the OPP method with the projection technique developed by Feschbach is given. Physical applications of the method formulated are discussed

  9. Extensive gene rearrangements in the mitochondrial genomes of two egg parasitoids, Trichogramma japonicum and Trichogramma ostriniae (Hymenoptera: Chalcidoidea: Trichogrammatidae).

    Science.gov (United States)

    Chen, Long; Chen, Peng-Yan; Xue, Xiao-Feng; Hua, Hai-Qing; Li, Yuan-Xi; Zhang, Fan; Wei, Shu-Jun

    2018-05-04

    Animal mitochondrial genomes usually exhibit conserved gene arrangement across major lineages, while those in the Hymenoptera are known to possess frequent rearrangements, as are those of several other orders of insects. Here, we sequenced two complete mitochondrial genomes of Trichogramma japonicum and Trichogramma ostriniae (Hymenoptera: Chalcidoidea: Trichogrammatidae). In total, 37 mitochondrial genes were identified in both species. The same gene arrangement pattern was found in the two species, with extensive gene rearrangement compared with the ancestral insect mitochondrial genome. Most tRNA genes and all protein-coding genes were encoded on the minority strand. In total, 15 tRNA genes and seven protein-coding genes were rearranged. The rearrangements of cox1 and nad2 as well as most tRNA genes were novel. Phylogenetic analysis based on nucleotide sequences of protein-coding genes and on gene arrangement patterns produced identical topologies that support the relationship of (Agaonidae + Pteromalidae) + Trichogrammatidae in Chalcidoidea. CREx analysis revealed eight rearrangement operations occurred from presumed ancestral gene order of Chalcidoidea to form the derived gene order of Trichogramma. Our study shows that gene rearrangement information in Chalcidoidea can potentially contribute to the phylogeny of Chalcidoidea when more mitochondrial genome sequences are available.

  10. Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

    Directory of Open Access Journals (Sweden)

    Sosale Chandrasekhar

    2012-08-01

    Full Text Available The titled approaches were effected with various 2-substituted benzoylacetic acid oximes 3 (Beckmann and 2-substituted malonamic acids 9 (Hofmann, their carboxyl groups being masked as a 2,4,10-trioxaadamantane unit (an orthoacetate. The oxime mesylates have been rearranged with basic Al2O3 in refluxing CHCl3, and the malonamic acids with phenyliodoso acetate and KOH/MeOH. Both routes are characterized by excellent overall yields. Structure confirmation of final products was conducted with X-ray diffraction in selected cases. The final N-benzoyl and N-(methoxycarbonyl products are α-amino acids with both carboxyl and amino protection; hence, they are of great interest in peptide synthesis.

  11. Quercetin alters the DNA damage response in human hematopoietic stem and progenitor cells via TopoII- and PI3K-dependent mechanisms synergizing in leukemogenic rearrangements.

    Science.gov (United States)

    Biechonski, Shahar; Gourevich, Dana; Rall, Melanie; Aqaqe, Nasma; Yassin, Muhammad; Zipin-Roitman, Adi; Trakhtenbrot, Luba; Olender, Leonid; Raz, Yael; Jaffa, Ariel J; Grisaru, Dan; Wiesmuller, Lisa; Elad, David; Milyavsky, Michael

    2017-02-15

    Quercetin (Que) is an abundant flavonoid in the human diet and high-concentration food supplement with reported pro- and anti-carcinogenic activities. Topoisomerase II (TopoII) inhibition and subsequent DNA damage induction by Que was implicated in the mixed lineage leukemia gene (MLL) rearrangements that can induce infant and adult leukemias. This notion raised concerns regarding possible genotoxicities of Que in hematopoietic stem and progenitor cells (HSPCs). However, molecular targets mediating Que effects on DNA repair relevant to MLL translocations have not been defined. In this study we describe novel and potentially genotoxic Que activities in suppressing non-homologous end joining and homologous recombination pathways downstream of MLL cleavage. Using pharmacological dissection of DNA-PK, ATM and PI3K signalling we defined PI3K inhibition by Que with a concomitant decrease in the abundance of key DNA repair genes to be responsible for DNA repair inhibition. Evidence for the downstream TopoII-independent mutagenic potential of Que was obtained by documenting further increased frequencies of MLL rearrangements in human HSPCs concomitantly treated with Etoposide and Que versus single treatments. Importantly, by engaging a tissue engineered placental barrier, we have established the extent of Que transplacental transfer and hence provided the evidence for Que reaching fetal HSPCs. Thus, Que exhibits genotoxic effects in human HSPCs via different mechanisms when applied continuously and at high concentrations. In light of the demonstrated Que transfer to the fetal compartment our findings are key to understanding the mechanisms underlying infant leukemia and provide molecular markers for the development of safety values. © 2016 UICC.

  12. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts........ In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  13. Mediating Business

    DEFF Research Database (Denmark)

    "Mediating Business" is a study of the expansion of business journalism. Building on evidence from Denmark, Finland, Norway and Sweden, "Mediating Business" is a comparative and multidisciplinary study of one of the major transformations of the mass media and the realm of business - nationally...... and globally. The book explores the history of key innovations and innovators in the business press. It analyzes changes in the discourse of business journalism associated with the growth in business news and the development of new ways of framing business issues and events. Finally, it examines...... the organizational implications of the increased media visibility of business and, in particular, the development of corporate governance and media relations....

  14. Reproductive Incompatibility Involving Senegalese Aedes aegypti (L Is Associated with Chromosome Rearrangements.

    Directory of Open Access Journals (Sweden)

    Laura B Dickson

    2016-04-01

    staining was used to identify AT-rich regions, chromomycin A3 following pretreatment with barium hydroxide stained for GC-rich regions and stained the ribosomal RNA locus and YOYO-1 was used to test for differential staining. Chromosome patterns in SenAae strains revealed by these three stains differed from those in IB12. For FISH, 40 BAC clones previously physically mapped on Aaa chromosomes were used to test for chromosome rearrangements in SenAae relative to IB12. Differences in the order of markers identified two chromosomal rearrangements between IB12 and SenAae strains. The first rearrangement involves two overlapping pericentric (containing the centromere inversions in chromosome 3 or an insertion of a large fragment into the 3q arm. The second rearrangement is close to the centromere on the p arm of chromosome 2. Linkage analysis of the SDL and the white-eye locus identified a likely chromosomal rearrangement on chromosome 1. The reproductive incompatibility observed within SenAae and between SenAae and Aaa may be generally associated with chromosome rearrangements on all three chromosomes and specifically caused by pericentric inversions on chromosomes 2 and 3.

  15. Reproductive Incompatibility Involving Senegalese Aedes aegypti (L) Is Associated with Chromosome Rearrangements

    Science.gov (United States)

    Dickson, Laura B.; Sharakhova, Maria V.; Timoshevskiy, Vladimir A.; Fleming, Karen L.; Caspary, Alex; Sylla, Massamba; Black, William C.

    2016-01-01

    was used to identify AT-rich regions, chromomycin A3 following pretreatment with barium hydroxide stained for GC-rich regions and stained the ribosomal RNA locus and YOYO-1 was used to test for differential staining. Chromosome patterns in SenAae strains revealed by these three stains differed from those in IB12. For FISH, 40 BAC clones previously physically mapped on Aaa chromosomes were used to test for chromosome rearrangements in SenAae relative to IB12. Differences in the order of markers identified two chromosomal rearrangements between IB12 and SenAae strains. The first rearrangement involves two overlapping pericentric (containing the centromere) inversions in chromosome 3 or an insertion of a large fragment into the 3q arm. The second rearrangement is close to the centromere on the p arm of chromosome 2. Linkage analysis of the SDL and the white-eye locus identified a likely chromosomal rearrangement on chromosome 1. The reproductive incompatibility observed within SenAae and between SenAae and Aaa may be generally associated with chromosome rearrangements on all three chromosomes and specifically caused by pericentric inversions on chromosomes 2 and 3. PMID:27105225

  16. A saturated SSR/DArT linkage map of Musa acuminata addressing genome rearrangements among bananas

    Directory of Open Access Journals (Sweden)

    Matsumoto Takashi

    2010-04-01

    Full Text Available Abstract Background The genus Musa is a large species complex which includes cultivars at diploid and triploid levels. These sterile and vegetatively propagated cultivars are based on the A genome from Musa acuminata, exclusively for sweet bananas such as Cavendish, or associated with the B genome (Musa balbisiana in cooking bananas such as Plantain varieties. In M. acuminata cultivars, structural heterozygosity is thought to be one of the main causes of sterility, which is essential for obtaining seedless fruits but hampers breeding. Only partial genetic maps are presently available due to chromosomal rearrangements within the parents of the mapping populations. This causes large segregation distortions inducing pseudo-linkages and difficulties in ordering markers in the linkage groups. The present study aims at producing a saturated linkage map of M. acuminata, taking into account hypotheses on the structural heterozygosity of the parents. Results An F1 progeny of 180 individuals was obtained from a cross between two genetically distant accessions of M. acuminata, 'Borneo' and 'Pisang Lilin' (P. Lilin. Based on the gametic recombination of each parent, two parental maps composed of SSR and DArT markers were established. A significant proportion of the markers (21.7% deviated (p Conclusions We propose a synthetic map with 11 linkage groups containing 489 markers (167 SSRs and 322 DArTs covering 1197 cM. This first saturated map is proposed as a "reference Musa map" for further analyses. We also propose two complete parental maps with interpretations of structural rearrangements localized on the linkage groups. The structural heterozygosity in P. Lilin is hypothesized to result from a duplication likely accompanied by an inversion on another chromosome. This paper also illustrates a methodological approach, transferable to other species, to investigate the mapping of structural rearrangements and determine their consequences on marker

  17. A Consensus Map in Cultivated Hexaploid Oat Reveals Conserved Grass Synteny with Substantial Subgenome Rearrangement

    Directory of Open Access Journals (Sweden)

    Ashley S. Chaffin

    2016-07-01

    Full Text Available Hexaploid oat ( L., 2 = 6 = 42 is a member of the Poaceae family and has a large genome (∼12.5 Gb containing 21 chromosome pairs from three ancestral genomes. Physical rearrangements among parental genomes have hindered the development of linkage maps in this species. The objective of this work was to develop a single high-density consensus linkage map that is representative of the majority of commonly grown oat varieties. Data from a cDNA-derived single-nucleotide polymorphism (SNP array and genotyping-by-sequencing (GBS were collected from the progeny of 12 biparental recombinant inbred line populations derived from 19 parents representing oat germplasm cultivated primarily in North America. Linkage groups from all mapping populations were compared to identify 21 clusters of conserved collinearity. Linkage groups within each cluster were then merged into 21 consensus chromosomes, generating a framework consensus map of 7202 markers spanning 2843 cM. An additional 9678 markers were placed on this map with a lower degree of certainty. Assignment to physical chromosomes with high confidence was made for nine chromosomes. Comparison of homeologous regions among oat chromosomes and matches to orthologous regions of rice ( L. reveal that the hexaploid oat genome has been highly rearranged relative to its ancestral diploid genomes as a result of frequent translocations among chromosomes. Heterogeneous chromosome rearrangements among populations were also evident, probably accounting for the failure of some linkage groups to match the consensus. This work contributes to a further understanding of the organization and evolution of hexaploid grass genomes.

  18. UV-rearranged PIM-1 polymeric membranes for advanced hydrogen purification and production

    Energy Technology Data Exchange (ETDEWEB)

    Li, Fu Yun; Ong, Yee Kang; Chung, Tai-Shung [Department of Chemical and Biomolecular Engineering, National University of Singapore, Singapore (Singapore); Xiao, Youchang [Suzhou Faith and Hope Membrane Technology Co. Ltd., Jiangsu Province (China)

    2012-12-15

    Polymers of intrinsic microporosity (PIM-1) have been known for their super high permeability but average selectivity for medium-size gas pairs. They have unimpressive selectivity for H{sub 2} and CO{sub 2} separation (i.e., {alpha} (H{sub 2}/CO{sub 2}) = 0.6). For the first time, we have discovered that ultraviolet (UV)-rearranged polymers of PIM-1 membranes can be used for H{sub 2}/CO{sub 2} separation with far superior separation performance to others in literatures. The PIM-1 membrane after UV radiation for 4 hours shows H{sub 2} permeability of 452 barrer with H{sub 2}/CO{sub 2} selectivity of 7.3. Experimental data and molecular simulation reveal that the polymer chains of PIM-1 undergo 1,2-migration reaction and transform to close-to-planar like rearranged structure after UV radiation. As a result, the UV-irradiated PIM-1 membrane shows considerable drops in both fractional free volume (FFV) and size of micro-pores. Positron annihilation lifetime (PAL) results have confirmed the chemical and structural changes, suggesting the FFV and pore size drops are mainly ascribed to the destructed spiro-carbon centre during UV radiation. Sorption and x-ray diffractor (XRD) analyses indicate that the impressive H{sub 2}/CO{sub 2} selectivity arises from the significantly enhanced diffusivity selectivity induced by UV radiation, followed by molecular rearrangement, conformation change and chain packing. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  19. A saturated SSR/DArT linkage map of Musa acuminata addressing genome rearrangements among bananas.

    Science.gov (United States)

    Hippolyte, Isabelle; Bakry, Frederic; Seguin, Marc; Gardes, Laetitia; Rivallan, Ronan; Risterucci, Ange-Marie; Jenny, Christophe; Perrier, Xavier; Carreel, Françoise; Argout, Xavier; Piffanelli, Pietro; Khan, Imtiaz A; Miller, Robert N G; Pappas, Georgios J; Mbéguié-A-Mbéguié, Didier; Matsumoto, Takashi; De Bernardinis, Veronique; Huttner, Eric; Kilian, Andrzej; Baurens, Franc-Christophe; D'Hont, Angélique; Cote, François; Courtois, Brigitte; Glaszmann, Jean-Christophe

    2010-04-13

    The genus Musa is a large species complex which includes cultivars at diploid and triploid levels. These sterile and vegetatively propagated cultivars are based on the A genome from Musa acuminata, exclusively for sweet bananas such as Cavendish, or associated with the B genome (Musa balbisiana) in cooking bananas such as Plantain varieties. In M. acuminata cultivars, structural heterozygosity is thought to be one of the main causes of sterility, which is essential for obtaining seedless fruits but hampers breeding. Only partial genetic maps are presently available due to chromosomal rearrangements within the parents of the mapping populations. This causes large segregation distortions inducing pseudo-linkages and difficulties in ordering markers in the linkage groups. The present study aims at producing a saturated linkage map of M. acuminata, taking into account hypotheses on the structural heterozygosity of the parents. An F1 progeny of 180 individuals was obtained from a cross between two genetically distant accessions of M. acuminata, 'Borneo' and 'Pisang Lilin' (P. Lilin). Based on the gametic recombination of each parent, two parental maps composed of SSR and DArT markers were established. A significant proportion of the markers (21.7%) deviated (p DArTs) covering 1197 cM. This first saturated map is proposed as a "reference Musa map" for further analyses. We also propose two complete parental maps with interpretations of structural rearrangements localized on the linkage groups. The structural heterozygosity in P. Lilin is hypothesized to result from a duplication likely accompanied by an inversion on another chromosome. This paper also illustrates a methodological approach, transferable to other species, to investigate the mapping of structural rearrangements and determine their consequences on marker segregation.

  20. Non-random distribution of instability-associated chromosomal rearrangement breakpoints in human lymphoblastoid cells

    International Nuclear Information System (INIS)

    Moore, Stephen R.; Papworth, David; Grosovsky, Andrew J.

    2006-01-01

    Genomic instability is observed in tumors and in a large fraction of the progeny surviving irradiation. One of the best-characterized phenotypic manifestations of genomic instability is delayed chromosome aberrations. Our working hypothesis for the current study was that if genomic instability is in part attributable to cis mechanisms, we should observe a non-random distribution of chromosomes or sites involved in instability-associated rearrangements, regardless of radiation quality, dose, or trans factor expression. We report here the karyotypic examination of 296 instability-associated chromosomal rearrangement breaksites (IACRB) from 118 unstable TK6 human B lymphoblast, and isogenic derivative, clones. When we tested whether IACRB were distributed across the chromosomes based on target size, a significant non-random distribution was evident (p < 0.00001), and three IACRB hotspots (chromosomes 11, 12, and 22) and one IACRB coldspot (chromosome 2) were identified. Statistical analysis at the chromosomal band-level identified four IACRB hotspots accounting for 20% of all instability-associated breaks, two of which account for over 14% of all IACRB. Further, analysis of independent clones provided evidence within 14 individual clones of IACRB clustering at the chromosomal band level, suggesting a predisposition for further breaks after an initial break at some chromosomal bands. All of these events, independently, or when taken together, were highly unlikely to have occurred by chance (p < 0.000001). These IACRB band-level cluster hotspots were observed independent of radiation quality, dose, or cellular p53 status. The non-random distribution of instability-associated chromosomal rearrangements described here significantly differs from the distribution that was observed in a first-division post-irradiation metaphase analysis (p = 0.0004). Taken together, these results suggest that genomic instability may be in part driven by chromosomal cis mechanisms

  1. Comprehensive preimplantation genetic screening and sperm deoxyribonucleic acid fragmentation from three males carrying balanced chromosome rearrangements.

    Science.gov (United States)

    Ramos, Laia; Daina, Gemma; Del Rey, Javier; Ribas-Maynou, Jordi; Fernández-Encinas, Alba; Martinez-Passarell, Olga; Boada, Montserrat; Benet, Jordi; Navarro, Joaquima

    2015-09-01

    To assess whether preimplantation genetic screening can successfully identify cytogenetically normal embryos in couples carrying balanced chromosome rearrangements in addition to increased sperm DNA fragmentation. Comprehensive preimplantation genetic screening was performed on three couples carrying chromosome rearrangements. Sperm DNA fragmentation was assessed for each patient. Academic center. One couple with the male partner carrying a chromosome 2 pericentric inversion and two couples with the male partners carrying a Robertsonian translocation (13:14 and 14:21, respectively). A single blastomere from each of the 18 cleavage-stage embryos obtained was analysed by metaphase comparative genomic hybridization. Single- and double-strand sperm DNA fragmentation was determined by the alkaline and neutral Comet assays. Single- and double-strand sperm DNA fragmentation values and incidence of chromosome imbalances in the blastomeres were analyzed. The obtained values of single-strand sperm DNA fragmentation were between 47% and 59%, and the double-strand sperm DNA fragmentation values were between 43% and 54%. No euploid embryos were observed in the couple showing the highest single-strand sperm DNA fragmentation. However, euploid embryos were observed in the other two couples: embryo transfer was performed, and pregnancy was achieved by the couple showing the lowest sperm DNA fragmentation values. Preimplantation genetic screening enables the detection of euploid embryos in couples affected by balanced chromosome rearrangements and increased sperm DNA fragmentation. Even though sperm DNA fragmentation may potentially have clinical consequences on fertility, comprehensive preimplantation genetic screening allows for the identification and transfer of euploid embryos. Copyright © 2015. Published by Elsevier Inc.

  2. Relative transmembrane segment rearrangements during BK channel activation resolved by structurally assigned fluorophore–quencher pairing

    Science.gov (United States)

    Pantazis, Antonios

    2012-01-01

    Voltage-activated proteins can sense, and respond to, changes in the electric field pervading the cell membrane by virtue of a transmembrane helix bundle, the voltage-sensing domain (VSD). Canonical VSDs consist of four transmembrane helices (S1–S4) of which S4 is considered a principal component because it possesses charged residues immersed in the electric field. Membrane depolarization compels the charges, and by extension S4, to rearrange with respect to the field. The VSD of large-conductance voltage- and Ca-activated K+ (BK) channels exhibits two salient inconsistencies from the canonical VSD model: (1) the BK channel VSD possesses an additional nonconserved transmembrane helix (S0); and (2) it exhibits a “decentralized” distribution of voltage-sensing charges, in helices S2 and S3, in addition to S4. Considering these unique features, the voltage-dependent rearrangements of the BK VSD could differ significantly from the standard model of VSD operation. To understand the mode of operation of this unique VSD, we have optically tracked the relative motions of the BK VSD transmembrane helices during activation, by manipulating the quenching environment of site-directed fluorescent labels with native and introduced Trp residues. Having previously reported that S0 and S4 diverge during activation, in this work we demonstrate that S4 also diverges from S1 and S2, whereas S2, compelled by its voltage-sensing charged residues, moves closer to S1. This information contributes spatial constraints for understanding the BK channel voltage-sensing process, revealing the structural rearrangements in a non-canonical VSD. PMID:22802360

  3. Molecular Subtyping of Primary Prostate Cancer Reveals Specific and Shared Target Genes of Different ETS Rearrangements

    Directory of Open Access Journals (Sweden)

    Paula Paulo

    2012-07-01

    Full Text Available This work aimed to evaluate whether ETS transcription factors frequently involved in rearrangements in prostate carcinomas (PCa, namely ERG and ETV1, regulate specific or shared target genes. We performed differential expression analysis on nine normal prostate tissues and 50 PCa enriched for different ETS rearrangements using exon-level expression microarrays, followed by in vitro validation using cell line models. We found specific deregulation of 57 genes in ERG-positive PCa and 15 genes in ETV1-positive PCa, whereas deregulation of 27 genes was shared in both tumor subtypes. We further showed that the expression of seven tumor-associated ERG target genes (PLA1A, CACNA1D, ATP8A2, HLA-DMB, PDE3B, TDRD1, and TMBIM1 and two tumor-associated ETV1 target genes (FKBP10 and GLYATL2 was significantly affected by specific ETS silencing in VCaP and LNCaP cell line models, respectively, whereas the expression of three candidate ERG and ETV1 shared targets (GRPR, KCNH8, and TMEM45B was significantly affected by silencing of either ETS. Interestingly, we demonstrate that the expression of TDRD1, the topmost overexpressed gene of our list of ERG-specific candidate targets, is inversely correlated with the methylation levels of a CpG island found at -66 bp of the transcription start site in PCa and that TDRD1 expression is regulated by direct binding of ERG to the CpG island in VCaP cells. We conclude that ETS transcription factors regulate specific and shared target genes and that TDRD1, FKBP10, and GRPR are promising therapeutic targets and can serve as diagnostic markers for molecular subtypes of PCa harboring specific fusion gene rearrangements.

  4. Diagnostic value of immunoglobulin κ light chain gene rearrangement analysis in B-cell lymphomas.

    Science.gov (United States)

    Kokovic, Ira; Jezersek Novakovic, Barbara; Novakovic, Srdjan

    2015-03-01

    Analysis of the immunoglobulin κ light chain (IGK) gene is an alternative method for B-cell clonality assessment in the diagnosis of mature B-cell proliferations in which the detection of clonal immunoglobulin heavy chain (IGH) gene rearrangements fails. The aim of the present study was to evaluate the added value of standardized BIOMED-2 assay for the detection of clonal IGK gene rearrangements in the diagnostic setting of suspected B-cell lymphomas. With this purpose, 92 specimens from 80 patients with the final diagnosis of mature B-cell lymphoma (37 specimens), mature T-cell lymphoma (26 specimens) and reactive lymphoid proliferation (29 specimens) were analyzed for B-cell clonality. B-cell clonality analysis was performed using the BIOMED-2 IGH and IGK gene clonality assays. The determined sensitivity of the IGK assay was 67.6%, while the determined sensitivity of the IGH assay was 75.7%. The sensitivity of combined IGH+IGK assay was 81.1%. The determined specificity of the IGK assay was 96.2% in the group of T-cell lymphomas and 96.6% in the group of reactive lesions. The determined specificity of the IGH assay was 84.6% in the group of lymphomas and 86.2% in the group of reactive lesions. The comparison of GeneScan (GS) and heteroduplex pretreatment-polyacrylamide gel electrophoresis (HD-PAGE) methods for the analysis of IGK gene rearrangements showed a higher efficacy of GS analysis in a series of 27 B-cell lymphomas analyzed by both methods. In the present study, we demonstrated that by applying the combined IGH+IGK clonality assay the overall detection rate of B-cell clonality was increased by 5.4%. Thus, we confirmed the added value of the standardized BIOMED-2 IGK assay for assessment of B-cell clonality in suspected B-cell lymphomas with inconclusive clinical and cyto/histological diagnosis.

  5. Clinical outcomes of myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement.

    Science.gov (United States)

    Umino, Kento; Fujiwara, Shin-Ichiro; Ikeda, Takashi; Toda, Yumiko; Ito, Shoko; Mashima, Kiyomi; Minakata, Daisuke; Nakano, Hirofumi; Yamasaki, Ryoko; Kawasaki, Yasufumi; Sugimoto, Miyuki; Yamamoto, Chihiro; Ashizawa, Masahiro; Hatano, Kaoru; Sato, Kazuya; Oh, Iekuni; Ohmine, Ken; Muroi, Kazuo; Kanda, Yoshinobu

    2018-02-28

    Myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement are hematopoietic stem cell disorders with a poor prognosis, but no established standard therapy. We experienced a patient with T-lymphoblastic lymphoma (LBL) associated with FGFR1 rearrangement who underwent cord blood transplantation, but died of pulmonary complication. We collected the clinical data of patients with FGFR1 rearrangement from the medical literature and analyzed 45 patients, including our patient. The primary diagnoses were myeloproliferative neoplasm (MPN) or myelodysplastic syndromes (MDS) in 14 and acute leukemia or LBL in 31. In MPN and MDS patients, the cumulative incidence of transformation to blast phase (BP) at 12 months was 46.2%. The 1-year overall survival (OS) from diagnosis in all cases was 43.1%. With regard to the impact of treatment response on survival, the achievement of complete response with a landmark at 2 months after diagnosis of BP was associated with a superior OS (40.0% vs. 26.0% P = 0.011 for 1-year OS from BP). Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 13 patients, and the 1-year OS from allogeneic HSCT was 61.5%. The hazard ratio for mortality was 0.34 (95% CI, 0.08-1.51, P = 0.15) for allogeneic HSCT treated as a time-dependent covariate, which suggests that allogeneic HSCT may confer a clinical benefit. The further accumulation of clinical data is needed to determine the optimal therapeutic approach for these neoplasms.

  6. Rearrangement of Upstream Sequences of the hTERT Gene During Cellular Immortalization

    Science.gov (United States)

    Zhao, Yuanjun; Wang, Shuwen; Popova, Evgenya Y.; Grigoryev, Sergei A.; Zhu, Jiyue

    2010-01-01

    Telomerase expression, resulting from transcriptional activation of the hTERT gene, allows cells to acquire indefinite proliferative potential during cellular immortalization and tumorigenesis. However, mechanisms of hTERT gene activation in many immortal cell lines and cancer cells are poorly understood. Here, we report our studies on hTERT activation using genetically related pairs of telomerase-negative (Tel−) and -positive (Tel+) fibroblast lines. First, whereas transiently transfected plasmid reporters did not recapitulate the endogenous hTERT promoter, the promoter in chromosomally integrated bacterial artificial chromosome (BAC) reporters was activated in a subset of Tel+ cells, indicating that activation of the hTERT promoter required native chromatin context and/or distal regulatory elements. Second, the hTERT gene, located near the telomere of chromosome 5p, was translocated in all three Tel+ cell lines but not in their parental pre-crisis cells and Tel− immortal siblings. The breakage points were mapped to regions upstream of the hTERT promoter, indicating that the hTERT gene was the target of these chromosomal rearrangements. In two Tel+ cell lines, translocation of the endogenous hTERT gene appeared to be the major mechanism of its activation as the activity of hTERT promoter in many chromosomally integrated BAC reporters, with intact upstream and downstream neighboring loci, remained relatively low. Therefore, our results suggest that rearrangement of upstream sequences is an important new mechanism of hTERT promoter activation during cellular immortalization. The chromosomal rearrangements likely occurred during cellular crisis and facilitated by telomere dysfunction. Such translocations allowed the hTERT promoter to escape from the native condensed chromatin environment. PMID:19672873

  7. Preimplantation genetic diagnosis for chromosomal rearrangements with the use of array comparative genomic hybridization at the blastocyst stage.

    Science.gov (United States)

    Christodoulou, Christodoulos; Dheedene, Annelies; Heindryckx, Björn; van Nieuwerburgh, Filip; Deforce, Dieter; De Sutter, Petra; Menten, Björn; Van den Abbeel, Etienne

    2017-01-01

    To establish the value of array comparative genomic hybridization (CGH) for preimplantation genetic diagnosis (PGD) in embryos of translocation carriers in combination with vitrification and frozen embryo transfer in nonstimulated cycles. Retrospective data analysis study. Academic centers for reproductive medicine and genetics. Thirty-four couples undergoing PGD for chromosomal rearrangements from October 2013 to December 2015. Trophectoderm biopsy at day 5 or day 6 of embryo development and subsequently whole genome amplification and array CGH were performed. This approach revealed a high occurrence of aneuploidies and structural rearrangements unrelated to the parental rearrangement. Nevertheless, we observed a benefit in pregnancy rates of these couples. We detected chromosomal abnormalities in 133/207 embryos (64.2% of successfully amplified), and 74 showed a normal microarray profile (35.7%). In 48 of the 133 abnormal embryos (36.1%), an unbalanced rearrangement originating from the parental translocation was identified. Interestingly, 34.6% of the abnormal embryos (46/133) harbored chromosome rearrangements that were not directly linked to the parental translocation in question. We also detected a combination of unbalanced parental-derived rearrangements and aneuploidies in 27 of the 133 abnormal embryos (20.3%). The use of trophectoderm biopsy at the blastocyst stage is less detrimental to the survival of the embryo and leads to a more reliable estimate of the genomic content of the embryo than cleavage-stage biopsy. In this small cohort PGD study, we describe the successful implementation of array CGH analysis of blastocysts in patients with a chromosomal rearrangement to identify euploid embryos for transfer. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  8. Early dengue virus protein synthesis induces extensive rearrangement of the endoplasmic reticulum independent of the UPR and SREBP-2 pathway.

    Directory of Open Access Journals (Sweden)

    José Peña

    Full Text Available The rearrangement of intracellular membranes has been long reported to be a common feature in diseased cells. In this study, we used dengue virus (DENV to study the role of the unfolded protein response (UPR and sterol-regulatory-element-binding-protein-2 (SREBP-2 pathway in the rearrangement and expansion of the endoplasmic reticulum (ER early after infection. Using laser scanning confocal and differential interference contrast microscopy, we demonstrate that rearrangement and expansion of the ER occurs early after DENV-2 infection. Through the use of mouse embryonic fibroblast cells deficient in XBP1 and ATF6, we show that ER rearrangement early after DENV infection is independent of the UPR. We then demonstrate that enlargement of the ER is independent of the SREBP-2 activation and upregulation of 3-hydroxy-3-methylglutaryl-Coenzyme-A reductase, the rate-limiting enzyme in the cholesterol biosynthesis pathway. We further show that this ER rearrangement is not inhibited by the treatment of DENV-infected cells with the cholesterol-inhibiting drug lovastatin. Using the transcription inhibitor actinomycin D and the translation elongation inhibitor cycloheximide, we show that de novo viral protein synthesis but not host transcription is necessary for expansion and rearrangement of the ER. Lastly, we demonstrate that viral infection induces the reabsorption of lipid droplets into the ER. Together, these results demonstrate that modulation of intracellular membrane architecture of the cell early after DENV-2 infection is driven by viral protein expression and does not require the induction of the UPR and SREBP-2 pathways. This work paves the way for further study of virally-induced membrane rearrangements and formation of cubic membranes.

  9. The incidence and distribution characteristics of MLL rearrangements in Chinese acute myeloid leukemia patients by multiplex nested RT-PCR.

    Science.gov (United States)

    Yang, Hua; Cao, Tingting; Gao, Li; Wang, Lili; Zhu, Chengying; Xu, Yuanyuan; Jing, Yu; Zhu, Haiyan; Lv, Na; Yu, Li

    2017-07-20

    Occurrence of MLL (Mixed Lineage Leukemia) gene rearrangements indicates poor prognosis in acute myeloid leukemia (AML) patients. This is the first study to report the positive rate and distribution characteristics of MLL rearrangements in AML patients in north China. We used multiplex nested real time PCR (RT-PCR) to screen for incidence of 11 MLL rearrangements in 433 AML patients. Eleven MLL rearrangements included (MLL-PTD, MLL-AF9, MLL-ELL, MLL-AF10, MLL-AF17, MLL-AF6, MLL-ENL, MLL-AF1Q, MLL-CBP, MLL-AF1P, MLL-AFX1). There were 68 AML patients with MLL rearrangements, and the positive rate was 15.7%. MLL-PTD (4.84%) was detected in 21 patients, MLL-AF9 in 15, (3.46%), MLL-ELL in 10 (2.31%), MLL-AF10 in 8 (1.85%), MLL-AF1Q in 2 (0.46%), 3 cases each of MLL-AF17, MLL-AF6, MLL-ENL (0.69% each), a and single case each of MLL-CBP, MLL-AF1P, and MLL-AFX1 (0.23% each). The highest rate of MLL rearrangements was found in 24 patients with M5 subtype AML, occurring in 24 cases (35.3%). MLL rearrangements occurred in 21 patients with M2 subtype AML (30.9%), and in 10 patients with M4 subtype AML (14.7%). Screening fusion genes by multiplex nested RT-PCR is a convenient, fast, economical, and accurate method for diagnosis and predicting prognosis of AML.

  10. Rearrangement and energy transfer collisions of few-body molecular systems

    International Nuclear Information System (INIS)

    Gentry, W.R.

    1981-01-01

    A great variety of experimental techniques now makes it possible to obtain dynamical information on single bimolecular collisions in a very direct way. These methods are too numerous to permit a comprehensive review in this article, but a few examples have been chosen to illustrate briefly the types of results being obtained in several areas. These include measurements of state-to-state differential cross sections for rotationally and vibrationally inelastic collisions, and rearrangement collisions studies by crossed-beam and merged-beam methods. (orig.)

  11. Inconsistent results in the analysis of ALK rearrangements in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Mattsson, Johanna S. M.; Brunnström, Hans; Jabs, Verena; Edlund, Karolina; Jirström, Karin; Mindus, Stephanie; Fleur, Linnéa la; Pontén, Fredrik; Karlsson, Mats G.; Karlsson, Christina; Koyi, Hirsh; Brandén, Eva; Botling, Johan; Helenius, Gisela; Micke, Patrick; Svensson, Maria A.

    2016-01-01

    Identification of targetable EML4-ALK fusion proteins has revolutionized the treatment of a minor subgroup of non-small cell lung cancer (NSCLC) patients. Although fluorescence in situ hybridization (FISH) is regarded as the gold standard for detection of ALK rearrangements, ALK immunohistochemistry (IHC) is often used as screening tool in clinical practice. In order to unbiasedly analyze the diagnostic impact of such a screening strategy, we compared ALK IHC with ALK FISH in three large representative Swedish NSCLC cohorts incorporating clinical parameters and gene expression data. ALK rearrangements were detected using FISH on tissue microarrays (TMAs), including tissue from 851 NSCLC patients. In parallel, ALK protein expression was detected using IHC, applying the antibody clone D5F3 with two different protocols (the FDA approved Ventana CDx assay and our in house Dako IHC protocol). Gene expression microarray data (Affymetrix) was available for 194 patients. ALK rearrangements were detected in 1.7 % in the complete cohort and 2.0 % in the non-squamous cell carcinoma subgroup. ALK protein expression was observed in 1.8 and 1.4 % when applying the Ventana assay or the in house Dako protocol, respectively. The specificity and accuracy of IHC was high (> 98 %), while the sensitivity was between 69 % (Ventana) and 62 % (in house Dako protocol). Furthermore, only 67 % of the ALK IHC positive cases were positive with both IHC assays. Gene expression analysis revealed that 6/194 (3 %) tumors showed high ALK gene expression (≥ 6 AU) and of them only three were positive by either FISH or IHC. The overall frequency of ALK rearrangements based on FISH was lower than previously reported. The sensitivity of both IHC assays was low, and the concordance between the FISH and the IHC assays poor, questioning current strategies to screen with IHC prior to FISH or completely replace FISH by IHC. The online version of this article (doi:10.1186/s12885-016-2646-x) contains

  12. Ethynamine - Ketenimine - Acetonitrile - Rearrangements: A computational Study of Flash Vacuum Pyrolysis Processes

    OpenAIRE

    Wentrup, Curt; Begue, Didier; Leung-Toung, Regis

    2017-01-01

    The rearrangements of ethynamine 3 (H-CºC-NH2) to ketenimine 4 (CH2=C=NH) and acetonitrile 5 (CH3CN) were investigated computationally up to the MP4(SDTQ)/6-31G*//MP2(FU)/6-31G* level. The calculated barrier for a concerted reaction 3 -> 4 is very high, 74 kcal/mol, the structure of the transition state very unusual, and this path is discredited. A lower barrier of about 60 kcal/mol via aminovinylidene 2 and imidoylcarbene 15 has been found. The calculated barrier for ...

  13. Cooperative rearranging region size and free volume in As-Se glasses

    Energy Technology Data Exchange (ETDEWEB)

    Saiter, A; Saiter, J-M [Laboratoire PBM, UMR 6522, LECAP, Institut des Materiaux de Rouen, Universite de Rouen, Faculte des Sciences, Avenue de l' Universite BP 12, 76801 Saint Etienne du Rouvray (France); Golovchak, R; Shpotyuk, M; Shpotyuk, O [Lviv Scientific Research Institute of Materials of SRC ' Carat' , 202, Stryjska street, Lviv, UA-79031 (Ukraine)

    2009-02-18

    Glasses of the As-Se system have been used as model objects of the covalent disordered inorganic polymers to investigate the correlation between the cooperative rearranging region (CRR) size determined at the glass transition temperature and the free volume fraction in the glassy state. The CRR size has been determined using temperature modulated differential scanning calorimetry data according to Donth's approach, while the free volume fraction in the investigated materials has been estimated using positron annihilation lifetime spectroscopy data. The obtained results testify that the appearance of open-volume defects greater than 80 A{sup 3} leads to a significant decrease in the CRR size.

  14. Cooperative rearranging region size and free volume in As-Se glasses

    International Nuclear Information System (INIS)

    Saiter, A; Saiter, J-M; Golovchak, R; Shpotyuk, M; Shpotyuk, O

    2009-01-01

    Glasses of the As-Se system have been used as model objects of the covalent disordered inorganic polymers to investigate the correlation between the cooperative rearranging region (CRR) size determined at the glass transition temperature and the free volume fraction in the glassy state. The CRR size has been determined using temperature modulated differential scanning calorimetry data according to Donth's approach, while the free volume fraction in the investigated materials has been estimated using positron annihilation lifetime spectroscopy data. The obtained results testify that the appearance of open-volume defects greater than 80 A 3 leads to a significant decrease in the CRR size.

  15. Molecular Rearrangement of an Aza-Scorpiand Macrocycle Induced by pH: A Computational Study

    Directory of Open Access Journals (Sweden)

    Jesus Vicente De Julián-Ortiz

    2016-07-01

    Full Text Available Rearrangements and their control are a hot topic in supramolecular chemistry due to the possibilities that these phenomena open in the design of synthetic receptors and molecular machines. Macrocycle aza-scorpiands constitute an interesting system that can reorganize their spatial structure depending on pH variations or the presence of metal cations. In this study, the relative stabilities of these conformations were predicted computationally by semi-empirical and density functional theory approximations, and the reorganization from closed to open conformations was simulated by using the Monte Carlo multiple minimum method.

  16. Nitrosation of amides involves a pseudopericyclic 1,3-sigmatropic rearrangement.

    Science.gov (United States)

    Birney, David M

    2004-03-04

    Two possible pathways for the nitrosation of formamide and N-methyl formamide by nitrosonium ion (NO(+)) have been investigated at the B3LYP/6-31G(d,p) level. The key steps are pseudopericyclic 1,3-sigmatropic rearrangements to give the observed N-nitrosamides. The transition structures (8a and 8b) are close to planar on the amide moiety and have remarkably low barriers of only 6.6 and 4.8 kcal/mol from the lowest energy conformations of 6a and 6b, respectively. [reaction: see text

  17. Actin cytoskeleton rearrangements in Arabidopsis roots under stress and during gravitropic response

    Science.gov (United States)

    Pozhvanov, Gregory; Medvedev, Sergei; Suslov, Dmitry; Demidchik, Vadim

    Among environmental factors, gravity vector is the only one which is constant in direction and accompanies the whole plant ontogenesis. That said, gravity vector can be considered as an essential factor for correct development of plants. Gravitropism is a plant growth response against changing its position relative to the gravity vector. It is well estableshed that gravitropism is directed by auxin redistribution across the gravistimulated organ. In addition to auxin, actin cytoskeleton was shown to be involved in gravitropism at different stages: gravity perception, signal transduction and gravitropic bending formation. However, the relationship between IAA and actin is still under discussion. In this work we studied rearrangements of actin cytoskeleton during root gravitropic response. Actin microfilaments were visualized in vivo in GFP-fABD2 transgenic Arabidopsis plants, and their angle distribution was acquired from MicroFilament Analyzer software. The curvature of actin microfilaments in root elongation zone was shown to be increased within 30-60 min of gravistimulation, the fraction of axially oriented microfilaments decreased with a concomitant increase in the fraction of oblique and transversally oriented microfilaments. In particular, the fraction of transversally oriented microfilaments (i.e. parallel to the gravity vector) increased 3-5 times. Under 10 min of sub-lethal salt stress impact, actin microfilament orientations widened from an initial axial orientation to a set of peaks at 15(°) , 45(°) and 90(°) . We conclude that the actin cytoskeleton rearrangements observed are associated with the regulation of basic mechanisms of cell extension growth by which the gravitropic bending is formed. Having common stress-related features, gravity-induced actin cytoskeleton rearrangement is slower but results in higher number of g-vector-parallel microfilaments when compared to salt stress-induced rearrangement. Also, differences in gravistimulated root

  18. Toward Singlet-Triplet Bistable Nonalternant Kekulé Hydrocarbons: Azulene-to-Naphthalene Rearrangement.

    Science.gov (United States)

    Das, Soumyajit; Wu, Jishan

    2015-12-04

    Recent developments of open-shell singlet diradicaloids motivated the search for stable singlet-triplet bistable nonalternant polycyclic hydrocarbons. During the synthesis of this type of molecule, such as the dibenzo-cyclohepta[def]fluorene 3, an unexpected azulene-to-naphthalene rearrangement was observed at room temperature, which resulted in new nonalternant hydrocarbons 8a/8b with a closed-shell singlet ground state. These studies provided insight into the unique chemistry of azulene and challenges for the synthesis of singlet-triplet bistable polycyclic hydrocarbons.

  19. Radiation induced chimeric rearrangement flower structure of Rhododendron simsii Planch. (Azaleaindica L. ) Use of recurrent irradiation

    Energy Technology Data Exchange (ETDEWEB)

    de Loose, R [IWONL (IRSIA) Irradiation Laboratory, Institute of Ornamental Plant Growing, Melle (Belgium)

    1979-02-01

    A radiation-induced chimeric flower colour sport of vegetatively propagated Rhododendron simsii Planch was recurrently irradiated (up to three times in three consecutive years) with soft X-rays (50kV-30mA), as compared to a single treatment. Because of the low true flower colour mutation frequency the efficiency of the different radiation treatments was compared on the basis of the number of chimeric rearrangements in flower structure i.e. the flower colour change from red with broad white edge towards either homogeneous carminered or white. It is quite clear that recurrent irradiation with appropiate doses is most efficient.

  20. Media Access Time-Rearrangement of Wireless LAN for a Multi-Radio Collocated Platform

    Science.gov (United States)

    Shin, Sang-Heon; Kim, Chul; Park, Sang Kyu

    With the advent of new Radio Access Technologies (RATs), it is inevitable that several RATs will co-exist, especially in the license-exempt band. In this letter, we present an in-depth adaptation of the proactive time-rearrangement (PATRA) scheme for IEEE 802.11 WLAN. The PATRA is a time division approach for reducing interference from a multi-radio device. Because IEEE 802.11 is based on carrier sensing and contention mechanism, it is the most suitable candidate to adapt the PATRA.

  1. Possible role of repetitious DNA in recombinatory joining during chromosome rearrangement in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Lee, C.S.

    1975-01-01

    It is postulated that certain repetitious DNA components play a role in the recombination processes during chromosome rearrangements. When the distribution of silver grain densities after the in situ hybridization of repetitious DNA and the distribution of chromosome breaks due to x-irradiation are compared, a strong correlation is found for the euchromatic portion of the D. melanogaster salivary X chromosome. These observations justify the postulate above that certain repetitious DNA provides homologous regions in the DNA of broken chromosome ends necessary for proper recombinatory joining. (U.S.)

  2. The enrichment secondary market

    International Nuclear Information System (INIS)

    Einbund, D.R.

    1986-01-01

    This paper will addresses two topics: the background to the present status of the enrichment secondary market and the future outlook of the secondary market in enrichment services, and the viability of the nuclear fuel brokerage industry. These two topics are inevitably connected, as most secondary market activity, not only in enrichment but also in natural uranium, has traditionally been conducted with the participation of brokers. Therefore, the author interrelates these topics

  3. Quantitative secondary electron detection

    Science.gov (United States)

    Agrawal, Jyoti; Joy, David C.; Nayak, Subuhadarshi

    2018-05-08

    Quantitative Secondary Electron Detection (QSED) using the array of solid state devices (SSD) based electron-counters enable critical dimension metrology measurements in materials such as semiconductors, nanomaterials, and biological samples (FIG. 3). Methods and devices effect a quantitative detection of secondary electrons with the array of solid state detectors comprising a number of solid state detectors. An array senses the number of secondary electrons with a plurality of solid state detectors, counting the number of secondary electrons with a time to digital converter circuit in counter mode.

  4. NUTM2A-CIC fusion small round cell sarcoma: a genetically distinct variant of CIC-rearranged sarcoma.

    Science.gov (United States)

    Sugita, Shintaro; Arai, Yasuhito; Aoyama, Tomoyuki; Asanuma, Hiroko; Mukai, Wakako; Hama, Natsuko; Emori, Makoto; Shibata, Tatsuhiro; Hasegawa, Tadashi

    2017-07-01

    CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic analysis revealed multinodular proliferation of small round tumor cells with mild nuclear pleomorphism. The sclerotic fibrous septa separated the tumor into multiple nodules. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin, focally positive for cytokeratin, and negative for CD99 and NKX2.2. Tumor cells were also negative for ETV4, which was recently identified as a specific marker for CIC-rearranged sarcoma. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded clinical sample unveiled a novel NUTM2A-CIC fusion between NUTM2A exon 7 and CIC exon 12, and fluorescence in situ hybridization identified CIC and NUTM2A split signals. This case shared several clinicopathological findings with previously reported CIC-rearranged cases. We recognized the tumor as a genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion. Copyright © 2017. Published by Elsevier Inc.

  5. Kinase Expression and Chromosomal Rearrangements in Papillary Thyroid Cancer Tissues: Investigations at the Molecular and Microscopic Levels

    International Nuclear Information System (INIS)

    Weier, Heinz-Ulrich; Kwan, Johnson; Lu, Chun-Mei; Ito, Yuko; Wang, Mei; Baumgartner, Adolf; Hayward, Simon W.; Weier, Jingly F.; Zitzelsberger, Horst F.

    2009-01-01

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, USSR, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the 'ret-negative' tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.

  6. Kinase Expression and Chromosomal Rearrangements in Papillary Thyroid Cancer Tissues: Investigations at the Molecular and Microscopic Levels

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz-Ulrich; Kwan, Johnson; Lu, Chun-Mei; Ito, Yuko; Wang, Mei; Baumgartner, Adolf; Hayward, Simon W.; Weier, Jingly F.; Zitzelsberger, Horst F.

    2009-07-07

    Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, USSR, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the 'ret-negative' tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.

  7. Management as a Symbolizing Construction? Re-Arranging the Understanding of Management

    Directory of Open Access Journals (Sweden)

    Katharina Mayr

    2010-09-01

    Full Text Available In this article, we outline the concept of management as a symbolizing construction. According to Niklas LUHMANN, organizations process by referring to decisions. But decisions are not simply "given" and in principle invisible. This is the reason why organizations institute formalities like protocols, signatures or other insignia of the official that symbolize the decision—without actually being a decision. These symbols allow for making decisions "process-able." And just like a protocol or a signature, management symbolizes decisions as well. Management provides an organizational practice with symbols of decision making without being the "unity" of the decisions, as decisions perpetually have to be reconstructed, redefined and rearranged in the communication of all organizational units. Therefore management symbolizes on the one hand more than it can achieve. On the other hand the importance of management as a symbolizing construction lies in allowing the reconstruction, redefining and rearrangement of decisions by making them visible and recognizable. Heroic managers, meetings, management tools and procedures are solutions to the paradox of decision making. By symbolizing decidedness they create credibilities that conceal the self-referential construction of organizational communication and the paradox of its decision praxis. URN: urn:nbn:de:0114-fqs1003218

  8. Data re-arranging techniques leading to proper variable selections in high energy physics

    Science.gov (United States)

    Kůs, Václav; Bouř, Petr

    2017-12-01

    We introduce a new data based approach to homogeneity testing and variable selection carried out in high energy physics experiments, where one of the basic tasks is to test the homogeneity of weighted samples, mainly the Monte Carlo simulations (weighted) and real data measurements (unweighted). This technique is called ’data re-arranging’ and it enables variable selection performed by means of the classical statistical homogeneity tests such as Kolmogorov-Smirnov, Anderson-Darling, or Pearson’s chi-square divergence test. P-values of our variants of homogeneity tests are investigated and the empirical verification through 46 dimensional high energy particle physics data sets is accomplished under newly proposed (equiprobable) quantile binning. Particularly, the procedure of homogeneity testing is applied to re-arranged Monte Carlo samples and real DATA sets measured at the particle accelerator Tevatron in Fermilab at DØ experiment originating from top-antitop quark pair production in two decay channels (electron, muon) with 2, 3, or 4+ jets detected. Finally, the variable selections in the electron and muon channels induced by the re-arranging procedure for homogeneity testing are provided for Tevatron top-antitop quark data sets.

  9. Consequences of Common Topological Rearrangements for Partition Trees in Phylogenomic Inference.

    Science.gov (United States)

    Chernomor, Olga; Minh, Bui Quang; von Haeseler, Arndt

    2015-12-01

    In phylogenomic analysis the collection of trees with identical score (maximum likelihood or parsimony score) may hamper tree search algorithms. Such collections are coined phylogenetic terraces. For sparse supermatrices with a lot of missing data, the number of terraces and the number of trees on the terraces can be very large. If terraces are not taken into account, a lot of computation time might be unnecessarily spent to evaluate many trees that in fact have identical score. To save computation time during the tree search, it is worthwhile to quickly identify such cases. The score of a species tree is the sum of scores for all the so-called induced partition trees. Therefore, if the topological rearrangement applied to a species tree does not change the induced partition trees, the score of these partition trees is unchanged. Here, we provide the conditions under which the three most widely used topological rearrangements (nearest neighbor interchange, subtree pruning and regrafting, and tree bisection and reconnection) change the topologies of induced partition trees. During the tree search, these conditions allow us to quickly identify whether we can save computation time on the evaluation of newly encountered trees. We also introduce the concept of partial terraces and demonstrate that they occur more frequently than the original "full" terrace. Hence, partial terrace is the more important factor of timesaving compared to full terrace. Therefore, taking into account the above conditions and the partial terrace concept will help to speed up the tree search in phylogenomic inference.

  10. Targeting brain metastases in ALK-rearranged non-small-cell lung cancer.

    Science.gov (United States)

    Zhang, Isabella; Zaorsky, Nicholas G; Palmer, Joshua D; Mehra, Ranee; Lu, Bo

    2015-10-01

    The incidence of brain metastases has increased as a result of improved systemic control and advances in imaging. However, development of novel therapeutics with CNS activity has not advanced at the same rate. Research on molecular markers has revealed many potential targets for antineoplastic agents, and a particularly important aberration is translocation in the ALK gene, identified in non-small-cell lung cancer (NSCLC). ALK inhibitors have shown systemic efficacy against ALK-rearranged NSCLC in many clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain barrier penetration and acquired drug resistance. In this Review, we discuss potential pathways to target ALK-rearranged brain metastases, including next generation ALK inhibitors with greater CNS penetration and mechanisms to overcome resistance. Other important mechanisms to control CNS disease include targeting pathways downstream of ALK phosphorylation, increasing the permeability of the blood-brain barrier, modifying the tumour microenvironment, and adding concurrent radiotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Electronic charge rearrangement at metal/organic interfaces induced by weak van der Waals interactions

    Science.gov (United States)

    Ferri, Nicola; Ambrosetti, Alberto; Tkatchenko, Alexandre

    2017-07-01

    Electronic charge rearrangements at interfaces between organic molecules and solid surfaces play a key role in a wide range of applications in catalysis, light-emitting diodes, single-molecule junctions, molecular sensors and switches, and photovoltaics. It is common to utilize electrostatics and Pauli pushback to control the interface electronic properties, while the ubiquitous van der Waals (vdW) interactions are often considered to have a negligible direct contribution (beyond the obvious structural relaxation). Here, we apply a fully self-consistent Tkatchenko-Scheffler vdW density functional to demonstrate that the weak vdW interactions can induce sizable charge rearrangements at hybrid metal/organic systems (HMOS). The complex vdW correlation potential smears out the interfacial electronic density, thereby reducing the charge transfer in HMOS, changes the interface work functions by up to 0.2 eV, and increases the interface dipole moment by up to 0.3 Debye. Our results suggest that vdW interactions should be considered as an additional control parameter in the design of hybrid interfaces with the desired electronic properties.

  12. 1,2-Fluorine Radical Rearrangements: Isomerization Events in Perfluorinated Radicals.

    Science.gov (United States)

    Van Hoomissen, Daniel J; Vyas, Shubham

    2017-11-16

    Devising effective degradation technologies for perfluoroalkyl substances (PFASs) is an active area of research, where the molecular mechanisms involving both oxidative and reductive pathways are still elusive. One commonly neglected pathway in PFAS degradation is fluorine atom migration in perfluoroalkyl radicals, which was largely assumed to be implausible because of the high C-F bond strength. Using density functional theory calculations, it was demonstrated that 1,2-F atom migrations are thermodynamically favored when the fluorine atom migrated from a less branched carbon center to a more branched carbon center. Activation barriers for these rearrangements were within 19-29 kcal/mol, which are possible to easily overcome at elevated temperatures or in photochemically activated species in the gas or aqueous phase. It was also found that the activation barriers for the 1,2-F atom migration are lowered as much as by 10 kcal/mol when common oxidative degradation products such as HF assisted the rearrangements or if the resulting radical center was stabilized by vicinal π-bonds. Natural bond orbital analyses showed that fluorine moves as a radical in a noncharge-separated state. These findings add an important reaction to the existing knowledge of mechanisms for PFAS degradation and highlights the fact that 1,2-F atom shifts may be a small channel for isomerization of these compounds, but upon availability of mineralization products, this isomerization process could become more prominent.

  13. Effects of chromosomal rearrangements on the zeste-white interaction in Drosophila melanogaster

    International Nuclear Information System (INIS)

    Smolik-Utlaut, S.M.; Gelbart, W.M.

    1987-01-01

    Three gene systems have been shown to exhibit proximity-dependent phenotypes in Drosophila melanogaster; bithorax (BX-C), decapentaplegic (DPP-C) and white (w). In structurally homozygous genotypes, specific allelic combinations at these loci exhibit one phenotype, while in certain rearrangement heterozygotes the same allelic combinations exhibit dramatically different phenotypes. The genetic properties of the proximity-dependent allelic complementation (termed transvection effects) at the BX-C and DPP-C, are quite similar. As determined by cytogenetic analysis of transvection-disrupting rearrangements, the critical regions for the BX-C and DDP-C transvection effects extend proximally from these loci for several hundred polytene chromosome bands. The interaction between the zeste and white loci appears to depend upon the proximity of the two w + alleles. By use of insertional duplications, displacement of w + homologues has been shown to interfere with the zeste-white interaction. In this report, the authors investigate the basis for the difference in the size of the BX-C and DPP-C critical regions from that of white using a 137 Cs-mutagenesis procedure. The authors test and eliminate the possibility that the difference is due to evidence strongly suggests that the zeste-white interaction is, at the phenotypic level, much less sensitive to displacement of the homologous genes than is transvection at either the BX-C or DPP-C. Given these results, they suggest that the zeste-white interaction and transvection are two different proximity-dependent phenomena

  14. Analysis of TCRAD gene recombination: radio-induct rearrangement and signal joint structure

    International Nuclear Information System (INIS)

    Touvrey, C.

    2005-09-01

    We have shown that irradiation of pre-TCR-deficient CD3ε -/- mice restores thymocyte differentiation, by a p53-dependent and by a p53-independent pathway. Events normally associated during normal thymocyte development are dissociated in response to radiation exposure. Both of these pathways require LAT expression. Therefore, radiation exposure activates pre-TCR-like signals. TCRA gene rearrangement is induced following radiation exposure. The signal joints resulting from TCRA gene rearrangement have the same structure than those found in wild type mice. All signal joint analyzed in un-manipulated wild type mice do exhibit junctional diversity. This diversity results mainly from TdT activity. We present evidences that proteins involved in DNA repair and genomic stability participated in SJ formation. We propose that signal joint diversity is not an aberrant process but is a key feature of V(D)J recombination. All our work increases our understanding of molecular events associated with V(D)J recombination. (author)

  15. Three-dimensional rearrangement of single atoms using actively controlled optical microtraps.

    Science.gov (United States)

    Lee, Woojun; Kim, Hyosub; Ahn, Jaewook

    2016-05-02

    We propose and demonstrate three-dimensional rearrangements of single atoms. In experiments performed with single 87Rb atoms in optical microtraps actively controlled by a spatial light modulator, we demonstrate various dynamic rearrangements of up to N = 9 atoms including rotation, 2D vacancy filling, guiding, compactification, and 3D shuffling. With the capability of a phase-only Fourier mask to generate arbitrary shapes of the holographic microtraps, it was possible to place single atoms at arbitrary geometries of a few μm size and even continuously reconfigure them by conveying each atom. For this purpose, we loaded a series of computer-generated phase masks in the full frame rate of 60 Hz of the spatial light modulator, so the animation of phase mask transformed the holographic microtraps in real time, driving each atom along the assigned trajectory. Possible applications of this method of transformation of single atoms include preparation of scalable quantum platforms for quantum computation, quantum simulation, and quantum many-body physics.

  16. Design of collimating and rearrangement systems of laser diode array beam

    Science.gov (United States)

    Gao, Runmei; Fang, Tao; Fu, Rulian; Yao, Jianquan

    2015-10-01

    To improve the laser diode output beam quality, micro-cylindrical lens and the step-type lens combination are designed. The former is used to collimate beam in fast-axis direction, while the latter plays a role in the slow-axis of splitting and the rearrangement. The micro-column semi-elliptical lens is made with the drops of spherical zoom lensin electric field and with the help of the material properties of light-cured production, which can reduce the reflection of the front surface and total reflection loss of the after. The divergence angle in the fast axis is compressed to roughly the same as that in the slow-axis direction; Stepped lens splits compressed long strip beam in the slow axis, with parallelogram style of level equidistant and rearrange in the fast axis direction. The spot in the slow axis gets smaller and the spot becomes larger in the fast axis. At last divergence angle and the beam spot achieve balanced in the fast axis and slow axis, optical parameters BPP integrates approximate the same, and beam quality can be improved.

  17. A mechanistic investigation on the formation and rearrangement of silaspiropentane: A theoretical study.

    Science.gov (United States)

    Yildiz, Cem Burak; Azizoglu, Akin

    2016-07-01

    The formation of silaspiropentane from addition of singlet silacyclopropylidene 1 and silacyclopropylidenoid 8 to ethylene has been investigated separately at the B3LYP, X3LYP, WB97XD, and M05-2X theories using the 6-31+G(d,p) basis set. The silacycloproylidenoid addition follows a stepwise route. In contrast, a concerted mechanism occurs for silacyclopropylidene addition. Moreover, the intramolecular rearrangements of silaspiropentane 9 to methylenesilacyclobutane 11 and 2-silaallene + ethylene 12 have been studied extensively. The required energy barrier for the isomerization of 9 to 10 was determined to be 44.0 kcal mol(-1) at the B3LYP/6-31+G(d,p) level. After formation of 10, the rearrangement to methylenesilacyclobutane 12 is highly exergonic by -15.9 kcal mol(-1), which makes this reaction promising. However, the conversion of 9 to 11 is calculated to be quite endergonic, by 26.5 kcal mol(-1).

  18. M to T Rearrangement: An Approach to Correct Webbed Neck Deformity

    Directory of Open Access Journals (Sweden)

    Ananth S. Murthy

    2014-01-01

    Full Text Available For the Noonan syndrome patient, the most concerning physical defect is often congenital webbing of the neck or pterygium colli. We present a patient with pterygium colli and a low and laterally displaced nuchal hairline. Since its description, various surgical approaches have been implemented to correct the deformity. Previously reported posterior and lateral approaches have notable disadvantages with regard to hairline displacement and recurrence. In order to address these disadvantages, a new surgical technique was used on this patient. We have termed this technique an M to T rearrangement. Using a lateral approach, the M and T incisions are made and the trapezial fascial web is directly visualized and able to be completely excised. This prevents the recurrence seen with the use of posterior techniques. Inferolateral displacement of hair-bearing skin can be removed with resection of the superior intervening triangle and improves the appearance of the low nuchal hairline. The excision of excess skin along with the zig-zag closure also prevents postoperative scar contraction and recurrence. An important effect of this technique is the prevention of anterior displacement of hair bearing skin. M to T rearrangement is an effective technique for the correction of webbed neck deformities seen in Noonan and Turner syndromes.

  19. The rearranged mitochondrial genome of Leptopilina boulardi (Hymenoptera: Figitidae, a parasitoid wasp of Drosophila

    Directory of Open Access Journals (Sweden)

    Daniel S. Oliveira

    Full Text Available Abstract The partial mitochondrial genome sequence of Leptopilina boulardi (Hymenoptera: Figitidae was characterized. Illumina sequencing was used yielding 35,999,679 reads, from which 102,482 were utilized in the assembly. The length of the sequenced region of this partial mitochondrial genome is 15,417 bp, consisting of 13 protein-coding, two rRNA, and 21tRNA genes (the trnaM failed to be sequenced and a partial A+T-rich region. All protein-coding genes start with ATN codons. Eleven protein-coding genes presented TAA stop codons, whereas ND6 and COII that presented TA, and T nucleotides, respectively. The gene pattern revealed extensive rearrangements compared to the typical pattern generally observed in insects. These rearrangements involve two protein-coding and two ribosomal genes, along with the 16 tRNA genes. This gene order is different from the pattern described for Ibalia leucospoides (Ibaliidae, Cynipoidea, suggesting that this particular gene order can be variable among Cynipoidea superfamily members. A maximum likelihood phylogenetic analysis of the main groups of Apocrita was performed using amino acid sequence of 13 protein-coding genes, showing monophyly for the Cynipoidea superfamily within the Hymenoptera phylogeny.

  20. Real-time 3D visualization of cellular rearrangements during cardiac valve formation.

    Science.gov (United States)

    Pestel, Jenny; Ramadass, Radhan; Gauvrit, Sebastien; Helker, Christian; Herzog, Wiebke; Stainier, Didier Y R

    2016-06-15

    During cardiac valve development, the single-layered endocardial sheet at the atrioventricular canal (AVC) is remodeled into multilayered immature valve leaflets. Most of our knowledge about this process comes from examining fixed samples that do not allow a real-time appreciation of the intricacies of valve formation. Here, we exploit non-invasive in vivo imaging techniques to identify the dynamic cell behaviors that lead to the formation of the immature valve leaflets. We find that in zebrafish, the valve leaflets consist of two sets of endocardial cells at the luminal and abluminal side, which we refer to as luminal cells (LCs) and abluminal cells (ALCs), respectively. By analyzing cellular rearrangements during valve formation, we observed that the LCs and ALCs originate from the atrium and ventricle, respectively. Furthermore, we utilized Wnt/β-catenin and Notch signaling reporter lines to distinguish between the LCs and ALCs, and also found that cardiac contractility and/or blood flow is necessary for the endocardial expression of these signaling reporters. Thus, our 3D analyses of cardiac valve formation in zebrafish provide fundamental insights into the cellular rearrangements underlying this process. © 2016. Published by The Company of Biologists Ltd.

  1. Recurrent Rearrangements of Human Amylase Genes Create Multiple Independent CNV Series.

    Science.gov (United States)

    Shwan, Nzar A A; Louzada, Sandra; Yang, Fengtang; Armour, John A L

    2017-05-01

    The human amylase gene cluster includes the human salivary (AMY1) and pancreatic amylase genes (AMY2A and AMY2B), and is a highly variable and dynamic region of the genome. Copy number variation (CNV) of AMY1 has been implicated in human dietary adaptation, and in population association with obesity, but neither of these findings has been independently replicated. Despite these functional implications, the structural genomic basis of CNV has only been defined in detail very recently. In this work, we use high-resolution analysis of copy number, and analysis of segregation in trios, to define new, independent allelic series of amylase CNVs in sub-Saharan Africans, including a series of higher-order expansions of a unit consisting of one copy each of AMY1, AMY2A, and AMY2B. We use fiber-FISH (fluorescence in situ hybridization) to define unexpected complexity in the accompanying rearrangements. These findings demonstrate recurrent involvement of the amylase gene region in genomic instability, involving at least five independent rearrangements of the pancreatic amylase genes (AMY2A and AMY2B). Structural features shared by fundamentally distinct lineages strongly suggest that the common ancestral state for the human amylase cluster contained more than one, and probably three, copies of AMY1. © 2017 WILEY PERIODICALS, INC.

  2. Secondary Leukemia Associated with the Anti-Cancer Agent, Etoposide, a Topoisomerase II Inhibitor

    Directory of Open Access Journals (Sweden)

    Sachiko Ezoe

    2012-07-01

    Full Text Available Etoposide is an anticancer agent, which is successfully and extensively used in treatments for various types of cancers in children and adults. However, due to the increases in survival and overall cure rate of cancer patients, interest has arisen on the potential risk of this agent for therapy-related secondary leukemia. Topoisomerase II inhibitors, including etoposide and teniposide, frequently cause rearrangements involving the mixed lineage leukemia (MLL gene on chromosome 11q23, which is associated with secondary leukemia. The prognosis is extremely poor for leukemias associated with rearrangements in the MLL gene, including etoposide-related secondary leukemias. It is of great importance to gain precise knowledge of the clinical aspects of these diseases and the mechanism underlying the leukemogenesis induced by this agent to ensure correct assessments of current and future therapy strategies. Here, I will review current knowledge regarding the clinical aspects of etoposide-related secondary leukemia, some probable mechanisms, and strategies for treating etoposide-induced leukemia.

  3. Design, development, mechanistic elucidation, and rational optimization of a tandem Ireland Claisen/Cope rearrangement reaction for rapid access to the (iso)cyclocitrinol core.

    Science.gov (United States)

    Plummer, Christopher W; Wei, Carolyn S; Yozwiak, Carrie E; Soheili, Arash; Smithback, Sara O; Leighton, James L

    2014-07-16

    An approach to the synthesis of the (iso)cyclocitrinol core structure is described. The key step is a tandem Ireland Claisen/Cope rearrangement sequence, wherein the Ireland Claisen rearrangement effects ring contraction to a strained 10-membered ring, and that strain in turn drives the Cope rearrangement under unusually mild thermal conditions. A major side product was identified as resulting from an unexpected and remarkably facile [1,3]-sigmatropic rearrangement, and a tactic to disfavor the [1,3] pathway and increase the efficiency of the tandem reaction was rationally devised.

  4. Nitrene-carbene-carbene rearrangement. Photolysis and thermolysis of tetrazolo[5,1- a ]phthalazine with formation of 1-phthalazinylnitrene, o-cyanophenylcarbene, and phenylcyanocarbene

    DEFF Research Database (Denmark)

    Høj, Martin; Kvaskoff, David; Wentrup, Curt

    2014-01-01

    ). The rearrangement of 12 â., 13 â., 14 constitutes a carbene-carbene rearrangement. 1-Phthalazinylnitrene 310 is observed by means of its UV-vis spectrum in Ar matrix following FVT of 9 above 550 C. Rearrangement to cyanophenylcarbenes also takes place on FVT of 9 as evidenced by observation of the products of ring...... contraction, viz., fulvenallenes and ethynylcyclopentadienes 16-18. Thus the overall rearrangement 10 → 11 → 12 â., 13 â., 14 can be formulated. © 2013 American Chemical Society....

  5. Secondary acute pneumonias

    International Nuclear Information System (INIS)

    Rozenshtraukh, L.C.; Rybakova, N.I.; Vinner, M.G.

    1987-01-01

    Pathological changes, promoting the development of secondary pneumonias, are investigated. To this group belong: blood circulation disturbance in small circle, bronchial passability disturbance, aspiration of liquids, gases and vapors, infections and purulent processes, intoxications, injuries, operative interference. Roetgenologic symptomatics of each secondary acute pneumonia form is presented in detail

  6. Ontogeny of human natural killer (NK) cells: fetal NK cells mediate cytolytic function and express cytoplasmic CD3 epsilon,delta proteins

    NARCIS (Netherlands)

    Phillips, J. H.; Hori, T.; Nagler, A.; Bhat, N.; Spits, H.; Lanier, L. L.

    1992-01-01

    Natural killer (NK) cells have been defined as CD3 epsilon-, CD16+ and/or CD56+ lymphocytes that mediate major histocompatibility complex (MHC)-unrestricted cytotoxicity against certain tumors and virus-infected cells. Unlike T lymphocytes, NK cells do not rearrange or productively express T cell

  7. Secondary fuel delivery system

    Science.gov (United States)

    Parker, David M.; Cai, Weidong; Garan, Daniel W.; Harris, Arthur J.

    2010-02-23

    A secondary fuel delivery system for delivering a secondary stream of fuel and/or diluent to a secondary combustion zone located in the transition piece of a combustion engine, downstream of the engine primary combustion region is disclosed. The system includes a manifold formed integral to, and surrounding a portion of, the transition piece, a manifold inlet port, and a collection of injection nozzles. A flowsleeve augments fuel/diluent flow velocity and improves the system cooling effectiveness. Passive cooling elements, including effusion cooling holes located within the transition boundary and thermal-stress-dissipating gaps that resist thermal stress accumulation, provide supplemental heat dissipation in key areas. The system delivers a secondary fuel/diluent mixture to a secondary combustion zone located along the length of the transition piece, while reducing the impact of elevated vibration levels found within the transition piece and avoiding the heat dissipation difficulties often associated with traditional vibration reduction methods.

  8. Secondary and tertiary hyperparathyroidism.

    Science.gov (United States)

    Jamal, Sophie A; Miller, Paul D

    2013-01-01

    We reviewed the etiology and management of secondary and tertiary hyperparathyroidism. Secondary hyperparathyroidism is characterized by an increase in parathyroid hormone (PTH) that is appropriate and in response to a stimulus, most commonly low serum calcium. In secondary hyperparathyroidism, the serum calcium is normal and the PTH level is elevated. Tertiary hyperparathyroidism is characterized by excessive secretion of PTH after longstanding secondary hyperparathyroidism, in which hypercalcemia has ensued. Tertiary hyperparathyroidism typically occurs in men and women with chronic kidney disease usually after kidney transplant. The etiology and treatment of secondary hyperparathyroidism is relatively straightforward whereas data on the management of tertiary hyperparathyroidism is limited to a few small trials with short follow-up. Copyright © 2013 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

  9. Aryl nitrene rearrangements: spectroscopic observation of a benzazirine and its ring expansion to a ketenimine by heavy-atom tunneling.

    Science.gov (United States)

    Inui, Hiroshi; Sawada, Kazuhiro; Oishi, Shigero; Ushida, Kiminori; McMahon, Robert J

    2013-07-17

    In the photodecompositions of 4-methoxyphenyl azide (1) and 4-methylthiophenyl azide (5) in argon matrixes at cryogenic temperatures, benzazirine intermediates were identified on the basis of IR spectra. As expected, the benzazirines photochemically rearranged to the corresponding ketenimines and triplet nitrenes. Interestingly, with the methylthio substituent, the rearrangement of benzazirine 8 to ketenimine 7 occurred at 1.49 × 10(-5) s(-1) even in the dark at 10 K, despite a computed activation barrier of 3.4 kcal mol(-1). Because this rate is 10(57) times higher than that calculated for passing over the barrier and because it shows no temperature dependence, the rearrangement mechanism is interpreted in terms of heavy-atom tunneling.

  10. Synthesis of the AB ring system of clifednamide utilizing Claisen rearrangement and Diels-Alder reaction as key steps.

    Science.gov (United States)

    Loke, Inga; Bentzinger, Guillaume; Holz, Julia; Raja, Aruna; Bhasin, Aman; Sasse, Florenz; Köhn, Andreas; Schobert, Rainer; Laschat, Sabine

    2016-01-21

    In order to construct the functionalized AB ring system of clifednamide, member of the class of macrocyclic tetramic acid lactams, a synthesis was developed which utilized an Ireland-Claisen rearrangement and an intramolecular Diels-Alder reaction. Starting from di-O-isopropylidene-d-mannitol the allyl carboxylate precursor for the sigmatropic rearrangement was prepared. This rearrangement proceeded diastereoselectively only in the presence of an allyl silyl ether instead of the parent enone in the side chain, as suggested by deuteration experiments. A subsequent Diels-Alder reaction yielded the target ethyl hexahydro-1H-indene-carboxylate with high diastereoselectivity. Quantum-chemical investigations of this intramolecular Diels-Alder reaction support the proposed configuration of the final product.

  11. Recurrent rearrangements of the PLAG1 and HMGA2 genes in lacrimal gland pleomorphic adenoma and carcinoma ex pleomorphic adenoma

    DEFF Research Database (Denmark)

    Andreasen, Simon; von Holstein, Sarah L; Homøe, Preben

    2018-01-01

    PURPOSE: Lacrimal gland tumours constitute a wide spectrum of neoplastic lesions that are histologically similar to tumours of the salivary gland. In the salivary gland, pleomorphic adenoma (PA) is frequently characterized by recurrent chromosomal rearrangements of the PLAG1 and HMGA2 genes......, a genetic feature retained in carcinoma ex pleomorphic adenoma (ca-ex-PA) that makes it possible to distinguish ca-ex-PA from de novo carcinomas. However, whether PLAG1 and HMGA2 gene rearrangements are found in lacrimal gland PA and ca-ex-PA is not known. METHODS: Twenty-one lacrimal gland PAs and four ca......-ex-PAs were retrospectively reviewed and subjected to break-apart fluorescence in situ hybridization (FISH) for rearrangements of the PLAG1 gene. Cases without PLAG1 abnormalities were subjected to HMGA2 break-apart FISH. Immunohistochemical staining for PLAG1 and HMGA2 protein was performed and correlated...

  12. Synthesis of Biologically Active Natural Component 4-Hydroxyderricin Through Water-Accelerated [3,3]-Sigmatropic Rearrangement

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sijun; Lee, Jaejun; Yoon, Hyunho; Jun, Jonggab [Hallym Univ., Chuncheon (Korea, Republic of)

    2013-09-15

    We report herein the practical and effective total synthesis of biologically active 4-hydroxyderricin, a poly-phenolic chalcone compound containing m-prenyl group at ring A. The key steps of the synthesis are Claisen-Schmidt condensation of the the two phenolic units 17 and 18 to chalcone 19 and the water-accelerated [3,3]-sigma-tropic rearrangement of 1,1-dimethyl-2-propenyl aryl ether 20 to introduce the m-prenyl unit in 4-hydroxyderricin. Two types of polyphenolic chalcones, 4-hydroxyderricin (1) and xanthoangelol (2), are especially rich in the plant, and the 4-hydroxyderricin exhibited the major responsibility for the various biological activities. Sugamoto reported the synthesis of 4-hydroxy-derricin via [1,3]-sigmatropic rearrangement of chalcone ether using montmorillonite K10 which showed relatively low rearrangement yield (Scheme 1), and this is the only reported total synthesis of 1 as far as we know.

  13. Chromogenic in situ hybridization is a reliable assay for detection of ALK rearrangements in adenocarcinomas of the lung.

    Science.gov (United States)

    Schildhaus, Hans-Ulrich; Deml, Karl-Friedrich; Schmitz, Katja; Meiboom, Maren; Binot, Elke; Hauke, Sven; Merkelbach-Bruse, Sabine; Büttner, Reinhard

    2013-11-01

    Reliable detection of anaplastic lymphoma kinase (ALK) rearrangements is a prerequisite for personalized treatment of lung cancer patients, as ALK rearrangements represent a predictive biomarker for the therapy with specific tyrosine kinase inhibitors. Currently, fluorescent in situ hybridization (FISH) is considered to be the standard method for assessing formalin-fixed and paraffin-embedded tissue for ALK inversions and translocations. However, FISH requires a specialized equipment, the signals fade rapidly and it is difficult to detect overall morphology and tumor heterogeneity. Chromogenic in situ hybridization (CISH) has been successfully introduced as an alternative test for the detection of several genetic aberrations. This study validates a newly developed ALK CISH assay by comparing FISH and CISH signal patterns in lung cancer samples with and without ALK rearrangements. One hundred adenocarcinomas of the lung were included in this study, among them 17 with known ALK rearrangement. FISH and CISH were carried out and evaluated according to the manufacturers' recommendations. For both assays, tumors were considered positive if ≥15% of tumor cells showed either isolated 3' signals or break-apart patterns or a combination of both. A subset of tumors was exemplarily examined by using a novel EML4 (echinoderm microtubule-associated protein-like 4) CISH probe. Red, green and fusion CISH signals were clearcut and different signal patterns were easily recognized. The percentage of aberrant tumor cells was statistically highly correlated (PCISH. On the basis of 86 samples that were evaluable by ALK CISH, we found a 100% sensitivity and 100% specificity of this assay. Furthermore, EML4 rearrangements could be recognized by CISH. CISH is a highly reliable, sensitive and specific method for the detection of ALK gene rearrangements in pulmonary adenocarcinomas. Our results suggest that CISH might serve as a suitable alternative to FISH, which is the current gold

  14. Stereoselective synthesis of functionalized cyclic amino acid derivatives via a [2,3]-Stevens rearrangement and ring-closing metathesis.

    Science.gov (United States)

    Nash, Aaron; Soheili, Arash; Tambar, Uttam K

    2013-09-20

    Unnatural cyclic amino acids are valuable tools in biomedical research and drug discovery. A two-step stereoselective strategy for converting simple glycine-derived aminoesters into unnatural cyclic amino acid derivatives has been developed. The process includes a palladium-catalyzed tandem allylic amination/[2,3]-Stevens rearrangement followed by a ruthenium-catalyzed ring-closing metathesis. The [2,3]-rearrangement proceeds with high diastereoselectivity through an exo transition state. Oppolzer's chiral auxiliary was utilized to access an enantiopure cyclic amino acid by this approach, which will enable future biological applications.

  15. Prognostic impact of concurrent MYC and BCL6 rearrangements and expression in de novo diffuse large B-cell lymphoma

    DEFF Research Database (Denmark)

    Ye, Qing; Xu-Monette, Zijun Y; Tzankov, Alexandar

    2016-01-01

    Double-hit B-cell lymphoma is a common designation for a group of tumors characterized by concurrent translocations of MYC and BCL2, BCL6, or other genes. The prognosis of concurrent MYC and BCL6 translocations is not well known. In this study, we assessed rearrangements and expression of MYC, BCL2...... frequent in activated B-cell like diffuse large B-cell lymphoma). In summary, diffuse large B-cell lymphoma patients with either MYC/BCL6 rearrangements or MYC/BCL6 co-expression did not always have poorer prognosis; MYC expression levels should be evaluated simultaneously; and double-hit B-cell lymphoma...

  16. Analysis of perturbation methods for rearrangement collisions: Comparison of distorted-wave and coupled-channel-wave transition amplitudes

    International Nuclear Information System (INIS)

    Suck Salk, S.H.

    1985-01-01

    With the use of projection operators, the formal expressions of distorted-wave and coupled-channel-wave transition amplitudes for rearrangement collisions are derived. Use of projection operators (for the transition amplitudes) sharpens our understanding of the structural differences between the two transition amplitudes. The merit of each representation of the transition amplitudes is discussed. Derived perturbation potentials are found to have different structures. The rigorously derived distorted-wave Born-approximation (DWBA) transition amplitude is shown to be a generalization of the earlier DWBA expression obtained from the assumption of the dominance of elastic scattering in rearrangement collisions

  17. Ph1 chromosomes and bcr gene rearrangements in chronic myelocytic leukemia patients developed from atomic bomb survivors

    International Nuclear Information System (INIS)

    Tanaka, Kimio; Takechi, Miho; Shigeta, Chiharu; Sakatani, Keiko; Oguma, Nobuo; Kamada, Nanao; Takimoto, Yasuo; Kuramoto, Atsushi

    1989-01-01

    This study compared findings of chronic myelocytic leukemia (CML) in A-bomb survivors (n=8) developing CML within 10 years after the bombing and in non-exposed CML patients (n=14). Both Ph 1 chromosomes and bcr rearrangement were observed in all patients in both exposed and non-exposed groups. There was no significant difference in distribution sites of bcr rearrangement between the groups. These results suggest that bcr-abl chimera mRNA and chimera protein associated with Ph 1 chromosomes have an important role in the development of CML among A-bomb survivors, as well as among non-exposed patients. (N.K.)

  18. Striving for Normalcy after Lower Extremity Reconstruction with Free Tissue: The Role of Secondary Esthetic Refinements.

    Science.gov (United States)

    Nelson, Jonas A; Fischer, John P; Haddock, Nicholas T; Mackay, Duncan; Wink, Jason D; Newman, Andrew S; Levin, L Scott; Kovach, Stephen J

    2016-02-01

    Many patients with successful lower extremity salvage have postoperative functional and esthetic concerns. Such concerns range from contour irregularity preventing proper shoe-fitting to esthetic concerns involving color, contour, and texture match. The purpose of this study is to determine the overall incidence as well as factors associated with an increased likelihood of undergoing secondary, esthetic refinements of lower extremity free flaps and to review current revision techniques. All patients undergoing lower extremity soft tissue coverage for limb salvage procedures between January 2007 and June 2013 at a single institution were included in the analysis. Patients who underwent secondary refinements for lower extremity free flaps were compared with patients not undergoing secondary procedures. During the study period, 152 patients underwent reconstruction and were eligible for inclusion. Of these, 32 (21.1%) patients underwent secondary, esthetic revisions. Few differences in patient or case characteristics were noted, although revision patients trended toward being younger, having lower body mass index, with defects secondary to acute trauma located below the ankle. The most common revision was complex soft tissue rearrangement or surgical flap debulking/direct excision (87.5% of patients), followed by scar revision (12.5%), suction-assisted lipectomy (3.1%), laser scar revision (3.1%), and tissue expansion with local tissue rearrangement (3.1%). A significant portion of patients desire secondary revisions following the initial procedure. This is especially true of younger patients with below ankle reconstruction. In many patients, an esthetic consideration should not be of secondary concern, but should be part of the ultimate reconstructive algorithm for lower extremity limb salvage. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  19. P-glycoprotein confers acquired resistance to 17-DMAG in lung cancers with an ALK rearrangement

    International Nuclear Information System (INIS)

    Kim, Hee Joung; Lee, Kye Young; Kim, Young Whan; Choi, Yun Jung; Lee, Jung-Eun; Choi, Chang Min; Baek, In-Jeoung; Rho, Jin Kyung; Lee, Jae Cheol

    2015-01-01

    Because anaplastic lymphoma kinase (ALK) is dependent on Hsp90 for protein stability, Hsp90 inhibitors are effective in controlling growth of lung cancer cells with ALK rearrangement. We investigated the mechanism of acquired resistance to 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), a geldanamycin analogue Hsp90 inhibitor, in H3122 and H2228 non-small cell lung cancer cell lines with ALK rearrangement. Resistant cell lines (H3122/DR-1, H3122/DR-2 and H2228/DR) were established by repeated exposure to increasing concentrations of 17-DMAG. Mechanisms for resistance by either NAD(P)H/quinone oxidoreductase 1 (NQO1), previously known as a factor related to 17-DMAG resistance, or P-glycoprotein (P-gp; ABCB1/MDR1) were queried using RT-PCR, western blot analysis, chemical inhibitors, the MTT cell proliferation/survival assay, and cellular efflux of rhodamine 123. The resistant cells showed no cross-resistance to AUY922 or ALK inhibitors, suggesting that ALK dependency persists in cells with acquired resistance to 17-DMAG. Although expression of NQO1 was decreased in H3122/DR-1 and H3122/DR-2, NQO1 inhibition by dicumarol did not affect the response of parental cells (H2228 and H3122) to 17-DMAG. Interestingly, all resistant cells showed the induction of P-gp at the protein and RNA levels, which was associated with an increased efflux of the P-gp substrate rhodamine 123 (Rho123). Transfection with siRNA directed against P-gp or treatment with verapamil, an inhibitor of P-gp, restored the sensitivity to the drug in all cells with acquired resistance to 17-DMAG. Furthermore, we also observed that the growth-inhibitory effect of 17-DMAG was decreased in A549/PR and H460/PR cells generated to over-express P-gp by long-term exposure to paclitaxel, and these cells recovered their sensitivity to 17-DMAG through the inhibition of P-gp. P-gp over-expression is a possible mechanism of acquired resistance to 17-DMAG in cells with ALK rearrangement. The online

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

    Directory of Open Access Journals (Sweden)

    Kamila Maliszewska-Olejniczak

    2015-07-01

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

  1. Teaching secondary mathematics

    CERN Document Server

    Rock, David

    2013-01-01

    Solidly grounded in up-to-date research, theory and technology,?Teaching Secondary Mathematics?is a practical, student-friendly, and popular text for secondary mathematics methods courses. It provides clear and useful approaches for mathematics teachers, and shows how concepts typically found in a secondary mathematics curriculum can be taught in a positive and encouraging way. The thoroughly revised fourth edition combines this pragmatic approach with truly innovative and integrated technology content throughout. Synthesized content between the book and comprehensive companion websi

  2. webMGR: an online tool for the multiple genome rearrangement problem.

    Science.gov (United States)

    Lin, Chi Ho; Zhao, Hao; Lowcay, Sean Harry; Shahab, Atif; Bourque, Guillaume

    2010-02-01

    The algorithm MGR enables the reconstruction of rearrangement phylogenies based on gene or synteny block order in multiple genomes. Although MGR has been successfully applied to study the evolution of different sets of species, its utilization has been hampered by the prohibitive running time for some applications. In the current work, we have designed new heuristics that significantly speed up the tool without compromising its accuracy. Moreover, we have developed a web server (webMGR) that includes elaborate web output to facilitate navigation through the results. webMGR can be accessed via http://www.gis.a-star.edu.sg/~bourque. The source code of the improved standalone version of MGR is also freely available from the web site. Supplementary data are available at Bioinformatics online.

  3. Two new types of chromosomal rearrangements in the swine species induced by semen irradiation

    International Nuclear Information System (INIS)

    Franceschini, P.H.; Mikich, A.B.; Garcia, J.M.; Almeida Junior, I.L.; Pinheiro, L.E.L.

    1991-01-01

    In the present experiment were used one boar and 5 descendent of Landrace and Large White cross-breeding were used, all the animals were healthy concerning to the reproductive aspect and chromosome constitution. Initially semen was collected from the boar through the glove hand method, diluted and submitted to gamma irradiation. The total applied dose was of 800 R, with an exposition period of 3,76 min. The artificial insemination of the females with the treated semen was performed from the time of observation of positive tolerance reflex, with each animal receiving 2 inseminations with a 12 hour interval in between. after birth, the piglets had their blood aseptically collected for karyotype preparation and analysis. From 17 piglets born and cytogenetically analysed, 2 chromosomal rearrangements were detected, namely, a reciprocal translocation or insertion, 8q-; 14p+ in a female a pericentric inversion in chromosome 1 in a male. (author). 18 refs, 2 figs

  4. Organocatalyzed Domino [3+2] Cycloaddition/Payne-Type Rearrangement using Carbon Dioxide and Epoxy Alcohols.

    Science.gov (United States)

    Kleij, Arjan Willem; Sopeña, Sergio; Cozzolino, Mariachiara; Escudero-Adán, Eduardo C; Martínez Belmonte, Marta; Maquilón, Cristina

    2018-05-09

    An unprecedented organocatalytic approach towards highly substituted cyclic carbonates from tri- and tetra-substituted oxiranes and carbon dioxide has been developed. The protocol involves the use of a simple and cheap superbase under mild, additive- and metal-free conditions towards the initial formation of a less substituted carbonate product that equilibrates to a tri- or even tetra-substituted cyclic carbonate under thermodynamic control. The latter are conveniently trapped in situ providing overall a new domino process for synthetically elusive heterocyclic scaffolds. Control experiments provide a rationale for the observed cascade reactions, which demonstrate high similarity with the well-known Payne rearrangement of epoxy alcohols. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Gravity-driven granular flow in a silo: Characterizing local forces and rearrangements

    Directory of Open Access Journals (Sweden)

    Thackray Emma

    2017-01-01

    Full Text Available While the gravity-driven flow of a granular material in a silo geometry can be modeled by the Beverloo equation, the mesoscale-level particle rearrangements and interactions that drive this flow are not wellunderstood. We have constructed a quasi-two-dimensional system of bidisperse, millimeter-scale disks with photoelastic properties that make force networks within the material visible. The system is contained in an acrylic box with an adjustable bottom opening. We can approach the clogging transition by adjusting this opening. By placing the system between cross-polarizers, we can obtain high-speed video of this system during flow, and extract intensity signals that can be used to identify and quantify localized, otherwise indeterminate forces. We can simultaneously track individual particle motions, which can be used to identify shear transformation zones in the system. In this paper, we present our results thus far.

  6. Solvent effects in the acid-catalysed rearrangements of 1,2-oxazines

    International Nuclear Information System (INIS)

    Yagoub, A.K.; Ogur, J.A.; Wanekaya, A.K.

    2005-12-01

    The rates of acid-catalyzed rearrangements of 6-ethoxy-5,6-dihydro-3-phenyl-4H-1,2-oxazines have been investigated in H 2 SO 4 /methanol, MeCN and Me 2 SO by means of spectrophotometric methods. Pseudo first order rate constants were obtained in each case. Results in methanol supported an A1 type mechanism. Also investigated were the correlation of reaction rates with Hammet acidity function (H 0 ) by application of the Bunnet criterion where a slope of -0.67 was obtained. Further, the solvent effect was considered from two points of mechanistic views: the thermodynamic transfer functions of MeOH to MeCN and Me 2 SO where the rate was found fast in MeCN and slow in Me 2 SO and the Kirkwood-Buff preferential solvation with aqueous MeOH, MeCN and Me 2 SO. The techniques supported the proposed transition state structure. (author)

  7. Theoretic investigation into polytopic rearrangements mechanism of molecules of sulfurans and their analogs

    International Nuclear Information System (INIS)

    Minkin, V.I.; Minyaev, R.M.

    1975-01-01

    The energy characteristics and electron distributions were calculated for the fundamental and transitional states in topomerization of configuration of sulfo-, selenium and tellurium-uranium compounds of the AX 4 type. Also mapping of the potential energies was made for the predominant topomerization mechanisms. The mechanisms were classified into rearrangement types according to exchange-responsible apical and equatorial ligands. The physical mechanisms of the topomerization were determined on the basis of symmetry requirements for transitional configuration with respect to non-interchanging ligands. The lowest activation barrier was characteristic for the Berry mechanism of pseudorotation; however, other mechanism (the lever and pyramidal type) can compete with the Berry mechanisms. The expanded method of Hukkel does not give correct values for the relative energy of the fundamental and transitional configurations for sulfouranium molecules and their analogs for two of the three exchange mechanisms examined. Tunnel ligand-exchange mechanism cannot compete with the kinetic path of psudorotation reaction even at very low temperatures

  8. Asymptotic form of the charge exchange cross section in the three body rearrangement collisions

    Science.gov (United States)

    Omidvar, K.

    1975-01-01

    A three body general rearrangement collision is considered where the initial and final bound states are described by the hydrogen-like wave functions. Mathematical models are developed to establish the relationships of quantum number, the reduced mass, and the nuclear charge of the final state. It is shown that for the low lying levels, the reciprocal of n cubed scaling law at all incident energies is only approximately satisfied. The case of the symmetric collisions is considered and it is shown that for high n and high incident energy, E, the cross section behaves as the reciprocal of E cubed. Zeros and minima in the differential cross sections in the limit of high n for protons on atomic hydrogen and positrons on atomic hydrogen are given.

  9. Suppression of gross chromosomal rearrangements by a new alternative replication factor C complex

    International Nuclear Information System (INIS)

    Banerjee, Soma; Sikdar, Nilabja; Myung, Kyungjae

    2007-01-01

    Defects in DNA replication fidelity lead to genomic instability. Gross chromosomal rearrangement (GCR), a type of genomic instability, is highly enhanced by various initial mutations affecting DNA replication. Frequent observations of GCRs in many cancers strongly argue the importance of maintaining high fidelity of DNA replication to suppress carcinogenesis. Recent genome wide screens in Saccharomyces cerevisiae identified a new GCR suppressor gene, ELG1, enhanced level of genome instability gene 1. Its physical interaction with proliferating cell nuclear antigen (PCNA) and complex formation with Rfc2-5p proteins suggest that Elg1 functions to load/unload PCNA onto DNA during a certain DNA metabolism. High level of DNA damage accumulation and enhanced phenotypes with mutations in genes involved in cell cycle checkpoints, homologous recombination (HR), or chromatin assembly in the elg1 strain suggest that Elg1p-Rfc2-5p functions in a fundamental DNA metabolism to suppress genomic instability

  10. Synthesis of enyne and aryl vinyl sulfoxides: functionalization via Pummerer rearrangement.

    Science.gov (United States)

    Souza, Frederico B; Shamim, Anwar; Argomedo, Luiz M Z; Pimenta, Daniel C; Stefani, Hélio A

    2015-11-01

    An efficient methodology for the synthesis of aryl-substituted vinyl sulfoxides through direct substitution of aryl-substituted alkynyl grignard reagents on menthyl-p-toluenesulfinate followed by Suzuki-Miyaura cross-coupling reaction has been developed. It has also been described that the reaction of alkyl-substituted and cycloalkyl-substituted alkynyl grignard reagents with menthyl-p-toluenesulfinate led to two products, i.e., alkynyl sulfoxide derivatives, as a result of substitution, and enyne sulfoxide derivatives, which resulted from substitution followed by Michael type addition. It was possible to selectively synthesize the enyne sulfoxide derivatives by changing the concentration of the grignard reagent. These alkenyl sulfoxides were transformed into the corresponding [Formula: see text]-thio aldehydes in high yields via additive Pummerer rearrangement.

  11. Hierarchical Oct4 Binding in Concert with Primed Epigenetic Rearrangements during Somatic Cell Reprogramming

    Directory of Open Access Journals (Sweden)

    Jun Chen

    2016-02-01

    Full Text Available The core pluripotency factor Oct4 plays key roles in somatic cell reprogramming through transcriptional control. Here, we profile Oct4 occupancy, epigenetic changes, and gene expression in reprogramming. We find that Oct4 binds in a hierarchical manner to target sites with primed epigenetic modifications. Oct4 binding is temporally continuous and seldom switches between bound and unbound. Oct4 occupancy in most of promoters is maintained throughout the entire reprogramming process. In contrast, somatic cell-specific enhancers are silenced in the early and intermediate stages, whereas stem cell-specific enhancers are activated in the late stage in parallel with cell fate transition. Both epigenetic remodeling and Oct4 binding contribute to the hyperdynamic enhancer signature transitions. The hierarchical Oct4 bindings are associated with distinct functional themes at different stages. Collectively, our results provide a comprehensive molecular roadmap of Oct4 binding in concert with epigenetic rearrangements and rich resources for future reprogramming studies.

  12. Human ETS2 gene on chromosome 21 is not rearranged in Alzheimer disease

    International Nuclear Information System (INIS)

    Sacchi, N.; Nalbantoglu, J.; Sergovich, F.R.; Papas, T.S.

    1988-01-01

    The human ETS2 gene, a member of the ETS gene family, with sequence homology with the retroviral ets sequence of the avian erythroblastosis retrovirus E26 is located on chromosome 21. Molecular genetic analysis of Down syndrome (DS) patients with partial trisomy 21 allowed us to reinforce the supposition that ETS2 may be a gene of the minimal DS genetic region. It was originally proposed that a duplication of a portion of the DS region represents the genetic basis of Alzheimer disease, a condition associated also with DS. No evidence of either rearrangements or duplications of ETS2 could be detected in DNA from fibroblasts and brain tissue of Alzheimer disease patients with either the sporadic or the familiar form of the disease. Thus, an altered ETS2 gene dosage does not seem to be a genetic cause or component of Alzheimer disease

  13. Intra-ring haptotropic rearrangements of Mn(CO3 in fluorenyl ligands

    Directory of Open Access Journals (Sweden)

    Souhila Laib

    2017-02-01

    Full Text Available Geometric parameters, and intra-ring haptotropic rearrangements π–π (intra-ring-HRs ŋ5⇌ŋ3 of the manganesetricarbonyl complexes (ŋ5-9-R-C13H8Mn(CO3, R = But and Ph in 18e zero-valence are carried out using density functional theory DFT at PBE/TZP level. The calculated activation barriers to ŋ5⇌ŋ3 intra-ring HR in (ŋ5-9-R-C13H8Mn(CO3, R = But and Ph are (28.5 and 69.5 kcal.mol−1 respectively. The compute of HOMA and FLU indexes indicates the reduction of aromaticity when going from free to coordinated complex. The energy decomposition analysis reveals the dominant ionic character in manganese–Cp bond in the presence of covalent contribution.

  14. Secondary amenorrhea (image)

    Science.gov (United States)

    Secondary amenorrhea is the cessation of menstrual flow for a period of 6 months or more in the absence ... as anxiety can be the root cause of amenorrhea. Treatment can range from behavior modification for excessive ...

  15. A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG.

    Science.gov (United States)

    Rumfelt, L L; Avila, D; Diaz, M; Bartl, S; McKinney, E C; Flajnik, M F

    2001-02-13

    In most vertebrate embryos and neonates studied to date unique antigen receptors (antibodies and T cell receptors) are expressed that possess a limited immune repertoire. We have isolated a subclass of IgM, IgM(1gj), from the nurse shark Ginglymostoma cirratum that is preferentially expressed in neonates. The variable (V) region gene encoding the heavy (H) chain underwent V-D-J rearrangement in germ cells ("germline-joined"). Such H chain V genes were discovered over 10 years ago in sharks but until now were not shown to be expressed at appreciable levels; we find expression of H(1gj) in primary and secondary lymphoid tissues early in life, but in adults only in primary lymphoid tissue, which is identified in this work as the epigonal organ. H(1gj) chain associates covalently with light (L) chains and is most similar in sequence to IgM H chains, but like mammalian IgG has three rather than the four IgM constant domains; deletion of the ancestral IgM C2 domain thus defines both IgG and IgM(1gj). Because sharks are the members of the oldest vertebrate class known to possess antibodies, unique or specialized antibodies expressed early in ontogeny in sharks and other vertebrates were likely present at the inception of the adaptive immune system.

  16. Mapping of genomic EGFRvIII deletions in glioblastoma: insight into rearrangement mechanisms and biomarker development.

    Science.gov (United States)

    Koga, Tomoyuki; Li, Bin; Figueroa, Javier M; Ren, Bing; Chen, Clark C; Carter, Bob S; Furnari, Frank B

    2018-04-12

    Epidermal growth factor receptor (EGFR) variant III (vIII) is the most common oncogenic rearrangement in glioblastoma (GBM) generated by deletion of exons two to seven of EGFR. The proximal breakpoints occur in variable positions within the 123-kb intron one, presenting significant challenges in terms of PCR-based mapping. Molecular mechanisms underlying these deletions remain unclear. We determined the presence of EGFRvIII and its breakpoints for 29 GBM samples using quantitative polymerase chain reaction (qPCR), arrayed PCR mapping, Sanger sequencing, and whole genome sequencing (WGS). Patient-specific breakpoint PCR was performed on tumors, plasma and cerebrospinal fluid (CSF) samples. The breakpoint sequences and single nucleotide polymorphisms (SNPs) were analyzed to elucidate the underlying biogenic mechanism. PCR mapping and WGS independently unveiled eight EGFRvIII breakpoints in six tumors. Patient-specific primers yielded EGFRvIII PCR amplicons in matched tumors, and in cell-free DNA (cfDNA) from a CSF sample, but not in cfDNA or extracellular-vesicle DNA from plasma. The breakpoint analysis revealed nucleotide insertions in four, an insertion of a region outside of EGFR locus in one, microhomologies in three, as well as a duplication or an inversion accompanied by microhomologies in two, suggestive of distinct DNA repair mechanisms. In the GBM samples that harbored distinct breakpoints, the SNP compositions of EGFRvIII and amplified non-vIII EGFR were identical, suggesting that these rearrangements arose from amplified non-vIII EGFR. Our approach efficiently "fingerprints" each sample's EGFRvIII breakpoints. Breakpoint sequence analyses suggest that independent breakpoints arose from precursor amplified non-vIII EGFR through different DNA repair mechanisms.

  17. Chromosomal rearrangements and protein globularity changes in Mycobacterium tuberculosis isolates from cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Seow Hoon Saw

    2016-09-01

    Full Text Available Background Meningitis is a major cause of mortality in tuberculosis (TB. It is not clear what factors promote central nervous system invasion and pathology but it has been reported that certain strains of Mycobacterium tuberculosis (Mtb might have genetic traits associated with neurotropism. Methods In this study, we generated whole genome sequences of eight clinical strains of Mtb that were isolated from the cerebrospinal fluid (CSF of patients presenting with tuberculous meningitis (TBM in Malaysia, and compared them to the genomes of H37Rv and other respiratory Mtb genomes either downloaded from public databases or extracted from local sputum isolates. We aimed to find genomic features that might be distinctly different between CSF-derived and respiratory Mtb. Results Genome-wide comparisons revealed rearrangements (translocations, inversions, insertions and deletions and non-synonymous SNPs in our CSF-derived strains that were not observed in the respiratory Mtb genomes used for comparison. These rearranged segments were rich in genes for PE (proline-glutamate/PPE (proline-proline-glutamate, transcriptional and membrane proteins. Similarly, most of the ns SNPs common in CSF strains were noted in genes encoding PE/PPE proteins. Protein globularity differences were observed among mycobacteria from CSF and respiratory sources and in proteins previously reported to be associated with TB meningitis. Transcription factors and other transcription regulators featured prominently in these proteins. Homologs of proteins associated with Streptococcus pneumoniae meningitis and Neisseria meningitidis virulence were identified in neuropathogenic as well as respiratory mycobacterial spp. examined in this study. Discussion The occurrence of in silico genetic differences in CSF-derived but not respiratory Mtb suggests their possible involvement in the pathogenesis of TBM. However, overall findings in this comparative analysis support the postulation that TB

  18. Nucleoplasmic bridges are a sensitive measure of chromosome rearrangement in the cytokinesis-block micronucleus assay

    International Nuclear Information System (INIS)

    Fenech, M.; Umegaki, K.

    2003-01-01

    Full text: We have performed experiments using the WIL2-NS human B-lymphoblastoid cell line and primary human lymphocytes to (a) determine the importance of including measurements of nucleoplasmic bridges (NPB) in the cytokinesis-block micronucleus (CBMN) assay and (b) provide evidence that NPB originate from dicentric chromosomes and centric ring chromosomes. In addition we describe theoretical models that explain how dicentric chromosomes and centric ring chromosomes may result in the formation of NPB at anaphase. The results with WIL2-NS showed that it was possible to distinguish genotoxic effects induced by different oxidizing agents in terms of the NPB/micronucleus frequency ratio. The results with lymphocytes indicated a strong correlation (a) between NPB, centric ring chromosomes and dicentric chromosomes in metaphases (R>0.93, P 0.93, P<0.0001). The dose-response curves with gamma rays were very similar for NPB, ring chromosomes and dicentric chromosomes, as were the dose-responses for MNi, acentric rings and fragments. However, not all acentric chromosomes and dicentric chromosomes/centric rings were converted to MNi and NPB respectively, depending on the dose of radiation. Preliminary data, using FISH, suggests that NPB often represent DNA from a structural rearrangement involving only one or two homologous chromosomes. The results from this study validate the inclusion of NPB in the CBMN assay which provides a valuable measure of chromosome breakage/ rearrangement that was otherwise not available in the micronucleus assay. The CBMN assay allows NPB measurement to be achieved reliably because inhibition of cytokinesis prevents the loss of NPB that would otherwise occur if cells were allowed to divide

  19. The impact of complex chromosomal rearrangements on the detection of radiosensitivity in cancer patients

    International Nuclear Information System (INIS)

    Neubauer, Susann; Dunst, Juergen; Gebhart, Erich

    1997-01-01

    Background and purpose: Lymphocytes of a small fraction of cancer patients responded to in vitro irradiation with an extreme chromosomal reaction. A large portion of the observed chromosome aberrations were complex chromosomal rearrangements (CCR). The present study is an attempt to define the impact of CCR on the predictive detection of an intrinsic clinical radiosensitivity in cancer patients in more detail. Materials and methods: A three-colour 'FISH-painting' technique (chromosome in situ suppression (CISS) hybridization) was used for the detection of chromosomal rearrangements, induced by in vitro irradiation, in 81 samples of peripheral blood lymphocytes from 66 cancer patients. Thirty-three of those were assigned for radiation therapy, the others having just undergone radiation therapy. Seven healthy individuals served as controls. Results: CCRs are a very rare event in non-irradiated cells. Lymphocytes of patients who had just undergone therapeutic irradiation, however, not only exhibited high basic frequencies of CCR but also responded to in vitro irradiation with a more drastic increase of CCR than did the lymphocytes of non-exposed patients. A high inter-individual variability of the reaction to in vitro irradiation could be generally stated. The lymphocytes of patients with clinical signs of an outstanding radiosensitivity responded with an unusually high frequency of CCR. The total number of CCRs detected by CISS was found to be dependent on the interval from a previous radiation therapy and was slightly influenced by previous cytostatic therapy. Irrespective of these influences, patients with clinically defined radiation hypersensitivity were those with the highest radiosensitivity also in cytogenetic terms (including CCR). Conclusion: The successful use of FISH-painting for the detection of CCR, in addition to the general breakage frequency, highlights its suitability in the identification of individual hypersensitivity to ionizing radiation. The

  20. Most ultraviolet irradiation induced mutations in the nematode Caenorhabditis elegans are chromosomal rearrangements

    International Nuclear Information System (INIS)

    Stewart, H.I.; Rosenbluth, R.E.; Baillie, D.L.

    1991-01-01

    In this study the utility of 254-nm ultraviolet light (UV) as a magnetic tool in C.elegans is determined. It is demonstrated that irradiation of adult hermaphrodites provides a simple method for the induction of heritable chromosomal rearrangements. A screening protocol was employed that identifies either recessive lethal mutations in the 40 map unit region balanced by the translocation eT1(III;V), or unc-36(III) duplications. Mutations were recovered in 3% of the chromosomes screened after a dose of 120 J/m 2 . This rate resembles that for 1500 R γ-ray-induced mutations selected in a similar manner. The mutations were classified either as lethals [mapping to Linkage Group (LG)III or LGV] or as putative unc-36 duplications. In contrast to the majority of UV-induced mutations analysed in micro-organisms, a large fraction of the C.elegans UV-induced mutations were found to be not simple intragenic lesions, but deficiencies for more than one adjacent gene or more complex events. Preliminary evidence for this conclusion came from the high frequency of mutations that had a dominant effect causing reduced numbers of adult progeny. Subsequently 6 out of 9 analysed LGV mutations were found to be deficiencies. Other specific rearrangements also identified were: one translocation, sT5(II;III), and two unc-36 duplications, sDp8 and sDp9. It was concluded that UV irradiation can easily be used as an additional tool for the analysis of C.elegans chromosomes, and that C.elegans should prove to be a useful organism in which to study the mechanisms whereby UV acts as a mutagen in cells of complex eukaryotes. (author). 46 refs.; 5 figs.; 4 tabs

  1. Towards secondary fingerprint classification

    CSIR Research Space (South Africa)

    Msiza, IS

    2011-07-01

    Full Text Available an accuracy figure of 76.8%. This small difference between the two figures is indicative of the validity of the proposed secondary classification module. Keywords?fingerprint core; fingerprint delta; primary classifi- cation; secondary classification I..., namely, the fingerprint core and the fingerprint delta. Forensically, a fingerprint core is defined as the innermost turning point where the fingerprint ridges form a loop, while the fingerprint delta is defined as the point where these ridges form a...

  2. Secondary Fire Analysis.

    Science.gov (United States)

    1981-09-01

    Megaton Weapons and Secondary Ignition There are very few well documented data on fires initiated by physical damage (i.e., secondary ignitions). Those data...where significant physical damage to buildings and/or contents can occur. Where this outer bound is located relative to the primary ignition range is...maintenance 7.9 Busline facilities, including shops 3.0 Convalescent homes8 3.1 Hospitals 8.0 Radio and television transmitters Collges and universities

  3. Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH)

    DEFF Research Database (Denmark)

    Staaf, Johan; Törngren, Therese; Rambech, Eva

    2008-01-01

    deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged...

  4. Cooperative use of VCD and XRD for the determination of tetrahydrobenzoisoquinolines absolute configuration: a reliable proof of memory of chirality and retention of configuration in enediyne rearrangements.

    Science.gov (United States)

    Mondal, Shovan; Naubron, Jean-Valère; Campolo, Damien; Giorgi, Michel; Bertrand, Michéle P; Nechab, Malek

    2013-12-01

    The absolute configurations (AC) of azaheterocylic compounds resulting from the cascade rearrangement of enediynes involving only light atoms were unambiguously assigned by the joint use of vibrational circular dichroism (VCD) and copper radiation single crystal X-ray diffraction (XRD). These AC determinations proved that the rearrangements of enediynes proceeded with memory of chirality and retention of configuration. © 2013 Wiley Periodicals, Inc.

  5. Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments

    NARCIS (Netherlands)

    Baer, R.; Boehm, T.; Yssel, H.; Spits, H.; Rabbitts, T. H.

    1988-01-01

    We have examined DNA rearrangements within a 120 kb cloned region of the human T cell receptor J delta-C delta/J alpha-C alpha locus. Three types of pattern emerge from an analysis of T cell lines and clones. Firstly, cells with two rearrangements within J delta-C delta; secondly, cells with one

  6. Immunoglobulin kappa deleting element rearrangements in precursor-B acute lymphoblastic leukemia are stable targets for detection of minimal residual disease by real-time quantitative PCR

    NARCIS (Netherlands)

    van der Velden, V. H. J.; Willemse, M. J.; van der Schoot, C. E.; Hählen, K.; van Wering, E. R.; van Dongen, J. J. M.

    2002-01-01

    Immunoglobulin gene rearrangements are used as PCR targets for detection of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). We Investigated the occurrence of monoclonal immunoglobulin kappa-deleting element (IGK-Kde) rearrangements by Southern blotting and PCR/heteroduplex

  7. Genome-wide sequencing for the identification of rearrangements associated with Tourette syndrome and obsessive-compulsive disorder

    Directory of Open Access Journals (Sweden)

    Hooper Sean D

    2012-12-01

    Full Text Available Abstract Background Tourette Syndrome (TS is a neuropsychiatric disorder in children characterized by motor and verbal tics. Although several genes have been suggested in the etiology of TS, the genetic mechanisms remain poorly understood. Methods Using cytogenetics and FISH analysis, we identified an apparently balanced t(6,22(q16.2;p13 in a male patient with TS and obsessive-compulsive disorder (OCD. In order to map the breakpoints and to identify additional submicroscopic rearrangements, we performed whole genome mate-pair sequencing and CGH-array analysis on DNA from the proband. Results Sequence and CGH array analysis revealed a 400 kb deletion located 1.3 Mb telomeric of the chromosome 6q breakpoint, which has not been reported in controls. The deletion affects three genes (GPR63, NDUFA4 and KLHL32 and overlaps a region previously found deleted in a girl with autistic features and speech delay. The proband’s mother, also a carrier of the translocation, was diagnosed with OCD and shares the deletion. We also describe a further potentially related rearrangement which, while unmapped in Homo sapiens, was consistent with the chimpanzee genome. Conclusions We conclude that genome-wide sequencing at relatively low resolution can be used for the identification of submicroscopic rearrangements. We also show that large rearrangements may escape detection using standard analysis of whole genome sequencing data. Our findings further provide a candidate region for TS and OCD on chromosome 6q16.

  8. Stereoselective synthesis of the 5'-aminofuranoside part of polyoxins via (3,3)-sigmatropic rearrangement of allylic thiocyanates

    Czech Academy of Sciences Publication Activity Database

    Gonda, J.; Martinkova, M.; Walko, M.; Zavacká, E.; Buděšínský, Miloš; Císařová, I.

    2001-01-01

    Roč. 42, č. 26 (2001), s. 4401-4404 ISSN 0040-4039 Grant - others:GA MŠSR(SK) 1/6080/99 Institutional research plan: CEZ:AV0Z4055905 Keywords : rearrangements * polyoxins Subject RIV: CC - Organic Chemistry Impact factor: 2.280, year: 2001

  9. Tandem electrophilic cyclization-[3+2] cycloaddition-rearrangement reactions of 2-alkynylbenzaldoxime, DMAD, and Br2.

    Science.gov (United States)

    Ding, Qiuping; Wang, Zhiyong; Wu, Jie

    2009-01-16

    Tandem electrophilic cyclization-[3+2] cycloaddition-rearrangement reactions of 2-alkynylbenzaldoximes, DMAD, and bromine are described, which afford the unexpected isoquinoline-based azomethine ylides in good to excellent yields. The products could be further elaborated via palladium-catalyzed cross-coupling reactions to generate highly functionalized isoquinoline-based stable azomethine ylides.

  10. NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements

    DEFF Research Database (Denmark)

    Weischelfeldt, Joachim Lütken; Damgaard, Inge; Bryder, David

    2008-01-01

    mildly affected in Upf2-null mice, suggesting that NMD is mainly essential for proliferating cells. Furthermore, we show that UPF2 loss resulted in the accumulation of nonproductive rearrangement by-products from the Tcrb locus and that this, as opposed to the general loss of NMD, was particularly...

  11. The strength of combined cytogenetic and mate-pair sequencing techniques illustrated by a germline chromothripsis rearrangement involving FOXP2

    DEFF Research Database (Denmark)

    Nazaryan, Lusine; Stefanou, Eunice G; Hansen, Claus

    2014-01-01

    Next-generation mate-pair sequencing (MPS) has revealed that many constitutional complex chromosomal rearrangements (CCRs) are associated with local shattering of chromosomal regions (chromothripsis). Although MPS promises to identify the molecular basis of the abnormal phenotypes associated with...... publication, 17 July 2013; doi:10.1038/ejhg.2013.147....

  12. Design and synthesis of fused polycycles via Diels-Alder reaction and ring-rearrangement metathesis as key steps.

    Science.gov (United States)

    Kotha, Sambasivarao; Ravikumar, Ongolu

    2015-01-01

    Atom efficient processes such as the Diels-Alder reaction (DA) and the ring-rearrangement metathesis (RRM) have been used to design new polycycles. In this regard, ruthenium alkylidene catalysts are effective in realizing the RRM of bis-norbornene derivatives prepared by DA reaction and Grignard addition. Here, fused polycycles are assembled which are difficult to produce by conventional synthetic routes.

  13. Chromosomal rearrangements and gene flow over time in an inter-specific hybrid zone of the Sorex araneus group.

    Science.gov (United States)

    Yannic, G; Basset, P; Hausser, J

    2009-06-01

    Most hybrid zones have existed for hundreds or thousands of years but have generally been observed for only a short time period. Studies extending over periods long enough to track evolutionary changes in the zones or assess the ultimate outcome of hybridization are scarce. Here, we describe the evolution over time of the level of genetic isolation between two karyotypically different species of shrews (Sorex araneus and Sorex antinorii) at a hybrid zone located in the Swiss Alps. We first evaluated hybrid zone movement by contrasting patterns of gene flow and changes in cline parameters (centre and width) using 24 microsatellite loci, between two periods separated by 10 years apart. Additionally, we tested the role of chromosomal rearrangements on gene flow by analysing microsatellite loci located on both rearranged and common chromosomes to both species. We did not detect any movement of the hybrid zone during the period analysed, suggesting that the zone is a typical tension zone. However, the gene flow was significantly lower among the rearranged than the common chromosomes for the second period, whereas the difference was only marginally significant for the first period. This further supports the role of chromosomal rearrangements on gene flow between these taxa.

  14. Extensive Pericentric Rearrangements in the Bread Wheat (Triticum aestivum L.) Genotype "Chinese Spring" Revealed from Chromosome Shotgun Sequence Data

    Czech Academy of Sciences Publication Activity Database

    Ma, J.; Stiller, J.; Wei, Y.M.; Zheng, Y.L.; Devos, K. M.; Doležel, Jaroslav; Liu, C.L.

    2014-01-01

    Roč. 6, č. 11 (2014), s. 3039-3048 ISSN 1759-6653 R&D Projects: GA ČR GBP501/12/G090 Institutional support: RVO:61389030 Keywords : chromosomal rearrangement * comparative genomics * pericentric inversion Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.229, year: 2014

  15. Excited- and Ground-State Versions of the Tri-.pi.-methane Rearrangement: Mechanistic and Exploratory Organic Photochemistry

    Czech Academy of Sciences Publication Activity Database

    Zimmerman, H. E.; Církva, Vladimír

    2001-01-01

    Roč. 66, č. 5 (2001), s. 1839-1851 ISSN 0022-3263 Grant - others:NSF(US) CHE-9709005 Keywords : Tri-.pi.-methane rearrangement * molecular systems * reaction Subject RIV: CH - Nuclear ; Quantum Chemistry Impact factor: 3.280, year: 2001

  16. Efficient Nazarov cyclization/Wagner-Meerwein rearrangement terminated by a Cu(II)-promoted oxidation: synthesis of 4-alkylidene cyclopentenones.

    Science.gov (United States)

    Lebœuf, David; Theiste, Eric; Gandon, Vincent; Daifuku, Stephanie L; Neidig, Michael L; Frontier, Alison J

    2013-04-08

    The discovery and elucidation of a new Nazarov cyclization/Wagner-Meerwein rearrangement/oxidation sequence is described that constitutes an efficient strategy for the synthesis of 4-alkylidene cyclopentenones. DFT computations and EPR experiments were conducted to gain further mechanistic insight into the reaction pathways. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Transient spontaneous remission in congenital MLL-AF10 rearranged acute myeloid leukemia presenting with cardiorespiratory failure and meconium ileus.

    Science.gov (United States)

    Gyárfás, Tobias; Wintgens, Juergen; Biskup, Wolfgang; Oschlies, Ilske; Klapper, Wolfram; Siebert, Reiner; Bens, Susanne; Haferlach, Claudia; Meisel, Roland; Kuhlen, Michaela; Borkhardt, Arndt

    2016-12-01

    Neonatal leukemia is a rare disease with an estimated prevalence of about one to five in a million neonates. The majority being acute myeloid leukemia (AML), neonatal leukemia can present with a variety of symptoms including hyperleucocytosis, cytopenia, hepatosplenomegaly, and skin infiltrates. Chromosomal rearrangements including mixed lineage leukemia (MLL) translocations are common in neonatal AML. A female neonate born at 34 weeks gestation presented with cardiorespiratory failure, hepatosplenomegaly, pancytopenia, and coagulopathy. She required intensive care treatment including mechanical ventilation, high-dose catecholamine therapy, and multiple transfusions. Small intestinal biopsy obtained during laparotomy for meconium ileus revealed an infiltrate by an undifferentiated monoblastic, MLL-rearranged leukemia. No other manifestations of leukemia could be detected. After spontaneous clinical remission, lasting 5 months without any specific treatment, the patient presented with leukemia cutis and full-blown monoblastic leukemia. MLL-AF10-rearranged AML could be re-diagnosed and successfully treated with chemotherapy and hematopoietic stem cell transplantation. Our patient exhibited a unique manifestation of neonatal MLL-AF10 rearranged AML with cardiorespiratory failure and intestinal infiltration. It highlights the importance of leukemia in the differential diagnosis of neonatal distress, congenital hematological abnormalities, and skin lesions.

  18. Simple and Rapid In Vivo Generation of Chromosomal Rearrangements using CRISPR/Cas9 Technology

    Directory of Open Access Journals (Sweden)

    Rafael B. Blasco

    2014-11-01

    Full Text Available Generation of genetically engineered mouse models (GEMMs for chromosomal translocations in the endogenous loci by a knockin strategy is lengthy and costly. The CRISPR/Cas9 system provides an innovative and flexible approach for genome engineering of genomic loci in vitro and in vivo. Here, we report the use of the CRISPR/Cas9 system for engineering a specific chromosomal translocation in adult mice in vivo. We designed CRISPR/Cas9 lentiviral vectors to induce cleavage of the murine endogenous Eml4 and Alk loci in order to generate the Eml4-Alk gene rearrangement recurrently found in non-small-cell lung cancers (NSCLCs. Intratracheal or intrapulmonary inoculation of lentiviruses induced Eml4-Alk gene rearrangement in lung cells in vivo. Genomic and mRNA sequencing confirmed the genome editing and the production of the Eml4-Alk fusion transcript. All mice developed Eml4-Alk-rearranged lung tumors 2 months after the inoculation, demonstrating that the CRISPR/Cas9 system is a feasible and simple method for the generation of chromosomal rearrangements in vivo.

  19. Partial 2p deletion in a girl with a complex chromosome rearrangement involving chromosomes 2, 6, 11, and 21.

    OpenAIRE

    Young, R S; Medrano, M A; Hansen, K L

    1985-01-01

    We describe the clinical and cytogenetic findings of a 9 1/2 month old girl with a complex chromosome rearrangement resulting in a probable deletion of band 2p14. She does not resemble other reported cases of del(2p).

  20. Reciprocal hybrid joints demonstrate successive V-J rearrangements on the same chromosome in the human TCR gamma locus

    NARCIS (Netherlands)

    Alexandre, D.; Chuchana, P.; Roncarolo, M. G.; Yssel, H.; Spits, H.; Lefranc, G.; Lefranc, M. P.

    1991-01-01

    Novel variable (V)--joining (J) gene rearrangements are described in the human T cell receptor gamma locus, in which, on the one hand, the V3 variable gene is joined to the heptamer--nonamer recombination signals of the J1 segment and, on the other hand, the J1 segment is joined to the V3